FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Dotson, VM Davatzikos, C Kraut, MA Resnick, SM AF Dotson, Vonetta M. Davatzikos, Christos Kraut, Michael A. Resnick, Susan M. TI Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID LATE-LIFE-DEPRESSION; CEREBRAL-BLOOD-FLOW; WHITE-MATTER HYPERINTENSITIES; ORBITOFRONTAL CORTEX VOLUME; RECURRENT MAJOR DEPRESSION; LATE-ONSET DEPRESSION; SCALE CES-D; GERIATRIC DEPRESSION; MOOD DISORDERS; PREFRONTAL CORTEX AB Background: Late-life depression is associated with decreased brain volumes, particularly in frontal and temporal areas. Evidence suggests that depressive symptoms at a subclinical level are also associated with brain atrophy in these regions, but most of these associations are based on cross-sectional data. Our objective was to investigate both cross-sectional and longitudinal relations between subthreshold depressive symptoms and brain volumes in older adults and to examine whether these associations are modified by age. Methods: In total, 110 dementia-free adults from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging aged 56 years and older at baseline participated in this study. Participants received annual evaluations for up to 9 years, during which structural magnetic resonance imaging (MRI) scans were acquired and depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Results: Mean depressive symptom scores over time were associated with grey matter volume reductions in the left temporal lobe. Depressive symptoms were associated with brain volume reductions with advancing age in the cingulate gyrus and orbitofrontal cortex. Moreover, individuals with higher mean depressive symptom scores showed a faster rate of volume decline in left frontal white matter. Depressive symptoms were not associated with hippocampus volumes. Limitations: Limitations include the relative homogeneity of our primarily white and highly educated sample, the lack of information about age at onset of depressive symptoms and potential limitations of the automated brain volume registration. Conclusion: Our results suggest that depressive symptoms, even at a subthreshold level, are associated with volume reductions in specific frontal and temporal brain regions, particularly with advancing age. C1 [Dotson, Vonetta M.; Resnick, Susan M.] NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. [Davatzikos, Christos] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Kraut, Michael A.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. RP Dotson, VM (reprint author), Univ Florida, Dept Clin & Hlth Psychol, POB 100165, Gainesville, FL 32610 USA. EM vonetta@phhp.ufl.edu RI Dotson, Vonetta/K-6090-2015; OI Dotson, Vonetta/0000-0002-3043-3320 FU National Institutes of Health FX The National Institute on Aging Intramural Research Program of the National Institutes of Health supported this research. The authors wish to thank Yang An, MS, for assistance with statistical analyses. NR 62 TC 60 Z9 61 U1 1 U2 8 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2009 VL 34 IS 5 BP 367 EP 375 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 488JV UT WOS:000269346800005 PM 19721847 ER PT J AU Basta, NE Edwards, SE Schulte, J AF Basta, Nicole E. Edwards, Sharlene E. Schulte, Joann TI Assessing Public Health Department Employees' Willingness to Report to Work During an Influenza Pandemic SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Article DE disaster response; disease outbreak; pandemic influenza; public health practice; public health workforce ID PREPAREDNESS; DUTY AB Objectives: During an influenza pandemic, public health employees will play a significant role in implementing community response and control protocols. We aimed to determine how informed health department employees are about pandemic response and how willing they are to report to work during a pandemic. Methods: We conducted an anonymous, electronic survey of 4 746 Florida county health department employees to assess willingness to respond. Results: Among the 2 414 respondents, willingness to report to work varied by the stage of the influenza pandemic and type of job duties, from 92.3 percent willingness given the lowest-risk scenario to 56.2 percent under the highest-risk scenario. Nurses and employees who had read one of the pandemic influenza plans were significantly more likely to be willing to respond. Conclusions: Nearly half of public health department employees are unwilling to report to work during the peak of an influenza pandemic when the public health response will be a vital component of pandemic containment and mitigation. In light of the current worldwide spread of novel influenza A (H1N1), there is an urgent need to better inform public health workers about their roles in pandemic response and to ensure that personal safety is a top priority. C1 [Basta, Nicole E.] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Basta, Nicole E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Edwards, Sharlene E.] Pinellas Cty Hlth Dept, St Petersburg, FL USA. [Schulte, Joann] NIH, Bethesda, MD 20892 USA. RP Basta, NE (reprint author), Univ Washington, Dept Epidemiol, Sch Publ Hlth, Box 357236, Seattle, WA 98195 USA. EM nbasta@u.washington.edu RI Basta, Nicole/B-4157-2013 NR 17 TC 7 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD SEP-OCT PY 2009 VL 15 IS 5 BP 375 EP 383 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 485OV UT WOS:000269134000002 PM 19704305 ER PT J AU McClain, JJ Tudor-Locke, C AF McClain, James J. Tudor-Locke, Catrine TI Objective monitoring of physical activity in children: considerations for instrument selection SO JOURNAL OF SCIENCE AND MEDICINE IN SPORT LA English DT Article DE Measurement; Physical activity; Children; Adolescent; Pedometer; Accelerometer ID ENERGY-EXPENDITURE; ACCELEROMETER OUTPUT; PRESCHOOL-CHILDREN; PEDOMETER ACCURACY; MEASURING STEPS; CALIBRATION; VALIDATION; ADULTS; RELIABILITY; EDUCATION AB There has been a rapid recent increase in both the number and type of objective physical activity (PA) assessment instruments which are commercially available to researchers, practitioners, and consumers. Although this has provided improved capacity for PA assessment, it also presents a somewhat bewildering range of options related to instrument selection for users of these technologies. The purpose of this review is to provide a primer to guide selection of instruments for the objective monitoring of children's PA. In an effort to inform without overwhelming, it is not intended to be exhaustive in terms of all available instruments. A general over-view is provided of two primary categories of objective monitors: pedometers and accelerometers. Within each category we focus on distinctly relevant options and features important to consider during instrument selection. In general, the desired outcome measure will determine the specific instrument category, options, and features from which the ultimate instrument choice is made. Other considerations include evidence of validity and reliability, cost, computer interface and download options, memory capacity, data aggregation and storage methods, and general participant and researcher burden associated with instrument use. There is no single objective PA assessment instrument that is appropriate for all situations, populations, and research questions. Further, we can anticipate that the commercial nature of these instruments will drive an even greater range of features and options in the future, increasing both the opportunity and the challenge for objectively assessing PA in children. (C) 2008 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved. C1 [McClain, James J.] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. RP McClain, JJ (reprint author), NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. EM james.mcclain@nih.gov NR 44 TC 32 Z9 32 U1 1 U2 13 PU SPORTS MEDICINE AUSTRALIA PI DICKSON PA PO BOX 237, DICKSON, ACT 2602, AUSTRALIA SN 1440-2440 J9 J SCI MED SPORT JI J. Sci. Med. Sport PD SEP PY 2009 VL 12 IS 5 BP 526 EP 533 DI 10.1016/j.jsams.2008.09.012 PG 8 WC Sport Sciences SC Sport Sciences GA 491BO UT WOS:000269552100004 PM 19054715 ER PT J AU West, S D'Aloisio, A Basson, R AF West, Suzanne D'Aloisio, Aimee Basson, Rosemary TI EMOTIONAL DISSATISFACTION AND ITS RELATION WITH HYPOACTIVE SEXUAL DESIRE DISORDER IN US WOMEN AGED 30 TO 70 YEARS BASED ON A RANDOM-DIGIT-DIAL SURVEY SO JOURNAL OF SEXUAL MEDICINE LA English DT Meeting Abstract C1 [West, Suzanne] RTI Int, Res Triangle Pk, NC USA. [D'Aloisio, Aimee] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Basson, Rosemary] Univ BC, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD SEP PY 2009 VL 6 BP 371 EP 371 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 490MO UT WOS:000269505300017 ER PT J AU Bivalacqua, TJ Musicki, B Hsu, LL Gladwin, MT Burnett, AL Champion, HC AF Bivalacqua, Trinity J. Musicki, Biljana Hsu, Lewis L. Gladwin, Mark T. Burnett, Arthur L. Champion, Hunter C. TI Establishment of a Transgenic Sickle-Cell Mouse Model to Study the Pathophysiology of Priapism SO JOURNAL OF SEXUAL MEDICINE LA English DT Article DE Erectile Dysfunction; Ischemic Priapism; Endothelium; Fibrosis; Cavolae; Nitric Oxide ID NITRIC-OXIDE SYNTHASE; PULMONARY-HYPERTENSION; RECURRENT PRIAPISM; ISCHEMIC PRIAPISM; PENILE ERECTION; SMOOTH-MUSCLE; RAT MODEL; DISEASE; TISSUE; EXPRESSION AB Introduction. Priapism is a poorly understood disease process with little information on the etiology and pathophysiology of this erectile disorder. One group of patients with a high prevalence of priapism is men with sickle-cell disease. Aim. Establish an in vivo transgenic sickle-cell mouse model to study the pathophysiology of sickle-cell disease-associated priapism. Methods. Transgenic sickle-cell disease mice, expressing human sickle hemoglobin, were utilized. Three groups of mice were used: (i) wild type (WT), (ii) sickle-cell heterozygotes (Hemi), and (ii) sickle-cell homozygotes (Sickle). Two age groups of each cohort of mice were utilized: young adult (4-6 months) and aged (18-22 months). Main Outcome Measures. Histological (trichrome stain to measure ratio of collagen to smooth muscle), penile hydroxyproline content (collagen content), and transmission electron microscopic analysis of WT, Hemi, and Sickle mice penes, as well as in vivo erectile responses [change in intracavernous pressure (ICP)] to cavernous nerve stimulation (CNS), were determined. The frequency of erectile responses (erections/hour) pre- and poststimulation was also measured in each of the experimental groups. Results. Sickle mice had increased (P < 0.05) collagen to smooth muscle ratio and hydroxyproline content in the penis when compared with WT and Hemi mice penes. Transmission electron microscopy demonstrated thickened smooth muscle cell bundles, disruption of the endothelial lining of the corporal sinusoids, and increased (P < 0.05) caveolae number. Sickle mice had significantly (P < 0.05) higher ICP to CNS and increased (P < 0.05) frequency of erections pre- and post-CNS when compared with WT and Hemi mice erectile responses. Sickle mice did develop ED (change in ICP in response to CNS) with increasing age. Conclusion. The morphometric changes of the penis and exaggerated in vivo erectile responses support the use of this transgenic sickle-cell disease animal model to study the pathophysiological mechanisms involved in sickle-cell disease-associated priapism. Bivalacqua TJ, Musicki B, Hsu LL, Gladwin MT, Burnett AL, and Champion HC. Establishment of a transgenic sickle-cell mouse model to study the pathophysiology of priapism. J Sex Med 2009;6:2494-2504. C1 [Champion, Hunter C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Bivalacqua, Trinity J.; Musicki, Biljana; Burnett, Arthur L.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Hsu, Lewis L.] Natl Heart Lung Blood Inst, Vasc Med Branch, NIH, Bethesda, MD USA. [Hsu, Lewis L.] Drexel Univ, Coll Med, St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA 19104 USA. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Chief Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. RP Champion, HC (reprint author), Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. EM hchampi@jhmi.edu FU American Urological Association (AUA) Foundation; Astellas USA Foundation; National Kidney Foundation; American Physiological Society; NIH [RO1 DK067223, U54HL090515, NO1-CO-12400]; National Cancer Institute; National Heart, Lung, and Blood Institute of the NIH FX The authors would like to thank Dr. Janice Taube, Warren Mason, and Carol Cooke for their help with analysis of trichrome stain and electron microscopy of the mice penes. Dr. Bivalacqua is supported by an American Urological Association (AUA) Foundation Astellas USA Foundation MD/PhD Fellowship and recipient of a National Kidney Foundation of Maryland Research Grant. Dr. Champion is supported in part by the Bernard A. and Rebecca S. Bernard Foundation, a Scientist Development Grant from the American Heart Association, the WW Smith Foundation, and NIH P50 Hl084946. He is a Recipient of the Zipes Distinguished Young Investigator Award of the American College of Cardiology, the Shin Chun-Wang Young Investigator Award and the Giles F. Filley Memorial Award from the American Physiological Society. Dr. Burnett is supported in part from NIH RO1 DK067223 and U54HL090515. Dr. Hsu and Gladwin are supported in part by federal funds from National Cancer Institute, NIH, under contract NO1-CO-12400 and the Intramural Program of the Vascular Medicine Branch of the National Heart, Lung, and Blood Institute of the NIH. The content of the article does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 35 TC 35 Z9 35 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD SEP PY 2009 VL 6 IS 9 BP 2494 EP 2504 DI 10.1111/j.1743-6109.2009.01359.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 488TN UT WOS:000269373100016 PM 19523035 ER PT J AU Roberts, MD Drinkard, B Ranzenhofer, LM Salaita, CG Sebring, NG Brady, SM Pinchbeck, C Hoehl, J Yanoff, LB Savastano, DM Han, JC Yanovski, JA AF Roberts, M. D. Drinkard, B. Ranzenhofer, L. M. Salaita, C. G. Sebring, N. G. Brady, S. M. Pinchbeck, C. Hoehl, J. Yanoff, L. B. Savastano, D. M. Han, J. C. Yanovski, J. A. TI Prediction of maximal oxygen uptake by bioelectrical impedance analysis in overweight adolescents SO JOURNAL OF SPORTS MEDICINE AND PHYSICAL FITNESS LA English DT Article DE Obesity; Pediatrics; Physical fitness ID SKELETAL-MUSCLE MASS; PHYSICAL-ACTIVITY; EXERCISE TOLERANCE; CROSS-VALIDATION; BLOOD-VOLUME; CHILDREN; FITNESS; OBESITY; PERFORMANCE; DISEASE AB Aim. Maximal oxygen uptake ((V) over dotO(2max)), the gold standard for measurement of cardiorespiratory fitness, is frequently difficult to assess in overweight individuals due to physical limitations. Reactance and resistance measures obtained from bioelectrical impedance analysis (BIA) have been suggested as easily obtainable predictors of cardiorespiratory fitness, but the accuracy with which ht(2)/Z can predict (V) over dotO(2max) has not previously been examined in overweight adolescents. Methods. The impedance index was used as a predictor of (V) over dotO(2max) in 87 overweight girls and 47 overweight boys ages 12 to 17 with mean BMI of 38.6+/-7.3 and 42.5+/-8.2 in girls and boys respectively. The Bland Altman procedure assessed agreement between predicted and actual (V) over dotO(2max). Results. Predicted (V) over dotO(2max) was significantly correlated with measured (V) over dotO(2max) (r(2)=0.48, P<0.0001). Using the Bland Altman procedure, there was significant magnitude bias (r(2)=0.10; P<0.002). The limits of agreement for predicted relative to actual (V) over dotO(2max) were -589 to 574 mL O(2)/min. Conclusion. The impedance index was highly correlated with (V) over dotO(2max) in overweight adolescents. However, using BIA, data to predict maximal oxygen uptake over-predicted (V) over dotO(2max) at low levels of oxygen consumption and under-predicted (V) over dotO(2max) at high levels of oxygen consumption. This magnitude bias, along with the large limits of agreement of BIA-derived predicted (V) over dotO(2max), limit its usefulness in the clinical setting for overweight adolescents. C1 [Drinkard, B.; Hoehl, J.; Yanovski, J. A.] NIH, Hatfield Clin Res Ctr, Dept Rehabil Med, Clin Res Ctr,DHHS, Bethesda, MD 20892 USA. [Roberts, M. D.; Ranzenhofer, L. M.; Brady, S. M.; Pinchbeck, C.; Yanoff, L. B.; Savastano, D. M.; Han, J. C.; Yanovski, J. A.] NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NICHD, Bethesda, MD 20892 USA. [Salaita, C. G.; Sebring, N. G.] NIH, Dept Nutr, Hatfield Clin Res Ctr, DHHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NIH, Hatfield Clin Res Ctr, Dept Rehabil Med, Clin Res Ctr,DHHS, Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM jy15i@.nih.gov FU NICHD/NIH [ZO1-RD-00641]; National Center for Minority Health and Health Disparities FX This research was supported by the Intramural Research Program of the NICHD/NIH, grant ZO1-RD-00641 to JAY and Supplemental funding from the National Center for Minority Health and Health Disparities to JAY. JAY, BD, NGS, and JCH are Commissioned Officers in the US Public Health Service, DHHS.The authors have no conflicts of interest to disclose. MR and BD contributed equally and are co-first authors. NR 44 TC 3 Z9 3 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0022-4707 J9 J SPORT MED PHYS FIT JI J. Sports Med. Phys. Fit. PD SEP PY 2009 VL 49 IS 3 BP 240 EP 245 PG 6 WC Sport Sciences SC Sport Sciences GA 538IZ UT WOS:000273179100002 PM 19861930 ER PT J AU Datta, S Lan, L Sundaram, R AF Datta, Somnath Lan, Ling Sundaram, Rajeshwari TI Nonparametric estimation of waiting time distributions in a Markov model based on current status data SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Current status data; Markov; Multistate models; Nonparametric regression; PAV; Waiting time distributions ID INTERVAL-CENSORED-DATA; STAGE OCCUPATION PROBABILITIES; INTEGRATED TRANSITION HAZARDS; MAXIMUM-LIKELIHOOD-ESTIMATION; COMPETING RISKS; SURVIVAL-DATA; EFFICIENT ESTIMATION; MULTISTAGE MODEL; LEFT TRUNCATION; REGRESSION AB We construct nonparametric estimators of state waiting time distribution functions in a Markov multistate model using current status data. This is a particularly difficult problem since neither the entry nor the exit times of a given state are directly observed. These estimators are obtained, using the Markov property, from estimators of counting processes of state entry and exit times, as well as, the size of "at risk" sets of state entry and transitions out of that state. Consistency of our estimators is established. Finite-sample behavior of our estimators is studied by simulation, in which we show that our estimators based on current status data compare well with those based on complete data. We also illustrate our method using a pubertal development data set obtained from the NHANES 111 [1997. NHANES III Reference Manuals and Reports (CD-ROM). Analytic and Reporting Guidelines: The Third National Health and Nutrition Examination Survey (1988-94). National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD] study. (C) 2009 Elsevier B.V. All rights reserved. C1 [Datta, Somnath] Univ Louisville, Dept Bioninformat & Biostat, Louisville, KY 40202 USA. [Lan, Ling] Med Coll Georgia, Dept Biostat, Augusta, GA 30912 USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Datta, S (reprint author), Univ Louisville, Dept Bioninformat & Biostat, Louisville, KY 40202 USA. EM somnath.datta@louisville.edu OI Sundaram, Rajeshwari/0000-0002-6918-5002 NR 46 TC 3 Z9 3 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD SEP 1 PY 2009 VL 139 IS 9 BP 2885 EP 2897 DI 10.1016/j.jspi.2009.01.010 PG 13 WC Statistics & Probability SC Mathematics GA 470EE UT WOS:000267956600003 ER PT J AU Djousse, L Himali, JJ Beiser, A Kelly-Hayes, M Wolf, PA AF Djousse, Luc Himali, Jayandra J. Beiser, Alexa Kelly-Hayes, Margaret Wolf, Philip A. TI Apolipoprotein E, Alcohol Consumption, and Risk of Ischemic Stroke: The Framingham Heart Study Revisited SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Alcohol drinking; ischemic stroke; apolipoprotein E gene; lipids ID HIGH-DENSITY-LIPOPROTEIN; INSULIN SENSITIVITY; WINE CONSUMPTION; E POLYMORPHISM; DISEASE; METAANALYSIS; ASSOCIATION; INTERVENTION; ADIPONECTIN; BIOMARKERS AB Background: Data on the association between alcohol consumption and ischemic stroke have been inconsistent. It is not known whether allele epsilon(4) of the apolipoprotein E (apoE) gene modifies the alcohol-stroke association. We sought to examine whether epsilon(4) allele of the apoE gene influences the association between alcohol consumption and ischemic stroke or high-density lipoprotein (HDL) cholesterol. Methods: We examined a cohort of 7676 person-observations of the Framingham Heart Study. Incident stroke was ascertained by standardized methods. We used Cox proportional hazard model to estimate hazard ratios of ischemic stroke. Results: The average age at baseline was 63 years and 55% of the participants were women. During a mean follow-up of 7.4 years, 222 new cases of ischemic stroke occurred (56 embolic and 166 atherothrombotic events). Comparing current drinkers with nondrinkers, multivariable adjusted hazard ratio (95% confidence interval) for ischemic stroke was 0.50 (0.24-1.07) in the absence Of epsilon(4) allele and 0.70 (0.24-2.05) in the presence Of epsilon(4) allele (P for interaction = .64) for those younger than 65 years. Similarly, we did not observe a statistically significant interaction between epsilon(4) allele and alcohol consumption on the risk of stroke among people aged 65 years and older (P for interaction = .17). Alcohol consumption was positively associated with HDL cholesterol independent of epsilon(4) allele and age. Conclusions: Our data do not provide evidence for an interaction between epsilon(4) allele and alcohol consumption on the risk of ischemic stroke in this population. Furthermore, apoE polymorphism did not influence the alcohol-HDL relation. C1 [Djousse, Luc] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02120 USA. [Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA. [Himali, Jayandra J.; Beiser, Alexa] Boston Univ, Sch Publ Hlth, Dept Biostat, Framingham, MA USA. [Himali, Jayandra J.; Beiser, Alexa; Kelly-Hayes, Margaret; Wolf, Philip A.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Beiser, Alexa; Kelly-Hayes, Margaret; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, Dept Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017; OI Djousse, Luc/0000-0002-9902-3047; Beiser, Alexa/0000-0001-8551-7778; /0000-0003-1391-9481 FU National Heart, Lung, and Blood Institute's (NHLBI) Framingham Heart Study [N01-HC-25195]; National Institute of Health, Bethesda, MD; National Institute of Neurological Disorders and Stroke [5R01-NS 017950]; NHLBI [K01 HL-70444] FX Supported by the National Heart, Lung, and Blood Institute's (NHLBI) Framingham Heart Study contract No. N01-HC-25195, National Institute of Health, Bethesda, MD, and a grant from the National Institute of Neurological Disorders and Stroke (5R01-NS 017950, Philip A. Wolf, MD, Principal Lnvestigator). Dr. Djousse was partially supported by K01 HL-70444 from the NHLBI. NR 35 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD SEP-OCT PY 2009 VL 18 IS 5 BP 384 EP 388 DI 10.1016/j.jstrokecerebrovasdis.2009.01.008 PG 5 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 493SS UT WOS:000269758900011 PM 19717024 ER PT J AU Chronis-Tuscano, A Degnan, KA Pine, DS Perez-Edgar, K Henderson, HA Diaz, Y Raggi, VL Fox, NA AF Chronis-Tuscano, Andrea Degnan, Kathryn Amey Pine, Daniel S. Perez-Edgar, Koraly Henderson, Heather A. Diaz, Yamalis Raggi, Veronica L. Fox, Nathan A. TI Stable Early Maternal Report of Behavioral Inhibition Predicts Lifetime Social Anxiety Disorder in Adolescence SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE temperament; behavioral inhibition; social anxiety disorder ID PSYCHIATRIC-DISORDERS; EARLY-CHILDHOOD; FOLLOW-UP; AGE 3; CHILDREN; TEMPERAMENT; RESPONSES; QUESTIONNAIRE; ASSOCIATION; FRAMEWORK AB Objective: Behavioral inhibition (BI), a temperamental style identifiable in early childhood, is considered a risk factor for the development of anxiety disorders, particularly social anxiety disorder (SAD). However, few studies examining this question have evaluated the stability of BI across multiple developmental time points and followed participants into adolescence-the developmental period during which risk for SAD onset is at its peak. The current study used a prospective longitudinal design to determine whether stable early BI predicted the presence of psychiatric disorders and continuous levels of social anxiety in adolescents. It was hypothesized that stable BI would predict the presence of adolescent psychiatric diagnoses, specifically SAD. Method: Participants included 126 adolescents aged 14 to 16 years who were first recruited at 4 months of age from hospital birth records. Temperament was measured at multiple time points between the ages of 14 months and 7 years. In adolescence, diagnostic interviews were conducted with parents and adolescents, and continuous measures of adolescent- and parent-reported social anxiety were collected. Results: Stable maternal-reported early BI was associated with 3.79 times increased odds of a lifetime SAD diagnosis, but not other diagnoses, during adolescence (95% confidence interval 1.18-12.12). Stable maternal-reported early BI also predicted independent adolescent and parent ratings of ongoing social anxiety symptoms. Conclusions: Findings suggesting that stable maternal-reported early BI predicts lifetime SAD have important implications for the early identification and prevention of SAD. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(9):928-935. C1 [Chronis-Tuscano, Andrea] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Pine, Daniel S.] NIMH, Bethesda, MD USA. [Perez-Edgar, Koraly] George Mason Univ, Fairfax, VA 22030 USA. [Henderson, Heather A.] Univ Miami, Coral Gables, FL 33124 USA. RP Chronis-Tuscano, A (reprint author), Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. EM achronis@psyc.umd.edu OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institute of Mental Health [R01MH074454]; National Institute of Child Health and Development [R01 HD017899] FX This research was supported by National Institute of Mental Health R01MH074454 and National Institute of Child Health and Development R01 HD017899 (PI: N.F.). NR 56 TC 165 Z9 165 U1 5 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2009 VL 48 IS 9 BP 928 EP 935 DI 10.1097/CHI.0b013e3181ae09df PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 488AW UT WOS:000269322300008 PM 19625982 ER PT J AU Thigpen, JE Caviness, GF Whiteside, TE Locklear, J Grant, M Forsythe, D AF Thigpen, J. E. Caviness, G. F. Whiteside, T. E. Locklear, J. Grant, M. Forsythe, D. TI The Use of ATP-Based Methods or RODAC Plates for Monitoring the Effectiveness of Sanitation Procedures in an Animal Facility SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J. E.; Caviness, G. F.; Whiteside, T. E.; Locklear, J.; Grant, M.; Forsythe, D.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 548 EP 548 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000063 ER PT J AU Tirabassi, RS Duclos, SK Moran-Paul, C Arreaza-Rubin, GA Spain, L Guberski, DL AF Tirabassi, R. S. Duclos, S. K. Moran-Paul, C. Arreaza-Rubin, G. A. Spain, L. Guberski, D. L. TI Development of Protocols to Optimize Treatment of Spontaneous Type 1 Diabetes in Nonobese Diabetic Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Tirabassi, R. S.; Duclos, S. K.; Moran-Paul, C.; Guberski, D. L.] Biomed Res Models Inc, Worcester, MA USA. [Arreaza-Rubin, G. A.; Spain, L.] NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 550 EP 550 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000070 ER PT J AU Tirabassi, RS Moran-Paul, C Duclos, SK Spain, L Arreaza-Rubin, G Guberski, DL AF Tirabassi, R. S. Moran-Paul, C. Duclos, S. K. Spain, L. Arreaza-Rubin, G. Guberski, D. L. TI Development of Glucose Testing Protocols to Identify Prediabetic Nonobese Diabetic Mice for Interventional Treatment SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Tirabassi, R. S.; Moran-Paul, C.; Duclos, S. K.; Guberski, D. L.] Biomed Res Models Inc, Worcester, MA USA. [Spain, L.; Arreaza-Rubin, G.] NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 550 EP 550 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000069 ER PT J AU Kercher, L LaCasse, RA Brining, DL Gardner, DJ Feldmann, R Rockx, B Marzi, A Safronetz, D Feldmann, H Parnell, MJ AF Kercher, L. LaCasse, R. A. Brining, D. L. Gardner, D. J. Feldmann, R. Rockx, B. Marzi, A. Safronetz, D. Feldmann, H. Parnell, M. J. TI Swine H2N3 Influenza A Virus Pathogenesis in a Macaque Model SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Kercher, L.; LaCasse, R. A.; Brining, D. L.; Gardner, D. J.; Feldmann, R.; Rockx, B.; Marzi, A.; Safronetz, D.; Feldmann, H.; Parnell, M. J.] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 556 EP 556 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000088 ER PT J AU Gyles, A AF Gyles, A. TI Technique for Footpad/Lateral Tarsal Region Injections in Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Gyles, A.] NIAMS, SoBran, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 563 EP 563 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000111 ER PT J AU Zegre-Cannon, C Waxer, D Myers, P Clark, J Goulding, DR King-Herbert, AP Blankenship-Paris, T AF Zegre-Cannon, C. Waxer, D. Myers, P. Clark, J. Goulding, D. R. King-Herbert, A. P. Blankenship-Paris, T. TI Evaluation of Route of Administration and Dosage of Tramadol as an Analgesic in the Rat SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Zegre-Cannon, C.; King-Herbert, A. P.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Zegre-Cannon, C.; Waxer, D.; Myers, P.; Clark, J.; Goulding, D. R.; Blankenship-Paris, T.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 564 EP 564 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000113 ER PT J AU Tubbs, JT Goulding, DR King-Herbert, AP Blankenship, TL Hess, H AF Tubbs, J. T. Goulding, D. R. King-Herbert, A. P. Blankenship, T. L. Hess, H. TI Botryomycosis with Eosinophilic Ym1-positive Crystals in a Transgenic Mouse SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Tubbs, J. T.; King-Herbert, A. P.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. [Goulding, D. R.; Blankenship, T. L.; Hess, H.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 567 EP 567 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000126 ER PT J AU Linkenhoker, JR Burkholder, TH Linton, C Walden, A Abusakran-Monday, K Rosero, A Foltz, C AF Linkenhoker, J. R. Burkholder, T. H. Linton, C. Walden, A. Abusakran-Monday, K. Rosero, A. Foltz, C. TI Effective and Safe Anesthesia for Yorkshire and Yucatan Swine with and without Cardiovascular Injury and Intervention SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Linkenhoker, J. R.; Burkholder, T. H.; Linton, C.; Walden, A.; Abusakran-Monday, K.; Rosero, A.; Foltz, C.] NIH, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 568 EP 568 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000127 ER PT J AU Byrum, R Lara, A Claire, MS AF Byrum, R. Lara, A. Claire, M. St. TI Nonbronchoscopic Technique for Performing Bronchoalveolar Lavage in Nonhuman Primates SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Byrum, R.] Charles River Labs, Germantown, MD USA. [Lara, A.] Midwest Res Inst, Frederick, MD USA. [Byrum, R.; Lara, A.; Claire, M. St.] NIAID, Div Clin Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 575 EP 575 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000152 ER PT J AU Myers, PH Blankenship, TL Clark, JA Waxer, DL Grant, MF Forsythe, DB AF Myers, P. H. Blankenship, T. L. Clark, J. A. Waxer, D. L. Grant, M. F. Forsythe, D. B. TI Adverse Effect of Supplemental Heat in Lipopolysaccharide-Treated Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Myers, P. H.; Blankenship, T. L.; Clark, J. A.; Waxer, D. L.; Grant, M. F.; Forsythe, D. B.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 576 EP 577 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000158 ER PT J AU Mensch, J AF Mensch, J. TI Surgical Support Procedures at NIAAA Facilities SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Mensch, J.] NIAAA, NIH, Rockville, MD 20852 USA. [Mensch, J.] SoBran, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 593 EP 593 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000214 ER PT J AU Goulding, DR Blankenship, TL Myers, PH Grant, MF Forsythe, DB AF Goulding, D. R. Blankenship, T. L. Myers, P. H. Grant, M. F. Forsythe, D. B. TI A Novel Method That Increases the Efficiency of Carbon Dioxide Euthanasia in a Rodent Facility SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Goulding, D. R.; Blankenship, T. L.; Myers, P. H.; Grant, M. F.; Forsythe, D. B.] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 609 EP 609 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000266 ER PT J AU Castranova, DA Lawrence, C Lawton, A Doherty, A Baumann, D Wang, C Wilson, C Ramos, J Best, J Adatto, I Weinstein, BM AF Castranova, D. A. Lawrence, C. Lawton, A. Doherty, A. Baumann, D. Wang, C. Wilson, C. Ramos, J. Best, J. Adatto, I. Weinstein, B. M. TI The Effects of Tank Density on Reproductive Performance in Zebrafish SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Castranova, D. A.; Wang, C.; Weinstein, B. M.] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. [Castranova, D. A.; Wang, C.] Charles River Labs, Germantown, MD USA. [Lawton, A.] Univ Queensland, Brisbane, Qld 4072, Australia. [Lawrence, C.; Best, J.; Adatto, I.] Childrens Hosp Boston, Boston, MA USA. [Wilson, C.] Univ Coll, London, England. [Doherty, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ramos, J.] Barcelona Biomed Res Pk, Barcelona, Spain. [Baumann, D.] Stowers Inst Med Res, Kansas City, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 614 EP 614 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000283 ER PT J AU Thigpen, JE Caviness, GF Whiteside, TE Locklear, J Grant, M Forsythe, D AF Thigpen, J. E. Caviness, G. F. Whiteside, T. E. Locklear, J. Grant, M. Forsythe, D. TI Efficacy of Various Disinfectants for the Elimination of Mycoplasma on Environmental Work Surfaces SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J. E.; Caviness, G. F.; Whiteside, T. E.; Locklear, J.; Grant, M.; Forsythe, D.] NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 623 EP 623 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000310 ER PT J AU Thigpen, JE Caviness, GF Whiteside, TE Locklear, J Kissling, G Laughter, A Chen, S Hollister, B Grant, M Forsythe, D AF Thigpen, J. E. Caviness, G. F. Whiteside, T. E. Locklear, J. Kissling, G. Laughter, A. Chen, S. Hollister, B. Grant, M. Forsythe, D. TI Comparison of the Adenosine Triphosphate Luminescence Assay to the Polymerase Chain Reaction Assay for the Detection of Mycoplasma in Cell Cultures SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J. E.; Caviness, G. F.; Whiteside, T. E.; Locklear, J.; Grant, M.; Forsythe, D.] NIH, Res Triangle Pk, NC USA. [Kissling, G.; Laughter, A.; Chen, S.; Hollister, B.] Piedmont Res Ctr, Morrisville, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2009 VL 48 IS 5 BP 623 EP 624 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 502SI UT WOS:000270480000311 ER PT J AU Cannon, RO AF Cannon, Richard O., III TI Microvascular Angina and the Continuing Dilemma of Chest Pain With Normal Coronary Angiograms SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE coronary; microcirculation; disease ID CARDIAC SYNDROME-X; SYNDROME EVALUATION WISE; ARTERY-DISEASE; MYOCARDIAL-ISCHEMIA; FOLLOW-UP; ENDOTHELIAL DYSFUNCTION; VASODILATOR RESERVE; RISK-FACTORS; L-ARGININE; SUBENDOCARDIAL ISCHEMIA AB Since initial reports over 4 decades ago, cases of patients with angina-like chest pain whose coronary angiograms show no evidence of obstructive coronary artery disease and who have no structural heart disease continue to be a common occurrence for cardiologists. Many features of this patient population have remained constant with successive reports over time: a female predominance, onset of symptoms commonly between 40 and 50 years of age, pain that is severe and disabling, and inconsistent responses to conventional anti-ischemic therapy. Because patients may have had abnormal noninvasive testing that led to performance of coronary angiography, investigators have sought to show an association of this syndrome with myocardial ischemia. Abnormalities in coronary flow and metabolic responses to stress have been reported by several groups, findings consistent with a microvascular etiology for ischemia and symptoms, but others have questioned the presence of ischemia, even in patients selected for abnormal noninvasive testing. Despite considerable efforts by many groups over 4 decades, the syndrome remains controversial with regard to pathophysiology, diagnosis, and management. (J Am Coll Cardiol 2009; 54:877-85) (C) 2009 by the American College of Cardiology Foundation C1 NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Translat Med Branch, NIH, Bldg 10 CRC,Room 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cannonr@nih.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health FX From the Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. The content of this article represents the opinions of the author and not necessarily those of the National Heart, Lung, and Blood Institute. Dr. Cannon is supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, National Institutes of Health, and has previously served on the Data Safety and Monitoring Board of the WISE (Women's Ischemia Syndrome Evaluation) study. NR 87 TC 54 Z9 58 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 1 PY 2009 VL 54 IS 10 BP 877 EP 885 DI 10.1016/j.jacc.2009.03.080 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 487WY UT WOS:000269309900001 PM 19712795 ER PT J AU Frankel, TL Burns, W Royal, RE AF Frankel, Timothy L. Burns, William Royal, Richard E. TI Regression of pancreatic cancer from ipilimumab (anti-CTLA-4) mediated by an NK-cell subset (CD56brightCD16dim) SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT 95th Annual Clinical Congress of the American-College-of-Surgeons/64th Annual Sessions of the Owen H Wangensteen Forum on Fundamental Surgical Problems CY OCT 11-15, 2009 CL Chicago, IL SP Amer Coll Surg C1 [Frankel, Timothy L.; Burns, William; Royal, Richard E.] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2009 VL 209 IS 3 SU S BP S120 EP S120 PG 1 WC Surgery SC Surgery GA 493RJ UT WOS:000269755300270 ER PT J AU Garcia, I Tabak, LA AF Garcia, Isabel Tabak, Lawrence A. TI A view of the future Dentistry and oral health in America SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Dental research; emerging technology AB Background. New tools are enabling researchers to understand the mysteries of oral biology and disease and to change profoundly the treatment of oral, dental and craniofacial diseases and disorders. The authors explore advances in modern science and technology and how they will change oral health care in the future. Results. Emerging technologies such as salivary diagnostics, high-resolution imaging and nanotechnologies, as well as other new tools win lead to efficient and highly effective personalized dental treatments. A new generation of cell-based,therapies will be available for regenerating tissues, and anti-inflammatory drugs and pain medications will be tailored to maximize efficacy and safety. Large teams of clinicians and scientists will tackle increasingly complex problems, and advances in computational sciences will make it possible to create virtual teams across the world. Information technology systems will enable clinicians to examine and integrate information obtained from all databases in cyberspace. Clinical Implications. As scientists discover newer and better methods to preempt and prevent disease, they must translate these methods into tools for people at greatest risk of developing disease. Conquering the array of complex diseases that affect the oral and craniofacial complex will require multifaceted strategies and multidisciplinary cooperation. C1 [Garcia, Isabel; Tabak, Lawrence A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Garcia, I (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 31 Ctr Dr,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. EM Garcial@mail.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 8 TC 7 Z9 7 U1 0 U2 5 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD SEP PY 2009 VL 140 BP 44S EP 48S PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 492RO UT WOS:000269677100007 PM 19723930 ER PT J AU Zhu, SH Patel, KV Bandinelli, S Ferrucci, L Guralnik, JM AF Zhu, Shuhan Patel, Kushang V. Bandinelli, Stefania Ferrucci, Luigi Guralnik, Jack M. TI Predictors of Interleukin-6 Elevation in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE inflammation; aging; interleukin-6 ID INFLAMMATORY MARKERS; CARDIOVASCULAR-DISEASE; HEART-FAILURE; HEALTH ABC; MORTALITY; RISK AB OBJECTIVES: To investigate the characteristics of older adults who develop high interleukin-6 (IL-6) levels at 3-year follow-up. DESIGN: Population-based study of adults living in Tuscany, Italy. SETTING: Community. PARTICIPANTS: Adults aged 65 and older and were selected for this study. Of 1,155 baseline participants aged 65 and older, 741 had IL-6 measurements at baseline and 3-year follow-up. MEASUREMENTS: The uppermost quartile of IL-6 was used as the threshold for defining high IL-6 (>= 4.18 pg/mL). Serum IL-6 levels were assessed using enzyme immunoassay. RESULTS: Of the 581 participants with IL-6 levels less than 4.18 pg/mL at baseline, 106 (18.2%) had developed high IL-6 at follow-up. Although women had lower IL-6 levels at baseline than men, the risk of developing high IL-6 did not differ according to sex. High adiposity, defined as a body mass index of 30.0 kg/m(2) or higher (odds ratio (OR) = 2.63, 95% confidence interval (CI) = 1.40-4.96), and large waist circumference, defined as 102 cm or greater for men and 8 8 cm or greater for women (OR = 2.05, 95% CI = 1.24-3.40), were significant predictors of developing high IL-6 at follow-up. Other significant predictors were presence of three or more chronic diseases (OR = 3.66,95% CI = 1.54-8.70), higher baseline 116 (OR = 1.82, 95% CI = 1.39-2.38) and higher white blood cell count (OR = 1.24, 95% CI = 1.06-1.45). Faster walking speed associated with decreased risk of progressing to elevated IL-6 (OR = 0.83, 95% CI = 0.74-0.92). CONCLUSION: Older age, greater adiposity, slower walking speed, higher disease burden, and higher white blood cell count were associated with greater risk of IL-6 elevation over a 3-year period. Future research should target older adults with these characteristics to prevent progression to a proinflammatory state. J Am Geriatr Soc 57:1672-1677, 2009. C1 [Zhu, Shuhan] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Zhu, Shuhan; Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. RP Zhu, SH (reprint author), 12469 Cedar Rd,8B, Cleveland, OH 44106 USA. EM sxz21@case.edu FU Italian Ministry of Health [ICS 1.10.1. RS97.71]; U.S. National Institute on Aging [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336]; National Institutes of Health FX The InCHIANTI Study was supported by the Italian Ministry of Health (ICS 1.10.1. RS97.71), by the U.S. National Institute on Aging (NIA; contracts N01-AG-916413, N01-AG-821336,263 MD 9164 13 and 263 MD 821336) and in part by the Intramural Research Program, NIA, National Institutes of Health. All authors with significant contributions have been listed. NR 25 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2009 VL 57 IS 9 BP 1672 EP 1677 DI 10.1111/j.1532-5415.2009.02426.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 492LQ UT WOS:000269659500021 PM 19694866 ER PT J AU Upadhyay, A Hwang, SJ Mitchell, GF Vasan, RS Vita, JA Stantchev, PI Meigs, JB Larson, MG Levy, D Benjamin, EJ Fox, CS AF Upadhyay, Ashish Hwang, Shih-Jen Mitchell, Gary F. Vasan, Ramachandran S. Vita, Joseph A. Stantchev, Plamen I. Meigs, James B. Larson, Martin G. Levy, Daniel Benjamin, Emelia J. Fox, Caroline S. TI Arterial Stiffness in Mild-to-Moderate CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; PULSE-WAVE VELOCITY; URINARY ALBUMIN EXCRETION; INCREASED AORTIC STIFFNESS; INTIMA-MEDIA THICKNESS; STAGE RENAL-DISEASE; SERUM CYSTATIN-C; ESSENTIAL-HYPERTENSION; SYSTOLIC HYPERTENSION AB Whether arterial stiffness correlates with mild-to-moderate CKD and albuminuria in the community is unclear. We studied the association between arterial stiffness and mild-to-moderate CKD and albuminuria in the Framingham Heart Study. CKD was present in 6.7% (181 of 2682) of participants and microalbuminuria was present in 8.2% (479 of 5818). The measures of arterial stiffness were the carotid femoral pulse wave velocity, forward pressure wave amplitude, central pulse pressure, augmentation pressure, augmentation index, and mean arterial pressure. In cross-sectional analyses, arterial stiffness did not associate with CKD (defined by estimated GFR <60 ml/min/1.73 m(2)) in either age- and gender-adjusted or multivariable-adjusted linear regression models. Carotid femoral pulse wave velocity associated with both urinary albumin-to-creatinine ratio and microalbuminuria (P < 0.0001 after multivariable adjustment). In longitudinal analyses, we used logistic regression models to examine the associations between baseline arterial stiffness measures (exposure variables) and incident CKD or microalbuminuria (n = 1675 for CKD analyses and n = 1252 for microalbuminuria analyses). Baseline arterial measures did not associate with incident CKD or incident microalbuminuria. In summary, arterial stiffness correlates with albuminuria but not with mild-to-moderate CKD. C1 [Hwang, Shih-Jen; Vasan, Ramachandran S.; Stantchev, Plamen I.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.; Fox, Caroline S.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA 01702 USA. [Upadhyay, Ashish] Boston Med Ctr, Renal Sect, Boston, MA USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Hwang, Shih-Jen; Vasan, Ramachandran S.; Stantchev, Plamen I.; Larson, Martin G.; Levy, Daniel; Benjamin, Emelia J.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA. [Vasan, Ramachandran S.; Vita, Joseph A.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Fox, CS (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Upadhyay, Ashish/0000-0002-0536-5776; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195, 2-K24HL04334]; National Institute of Health [R01-HL-077477, RO1-HL076784, RO1-AG028321, R01-HL70100, RO1-HL60040, RO1-HL080124]; American Diabetes Association research grant; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK080140] FX The Framingham Heart Study is supported by National Heart, Lung, and Blood Institute Grant N01-HC-25195. Additional funding provided by National Heart, Lung, and Blood Institute Grant 2-K24HL04334 and National Institute of Health Grant R01-HL-077477 to R.S.V., an American Diabetes Association research grant and National Institute of Diabetes and Digestive and Kidney Diseases Grant K24-DK080140 to J.B.M., and National Institute of Health Grants RO1-HL076784, RO1-AG028321, R01-HL70100, RO1-HL60040, and RO1-HL080124 to E.J.B. NR 53 TC 58 Z9 63 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2009 VL 20 IS 9 BP 2044 EP 2053 DI 10.1681/ASN.2009010074 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 499TL UT WOS:000270248700027 PM 19608701 ER PT J AU Huang, L Tiwari, RC Zou, ZH Kulldorff, M Feuer, EJ AF Huang, Lan Tiwari, Ram C. Zou, Zhaohui Kulldorff, Martin Feuer, Eric J. TI Weighted Normal Spatial Scan Statistic for Heterogeneous Population Data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Breast cancer mortality; Cluster detection; Continuous regional data; Geographic variation; Lung cancer survival; Weighted normal spatial scan statistic ID CANCER SURVIVAL; DISEASE; CLUSTERS; POINT; TESTS; MORTALITY; CHOICE; WOMEN; RATES; RISK AB In geographical spatial epidemiology and disease surveillance, all the existing spatial scan methods for cluster detection using continuous data are designed for evaluating clusters of individuals and analyzing individual-level data. Motivated by growing demands to study the spatial heterogeneity of continuous measures in population data, such as mortality rates, survival rates, average body mass indexes and pollution at state, county, and census tract levels. we propose a weighted normal scan statistic for investigating the clusters of the cells (geographic units such as counties) with unusual high/low continuous regional measures, where the weights reflect the uncertainty of the regional measures or sample size (number of observed cases) in the cells. Power, precision, the effect of the weights, and the sensitivity of the proposed test statistic to data from various distributions are investigated through intensive simulation. The method is applied to 1988-2002 stage I and II lung cancer survival data in Los Angeles County in order to search for clusters of geographic units with high/low survival rates in a short-term/long-term survival after diagnosis, and to 1999-2003 breast cancer age-adjusted mortality rate data in the U.S. collected by the Surveillance, Epidemiology and End Results (SEER) program in order to evaluate the clustering pattern of counties with high mortality rate, The proposed method is included in the latest release of the SaTScan software (www.satscan.org). C1 [Huang, Lan; Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Tiwari, Ram C.] US FDA, Off Biostat, CDER, Silver Spring, MD 20993 USA. [Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Kulldorff, Martin] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Kulldorff, Martin] Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. RP Huang, L (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. EM huangla@mail.nih.gov; ram.tiwari@fda.hhs.gov; zouj@imsweb.com; martin_kulldorff@hms.Harvard.edu; feuerr@mail.nih.gov RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 FU National Institute of Child Health and Human Development [R01 HD048852] FX Eric J. Feuer is Chief, Statistical Research and Applications Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD 20852 (E-mail: feuerr@mail.nih.gov). Most of Ram C. Tiwari's work was done while he was at the National Cancer Institute, NIH. The views expressed in this article do not necessarily represent those of the U.S. Food and Drug Administration, and of the National Cancer Institute. The authors wish to thank the editor, associate editor, and the referees for their valuable comments and suggestions. Kulldorff gratefully acknowledge the support of National Institute of Child Health and Human Development grant R01 HD048852. NR 42 TC 16 Z9 18 U1 2 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 886 EP 898 DI 10.1198/jasa.2009.ap07613 PG 13 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100002 ER PT J AU Shen, Y Ning, J Qin, J AF Shen, Yu Ning, Jing Qin, Jing TI Analyzing Length-Biased Data With Semiparametric Transformation and Accelerated Failure Time Models SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Accelerated failure time models; Estimating equation; Informative censoring; Length-biased sampling; Prevalent cohort; Right-censored data; Transformation models ID KAPLAN-MEIER STATISTICS; LARGE SAMPLE THEORY; LINEAR RANK-TESTS; CENSORED-DATA; NONPARAMETRIC-ESTIMATION; SURVIVAL-DATA; EMPIRICAL DISTRIBUTIONS; REGRESSION PARAMETERS; PREVALENT COHORT AB Right-censored time-to-event data are often observed from a cohort of prevalent cases that are subject to length-biased sampling. Informative right censoring of data from the prevalent cohort within the population often makes it difficult to model risk factors on the unbiased failure times for the general population. because the observed failure times are length biased. In this paper. we consider two classes of flexible semiparametric models: the transformation models and the accelerated failure time models, to assess covariate effects on the population failure times by modeling the length-biased times. We develop unbiased estimating equation approaches to obtain the consistent estimators of the regression coefficients. Large sample properties for the estimators are derived. The methods are confirmed through simulations and illustrated by application to data from a study of a prevalent cohort of dementia patients. C1 [Shen, Yu] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Qin, Jing] NIAID, Bethesda, MD 20817 USA. RP Shen, Y (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, Holcombe Blvd,Unit 1411, Houston, TX 77030 USA. EM yshen@mdanderson.org; jning@mdanderson.org; jingqin@niaid.nih.gov OI Shen, Yu/0000-0002-3899-7868 FU U.S. National Institute of Health [R01-CA079466]; National Health Research and Development Program of Health Canada [6606-3954-MC(S)]; Canada Health Activity Program; NHRDP [6603-1417-302(R)]; Bayer Incorporated; British Columbia Health Research Foundation [38 (93-2), 34 (96-1)] FX Yu Shen is Professor, Department of Biostatistics. M. D. Anderson Cancer Center. Holcombe Blvd, Unit 1411. Houston. TX 77030 (E-mail: yshen@ mdanderson.org). Jing Ning is Postdoctoral Fellow, Department of Biostatistics, M. D. Anderson Cancer Center, Holcombe Blvd, Unit 1411, Houston, TX 77030 (E-mail: jning@mdanderson.org). Jing Qin is, Mathematical Statistician, National Institution of Allergy and Infectious Diseases. Bethesda, MD 208 17 (E-mail: jingqin@niaid.nih.gov). This research was partially supported by the U.S. National Institute of Health grant R01-CA079466. We thank the editor. the associate editor, and three referees for their constructive suggestions that improved the article. We also thank Professor Masoud Asgharian and investigators of the Canadian Study of Health and Aging (CHSA) for providing us the dementia data from CHSA. The data reported in the example were collected as part of the CHSA. The core study was funded by the Seniors' Independence Research Program, through the National Health Research and Development Program of Health Canada [Project no. 6606-3954-MC(S)]. Additional funding was provided by Pfizer Canada Incorporated through the Medical Research Council/Pharmaceutical Manufacturers Association of Canada Health Activity Program, NHRDP Project 6603-1417-302(R), Bayer Incorporated, and the British Columbia Health Research Foundation Projects 38 (93-2) and 34 (96-1). The study was coordinated through the University of Ottawa and the Division of Aging and Seniors, Health Canada. NR 36 TC 39 Z9 41 U1 3 U2 8 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 1192 EP 1202 DI 10.1198/jasa.2009.tm08614 PG 11 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100031 PM 21057599 ER PT J AU Othus, M Li, Y Tiwari, RC AF Othus, Megan Li, Yi Tiwari, Ram C. TI A Class of Semiparametric Mixture Cure Survival Models With Dependent Censoring SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Estimating equation; Proportional hazards model; Proportional odds model; Right censoring; Transformation model ID COMPETING RISKS MODEL; PROSTATE-CANCER CELLS; SUFFICIENT FOLLOW-UP; TRANSFORMATION MODELS; REGRESSION-MODELS; FAILURE TIMES; IDENTIFIABILITY; PROBABILITY; CHOLESTEROL; DISEASE AB Modern cancer treatments have substantially improved cure rates and have generated a great interest in and need for proper statistical tools to analyze survival data with nonnegligible cure fractions. Data with Cure fractions often ire complicated by dependent censoring, and the analysis of this type of data typically involves untestable parametric assumptions on the dependence of the censoring mechanism and the true survival times. Motivated by the analysis of prostate cancer survival trends, we propose a class of semiparametric transformation cure models that allows for dependent censoring without making parametric assumptions on the dependence relationship. The proposed class of models encompasses a number of common models for the latency survival function, including the proportional hazards model and the proportional odds model, and also allows for time-dependent covariates. An inverse censoring probability reweighting scheme is used to derive unbiased estimating equations. Small-sample properties with simulations are derived, and the method is demonstrated with a data application. C1 [Othus, Megan; Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Othus, Megan; Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Othus, M (reprint author), Harvard Univ, Dept Biostat, Boston, MA 02115 USA. EM mothus@fas.harvard.edu; yili@jimmy.harvard.edu; ram.tiwari@fda.hhs.gov FU National Institutes of Health [CA09337-25, ES07142-24] FX Megan Othus is Graduate Student, Department of Biostatistics, Harvard University and Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: mothus@fas.harvard.edu). Yi Li is Associate Professor, Department of Biostatistics, Harvard University, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115 (E-mail: yili@jimmy.harvard.edu). Ram Tiwari is Associate Director for Statistical Science and Policy, Office of Biostatistics, Center for Drug Evaluation & Research, Food and Drug Administration, Silver Springs, MD 20993 (E-mail: ram.tiwari@fda.hhs.gov). The work of Tiwari was conducted while he was at the National Cancer Institute. The views expressed in this article are his own and do not necessarily represent those of the National Cancer Institue or the Food and Drug Administration. This work was supported in part by National Institutes of Health grants CA09337-25 and ES07142-24. The authors thank Eric (Rocky) Feuer and Angela Mariotto for their extensive and insightful comments on the manuscript. NR 61 TC 6 Z9 6 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2009 VL 104 IS 487 BP 1241 EP 1250 DI 10.1198/jasa.2009.tm08033 PG 10 WC Statistics & Probability SC Mathematics GA 508FX UT WOS:000270916100036 PM 20706564 ER PT J AU Simmons, WK Martin, A AF Simmons, W. Kyle Martin, Alex TI The anterior temporal lobes and the functional architecture of semantic memory SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE Knowledge; Concepts; Lesion; fMRI; PET; Prosopagnosias ID NEURAL SYSTEMS; PEOPLES NAMES; FACE; DEMENTIA; CORTEX; BRAIN; RECOGNITION; REPRESENTATION; RETRIEVAL; EPILEPSY AB Recently, three accounts have emerged on the role of the interior temporal lobes (ATLs) in semantic memory. One account claims that the ATLs are domain-general semantic hubs, another claims that they underlie knowledge Of unique entities specifically, and yet another account claims that they support social conceptual knowledge generally. Here, we review neuropsychological and neuroimaging Studies that bear on these three accounts and offer suggestions for future research to elucidate the roles of the ATLs in semantic memory. (JINS, 2009, 15, 645-649.) C1 [Simmons, W. Kyle; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Simmons, WK (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C-104,MSC 1366, Bethesda, MD 20892 USA. EM simmonswkyle@mail.nih.gov RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU NIMH-DIRP FX This work was supported by the NIMH-DIRP. NR 48 TC 89 Z9 90 U1 0 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 2009 VL 15 IS 5 BP 645 EP 649 DI 10.1017/S1355617709990348 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 489IZ UT WOS:000269415100001 PM 19631024 ER PT J AU Engstrom, PF AF Engstrom, Paul F. TI Discussing Colorectal Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Engstrom, Paul F.] Fox Chase Canc Ctr, Fox Chase Partners, Philadelphia, PA 19111 USA. [Engstrom, Paul F.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Engstrom, Paul F.] NCI, Board Sci Counselors, DCPC, Bethesda, MD 20892 USA. [Engstrom, Paul F.] Armed Forces Inst Pathol, Sci Advisory Board, Washington, DC 20306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD SEP PY 2009 VL 7 IS 8 BP 776 EP 776 PG 1 WC Oncology SC Oncology GA 501YR UT WOS:000270421100002 PM 19755045 ER PT J AU Leighl, NB Laurie, SA Chen, XYE Ellis, P Shepherd, FA Knox, JJ Goss, G Burkes, RL Pond, GR Dick, C Yun, Y Zwiebel, JA Moore, MJ AF Leighl, Natasha B. Laurie, Scott A. Chen, Xueyu E. Ellis, Peter Shepherd, Frances A. Knox, Jennifer J. Goss, Glenwood Burkes, Ronald L. Pond, Gregory R. Dick, Christopher Yun, Yun Zwiebel, James A. Moore, Malcolm J. TI A Phase I/II Study of GTI-2040 Plus Docetaxel as Second-Line Treatment in Advanced Non-small Cell Lung Cancer A Study of the PMH Phase II Consortium SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Antisense oligonucleotide; Lung cancer; Second-line; Docetaxel; GTI-2040; Ribonucleotide reductase; R2 subunit ID BCL-2 ANTISENSE OLIGONUCLEOTIDE; SOLID TUMORS; CHEMOTHERAPY; TRIAL; STRATEGIES; PLASMA; G3139 AB Introduction: GTI-2040, an antisense oligonucleotide, targets the ribonucleotide reductase R2 subunit, critical for DNA synthesis. This study determined the recommended phase 11 dose (RP2D) of docetaxel plus GTI-2040, toxicity, and response rate in advanced non-small cell lung cancer (NSCLC). Patients and Methods: Advanced solid tumor patients, preferably with platinum-treated NSCLC, performance status 0 to 2, no symptomatic central nervous system metastases, adequate organ and bone marrow function, and ! I prior chemotherapy regimen were treated with escalating doses of GTI-2040 given by 14-day continuous intravenous infusion (CVI) plus docetaxel every 21 days. Results: Twenty-nine patients were treated, (24 NSCLC, 3 hermone-refractory prostate cancer, I head and neck, and I small cell lung cancer). GTI-2040 5 mg/kg as CVI for 14 days plus docetaxel 75 mg/m(2) intravenously every 21 days was determined as the RP2D. Dose-limiting toxicity was not seen. Two patients at RP2D developed grade 4/5 febrile neutropenia. One prostate specific antigen response was seen in phase 1, but no objective tumor responses in the NSCLC patients. Median time to progression was 3.4 months, 3.2 months in the NSCLC patients treated at RP2D. Conclusions: Activity of the combination at RP2D, GTI-2040 5 mg/kg/d x 14 days by CVI plus docetaxel 75 mg/m(2) does not seem superior to docetaxel alone in previously treated NSCLC. C1 [Leighl, Natasha B.] Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M5G 2M9, Canada. [Leighl, Natasha B.; Laurie, Scott A.; Chen, Xueyu E.; Ellis, Peter; Shepherd, Frances A.; Knox, Jennifer J.; Goss, Glenwood; Burkes, Ronald L.; Pond, Gregory R.; Dick, Christopher; Moore, Malcolm J.] Princess Margaret Hosp, Phase Consortium 2, Toronto, ON M4X 1K9, Canada. [Laurie, Scott A.; Goss, Glenwood] Ottawa Hosp, Reg Canc Ctr, Ottawa, ON, Canada. [Ellis, Peter] Juravinski Canc Ctr, Hamilton, ON, Canada. [Burkes, Ronald L.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Pond, Gregory R.] McMaster Univ, Dept Biostat, Hamilton, ON, Canada. [Yun, Yun] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Zwiebel, James A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Leighl, NB (reprint author), Univ Toronto, Princess Margaret Hosp, Univ Hlth Network, 5-105 610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Natasha.Leighl@unh.on.ca FU NIH/NCI Phase 2 Consortium [N01-CM-17107] FX The authors thank the contribution of the patients who participated, as well as Dianne Zawisza, Jasmine Brown, Meri Klein, Pain Degendorfer, Nana Adjei, Beverly Gill (Princess Margaret Hospital.), Caroline Lalonde, Alison Irwin, Amy VandenEykel, Katherine Shay, Kara Lee (Ottawa Hospital Regional Cancer Center; Barbara Phillips, Brenda Kowalewski, Karen Infanti (Juravinski Cancer Center) for nursing and data management support. They also thank Lorus Therapeutics (including P. Murray, Y. Lee, A. Huang and J Wright).for thoughtful comments on the manuscript, and Dr. I. Espinoza-Delgado (Cancer Therapy Evaluation Program, National Cancer Institute). NR 21 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP 1163 EP 1169 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490IX UT WOS:000269495500016 PM 19704337 ER PT J AU Cappuzzo, F Coudert, B Wierzbicki, R Wu, YL Gonzalez, EE Davidson, N Giaccone, G Chang, JH Klingelschmitt, G Ciuleanu, TE AF Cappuzzo, Federico Coudert, Bruno Wierzbicki, Rafal Wu Yi-Long Gonzalez, Emilio E. Davidson, Neville Giaccone, Giuseppe Chang, Jian H. Klingelschmitt, Gaelle Ciuleanu, Tudor E. CA SATURN Investigators TI Efficacy and safety of erlotinib as first-line maintenance in NSCLC following non-progression with chemotherapy: results from the phase III SATURN study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Cappuzzo, Federico] IRCCS, Ist Clin Humanitas, Rozzano, Italy. [Coudert, Bruno] Ctr GF Leclerc, Dijon, France. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Wu Yi-Long] Guangdong Gen Hosp, Guangzhou, Guangdong, Peoples R China. [Davidson, Neville] Broomfield Hosp, Chelmsford, Essex, England. [Gonzalez, Emilio E.] Hosp Univ Cent Asturias, Oviedo, Spain. [Chang, Jian H.] Fudan Univ, Tumor Hosp, Shanghai 200433, Peoples R China. [Klingelschmitt, Gaelle] F Hoffmann La Roche Ltd, Basel, Switzerland. [Ciuleanu, Tudor E.] Inst Oncol, Cluj Napoca, Romania. RI Ciuleanu, Tudor Eliade/C-3996-2011 NR 0 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S289 EP S289 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000287 ER PT J AU Dennis, P AF Dennis, Phillip TI Targeting mTOR for lung cancer prevention SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Dennis, Phillip] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S136 EP S136 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000127 ER PT J AU Giaccone, G Rajan, A Carter, CA Kelly, RJ Berman, A Trepel, J Lee, MJ Espinoza-Delgado, I Spittler, J Loehrer, PJ AF Giaccone, Giuseppe Rajan, Arun Carter, Corey A. Kelly, Ronan J. Berman, Arlene Trepel, Jane Lee, Min J. Espinoza-Delgado, Igor Spittler, John Loehrer, Patrick J. TI Phase II study of the Histone Deacetylase (HDAC) Inhibitor Belinostat in thymic malignancies SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Giaccone, Giuseppe; Rajan, Arun; Carter, Corey A.; Kelly, Ronan J.; Berman, Arlene; Trepel, Jane; Lee, Min J.; Espinoza-Delgado, Igor] NCI, NIH, Bethesda, MD 20892 USA. [Spittler, John; Loehrer, Patrick J.] Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S758 EP S759 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002318 ER PT J AU Hunsberger, S AF Hunsberger, Sally TI Dose escalation trials based on a molecularly targeted endpoint SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Hunsberger, Sally] NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S75 EP S76 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000071 ER PT J AU Jackman, DM Miller, VA Cioffredi, LA Yeap, BY Janne, PA Riely, GJ Ruiz, MG Giaccone, G Sequist, LV Johnson, BE AF Jackman, David M. Miller, Vincent A. Cioffredi, Leigh-Anne Yeap, Beow Y. Janne, Pasi A. Riely, Gregory J. Ruiz, Gallegos Marielle Giaccone, Giuseppe Sequist, Lecia, V Johnson, Bruce E. TI Impact of EGFR and KRAS mutations on clinical outcomes in previously untreated patients with advanced NSCLC treated with gefitinib or erlotinib: results of an online tumor registry of clinical trials SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Jackman, David M.; Cioffredi, Leigh-Anne; Janne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, Vincent A.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yeap, Beow Y.; Sequist, Lecia, V] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ruiz, Gallegos Marielle] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S349 EP S350 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001075 ER PT J AU Janne, PA Reckamp, K Koczywas, M Camidge, DR Engelman, JA Khuri, F Rajan, A Gadgeel, S Taylor, I Liang, J O'Connell, J Giaccone, G AF Janne, Pasi A. Reckamp, Karen Koczywas, Marianna Camidge, David R. Engelman, Jeffery A. Khuri, Fadlo Rajan, Arun Gadgeel, Shirish Taylor, Ian Liang, Jane O'Connell, Joseph Giaccone, Giuseppe TI A phase 2 trial of PF-00299804 (PF299), an oral irreversible HER tyrosine kinase inhibitor (TKI), in patients (pts) with advanced NSCLC after failure of prior chemotherapy and erlotinib: preliminary efficacy and safety results SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Taylor, Ian; Liang, Jane; O'Connell, Joseph] Pfizer Global Res & Dev, New London, CT USA. [Janne, Pasi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Reckamp, Karen; Koczywas, Marianna] City Hope Natl Med Ctr, Duarte, CA USA. [Engelman, Jeffery A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Camidge, David R.] Univ Colorado, Ctr Canc, Aurora, CO USA. [Rajan, Arun; Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Khuri, Fadlo] Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. [Gadgeel, Shirish] Karmanos Canc Inst, Troy, MI USA. NR 0 TC 12 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S293 EP S294 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000294 ER PT J AU Kitano, H Chung, JY Ylaya, K Takikita, M Fukuoka, J Tezuka, N Hewitt, SM AF Kitano, Haruhisa Chung, Joon-Yong Ylaya, Kris Takikita, Mikiko Fukuoka, Junya Tezuka, Noriaki Hewitt, Stephen M. TI The combination of phospho-AKT, phospho-MTOR, phospho-MAPK and EGFR predicts survival in non-small cell lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Kitano, Haruhisa; Tezuka, Noriaki] Shiga Univ Med Sci, Dept Thorac Surg, Shiga, Japan. [Chung, Joon-Yong; Ylaya, Kris; Takikita, Mikiko; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Fukuoka, Junya] Toyama Univ Hosp, Pathol Lab, Toyama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S485 EP S485 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001336 ER PT J AU Kucuk, O Pass, H Lonardo, F Gazdar, A Madan, S Abrams, J Maddipati, KR Upfal, M Soubani, AO Honn, K Szabo, E AF Kucuk, Omer Pass, Harvey Lonardo, F. Gazdar, Adi Madan, S. Abrams, J. Maddipati, K. R. Upfal, M. Soubani, Ayman O. Honn, K. Szabo, E. TI Phase II clinical trial of zileuton in persons with bronchial dysplasia SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. NYU, Sch Med, New York, NY USA. NYU, Ctr Canc, New York, NY USA. UT SW Hamon Canc Ctr, Dallas, TX USA. NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S137 EP S137 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000128 ER PT J AU Linnoila, I AF Linnoila, Ilona TI Advances in mouse models of lung cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract ID A/J MICE; DIFFERENTIATION; CARCINOGENESIS; TUMORIGENESIS; TUMORS; SMOKE C1 [Linnoila, Ilona] NCI, NIH, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S125 EP S127 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496000117 ER PT J AU Mencoboni, M Bruzzone, A Figliomeni, M Racchi, O Migliazzi, L Cioe, A Mortara, V Marroni, P Serra, M Bergaglio, M Filiberti, R Spigno, F AF Mencoboni, Manlio Bruzzone, Andrea Figliomeni, Mirna Racchi, Omar Migliazzi, Luca Cioe, Alex Mortara, Virginia Marroni, Paola Serra, Maria Bergaglio, Marina Filiberti, Rosangela Spigno, Fabio TI Correlation between serum mesothelin related proteins and quantitative exposure to asbestos in occupationally exposed to asbestos: an exploratory preliminary analysis SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Mencoboni, Manlio; Figliomeni, Mirna; Racchi, Omar; Serra, Maria; Bergaglio, Marina] Villa Scassi Hosp, Genoa, Italy. [Bruzzone, Andrea] Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. [Migliazzi, Luca; Cioe, Alex; Spigno, Fabio] Univ Genoa, Dept Occupat Med, I-16126 Genoa, Italy. [Mortara, Virginia] INAIL Natl Inst Safe Work, Genoa, Italy. [Marroni, Paola; Filiberti, Rosangela] Natl Canc Inst, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S769 EP S770 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496002342 ER PT J AU Molina, JR Foster, NR Nelson, GD Ger, AVG Steen, PD Nikcevich, DA Schild, SE Wright, J Adjei, AA AF Molina, Julian R. Foster, Nathan R. Nelson, Garth D. Ger, Grain Andrew, V Steen, Preston D. Nikcevich, Daniel A. Schild, Steven E. Wright, John Adjei, Alex A. TI Phase II trial (N0621) of the c-Src inhibitor AZD-0530 after 4 cycles of chemotherapy for patients with extensive stage small cell lung cancer (ED-SCLC) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Molina, Julian R.; Foster, Nathan R.; Nelson, Garth D.] Mayo Clin, Rochester, MN USA. [Ger, Grain Andrew, V] Columbus Oncol & Hematol Associates, Columbus, OH USA. [Steen, Preston D.] MeritCare Hosp CCOP, Fargo, ND USA. [Nikcevich, Daniel A.] Duluth Clin, Duluth, MN USA. [Schild, Steven E.] Mayo Clin, Scottsdale, AZ USA. [Wright, John] NCI, Bethesda, MD 20892 USA. [Adjei, Alex A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S465 EP S465 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001293 ER PT J AU Molina, JR Mandrekar, SJ Ziegler, KLA Soori, GS Rowland, KM Schild, SE Ivy, P Adjei, AA AF Molina, Julian R. Mandrekar, Sumithra J. Ziegler, Allen Katie L. Soori, Gamini S. Rowland, Kendrith M. Schild, Steven E. Ivy, Percy Adjei, Alex A. TI A phase II study of the VEGFR inhibitor pazopanib (P) in patients with newly diagnosed or relapsed malignant pleural mesothelioma (MPM): an NCCTG study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Molina, Julian R.; Mandrekar, Sumithra J.; Ziegler, Allen Katie L.] Mayo Clin, Rochester, MN USA. [Soori, Gamini S.] Missouri Valley Canc Consortium CCOP, Omaha, NE USA. [Rowland, Kendrith M.] Carle Canc Ctr, Urbana, IL USA. [Schild, Steven E.] Mayo Clin, Scottsdale, AZ USA. [Ivy, Percy] NCI, Canc Therapy Evaluat Program, Rockville, MD USA. [Adjei, Alex A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S456 EP S456 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001277 ER PT J AU Rajan, A Carter, CA Gutierrez, M Kummar, S Yancey, MA Ji, JP Zhang, YP Simmons, D Parchment, R Tomaszewski, J Doroshow, JH Giaccone, G AF Rajan, Arun Carter, Corey A. Gutierrez, Martin Kummar, Shivaani Yancey, Mary Ann Ji Jiuping Zhang Yiping Simmons, Dwight Parchment, Ralph Tomaszewski, Joseph Doroshow, James H. Giaccone, Giuseppe TI A phase I combination study of olaparib (AZD2281; KU-0059436) and cisplatin plus gemcitabine in adults with solid tumors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Rajan, Arun; Carter, Corey A.; Gutierrez, Martin; Kummar, Shivaani; Yancey, Mary Ann; Ji Jiuping; Zhang Yiping; Simmons, Dwight; Parchment, Ralph; Tomaszewski, Joseph; Doroshow, James H.; Giaccone, Giuseppe] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S598 EP S599 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001563 ER PT J AU Ramalingam, SS Maitland, M Frankel, P Argiris, A Thomas, S Gitlitz, B Koczywas, M Espinoza-Delgado, I Vokes, EE Gandara, DR Belani, CP AF Ramalingam, Suresh S. Maitland, Michael Frankel, Paul Argiris, Athanassios Thomas, Sachdev Gitlitz, Barbara Koczywas, Marianna Espinoza-Delgado, Igor Vokes, Everett E. Gandara, David R. Belani, Chandra P. TI Randomized, double-blind, phase II study of carboplatin and paclitaxel with either vorinostat, a histone deacetylase inhibitor (HDAC), or placebo for first line therapy of advanced non-small cell lung cancer (NCI 7863) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Argiris, Athanassios] Univ Pittsburgh, Pittsburgh, PA USA. [Maitland, Michael; Thomas, Sachdev; Vokes, Everett E.] Illinois Oncol Res Assoc, Peoria, IL USA. [Frankel, Paul; Koczywas, Marianna] City Hope Canc Ctr, Duarte, CA USA. [Gitlitz, Barbara] Univ So Calif, Los Angeles, CA USA. [Espinoza-Delgado, Igor] NCI, Bethesda, MD 20892 USA. [Gandara, David R.] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. [Belani, Chandra P.] Penn State Univ, Hershey, PA USA. [Ramalingam, Suresh S.] Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S382 EP S383 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001136 ER PT J AU Simone, CB Vapiwala, N Hampshire, MK Metz, JM AF Simone, Charles B. Vapiwala, Neha Hampshire, Margaret K. Metz, James M. TI The utilization of pain medications and the attitudes of lung cancer patients towards pain intervention SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Simone, Charles B.] NCI, NIH, Bethesda, MD 20892 USA. [Simone, Charles B.; Vapiwala, Neha; Hampshire, Margaret K.; Metz, James M.] Hosp Univ Penn, Philadelphia, PA 19104 USA. RI Vapiwala, Neha/A-5445-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S433 EP S434 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001230 ER PT J AU Zucali, PA Giovannetti, E Peters, G Cortesi, F D'Incecco, A Smit, E Falcone, A Burgers, S Santoro, A Danesi, R Giaccone, G Tibaldi, C AF Zucali, Paolo A. Giovannetti, Elisa Peters, Godefridus Cortesi, Filippo D'Incecco, Armida Smit, Egbert Falcone, Alfredo Burgers, Sjaak Santoro, Armando Danesi, Romano Giaccone, Giuseppe Tibaldi, Carmelo TI Association of polymorphisms in AKT1 and EGFR with clinical outcome and toxicity in non-small cell lung cancer patients treated with gefitinib SO JOURNAL OF THORACIC ONCOLOGY LA English DT Meeting Abstract C1 [Zucali, Paolo A.; Santoro, Armando] Ist Clin Humanitas, Rozzano, MI USA. [Giovannetti, Elisa; Peters, Godefridus; Cortesi, Filippo; Smit, Egbert] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [D'Incecco, Armida; Tibaldi, Carmelo] Azienda USL 6 Livorno, Livorno, Italy. [Falcone, Alfredo; Danesi, Romano] Univ Pisa, Pisa, Italy. [Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. [Burgers, Sjaak] Nederlands Kanker Inst, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2009 VL 4 IS 9 BP S510 EP S510 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 490JC UT WOS:000269496001383 ER PT J AU Sarin, H AF Sarin, Hemant TI Recent progress towards development of effective systemic chemotherapy for the treatment of malignant brain tumors SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; PHASE-II TRIAL; POLY(BUTYL CYANOACRYLATE) NANOPARTICLES; DIAGNOSED GLIOBLASTOMA-MULTIFORME; BORONATED MONOCLONAL-ANTIBODIES; NEUTRON-CAPTURE THERAPY; EPIDERMAL-GROWTH-FACTOR; STEM-CELL RESCUE; BLOOD-BRAIN; DRUG-DELIVERY AB Systemic chemotherapy has been relatively ineffective in the treatment of malignant brain tumors even though systemic chemotherapy drugs are small molecules that can readily extravasate across the porous blood-brain tumor barrier of malignant brain tumor microvasculature. Small molecule systemic chemotherapy drugs maintain peak blood concentrations for only minutes, and therefore, do not accumulate to therapeutic concentrations within individual brain tumor cells. The physiologic upper limit of pore size in the blood-brain tumor barrier of malignant brain tumor microvasculature is approximately 12 nanometers. Spherical nanoparticles ranging between 7 nm and 10 nm in diameter maintain peak blood concentrations for several hours and are sufficiently smaller than the 12 nm physiologic upper limit of pore size in the blood-brain tumor barrier to accumulate to therapeutic concentrations within individual brain tumor cells. Therefore, nanoparticles bearing chemotherapy that are within the 7 to 10 nm size range can be used to deliver therapeutic concentrations of small molecule chemotherapy drugs across the blood-brain tumor barrier into individual brain tumor cells. The initial therapeutic efficacy of the Gd-G5-doxorubicin dendrimer, an imageable nanoparticle bearing chemotherapy within the 7 to 10 nm size range, has been demonstrated in the orthotopic RG-2 rodent malignant glioma model. Herein I discuss this novel strategy to improve the effectiveness of systemic chemotherapy for the treatment of malignant brain tumors and the therapeutic implications thereof. C1 Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Sarin, H (reprint author), Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. EM sarinh@mail.nih.gov FU National Institute of Biomedical Imaging and Bioengineering; Clinical Center Radiology and Imaging Sciences Program FX This study was funded by the National Institute of Biomedical Imaging and Bioengineering, and the Clinical Center Radiology and Imaging Sciences Program. The synthesis and preliminary characterization of the functionalized dendrimers was performed by the Imaging Probe Development Center of the National Heart, Lung, and Blood Institute. The in vitro characterization of the functionalized dendrimers was performed by the Laboratory of Cell Biology of the National Cancer Institute. NR 137 TC 29 Z9 29 U1 1 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD SEP 1 PY 2009 VL 7 AR 77 DI 10.1186/1479-5876-7-77 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495DQ UT WOS:000269870900001 PM 19723323 ER PT J AU Russell, RS Kawaguchi, K Meunier, JC Takikawa, S Faulk, K Bukh, J Purcell, RH Emerson, SU AF Russell, R. S. Kawaguchi, K. Meunier, J. -C. Takikawa, S. Faulk, K. Bukh, J. Purcell, R. H. Emerson, S. U. TI Mutational analysis of the hepatitis C virus E1 glycoprotein in retroviral pseudoparticles and cell-culture-derived H77/JFH1 chimeric infectious virus particles SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE glycoprotein; glycosylation; HCV entry; HCVcc; HCVpp; hepatitis C virus ID MEMBRANE-FUSION PROTEINS; LARGE EXTRACELLULAR LOOP; E2 GLYCOPROTEIN; ENVELOPE GLYCOPROTEINS; TRANSMEMBRANE DOMAIN; CD81; BINDING; RESIDUES; PEPTIDE; ENTRY AB Cell entry by enveloped viruses is mediated by viral glycoproteins, and generally involves a short hydrophobic peptide (fusion peptide) that inserts into the cellular membrane. An internal hydrophobic domain within E1 (aa262-290) of hepatitis C virus (HCV) may function as a fusion peptide. Retrovirus-based HCV-pseudotyped viruses (HCVpp; genotype 1a) containing Ala or Pro substitutions at conserved amino acid positions within this putative fusion peptide were generated. Mutation of conserved residues significantly reduced efficiency of HCVpp entry into Huh-7 cells. The majority of amino acid substitutions appeared to disrupt necessary interactions between E1 and E2. For some mutants, reductions in HCVpp-associated E1 were associated with the incorporation of a high molecular weight, hyperglycosylated E2 that displayed decreased CD81-binding. Other entry-deficient mutants displayed normal E1E2 incorporation into pseudoparticles and normal CD81-binding, and therefore might affect viral fusion. One mutant (S283P) consistently displayed two- to threefold higher infectivity than did wild-type. Three mutations that decreased HCVpp infectivity also reduced levels of HCVcc infectious virus production. However, the S283P mutation had a different effect in the two systems as it did not increase production of infectious HCVcc. This comprehensive mutational analysis of the putative HCV fusion peptide provides insight into the role of E1 in its interaction with E2 and in HCV entry. C1 [Russell, R. S.; Kawaguchi, K.; Meunier, J. -C.; Takikawa, S.; Faulk, K.; Bukh, J.; Purcell, R. H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Bukh, J.] Copenhagen Univ Hosp, Dept Infect Dis, Hvidovre, Denmark. [Bukh, J.] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Fac Hlth Sci, Copenhagen, Denmark. [Emerson, S. U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Russell, RS (reprint author), Mem Univ Newfoundland, Fac Med, Immunol & Infect Dis Program, Rm H1815,300 Prince Philip Dr, St John, NF A1B 3V6, Canada. EM rodney.russell@med.mun.ca FU National Institutes of Health; National Institute of Allergy and Infectious Diseases; Canadian Institutes of Health Research FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. RSR was a recipient of a Fellowship from the Canadian Institutes of Health Research. The authors thank Judith Graff for frequent discussion of results and Jane Mirro from Alan Rein's lab (NCI-Frederick, USA) for antibodies and advice regarding anti-MLV Gag Western blotting. The authors are grateful to Birke Bartosch and Francois-Loic Cosset (Ecole Normale Superieure de Lyon, France) for plasmids used in the HCVpp system, as well as Harry Greenberg (Stanford University, USA) for providing the A4 monoclonal antibody and Shoshana Levy (Stanford University, USA) for bacteria-expressing GST-CD81 fusion proteins. We especially want to thank Mario Barro (NIH, USA) for valuable assistance in the setup of the GST-CD81 fusion protein expression/purification and binding assays. The HJ3/QL infectious clone was a gift from Stan Lemon (University of Texas Medical Branch, USA). Huh-7.5 cells were a gift from Charles Rice (Rockefeller University, USA). NR 58 TC 18 Z9 19 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD SEP PY 2009 VL 16 IS 9 BP 621 EP 632 DI 10.1111/j.1365-2893.2009.01111.x PG 12 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 483SF UT WOS:000268987500003 PM 19302336 ER PT J AU Hansen, N Obel, N Christensen, PB Krarup, H Laursen, AL Clausen, MR Lunding, S Moller, A Schlichting, P Kromann-Andersen, H Bukh, J Weis, N AF Hansen, N. Obel, N. Christensen, P. B. Krarup, H. Laursen, A. L. Clausen, M. R. Lunding, S. Moller, A. Schlichting, P. Kromann-Andersen, H. Bukh, J. Weis, N. CA DANHEP Grp TI Predictors of antiviral treatment initiation in hepatitis C virus-infected patients: a Danish cohort study SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE antiviral therapy; chronic hepatitis C; cohort study; genotype; predictors; treatment initiation ID PLUS RIBAVIRIN; MANAGEMENT; DRUGS AB Predictive factors for initiation of antiviral therapy in chronically infected hepatitis C virus (HCV) patients are not fully elucidated. The aim of this study was to determine predictive factors for initiation of treatment with standard or pegylated interferon either alone or combined with ribavirin. A Danish cohort of individuals chronically infected with HCV was used and observation time was calculated from the date of inclusion in the cohort to date of death, last clinical observation, 1 January 2007, or start of HCV antiviral treatment in treatment-naive patients. Kaplan-Meier survival analysis was used to construct time to event curves. Cox regression was used to determine the incidence rate ratios as estimates of relative risk (RR) and 95% confidence intervals (CI). A total of 1780 patients were enrolled in the study. The cumulative chance of treatment initiation over 5 years was 33.0%. We found several strong predictors of treatment initiation: elevated alanine aminotransferase [> 2 times upper limit (RR = 2.17, 95% CI 1.64-2.87), > 3 times upper limit (RR = 3.64, 95% CI 2.75-4.81)], genotype 2 or 3 (RR = 1.86, 95% CI 1.49-2.31) and HIV co-infection (RR = 0.28, 95% CI 0.15-0.53). To our knowledge, this study is the first to estimate factors predicting initiation of antiviral treatment in patients with chronic HCV infection on a nationwide scale. We found that several of the factors predicting initiation of antiviral treatment correlate with factors known to predict a better response to treatment and factors known to increase the progression of liver disease. C1 [Obel, N.; Weis, N.] Copenhagen Univ Hosp, Dept Infect Dis, Rigshosp, DK-2650 Hvidovre, Denmark. [Christensen, P. B.] Odense Univ Hosp, Dept Infect Dis, Odense, Denmark. [Krarup, H.] Aalborg Univ Hosp, Unit Mol Diagnost, Dept Gastroenterol, Aalborg, Denmark. [Krarup, H.] Aalborg Univ Hosp, Unit Mol Diagnost, Dept Clin Biochem, Aalborg, Denmark. [Laursen, A. L.] Skejby Univ Hosp, Dept Infect Dis, Skejby, Denmark. [Clausen, M. R.] Copenhagen Univ Hosp, Dept Hepatol, Rigshosp, DK-2650 Hvidovre, Denmark. [Lunding, S.] Helsingoer Hosp, Dept Internal Med, Helsingoer, Denmark. [Moller, A.] Kolding Cty Hosp, Dept Internal Med, Kolding, Denmark. [Schlichting, P.] Herlev Univ Hosp, Dept Gastroenterol, DK-2730 Herlev, Denmark. [Kromann-Andersen, H.] Koege Hosp, Dept Internal Med, Koege, Denmark. [Bukh, J.] Copenhagen Univ Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis, DK-2650 Hvidovre, Denmark. [Bukh, J.] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark. [Bukh, J.] Univ Copenhagen, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Bukh, J.] NIAID, Hepatitis Viruses Sect, LID, NIH, Bethesda, MD 20892 USA. RP Weis, N (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Rigshosp, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. EM ninaweis@dadlnet.dk RI Christensen, Peer/B-8042-2015; OI Schaffalitzky de Muckadell, Ove B/0000-0003-1969-2329 NR 21 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD SEP PY 2009 VL 16 IS 9 BP 659 EP 665 DI 10.1111/j.1365-2893.2009.01126.x PG 7 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 483SF UT WOS:000268987500007 PM 19486467 ER PT J AU Kassa, A Madani, N Schon, A Haim, H Finzi, A Xiang, SH Wang, LP Princiotto, A Pancera, M Courter, J Smith, AB Freire, E Kwong, PD Sodroski, J AF Kassa, Aemro Madani, Navid Schoen, Arne Haim, Hillel Finzi, Andres Xiang, Shi-Hua Wang, Liping Princiotto, Amy Pancera, Marie Courter, Joel Smith, Amos B., III Freire, Ernesto Kwong, Peter D. Sodroski, Joseph TI Transitions to and from the CD4-Bound Conformation Are Modulated by a Single-Residue Change in the Human Immunodeficiency Virus Type 1 gp120 Inner Domain SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN MONOCLONAL-ANTIBODY; VIRAL ENVELOPE GLYCOPROTEINS; HUMAN CELL-LINES; SOLUBLE CD4; HIV-1 GP120; CHEMOKINE RECEPTOR; NEUTRALIZATION SENSITIVITY; CYTOPLASMIC DOMAIN; VARIABLE REGIONS; RHESUS-MONKEYS AB Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the probability of CD4-induced inactivation and revealing the enhancing effects of soluble CD4 binding on HIV-1 infection. In the CD4-bound conformation, the highly conserved histidine 66 is located between the receptor-binding and gp41-interactive surfaces of gp120. Thus, a single amino acid change in this strategically positioned gp120 inner domain residue influences the propensity of the HIV-1 envelope glycoproteins to negotiate conformational transitions to and from the CD4-bound state. C1 [Kassa, Aemro; Madani, Navid; Haim, Hillel; Finzi, Andres; Xiang, Shi-Hua; Wang, Liping; Princiotto, Amy; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Schoen, Arne; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Pancera, Marie; Kwong, Peter D.] NIAID, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Courter, Joel; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst,Dept Pathol,Div AIDS, Ctr Life Sci Bldg,Room 1009,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIH [AI24755, AI39420, AI40895]; Center for HIV/AIDS Vaccine Immunology [AI67854]; Center for AIDS Research [AI42848]; Bristol- Myers Squibb Foundation; International AIDS Vaccine Initiative FX This work was supported by NIH grants (AI24755, AI39420, and AI40895), by a Center for HIV/AIDS Vaccine Immunology grant (AI67854), by a Center for AIDS Research grant (AI42848), by an unrestricted research grant from the Bristol- Myers Squibb Foundation, by a gift from the late William F. McCarty- Cooper, and by funds from the International AIDS Vaccine Initiative. NR 103 TC 32 Z9 32 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8364 EP 8378 DI 10.1128/JVI.00594-09 PG 15 WC Virology SC Virology GA 485LF UT WOS:000269122300006 PM 19535453 ER PT J AU Satheshkumar, PS Weisberg, A Moss, B AF Satheshkumar, P. S. Weisberg, Andrea Moss, Bernard TI Vaccinia Virus H7 Protein Contributes to the Formation of Crescent Membrane Precursors of Immature Virions SO JOURNAL OF VIROLOGY LA English DT Article ID GOLGI INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; INITIATE MORPHOGENESIS; ESSENTIAL COMPONENT; A14 PHOSPHOPROTEIN; GENE ENCODES; F10 KINASE; EARLY STEP; TEMPERATURE; STAGE AB Crescent membranes are the first viral structures that can be discerned during poxvirus morphogenesis. The crescents consist of a lipoprotein membrane and an outer lattice scaffold, which provides uniform curvature. Relatively little is known regarding the composition of the crescent membrane or its mode of formation. Here, we show that the H7 protein, which is conserved in all vertebrate poxviruses but has no discernible functional motifs or nonpoxvirus homologs, contributes to the formation of crescents and immature virions. Synthesis of the 17-kDa H7 protein was dependent on DNA replication and occurred late during vaccinia virus infection. Unlike many late proteins, however, H7 was not incorporated into mature virions or localized in cellular organelles. To gain insight into the role of H7, an inducible mutant was constructed and shown to have a conditional lethal phenotype: H7 expression and infectious virus formation were dependent on isopropyl-beta-D-thiogalactopyranoside. In the absence of inducer, viral late proteins were made, but membrane and core proteins were not processed by the I7 protease. A block in morphogenesis was demonstrated by transmission electron microscopy: neither typical crescents nor immature virions were detected in the absence of inducer. Instead, factory areas of the cytoplasm contained large, electron-dense inclusions, some of which had partially coated membrane segments at their surfaces. Separate, lower-density inclusions containing the D13 scaffold protein and endoplasmic reticulum membranes were also present. These features are most similar to those previously seen when expression of A11, another conserved nonvirion protein, is repressed. C1 [Satheshkumar, P. S.; Weisberg, Andrea; Moss, Bernard] NIAID, Viral Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, Natl Inst Hlth, 33 N Dr,MSC 3210, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Division of Intramural Research of the NIAID, National Institutes of Health FX The research was supported by the Division of Intramural Research of the NIAID, National Institutes of Health. NR 42 TC 17 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8439 EP 8450 DI 10.1128/JVI.00877-09 PG 12 WC Virology SC Virology GA 485LF UT WOS:000269122300012 PM 19553304 ER PT J AU Delviks-Frankenberry, KA Nikolenko, GN Maldarelli, F Hase, S Takebe, Y Pathak, VK AF Delviks-Frankenberry, Krista A. Nikolenko, Galina N. Maldarelli, Frank Hase, Saiki Takebe, Yutaka Pathak, Vinay K. TI Subtype-Specific Differences in the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Connection Subdomain of CRF01_AE Are Associated with Higher Levels of Resistance to 3 '-Azido-3 '-Deoxythymidine SO JOURNAL OF VIROLOGY LA English DT Article ID CIRCULATING RECOMBINANT FORM; LENGTH SEQUENCE-ANALYSIS; INJECTING DRUG-USERS; RNASE-H DOMAINS; KUALA-LUMPUR; HIV TYPE-1; MOLECULAR EPIDEMIOLOGY; RISK POPULATIONS; DUAL RESISTANCE; DNA-SYNTHESIS AB We previously shown that mutations in the connection (CN) subdomain of human immunodeficiency virus type 1 (HIV-1) subtype B reverse transcriptase (RT) increase 3'-azido-3'-deoxythymidine (AZT) resistance in the context of thymidine analog mutations (TAMs) by affecting the balance between polymerization and RNase H activity. To determine whether this balance affects drug resistance in other HIV-1 subtypes, recombinant subtype CRF01_AE was analyzed. Interestingly, CRF01_AE containing TAMs exhibited 64-fold higher AZT resistance relative to wild-type B, whereas AZT resistance of subtype B containing the same TAMs was 13-fold higher, which in turn correlated with higher levels of AZT-monophosphate (AZTMP) excision on both RNA and DNA templates. The high level of AZT resistance exhibited by CRF01_AE was primarily associated with the T400 residue in wild-type subtype AE CN subdomain. An A400T substitution in subtype B enhanced AZT resistance, increased AZTMP excision on both RNA and DNA templates, and reduced RNase H cleavage. Replacing the T400 residue in CRF01_AE with alanine restored AZT sensitivity and reduced AZTMP excision on both RNA and DNA templates, suggesting that the T400 residue increases AZT resistance in CRF01_AE at least in part by directly increasing the efficiency of AZTMP excision. These results show for the first time that CRF01_AE exhibits higher levels of AZT resistance in the presence of TAMs and that this resistance is primarily associated with T400. Our results also show that mixing the RT polymerase, CN, and RNase H domains from different subtypes can underestimate AZT resistance levels, and they emphasize the need to develop subtype-specific genotypic and phenotypic assays to provide more accurate estimates of clinical drug resistance. C1 [Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA. [Maldarelli, Frank] NCI, HIV Drug Resistance Program, Host Virus Interact Branch, Frederick, MD 21702 USA. [Hase, Saiki; Takebe, Yutaka] Natl Inst Infect Dis, AIDS Res Ctr, Lab Mol Virol & Epidemiol, Tokyo, Japan. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Viral Mutat Sect, Bldg 535,Room 334, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov RI Delviks-Frankenberry, Krista/M-4822-2013 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Center for Cancer Research; Intramural AIDS Targeted Antiviral Program FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and the Intramural AIDS Targeted Antiviral Program. NR 47 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8502 EP 8513 DI 10.1128/JVI.00859-09 PG 12 WC Virology SC Virology GA 485LF UT WOS:000269122300018 PM 19553318 ER PT J AU Iyer, SR Yu, DY Biancotto, A Margolis, LB Wu, YT AF Iyer, Subashini R. Yu, Dongyang Biancotto, Angelique Margolis, Leonid B. Wu, Yuntao TI Measurement of Human Immunodeficiency Virus Type 1 Preintegration Transcription by Using Rev-Dependent Rev-CEM Cells Reveals a Sizable Transcribing DNA Population Comparable to That from Proviral Templates SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS MOLECULAR CLONE; UNINTEGRATED HIV-1 DNA; MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; LENTIVIRAL VECTORS; GENE-EXPRESSION; IN-VITRO; RETROVIRUS INTEGRATION; QUANTITATIVE ASSAY; VIRAL REPLICATION AB Preintegration transcription is an early process in human immunodeficiency virus type 1 infection and has been suggested to occur at a low level. The templates have also been suggested to represent a small population of nonintegrated viral DNA, particularly the two-long-terminal-repeat (2-LTR) circles. However, these determinations were made by either using PCR amplification of viral transcripts in bulk cell populations or utilizing the LTR-driving reporter cells that measure the synthesis of Tat. The intrinsic leakiness of LTR often makes the measurement of low-level viral transcription inaccurate. Since preintegration transcription also generates Rev, to eliminate the nonspecificity associated with the use of LTR alone we have developed a novel Rev-dependent indicator cell, Rev-CEM, to measure preintegration transcription based on the amount of Rev generated. In this report, using Rev-CEM cells, we demonstrate that preintegration transcription occurs on a much larger scale than expected. The transcribing population derived from nonintegrated viral DNA was comparable (at approximately 70%) to that derived from provirus in a productive viral replication cycle. Nevertheless, each nonintegrated viral DNA template exhibited a significant reduction in the level of transcriptional activity in the absence of integration. We also performed flow cytometry sorting of infected cells to identify viral templates. Surprisingly, our results suggest that the majority of 2-LTR circles are not active in directing transcription. It is likely that the nonintegrated templates are from the predominant DNA species, such as the full-length, linear DNA. Our results also suggest that a nonintegrating lentiviral vector can be as effective as an integrating vector in directing gene expression in nondividing cells, with the proper choice of an internal promoter. C1 [Iyer, Subashini R.; Yu, Dongyang; Wu, Yuntao] George Mason Univ, Dept Mol & Microbiol, Manassas, VA 20110 USA. [Biancotto, Angelique; Margolis, Leonid B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, Bethesda, MD 20892 USA. RP Wu, YT (reprint author), George Mason Univ, Dept Mol & Microbiol, 10900 Univ Blvd,MS 4E3, Manassas, VA 20110 USA. EM ywu8@gmu.edu FU GMU Provost Fellowship; NIAID [AI069981]; NICHD FX S. Iyer was supported by a GMU Provost Fellowship. This work was supported by Public Health Service grant AI069981 from NIAID to Y.W. and by the NICHD Intramural Program ( L. B. M. and A. B.). NR 66 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8662 EP 8673 DI 10.1128/JVI.00874-09 PG 12 WC Virology SC Virology GA 485LF UT WOS:000269122300034 PM 19553325 ER PT J AU Ghedin, E Fitch, A Boyne, A Griesemer, S DePasse, J Bera, J Zhang, X Halpin, RA Smit, M Jennings, L St George, K Holmes, EC Spiro, DJ AF Ghedin, Elodie Fitch, Adam Boyne, Alex Griesemer, Sara DePasse, Jay Bera, Jayati Zhang, Xu Halpin, Rebecca A. Smit, Marita Jennings, Lance St George, Kirsten Holmes, Edward C. Spiro, David J. TI Mixed Infection and the Genesis of Influenza Virus Diversity SO JOURNAL OF VIROLOGY LA English DT Article ID HEMAGGLUTININ MEMBRANE GLYCOPROTEIN; GENOME ANALYSIS; H3N2 VIRUSES; A VIRUS; REASSORTMENT; REVEALS; H2N2 AB The emergence of viral infections with potentially devastating consequences for human health is highly dependent on their underlying evolutionary dynamics. One likely scenario for an avian influenza virus, such as A/H5N1, to evolve to one capable of human-to-human transmission is through the acquisition of genetic material from the A/H1N1 or A/H3N2 subtypes already circulating in human populations. This would require that viruses of both subtypes coinfect the same cells, generating a mixed infection, and then reassort. Determining the nature and frequency of mixed infection with influenza virus is therefore central to understanding the emergence of pandemic, antigenic, and drug-resistant strains. To better understand the potential for such events, we explored patterns of intrahost genetic diversity in recently circulating strains of human influenza virus. By analyzing multiple viral genome sequences sampled from individual influenza patients we reveal a high level of mixed infection, including diverse lineages of the same influenza virus subtype, drug-resistant and-sensitive strains, those that are likely to differ in antigenicity, and even viruses of different influenza virus types ( A and B). These results reveal that individuals can harbor influenza viruses that differ in major phenotypic properties, including those that are antigenically distinct and those that differ in their sensitivity to antiviral agents. C1 [Ghedin, Elodie] Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, Pittsburgh, PA 15261 USA. [Ghedin, Elodie; Fitch, Adam; DePasse, Jay; Zhang, Xu] Univ Pittsburgh, Sch Med, Dept Computat Biol, Pittsburgh, PA 15261 USA. [Boyne, Alex; Bera, Jayati; Halpin, Rebecca A.; Spiro, David J.] J Craig Venter Inst, Rockville, MD 20850 USA. [Griesemer, Sara; St George, Kirsten] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. [Smit, Marita; Jennings, Lance] Canterbury Hlth Labs, Christchurch, New Zealand. [Holmes, Edward C.] Penn State Univ, University Pk, PA 16802 USA. [Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Ghedin, E (reprint author), Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, 3550 Terrace St,Room 830, Pittsburgh, PA 15261 USA. EM elg21@pitt.edu OI Holmes, Edward/0000-0001-9596-3552 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services [N01-AI-30071] FX The work was supported in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number N01-AI-30071. NR 22 TC 66 Z9 67 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8832 EP 8841 DI 10.1128/JVI.00773-09 PG 10 WC Virology SC Virology GA 485LF UT WOS:000269122300050 PM 19553313 ER PT J AU Garidou, L Heydari, S Truong, P Brooks, DG McGavern, DB AF Garidou, Lucile Heydari, Sara Truong, Phi Brooks, David G. McGavern, Dorian B. TI Therapeutic Memory T Cells Require Costimulation for Effective Clearance of a Persistent Viral Infection SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MARROW-DERIVED CELLS; VIRUS CARRIER MICE; ADOPTIVE TRANSFER; BONE-MARROW; IMMUNOLOGICAL TOLERANCE; LCM VIRUS; IN-VIVO; ANTIGEN; IMMUNITY AB Persistent viral infections are a major health concern worldwide. During persistent infection, overwhelming viral replication and the rapid loss of antiviral T-cell function can prevent immune-mediated clearance of the infection, and therapies to reanimate the immune response and purge persistent viruses have been largely unsuccessful. Adoptive immunotherapy using memory T cells is a highly successful therapeutic approach to eradicate a persistent viral infection. Understanding precisely how therapeutically administered memory T cells achieve clearance should improve our ability to terminate states of viral persistence in humans. Mice persistently infected from birth with lymphocytic choriomeningitis virus are tolerant to the pathogen at the T-cell level and thus provide an excellent model to evaluate immunotherapeutic regimens. Previously, we demonstrated that adoptively transferred memory T cells require recipient dendritic cells to effectively purge an established persistent viral infection. However, the mechanisms that reactivate and sustain memory T-cell responses during clearance of such an infection remain unclear. Here we establish that therapeutic memory T cells require CD80 and CD86 costimulatory signals to efficiently clear an established persistent viral infection in vivo. Early blockade of costimulatory pathways with CTLA-4-Fc decreased the secondary expansion of virus-specific CD8(+) and CD4(+) memory T cells as well as their ability to produce antiviral cytokines and purge the persistent infection. Late costimulation blockade also reduced virus-specific T-cell numbers, illustrating that sustained interactions with costimulatory molecules is required for efficient T-cell expansion. These findings indicate that antiviral memory T cells require costimulation to efficiently clear a persistent viral infection and that costimulatory pathways can be targeted to modulate the magnitude of an adoptive immunotherapeutic regimen. C1 [Brooks, David G.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, UCLA AIDS Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Garidou, Lucile; Heydari, Sara; Truong, Phi; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20882 USA. RP Brooks, DG (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, UCLA AIDS Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM dbrooks@em.ucla.edu; mcgavernd@mail.nih.gov OI McGavern, Dorian/0000-0001-9568-545X FU National Institutes of Health [AI070967-01, AI77012-03]; Ray Thomas Edwards Foundation; Association pour la recherche sur la sclerose en plaques FX This work was supported by National Institutes of Health grants AI070967-01 ( to D. B. McGavern) and AI77012-03 ( to D. G. Brooks) and a grant from the Ray Thomas Edwards Foundation ( to D. B. McGavern). L. Garidou was supported by a fellowship from the Association pour la recherche sur la sclerose en plaques. NR 33 TC 16 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8905 EP 8915 DI 10.1128/JVI.00027-09 PG 11 WC Virology SC Virology GA 485LF UT WOS:000269122300057 PM 19553326 ER PT J AU Gray, ES Taylor, N Wycuff, D Moore, PL Tomaras, GD Wibmer, CK Puren, A DeCamp, A Gilbert, PB Wood, B Montefiori, DC Binley, JM Shaw, GM Haynes, BF Mascola, JR Morris, L AF Gray, Elin S. Taylor, Natasha Wycuff, Diane Moore, Penny L. Tomaras, Georgia D. Wibmer, Constantinos Kurt Puren, Adrian DeCamp, Allan Gilbert, Peter B. Wood, Blake Montefiori, David C. Binley, James M. Shaw, George M. Haynes, Barton F. Mascola, John R. Morris, Lynn TI Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors SO JOURNAL OF VIROLOGY LA English DT Article ID PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODY; CORECEPTOR BINDING-SITE; HIV VACCINE DESIGN; ANTICARDIOLIPIN ANTIBODIES; ENV CLONES; GP120; ENVELOPE; RESPONSES; EPITOPE AB Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon. C1 [Gray, Elin S.; Taylor, Natasha; Moore, Penny L.; Wibmer, Constantinos Kurt; Morris, Lynn] Natl Inst Communicable Dis, AIDS Virus Res Unit, ZA-2193 Johannesburg, South Africa. [Puren, Adrian] Natl Inst Communicable Dis, Specialized Mol Diagnost Unit, ZA-2193 Johannesburg, South Africa. [Wycuff, Diane; Mascola, John R.] NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Tomaras, Georgia D.; Montefiori, David C.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [DeCamp, Allan; Gilbert, Peter B.; Wood, Blake] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98109 USA. [Binley, James M.] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. [Shaw, George M.] Univ Alabama, Birmingham, AL 35294 USA. RP Morris, L (reprint author), Natl Inst Communicable Dis, AIDS Virus Res Unit, Private Bag X4,Sandringham 2131, ZA-2193 Johannesburg, South Africa. EM lynnm@nicd.ac.za RI Tomaras, Georgia/J-5041-2016; OI Moore, Penny/0000-0001-8719-4028; , Lynn/0000-0003-3961-7828; Wibmer, Constantinos Kurt/0000-0003-2329-2280; Gray, Elin/0000-0002-8613-3570 FU South African Vaccine Initiative (SAAVI); Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery (CAVD); Vaccine Immune Monitoring Consortium (VIMC) [38619]; HIV/AIDS Vaccine Immunology [AI64518]; Vaccine Research Center of the U. S. National Institute of Allergy and Infectious Diseases FX This work was funded by the South African Vaccine Initiative (SAAVI) and the Bill and Melinda Gates Collaboration for AIDS Vaccine Discovery (CAVD), Vaccine Immune Monitoring Consortium (VIMC) grant number 38619, a Bill and Melinda Gates CAVD Vaccine Development Center (VDC) grant to B. F. H., and the Center for HIV/AIDS Vaccine Immunology grant AI64518, and in part by the Vaccine Research Center of the U. S. National Institute of Allergy and Infectious Diseases (J.R.M. and D. W.). NR 57 TC 120 Z9 123 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2009 VL 83 IS 17 BP 8925 EP 8937 DI 10.1128/JVI.00758-09 PG 13 WC Virology SC Virology GA 485LF UT WOS:000269122300059 PM 19553335 ER PT J AU Merz, CNB Johnson, BD Berga, SL Braunstein, GD Azziz, R Yang, YC Reis, SE Bittner, V Hodgson, TK Pepine, CJ Sharaf, BL Sopko, G Kelsey, SF AF Merz, C. Noel Bairey Johnson, B. Delia Berga, Sarah L. Braunstein, Glenn D. Azziz, Ricardo Yang, YuChing Reis, Steven E. Bittner, Vera Hodgson, T. Keta Pepine, Carl J. Sharaf, Barry L. Sopko, George Kelsey, Sheryl F. CA WISE Study Grp TI Total Estrogen Time and Obstructive Coronary Disease in Women: Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) SO JOURNAL OF WOMENS HEALTH LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; RANDOMIZED CONTROLLED TRIAL; HEART-DISEASE; REPLACEMENT THERAPY; ARTERY ATHEROSCLEROSIS; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; PLUS PROGESTIN; RISK; MENOPAUSE AB Objective: It has been suggested that both endogenous reproductive hormones and hormone therapy may play a protective role against coronary artery disease (CAD). However, recent clinical trials have failed to demonstrate the benefit of a variety of forms of hormone therapy. The observational data on the role of endogenous reproductive hormones, using surrogate measures such as number of birth, age at menarche, and age at menopause are inconsistent. In addition, the longer-term associations have not been evaluated. The aim of this study was to evaluate the relationships between detailed measurements of endogenous and exogenous estrogen exposure time with angiographic CAD and major adverse cardiovascular events. Methods: We assessed total estrogen exposure time, quantitative CAD by a core angiography laboratory, and prospectively measured major adverse cardiovascular events in 646 postmenopausal women undergoing coronary angiography for evaluation for suspected ischemia in the Women's Ischemia Syndrome Evaluation (WISE) study. Results: Timing of postmenopausal exogenous hormone therapy (HT) use was associated with reduced CAD. Two summarized total estrogen time scores (TET and sTET) were not related to angiographic CAD after accounting for HT use. In addition, these scores were not related to cardiovascular events over a median of 6.0 years of follow-up. Conclusions: There was no independent relation of estrogen exposure time to angiographic CAD or major adverse cardiovascular events in a contemporary cohort of postmenopausal women evaluated for suspected ischemia. Our results suggest that the paradigm of estrogen protection from CAD in women may be more complex than estrogen exposure duration alone. C1 [Merz, C. Noel Bairey; Braunstein, Glenn D.; Azziz, Ricardo; Yang, YuChing; Hodgson, T. Keta] Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. [Merz, C. Noel Bairey; Braunstein, Glenn D.] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Johnson, B. Delia; Reis, Steven E.; Kelsey, Sheryl F.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Berga, Sarah L.] Univ Pittsburgh, Dept Med, Div Cardiol, Pittsburgh, PA 15261 USA. [Bittner, Vera] Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. [Pepine, Carl J.] Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. [Sharaf, Barry L.] Rhode Isl Hosp, Providence, RI USA. [Sopko, George] NHLBI, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, WISE Coordinating Ctr, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM merz@cshs.org RI Reis, Steven/J-3957-2014; Azziz, Ricardo/N-7229-2014; OI Azziz, Ricardo/0000-0002-3917-0483; Bittner, Vera/0000-0001-9456-850X FU National Heart, Lung and Blood Institutes [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164]; National Center for Research Resources [MO1-RR00425] FX This work was supported by the National Heart, Lung and Blood Institutes (contracts N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164), the National Center for Research Resources (GCRC grant MO1-RR00425), and the Gustavus and Louis Pfeiffer Research Foundation (Denville, NJ), The Women's Guild of Cedars-Sinai Medical Center ( Los Angeles, CA), and The Ladies Hospital Aid Society of Western Pennsylvania ( Pittsburgh, PA), and the Edythe Broad Women's Heart Disease Research Endowment, Cedars-Sinai Medical Center ( Los Angeles, CA). NR 27 TC 13 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2009 VL 18 IS 9 BP 1315 EP 1322 DI 10.1089/jwh.2008.1063 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 492ZI UT WOS:000269701600005 PM 19702477 ER PT J AU Longo, DL AF Longo, Dan L. TI Telomere Dynamics in Aging: Much Ado About Nothing? SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID LENGTH; DISEASE; WOMEN C1 NIA, Natl Inst Hlth, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Natl Inst Hlth, 251 Bayview Blvd,Suite 100,RM 04C224, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.org NR 11 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2009 VL 64 IS 9 BP 963 EP 964 DI 10.1093/gerona/glp071 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 488IP UT WOS:000269343000005 PM 19505961 ER PT J AU Eggers, PW AF Eggers, Paul W. TI Racial disparities in access to transplantation: a tough nut to crack SO KIDNEY INTERNATIONAL LA English DT Editorial Material AB Racial disparities in access to kidney transplantation continue to exist despite determined efforts to improve minority access. Subtle barriers to transplant access will be difficult to overcome. However, the gap between the number of persons needing transplant and the available organs is the greatest impediment to transplantation equality. C1 NIDDK, Kidney & Urol Epidemiol Programs, Bethesda, MD 20892 USA. RP Eggers, PW (reprint author), NIDDK, Kidney & Urol Epidemiol Programs, Room 615,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM eggersp@extra.niddk.nih.gov NR 8 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2009 VL 76 IS 6 BP 589 EP 590 DI 10.1038/ki.2009.256 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 493EZ UT WOS:000269718400002 PM 19721423 ER PT J AU Kalaiselvan, P Vijayakumar, S Hemalatha, K Murkunde, YV Herbert, RA Wells, MY AF Kalaiselvan, Ponnusamy Vijayakumar, Subramaniyan Hemalatha, Kuppusamy Murkunde, Yogeshkumar V. Herbert, Ronald A. Wells, Monique Y. TI Mass in the lateral cervical-thoracic region in a male Wistar rat SO LAB ANIMAL LA English DT Article C1 [Wells, Monique Y.] Toxicol Pathol Serv Inc, Paris, France. [Herbert, Ronald A.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Wells, MY (reprint author), Toxicol Pathol Serv Inc, Paris, France. EM mywells@toxpath.com FU Intramural NIH HHS NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2009 VL 38 IS 9 BP 288 EP 289 DI 10.1038/laban0909-288 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 517KG UT WOS:000271611700010 PM 19701177 ER PT J AU Jarvik, JG Comstock, BA Kliot, M Turner, JA Chan, L Heagerty, PJ Hollingworth, W Kerrigan, CL Deyo, RA AF Jarvik, Jeffrey G. Comstock, Bryan A. Kliot, Michel Turner, Judith A. Chan, Leighton Heagerty, Patrick J. Hollingworth, William Kerrigan, Carolyn L. Deyo, Richard A. TI Surgery versus non-surgical therapy for carpal tunnel syndrome: a randomised parallel-group trial SO LANCET LA English DT Article ID WORKERS COMPENSATION; STEROID INJECTION; CLINICAL-TRIAL; HEALTH; RESPONSIVENESS; QUESTIONNAIRE; POPULATION; ULTRASOUND; SYMPTOMS AB Background A previous randomised controlled trial reported greater efficacy of surgery than of splinting for patients with carpal tunnel syndrome. Our aim was to compare surgical versus multi-modality, non-surgical treatment for patients with carpal tunnel syndrome without denervation. We hypothesised that surgery would result in improved functional and symptom outcomes. Methods In this parallel-group randomised controlled trial, we randomly assigned 116 patients from eight academic and private practice centres, using computer-generated random allocation stratified by site, to carpal tunnel surgery (n=57) or to a well-defined, non-surgical treatment (including hand therapy and ultrasound; n=59). The primary outcome was hand function measured by the Carpal Tunnel Syndrome Assessment Questionnaire (CTSAQ) at 12 months assessed by research personnel unaware of group assignment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00032227. Findings 44 (77%) patients assigned to surgery underwent surgery. At 12 months, 101 (87%) completed follow-up and were analysed (49 of 57 assigned to surgery and 52 of 59 assigned to non-surgical treatment). Analyses showed a significant 12-month adjusted advantage for surgery in function (CTSAQ function score: Delta -0.40, 95% CI 0.11-0.70, p=0.0081) and symptoms (CTSAQ symptom score: 0.34, 0.02-0.65, p=0.0357). There were no clinically important adverse events and no surgical complications. Interpretation Symptoms in both groups improved, but surgical treatment led to better outcome than did non-surgical treatment. However, the clinical relevance of this difference was modest. Overall, our study confirms that surgery is useful for patients with carpal tunnel syndrome without denervation. Funding NIH/NIAMS 5P60AR048093 and the Intramural Research Program of the NIH Clinical Center. C1 [Jarvik, Jeffrey G.] Univ Washington, Dept Radiol, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.; Kliot, Michel] Univ Washington, Dept Neurol Surg, Sch Med, Seattle, WA 98104 USA. [Turner, Judith A.] Univ Washington, Dept Psychiat & Behav Sci, Sch Med, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98104 USA. [Comstock, Bryan A.; Heagerty, Patrick J.] Univ Washington, Dept Biostat, Sch Publ Hlth, Seattle, WA 98104 USA. [Jarvik, Jeffrey G.; Comstock, Bryan A.; Turner, Judith A.; Heagerty, Patrick J.] Univ Washington, Comparat Effectiveness Cost & Outcomes Res Ctr, Seattle, WA 98104 USA. [Kliot, Michel] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Chan, Leighton] NIH, Intramural Res Program, Ctr Clin, Bethesda, MD 20892 USA. [Kerrigan, Carolyn L.] Dartmouth Hitchcock Med Ctr, Sect Plast Surg, Lebanon, NH 03766 USA. [Hollingworth, William] Univ Bristol, Dept Social Med, Bristol, Avon, England. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Jarvik, JG (reprint author), Univ Washington, Dept Radiol, Harborview Med Ctr, Sch Med, Box 359728,325 Ninth Ave, Seattle, WA 98104 USA. EM jarviks@comcast.net FU NIH/NIAMS [SP60AR048093]; Intramural Research Program of the NIH FX NIH/NIAMS SP60AR048093 and the Intramural Research Program of the NIH Clinical Center. NR 31 TC 31 Z9 33 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD SEP-OCT PY 2009 VL 374 IS 9695 BP 1074 EP 1081 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 501HA UT WOS:000270370900029 ER PT J AU Lisco, A Vanpouille, C Margolis, L AF Lisco, Andrea Vanpouille, Christophe Margolis, Leonid TI A missed point in deciphering the viral synergy between herpes simplex virus and HIV SO LANCET INFECTIOUS DISEASES LA English DT Letter ID DOUBLE-BLIND; ACYCLOVIR; SUPPRESSION; VALACYCLOVIR; ACQUISITION; TRIAL; WOMEN; MEN C1 [Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid] Eunice Kennedy Shriver Natl Inst Child & Human De, Program Phys Biol, NIH, Bethesda, MD USA. RP Lisco, A (reprint author), Eunice Kennedy Shriver Natl Inst Child & Human De, Program Phys Biol, NIH, Bethesda, MD USA. EM liscoa@mail.nih.gov FU Intramural NIH HHS [ZIA HD001416-18] NR 16 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2009 VL 9 IS 9 BP 522 EP 523 PG 2 WC Infectious Diseases SC Infectious Diseases GA 489PC UT WOS:000269431700002 PM 19695487 ER PT J AU Sasieni, P Castle, PE Cuzick, J AF Sasieni, Peter Castle, Philip E. Cuzick, Jack TI Further analysis of the ARTISTIC trial SO LANCET ONCOLOGY LA English DT Editorial Material ID CYTOLOGY; COHORT C1 [Sasieni, Peter; Cuzick, Jack] Queen Mary Univ London, Canc Res UK Ctr Epidemiol Math & Stat, London EC1M 6BQ, England. [Castle, Philip E.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Sasieni, P (reprint author), Queen Mary Univ London, Canc Res UK Ctr Epidemiol Math & Stat, London EC1M 6BQ, England. EM p.sasieni@qmul.ac.uk NR 5 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2009 VL 10 IS 9 BP 841 EP 842 PG 2 WC Oncology SC Oncology GA 496EX UT WOS:000269953400006 PM 19717086 ER PT J AU Cantor, D AF Cantor, David TI Choosing to Live: Cancer Education, Movies, and the Conversion Narrative in America, 1921-1960 SO LITERATURE AND MEDICINE LA English DT Article C1 NIH, Off Hist, Bethesda, MD 20892 USA. RP Cantor, D (reprint author), NIH, Off Hist, Bldg 10, Bethesda, MD 20892 USA. NR 123 TC 3 Z9 3 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0278-9671 EI 1080-6571 J9 LIT MED JI Lit. Med. PD FAL PY 2009 VL 28 IS 2 BP 278 EP 332 PG 55 WC Literature SC Literature GA 680PE UT WOS:000284246100009 PM 21141799 ER PT J AU Liu, J Zhou, ZX Zhang, W Bell, MW Waalkes, MP AF Liu, Jie Zhou, Zhan-Xiang Zhang, Wei Bell, Matthew W. Waalkes, Michael P. TI Changes in hepatic gene expression in response to hepatoprotective levels of zinc SO LIVER INTERNATIONAL LA English DT Article DE gene expression; hepatoprotection; metallothionein; Nrf2; zinc ID ACETAMINOPHEN-INDUCED HEPATOTOXICITY; TETRACHLORIDE-INDUCED HEPATOTOXICITY; CISPLATIN-INDUCED HEPATOTOXICITY; ALCOHOLIC LIVER-INJURY; I/II KNOCKOUT MICE; CARBON-TETRACHLORIDE; METALLOTHIONEIN; PROTECTION; SUPPLEMENTATION; TOXICITY AB Background Zinc (Zn) administration at non-toxic doses protects against the hepatotoxicity produced by many agents, but the underlying mechanisms remain elusive. Aim To examine the basis of Zn-induced generalised hepatoprotective effects. Methods Rats and mice were given Zn at known hepatoprotective levels (100 mu mol ZnCl(2)/kg/day, s.c., for 4 days) and molecular responses were assessed. Results Zn treatment produced changes in 5% of the genes on custom-designed mouse liver array and Rat Toxicology-II array. Changes in gene expression were further confirmed and extended by real-time reverse transcriptase-polymerase chain reaction. Zn treatment dramatically increased the expression of the metallothionein (Mt), and modestly increased the expression of acute-phase protein genes (ceruloplasmin, Stat3, egr1, Cxc chemokines and heat-shock proteins). For genes encoding for antioxidant enzymes, some were increased (Nrf2 and Nqo1), while others remained unaltered (Cu, Zn SOD and glutathione S-transferases). Expressions of cytokine and pro-inflammatory genes were not affected, while genes related to cell proliferation (cyclin D1) were modestly upregulated. Some metabolic enzyme genes, including cytochrome P450s and UDP-glucuronosyltransferase, were modestly suppressed, perhaps to switch cellular metabolic energy to acute-phase responses. Liver Zn content was increased between 1.6- and 2.1-fold, while hepatic MT protein was increased between 50 and 200-fold. Mice typically showed greater responses than rats. Conclusion Such gene expression changes, particularly the dramatic induction of MT and Nrf2 antioxidant pathway, occur in the absence of overt liver injury, and are probably important in the hepatoprotective effects of Zn against toxic insults. C1 [Liu, Jie; Bell, Matthew W.; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. [Zhou, Zhan-Xiang] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Zhang, Wei] NIEHS, Pharmacol Lab, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, POB 12233, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; National Institute of Environmental Health Sciences and by the NIH [AA014623] FX The authors thank Drs Erik Tokar, Wei Qu and Larry Keefer for their critical review of this manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by the National Institute of Environmental Health Sciences and by the NIH grant AA014623 for Dr Zhou. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 45 TC 15 Z9 18 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD SEP PY 2009 VL 29 IS 8 BP 1222 EP 1229 DI 10.1111/j.1478-3231.2009.02007.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 479IP UT WOS:000268653200016 PM 19490425 ER PT J AU Zhang, MY Feng, Y Wang, YP Dimitrov, DS AF Zhang, Mei-Yun Feng, Yang Wang, Yanping Dimitrov, Dimiter S. TI Characterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor SO MABS LA English DT Article DE antibody; IGF-IR; phosphorylation; signal transduction ID BREAST-CANCER; PHASE-I; CP-751,871; THERAPY; INHIBITION; RESISTANCE; MYELOMA; CELLS AB The insulin-like growth factors (IGFs) signaling system has been shown to play important roles in neoplasia. The IGF receptor type I (IGF-IR) is overexpressed in many types of solid and hematopoietic malignancies, and there is substantial experimental and clinical evidence that targeting IGF-IR is a promising therapeutic strategy against cancer. It has been previously reported that a mouse monoclonal antibody (mAb), 4GII, blocked IGF-I binding to IGF-IR and downregulated the IGF-IR in MCF-7 cells. We cloned this antibody, constructed a human-mouse chimeric antibody, designated m590, and characterized it. The chimeric IgGI m590 bound to cell-associated IGF-IR on NWT c43 stably transfected cells and MCF-7 breast cancer cells as efficiently as the parental murine antibody. Using purified IGF-IR extracellular domains, we found that both the chimeric m590 and the parental 4GII antibodies bind to conformational epitopes on IGF-IR. Neither of these antibodies bound to the insulin receptor (IR) ectodomain. Furthermore, IgGI m590 blocked the binding of IGF-I and IGF-II to IGF-IR, and inhibited both IGF-I and IGF-II induced phosphorylation of IGF-IR in MCF-7 cells. These results suggest that m590 could be an useful antibody in diagnosis and treatment of cancer, as well as a research tool. C1 [Zhang, Mei-Yun; Feng, Yang; Wang, Yanping; Dimitrov, Dimiter S.] NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21701 USA. [Zhang, Mei-Yun; Wang, Yanping] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Zhang, MY (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, Pokfulam, Hong Kong, Peoples R China. EM zhangmy@hku.hk RI Zhang, Mei-Yun/E-9908-2010 FU NIH; National Cancer Institute [NO1-CO-12400]; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by federal funds from the NIH, National Cancer institute, under contract no. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 15 TC 3 Z9 4 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS JI mAbs PD SEP-OCT PY 2009 VL 1 IS 5 BP 475 EP 480 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 522HU UT WOS:000271989300009 PM 20065647 ER PT J AU Li, SZ Zhang, Y Wang, SM Yang, J Araneta, MF Farris, A Johnson, C Fox, S Innis, R Shen, J AF Li, Shizhe Zhang, Yan Wang, Shumin Yang, Jehoon Araneta, Maria Ferraris Farris, Amanda Johnson, Christopher Fox, Stephen Innis, Robert Shen, Jun TI In Vivo (13)C Magnetic Resonance Spectroscopy of Human Brain on a Clinical 3 T Scanner Using [2-(13)C]Glucose Infusion and Low-Power Stochastic Decoupling SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE decoupling; in vivo (13)C MRS; human brain ID TRICARBOXYLIC-ACID CYCLE; NMR-SPECTROSCOPY; 4 TESLA; GLUTAMATE METABOLISM; MR SPECTROSCOPY; SINGLE-SHOT; RAT-BRAIN; GLUCOSE; 1-C-13; COIL AB This study presents the detection of [2-(13)C]glucose metabolism in the carboxylic/amide region in the human brain, and demonstrates that the cerebral metabolism of [2-(13)C]glucose can be studied in human subjects in the presence of severe hardware constraints of widely available 3 T clinical scanners and with low-power stochastic decoupling. In the carboxylic/amide region of human brain, the primary products of (13)C lab I incorporation from [2-(13)C]glucose into glutamate, glutamine, aspartate, gamma-aminobutyric acid, and N-acetylaspartate were detected. Unlike the commonly used alkanyl region where lipid signals spread over a broad frequency range, the carboxylic carbon signal of lipids was found to be confined to a narrow range centered at 172.5 ppm and present no spectral interference in the absence of lipid suppression. Comparison using phantoms shows that stochastic decoupling is far superior to the commonly used WALTZ sequence at very low decoupling power at 3 T. It was found that glutamine C1 and C5 can be decoupled using stochastic decoupling at 2.2 W, although glutamine protons span a frequency range of approximate to 700 Hz. Detailed specific absorption rate analysis was also performed using finite difference time domain numerical simulation. Magn Reson Med 62: 565-573, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Yang, Jehoon; Araneta, Maria Ferraris; Farris, Amanda; Johnson, Christopher; Innis, Robert; Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Li, Shizhe; Zhang, Yan; Shen, Jun] NIMH, Magnet Resonance Spect Core Facil, NIH, Bethesda, MD 20892 USA. [Wang, Shumin] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Fox, Stephen] NCI, Lab Proteom & Analyt Technol, NIH, Bethesda, MD USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@mail.nih.gov FU NIMH-NIH FX Grant sponsor: Intramural Research Program of the NIMH-NIH. NR 49 TC 17 Z9 17 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2009 VL 62 IS 3 BP 565 EP 573 DI 10.1002/mrm.22044 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 489FG UT WOS:000269404900002 PM 19526500 ER PT J AU Aberegg, SK O'Brien, JM Khoury, P Patel, R Arkes, HR AF Aberegg, Scott K. O'Brien, James M., Jr. Khoury, Paneez Patel, Roocha Arkes, Hal R. TI The Influence of Treatment Effect Size on Willingness to Adopt a Therapy SO MEDICAL DECISION MAKING LA English DT Article DE evidence-based medicine (EBM); expected utility theory; effect size; randomized controlled trial; critical care ID ACUTE CORONARY SYNDROMES; CLINICAL-PRACTICE; PHYSICIANS; GUIDELINES; CARE; INFORMATION; DECISION; RISK AB Background. Physicians are slow to adopt novel therapies, and the reasons for this are poorly understood. The authors sought to determine if the size of the treatment effect of a novel therapy influences willingness to adopt it. Methods. We developed 2 experimental vignette pairs describing a trial of a therapy for a hypothetical disease that showed a statistically significant mortality benefit. The size of the mortality effect was varied in vignettes of a pair (3% v. 10%). The 2 experimental vignette pairs differed in Whether study enrollment was reported. Vignettes were mailed to a random sample of physicians using an intersubject design. The main Study outcome was respondents' willingness to adopt the hypothetical therapy, based on the results of the hypothetical trial. Results. There were 124 and 89 respondents to vignette pairs 1 and 2, respectively. In vignette pair 1, 91% versus 71% of respondents adopted the therapy when it reduced mortality by 10% and 3%, respectively (P = 0.0058). For vignette pair 2, 88% versus 51% of respondents adopted the therapy when it reduced mortality by 10% and 3%, respectively (P = 0.0002). In both vignette pairs, nonadopters were more likely than adopters to report side effects of the therapy as a principal reason far their decision. Conclusions. In this study, respondents were less likely to adopt a lifesaving therapy if its associated mortality reduction was 3% compared to 10%. Because most therapies for major medical conditions reduce mortality within or below, this range, and because there were no opportunity costs associated with the adoption of the therapy, we believe that this effect represents a bias. Further investigation will be required to determine its prevalence and mechanism. C1 [Aberegg, Scott K.] Pioneer Valley Hosp, W Valley City, UT 84120 USA. [O'Brien, James M., Jr.; Patel, Roocha] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Arkes, Hal R.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Khoury, Paneez] NIH, Bethesda, MD 20892 USA. RP Aberegg, SK (reprint author), Pioneer Valley Hosp, 3460 S Pioneer Pkwy, W Valley City, UT 84120 USA. EM scottaberegg@gmail.com RI O'Brien, James/A-2624-2009 NR 26 TC 1 Z9 1 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2009 VL 29 IS 5 BP 599 EP 605 DI 10.1177/0272989X09336078 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 505GF UT WOS:000270679300006 PM 19498080 ER PT J AU van Faassen, EE Babrami, S Feelisch, M Hogg, N Kelm, M Kim-Shapiro, DB Kozlov, AV Li, HT Lundberg, JO Mason, R Nohl, H Rassaf, T Samouilov, A Slama-Schwok, A Shiva, S Vanin, AF Weitzberg, E Zweier, J Gladwin, MT AF van Faassen, Ernst E. Babrami, Sobeyl Feelisch, Martin Hogg, Neil Kelm, Malte Kim-Shapiro, Daniel B. Kozlov, Andrey V. Li, Haitao Lundberg, Jon O. Mason, Ron Nohl, Hans Rassaf, Tienush Samouilov, Alexandre Slama-Schwok, Anny Shiva, Sruti Vanin, Anatoly F. Weitzberg, Eddie Zweier, Jay Gladwin, Mark T. TI Nitrite as Regulator of Hypoxic Signaling in Mammalian Physiology SO MEDICINAL RESEARCH REVIEWS LA English DT Review DE nitrite; vasodilation; ischemia/reperfusion; nitric oxide; hypoxia ID ENDOTHELIAL PROGENITOR CELLS; ISCHEMIA-REPERFUSION INJURY; MITOCHONDRIAL RESPIRATORY-CHAIN; ELECTRON-SPIN-RESONANCE; SYNTHASE REDUCES NITRITE; SOLUBLE GUANYLYL CYCLASE; CORONARY-ARTERY-DISEASE; HUMAN SKELETAL-MUSCLE; CYTOCHROME-C-OXIDASE; REGIONAL BLOOD-FLOW AB In this review we consider the effects of endogenous and pharmacological levels of nitrite under conditions of hypoxia. In humans, the nitrite anion has long been considered as metastable intermediate in the oxidation of nitric oxide radicals to the stable metabolite nitrate. This oxidation cascade was thought to be irreversible under physiological conditions. However, a growing body of experimental observations attests that the presence of endogenous nitrite regulates a number of signaling events along the physiological and pathophysiological oxygen gradient. Hypoxic signaling events include vasodilation, modulation of mitochondrial respiration, and cytoprotection following ischemic insult. These phenomena are attributed to the reduction of nitrite anions to nitric oxide if local oxygen levels in tissues decrease. Recent research identified a growing list of enzymatic and nonenzymatic pathways for this endogenous reduction of nitrite. Additional direct signaling events not involving free nitric oxide are proposed. We here discuss the mechanisms and properties of these various pathways and the role played by the local concentration of free oxygen in the affected tissue. (C) 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 5, 683-741, 2009 C1 [van Faassen, Ernst E.] Univ Utrecht, Debye Inst, Dept Interface Phys, NL-3508 GA Utrecht, Netherlands. [Babrami, Sobeyl; Kozlov, Andrey V.] AUVA Res Ctr, L Boltzmann Inst Expt & Clin Traumatol, Vienna, Austria. [Feelisch, Martin] Univ Warwick, Warwick Med Sch, Clin Sci Res Inst, Coventry CV4 7AL, W Midlands, England. [Hogg, Neil] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. [Hogg, Neil] Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. [Kelm, Malte; Rassaf, Tienush] Univ Hosp Aachen, Div Cardiol Pulmonol & Vasc Med, D-52074 Aachen, Germany. [Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. [Li, Haitao; Samouilov, Alexandre; Zweier, Jay] Ohio State Univ, Davis Res Inst, Columbus, OH 43210 USA. [Lundberg, Jon O.; Weitzberg, Eddie] Karolinska Inst, Stockholm, Sweden. [Mason, Ron] NIEHS, Res Triangle Pk, NC 27709 USA. [Nohl, Hans] Univ Vet Med, Res Inst Biochem Pharmacol & Toxicol, Vienna, Austria. [Slama-Schwok, Anny] INRA UR892, Jouy En Josas, France. [Shiva, Sruti] NIH, Pulm & Vasc Med Branch, Bethesda, MD 20892 USA. [Vanin, Anatoly F.] Russian Acad Sci, NN Semenov Chem Phys Inst, Moscow, Russia. [Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. RP van Faassen, EE (reprint author), Univ Utrecht, Debye Inst, Dept Interface Phys, Princetonpl 1, NL-3508 GA Utrecht, Netherlands. EM faassen@phys.uu.nl RI Samouilov, Alexandre/E-4010-2011; Feelisch, Martin/C-3042-2008; Samouilov, Alexandre/B-5824-2014; Institute (DINS), Debye/G-7730-2014; Vanin, Anatoly/I-1069-2016 OI Feelisch, Martin/0000-0003-2320-1158; Vanin, Anatoly/0000-0001-8392-4601 FU Medical Research Council; NIH [GM55792, HL05891, HL078706]; National Institute of General Medicine; DFG [RA 969/4-1, KE 405/5-1]; Division of Intramural Research of the National Heart, Lung and Blood Institute; Russian Foundation for Basic Research [04-05-49383, 07-04-1350ofi_c]; French ECONET FX M. Feelisch acknowledges support from the Medical Research Council (Strategic Appointment Scheme). N. Hogg acknowledges support from NIH grant GM55792 from the National Institute of General Medicine. D. Kim-Shapiro acknowledges support from NIH grants HL05891 and HL078706. T. Rassaf and M. Kelm are supported by grants from the DFG (RA 969/4-1 to T. R. and KE 405/5-1 to M. K.). S. Shiva acknowledges generous support by NIH grants HL058091 and HL078706 and by the Division of Intramural Research of the National Heart, Lung and Blood Institute. A. Vanin thanks the Russian Foundation for Basic Research (grants 04-05-49383 and 07-04-1350ofi_c) and the French ECONET 2005 program (to Army Slama-Schwok, dossier 10275). We thank Prof. A. J. Rabelink (Leiden) for careful reading of the manuscript and helpful comments. NR 268 TC 195 Z9 203 U1 2 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD SEP PY 2009 VL 29 IS 5 BP 683 EP 741 DI 10.1002/med.20151 PG 59 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 484KY UT WOS:000269044700001 PM 19219851 ER PT J AU Dunton, GF Berrigan, D Ballard-Barbash, R Graubard, BI Atienza, AA AF Dunton, Genevieve F. Berrigan, David Ballard-Barbash, Rachel Graubard, Barry I. Atienza, Audie A. TI Environmental Influences on Exercise Intensity and Duration in a US Time Use Study SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE SOCIAL FACTORS; HOME; WORK; OUTDOORS; SPORTS; POPULATION STUDY ID PHYSICAL-ACTIVITY; INTRINSIC MOTIVATION; OLDER-ADULTS; WALKING; DETERMINANTS; PARTICIPATION; COOPERATION; COMPETITION; APPRAISAL; SPORTS AB DUNTON, G. F., D. BERRIGAN, R. BALLARD-BARBASH, B. I. GRAUBARD, and A. A. ATIENZA. Environmental Influences on Exercise Intensity and Duration in a U.S. Time Use Study. Med. Sci. Sports Exerc., Vol. 41, No. 9, pp. 1698-1705, 2009. Purpose: Rising rates of physical inactivity and obesity in the United States highlight the critical need to identify contexts and settings that are conducive to the promotion of recreational physical activity. The current study investigated whether the intensity and duration of sports and exercise bouts differ across physical and social environments as reported in a nationally representative time use survey of U.S. adults. Methods: From the American Time Use Survey (years 2003-2006), adult participants (ages >= 21 yr) who reported at least one bout of sports or exercise on the previous day were selected (N = 7700). For each exercise bout, respondents reported the activity type, its duration (in minutes), its location (e.g., outdoors, home, work, health club/gym), and with whom it occurred (e.g., alone, family members, coworkers, friends/acquaintances). Sample-weighted logistic and linear regression analyses examined differences in intensity expressed as METs (moderate, 3.0-6.0 METs, vigorous, >6.0 METs) and in duration of exercise bouts across environments. Results: Vigorous-intensity exercise was more likely when the bout occurred alone as compared with other social situations (P values < 0.001) and when at a gym/health club and at home as compared with outdoors (P values < 0.001). For both moderate and vigorous activities, exercise bouts were shorter when exercising alone versus with family members, friends/acquaintances, or multiple categories (P values < 0.001). Mean duration of exercise bouts was greater when exercising outdoors than when exercising at home, work, or at gym/health club (P values < 0.001). Conclusions: Nationally representative time use data for U.S. adults suggest that the intensity and duration of exercise bouts are differentially affected by social contexts and physical settings. C1 [Dunton, Genevieve F.; Atienza, Audie A.] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Berrigan, David; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Graubard, Barry I.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Biostat, Bethesda, MD 20892 USA. RP Dunton, GF (reprint author), Univ So Calif, Dept Prevent Med, 1000 S Fremont Ave,Unit 8,Bldg 5,Rm 5229, Alhambra, CA 91803 USA. EM dunton@usc.edu FU Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health FX The first author was supported by the Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health during the preparation of this article. NR 44 TC 22 Z9 22 U1 8 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 2009 VL 41 IS 9 BP 1698 EP 1705 DI 10.1249/MSS.0b013e3181a06c9b PG 8 WC Sport Sciences SC Sport Sciences GA 488GU UT WOS:000269338200002 PM 19657302 ER PT J AU Chamberlain, AM Schreiner, PJ Fornage, M Loria, CM Siscovick, D Boerwinkle, E AF Chamberlain, Alanna M. Schreiner, Pamela J. Fornage, Myriam Loria, Catherine M. Siscovick, David Boerwinkle, Eric TI Ala54Thr polymorphism of the fatty acid binding protein 2 gene and saturated fat intake in relation to lipid levels and insulin resistance: the Coronary Artery Risk Development in Young Adults (CARDIA) study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; ASSOCIATION; EXPRESSION; OXIDATION; CODON-54; GLUCOSE; PLASMA; WOMEN; MEN AB The Thr54 allele of the intestinal fatty acid-binding protein Ala54Thr functional polymorphism (FABP2) is associated with increased fat oxidation and insulin resistance. We determined the cross-sectional associations of the FABP2 gene with lipid levels and insulin resistance in 2148 participants who completed the year-20 examination of the Coronary Artery Risk Development in Young Adults (CARDIA) study. No significant difference in total cholesterol, low-density or high-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol to total cholesterol ratio, or homeostasis model assessment of insulin resistance (HOMA-IR) was found between FABP2 genotypes. However, in the presence of a high-saturated fat diet (>= 53.2 g/d, the 90th percentile for the population), the AA/AG genotypes (carriers of the Thr54 allele) of FABP2 had statistically significantly higher levels of log(HOMA-IR) (P = .006) and a lower high-density lipoprotein cholesterol to total cholesterol ratio (P = .03), and borderline statistically significantly higher levels of total cholesterol, low-density lipoprotein cholesterol, and log(triglycerides) (P values = .08, .07, and .05, respectively) compared with those with the GG genotype (Ala54 homozygotes). Lipid levels and log(HOMA-IR) did not vary by genotype with saturated fat intake less than 53.2 g/d. Limiting dietary saturated fat intake may be particularly important among carriers of the A allele of FABP2. (C) 2009 Elsevier Inc. All rights reserved. C1 [Chamberlain, Alanna M.; Schreiner, Pamela J.] Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. [Fornage, Myriam] Univ Texas Houston Hlth Sci Ctr, Brown Fdn, Inst Mol Med, Houston, TX USA. [Fornage, Myriam] Univ Texas Houston Hlth Sci Ctr, Grad Sch Biomed Sci, Houston, TX USA. [Loria, Catherine M.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Siscovick, David] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Boerwinkle, Eric] Univ Texas Houston Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. RP Schreiner, PJ (reprint author), Univ Minnesota, Div Epidemiol & Community Hlth, Sch Publ Hlth, Minneapolis, MN 55454 USA. EM schre012@umn.edu FU University of Alabama at Birmingham, Coordinating Center; University of Alabama at Birmingham; University of Minnesota, Field Center and Diet Reading Center; Northwestem University, Field Center; Kaiser Foundation Research Institute; University of California, Irvine, Echocardiography Reading Center; Harbor-UCLA Research Education Institute, Computed Tomography Reading Center; Wake Forest University; National Heart, Lung, and Blood Institute [N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, N01-HC-45205, N01-HC-45204, T32-HL-007779] FX Work on this manuscript was supported (or partially supported) by contracts: University of Alabama at Birmingham, Coordinating Center, N01-HC-95095; University of Alabama at Birmingham, Field Center, N01-HC-48047; University of Minnesota, Field Center and Diet Reading Center (year-20 examination), N01-HC-48048; Northwestem University, Field Center, N01-HC-48049; Kaiser Foundation Research Institute, N01-HC-48050; University of California, Irvine, Echocardiography Reading Center (years 5 and 10), N01-HC-45134; Harbor-UCLA Research Education Institute, Computed Tomography Reading Center (year-15 examination), N01-HC-05187; Wake Forest University (year-20 examination), N01-HC-45205; New England Medical Center (year-20 examination), N01-HC-45204 from the National Heart, Lung, and Blood Institute. AMC was supported by NHLBI grant T32-HL-007779. NR 24 TC 11 Z9 14 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD SEP PY 2009 VL 58 IS 9 BP 1222 EP 1228 DI 10.1016/j.metabol.2009.04.007 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 487XB UT WOS:000269310300003 PM 19439328 ER PT J AU Barr, CS AF Barr, Christina S. TI Strategies for performing genotype-phenotype association studies in nonhuman primates SO METHODS LA English DT Review DE Macaque; Genetic; Comparative; Primate; EMSA; Reporter assay; GxE interactions ID SEROTONIN TRANSPORTER GENE; OPIOID-RECEPTOR GENE; RHESUS MACAQUES; TRANSCRIPTIONAL REGULATION; PROMOTER VARIATION; REARING CONDITION; STRESS-RESPONSE; CHIP-SEQ; POLYMORPHISM; ALCOHOL AB Anthropoid primate models offer opportunities to study genetic influence on alcohol consumption and alcohol-related intermediate phenotypes in socially and behaviorally complex animal models that are closely related to humans, and in which functionally equivalent or orthologous genetic variants exist. This review will discuss the methods commonly used for performing candidate gene-based studies in rhesus macaques in order to model how functional genetic variation moderates risk for human psychiatric disorders. Various in silico and in vitro approaches to identifying functional genetic variants for performance of these studies will be discussed. Next, I will provide examples of how this approach can be used for performing candidate gene-based studies and for examining gene by environment interactions. Finally, these approaches will then be placed in the context of how function-guided studies can inform us of genetic variants that may be under selection across species, demonstrating how functional genetic variants that may have conferred selective advantage at some point in the evolutionary history of humans could increase risk for addictive disorders in modern society. Published by Elsevier Inc. C1 NIAAA, Labs Neurogenet & Clin & Translat Studies, NIH, Rockville, MD 20852 USA. RP Barr, CS (reprint author), NIAAA, Labs Neurogenet & Clin & Translat Studies, NIH, 5625 Fishers Lane,Rm 3S-32, Rockville, MD 20852 USA. EM cbarr@mail.nih.gov FU NIAAA; NICHD FX The author thanks Qiaoping Yuan for the recombination hotspot figure, and the investigators at NIAAA and NICHD for their contributions to the work discussed in this review. The work described was funded by the NIAAA and NICHD intramural programs. NR 57 TC 1 Z9 1 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD SEP PY 2009 VL 49 IS 1 BP 56 EP 62 DI 10.1016/j.ymeth.2009.05.014 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 555SC UT WOS:000274533600010 PM 19505576 ER PT J AU Chan, SSL Naviaux, RK Basinger, AA Casas, KA Copeland, WC AF Chan, Sherine S. L. Naviaux, Robert K. Basinger, Alice A. Casas, Kari A. Copeland, William C. TI De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome SO MITOCHONDRION LA English DT Article DE Mitochondrial disease; Mitochondrial DNA replication; Alpers syndrome; Nonsense-mediated decay; De novo mutation; Haplotype insufficiency ID DNA-POLYMERASE-GAMMA; PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; MITOCHONDRIAL-DNA; ACCESSORY SUBUNIT; MESSENGER-RNA; DEPLETION; DISEASE; ANT1; DEGENERATION; CONSEQUENCE AB Mutations in POLG are a major contributor to pediatric and adult mitochondrial diseases. However, the consequences of many POLG mutations are not well understood. We investigated the molecular cause of Alpers syndome in a patient harboring the POLG mutations A467T in trans with c.2157+5_+6 gc-->ag in intron 12. Analysis of transcripts arising from the c.2157+5_+ 6 gc-->ag allele revealed alternative splicing with an insertion of 30 intronic nucleotides leading to a premature termination codon. These transcripts were subsequently removed through nonsense-mediated decay, leading to haplotype insufficiency due to expression of the A467T allele and decreased expression of the c.2157+5_+ 6 gc-->ag allele, which is likely responsible for the Alpers syndrome phenotype. Published by Elsevier B. V. on behalf of Mitochondrion Research Society. C1 [Chan, Sherine S. L.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Basinger, Alice A.] Cook Childrens Phys Network, Div Genet, Ft Worth, TX 76102 USA. [Casas, Kari A.] Trinity Mother Frances Hosp & Clin, Tyler, TX 75702 USA. [Naviaux, Robert K.] Univ Calif San Diego, Mitochondrial & Metab Dis Ctr, Dept Med, San Diego, CA 92103 USA. [Naviaux, Robert K.] Univ Calif San Diego, Mitochondrial & Metab Dis Ctr, Dept Pediat, San Diego, CA 92103 USA. RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM copelan1@niehs.nih.gov FU National Institutes of Health Career Development Award [1K99-ES015555-01]; National Institute of Environmental Health Sciences, NIH [Z01ES065078] FX We thank Drs. Janssen Daly and Raghuvar Dronamraju for critically reviewing this manuscript. Funding was provided from a National Institutes of Health Career Development Award to SSLC (1K99-ES015555-01), and Intramural Research funds (Z01ES065078) from the National Institute of Environmental Health Sciences, NIH to WCC. NR 30 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2009 VL 9 IS 5 BP 340 EP 345 DI 10.1016/j.mito.2009.05.002 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 541LC UT WOS:000273416200008 PM 19501198 ER PT J AU Gaiser, T Waha, A Moessler, F Bruckner, T Pietsch, T von Deimling, A AF Gaiser, Timo Waha, Andreas Moessler, Franziska Bruckner, Thomas Pietsch, Torsten von Deimling, Andreas TI Comparison of automated silver enhanced in situ hybridization and fluorescence in situ hybridization for evaluation of epidermal growth factor receptor status in human glioblastomas SO MODERN PATHOLOGY LA English DT Article DE EGFR; glioblastoma; silver enhanced in situ hybridization; fluorescence in situ hybridization; immunohistochemistry; SISH; FISH ID HIGH-GRADE GLIOMAS; EGFR GENE AMPLIFICATION; PHASE-I/II TRIAL; PROTEIN EXPRESSION; BREAST-CARCINOMA; MULTIFORME; OVEREXPRESSION; TEMOZOLOMIDE; PATHOLOGISTS; GUIDELINES AB The epidermal growth factor receptor (EGFR) is amplified in approximately 40% of glioblastomas making it a compelling molecular target for therapy. Before starting a therapy targeting the EGFR pathway, accurate determining of EGFR status is a prerequisite. We evaluated the reliability of the novel automated silver enhanced in situ hybridization for the detection of EGFR gene amplification in human glioblastomas. EGFR-amplification status was assessed in 93 cases of glioblastoma by silver enhanced in situ hybridization and compared with results of fluorescence in situ hybridization and immunohistochemistry. In a second cohort, silver enhanced in situ hybridization status was correlated with EGFR gene expression data. The EGFR gene was amplified in 25/90 tumours (28%) by silver enhanced in situ hybridization, and in 28/93 tumours (30%) by fluorescence in situ hybridization. The concordance rate for silver enhanced in situ hybridization and fluorescence in situ hybridization was 98%. Two glioblastomas were scored as being amplified by fluorescence in situ hybridization but not by silver enhanced in situ hybridization. Polymerase chain reaction-based EGFR-amplification data were highly correlated with EGFR silver enhanced in situ hybridization. Altogether, 81 of 91 cases (89%) showed positivity for EGFR expression by immunohistochemistry. Although EGFR protein over expression was associated with gene amplification (r = 0.40, P < 0.001), there were 29 of 91 cases that showed a high EGFR protein level and no EGFR amplification by fluorescence in situ hybridization. The high concordance rate of silver enhanced in situ hybridization and fluorescence in situ hybridization for the detection of EGFR amplification in paraffin-embedded glioblastomas samples demonstrates that silver enhanced in situ hybridization is a valid and attractive alternative to fluorescence in situ hybridization. Silver enhanced in situ hybridization combines the advantages of bright field microscopy with fully automated analysis in a cost-effective way thereby emphasizing its use for routine application in surgical pathology. Modern Pathology (2009) 22, 1263-1271; doi:10.1038/modpathol.2009.86; published online 12 June 2009 C1 [Gaiser, Timo; von Deimling, Andreas] Univ Heidelberg, Inst Pathol, Dept Neuropathol, D-6900 Heidelberg, Germany. [Waha, Andreas; Pietsch, Torsten] Univ Bonn, Inst Neuropathol, D-5300 Bonn, Germany. [Moessler, Franziska; von Deimling, Andreas] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, D-6900 Heidelberg, Germany. [Bruckner, Thomas] Univ Heidelberg, Inst Med Biometry & Informat, Heidelberg, Germany. RP Gaiser, T (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 50,Room 1408,50 S Dr, Bethesda, MD 20892 USA. EM gaisert@mail.nih.gov RI Waha, Andreas/J-2950-2014; von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 35 TC 8 Z9 8 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 2009 VL 22 IS 9 BP 1263 EP 1271 DI 10.1038/modpathol.2009.86 PG 9 WC Pathology SC Pathology GA 489UQ UT WOS:000269448700017 PM 19525925 ER PT J AU Marshall, JC Lee, JH Steeg, PS AF Marshall, Jean-Claude Lee, Jong Heun Steeg, Patricia S. TI Clinical-translational strategies for the elevation of Nm23-H1 metastasis suppressor gene expression SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Nm23; Metastasis suppressor genes; Gene expression ID MEDROXYPROGESTERONE ACETATE; BREAST-CANCER; PROTEIN EXPRESSION; RANDOMIZED TRIAL; YOUNG-WOMEN; N-MYC; CARCINOMA; CELLS; THERAPY; CYCLOPHOSPHAMIDE AB Interruption of the tumor metastatic process is a new, thought provoking molecular target for the treatment of cancer. The Nm23-H1 metastasis suppressor gene stands as a validated molecular target owing to its reduced expression in many aggressive human tumors, and the reduction in metastatic potential in vivo upon re-expression in multiple cell lines. Several compounds have been identified which elevate Nm23-H1 expression in vitro including indomethacin, gamma Linolenic Acid, trichostatin A, 5-aza-deoxycytidine, and high dose medroxyprogesterone acetate. Using a model of lung metastatic colonization by MDA-MB-231 human breast carcinoma cells, we demonstrated that high dose MPA reduced the formation of overt lung metastases by 37-46% and those metastases that formed were statistically smaller. A Phase II clinical trial of high dose MPA, alone or in combination with metronomic chemotherapy has recently opened. C1 [Marshall, Jean-Claude; Lee, Jong Heun; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), 37 Convent Dr,Room 1122, Bethesda, MD 20892 USA. EM marshallje@mail.nih.gov; Steegp@mail.nih.gov FU Intramural NIH HHS [Z01 SC000892-24] NR 36 TC 13 Z9 16 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 2009 VL 329 IS 1-2 BP 115 EP 120 DI 10.1007/s11010-009-0116-3 PG 6 WC Cell Biology SC Cell Biology GA 480IO UT WOS:000268727600010 PM 19387797 ER PT J AU Lee, JH Marshall, JC Steeg, PS Horak, CE AF Lee, Jong Heun Marshall, Jean-Claude Steeg, Patricia S. Horak, Christine E. TI Altered gene and protein expression by Nm23-H1 in metastasis suppression SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Nm23; Metastasis suppressor genes; Gene expression ID BREAST-CARCINOMA CELLS; NUCLEOSIDE DIPHOSPHATE KINASE; AUTONOMOUS LETHAL MUTATION; ACID RECEPTOR EDG2; CANCER-CELLS; TUMOR-METASTASIS; ADENOCARCINOMA CELLS; ENZYMATIC-ACTIVITY; HYBRID DYSGENESIS; MELANOMA-CELLS AB Metastasis suppressor genes (MSG) are characterized by their ability to inhibit the formation of metastasis, while not affecting the growth of the primary tumor in vivo. Nm23-H1, the first MSG to be characterized, has been shown to alter both gene and protein expression in cancer cells. Recently, microarray expression profiling revealed that Nm23-H1 downregulated EDG2, which encodes for a lysophosphatidic acid (LPA) receptor. Reintroduction of EDG2 into cells that express Nm23-H1 overcame the metastasis suppressive ability of Nm23-H1 in both in vivo pulmonary colonization and spontaneous metastasis assays. In addition, isotope capture affinity tag (ICAT) proteomic analysis was performed to identify differentially expressed proteins not accounted for by microarray analysis. ICAT identified several differentially regulated proteins, including GEMIN5, a protein involved in differential mRNA splicing. The contribution of alternative mRNA splicing to cancer and cancer metastasis is poorly defined. It is possible that Nm23-H1, through the regulation of RNA processing proteins, may play a role in proteome stability. C1 [Lee, Jong Heun; Marshall, Jean-Claude; Steeg, Patricia S.; Horak, Christine E.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, 37 Convent Dr,Room 1122, Bethesda, MD 20892 USA. EM Steegp@mail.nih.gov FU Intramural NIH HHS [Z01 SC000892-24] NR 50 TC 13 Z9 16 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD SEP PY 2009 VL 329 IS 1-2 BP 141 EP 148 DI 10.1007/s11010-009-0124-3 PG 8 WC Cell Biology SC Cell Biology GA 480IO UT WOS:000268727600013 PM 19415462 ER PT J AU Dagley, MJ Dolezal, P Likic, VA Smid, O Purcell, AW Buchanan, SK Tachezy, J Lithgow, T AF Dagley, Michael J. Dolezal, Pavel Likic, Vladimir A. Smid, Ondrej Purcell, Anthony W. Buchanan, Susan K. Tachezy, Jan Lithgow, Trevor TI The Protein Import Channel in the Outer Mitosomal Membrane of Giardia intestinalis SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE mitochondria; mitosomes; Giardia intestinalis; protein translocation; evolution ID MITOCHONDRIAL-MEMBRANE; MICROSPORIDIAN MITOSOMES; INTERMEMBRANE SPACE; YEAST MITOCHONDRIA; LAMBLIA; MATURATION; RECEPTORS; EVOLUTION; TRYPANOSOMA; TRANSLOCASE AB The identification of mitosomes in Giardia generated significant debate on the evolutionary origin of these organelles, whether they were highly reduced mitochondria or the product of a unique endosymbiotic event in an amitochondrial organism. As the protein import pathway is a defining characteristic of mitochondria, we sought to discover a TOM (translocase in the outer mitochondrial membrane) complex in Giardia. A Hidden Markov model search of the Giardia genome identified a Tom40 homologous sequence (GiTom40), where Tom40 is the protein translocation channel of the TOM complex. The GiTom40 protein is located in the membrane of mitosomes in a similar to 200-kDa TOM complex. As Tom40 was derived in the development of mitochondria to serve as the protein import channel in the outer membrane, its presence in Giardia evidences the mitochondrial ancestry of mitosomes. C1 [Dagley, Michael J.; Purcell, Anthony W.; Lithgow, Trevor] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3052, Australia. [Dagley, Michael J.; Likic, Vladimir A.; Purcell, Anthony W.] Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Parkville, Vic 3052, Australia. [Dolezal, Pavel; Smid, Ondrej; Tachezy, Jan] Charles Univ Prague, Fac Sci, Dept Parasitol, Prague 2, Czech Republic. [Buchanan, Susan K.] NIDDK, Mol Biol Lab, US NIH, Bethesda, MD USA. [Lithgow, Trevor] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia. RP Dagley, MJ (reprint author), Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3052, Australia. EM trevor.lithgow@med.monash.edu.au OI Purcell, Anthony/0000-0003-0532-8331 FU Australian Research Council; Australian Research Council Federation Fellow; Australian Postgraduate Award; Senior Research Fellow; National Health and Medical Research Council; Marie Curie Outgoing International Fellowship; Ministry of Education [MSM0021620858]; Intramural Research Program of the National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX Giardia strains were a kind gift from Jacqui Upcroft (Queensland Institute of Medical Research, Australia) and GiPDI1 antibodies from Adrian Hehl (University of Zurich, Switzerland). We thank Andrew Perry for his help in the CLANS analysis, Dallas Hartman for his advice and expertise with N-terminal sequencing, and Sri Harsha Ramarathinam for expert assistance with mass spectrometry. This work was supported by a grant from the Australian Research Council (to T. L.). T. L. is an Australian Research Council Federation Fellow, M.J.D. is the recipient of an Australian Postgraduate Award, A. W. P. is a Senior Research Fellow of the National Health and Medical Research Council, and P. D. is the recipient of a Marie Curie Outgoing International Fellowship. J.T. is supported by a grant from the Ministry of Education MSM0021620858. S. K. B. is supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 44 TC 38 Z9 40 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD SEP PY 2009 VL 26 IS 9 BP 1941 EP 1947 DI 10.1093/molbev/msp117 PG 7 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 483WG UT WOS:000269001500002 PM 19531743 ER PT J AU Srivastava, S Di, L Zhdanova, O Li, Z Vardhana, S Wan, Q Yan, Y Varma, R Backer, J Wulff, H Dustin, ML Skolnik, EY AF Srivastava, Shekhar Di, Lie Zhdanova, Olga Li, Zhai Vardhana, Santosha Wan, Qi Yan, Ying Varma, Rajat Backer, Jonathan Wulff, Heike Dustin, Michael L. Skolnik, Edward Y. TI The Class II Phosphatidylinositol 3 kinase C2 beta Is Required for the Activation of the K+ Channel KCa3.1 and CD4 T-Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID IMMUNOLOGICAL SYNAPSE; PHOSPHOINOSITIDE 3-KINASE; POTASSIUM CHANNELS; RECEPTOR MICROCLUSTERS; PATHWAY; DIFFERENTIATION; 3-PHOSPHATE; LYMPHOCYTES; CALMODULIN; PI3K-GAMMA AB The Ca2+-activated K+ channel KCa3.1 is required for Ca2+ influx and the subsequent activation of T-cells. We previously showed that nucleoside diphosphate kinase beta (NDPK-B), a mammalian histidine kinase, directly phosphorylates and activates KCa3.1 and is required for the activation of human CD4 T lymphocytes. We now show that the class II phosphatidylinositol 3 kinase C2 beta (PI3K-C2 beta) is activated by the T-cell receptor (TCR) and functions upstream of NDPK-B to activate KCa3.1 channel activity. Decreased expression of PI3K-C2 beta by siRNA in human CD4 T-cells resulted in inhibition of KCa3.1 channel activity. The inhibition was due to decreased phosphatidylinositol 3-phosphate [ PI( 3) P] because dialyzing PI3K-C2 beta siRNA-treated T-cells with PI(3) P rescued KCa3.1 channel activity. Moreover, overexpression of PI3K-C2 beta in KCa3.1-transfected Jurkat T-cells led to increased TCR-stimulated activation of KCa3.1 and Ca2+ influx, whereas silencing of PI3K-C2 beta inhibited both responses. Using total internal reflection fluorescence microscopy and planar lipid bilayers, we found that PI3K-C2 beta colocalized with Zap70 and the TCR in peripheral microclusters in the immunological synapse. This is the first demonstration that a class II PI3K plays a critical role in T-cell activation. C1 [Srivastava, Shekhar; Di, Lie; Li, Zhai; Skolnik, Edward Y.] NYU, Dept Pharmacol, Langone Med Ctr, New York, NY 10016 USA. [Zhdanova, Olga; Skolnik, Edward Y.] NYU, Div Nephrol, Langone Med Ctr, New York, NY 10016 USA. [Vardhana, Santosha; Wan, Qi; Dustin, Michael L.] NYU, Dept Pharmacol, Langone Med Ctr, Helen L & Martin S Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Varma, Rajat] NIAID, T Cell Biophys Unit, Bethesda, MD 20892 USA. [Yan, Ying; Backer, Jonathan] Albert Einstein Coll Med, Dept Pharmacol, Bronx, NY 10461 USA. [Wulff, Heike] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA. RP Skolnik, EY (reprint author), NYU, Dept Pharmacol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. EM edward.skolnik@nyumc.org RI Varma, Rajat/I-1209-2012; Wan, Qi/F-1694-2013; OI Varma, Rajat/0000-0001-5131-0402; Wan, Qi/0000-0003-3726-5187; Srivastava, Shekhar/0000-0001-5165-7385; Dustin, Michael/0000-0003-4983-6389 FU National Institutes of Health [RO1GM084195, RO1AI052459] FX We thank J. Domin ( Imperial College, London) for the GFP-PI3K-C2 alpha and PI3K-C2 beta constructs and K. Shokat (UCSF Medical Center) for the class I PI3K inhibitors. E.Y.S. is supported by National Institutes of Health Grants RO1GM084195 and RO1AI052459. NR 49 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2009 VL 20 IS 17 BP 3783 EP 3791 DI 10.1091/mbc.E09-05-0390 PG 9 WC Cell Biology SC Cell Biology GA 489SP UT WOS:000269443100002 PM 19587117 ER PT J AU Palmieri, D Fitzgerald, D Shreeve, SM Hua, E Bronder, JL Weil, RJ Davis, S Stark, AM Merino, MJ Kurek, R Mehdorn, HM Davis, G Steinberg, SM Meltzer, PS Aldape, K Steeg, PS AF Palmieri, Diane Fitzgerald, Daniel Shreeve, S. Martin Hua, Emily Bronder, Julie L. Weil, Robert J. Davis, Sean Stark, Andreas M. Merino, Maria J. Kurek, Raffael Mehdorn, H. Maximilian Davis, Gary Steinberg, Seth M. Meltzer, Paul S. Aldape, Kenneth Steeg, Patricia S. TI Analyses of Resected Human Brain Metastases of Breast Cancer Reveal the Association between Up-Regulation of Hexokinase 2 and Poor Prognosis SO MOLECULAR CANCER RESEARCH LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; MELANOMA-CELLS; ENZYME-ACTIVITIES; CNS METASTASES; IN-VITRO; EXPRESSION; CARCINOMA; RISK; MITOCHONDRIA; THERAPY AB Brain metastases of breast cancer seem to be increasing in incidence as systemic therapy improves. Metastatic disease in the brain is associated with high morbidity and mortality. We present the first gene expression analysis of laser-captured epithelial cells from resected human brain metastases of breast cancer compared with unlinked primary breast tumors. The tumors were matched for histology, tumor-node-metastasis stage, and hormone receptor status. Most differentially expressed genes were down-regulated in the brain metastases, which included, surprisingly, many genes associated with metastasis. Quantitative real-time PCR analysis confirmed statistically significant differences or strong trends in the expression of six genes: BMP1, PEDF, LAMy3, SIAH, STHMN3, and TSPD2. Hexokinase 2 (HK2) was also of interest because of its increased expression in brain metastases. HK2 is important in glucose metabolism and apoptosis. In agreement with our microarray results, HK2 levels (both mRNA and protein) were elevated in a brain metastatic derivative (231-BR) of the human breast carcinoma cell line MDA-MB-231 relative to the parental cell line (231-P) in vitro. Knockdown of HK2 expression in 231-BR cells using short hairpin RNA reduced cell proliferation when cultures were maintained in glucose-limiting conditions. Finally, HK2 expression was analyzed in a cohort of 123 resected brain metastases of breast cancer. High HK2 expression was significantly associated with poor patient survival after craniotomy (P = 0.028). The data suggest that HK2 overexpression is associated with metastasis to the brain in breast cancer and it may be a therapeutic target. (Mol Cancer Res 2009;7(9):1438-45) C1 [Palmieri, Diane; Fitzgerald, Daniel; Shreeve, S. Martin; Hua, Emily; Bronder, Julie L.; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Mehdorn, H. Maximilian; Meltzer, Paul S.] NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. [Merino, Maria J.] NCI, Ctr Canc Res, Surg Pathol Sect, Pathol Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Weil, Robert J.] Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. [Davis, Sean; Stark, Andreas M.] Univ Schleswig Holstein, Med Ctr, Kiel, Germany. [Kurek, Raffael] Univ Tubingen, Tubingen, Germany. [Davis, Gary] Sigma Aldrich Biotechnol, St Louis, MO USA. [Aldape, Kenneth] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 1122,9000 Rockville Pike, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov RI Mehdorn, Maximilian /D-2495-2010; Palmieri, Diane/B-4258-2015; OI Mason, Julie/0000-0002-5144-175X; Davis, Sean/0000-0002-8991-6458 FU National Cancer Institute Intramural program and Department of Defense Breast Cancer Research Program [W81XWH-062-0033] FX Grant support: National Cancer Institute Intramural program and Department of Defense Breast Cancer Research Program grant W81XWH-062-0033. NR 40 TC 81 Z9 84 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2009 VL 7 IS 9 BP 1438 EP 1445 DI 10.1158/1541-7786.MCR-09-0234 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 496ZM UT WOS:000270019700003 PM 19723875 ER PT J AU Jain, L Vargo, CA Danesi, R Sissung, TM Price, DK Venzon, D Venitz, J Figg, WD AF Jain, Lokesh Vargo, Craig A. Danesi, Romano Sissung, Tristan M. Price, Douglas K. Venzon, David Venitz, Juergen Figg, William D. TI The role of vascular endothelial growth factor SNPs as predictive and prognostic markers for major solid tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID GENOME-WIDE ASSOCIATION; CELL LUNG-CANCER; ADVANCED BREAST-CANCER; SINGLE NUCLEOTIDE POLYMORPHISMS; CYTOKINE GENE POLYMORPHISMS; GENDER-SPECIFIC ASSOCIATION; COLORECTAL-CANCER; PROSTATE-CANCER; VEGF GENE; COLON-CANCER AB Angiogenesis is crucial for development and metastasis of tumors, and vascular endothelial growth factor (VEGF) is a key mediator of this process. The importance of VEGF in tumorigenesis and tumor progression makes it an attractive target for the development of anticancer therapies. Inhibition of angiogenesis has shown promising clinical efficacy; however, not all patients treated with antiangiogenic agents derive benefit from them. Some patients are predisposed to refractory disease, whereas others develop resistance after initial response. Patients may also have different severity of drug-related adverse events. Optimization of drug administration based on disease status and individual responsiveness is important in limiting the treatment failure and minimization of side-effects. Single nucleotide polymorphisms (SNP) in VEGF may alter VEGF protein concentrations, influence the process of angiogenesis, and may relate to interindividual variation in the risk and progression of selected tumors, and their resistance to treatments. This review examines the role of SNPs in the VEGF gene as predictive and prognostic markers for major solid tumors, including the breast, non-small cell lung, colorectal, and prostate cancers. Selected VEGF SNPs seem to be associated with risk of these cancers; however, there is lack of unanimity in findings, in part influenced by differences in study design and analysis. [Mol Cancer Ther 2009;8(9):2496-508] C1 [Figg, William D.] NCI, Med Oncol Branch, CCR, NIH,Clin Pharmacol Program, Bethesda, MD 20892 USA. [Jain, Lokesh; Venitz, Juergen; Figg, William D.] Virginia Commonwealth Univ, Dept Pharmaceut, Sch Pharm, Richmond, VA USA. [Danesi, Romano] Univ Pisa, Dept Internal Med, Pisa, Italy. [Sissung, Tristan M.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, CCR, NIH,Clin Pharmacol Program, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Cancer Institute (NCI); National Institutes of Health (NIH); U.S. Department of Health and Human Services FX Intramural Research Program of the National Cancer Institute (NCI), National Institutes of Health (NIH), U.S. Department of Health and Human Services. NR 72 TC 102 Z9 106 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2009 VL 8 IS 9 BP 2496 EP 2508 DI 10.1158/1535-7163.MCT-09-0302 PG 13 WC Oncology SC Oncology GA 496JY UT WOS:000269968900002 PM 19755511 ER PT J AU Salerno, E Scaglione, BJ Coffman, FD Brown, BD Baccarini, A Fernandes, H Marti, G Raveche, ES AF Salerno, Erica Scaglione, Brian J. Coffman, Frederick D. Brown, Brian D. Baccarini, Alessia Fernandes, Helen Marti, Gerald Raveche, Elizabeth S. TI Correcting miR-15a/16 genetic defect in New Zealand Black mouse model of CLL enhances drug sensitivity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANTLE CELL LYMPHOMA; MALIGNANT B-1 CELLS; B-CELL; LYMPHOPROLIFERATIVE DISORDERS; TUMOR-SUPPRESSOR; CYCLIN D1; TRANSGENE EXPRESSION; ENDOGENOUS MICRORNA; LENTIVIRAL VECTORS AB Alterations in the human 13q14 genomic region containing microRNAs mir-15a and mir-16-1 are present in Most human chronic lymphocytic leukemia (CLL). We have previously found the development of CLL in the New Zealand Black murine model to be associated with a point mutation in the primary mir-15a/16-1 region, which correlated with a decrease in mature miR-16 and miR-15a levels. In this study, addition of exogenous miR-15a and miR-16 led to an accumulation of cells in G(1) in non-New Zealand Black B cell and New Zealand Black-derived malignant B-1 cell lines. However, the New Zealand Black line had significantly greater G(1) accumulation, suggesting a restoration of cell cycle control upon exogenous miR-15a/16 addition. Our experiments showed a reduction in protein levels of cyclin D1, a miR-15a/16 target and cell cycle regulator of G(1)/S transition, in the New Zealand Black cell line following miR-15a/16 addition. These microRNAs were shown to directly target the cyclin D1 3' untranslated region using a green fluorescent protein lentiviral expression system. miR-16 was also shown to augment apoptosis induction by nutlin, a mouse double minute 2 (MDM2) antagonist, and genistein, a tyrosine kinase inhibitor, when added to a B-1 cell line derived from multiple in vivo pas-sages of malignant B-1 cells from New Zealand Black mice with CLL. miR-16 synergized with nutlin and genistein to induce apoptosis. Our data support a role for the mir-15a/16-1 cluster in cell cycle regulation and suggest that these mature microRNAs in both the New Zealand Black model and human CLL may be targets for therapeutic efficacy in this disease. [Mol Cancer Ther 2009;8(9):2684-92] C1 [Salerno, Erica; Scaglione, Brian J.; Coffman, Frederick D.; Fernandes, Helen; Raveche, Elizabeth S.] Univ Med & Dent New Jersey, Dept Pathol & Lab Med, New Jersey Med Sch, Newark, NJ 07103 USA. [Scaglione, Brian J.; Brown, Brian D.; Baccarini, Alessia] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Marti, Gerald] NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. RP Raveche, ES (reprint author), Univ Med & Dent New Jersey, Dept Pathol & Lab Med, New Jersey Med Sch, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU New Jersey Commission on Cancer Research FX This research was funded in part by the New Jersey Commission on Cancer Research predoctoral fellowship awarded (E. Salerno). NR 49 TC 37 Z9 41 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD SEP PY 2009 VL 8 IS 9 BP 2684 EP 2692 DI 10.1158/1535-7163.MCT-09-0127 PG 9 WC Oncology SC Oncology GA 496JY UT WOS:000269968900021 PM 19723889 ER PT J AU Boman, B Kopellovich, L Siracusa, LD Zhang, T Henderson, K Cofer, Z Buchberg, AM Fields, JZ Otevrel, T AF Boman, Bruce Kopellovich, Levy Siracusa, Linda D. Zhang, Tao Henderson, Kim Cofer, Zenobia Buchberg, Arthur M. Fields, Jeremy Z. Otevrel, Tomas TI A Tcf4-GFP Reporter Mouse Model for Monitoring Effects of Apc Mutations During Intestinal Tumorigenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE stem cells; colorectal cancer; Tcf4; adenomatous polyposis coli; survivin; adenoma ID TUMOR-SUPPRESSOR PROTEIN; BETA-CATENIN; STEM-CELL; COLON-CANCER; ADENOMATOUS POLYPOSIS; COLORECTAL TUMORS; GENE-PRODUCT; MICE; EXPRESSION; ASSOCIATION AB Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and transfected it into SW480 cells that have constitutively activated Tcf4. Reporter activity increased 47-fold. Next, we created transgenic (Tg) mice by transducing the construct into C57BL/6J mice. Fluorescence microscopy did not detect GFP in intestinal sections, but flow cytometry showed 5% of crypt cells to be GFP(+). We then established cross-bred mice (Tg x Apc(Min/+)), which have a germline Apc mutation and sustained Tcf4 activation. Here, fluorescence microscopy showed GFP(+) cells at or near the base of normal-appearing crypts. In adenomas, in which Apc is inactivated, GFP(+) signal was even greater. Immunostaining for the Tcf4 target genes survivin (BIRC5) and cyclin D1 (CCND1) showed that their expression also paralleled GFP positivity. We conclude that GFP directly reports Tcf4 activation in vivo and tracks the predicted increases in Tcf4 activation that result from Apc inactivation, and that Apc mutation contributes to survivin and cyclin D1 overexpression through Tcf4 activation. Our Tcf4 mouse should be useful in studying the effects of chemopreventive agents on Wnt signaling and changes in proliferative crypt cell populations-including stem cells-during intestinal tumorigenesis. (C) 2009 Wiley-Liss, Inc. C1 [Boman, Bruce; Siracusa, Linda D.; Zhang, Tao; Henderson, Kim; Cofer, Zenobia; Buchberg, Arthur M.; Otevrel, Tomas] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Kopellovich, Levy] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. [Fields, Jeremy Z.] CA TX Inc, Gladwyne, PA USA. RP Boman, B (reprint author), Christiana Care Hlth Syst, Helen F Graham Canc Ctr, Ctr Translat Canc Res, 4701 Ogletown Stanton Rd, Newark, DE 19713 USA. OI Buchberg, Arthur/0000-0002-0543-5631 FU NCI [N01-CN-35106, R21-CA095667-01]; Pennsylvania Department of Health FX This research was supported in part by NCI (grants N01-CN-35106 and R21-CA095667-01) and from the Pennsylvania Department of Health. We would like to thank Dr. Juan Palazzo and Dr. Peter McCue of Thomas Jefferson University for assistance in immunohistochemistry and tissue processing through the Kimmel Cancer Center Pathology Core Facility. We thank the Kimmel Cancer Center Transgenic and Gene Targeting Facility, especially Jan Guz and Jennifer Dunlap, for generating and genotyping the transgenic mice. NR 36 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2009 VL 48 IS 9 BP 821 EP 831 DI 10.1002/mc.20526 PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 492EB UT WOS:000269636300006 PM 19263440 ER PT J AU Payton-Stewart, F Schoene, NW Kim, YS Burow, ME Cleveland, TE Boue, SM Wang, TTY AF Payton-Stewart, Florastina Schoene, Norberta W. Kim, Young S. Burow, Matthew E. Cleveland, Thomas E. Boue, Stephen M. Wang, Thomas T. Y. TI Molecular Effects of Soy Phytoalexin Glyceollins in Human Prostate Cancer Cells LNCaP SO MOLECULAR CARCINOGENESIS LA English DT Article DE androgen; estrogen; cancer prevention; cell cycle; gene expression ID ANDROGEN-RESPONSIVE GENES; ESTROGEN-RECEPTOR-BETA; CLINICAL-TRIALS; HUMAN BREAST; GENISTEIN; GROWTH; ISOFLAVONES; INHIBITION; PATHWAYS; P21(WAF1/CIP1) AB Glyceollins are soy-derived phytoalexins that have been proposed to be candidate cancer preventive compounds. The effect of the glyceollins on prostate cancer is unknown. The present study examined the molecular effects of soy phytoalexin, glyceollins, on human prostate cancer cell LNCaP to further elucidate its potential effects on prostate cancer prevention. We found that the glyceollins inhibited LNCaP cell growth similar to that of the soy isoflavone genistein. The growth inhibitory effects of the glyceollins appeared to be due to an inhibition of G1/S progression and correlated with an up-regulation of cyclin-dependent kinase inhibitor 1 A and B mRNA and protein levels. By contrast, genistein only up-regulates cyclin-dependent kinase inhibitor 1A. In addition, glyceollin treatments led to down-regulated mRNA levels for androgen responsive genes. In contrast to genistein, this effect of glyceollins on androgen responsive genes appeared to be mediated through modulation of an estrogen- but not androgen-mediated pathway. Hence, the glyceollins exerted multiple effects on LNCaP cells that may be considered cancer preventive and the mechanisms of action appeared to be different from other soy-derived phytochemicals. (C) 2009 Wiley-Liss, Inc. C1 [Schoene, Norberta W.; Wang, Thomas T. Y.] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. [Payton-Stewart, Florastina; Burow, Matthew E.] Tulane Univ, Sch Med, Sect Hematol & Med Oncol, New Orleans, LA 70112 USA. [Kim, Young S.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Cleveland, Thomas E.; Boue, Stephen M.] USDA, So Reg Res Ctr, New Orleans, LA 70179 USA. RP Wang, TTY (reprint author), ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, 10300 Baltimore Ave,Bldg 307C,Room 132, Beltsville, MD 20705 USA. RI Burow, Matthew/D-6351-2013 OI Burow, Matthew/0000-0002-0642-6630 FU U.S appropriated funds [1235-51530-052-00, 59-6435-7-188]; National Cancer Institute; National Institute [DK059389] FX This work was supported by U.S appropriated funds to USDA project number 1235-51530-052-00 (TTYW, NWS), 59-6435-7-188 (TEC, SMB), the National Cancer Institute (YSK) and National Institute grant DK059389 (MEB). NR 33 TC 32 Z9 34 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2009 VL 48 IS 9 BP 862 EP 871 DI 10.1002/mc.20532 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 492EB UT WOS:000269636300010 PM 19263441 ER PT J AU Rahman, S Duncan, AJ Bitner-Glindziez, M Meunier, B Costello, H Hargreaves, IP Lopez, LC Hirano, M Quinzii, CM Sadowski, MI Singleton, A Clayton, PT AF Rahman, S. Duncan, A. J. Bitner-Glindziez, M. Meunier, B. Costello, H. Hargreaves, I. P. Lopez, L. C. Hirano, M. Quinzii, C. M. Sadowski, M. I. Singleton, A. Clayton, P. T. TI A NEW GENETIC CAUSE OF PRIMARY COENZYME Q10 DEFICIENCY SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Rahman, S.; Duncan, A. J.; Bitner-Glindziez, M.; Costello, H.; Clayton, P. T.] UCL Inst Child Hlth, Clin & Mol Genet Unit, London, England. [Rahman, S.] Natl Hosp Neurol & Neurosurg, MRC, Neuromuscular Res Ctr, London WC1N 3BG, England. [Meunier, B.] CNRS, Ctr Genet Mol, Gif Sur Yvette, France. [Hargreaves, I. P.] Natl Hosp Neurol & Neurosurg, Neurometab Unit, London WC1N 3BG, England. [Lopez, L. C.; Hirano, M.; Quinzii, C. M.] Columbia Univ, Med Ctr, New York, NY USA. [Sadowski, M. I.] Natl Inst Med Res, Div Math Biol, London NW7 1AA, England. [Singleton, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RI Sadowski, Michael/F-4475-2010; Singleton, Andrew/C-3010-2009; Rahman, Shamima/C-5232-2008 OI Sadowski, Michael/0000-0002-4546-2159; Rahman, Shamima/0000-0003-2088-730X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 113 BP 5 EP 5 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600014 ER PT J AU Sloan, JL Blake, TL Chandler, RJ Tsai, MS Brooks, BP Sood, RB Venditti, CP AF Sloan, J. L. Blake, T. L. Chandler, R. J. Tsai, M. S. Brooks, B. P. Sood, R. B. Venditti, C. P. TI A ZEBRAFISH MODEL OF COBALAMIN C DEFICIENCY DISPLAYS GROWTH RETARDATION, DEVELOPMENT DEFECTS OF THE CENTRAL NERVOUS SYSTEM AND METABOLIC ABNORMALITIES SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Blake, T. L.; Sood, R. B.] NHGRI, Zebrafish Core Facil, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Brooks, B. P.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 141 BP 13 EP 13 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600042 ER PT J AU Faghfoury, H Shroff, M Blaser, S Mudd, SH Wagner, C Corrales, FJ Stockley, T Schulze, AJ AF Faghfoury, H. Shroff, M. Blaser, S. Mudd, S. H. Wagner, C. Corrales, F. J. Stockley, T. Schulze, A. J. TI CEREBRAL HYPOMYELINATION AND MATERNAL UNIPARENTAL DISOMY 10 IN A PATIENT WITH MAT I/III DEFICIENCY SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Faghfoury, H.; Shroff, M.; Blaser, S.; Stockley, T.; Schulze, A. J.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Mudd, S. H.] NIMH, Bethesda, MD 20892 USA. [Wagner, C.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Corrales, F. J.] Univ Navarra, E-31080 Pamplona, Spain. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 177 BP 21 EP 22 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600078 ER PT J AU Leonard, SC Carlson, JE Wainer, I Wang, Y AF Leonard, S. C. Carlson, J. E. Wainer, I. Wang, Y. TI QUANTITATION OF UNDERIVATIZED ACYLCARNITINES IN HUMAN MITOCHONDRIAL SAMPLES USING TRIPLE QUADRUPOLE MASS SPECTROMETRY SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Leonard, S. C.] Prod Applicat Lab, Framingham, MA USA. [Wainer, I.; Wang, Y.] NIA, NIH, Baltimore, MD 21224 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 318 BP 53 EP 53 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600219 ER PT J AU DePaolo, JS Goker-Alpan, O Tayebi, N Stubblefield, B Gupta, N Goldin, E Sidransky, E AF DePaolo, J. S. Goker-Alpan, O. Tayebi, N. Stubblefield, B. Gupta, N. Goldin, E. Sidransky, E. TI A MUTATION IN LYSOSOMAL INTEGRAL MEMBRANE PROTEIN TYPE 2 (LIMP2) ASSOCIATED WITH MYOCLONIC EPILEPSY IN A PATIENT WITH TYPE 3 GAUCHER DISEASE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [DePaolo, J. S.; Goker-Alpan, O.; Tayebi, N.; Stubblefield, B.; Gupta, N.; Goldin, E.; Sidransky, E.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 458 BP 84 EP 84 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600357 ER PT J AU Choi, JH Lopez, G Gupta, N Stubblefield, B Goker-Alpan, O Tayebi, N Sidransky, E AF Choi, J. H. Lopez, G. Gupta, N. Stubblefield, B. Goker-Alpan, O. Tayebi, N. Sidransky, E. TI GBA MUTATIONS AND CLINICAL FEATURES OF PATIENTS EVALUATED AT A REFERRAL CLINIC FOR PARKINSON DISEASE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Choi, J. H.; Gupta, N.; Stubblefield, B.; Goker-Alpan, O.; Tayebi, N.; Sidransky, E.] NHGRI, NIH, Bethesda, MD 20892 USA. [Lopez, G.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 465 BP 85 EP 86 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600364 ER PT J AU Sidranskyl, E AF Sidranskyl, E. TI INTERNATIONAL MULTI-CENTER ANALYSIS OF GLUCOCEREBROSIDASE MUTATIONS IN PARKINSON DISEASE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Sidranskyl, E.] NHGRI, Int Working Grp GBA Mutat PD2, Med Genet Branch 1, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 462 BP 85 EP 85 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600361 ER PT J AU Hauser, NS Graf, JC Sloan, J Manoli, I Venditti, CP AF Hauser, N. S. Graf, J. C. Sloan, J. Manoli, I. Venditti, C. P. TI VARIABLE DIETARY MANAGEMENT OF METHYLMALONIC ACIDEMIA: METABOLIC AND ENERGETIC CORRELATIONS SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Hauser, N. S.; Sloan, J.; Manoli, I.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 604 BP 119 EP 119 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600503 ER PT J AU Manoli, I Chandler, RJ Zerfas, P Hoffmann, V Venditti, CP AF Manoli, I. Chandler, R. J. Zerfas, P. Hoffmann, V. Venditti, C. P. TI A MURINE MODEL OF MUT (0) METHYLMALONIC ACIDEMIA (MMA) TREATED BY ORTHOTOPIC LIVER TRANSPLANTATION SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Manoli, I.; Chandler, R. J.; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Zerfas, P.; Hoffmann, V.] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 614 BP 121 EP 122 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600513 ER PT J AU Raymond, K Loken, PR Magera, MJ Introne, W Tortorelli, S Gavrilov, D Oglesbee, D Rinaldo, P Matern, D AF Raymond, K. Loken, P. R. Magera, M. J. Introne, W. Tortorelli, S. Gavrilov, D. Oglesbee, D. Rinaldo, P. Matern, D. TI HOMOGENTISIC ACID INTERFERES WITH ROUTINE URINE CREATININE DETERMINATION SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Raymond, K.; Loken, P. R.; Magera, M. J.; Tortorelli, S.; Gavrilov, D.; Oglesbee, D.; Rinaldo, P.; Matern, D.] Mayo Clin, Coll Med, Rochester, MN USA. [Introne, W.] NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 630 BP 125 EP 125 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600528 ER PT J AU Chandler, RJ Venditti, CP AF Chandler, Randy J. Venditti, Charles P. TI LETHAL MURINE MODEL OF METHYLMALONIC ACIDEMIA RESCUED IN EXCESS OF A YEAR FOLLOWING RAAV8 MEDIATED GENE THERAPY SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, NIH, Bethesda, MD 20892 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 639 BP 126 EP 127 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600537 ER PT J AU Adams, DR Sloan, JL Munasinghe, JP Baker, EH Braverman, N Venditti, CP AF Adams, D. R. Sloan, J. L. Munasinghe, J. P. Baker, E. H. Braverman, N. Venditti, C. P. TI CSF METHYLMALONIC ACID AND 2-METHYLCITRATE LEVELS IN METHYLMALONIC ACIDEMIA: PRACTICAL AND THEORETICAL CONSIDERATIONS SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Adams, D. R.; Sloan, J. L.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. [Munasinghe, J. P.] NINDS, NIH, Bethesda, MD 20892 USA. [Baker, E. H.] NIH, CC, Bethesda, MD 20892 USA. [Braverman, N.] McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 643 BP 127 EP 128 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600541 ER PT J AU O'Shea, CJ Wiggs, E Pao, M Sloan, JL Manoli, I Venditti, CP Snow, J AF O'Shea, C. J. Wiggs, E. Pao, M. Sloan, J. L. Manoli, I. Venditti, C. P. Snow, J. TI NEUROCOGNITIVE OUTCOME IN ISOLATED METHYLMALONIC ACIDEMIA (MMA) AND CBLC SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [O'Shea, C. J.; Wiggs, E.; Pao, M.; Snow, J.] NIMH, NIH, Bethesda, MD 20892 USA. [Sloan, J. L.; Manoli, I.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 646 BP 128 EP 128 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600544 ER PT J AU Venditti, CP Manoli, I Chandler, RJ AF Venditti, C. P. Manoli, I. Chandler, R. J. TI A METHOD TO DETERMINE THE IN VIVO OXIDATIVE CAPACITY FOR 13C ISOTOPOMERS IN MICE: USE TO STUDY INTERMEDIARY METABOLISM AND TO MONITOR TRANSGENE ACTIVITY SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Venditti, C. P.; Manoli, I.; Chandler, R. J.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 645 BP 128 EP 128 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600543 ER PT J AU Carrillo-Carrasco, N Sloan, J Hamosh, A Valle, D Venditti, CP AF Carrillo-Carrasco, N. Sloan, J. Hamosh, A. Valle, D. Venditti, C. P. TI HYDROXYCOBALAMIN DOSE ESCALATION OPTIMIZES METABOLIC CONTROL IN CBLC SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Carrillo-Carrasco, N.; Sloan, J.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hamosh, A.; Valle, D.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 657 BP 131 EP 131 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600555 ER PT J AU Faghfoury, H Hyland, K Rosenblatt, DS da Costa, K Wagner, C Mudd, H Blaser, S Schulze, A AF Faghfoury, H. Hyland, K. Rosenblatt, D. S. da Costa, K. Wagner, C. Mudd, H. Blaser, S. Schulze, A. TI CLINICAL AND BIOCHEMICAL CHARACTERIZATION OF A PATIENT WITH SEVERE MTHFR DEFICIENCY CAUSED BY A NOVEL MUTATION IN THE MTHFR GENE SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Faghfoury, H.; Blaser, S.; Schulze, A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Rosenblatt, D. S.] McGill Univ, Montreal, PQ, Canada. [da Costa, K.] Univ N Carolina, Chapel Hill, NC USA. [Wagner, C.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Mudd, H.] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 682 BP 136 EP 137 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600580 ER PT J AU Markello, TC Hart, TC Hart, PS Adams, DR Gahl, WA AF Markello, T. C. Hart, T. C. Hart, P. S. Adams, D. R. Gahl, W. A. TI USING HOMOZYGOSITY MAPPING AND IDENTITY BY DESCENT TO IDENTIFY LINKAGE REGIONS EFFICIENTLY FROM HIGH-DENSITY SNP OLIGONUCLEOTIDE ARRAY DATA: A STRATEGY FOR FINDING GENES FOR RECESSIVE METABOLIC DISORDERS IN VERY SMALL PEDIGREES SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Markello, T. C.; Hart, P. S.; Adams, D. R.; Gahl, W. A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Hart, T. C.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 694 BP 139 EP 139 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600592 ER PT J AU Nesterova, G Ausavarat, S Huizing, M Adams, D Ciccone, C Ziegler, S Collins, M Gahl, W AF Nesterova, G. Ausavarat, S. Huizing, M. Adams, D. Ciccone, C. Ziegler, S. Collins, M. Gahl, W. TI CASE REPORT: PATIENT WITH HYPERVITAMINOSIS D, HYPERCALCIURIA AND NEPHROLITHIASIS SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 11th International Conference of Inborn Errors of Metabolism CY AUG 29-SEP 02, 2009 CL San Diego, CA C1 [Nesterova, G.; Ausavarat, S.; Huizing, M.; Adams, D.; Ciccone, C.; Ziegler, S.; Collins, M.; Gahl, W.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 MA 731 BP 148 EP 148 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600629 ER PT J AU Tsai, MY Loria, CM Cao, J Kim, Y Siscovick, DS Schreiner, PJ Hanson, NQ AF Tsai, Michael Y. Loria, Catherine M. Cao, Jing Kim, Yongin Siscovick, David S. Schreiner, Pamela J. Hanson, Naomi Q. TI Polygenic association with total homocysteine in the post-folic acid fortification era: The CARDIA study SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Cystathionine beta-synthase; Folic acid; Homocysteine; Methylenetetrahydrofolate reductase; Methionine synthase; Methionine synthase reductase ID CYSTATHIONINE BETA-SYNTHASE; CORONARY-ARTERY-DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; PLASMA HOMOCYSTEINE; METHIONINE SYNTHASE; RISK-FACTOR; CARDIOVASCULAR-DISEASE; COMMON MUTATION; VASCULAR-DISEASE; HEART-DISEASE AB Elevated plasma concentration of total homocysteine (tHcy) has been linked with many diseases. tHcy is associated with a variety of factors, including polymorphisms in genes involved in homocysteine metabolism. It is not clear whether US-mandated fortification of grain products With folic acid has affected the association of genetic variants with tHcy levels. We determined tHcy concentrations in sera from 997 Caucasians and 692 African Americans participants in the Corollary Artery Risk Development in Young Adults (CARDIA) study before and after folic acid fortification, DNA was genotyped for variants present in four genes involved in homocysteine metabolism: cystathionine beta-synthase (CBS) 844ins68, methionine synthase (MS) 2756A>G; methionine synthase reductase (MTRR) 66A>G and methylenetetrahydrofolate reductase (MTHFR) 677C>T and 1298A>C. A greater number of African Americans were homozygous for the MS 2756GG, MTRR 66GG and CBS 844ins68 genotypes compared to Caucasians, while prevalence of MTHFR 677TT and 1298CC genotypes was Substantially lower in African Americans compared to Caucasians. The overall variance in tHcy levels at y 0, 7 and 15 that call be explained by the combined presence of all five variants increased slightly over time in Caucasians (17%, y 0; 21%, y 7; and 26%, y 15) and in African Americans (13%, y 0; 17% y 7; and 18% y 15) largely due to decrease in tHcy variance. (C) 2009 Elsevier Inc. All rights reserved. C1 [Tsai, Michael Y.; Cao, Jing; Hanson, Naomi Q.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Loria, Catherine M.] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Kim, Yongin] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Schreiner, Pamela J.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Tsai, MY (reprint author), 420 Delaware St SE,Mayo Mail Code 609, Minneapolis, MN 55455 USA. EM tsaix001@tc.umn.edu FU National Heart, Lung, and Blood Institute [N01-HC-95095, N01-HC-48047-48050, N01-HC-05187] FX CARDIA is Supported by the National Heart, Lung, and Blood Institute (N01-HC-95095, N01-HC-48047-48050, and N01-HC-05187). NR 37 TC 5 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 BP 181 EP 186 DI 10.1016/j.ymgme.2009.05.012 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600635 PM 19577940 ER PT J AU Roessler, E Pei, WH Ouspenskaia, MV Karkera, JD Velez, JI Banerjee-Basu, S Gibney, G Lupo, PJ Mitchell, LE Towbin, JA Bowers, P Belmont, JW Goldmuntz, E Baxevanis, AD Feldman, B Muenke, M AF Roessler, Erich Pei, Wuhong Ouspenskaia, Maia V. Karkera, Jayaprakash D. Velez, Jorge Ivan Banerjee-Basu, Sharmilla Gibney, Gretchen Lupo, Philip J. Mitchell, Laura E. Towbin, Jeffrey A. Bowers, Peter Belmont, John W. Goldmuntz, Elizabeth Baxevanis, Andreas D. Feldman, Benjamin Muenke, Maximilian TI Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE NODAL; GDF1; TOF; TGA; DORV; Cardiac defects; Laterality; HPE ID CHROMOSOME 22Q11 DELETION; OF-FUNCTION MUTATIONS; LEFT-RIGHT ASYMMETRY; AXIS DEVELOPMENT; MOUSE EMBRYO; LATERALITY DEFECTS; GREAT-ARTERIES; ANTERIOR AXIS; GASTRULATION; SIGNALS AB The cyclopic and laterality phenotypes in model organisms linked to disturbances in the generation Or propagation of Nodal-like signals are potential examples of similar impairments resulting in birth defects in humans. However, the types of gene mutation(s) and their pathogenetic combinations in humans are poorly understood. Here we describe a mutational analysis of the human NODAL gene in a large panel of patients with phenotypes compatible with diminished NODAL ligand function. Significant reductions in the biological activity of NODAL alleles are detected among patients with congenital heart defects (CHD), laterality anomalies (e.g. left-right mis-specification phenotypes), and only rarely holoprosencephaly (HPE). While many of these NODAL variants are typical for family-specific mutations, we also report the presence of alleles with significantly reduced activity among common population variants. We propose that some of these common variants act as modifiers and contribute to the ultimate phenotypic outcome in these patients; furthermore, we draw parallels with strain-specific modifiers in model organisms to bolster this interpretation. Published by Elsevier Inc. C1 [Roessler, Erich; Pei, Wuhong; Ouspenskaia, Maia V.; Karkera, Jayaprakash D.; Velez, Jorge Ivan; Feldman, Benjamin; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Banerjee-Basu, Sharmilla; Gibney, Gretchen; Baxevanis, Andreas D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Lupo, Philip J.; Mitchell, Laura E.] Texas A&M Univ, Syst Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX USA. [Towbin, Jeffrey A.; Belmont, John W.] Baylor Coll Med, Dept Pediat, Div Cardiol, Houston, TX 77030 USA. [Bowers, Peter] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Goldmuntz, Elizabeth] Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov OI Lupo, Philip/0000-0003-0978-5863; Belmont, John/0000-0001-7409-3578; Feldman, Benjamin/0000-0003-4838-8641 FU Intramural NIH HHS [Z01 HG000209-06]; NHLBI NIH HHS [P50 HL074731, P50 HL74731] NR 60 TC 34 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2009 VL 98 IS 1-2 BP 225 EP 234 DI 10.1016/j.ymgme.2009.05.005 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 483DQ UT WOS:000268942600641 PM 19553149 ER PT J AU Spence, AM Muzi, M Link, JM O'Sullivan, F Eary, JF Hoffman, JM Shankar, LK Krohn, KA AF Spence, Alexander M. Muzi, Mark Link, Jeanne M. O'Sullivan, Finbarr Eary, Janet F. Hoffman, John M. Shankar, Lalitha K. Krohn, Kenneth A. TI NCI-Sponsored Trial for the Evaluation of Safety and Preliminary Efficacy of 3'-Deoxy-3'-[F-18]fluorothymidine (FLT) as a Marker of Proliferation in Patients with Recurrent Gliomas: Preliminary Efficacy Studies SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE 3 '-[F-18]fluoro-3 '-deoxythymidine; FLT; Fluorothymidine; Positron emission tomography (PET); Glioma; Radionecrosis; Proliferation imaging ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE-SPECTROSCOPY; H-1 MR-SPECTROSCOPY; BRAIN-TUMORS; RADIATION-INJURY; DIAGNOSTIC-ACCURACY; FDG-PET; DIFFERENTIAL-DIAGNOSIS; C-11-METHIONINE PET; TRANSFER CONSTANTS AB 3'-Deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) is being developed for imaging cellular proliferation. The goals were to explore the capacity of FLT-positron emission tomography (PET) to distinguish between recurrence and radionecrosis in gliomas and compare the results to those obtained with 2-fluoro-2-deoxy-d-glucose (FDG). Fifteen patients with tumor recurrence and four with radionecrosis, determined by clinical course and magnetic resonance imaging results, were studied by dynamic [F-18]FLT-PET with arterial blood sampling. A two-tissue compartment four-rate constant model was used to determine metabolic flux (K (FLT)), blood to tissue transport (K (1)), and phosphorylation (k (3)). FDG-PET scans were obtained 75-90 min postinjection. K (FLT) and k (3), but not K (1) or k (3)/k (2) + k (3), reached significance for separating the recurrence from radionecrosis groups. Standardized uptake value and visual analyses of FLT or FDG images did not reach significance. K (FLT) (flux) appears to distinguish recurrence from radionecrosis better than other parameters, FLT and FDG semiquantitative approaches, or visual analysis of images of either tracer. C1 [Spence, Alexander M.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Muzi, Mark; Link, Jeanne M.; Eary, Janet F.; Krohn, Kenneth A.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [O'Sullivan, Finbarr] Natl Univ Ireland Univ Coll Cork, Dept Stat, Cork, Ireland. [Hoffman, John M.] Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. [Hoffman, John M.] Univ Utah, Dept Neurol, Salt Lake City, UT USA. [Shankar, Lalitha K.] NCI, Canc Imaging Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Spence, AM (reprint author), Univ Washington, Dept Neurol, Mailstop 356465,1959 NE Pacific St, Seattle, WA 98195 USA. EM aspence@u.washington.edu FU National Cancer Institute [N01-CM-37008]; NIH [CA42045, S10 RR17229] FX Pam Pham, Michele F. Wanner, Jeffrey Scharnhorst, and Neha Patel are gratefully acknowledged for their indispensable help. Supported by National Cancer Institute Contract N01-CM-37008 and NIH grants CA42045 and S10 RR17229. NR 57 TC 34 Z9 34 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD SEP PY 2009 VL 11 IS 5 BP 343 EP 355 DI 10.1007/s11307-009-0215-2 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 478JP UT WOS:000268584000008 PM 19326172 ER PT J AU Banki, Z Ammann, CG Ejaz, A Dittmer, U Hasenkrug, K Dierich, MP Stoiber, H Wilflingseder, D AF Banki, Z. Ammann, C. G. Ejaz, A. Dittmer, U. Hasenkrug, K. Dierich, M. P. Stoiber, H. Wilflingseder, D. TI Role of complement in virus-specific CTL response induced by bone-marrow derived DCs SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 12th European Meeting on Complement in Human Disease CY SEP 05-08, 2009 CL Visegrad, HUNGARY C1 [Banki, Z.; Ejaz, A.; Dierich, M. P.; Stoiber, H.; Wilflingseder, D.] Innsbruck Med Univ, Dept Hyg Microbiol & Social Med, Innsbruck, Austria. [Ammann, C. G.; Hasenkrug, K.] NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. [Dittmer, U.] Univ Duisburg Essen, Inst Virol, Essen, Germany. NR 0 TC 0 Z9 0 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2009 VL 46 IS 14 BP 2844 EP 2844 DI 10.1016/j.molimm.2009.05.257 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 491CM UT WOS:000269554500082 ER PT J AU Grodzinski, P AF Grodzinski, Piotr TI Nanoparticles for Imaging, Diagnosis, and Therapeutics preface SO MOLECULAR PHARMACEUTICS LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Grodzinski, P (reprint author), NCI, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD SEP-OCT PY 2009 VL 6 IS 5 BP 1263 EP 1263 DI 10.1021/mp900080n PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 501BR UT WOS:000270354400002 ER PT J AU Hou, ZC Romero, R Wildman, DE AF Hou, Zhuo-cheng Romero, Roberto Wildman, Derek E. TI Phylogeny of the Ferungulata (Mammalia: Laurasiatheria) as determined from phylogenomic data SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article DE Ferungulata; Carnivora; Perissodactyla; Cetartiodactyla; Molecular phylogeny ID PLACENTAL MAMMALS; MAXIMUM-LIKELIHOOD; GENOME SEQUENCE; EVOLUTION; MORPHOLOGY; CETACEANS; RADIATION; GENES; CLADE; SETS AB Great progress has been made toward resolving the evolutionary relationships among extant mammals, yet there are still areas of disagreement. The relationships among ferungulates that have high quality draft genome sequences available (i.e. dog, cow, horse) are unresolved, and thus we examined their phylogeny using currently known mammalian 1:1 orthologs. This dataset consists of 40 million base pairs from 2705 protein-coding genes. Maximum likelihood and Bayesian analyses of the combined and individual gene phylogenies strongly support a sister grouping of cow and horse to the exclusion of dog although topology tests could not rule out a horse and dog sister group relationship. (C) 2009 Published by Elsevier Inc. C1 [Hou, Zhuo-cheng; Romero, Roberto; Wildman, Derek E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. [Hou, Zhuo-cheng; Romero, Roberto; Wildman, Derek E.] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Wildman, Derek E.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Hou, Zhuo-cheng] China Agr Univ, Dept Anim Genet, Beijing 100094, Peoples R China. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch,NIH,DHHS, 3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu; dwildman@med.wayne.edu FU Intramural Research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/DHHS FX This research was supported in part by the Intramural Research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/DHHS. We thank the Wayne State University (Detroit, MI, USA) high performance grid for access to computing resources. NR 34 TC 12 Z9 17 U1 3 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD SEP PY 2009 VL 52 IS 3 BP 660 EP 664 DI 10.1016/j.ympev.2009.05.002 PG 5 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 474ER UT WOS:000268265800008 PM 19435603 ER PT J AU Liu, W Ding, JH Gibbs, JR Wang, SJ Hardy, J Singleton, A AF Liu, Wei Ding, Jinhui Gibbs, Jesse Raphael Wang, Sue Jane Hardy, John Singleton, Andrew TI A simple and efficient algorithm for genome-wide homozygosity analysis in disease SO MOLECULAR SYSTEMS BIOLOGY LA English DT Article DE disease network; homozygous segments; risk loci; statistical algorithm; whole-genome screening ID ALZHEIMERS-DISEASE; ASSOCIATION; GENE; AGE; POLYMORPHISMS; GENOTYPE; REVEALS; APOE; DNA AB Here we propose a simple statistical algorithm for rapidly scoring loci associated with disease or traits due to recessive mutations or deletions using genome-wide single nucleotide polymorphism genotyping case-control data in unrelated individuals. This algorithm identifies loci by defining homozygous segments of the genome present at significantly different frequencies between cases and controls. We found that false positive loci could be effectively removed from the output of this procedure by applying different physical size thresholds for the homozygous segments. This procedure is then conducted iteratively using random sub-datasets until the number of selected loci converges. We demonstrate this method in a publicly available data set for Alzheimer's disease and identify 26 candidate risk loci in the 22 autosomes. In this data set, these loci can explain 75% of the genetic risk variability of the disease. Molecular Systems Biology 5: 304; published online 15 September 2009; doi:10.1038/msb.2009.53 C1 [Liu, Wei; Wang, Sue Jane] US FDA, Off Biostat, OTS, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Liu, Wei; Ding, Jinhui; Gibbs, Jesse Raphael; Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Gibbs, Jesse Raphael; Hardy, John] UCL, Dept Mol Neurosci, London, England. [Gibbs, Jesse Raphael; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. RP Liu, W (reprint author), US FDA, Off Biostat, OTS, Ctr Drug Evaluat & Res, DB2,WO 21,Mail Stop 3562, Silver Spring, MD 20993 USA. EM Wei.Liu@fda.hhs.gov RI Gibbs, J. Raphael/A-3984-2010; Singleton, Andrew/C-3010-2009; Sincan, Murat /A-3794-2010; Hardy, John/C-2451-2009 FU National Institute on Aging; National Institutes of Health and Department of Health and Human Services [AG000950-07] FX This study was supported by the Intramural Program of the National Institute on Aging, National Institutes of Health and Department of Health and Human Services, project number AG000950-07. This study used high-performance computational capabilities of the Biowulf Systems at the National Institutes of Health, Bethesda, MD (http://helix.nih.gov). NR 20 TC 1 Z9 1 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1744-4292 J9 MOL SYST BIOL JI Mol. Syst. Biol. PD SEP PY 2009 VL 5 AR 304 DI 10.1038/msb.2009.53 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502JZ UT WOS:000270456400004 PM 19756043 ER PT J AU Carlson, BA Yoo, MH Tsuji, PA Gladyshev, VN Hatfield, DL AF Carlson, Bradley A. Yoo, Min-Hyuk Tsuji, Petra A. Gladyshev, Vadim N. Hatfield, Dolph L. TI Mouse Models Targeting Selenocysteine tRNA Expression for Elucidating the Role of Selenoproteins in Health and Development SO MOLECULES LA English DT Review DE mouse models; selenium; selenocysteine tRNA; selenoproteins ID TRANSCRIPTION-ACTIVATING FACTOR; PHOSPHOSERINE TRANSFER-RNA; SMALL NUCLEAR-RNA; GLUTATHIONE-PEROXIDASE; ZINC-FINGER; THIOREDOXIN REDUCTASE; TRANSFER RNASEC; GENE-TRANSCRIPTION; CANCER PREVENTION; IMMUNE-RESPONSES AB Selenium (Se) deficiency has been known for many years to be associated with disease, impaired growth and a variety of other metabolic disorders in mammals. Only recently has the major role that Se-containing proteins, designated selenoproteins, play in many aspects of health and development begun to emerge. Se is incorporated into protein by way of the Se-containing amino acid, selenocysteine (Sec). The synthesis of selenoproteins is dependent on Sec tRNA for insertion of Sec, the 21(st) amino acid in the genetic code, into protein. We have taken advantage of this dependency to modulate the expression of Sec tRNA that in turn modulates the expression of selenoproteins by generating transgenic, conditional knockout, transgenic/standard knockout and transgenic/conditional knockout mouse models, all of which involve the Sec tRNA gene, to elucidate the intracellular roles of this protein class. C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Tsuji, Petra A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Tsuji, Petra A.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Tsuji, Petra A.] NCI, Nutr Sci Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. RP Carlson, BA (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM carlsonb@mail.nih.gov; yoom@mail.nih.gov; tsujipa@mail.nih.gov; vgladysh@unlnotes.unl.edu; hatfield@mail.nih.gov RI Gladyshev, Vadim/A-9894-2013 FU National Institutes of Health NCI Intramural Research Program; Center for Cancer Research; National Institutes of Health [GM065204, CA080946] FX This work was supported by the National Institutes of Health NCI Intramural Research Program and the Center for Cancer Research (to DLH) and by National Institutes of Health Grants GM065204 and CA080946 (to VNG). NR 78 TC 19 Z9 19 U1 0 U2 5 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD SEP PY 2009 VL 14 IS 9 BP 3509 EP 3527 DI 10.3390/molecules14093509 PG 19 WC Chemistry, Organic SC Chemistry GA 499FB UT WOS:000270201900030 PM 19783940 ER PT J AU Kader, M Wang, X Piatak, M Lifson, J Roederer, M Veazey, R Mattapallil, JJ AF Kader, M. Wang, X. Piatak, M. Lifson, J. Roederer, M. Veazey, R. Mattapallil, J. J. TI alpha 4(+)beta 7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; LYMPHOID-TISSUE; GASTROINTESTINAL-TRACT; ADHESION MOLECULE-1; TYPE-1 INFECTION; RHESUS MACAQUES; CD4(+); DEPLETION; LYMPHOCYTES; CCR5 AB Human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infections are believed to infect minimally activated CD4(+) T cells after viral entry. Not much is known about why SIV selectively targets these cells. Here we show that CD4(+) T cells that express high levels of the alpha 4 beta 7 heterodimer are preferentially infected very early during the course of SIV infection. At days 2-4 post infection, alpha 4(+)beta 7(hi)CD4(+) T cells had similar to 5x more SIV-gag DNA than beta 7-CD4(+) T cells. alpha 4(+)beta 7(hi)CD4(+) T cells displayed a predominantly central memory (CD45RA(-)CD28(+)CCR7(+)) and a resting (CD25(-)CD69(-)HLA-DR(-)Ki67(-)) phenotype. Although the expression of detectable CCR5 was variable on alpha 4(+)beta 7(hi) and beta 7-CD4(+) T cells, both CCR5(+) and CCR5(-) subsets of alpha 4(+)beta 7(hi) and beta 7(-)CD4(+) T cells were found to express sufficient levels of CCR5 mRNA, suggesting that both these subsets could be efficiently infected by SIV. In line with this, we found similar levels of SIV infection in beta 7(-)CD4(+)CCR5(+) and beta 7(-)CD4(+)CCR5(-) T cells. alpha 4 beta 7(hi)CD4(+) T cells were found to harbor most T helper (Th)-17 cells that were significantly depleted during acute SIV infection. Taken together, our results show that resting memory alpha 4+beta 7(hi)CD4(+) T cells in the blood are preferentially infected and depleted during acute SIV infection, and the loss of these cells alters the balance between Th-17 and Th-1 responses, thereby contributing to disease pathogenesis. C1 [Kader, M.; Mattapallil, J. J.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Wang, X.; Veazey, R.] Tulane Natl Reg Primate Ctr, Covington, LA USA. [Piatak, M.; Lifson, J.] NCI, SAIC, Frederick, MD 21701 USA. [Roederer, M.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Mattapallil, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. EM jmattapallil@usuhs.mil FU National Institutes of Allergy and Infectious diseases (NIAID) [K22AI07812]; National Institute of Dental and Craniofacial Research (NIDCR) [R21DE018339]; National Cancer Institute; National Institutes of Health [N01-CO-12400, HHSN266200400088C] FX We thank Nancy Miller at the SVEU of the NIAID for help with the animals; Karen Wolcott and Kateryna Lund at the Biomedical Instrumentation Core facility at the USUHS for help with flow cytometry; Dr Deborah Weiss and Jim Treece at ABL Inc. (Rockville, MD) for expert assistance with the animals. This project was supported by Grant number K22AI07812 from the National Institutes of Allergy and Infectious diseases ( NIAID) and by Grant number R21DE018339 from the National Institute of Dental and Craniofacial Research (NIDCR) to J.J.M., and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts N01-CO-12400 and HHSN266200400088C. The content is solely the responsibility of the authors and does not represent the official views of NIAID, NIDCR or NCI. NR 42 TC 94 Z9 95 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2009 VL 2 IS 5 BP 439 EP 449 DI 10.1038/mi.2009.90 PG 11 WC Immunology SC Immunology GA 484FY UT WOS:000269030500008 PM 19571800 ER PT J AU Isakov, D Dzutsev, A Belyakov, IM Berzofsky, JA AF Isakov, D. Dzutsev, A. Belyakov, I. M. Berzofsky, J. A. TI Non-equilibrium and differential function between intraepithelial and lamina propria virus-specific TCR alpha beta(+) CD8 alpha beta(+) T cells in the small intestinal mucosa SO MUCOSAL IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; INTRARECTAL IMMUNIZATION; LYMPHOCYTE-RESPONSE; PROTECTIVE IMMUNITY; VIRAL REPLICATION; IN-VIVO; INFECTION; AVIDITY; HIV AB The gastrointestinal mucosa regularly encounters commensal and pathogenic microbiota. Gut mucosal lymphocytes consist of two phenotypically different populations residing in the intestinal intraepithelial (IEL) compartment and lamina propria (LP). Little is known about compositional and functional differences of antigen-specific T cells from these mucosal compartments after mucosal infection, or the degree of trafficking between them. We here studied the B8R(20-27)-specific CD8 T-cell response in LP and IEL compartments after intrarectal immunization with modified vaccinia virus Ankara (MVA). CD8(+) T cells in the IEL compartment had much lower avidity than in the LP or spleen during acute and memory phases. Surprisingly, the TCR V beta-chain distribution of antigen-specific T cells and the length of the CDR3 region of the dominant V beta genes showed substantial dissimilarities between IEL and LP antigen-specific CD8 alpha beta T cells in individual mice, increasing with time. We show functional and compositional differences between these mucosal compartments during the effector and memory phases of the immune response, indicating limited crosstalk and microenvironmental differences between the IEL, LP, and spleen. The restricted migration of cells from each of these mucosal compartments could partly account for a founder effect we observed in the IEL TCR alpha beta CD8 alpha beta epitope-specific repertoire that might impact protective efficacy. C1 [Isakov, D.; Dzutsev, A.; Belyakov, I. M.; Berzofsky, J. A.] NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Belyakov, I. M.] Midwest Res Inst, Frederick, MD USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM igorbelyakov@yahoo.com FU NIH FX We thank Susan Sharrow and Larry Granger for the cell sorting. We thank Evgeny Arons for his help and valuable advice in the immunoscope analysis. We also thank Kathleen Hartman and the staff of the DNA Minicore Facility of the NCI for genescan run. We thank Bernard Moss, Patricia Earl, and Linda Wyatt (NIAID, Bethesda, MD) for the gift of MVA and David Venzon and David Liewehr for consultation on statistical issues. We thank Dr Brian Kelsall and Dr Warren Strober for critical reading of the paper and helpful suggestions. This study was supported by the NIH intramural program of the Center for Cancer Research, NCI. NR 66 TC 7 Z9 7 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2009 VL 2 IS 5 BP 450 EP 461 DI 10.1038/mi.2009.95 PG 12 WC Immunology SC Immunology GA 484FY UT WOS:000269030500009 PM 19571797 ER PT J AU Bagnato, F Auh, S Gallo, A Ikonomidou, V Salman, Z Bomboi, G Cantor, F Ehrmantraut, M Evangelou, I Ohayon, J Pellicano, C Pellegrini, S Stern, S McFarland, H AF Bagnato, F. Auh, S. Gallo, A. Ikonomidou, V. Salman, Z. Bomboi, G. Cantor, F. Ehrmantraut, M. Evangelou, I. Ohayon, J. Pellicano, C. Pellegrini, S. Stern, S. McFarland, H. TI The relationships between focal and diffuse cortical pathology in patients with multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 25th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY SEP 09-12, 2009 CL Dusseldorf, GERMANY SP European Comm Treatment & Res Multiple Sclerosis C1 [Bagnato, F.; Auh, S.; Gallo, A.; Ikonomidou, V.; Salman, Z.; Bomboi, G.; Cantor, F.; Ehrmantraut, M.; Evangelou, I.; Ohayon, J.; Pellicano, C.; Pellegrini, S.; Stern, S.; McFarland, H.] NINDS, NIB, NIH, Bethesda, MD 20892 USA. RI Pellicano, Clelia/K-1062-2016 OI Pellicano, Clelia/0000-0002-3272-1094 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2009 VL 15 IS 9 BP S105 EP S105 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 492JW UT WOS:000269652500311 ER PT J AU Campbell, Z Sahm, D Donohue, K Jamison, J Davis, M Pellicano, C Daniels, C Ostuni, J Ohayon, J Frank, J Richert, N McFarland, H Bagnato, F AF Campbell, Z. Sahm, D. Donohue, K. Jamison, J. Davis, M. Pellicano, C. Daniels, C. Ostuni, J. Ohayon, J. Frank, J. Richert, N. McFarland, H. Bagnato, F. TI Contrast-enhancing and re-enhancing lesions are a patient-dependent phenomenon in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 25th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY SEP 09-12, 2009 CL Dusseldorf, GERMANY SP European Comm Treatment & Res Multiple Sclerosis C1 [Campbell, Z.; Sahm, D.; Donohue, K.; Jamison, J.; Davis, M.; Pellicano, C.; Daniels, C.; Ostuni, J.; Ohayon, J.; Frank, J.; Richert, N.; McFarland, H.; Bagnato, F.] NIB NINDS NIH, Bethesda, MD USA. RI Pellicano, Clelia/K-1062-2016 OI Pellicano, Clelia/0000-0002-3272-1094 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2009 VL 15 IS 9 BP S100 EP S100 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 492JW UT WOS:000269652500297 ER PT J AU Davis, M Auh, S Riva, M Richert, N Frank, JA McFarland, H Bagnato, F AF Davis, M. Auh, S. Riva, M. Richert, N. Frank, J. A. McFarland, H. Bagnato, F. TI Variability among multiple sclerosis patients in the development and significance of ring contrast-enhancing lesions: a 2-year monthly imaging study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 25th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY SEP 09-12, 2009 CL Dusseldorf, GERMANY SP European Comm Treatment & Res Multiple Sclerosis C1 [Davis, M.; Auh, S.; Riva, M.; Richert, N.; Frank, J. A.; McFarland, H.; Bagnato, F.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2009 VL 15 IS 9 BP S107 EP S108 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 492JW UT WOS:000269652500318 ER PT J AU Rudick, RA Polman, CH O'Connor, PW Goodman, A Ray, S Ryschkewitsch, C Jurgensen, S Goelz, S Forrestal, F Gorelik, L Panzara, MA Sandrock, AW Major, EO AF Rudick, R. A. Polman, C. H. O'Connor, P. W. Goodman, A. Ray, S. Ryschkewitsch, C. Jurgensen, S. Goelz, S. Forrestal, F. Gorelik, L. Panzara, M. A. Sandrock, A. W. Major, E. O. TI Evaluation of natalizumab treatment on the presence of JC virus in blood and urine from multiple sclerosis patients SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 25th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY SEP 09-12, 2009 CL Dusseldorf, GERMANY SP European Comm Treatment & Res Multiple Sclerosis C1 St Michaels Hosp, Toronto, ON M5B 1W8, Canada. VU Med Ctr, Amsterdam, Netherlands. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Rochester, Med Ctr, Rochester, NY 14627 USA. Biogen Idec Inc, Cambridge, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2009 VL 15 IS 9 BP S274 EP S275 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 492JW UT WOS:000269652500824 ER PT J AU Waubant, E Pelletier, D Mass, M Cohen, J Kita, M Cross, A Bar-Or, A Vollmer, T Racke, M Stuve, O Schwid, S Goodman, A Kachuck, N Preiningerova, J Weinstock-Guttman, B Calabresi, P Miller, A Mokhtarani, M Ding, L Rosenberg, E Ikle, D Spencer, C Zamvil, SS AF Waubant, E. Pelletier, D. Mass, M. Cohen, J. Kita, M. Cross, A. Bar-Or, A. Vollmer, T. Racke, M. Stueve, O. Schwid, S. Goodman, A. Kachuck, N. Preiningerova, J. Weinstock-Guttman, B. Calabresi, P. Miller, A. Mokhtarani, M. Ding, L. Rosenberg, E. Ikle, D. Spencer, C. Zamvil, S. S. CA ITN020AI Study Management Team TI Atorvastatin therapy in patients with clinically isolated syndrome and high-risk for conversion to multiple sclerosis: the STAyCIS study SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 25th Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis CY SEP 09-12, 2009 CL Dusseldorf, GERMANY SP European Comm Treatment & Res Multiple Sclerosis C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Washington Univ, St Louis, MO USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Univ Rochester, Rochester, NY 14627 USA. Univ So Calif, Los Angeles, CA USA. Yale Univ, New Haven, CT USA. Jacobs Neurol Inst, Buffalo, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Mt Sinai Sch Med, New York, NY USA. Immune Tolerance Network, San Francisco, CA USA. NIAID, Bethesda, MD 20892 USA. Rho Inc, Chapel Hill, NC USA. RI Bar-Or, Amit/C-4213-2011 NR 0 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD SEP PY 2009 VL 15 IS 9 BP S272 EP S272 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 492JW UT WOS:000269652500817 ER PT J AU Semberova, J Lacerda, SHDP Simakova, O Holada, K Gelderman, MP Simak, J AF Semberova, Jana Lacerda, Silvia H. De Paoli Simakova, Olga Holada, Karel Gelderman, Monique P. Simak, Jan TI Carbon Nanotubes Activate Blood Platelets by Inducing Extracellular Ca2+ Influx Sensitive to Calcium Entry Inhibitors SO NANO LETTERS LA English DT Article ID CELL-MEMBRANE MICROPARTICLES; TOXICITY; NANOPARTICLES; NANOMATERIALS; AGGREGATION; MECHANISM; PENETRATION; PARTICLES; CHANNELS; RELEASE AB To elucidate a mechanism of prothrombotic effects of carbon nanotubes (CNTs), we report here that multiwalled CNTs activate blood platelets by inducing extracellular Ca2+ influx that could be inhibited by calcium channel blockers; SKF 96365 and 2-APB. We also demonstrate platelet aggregating activity of different single-walled and multiwalled CNTs. In addition, we show that CNT-induced platelet activation is associated with a marked release of platelet membrane microparticles positive for the granular secretion markers CD62P and CD63. C1 [Semberova, Jana; Lacerda, Silvia H. De Paoli; Gelderman, Monique P.; Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Semberova, Jana] Inst Care Mother & Child, Prague, Czech Republic. [Holada, Karel] Charles Univ Prague, Sch Med 1, Prague, Czech Republic. [Simakova, Olga] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Simak, Jan/C-1153-2011 FU Ministry of Education, Youth, and Sport of the Czech Republic [MSM 0021620806] FX We thank Gerald Sando, Ph.D., Malvern Instruments, Columbia, MD, for the flow particle image analysis of nanomaterial suspensions. K.H. was supported by grant MSM 0021620806 of the Ministry of Education, Youth, and Sport of the Czech Republic. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 35 TC 54 Z9 54 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD SEP PY 2009 VL 9 IS 9 BP 3312 EP 3317 DI 10.1021/nl901603k PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 492KQ UT WOS:000269654900039 PM 19736974 ER PT J AU Stavreva, DA Wiench, M John, S Conway-Campbell, BL McKenna, MA Pooley, JR Johnson, TA Voss, TC Lightman, SL Hager, GL AF Stavreva, Diana A. Wiench, Malgorzata John, Sam Conway-Campbell, Becky L. McKenna, Mervyn A. Pooley, John R. Johnson, Thomas A. Voss, Ty C. Lightman, Stafford L. Hager, Gordon L. TI Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription SO NATURE CELL BIOLOGY LA English DT Article ID LIGAND-SPECIFIC DYNAMICS; LIVING CELLS; CHROMATIN DYNAMICS; ANDROGEN RECEPTOR; NATURAL PROMOTER; EXPRESSION; MECHANISM; EXCHANGE; CORTICOSTERONE; OSCILLATIONS AB Studies on glucocorticoid receptor (GR) action typically assess gene responses by long-term stimulation with synthetic hormones. As corticosteroids are released from adrenal glands in a circadian and high-frequency (ultradian) mode, such treatments may not provide an accurate assessment of physiological hormone action. Here we demonstrate that ultradian hormone stimulation induces cyclic GR-mediated transcriptional regulation, or gene pulsing, both in cultured cells and in animal models. Equilibrium receptor-occupancy of regulatory elements precisely tracks the ligand pulses. Nascent RNA transcripts from GR-regulated genes are released in distinct quanta, demonstrating a profound difference between the transcriptional programs induced by ultradian and constant stimulation. Gene pulsing is driven by rapid GR exchange with response elements and by GR recycling through the chaperone machinery, which promotes GR activation and reactivation in response to the ultradian hormone release, thus coupling promoter activity to the naturally occurring fluctuations in hormone levels. The GR signalling pathway has been optimized for a prompt and timely response to fluctuations in hormone levels, indicating that biologically accurate regulation of gene targets by GR requires an ultradian mode of hormone stimulation. C1 [Stavreva, Diana A.; Wiench, Malgorzata; John, Sam; Johnson, Thomas A.; Voss, Ty C.; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Conway-Campbell, Becky L.; McKenna, Mervyn A.; Pooley, John R.; Lightman, Stafford L.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Ctr Canc Res, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research; BBSRC [BB/C51297X/1]; Wellcome Trust [074112/Z/04/Z, 075548/Z/04/Z] FX We thank T. Karpova and J. McNally for assistance, C. Zeiss Inc. for the opportunity to carry out live cell experiments on a Zeiss Duoscan microscope, D. Shatti for technical assistance with nuclear extract preparation and Y. Kershaw for assistance with the in vivo experiments. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The animal work was supported by a BBSRC grant (BB/C51297X/1) and a Wellcome Trust Programme Grant (074112/Z/04/Z) to S.L. The qPCR was performed on an Applied Biosystems 7500 System funded by a Wellcome Trust Equipment Grant (075548/Z/04/Z). NR 43 TC 175 Z9 178 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2009 VL 11 IS 9 BP 1093 EP U111 DI 10.1038/ncb1922 PG 25 WC Cell Biology SC Cell Biology GA 490EW UT WOS:000269482500010 PM 19684579 ER PT J AU Ro, H Dawid, IB AF Ro, Hyunju Dawid, Igor B. TI Organizer restriction through modulation of Bozozok stability by the E3 ubiquitin ligase Lnx-like SO NATURE CELL BIOLOGY LA English DT Article ID NUMB PROTEIN-X; HOMEOBOX GENE; ANTERIOR NEUROECTODERM; PATTERN-FORMATION; DORSAL ORGANIZER; XENOPUS EMBRYOS; BETA-CATENIN; ZEBRAFISH; PATHWAY; AXIS AB The organizer anchors the primary embryonic axis, and balance between dorsal (organizer) and ventral domains is fundamental to body patterning. LNX (ligand of Numb protein-X) is a RING finger and four PDZ domain-containing E3 ubiquitin ligase(1,2). LNX serves as a binding platform and may have a role in cell fate determination, but its in vivo functions are unknown(1-5). Here we show that Lnx-l (Lnx-like) functions as a critical regulator of dorso-ventral axis formation in zebrafish. Depletion of Lnx-l using specific antisense morpholinos (MOs) caused strong embryonic dorsalization. We identified Bozozok (Boz, also known as Dharma or Nieuwkoid) as a binding partner and substrate of Lnx-l. Boz is a homeodomain-containing transcriptional repressor induced by canonical Wnt signalling that is critical for dorsal organizer formation (6-12). Lnx-l induced K48-linked polyubiquitylation of Boz, leading to its proteasomal degradation in human 293T cells and in zebrafish embryos. Dorsalization induced by Boz overexpression was suppressed by raising the level of Lnx-l, but Lnx-l failed to counteract dorsalization caused by mutant Boz lacking a critical motif for Lnx-l binding. Furthermore, dorsalization induced by depletion of Lnx-l was alleviated by attenuation of Boz expression. We conclude that Lnx-l modulates Boz activity to prevent the invasion of ventral regions of the embryo by organizer tissue. These studies introduce a ubiquitin ligase, Lnx-l, as a balancing modulator of axial patterning in the zebrafish embryo. C1 [Ro, Hyunju; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health FX We thank M. Rath and J. Gonzales for help with fish maintenance, and S.-Y. Choi for helpful comments. This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health. NR 32 TC 16 Z9 18 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2009 VL 11 IS 9 BP 1121 EP U165 DI 10.1038/ncb1926 PG 15 WC Cell Biology SC Cell Biology GA 490EW UT WOS:000269482500014 PM 19668196 ER PT J AU Fujita, K Mondal, AM Horikawa, I Nguyen, GH Kumamoto, K Sohn, JJ Bowman, ED Mathe, EA Schetter, AJ Pine, SR Ji, H Vojtesek, B Bourdon, JC Lane, DP Harris, CC AF Fujita, Kaori Mondal, Abdul M. Horikawa, Izumi Nguyen, Giang H. Kumamoto, Kensuke Sohn, Jane J. Bowman, Elise D. Mathe, Ewy A. Schetter, Aaron J. Pine, Sharon R. Ji, Helen Vojtesek, Borivoj Bourdon, Jean-Christophe Lane, David P. Harris, Curtis C. TI p53 isoforms Delta 133p53 and p53 beta are endogenous regulators of replicative cellular senescence SO NATURE CELL BIOLOGY LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; HUMAN-COLON; DNA-DAMAGE; DOWNSTREAM TARGET; EXPRESSION; MIR-34A; CANCER; GENE; APOPTOSIS; CELLS AB The finite proliferative potential of normal human cells leads to replicative cellular senescence, which is a critical barrier to tumour progression in vivo(1-3). We show that the human p53 isoforms Delta 133p53 and p53 beta(4) function in an endogenous regulatory mechanism for p53-mediated replicative senescence. Induced p53 beta and diminished Delta 133p53 were associated with replicative senescence, but not oncogene-induced senescence, in normal human fibroblasts. The replicatively senescent fibroblasts also expressed increased levels of miR-34a, a p53-induced microRNA(5-9), the antisense inhibition of which delayed the onset of replicative senescence. The siRNA (short interfering RNA)-mediated knockdown of endogenous Delta 133p53 induced cellular senescence, which was attributed to the regulation of p21(WAF1) and other p53 transcriptional target genes. In overexpression experiments, whereas p53 beta cooperated with full-length p53 to accelerate cellular senescence, Delta 133p53 repressed miR-34a expression and extended the cellular replicative lifespan, providing a functional connection of this microRNA to the p53 isoform-mediated regulation of senescence. The senescence-associated signature of p53 isoform expression (that is, elevated p53 beta and reduced Delta 133p53) was observed in vivo in colon adenomas with senescent phenotypes(10,11). The increased Delta 133p53 and decreased p53 beta isoform expression found in colon carcinoma may signal an escape from the senescence barrier during the progression from adenoma to carcinoma. C1 [Fujita, Kaori; Mondal, Abdul M.; Horikawa, Izumi; Nguyen, Giang H.; Kumamoto, Kensuke; Sohn, Jane J.; Bowman, Elise D.; Mathe, Ewy A.; Schetter, Aaron J.; Pine, Sharon R.; Ji, Helen; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Nguyen, Giang H.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. [Vojtesek, Borivoj] Masaryk Mem Canc Inst, Brno 65653, Czech Republic. [Bourdon, Jean-Christophe; Lane, David P.] Univ Dundee, Ninewells Hosp, Dept Surg & Mol Oncol, Inserm European Associated Lab, Dundee DD1 9SY, Scotland. [Lane, David P.] Inst Mol & Cell Biol, Singapore 138673, Singapore. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov RI ASTAR, IMCB/E-2320-2012; bourdon, jean-christophe/A-4439-2008 FU NIH, National Cancer Institute (NCI); Grant Agency of the Czech Republic (GACR) [301/08/1468]; Internal Grant Agency of Health of Czech Republic (IGA MZ CR) [NS/9812-4]; Breast Cancer Campaign, Cancer-Research UK (CRUK); Institut National de la Same et de la Recherche Medicale (Inserm) FX We thank M. Serrano, M. Tainsky, M. Oshimura, G. Hannon, T. de Lange and J. Khan for cells and reagents, X. Wang for helpful discussions, E. Spillare for continuous support and E. Michalova for technical assistance. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute (NCI). B.V. was supported by the grants from the Grant Agency of the Czech Republic (GACR; number 301/08/1468) and the Internal Grant Agency of Health of Czech Republic (IGA MZ CR; number NS/9812-4). J.C.B. was supported by Breast Cancer Campaign, Cancer-Research UK (CRUK) and the Institut National de la Same et de la Recherche Medicale (Inserm). D.L. is a Gibb fellow of CRUK. H. J. participated in the NIH Summer Internship Program. NR 44 TC 122 Z9 123 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2009 VL 11 IS 9 BP 1135 EP U208 DI 10.1038/ncb1928 PG 24 WC Cell Biology SC Cell Biology GA 490EW UT WOS:000269482500016 PM 19701195 ER PT J AU Jones, MR Quinton, LJ Blahna, MT Neilson, JR Fu, SN Ivanov, AR Wolf, DA Mizgerd, JP AF Jones, Matthew R. Quinton, Lee J. Blahna, Matthew T. Neilson, Joel R. Fu, Suneng Ivanov, Alexander R. Wolf, Dieter A. Mizgerd, Joseph P. TI Zcchc11-dependent uridylation of microRNA directs cytokine expression SO NATURE CELL BIOLOGY LA English DT Article ID CYTOPLASMIC POLY(A) POLYMERASE; MESSENGER-RNA; MECHANISMS; FAMILY; MIRNA; IDENTIFICATION; DETERMINANTS; INVOLVEMENT; INHIBITION; PROTEINS AB Mounting an effective host immune response without incurring inflammatory injury requires the precise regulation of cytokine expression(1,2). To achieve this, cytokine mRNAs are post-transcriptionally regulated by diverse RNA-binding proteins and microRNAs (miRNAs) targeting their 3' untranslated regions (UTRS)(3,4). Zcchc11 (zinc-finger, CCHC domain-containing protein 11) contains RNA-interacting motifs(5), and has been implicated in signalling pathways involved in cytokine expression(6). The nature of the Zcchc11 protein and how it influences cytokine expression are unknown. Here we show that Zcchc11 directs cytokine expression by uridylating cytokine-targeting miRNAs. Zcchc11 is a ribonucleotidyltransferase with a preference for uridine and is essential for maintaining the poly(A) tail length and stability of transcripts for interleukin-6 (IL-6) and other specific cytokines. The miR-26 family of miRNAs targets IL-6, and the addition of terminal uridines to the miR-26 3' end abrogates IL-6 repression. Whereas 78% of miR-26a sequences in control cells contained 1-3 uridines on their 3' ends, less than 0.1% did so in Zcchc11-knockdown cells. Thus, Zcchc11 fine tunes IL-6 production by uridylating miR-26a, which we propose is an enzymatic modification of the terminal nucleotide sequence of mature miRNA as a means to regulate gene expression. C1 [Jones, Matthew R.; Quinton, Lee J.; Blahna, Matthew T.; Mizgerd, Joseph P.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Fu, Suneng; Ivanov, Alexander R.; Wolf, Dieter A.] Harvard Univ, Sch Publ Hlth, Dept Genet, Boston, MA 02115 USA. [Fu, Suneng; Ivanov, Alexander R.; Wolf, Dieter A.] Harvard Univ, Sch Publ Hlth, Complex Dis & NIEHS Ctr, Prote Facil, Boston, MA 02115 USA. [Neilson, Joel R.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Mizgerd, JP (reprint author), Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. EM jmizgerd@bu.edu RI Blahna, Matthew/F-3172-2013; OI Quinton, Lee/0000-0003-1938-2507; Mizgerd, Joseph/0000-0002-4042-3169; Wolf, Dieter/0000-0002-3761-1070 FU NCI NIH HHS [K99 CA131474, K99 CA131474-02, P01 CA042063, P01 CA042063-249002, P01 CA42063]; NCRR NIH HHS [S10 RR019028]; NHLBI NIH HHS [R01 HL068153, K99 HL092956, K99 HL092956-02, R01 HL068153-06, R01 HL079392, R01 HL079392-04]; NIEHS NIH HHS [P01 ES00002, P30 ES000002]; NIGMS NIH HHS [R01 GM059780] NR 40 TC 143 Z9 158 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD SEP PY 2009 VL 11 IS 9 BP 1157 EP U258 DI 10.1038/ncb1931 PG 15 WC Cell Biology SC Cell Biology GA 490EW UT WOS:000269482500019 PM 19701194 ER PT J AU Amundadottir, L Kraft, P Stolzenberg-Solomon, RZ Fuchs, CS Petersen, GM Arslan, AA Bueno-De-Mesquita, HB Gross, M Helzlsouer, K Jacobs, EJ LaCroix, A Zheng, W Albanes, D Bamlet, W Berg, CD Berrino, F Bingham, S Buring, JE Bracci, PM Canzian, F Clavel-Chapelon, F Clipp, S Cotterchio, M de Andrade, M Duell, EJ Fox, JW Gallinger, S Gaziano, JM Giovannucci, EL Goggins, M Gonzalez, CA Hallmans, G Hankinson, SE Hassan, M Holly, EA Hunter, DJ Hutchinson, A Jackson, R Jacobs, KB Jenab, M Kaaks, R Klein, AP Kooperberg, C Kurtz, RC Li, DH Lynch, SM Mandelson, M McWilliams, RR Mendelsohn, JB Michaud, DS Olson, SH Overvad, K Patel, AV Peeters, PHM Rajkovic, A Riboli, E Risch, HA Shu, XO Thomas, G Tobias, GS Trichopoulos, D Van Den Eeden, SK Virtamo, J Wactawski-Wende, J Wolpin, BM Yu, H Yu, K Zeleniuch-Jacquotte, A Chanock, SJ Hartge, P Hoover, RN AF Amundadottir, Laufey Kraft, Peter Stolzenberg-Solomon, Rachael Z. Fuchs, Charles S. Petersen, Gloria M. Arslan, Alan A. Bueno-de-Mesquita, H. Bas Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Zheng, Wei Albanes, Demetrius Bamlet, William Berg, Christine D. Berrino, Franco Bingham, Sheila Buring, Julie E. Bracci, Paige M. Canzian, Federico Clavel-Chapelon, Francoise Clipp, Sandra Cotterchio, Michelle de Andrade, Mariza Duell, Eric J. Fox, John W., Jr. Gallinger, Steven Gaziano, J. Michael Giovannucci, Edward L. Goggins, Michael Gonzalez, Carlos A. Hallmans, Goran Hankinson, Susan E. Hassan, Manal Holly, Elizabeth A. Hunter, David J. Hutchinson, Amy Jackson, Rebecca Jacobs, Kevin B. Jenab, Mazda Kaaks, Rudolf Klein, Alison P. Kooperberg, Charles Kurtz, Robert C. Li, Donghui Lynch, Shannon M. Mandelson, Margaret McWilliams, Robert R. Mendelsohn, Julie B. Michaud, Dominique S. Olson, Sara H. Overvad, Kim Patel, Alpa V. Peeters, Petra H. M. Rajkovic, Aleksandar Riboli, Elio Risch, Harvey A. Shu, Xiao-Ou Thomas, Gilles Tobias, Geoffrey S. Trichopoulos, Dimitrios Van Den Eeden, Stephen K. Virtamo, Jarmo Wactawski-Wende, Jean Wolpin, Brian M. Yu, Herbert Yu, Kai Zeleniuch-Jacquotte, Anne Chanock, Stephen J. Hartge, Patricia Hoover, Robert N. TI Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer SO NATURE GENETICS LA English DT Article ID BASE-LINE CHARACTERISTICS; WOMENS HEALTH; BLOOD-GROUP; RISK; DESIGN; GENES; POLYMORPHISMS; RATIONALE; MORTALITY; ALLERGIES AB We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. C1 [Amundadottir, Laufey; Chanock, Stephen J.] Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlt & Human Serv, Bethesda, MD 20892 USA. [Amundadottir, Laufey; Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius; Hutchinson, Amy; Mendelsohn, Julie B.; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Chanock, Stephen J.; Hartge, Patricia; Hoover, Robert N.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Kraft, Peter; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Michaud, Dominique S.; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fuchs, Charles S.; Giovannucci, Edward L.; Hankinson, Susan E.; Hunter, David J.; Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Petersen, Gloria M.; Bamlet, William; de Andrade, Mariza] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.] NYU, Dept Obstet & Gynecol, Sch Med, New York, NY 10016 USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles; Mandelson, Margaret] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Berg, Christine D.] Natl Canc Inst, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Berrino, Franco] Ist Nazl Tumori, Etiol Epidemiol & Prevent Unit, Fdn IRCCS, I-20133 Milan, Italy. [Bingham, Sheila] Univ Cambridge, MRC, Dunn Human Nutr Unit, Cambridge, England. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Buring, Julie E.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Canzian, Federico; Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, DKFZ, D-6900 Heidelberg, Germany. [Clavel-Chapelon, Francoise] INSERM, Villejuif, France. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France. [Clipp, Sandra] Johns Hopkins Bloomberg Sch Publ Hlth, George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada. [Duell, Eric J.; Jenab, Mazda] Int Agcy Res Canc, F-69372 Lyon, France. [Fox, John W., Jr.] Michigan State Univ, Coll Human Med, E Lansing, MI 48824 USA. [Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Oncol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Goggins, Michael] Johns Hopkins Univ, Sch Med, Dept Med, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Gonzalez, Carlos A.] ICO, Unit Nutr Environm & Canc, Canc Epidemiol Res Programme, Barcelona, Spain. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Hassan, Manal; Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Hutchinson, Amy; Jacobs, Kevin B.] SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, NCI, Frederick, MD USA. [Jackson, Rebecca] Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. [Jackson, Rebecca] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA. [Jacobs, Kevin B.] Bioinformed LLC, Gaithersburg, MD USA. [Klein, Alison P.] Johns Hopkins Med Inst, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Sol Goldman Pancreat Res Ctr, Baltimore, MD 21205 USA. [Lynch, Shannon M.] Natl Canc Inst, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD USA. [Kurtz, Robert C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Mandelson, Margaret] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [McWilliams, Robert R.] Mayo Clin, Dept Oncol, Coll Med, Rochester, MN USA. [Michaud, Dominique S.; Peeters, Petra H. M.; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Cardiol, Aalborg, Denmark. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, Aalborg, Denmark. [Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Rajkovic, Aleksandar] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Risch, Harvey A.; Yu, Herbert] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Van Den Eeden, Stephen K.] No Calif Reg, Div Res, Kaiser Permanente, Oakland, CA USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Chanock, SJ (reprint author), Natl Canc Inst, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlt & Human Serv, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov RI Tobias, Geoffrey/M-4135-2016; Gallinger, Steven/E-4575-2013; Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014; Gonzalez, Carlos A/O-4651-2014; Albanes, Demetrius/B-9749-2015; Amundadottir, Laufey/L-7656-2016 OI Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163; Gonzalez, Carlos A/0000-0003-2822-9715; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303; Amundadottir, Laufey/0000-0003-1859-8971 FU Intramural NIH HHS [Z01 CP010193-01]; NCI NIH HHS [P50 CA062924, P50 CA062924-140011, P50 CA062924-150011, P50 CA062924-160011, P50 CA102701, P50 CA102701-08, R01 CA082729, R01 CA097193, R01 CA124908] NR 44 TC 260 Z9 270 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2009 VL 41 IS 9 BP 986 EP U47 DI 10.1038/ng.429 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 488WX UT WOS:000269382100009 PM 19648918 ER PT J AU Wu, XF Ye, YQ Kiemeney, LA Sulem, P Rafnar, T Matullo, G Seminara, D Yoshida, T Saeki, N Andrew, AS Dinney, CP Czerniak, B Zhang, ZF Kiltie, AE Bishop, DT Vineis, P Porru, S Buntinx, F Kellen, E Zeegers, MP Kumar, R Rudnai, P Gurzau, E Koppova, K Mayordomo, JI Sanchez, M Saez, B Lindblom, A de Verdier, P Steineck, G Mills, GB Schned, A Guarrera, S Polidoro, S Chang, SC Lin, J Chang, DW Hale, KS Majewski, T Grossman, HB Thorlacius, S Thorsteinsdottir, U Aben, KKH Witjes, JA Stefansson, K Amos, CI Karagas, MR Gu, J AF Wu, Xifeng Ye, Yuanqing Kiemeney, Lambertus A. Sulem, Patrick Rafnar, Thorunn Matullo, Giuseppe Seminara, Daniela Yoshida, Teruhiko Saeki, Norihisa Andrew, Angeline S. Dinney, Colin P. Czerniak, Bogdan Zhang, Zuo-feng Kiltie, Anne E. Bishop, D. Timothy Vineis, Paolo Porru, Stefano Buntinx, Frank Kellen, Eliane Zeegers, Maurice P. Kumar, Rajiv Rudnai, Peter Gurzau, Eugene Koppova, Kvetoslava Ignacio Mayordomo, Jose Sanchez, Manuel Saez, Berta Lindblom, Annika de Verdier, Petra Steineck, Gunnar Mills, Gordon B. Schned, Alan Guarrera, Simonetta Polidoro, Silvia Chang, Shen-Chih Lin, Jie Chang, David W. Hale, Katherine S. Majewski, Tadeusz Grossman, H. Barton Thorlacius, Steinunn Thorsteinsdottir, Unnur Aben, Katja K. H. Witjes, J. Alfred Stefansson, Kari Amos, Christopher I. Karagas, Margaret R. Gu, Jian TI Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; TUMOR-GROWTH; CARCINOMA; RISK; METASTASIS; EXPRESSION; VARIANT; MARKER; LOCUS; SCAN AB We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (Irs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus. C1 [Wu, Xifeng; Ye, Yuanqing; Lin, Jie; Chang, David W.; Amos, Christopher I.; Gu, Jian] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Biostat & Hlth Technol Assessment, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.; Witjes, J. Alfred] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands. [Kiemeney, Lambertus A.; Aben, Katja K. H.] Comprehens Canc Ctr E, Nijmegen, Netherlands. [Sulem, Patrick; Rafnar, Thorunn; Thorlacius, Steinunn; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet, Reykjavik, Iceland. [Matullo, Giuseppe] Univ Turin, Dept Genet Biol & Biochem, Turin, Italy. [Matullo, Giuseppe; Vineis, Paolo; Guarrera, Simonetta; Polidoro, Silvia] ISI Fdn, Villa Gualino, Turin, Italy. [Seminara, Daniela] Natl Canc Inst, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. [Yoshida, Teruhiko; Saeki, Norihisa] Natl Canc Ctr, Div Genet, Tokyo, Japan. [Andrew, Angeline S.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med,Sect Biostat & Epidem, Hanover, NH 03756 USA. [Schned, Alan] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pathol, Hanover, NH 03756 USA. [Dinney, Colin P.; Grossman, H. Barton] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Czerniak, Bogdan; Majewski, Tadeusz] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Zhang, Zuo-feng; Chang, Shen-Chih] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Kiltie, Anne E.] St James Univ Hosp, Leeds Inst Mol Med, Sect Expt Oncol, Leeds, W Yorkshire, England. [Bishop, D. Timothy] St James Univ Hosp, Leeds Inst Mol Med, Epidemiol & Biostat Sect, Leeds, W Yorkshire, England. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London, England. [Porru, Stefano] Univ Brescia, Dept Expt & Appl Med, Brescia, Italy. [Buntinx, Frank] Catholic Univ Louvain, Dept Gen Practice, B-3000 Leuven, Belgium. [Buntinx, Frank] Maastricht Univ, Dept Gen Practice, Maastricht, Netherlands. [Kellen, Eliane] Leuven Univ, Ctr Canc Prevent, Leuven, Belgium. [Kellen, Eliane; Zeegers, Maurice P.] Univ Birmingham, Dept Epidemiol & Publ Hlth, Birmingham, W Midlands, England. [Zeegers, Maurice P.] Maastricht Univ, Dept Complex Genet, Cluster Genet & Cell Biol, Nutr & Toxicol Res Inst, Maastricht, Netherlands. [Kumar, Rajiv] German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Gurzau, Eugene] Ctr Environm Hlth, Cluj Napoca, Romania. [Koppova, Kvetoslava] State Hlth Inst, Banska Bystrica, Slovakia. [Ignacio Mayordomo, Jose] Univ Hosp, Div Med Oncol, Zaragoza, Spain. [Sanchez, Manuel] Univ Hosp, Div Urol, Zaragoza, Spain. [Ignacio Mayordomo, Jose] Hlth Sci Inst, Nanotechnol Inst Aragon, Zaragoza, Spain. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [de Verdier, Petra] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden. [Steineck, Gunnar] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Mills, Gordon B.; Hale, Katherine S.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. RP Wu, XF (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. EM xwu@mdanderson.org RI Buntinx, Frank/E-4950-2011; Mayordomo, Jose/K-3453-2013; Witjes, Fred/N-9665-2013; Kiemeney, Lambertus/D-3357-2009; Aben, Katja/G-9686-2016; Matullo, Giuseppe/K-6383-2016; OI Bishop, Tim/0000-0002-8752-8785; Steineck, Gunnar/0000-0002-0787-3969; Kiemeney, Lambertus/0000-0002-2368-1326; Aben, Katja/0000-0002-0214-2147; Kumar, Rajiv/0000-0002-6093-0395; MATULLO, Giuseppe/0000-0003-0674-7757; Kiltie, Anne/0000-0001-7208-2912 FU NIH [U01 CA 127615, R01 CA 74880, P50 CA 91846, R01 CA 133996, P42 ES07373, R01 CA 57494, R01 CA 131335]; Kleberg Center for Molecular Markers FX The study was partially supported by NIH grants U01 CA 127615 (X. W.), R01 CA 74880 (X. W.), P50 CA 91846 (X. W., C. P. D.), R01 CA 133996 (C. I. A), P42 ES07373 (M. R. K.) and R01 CA 57494 (M. R. K.), R01 CA 131335 (J. G.) and the Kleberg Center for Molecular Markers at MDACC. We thank the genotyping personnel, study coordinators and interviewers for performing experiments and recruiting participants. We are especially thankful for all the study participants who made the population- based research possible. NR 31 TC 155 Z9 158 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2009 VL 41 IS 9 BP 991 EP U54 DI 10.1038/ng.421 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 488WX UT WOS:000269382100010 PM 19648920 ER PT J AU Song, HL Ramus, SJ Tyrer, J Bolton, KL Gentry-Maharaj, A Wozniak, E Anton-Culver, H Chang-Claude, J Cramer, DW DiCioccio, R Dork, T Goode, EL Goodman, MT Schildkraut, JM Sellers, T Baglietto, L Beckmann, MW Beesley, J Blaakaer, J Carney, ME Chanock, S Chen, ZH Cunningham, JM Dicks, E Doherty, JA Durst, M Ekici, AB Fenstermacher, D Fridley, BL Giles, G Gore, ME De Vivo, I Hillemanns, P Hogdall, C Hogdall, E Iversen, ES Jacobs, IJ Jakubowska, A Li, D Lissowska, J Lubinski, J Lurie, G McGuire, V McLaughlin, J Medrek, K Moorman, PG Moysich, K Narod, S Phelan, C Pye, C Risch, H Runnebaum, IB Severi, G Southey, M Stram, DO Thiel, FC Terry, KL Tsai, YY Tworoger, SS Van Den Berg, DJ Vierkant, RA Wang-Gohrke, S Webb, PM Wilkens, LR Wu, AH Yang, HN Brewster, W Ziogas, A Houlston, R Tomlinson, I Whittemore, AS Rossing, MA Ponder, BAJ Pearce, CL Ness, RB Menon, U Kjaer, SK Gronwald, J Garcia-Closas, M Fasching, PA Easton, DF Chenevix-Trench, G Berchuck, A Pharoah, PDP Gayther, SA AF Song, Honglin Ramus, Susan J. Tyrer, Jonathan Bolton, Kelly L. Gentry-Maharaj, Aleksandra Wozniak, Eva Anton-Culver, Hoda Chang-Claude, Jenny Cramer, Daniel W. DiCioccio, Richard Doerk, Thilo Goode, Ellen L. Goodman, Marc T. Schildkraut, Joellen M. Sellers, Thomas Baglietto, Laura Beckmann, Matthias W. Beesley, Jonathan Blaakaer, Jan Carney, Michael E. Chanock, Stephen Chen, Zhihua Cunningham, Julie M. Dicks, Ed Doherty, Jennifer A. Duerst, Matthias Ekici, Arif B. Fenstermacher, David Fridley, Brooke L. Giles, Graham Gore, Martin E. De Vivo, Immaculata Hillemanns, Peter Hogdall, Claus Hogdall, Estrid Iversen, Edwin S. Jacobs, Ian J. Jakubowska, Anna Li, Dong Lissowska, Jolanta Lubinski, Jan Lurie, Galina McGuire, Valerie McLaughlin, John Medrek, Krzysztof Moorman, Patricia G. Moysich, Kirsten Narod, Steven Phelan, Catherine Pye, Carole Risch, Harvey Runnebaum, Ingo B. Severi, Gianluca Southey, Melissa Stram, Daniel O. Thiel, Falk C. Terry, Kathryn L. Tsai, Ya-Yu Tworoger, Shelley S. Van Den Berg, David J. Vierkant, Robert A. Wang-Gohrke, Shan Webb, Penelope M. Wilkens, Lynne R. Wu, Anna H. Yang, Hannah Brewster, Wendy Ziogas, Argyrios Houlston, Richard Tomlinson, Ian Whittemore, Alice S. Rossing, Mary Anne Ponder, Bruce A. J. Pearce, Celeste Leigh Ness, Roberta B. Menon, Usha Kjaer, Susanne Krueger Gronwald, Jacek Garcia-Closas, Montserrat Fasching, Peter A. Easton, Douglas F. Chenevix-Trench, Georgia Berchuck, Andrew Pharoah, Paul D. P. Gayther, Simon A. CA Australian Canc Ovarian Study Australian Ovarian Canc Study Grp Ovarian Canc Assoc Consortium TI A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2 SO NATURE GENETICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISMS; BASAL-CELL CARCINOMA; PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; INVASIVE OVARIAN; PARP INHIBITORS; CANDIDATE SNPS; MULTIPLE LOCI; RISK AB Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk(1). We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and similar to 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) - 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, Ptrend 4.1 x 10(-21)). C1 [Song, Honglin; Tyrer, Jonathan; Bolton, Kelly L.; Dicks, Ed; Pye, Carole; Ponder, Bruce A. J.; Pharoah, Paul D. P.] Univ Cambridge, Canc Res UK Dept Oncol, Strangeways Res Lab, Cambridge, England. [Ramus, Susan J.; Gentry-Maharaj, Aleksandra; Wozniak, Eva; Jacobs, Ian J.; Menon, Usha; Gayther, Simon A.] UCL, Dept Gynaecol Oncol, Inst Womens Hlth, London, England. [Bolton, Kelly L.; Chanock, Stephen; Yang, Hannah] NIH, Div Canc Epidemiol & Genet, Rockville, MD USA. [Anton-Culver, Hoda; Li, Dong; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [DiCioccio, Richard] Dept Canc Genet, Buffalo, NY USA. [DiCioccio, Richard] Gilda Radner Familial Ovarian Canc Registry, Buffalo, NY USA. [Doerk, Thilo; Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol, D-3000 Hannover, Germany. [Goode, Ellen L.; Cunningham, Julie M.; Fridley, Brooke L.; Vierkant, Robert A.] Mayo Clin, Coll Med, Rochester, MN USA. [Goodman, Marc T.; Carney, Michael E.; Lurie, Galina; Wilkens, Lynne R.] Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. [Schildkraut, Joellen M.; Moorman, Patricia G.; Berchuck, Andrew] Duke Univ, Med Ctr, Ctr Comprehens Canc, Durham, NC 27710 USA. [Sellers, Thomas; Chen, Zhihua; Fenstermacher, David; Phelan, Catherine; Tsai, Ya-Yu] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Baglietto, Laura; Hillemanns, Peter] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia. [Baglietto, Laura; Giles, Graham; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. [Beckmann, Matthias W.; Thiel, Falk C.; Fasching, Peter A.] Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen, Germany. [Beesley, Jonathan; Webb, Penelope M.; Chenevix-Trench, Georgia] PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld, Australia. [Blaakaer, Jan; Garcia-Closas, Montserrat] Skejby Univ Hosp, Dept Obstet & Gynaecol, Aarhus, Denmark. [Doherty, Jennifer A.; Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Duerst, Matthias; Runnebaum, Ingo B.] Univ Hosp Jena, Dept Obstet & Gynaecol, Jena, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-8520 Erlangen, Germany. [Gore, Martin E.] Royal Marsden Hosp, Gynecol Oncol Unit, London SW3 6JJ, England. [De Vivo, Immaculata; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [De Vivo, Immaculata; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA USA. [Hogdall, Claus] Rigshosp, Gynaecol Clin, Juliane Marie Ctr, DK-2100 Copenhagen, Denmark. [Hogdall, Estrid; Kjaer, Susanne Krueger] Danish Canc Soc, Dept Viruses Hormones & Canc, Inst Canc Epidemiol, Copenhagen, Denmark. [Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA. [Jakubowska, Anna; Lubinski, Jan; Medrek, Krzysztof; Gronwald, Jacek] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [McGuire, Valerie] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Moysich, Kirsten] Roswell Pk Canc Ctr, Buffalo, NY USA. [Narod, Steven] Ctr Res Womens Hlth, Toronto, ON, Canada. [Risch, Harvey] Yale Univ, New Haven, CT USA. [Southey, Melissa] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic, Australia. [Stram, Daniel O.; Van Den Berg, David J.; Wu, Anna H.; Pearce, Celeste Leigh] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynaecol, Ulm, Germany. [Brewster, Wendy] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Australian Canc Ovarian Study; Australian Ovarian Canc Study Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Tomlinson, Ian] Wellcome Trust Ctr Human Genet, Populat & Funct Genet Lab, Oxford, England. [Houlston, Richard; Ovarian Canc Assoc Consortium] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. [Easton, Douglas F.] Univ Cambridge, CR UK Genet Epidemiol Unit, Strangeways Res Lab, Cambridge, England. RP Pharoah, PDP (reprint author), Univ Cambridge, Canc Res UK Dept Oncol, Strangeways Res Lab, Cambridge, England. EM paul1@srl.cam.ac.uk RI Menon, Usha/C-4716-2008; Ekici, Arif/C-3971-2013; Jacobs, Ian/F-1743-2013; McLaughlin, John/E-4577-2013; Jakubowska, Anna/O-8050-2014; Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Gronwald, Jacek/A-4576-2017; OI Kjaer, Susanne/0000-0002-8347-1398; Vierkant, Robert/0000-0001-6242-5221; Jacobs, Ian/0000-0002-8112-4624; Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat /0000-0003-1033-2650; Bowtell, David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871; Ramus, Susan/0000-0003-0005-7798; Webb, Penelope/0000-0003-0733-5930; Lissowska, Jolanta/0000-0003-2695-5799; Giles, Graham/0000-0003-4946-9099; Tworoger, Shelley/0000-0002-6986-7046; Houlston, Richard/0000-0002-5268-0242 FU Cancer Research UK [A6187, , 10118, 10119, 10124, 11021, A10119, A10124, A8339]; Department of Health; Medical Research Council [G0000934, G0801875]; NCI NIH HHS [CA-58860, CA-92044, CA16056, CA71766, K07 CA092044, K07 CA092044-04, N01 PC035137, N01-CN-55424, N01-PC-35137, N01PC35137, P30 CA016056, P30 CA016056-33, P50 CA105009, P50 CA105009-05, P50 CA136393, R01 CA054419, R01 CA054419-15, R01 CA058598, R01 CA058598-10, R01 CA058860, R01 CA058860-14, R01 CA087538, R01 CA087538-05, R01 CA112523, R01 CA112523-04, R01 CA114343, R01 CA114343-03, R01 CA122443, R01 CA122443-02, R01 CA61107, R01 CA87538, R01-CA- 58598, R01-CA-122443, R01CA114343, U01 CA058860] NR 40 TC 174 Z9 176 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2009 VL 41 IS 9 BP 996 EP U60 DI 10.1038/ng.424 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 488WX UT WOS:000269382100011 PM 19648919 ER PT J AU Yu, Q Sharma, A Oh, SY Moon, HG Hossain, MZ Salay, TM Leeds, KE Du, HS Wu, BB Waterman, ML Zhu, Z Sen, JM AF Yu, Qing Sharma, Archna Oh, Sun Young Moon, Hyung-Geun Hossain, M. Zulfiquer Salay, Theresa M. Leeds, Karen E. Du, Hansen Wu, Beibei Waterman, Marian L. Zhu, Zhou Sen, Jyoti Misra TI T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma SO NATURE IMMUNOLOGY LA English DT Article ID BETA-CATENIN; LINEAGE COMMITMENT; PROSTAGLANDIN E-2; GENE-EXPRESSION; IMMUNE-SYSTEM; COLON-CANCER; TH2 CELLS; IN-VITRO; WNT; RESPONSES AB The differentiation of activated CD4(+) T cells into the T helper type 1 (T(H)1) or T(H)2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the T(H)1 fate, signals that initiate the T(H)2 fate are not completely characterized. Here we show that early GATA-3 expression, required for T(H)2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor beta-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked T(H)1 fate by negatively regulating interferon-gamma (IFN-gamma) expression independently of beta-catenin. Thus, TCF-1 initiates T(H)2 differentiation of activated CD4(+) T cells by promoting GATA-3 expression and suppressing IFN-gamma expression. C1 [Yu, Qing; Sharma, Archna; Hossain, M. Zulfiquer; Salay, Theresa M.; Leeds, Karen E.; Du, Hansen; Sen, Jyoti Misra] NIA, Lymphocyte Dev Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA. [Oh, Sun Young; Moon, Hyung-Geun; Zhu, Zhou] Johns Hopkins Univ, Sch Med, Div Clin Immunol & Allergy, Baltimore, MD USA. [Wu, Beibei; Waterman, Marian L.] Univ Calif Irvine, Irvine, CA USA. RP Sen, JM (reprint author), NIA, Lymphocyte Dev Unit, Immunol Lab, NIH, Baltimore, MD 21224 USA. EM jyoti-sen@nih.gov RI Wu, Beibei/B-7463-2011; Wu, Beibei/B-5169-2010; Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 FU Intramural Research Program of the National Institute on Aging of the National Institutes of Health; Oak Ridge Institute for Science and Education's Research Associates Program of the National Institutes of Health FX We thank R. Wersto and team for cell sorting; the animal facility of the National Institute on Aging for maintaining animals; S. Luo and team for genotyping; H. Clevers (Hubrecht Institute) for TCF-1-deficient mice; W. Pear (University of Pennsylvania) for the dnMAML retroviral construct; and N. Taylor, A. Singer, R. Bosselut, R. Sen and A. Bhandoola for critically reading the manuscript. Supported by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health and the Oak Ridge Institute for Science and Education's Research Associates Program of the National Institutes of Health. NR 49 TC 92 Z9 98 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2009 VL 10 IS 9 BP 992 EP U85 DI 10.1038/ni.1762 PG 10 WC Immunology SC Immunology GA 485KV UT WOS:000269120900013 PM 19648923 ER PT J AU Zhao, BH Takami, M Yamada, A Wang, XG Koga, T Hu, XY Tamura, T Ozato, K Choi, YW Ivashkiv, LB Takayanagi, H Kamijo, R AF Zhao, Baohong Takami, Masamichi Yamada, Atsushi Wang, Xiaogu Koga, Takako Hu, Xiaoyu Tamura, Tomohiko Ozato, Keiko Choi, Yongwon Ivashkiv, Lionel B. Takayanagi, Hiroshi Kamijo, Ryutaro TI Interferon regulatory factor-8 regulates bone metabolism by suppressing osteoclastogenesis SO NATURE MEDICINE LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TOLL-LIKE RECEPTORS; NF-KAPPA-B; DENDRITIC CELLS; KEY REGULATOR; CROSS-TALK; IFN-GAMMA; C-FOS; DIFFERENTIATION; ACTIVATION AB Bone metabolism results from a balance between osteoclast-driven bone resorption and osteoblast-mediated bone formation. Diseases such as periodontitis and rheumatoid arthritis are characterized by increased bone destruction due to enhanced osteoclastogenesis(1,2). Here we report that interferon regulatory factor-8 (IRF-8), a transcription factor expressed in immune cells, is a key regulatory molecule for osteoclastogenesis. IRF-8 expression in osteoclast precursors was downregulated during the initial phase of osteoclast differentiation induced by receptor activator of nuclear factor-kappa B ligand (RANKL), which is encoded by the Tnfsf11 gene. Mice deficient in Irf8 showed severe osteoporosis, owing to increased numbers of osteoclasts, and also showed enhanced bone destruction after lipopolysaccharide (LPS) administration. Irf8(-/-) osteoclast precursors underwent increased osteoclastogenesis in response to RANKL and tumor necrosis factor-alpha (TNF-alpha). IRF-8 suppressed osteoclastogenesis by inhibiting the function and expression of nuclear factor of activated T cells c1 (NFATc1). Our results show that IRF-8 inhibits osteoclast formation under physiological and pathological conditions and suggest a model where downregulation of inhibitory factors such as IRF-8 contributes to RANKL-mediated osteoclastogenesis. C1 [Zhao, Baohong; Takami, Masamichi; Yamada, Atsushi; Wang, Xiaogu; Kamijo, Ryutaro] Showa Univ, Sch Dent, Dept Biochem, Shinagawa Ku, Tokyo 142, Japan. [Zhao, Baohong; Hu, Xiaoyu; Ivashkiv, Lionel B.] Hosp Special Surg, Arthritis & Tissue Degenerat Program, New York, NY 10021 USA. [Koga, Takako; Takayanagi, Hiroshi] Tokyo Med & Dent Univ, Dept Cell Signaling, Grad Sch, Bunkyo Ku, Tokyo, Japan. [Koga, Takako; Takayanagi, Hiroshi] Int Res Ctr Mol Sci Tooth & Bone Dis, Global Ctr Excellence Program, Tokyo, Japan. [Hu, Xiaoyu; Ivashkiv, Lionel B.] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Tamura, Tomohiko; Ozato, Keiko] NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. [Choi, Yongwon] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Ivashkiv, Lionel B.] Cornell Univ, Grad Program Immunol & Microbial Pathogenesis, Weill Grad Sch Med Sci, New York, NY 10021 USA. RP Takami, M (reprint author), Showa Univ, Sch Dent, Dept Biochem, Shinagawa Ku, Tokyo 142, Japan. EM takami@dent.showa-u.ac.jp RI Hu, Xiaoyu/D-5403-2017 OI Hu, Xiaoyu/0000-0002-4289-6998 FU Ministry of Education, Culture, Sports, Science and Technology, Japan; Japan Society for the Promotion of Science [20390474]; US National Institutes of Health [AR053843, DE19381, DE019420, AR46713] FX We are grateful to M. Asagiri for technical assistance. We thank T. Kitamura ( University of Tokyo) for providing the retrovirus expression system. We also thank A. Mochizuki and all members of the Department of Biochemistry, School of Dentistry, Showa University for valuable discussions. This work is supported in part by the High-Tech Research Center Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology, Japan, 2005-2009, by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science ( 20390474 to M. T.) and by grants from the US National Institutes of Health (AR053843 and DE19381 to Y. C. and DE019420 and AR46713 to L. B. I.). NR 29 TC 94 Z9 98 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2009 VL 15 IS 9 BP 1066 EP U121 DI 10.1038/nm.2007 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 496MT UT WOS:000269979200028 PM 19718038 ER PT J AU Barrett, J Rezvani, K AF Barrett, John Rezvani, Katayoun TI Can we include vaccines with stem-cell transplantation? SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID T-LYMPHOCYTES; MYELOID-LEUKEMIA; RESPONSES; IMATINIB C1 [Barrett, John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Rezvani, Katayoun] Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London, England. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 10 TC 10 Z9 10 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD SEP PY 2009 VL 6 IS 9 BP 503 EP 505 DI 10.1038/nrclinonc.2009.115 PG 3 WC Oncology SC Oncology GA 487FD UT WOS:000269255300005 PM 19707241 ER PT J AU Mueller, SN Germain, RN AF Mueller, Scott N. Germain, Ronald N. TI Stromal cell contributions to the homeostasis and functionality of the immune system SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID FIBROBLASTIC RETICULAR CELLS; HIGH ENDOTHELIAL VENULES; PERIPHERAL LYMPHOID ORGANS; TISSUE-INDUCER CELLS; LYMPHOCYTES IN-VIVO; NAIVE T-LYMPHOCYTES; SPLENIC WHITE PULP; DENDRITIC CELLS; B-CELLS; NODE CORTEX AB A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non-haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response. C1 [Mueller, Scott N.] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. [Mueller, Scott N.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mueller, SN (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. EM smue@unimelb.edu.au; rgermain@niaid.nih.gov RI Mueller, Scott/B-1918-2012 OI Mueller, Scott/0000-0002-3838-3989 FU US National Institutes of Health, National Institute of Allergy and Infectious Diseases [AI30048] FX The authors thank I. Ifrim for invaluable assistance with immunohistochemistry to generate the images in the figures, A.O. Anderson, J. Egen and W. Kastenmuller for helpful comments on the manuscript and R. Ahmed for support. The authors were supported by the Intramural Research Program of the US National Institutes of Health, National Institute of Allergy and Infectious Diseases and grant AI30048 (to S.N.M.). NR 128 TC 234 Z9 236 U1 4 U2 26 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD SEP PY 2009 VL 9 IS 9 BP 618 EP 629 DI 10.1038/nri2588 PG 12 WC Immunology SC Immunology GA 487HU UT WOS:000269263400009 PM 19644499 ER PT J AU Chambers, HF Deleo, FR AF Chambers, Henry F. DeLeo, Frank R. TI Waves of resistance: Staphylococcus aureus in the antibiotic era SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID PANTON-VALENTINE LEUKOCIDIN; CASSETTE CHROMOSOME MEC; BLOOD-STREAM INFECTIONS; SOFT-TISSUE INFECTIONS; METHICILLIN-RESISTANT; UNITED-STATES; MOLECULAR EPIDEMIOLOGY; NASAL COLONIZATION; HUMAN NEUTROPHILS; IN-VITRO AB Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections that are caused by antibiotic-resistant strains often occur in epidemic waves that are initiated by one or a few successful clones. Methicillin-resistant S. aureus (MRSA) features prominently in these epidemics. Historically associated with hospitals and other health care settings, MRSA has now emerged as a widespread cause of community infections. Community or community-associated MRSA (CA-MRSA) can spread rapidly among healthy individuals. Outbreaks of CA-MRSA infections have been reported worldwide, and CA-MRSA strains are now epidemic in the United States. Here, we review the molecular epidemiology of the epidemic waves of penicillin-and methicillin-resistant strains of S. aureus that have occurred since 1940, with a focus on the clinical and molecular epidemiology of CA-MRSA. C1 [Chambers, Henry F.] Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Div Infect Dis, San Francisco, CA 94110 USA. [DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chambers, HF (reprint author), Univ Calif San Francisco, Dept Med, San Francisco Gen Hosp, Div Infect Dis, San Francisco, CA 94110 USA. EM hchambers@medsfgh.ucsf.edu OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH) [R01 AI070289] FX F. R. D. is supported by the Intramural Research Program of the National Institute of Allergy and Infectious Disease (NIAID) and the National Institutes of Health (NIH) and H. F. C. is supported by the NIH, NIAID grant number R01 AI070289. NR 179 TC 719 Z9 757 U1 54 U2 320 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD SEP PY 2009 VL 7 IS 9 BP 629 EP 641 DI 10.1038/nrmicro2200 PG 13 WC Microbiology SC Microbiology GA 483DP UT WOS:000268942500010 PM 19680247 ER PT J AU Milne, JLS Subramaniam, S AF Milne, Jacqueline L. S. Subramaniam, Sriram TI Cryo-electron tomography of bacteria: progress, challenges and future prospects SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID TRANSMISSION ELECTRON-MICROSCOPY; FROZEN-HYDRATED SECTIONS; CHEMOTAXIS RECEPTOR TSR; X-RAY-DIFFRACTION; ESCHERICHIA-COLI; VITREOUS SECTIONS; PERIPLASMIC SPACE; CAULOBACTER-CRESCENTUS; DIRECT VISUALIZATION; 3-DIMENSIONAL STRUCTURE AB Recent advances in three-dimensional electron microscopy provide remarkable tools to image the interior of bacterial cells. Glimpses of cells at resolutions that are 1-2 orders of magnitude higher than those currently attained with light microscopy can now be obtained with cryo-electron tomography, especially when used in combination with new tools for image averaging. This Review highlights recent advances in this area and provides an assessment of the general applicability, current limitations and type of structural information that can be obtained about the organization of intact cells using tomography. Possible future directions for whole cell imaging are also discussed. C1 [Milne, Jacqueline L. S.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM subramas@mail.nih.gov RI Usher, Kayley/F-7342-2011 FU National Cancer Institute; National Institues of Health (NIH), USA FX This work was supported by funds from the intramural research program of the National Cancer Institute, National Institues of Health (NIH), USA. NR 91 TC 79 Z9 80 U1 2 U2 36 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD SEP PY 2009 VL 7 IS 9 BP 666 EP 675 DI 10.1038/nrmicro2183 PG 10 WC Microbiology SC Microbiology GA 483DP UT WOS:000268942500013 PM 19668224 ER PT J AU Grant, BD Donaldson, JG AF Grant, Barth D. Donaldson, Julie G. TI Pathways and mechanisms of endocytic recycling SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID CLATHRIN-INDEPENDENT ENDOCYTOSIS; CLEAVAGE FURROW INGRESSION; DISTINCT MEMBRANE DOMAINS; EARLY ENDOSOMAL TRANSPORT; LONG-TERM POTENTIATION; PLASMA-MEMBRANE; CAENORHABDITIS-ELEGANS; AMPA RECEPTORS; E-CADHERIN; MYOBLAST FUSION AB Endocytic recycling is coordinated with endocytic uptake to control the composition of the plasma membrane. Although much of our understanding of endocytic recycling has come from studies on the transferrin receptor, a protein internalized through clathrin-dependent endocytosis, increased interest in clathrin-independent endocytosis has led to the discovery of new endocytic recycling systems. Recent insights into the regulatory mechanisms that control endocytic recycling have focused on recycling through tubular carriers and the return to the cell surface of cargoes that enter cells through clathrin-independent mechanisms. Recent work emphasizes the importance of regulated recycling in processes as diverse as cytokinesis, cell adhesion, morphogenesis, cell fusion, learning and memory. C1 [Grant, Barth D.] Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. [Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grant, BD (reprint author), Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. EM grant@biology.rutgers.edu; jdonalds@helix.nih.gov OI Grant, Barth/0000-0002-5943-8336 FU National Institutes of Health (NIH) [R01 GM067237]; National Heart, Lung, and Blood Institute, NIH FX We apologize to colleagues whose work we could not cite owing to length restrictions. We thank S. Caplan and members of the Grant and Donaldson laboratories for comments. B. D. G. is supported by National Institutes of Health (NIH) grant R01 GM067237. J.G.D. is supported by the Intramural Research Program of the National Heart, Lung, and Blood Institute, NIH. NR 124 TC 499 Z9 501 U1 16 U2 95 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD SEP PY 2009 VL 10 IS 9 BP 597 EP 608 DI 10.1038/nrm2755 PG 12 WC Cell Biology SC Cell Biology GA 491QN UT WOS:000269594300010 PM 19696797 ER PT J AU Garcia-Diaz, M Bebenek, K Larrea, AA Havener, JM Perera, L Krahn, JM Pedersen, LC Ramsden, DA Kunkel, TA AF Garcia-Diaz, Miguel Bebenek, Katarzyna Larrea, Andres A. Havener, Jody M. Perera, Lalith Krahn, Joseph M. Pedersen, Lars C. Ramsden, Dale A. Kunkel, Thomas A. TI Template strand scrunching during DNA gap repair synthesis by human polymerase lambda SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID BASE EXCISION-REPAIR; RNA-POLYMERASE; NUCLEIC-ACIDS; FORCE-FIELD; BETA; MECHANISM; TRANSCRIPTION; INITIATION; PROTEINS; MISALIGNMENT AB Family X polymerases such as DNA polymerase lambda (Pol lambda) are well suited for filling short gaps during DNA repair because they simultaneously bind both the 5' and 3' ends of short gaps. DNA binding and gap filling are well characterized for 1-nucleotide (nt) gaps, but the location of yet-to-be-copied template nucleotides in longer gaps is unknown. Here we present crystal structures revealing that, when bound to a 2-nt gap, Pol lambda scrunches the template strand and binds the additional uncopied template base in an extrahelical position within a binding pocket that comprises three conserved amino acids. Replacing these amino acids with alanine results in less processive gap filling and less efficient NHEJ when 2-nt gaps are involved. Thus, akin to scrunching by RNA polymerase during transcription initiation, scrunching occurs during gap filling DNA synthesis associated with DNA repair. C1 [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Larrea, Andres A.; Perera, Lalith; Krahn, Joseph M.; Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Garcia-Diaz, Miguel; Bebenek, Katarzyna; Larrea, Andres A.; Kunkel, Thomas A.] NIEHS, Genet Mol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Havener, Jody M.; Ramsden, Dale A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov RI perera, Lalith/B-6879-2012 OI perera, Lalith/0000-0003-0823-1631 FU Division of Intramural Research of the US National Institutes of Health (NIH) [Z01 ES065070]; National Institute of Environmental Health Sciences and by NIH [CA 097096]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank L. Pedersen, W. Beard and B. Van Houten for critical reading of the manuscript. This work was partly supported by Project Z01 ES065070 to T. A. K. from the Division of Intramural Research of the US National Institutes of Health (NIH), National Institute of Environmental Health Sciences and by NIH grant CA 097096 to D. A. R. Use of the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. NR 40 TC 34 Z9 35 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD SEP PY 2009 VL 16 IS 9 BP 967 EP U91 DI 10.1038/nsmb.1654 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 490TS UT WOS:000269528700014 PM 19701199 ER PT J AU Holden, KF Lindquist, K Tylavsky, FA Rosano, C Harris, TB Yaffe, K AF Holden, Karen F. Lindquist, Karla Tylavsky, Frances A. Rosano, Caterina Harris, Tamara B. Yaffe, Kristine CA Hlth ABC Study TI Serum leptin level and cognition in the elderly: Findings from the Health ABC Study SO NEUROBIOLOGY OF AGING LA English DT Article DE Leptin; Cognition; Learning; Memory; Elderly; Aging; Dementia; Alzheimer's disease; Obesity; Hyperleptinemia; Leptin resistance; Metabolic syndrome ID HIPPOCAMPAL SYNAPTIC PLASTICITY; MICE OVEREXPRESSING LEPTIN; LONG-TERM POTENTIATION; BLOOD-BRAIN-BARRIER; INSULIN SENSITIVITY; GLUCOSE-METABOLISM; OLDER WOMEN; RESISTANCE; OBESITY; RATS AB Leptin is a peptide hormone secreted by adipocytes. It has been shown to modulate production and clearance of amyloid beta (A beta) in rodent models. We sought to determine if serum leptin was associated with cognitive decline in the elderly. We studied 2871 well-functioning elders, aged 70-79, who were enrolled in a prospective study. Serum leptin concentrations were measured at baseline and analyzed by mean +/- 1S.D. Clinically significantly cognitive decline over 4 years was defined as >= 5-point drop on the Modified Mini Mental State Exam (3MS). Compared to those in the lower leptin groups, elders in the high leptin group had less cognitive decline, 20.5% versus 24.7% (OR=0.79; 95% CI 0.61-1.02, p = 0.07). After adjustment for demographic and clinical variables, including body mass index and total percent body fat, those in the high leptin group had significantly less likelihood of cognitive decline, OR = 0.66 (95% CI 0.48-0.91). We conclude that in elderly individuals, higher serum leptin appears to protect against cognitive decline, independent of comorbidites and body fat. (C) 2007 Elsevier Inc. All rights reserved. C1 [Holden, Karen F.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Lindquist, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. [Rosano, Caterina] Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Holden, KF (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. EM karenholden@mac.com OI Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU Paul Beeson Faculty Scholar in Aging Program; NIH [R01 AG021918-01]; NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-21] FX Dr. Yaffe is supported by the Paul Beeson Faculty Scholar in Aging Program and NIH grant R01 AG021918-01. This research was supported in part by the Intramural Research program of the NIA, National Institute of Aging, as well as NIA contracts N01-AG-6-2101, N01-AG-6-2103 and N01-AG-6-21. NR 58 TC 88 Z9 90 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2009 VL 30 IS 9 BP 1483 EP 1489 DI 10.1016/j.neurobiolaging.2007.11.024 PG 7 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 481CA UT WOS:000268783200014 PM 18358569 ER PT J AU Bras, J Paisan-Ruiz, C Guerreiro, R Ribeiro, MH Morgadinho, A Januario, C Sidransky, E Oliveira, C Singleton, A AF Bras, Jose Paisan-Ruiz, Coro Guerreiro, Rita Ribeiro, Maria Helena Morgadinho, Ana Januario, Cristina Sidransky, Ellen Oliveira, Catarina Singleton, Andrew TI Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal SO NEUROBIOLOGY OF AGING LA English DT Article DE Case control study; Genetic association; Parkinson disease ID GAUCHER-DISEASE; GENE AB Mutations in the gene encoding beta-glucocerebrosidase, a lysosomal degrading enzyme, have recently been associated with the development of Parkinson disease. Here we report the results found in a cohort of Portuguese Parkinson disease patients and healthy age-matched controls for mutations in the aforementioned gene. This screening was accomplished by sequencing the complete open-reading frame, as well as intron/exon boundaries, of the glucocerebrosidase gene, in a total of 230 patients and 430 controls. We have found an increased number of Parkinson disease patients presenting mutations in GBA when compared to controls. These results, together with recent literature, clearly suggest a role of glucocerebrosidase in the development of Parkinson disease. (C) 2007 Elsevier Inc. All rights reserved. C1 [Bras, Jose; Paisan-Ruiz, Coro; Guerreiro, Rita; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Bras, Jose; Guerreiro, Rita; Ribeiro, Maria Helena; Oliveira, Catarina] Univ Coimbra, Fac Med, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Morgadinho, Ana; Januario, Cristina] Coimbra Univ Hosp, Neurol Serv, Coimbra, Portugal. [Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Singleton, A (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A1014,35 Lincoln Dr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Oliveira, Catarina/F-3685-2010; Bras, Jose/A-1428-2011; Guerreiro, Rita/A-1327-2011; OI Oliveira, Catarina/0000-0001-6942-4328 FU Intramural program of the National Institute on Aging; National Institutes of Health; Department of Health and Human Services; Fundacao para a Ciencia e Tecnologia [SFRH/BD/29647/2006, SFRH/BD/27442/2006] FX This work was supported in part by the Intramural program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services and Fundacao para a Ciencia e Tecnologia grants (SFRH/BD/29647/2006) and (SFRH/BD/27442/2006). NR 7 TC 57 Z9 58 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP PY 2009 VL 30 IS 9 BP 1515 EP 1517 DI 10.1016/j.neurobiolaging.2007.11.016 PG 3 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 481CA UT WOS:000268783200019 PM 18160183 ER PT J AU Astradsson, A Jenkins, BG Choi, JK Hallett, PJ Levesque, MA McDowell, JS Brownell, AL Spealman, RD Isacson, O AF Astradsson, Arnar Jenkins, Bruce G. Choi, Ji-Kyung Hallett, Penelope J. Levesque, Michele A. McDowell, Jack S. Brownell, Anna-Liisa Spealman, Roger D. Isacson, Ole TI The blood-brain barrier is intact after levodopa-induced dyskinesias in parkinsonian primates-Evidence from in vivo neuroimaging studies SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Levodopa; Dyskinesia; Primates; Blood-brain barrier; Imaging; Gadolinium-DTPA ID MULTIPLE-SCLEROSIS; DISEASE; PERMEABILITY; MODEL; MRI; SUBTYPES AB It has been suggested, based on rodent studies, that levodopa (L-dopa) induced dyskinesia is associated with a disrupted blood-brain barrier (BBB). We have investigated BBB integrity with in vivo neuroimaging techniques in six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned primates exhibiting dopa-induced dyskinesia. Magnetic resonance imaging (MRI) performed before and after injection of Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) revealed an intact BBB in the basal ganglia showing that L-dopa-induced dyskinesia is not associated with a disrupted BBB in this model. (C) 2009 Elsevier Inc. All rights reserved. C1 [Astradsson, Arnar; Jenkins, Bruce G.; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Brownell, Anna-Liisa; Spealman, Roger D.; Isacson, Ole] Harvard Univ, Belmont, MA 02478 USA. [Astradsson, Arnar; Jenkins, Bruce G.; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Brownell, Anna-Liisa; Spealman, Roger D.; Isacson, Ole] McLean Hosp, NINDS Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02178 USA. [Jenkins, Bruce G.; Choi, Ji-Kyung] Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Brownell, Anna-Liisa] Massachusetts Gen Hosp, MGH Positron Emiss Tomog Ctr, Boston, MA 02114 USA. [Astradsson, Arnar; Hallett, Penelope J.; Levesque, Michele A.; McDowell, Jack S.; Spealman, Roger D.; Isacson, Ole] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Ctr Neuroregenerat Res, MRC 130,115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu OI Hallett, Penelope/0000-0002-8858-9096 FU US National Institutes of Health [P50 NS39793, RR00168]; Michael Stern Foundation; Consolidated Anti-Aging Foundation; Orchard Foundation FX This work was supported by the US National Institutes of Health NINDS Udall Parkinson's Disease Research Center of Excellence (P50 NS39793), The Michael Stern Foundation, the Consolidated Anti-Aging Foundation, the Orchard Foundation, and an NIH base grant to NEPRC (RR00168). The authors declare no financial conflict of interest. We thank Angela Carville and Shannon Luboyeski for veterinary assistance. NR 25 TC 17 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD SEP PY 2009 VL 35 IS 3 BP 348 EP 351 DI 10.1016/j.nbd.2009.05.018 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 486ET UT WOS:000269179400003 PM 19501164 ER PT J AU King, AP Abelson, JL Britton, JC Phan, KL Taylor, SF Liberzon, I AF King, Anthony P. Abelson, James L. Britton, Jennifer C. Phan, K. Luan Taylor, Stephan F. Liberzon, Israel TI Medial prefrontal cortex and right insula activity predict plasma ACTH response to trauma recall SO NEUROIMAGE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SCRIPT-DRIVEN IMAGERY; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; ABUSE-RELATED PTSD; CORTISOL-LEVELS; SYMPTOM PROVOCATION; ANXIETY DISORDER; NEGATIVE AFFECT; LIMBIC SYSTEM AB Neural substrates underlying psychological activation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis are not well understood in humans. Trauma recall (using autobiographical script-driven imagery) may provide a model to study neural circuitry involved in LHPA axis activation to personally threatening psychological Stimuli. This study sought to identify brain activation patterns that differentiated combat veterans who mounted an LHPA response to trauma recall from those who did not. Twenty-five Vietnam combat veterans (14 with current PTSD, 11 with no PTSD history) experienced autobiographic script-driven imagery in an [(15)O] H(2)O positron emission tomography (PET) paradigm with recurrent blood sampling. Trauma recall elicited acute ACTH responses in some but not all veterans, regardless of the PTSD status and independent of emotional responses. ACTH responders (mean ACTH increase of 24 +/- 7 pg/ml, n = 13) were compared to non-responders (mean decrease of -0.6 +/- 0.6 pg/ml, n = 12) in regional cerebral blood flow (rCBF). Both groups activated right insula (BA13) in response to trauma recall, However, ACTH responders deactivated rostral mPFC (BA10)/rostral ACC (BA32), whereas non-responders activated this same mPFC region, and deactivated amygdala, hippocampus, and temporal pole. In group contrasts comparing ACTH responders to non-responders, the responders had significantly higher rCBF in right insula and right temporal pole, whereas non-responders had higher rCBF in rostral mPFC and dorsal ACC. These results Support the hypotheses that right insula is involved in psychological activation of the LHPA axis and that rostral mPFC may negatively modulate LHPA axis responses. (C) 2009 Elsevier Inc. All rights reserved. C1 [King, Anthony P.; Abelson, James L.; Phan, K. Luan; Taylor, Stephan F.; Liberzon, Israel] Univ Michigan, Ann Arbor, MI 48109 USA. [King, Anthony P.; Phan, K. Luan; Liberzon, Israel] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. [Britton, Jennifer C.] NIMH, Bethesda, MD USA. RP Liberzon, I (reprint author), 2756 Rachel Upjohn Bldg,4250 Plymouth Rd, Ann Arbor, MI 48109 USA. EM liberzon@umich.edu RI Taylor, Stephan/A-1211-2007; Britton, Jennifer/J-4501-2013; OI King, Anthony/0000-0002-0764-9625; Liberzon, Israel/0000-0002-4990-556X NR 74 TC 20 Z9 21 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 872 EP 880 DI 10.1016/j.neuroimage.2009.05.088 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200011 PM 19501653 ER PT J AU Thayer, JF Sternberg, EM AF Thayer, Julian F. Sternberg, Esther M. TI Neural concomitants of immunity-Focus on the vagus nerve SO NEUROIMAGE LA English DT Editorial Material ID TO-BRAIN COMMUNICATION; CHOLINERGIC ANTIINFLAMMATORY PATHWAY; HEART-RATE-VARIABILITY; SYSTEM; NOREPINEPHRINE; STIMULATION; INHIBITION; MECHANISMS; EMOTION; CORTEX C1 [Thayer, Julian F.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. [Thayer, Julian F.] Mannheim Inst Publ Hlth, Mannheim, Germany. [Sternberg, Esther M.] NIMH, NIH, Bethesda, MD 20892 USA. RP Thayer, JF (reprint author), Ohio State Univ, Dept Psychol, 1835 Neil Ave, Columbus, OH 43210 USA. EM Thayer.39@osu.edu FU Intramural NIH HHS [Z01 MH002585-17] NR 29 TC 11 Z9 11 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 908 EP 910 DI 10.1016/j.neuroimage.2009.05.058 PG 3 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200015 PM 19481613 ER PT J AU Birn, RM Murphy, K Handwerker, DA Bandettini, PA AF Birn, Rasmus M. Murphy, Kevin Handwerker, Daniel. A. Bandettini, Peter A. TI fMRI in the presence of task-correlated breathing variations SO NEUROIMAGE LA English DT Article ID INDEPENDENT COMPONENT ANALYSIS; HEART-RATE-VARIABILITY; FUNCTIONAL MRI; BOLD SIGNAL; RESPONSE FUNCTION; FLUCTUATIONS; BRAIN; STATE; RESPIRATION; IMPACT AB Variations in the subject's heart rate and breathing pattern have been shown to result in significant fMRI signal changes, mediated in part by non-neuronal physiological mechanisms such as global changes in levels of arterial CO(2). When these physiological changes are correlated with a task, as may happen in response to emotional stimuli or tasks that change levels of arousal, a concern arises that non-neuronal physiologically-induced signal changes may be in is interpreted as reflecting task-related neuronal activation. The purpose of this study is to provide information that can help in determining whether task activation maps are influenced by task-correlated physiological noise, particularly task-correlated breathing changes. We also compare different strategies to reduce the influence of physiological noise. Two paradigms are investigated - 1) a lexical decision task where some subjects showed task-related breathing changes, and 2) a task where subjects were instructed to hold their breath during the presentation of contrast-reversing checkerboard, an extreme case of task-correlated physiological noise. Consistent with previous literature, we find that MRI signal changes correlated with variations in breathing depth and rate have a characteristic spatial and temporal profile that is different from the typical activation-induced BOLD response. The delineation of activation in the presence of task correlated breathing changes was improved either by independent component analysis, or by including specific nuisance regressors in a regression analysis. The difference in the spatial and temporal characteristics of physiological-induced and neuronal-induced fluctuations exploited by these strategies suggests that activation can be studied even in the presence of task-correlated physiological changes. Published by Elsevier Inc. C1 [Birn, Rasmus M.; Handwerker, Daniel. A.; Bandettini, Peter A.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Murphy, Kevin] Cardiff Univ, Brain Res Imaging Ctr, Cardiff, S Glam, Wales. RP Birn, RM (reprint author), NIMH, Lab Brain & Cognit, NIH, 10 Ctr Dr,Bldg 10,Rm 1D80, Bethesda, MD 20892 USA. EM rbirn@mail.nih.gov RI Murphy, Kevin/A-1581-2010 OI Murphy, Kevin/0000-0002-6516-313X FU National Institutes of Mental Health Intramural Research Program FX This research was funded by the National Institutes of Mental Health Intramural Research Program. NR 35 TC 64 Z9 64 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 1092 EP 1104 DI 10.1016/j.neuroimage.2009.05.030 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200037 PM 19460443 ER PT J AU Bullmore, ET Barnes, A Bassett, DS Fornito, A Kitzbichler, M Meunier, D Suckling, J AF Bullmore, Edward T. Barnes, Anna Bassett, Danielle S. Fornito, Alex Kitzbichler, Manfred Meunier, David Suckling, John TI Generic aspects of complexity in brain imaging data and other biological systems SO NEUROIMAGE LA English DT Review ID SELF-ORGANIZED CRITICALITY; SMALL-WORLD NETWORKS; MAGNETIC-RESONANCE IMAGES; CORTICAL NETWORKS; COMMUNITY STRUCTURE; FUNCTIONAL NETWORKS; HEARTBEAT DYNAMICS; HIERARCHICAL ORGANIZATION; FRACTAL SIGNALS; LOW-FREQUENCY AB A key challenge for systems neuroscience is the question of how to understand the complex network organization of the brain oil the basis of neuroimaging data. Similar challenges exist in other specialist areas of systems biology because complex networks emerging from the interactions between Multiple non-trivially interacting agents are found quite ubiquitously in nature, from protein interactomes to ecosystems. We suggest that one way forward for analysis of brain networks will be to quantify aspects of their organization which are likely to be generic properties of a broader class of biological systems. In this introductory review article we will highlight four important aspects of complex systems in general: fractality or scale-invariance: criticality; small-world and related topological attributes; and modularity. For each concept we will provide an accessible introduction, an illustrative data-based example of flow it can be used to investigate aspects of brain organization in neuroimaging experiments, and a brief review of how this concept has been applied and developed in other fields of biomedical and physical science. The ann is to provide a didactic, focussed and user-friendly introduction to the concepts of complexity science for neuroscientists and neuroimagers. (C) 2009 Elsevier Inc. All rights reserved. C1 [Bullmore, Edward T.; Barnes, Anna; Bassett, Danielle S.; Fornito, Alex; Kitzbichler, Manfred; Meunier, David; Suckling, John] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England. [Bassett, Danielle S.] Univ Cambridge, Dept Phys, Biol Soft Syst Sector, Cambridge CB2 2QQ, England. [Bassett, Danielle S.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. [Fornito, Alex] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Parkville, Vic 3052, Australia. RP Bullmore, ET (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England. EM etb23@cam.ac.uk RI Meunier, David/F-2466-2011; Bullmore, Edward/C-1706-2012; Alex, Fornito/N-8214-2013 OI Bullmore, Edward/0000-0002-8955-8283; Alex, Fornito/0000-0001-9134-480X NR 124 TC 50 Z9 51 U1 2 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2009 VL 47 IS 3 BP 1125 EP 1134 DI 10.1016/j.neuroimage.2009.05.032 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 482YI UT WOS:000268926200040 PM 19460447 ER PT J AU Hutchison, ER Okun, E Mattson, MP AF Hutchison, Emmette R. Okun, Eitan Mattson, Mark P. TI The Therapeutic Potential of microRNAs in Nervous System Damage, Degeneration, and Repair SO NEUROMOLECULAR MEDICINE LA English DT Article DE miRNAs; Neurodegenerative disease; Alzheimer's disease; Parkinson's disease; Huntington's disease; Transplantation ID MEDIATED RNA INTERFERENCE; TRANSIENT FOCAL ISCHEMIA; TARGET MESSENGER-RNAS; NUCLEIC-ACID PROBES; ALZHEIMERS-DISEASE; HUNTINGTONS-DISEASE; ALPHA-SYNUCLEIN; NEURONAL DIFFERENTIATION; MICROARRAY ANALYSIS; PARKINSONS-DISEASE AB MicroRNAS (miRNAs) have been suggested to play important roles in the central nervous system during development as well as disease. miRNAs appear to be dysregulated in a number of neurodegenerative diseases, developmental disorders, and as a result of stroke. Each miRNA has the ability to regulate hundreds of messenger RNA transcripts, both by causing degradation of the mRNA and by inhibition of protein translation. Recent findings suggest that it may eventually be possible to treat some neurological disorders by restoring or inhibiting miRNAs altered by disease pathology. Both viral delivery and administration of modified oligonucleotides mimicking or inhibiting specific miRNAs have been effective in model systems. Artificial miRNAs have also been generated for the repression of specific transcripts. Alteration of miRNA expression by disease and insult also holds the potential for improved diagnostic tools. Finally, miRNAs have been shown to control cellular proliferation and specification, suggesting that manipulation of miRNAs in cultured cells could result in more convenient generation of pure cell populations for transplantation. C1 [Hutchison, Emmette R.; Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Hutchison, Emmette R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM hutchisone@mail.nih.gov; mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 FU Intramural NIH HHS [Z01 AG000312-07, Z01 AG000313-07, Z01 AG000314-07] NR 68 TC 23 Z9 27 U1 1 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD SEP PY 2009 VL 11 IS 3 BP 153 EP 161 DI 10.1007/s12017-009-8086-x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 500FQ UT WOS:000270284500003 PM 19763905 ER PT J AU Hunsberger, JG Austin, DR Chen, G Manji, HK AF Hunsberger, Joshua G. Austin, Daniel R. Chen, Guang Manji, Husseini K. TI MicroRNAs in Mental Health: From Biological Underpinnings to Potential Therapies SO NEUROMOLECULAR MEDICINE LA English DT Article DE MicroRNA (miRNA); Psychiatric disorders; Schizophrenia; Bipolar disorder; Depression; Stress; Glucocorticoids; Mood stabilizers ID MEDIAL PREFRONTAL CORTEX; LONG-TERM POTENTIATION; BIPOLAR DISORDER; MOOD DISORDERS; GLUCOCORTICOID-RECEPTOR; MAJOR DEPRESSION; STRESS RESPONSES; HUMAN BRAIN; SCHIZOPHRENIA; MECHANISMS AB Psychiatric illnesses are disabling disorders with poorly understood underlying pathophysiologies. However, it is becoming increasingly evident that these illnesses result from disruptions across whole cellular networks rather than any particular monoamine system. Recent evidence continues to support the hypothesis that these illnesses arise from impairments in cellular plasticity cascades, which lead to aberrant information processing in the circuits that regulate mood, cognition, and neurovegetative functions (sleep, appetite, energy, etc.). As a result, many have begun to consider future therapies that would be capable of affecting global changes in cellular plasticity to restore appropriate synaptic function and neuronal connectivity. MicroRNAs (miRNAs) are non-coding RNAs that can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. Here, we review some properties of miRNAs and show they are altered by stress, glucocorticoids, mood stabilizers, and in a particular psychiatric disorder, schizophrenia. While this field is still in its infancy, we consider their potential for regulating behavioral phenotypes and targeting key predicted signaling cascades that are implicated in psychiatric illness. Clearly, considerable research is required to better determine any therapeutic potential of targeting miRNAs; however, these agents may provide the next generation of effective therapies for psychiatric illnesses. C1 [Hunsberger, Joshua G.; Austin, Daniel R.; Chen, Guang; Manji, Husseini K.] NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mol Pathophysiol Lab, NIH, 9000 Rockville Pike,Bldg 35,1C912, Bethesda, MD 20892 USA. EM hunsbergerj@mail.nih.gov; manji@nih.gov RI Chen, Guang/A-2570-2017 FU Intramural NIH HHS [Z99 MH999999] NR 58 TC 46 Z9 49 U1 10 U2 15 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1535-1084 J9 NEUROMOL MED JI Neuromol. Med. PD SEP PY 2009 VL 11 IS 3 BP 173 EP 182 DI 10.1007/s12017-009-8070-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 500FQ UT WOS:000270284500005 PM 19544012 ER PT J AU Adlam, ALR Malloy, M Mishkin, M Vargha-Khadem, F AF Adlam, Anna-Lynne R. Malloy, Megan Mishkin, Mortimer Vargha-Khadem, Faraneh TI Dissociation between recognition and recall in developmental amnesia SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT Meeting on Episodic Memory and the Brain CY MAR, 2009 CL Tallinn, ESTONIA DE Hippocampus; Hypoxia; Familiarity; Recollection; Doors and People test ID MEDIAL TEMPORAL-LOBE; HIPPOCAMPAL DAMAGE; SEMANTIC MEMORY; RECOLLECTION; FAMILIARITY; BRAIN AB Developmental amnesia (DA) is a memory disorder due to hypoxia/ischaemia-induced damage to the hippocampus early in life. To test the hypothesis that this disorder is associated with a disproportionate impairment in recall vis-a-vis recognition, we examined a group of 10 patients with DA on the Doors and People test, which affords a quantitative comparison between measures of the two memory processes. The results supported the hypothesis in that the patients showed a sharp, though not complete, recall-recognition dissociation, exhibiting impairment on both measures relative to their matched controls, but with a far greater loss in recall than in recognition. Whether their relatively spared recognition ability is due to restriction of their medial temporal lobe damage to the hippocampus or whether it is due instead to their early age at injury is still uncertain. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Adlam, Anna-Lynne R.; Vargha-Khadem, Faraneh] UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, London WC1N 1EH, England. [Malloy, Megan; Mishkin, Mortimer] NIMH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Vargha-Khadem, F (reprint author), UCL, Inst Child Hlth, Dev Cognit Neurosci Unit, 30 Guilford St, London WC1N 1EH, England. RI Adlam, Anna/F-8400-2010; Vargha-Khadem, Faraneh/C-2558-2008; OI Adlam, Anna/0000-0001-7212-4051 FU Intramural NIH HHS [Z99 MH999999]; Medical Research Council [G0300117/65439, G0300117]; Wellcome Trust NR 28 TC 28 Z9 29 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 2009 VL 47 IS 11 BP 2207 EP 2210 DI 10.1016/j.neuropsychologia.2009.01.038 PG 4 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 468SF UT WOS:000267839900008 PM 19524088 ER PT J AU Vartanian, O Goel, V Tierney, M Huey, ED Grafman, J AF Vartanian, Oshin Goel, Vinod Tierney, Michael Huey, Edward D. Grafman, Jordan TI Frontotemporal Dementia Selectively Impairs Transitive Reasoning About Familiar Spatial Environments SO NEUROPSYCHOLOGY LA English DT Article DE executive function; frontotemporal dementia; reasoning; semantic memory ID VOXEL-BASED MORPHOMETRY; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; PICKS-DISEASE; 2 SYSTEMS; DISSOCIATION; COGNITION AB Although patients with frontotemporal dementia (FTD) are known to exhibit a wide range of cognitive and personality difficulties, some evidence suggests that there may be a degree of selectivity in their reasoning impairments. Based on a recent review of the neuroimaging literature on reasoning, the authors hypothesized that the presence or absence of familiar content may have a selective impact on the reasoning abilities of patients with FTD. Specifically, the authors predicted that patients with frontal-variant FTD would be more impaired when reasoning about transitive arguments involving familiar spatial environments than when reasoning about identical logical arguments involving unfamiliar spatial environments. As predicted, patients with FTD were less accurate than normal controls only when the content of arguments involved familiar spatial environments. These results indicate a degree of selectivity in the cognitive deficits of this patient population and suggest that the frontal-temporal lobe system may play a necessary role in reasoning about familiar material. C1 [Vartanian, Oshin; Goel, Vinod] York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. [Goel, Vinod] Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England. [Tierney, Michael; Huey, Edward D.; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. RP Vartanian, O (reprint author), York Univ, Dept Psychol, 4700 Keele St, Toronto, ON M3J 1P3, Canada. EM oshinv1@mac.com OI Grafman, Jordan H./0000-0001-8645-4457 FU Canadian Institutes of Health Research; National Science & Engineering Research Council of Canada; Premier's Research Excellence Award FX This study was supported by grants from the Canadian Institutes of Health Research, National Science & Engineering Research Council of Canada, and a Premier's Research Excellence Award to the second author. NR 47 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD SEP PY 2009 VL 23 IS 5 BP 619 EP 626 DI 10.1037/a0015810 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 490CY UT WOS:000269476300008 PM 19702415 ER PT J AU Perlis, RH Patrick, A Smoller, JW Wang, PS AF Perlis, Roy H. Patrick, Amanda Smoller, Jordan W. Wang, Philip S. TI When is Pharmacogenetic Testing for Antidepressant Response Ready for the Clinic? A Cost-effectiveness Analysis Based on Data from the STAR*D Study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE pharmacogenetics; major depressive disorder; cost effectiveness; serotonin ID MAJOR DEPRESSIVE DISORDER; PRIMARY-CARE; SEROTONIN TRANSPORTER; CITALOPRAM TREATMENT; ECONOMIC EVALUATIONS; SUICIDAL IDEATION; MANAGED CARE; OUTCOMES; HEALTH; POLYMORPHISMS AB The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93 520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50 000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios similar to 1.8-2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings. Neuropsychopharmacology (2009) 34, 2227-2236; doi: 10.1038/npp.2009.50; published online 3 June 2009 C1 [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Perlis, Roy H.; Smoller, Jordan W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Genet Program, Boston, MA 02114 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. [Patrick, Amanda] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02114 USA. [Wang, Philip S.] NIMH, Bethesda, MD 20892 USA. RP Perlis, RH (reprint author), Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM rperlis@partners.org FU NIMH [K23-MH67060]; NARSAD [R01MH6194]; Sydney R Baer, Jr Foundation; Bowman Family Foundation FX This work was supported by NIMH K23-MH67060, NARSAD and the Sydney R Baer, Jr Foundation, and the Bowman Family Foundation (Dr Perlis) and NIMH R01MH6194 (Dr Wang). No pharmaceutical company was involved in any way in initiating, conducting, or supporting this research. NR 54 TC 36 Z9 37 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2009 VL 34 IS 10 BP 2227 EP 2236 DI 10.1038/npp.2009.50 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 482VY UT WOS:000268919100004 PM 19494805 ER PT J AU Wu, HM Tzeng, NS Qian, L Wei, SJ Hu, XM Chen, SH Rawls, SM Flood, P Hong, JS Lu, RB AF Wu, Hung-Ming Tzeng, Nian-Sheng Qian, Li Wei, Sung-Jen Hu, Xiaoming Chen, Shih-Heng Rawls, Scott M. Flood, Patrick Hong, Jau-Shyong Lu, Ru-Band TI Novel Neuroprotective Mechanisms of Memantine: Increase in Neurotrophic Factor Release from Astroglia and Anti-Inflammation by Preventing Microglial Activation SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE GDNF; neuroinflammation; neuroprotection; neurodegenerative disease; HDAC ID NMDA RECEPTOR ANTAGONIST; C6 GLIOMA-CELLS; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; MESENCEPHALIC NEURONS; GENE-EXPRESSION; DOUBLE-BLIND; CHRONIC NEUROINFLAMMATION; GLUTAMATE TOXICITY AB Memantine shows clinically relevant efficacy in patients with Alzheimer's disease and Parkinson's disease. Most in vivo and in vitro studies attribute the neuroprotective effects of memantine to the blockade of N-methyl-D-aspartate (NMDA) receptor on neurons. However, it cannot be excluded that mechanisms other than NMDA receptor blockade may contribute to the neuroprotective effects of this compound. To address this question, primary midbrain neuron-glia cultures and reconstituted cultures were used, and lipopolysaccharide (LPS), an endotoxin from bacteria, was used to produce inflammation-mediated dopaminergic (DA) neuronal death. Here, we show that memantine exerted both potent neurotrophic and neuroprotective effects on DA neurons in rat neuron-glia cultures. The neurotrophic effect of memantine was glia dependent, as memantine failed to show any positive effect on DA neurons in neuron-enriched cultures. More specifically, it seems to be that astroglia, not microglia, are the source of the memantine-elicited neurotrophic effects through the increased production of glial cell line-derived neurotrophic factor (GDNF). Mechanistic studies showed that GDNF upregulation was associated with histone hyperacetylation by inhibiting the cellular histone deacetylase activity. In addition, memantine also displays neuroprotective effects against LPS-induced DA neuronal damage through its inhibition of microglia activation showed by both OX-42 immunostaining and reduction of pro-inflammatory factor production, such as extracellular superoxide anion, intracellular reactive oxygen species, nitric oxide, prostaglandin E(2), and tumor necrosis factor-alpha. These results suggest that the neuroprotective effects of memantine shown in our cell culture studies are mediated in part through alternative novel mechanisms by reducing microglia-associated inflammation and by stimulating neurotrophic factor release from astroglia. Neuropsychopharmacology (2009) 34, 2344-2357; doi: 10.1038/npp.2009.64; published online 17 June 2009 C1 [Wu, Hung-Ming; Chen, Shih-Heng; Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Coll Med, Tainan 70428, Taiwan. [Wu, Hung-Ming; Chen, Shih-Heng; Lu, Ru-Band] Natl Cheng Kung Univ Hosp, Dept Psychiat, Tainan 70428, Taiwan. [Wu, Hung-Ming; Tzeng, Nian-Sheng; Qian, Li; Hu, Xiaoming; Chen, Shih-Heng; Hong, Jau-Shyong] NIEHS, Pharmacol Lab, Neuropharmacol Sect, NIH, Durham, NC USA. [Tzeng, Nian-Sheng] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Psychiat, Taipei, Taiwan. [Qian, Li; Flood, Patrick] Univ N Carolina, Comprehens Ctr Inflammatory Disorders, Chapel Hill, NC USA. [Wei, Sung-Jen] NIEHS, Canc Biol Grp, Mol Toxicol Lab, NIH, Durham, NC USA. [Wei, Sung-Jen] Univ Texas Hlth Sci Ctr San Antonio, Edinburg Reg Acad Hlth Ctr, Dept Pharmacol, Div Med Res, Edinburg, TX USA. [Rawls, Scott M.] Temple Univ, Sch Pharm, Dept Pharmaceut Sci, Philadelphia, PA 19122 USA. [Rawls, Scott M.] Temple Univ, Sch Pharm, Ctr Subst Abuse Res, Philadelphia, PA 19122 USA. RP Lu, RB (reprint author), Natl Cheng Kung Univ, Coll Med & Hosp, Dept Psychiat, 138 Sheng Li Rd, Tainan 70428, Taiwan. EM rblu@mail.ncku.edu.tw FU National Cheng Kung University, Project of Promoting Academic Excellence & Developing World Class Research Centers, Taiwan, Republic of China; Intramural Research Program of the NIH/NIEHS FX This project was supported by a grant from the National Cheng Kung University, Project of Promoting Academic Excellence & Developing World Class Research Centers, Taiwan, Republic of China. This research was also supported in part by the Intramural Research Program of the NIH/NIEHS. We gratefully acknowledge the technical assistance of Belinda Wilson and Dr Hui-Ling Chen, and the statistical analysis of Dr Zongli Xu. NR 54 TC 66 Z9 68 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2009 VL 34 IS 10 BP 2344 EP 2357 DI 10.1038/npp.2009.64 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 482VY UT WOS:000268919100014 PM 19536110 ER PT J AU Stuart, M Benvenuti, F Macko, R Taviani, A Segenni, L Mayer, F Sorkin, JD Stanhope, SJ Macellari, V Weinrich, M AF Stuart, Mary Benvenuti, Francesco Macko, Richard Taviani, Antonio Segenni, Lucianna Mayer, Federico Sorkin, John D. Stanhope, Steven J. Macellari, Velio Weinrich, Michael TI Community-Based Adaptive Physical Activity Program for Chronic Stroke: Feasibility, Safety, and Efficacy of the Empoli Model SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE Stroke; Exercise; Community; Rehabilitation ID RANDOMIZED CONTROLLED-TRIAL; LOWER-EXTREMITY FUNCTION; 6-MINUTE WALK TEST; QUALITY-OF-LIFE; EXERCISE BEHAVIOR; SUBACUTE STROKE; OLDER-ADULTS; CARDIOVASCULAR FITNESS; THERAPEUTIC EXERCISE; PERFORMANCE BATTERY AB Objective. To determine whether Adaptive Physical Activity (APA-stroke), a community-based exercise program for participants with hemiparetic stroke, improves function in the community. Methods. Nonrandomized controlled study in Tuscany, Italy, of participants with mild to moderate hemiparesis at least 9 months after stroke. Forty-nine participants in a geographic health authority (Empoli) were offered APA-stroke (40 completed the study). Forty-four control participants in neighboring health authorities (Florence and Pisa) received usual care (38 completed the study). The APA intervention was a community-based progressive group exercise regimen that included walking, strength, and balance training for 1 hour, thrice a week, in local gyms, supervised by gym instructors. No serious adverse clinical events occurred during the exercise intervention. Outcome measures included the following: 6-month change in gait velocity (6-Minute Timed Walk), Short Physical Performance Battery (SPPB), Berg Balance Scale, Stroke Impact Scale (SIS), Barthel Index, Hamilton Rating Scale for Depression, and Index of Caregivers Strain. Results. After 6 months, the intervention group improved whereas controls declined in gait velocity, balance, SPPB, and SIS social participation domains. These between-group comparisons were statistically significant at P<.00015. Individuals with depressive symptoms at baseline improved whereas controls were unchanged (P<.003). Oral glucose tolerance tests were performed on a subset of participants in the intervention group. For these individuals, insulin secretion declined 29% after 6 months (P=.01). Conclusion. APA-stroke appears to be safe, feasible, and efficacious in a community setting. C1 [Stuart, Mary; Benvenuti, Francesco] Univ Maryland Baltimore Cty, Hlth Adm & Policy Program, Baltimore, MD 21250 USA. [Benvenuti, Francesco; Taviani, Antonio] Azienda Unita Sanit Locale 11 Empoli, Dipartimento Riabilitaz & Fragilita, Empoli, Italy. [Macko, Richard] Univ Maryland, Dept Neurol & Med, Div Gerontol, Sch Med, Baltimore, MD 21201 USA. [Macko, Richard] Univ Maryland, Dept Phys Therapy & Rehabil Sci, Sch Med, Baltimore, MD 21201 USA. [Segenni, Lucianna] Azienda Unita Sanit Locale 5 Pisa, Unita Operat Recupero & Riabilitaz Funz, Pisa, Italy. [Mayer, Federico] Unita Operat Riabilitaz, Florence, Italy. [Sorkin, John D.] Univ Maryland, Sch Med, Claude D Pepper Older Amer Independence Ctr, Baltimore, MD 21201 USA. [Stanhope, Steven J.] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE USA. [Macellari, Velio] Ist Super Sanita, Dipartimento Tecnol & Salute, I-00161 Rome, Italy. [Weinrich, Michael] NICHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD USA. RP Stuart, M (reprint author), Univ Maryland Baltimore Cty, Hlth Adm & Policy Program, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM stuart@umbc.edu FU Istituto Superiore di Sanita; US National Institutes of Health [530/F20/2]; Italy's Ministry of Health; National Institute of Child Health; National Institutes of Health FX This study was funded by the Istituto Superiore di Sanita within the research project "Obtaining Optimal Functional Recovery and Efficient Managed Care for the Chronic Stroke Population" (convenzione n. 530/F20/2) within the framework of the 2003 Memorandum of Understanding between the US National Institutes of Health and Italy's Ministry of Health. This work was also supported by an Intramural Research Program of the National Institute of Child Health and Human Development and the Clinical Center of the National Institutes of Health. The opinions presented in this report reflect the views of the authors and not those of the National Institutes of Health or the US Public Health Service. NR 57 TC 54 Z9 56 U1 2 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD SEP PY 2009 VL 23 IS 7 BP 726 EP 734 DI 10.1177/1545968309332734 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 487ZB UT WOS:000269317100011 PM 19318465 ER PT J AU Levin, ED Aschner, M Heberlein, U Ruden, D Welsh-Bohmer, KA Bartlett, S Berger, K Chen, L Corl, AB Eddins, D French, R Hayden, KM Helmcke, K Hirsch, HVB Linney, E Lnenicka, G Page, GP Possidente, D Possidente, B Kirshner, A AF Levin, Edward D. Aschner, Michael Heberlein, Ulrike Ruden, Douglas Welsh-Bohmer, Kathleen A. Bartlett, Selena Berger, Karen Chen, Lang Corl, Ammon B. Eddins, Donnie French, Rachael Hayden, Kathleen M. Helmcke, Kirsten Hirsch, Helmut V. B. Linney, Elwood Lnenicka, Greg Page, Grier P. Possidente, Debra Possidente, Bernard Kirshner, Annette TI Genetic aspects of behavioral neurotoxicology SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 25th International Neurotoxicology Conference CY OCT 12-16, 2008 CL Rochester, NY DE Genetics; Behavioral neurotoxicology; C. elegans; Drosophilia; Zebrafish; Mice ID NEMATODE CAENORHABDITIS-ELEGANS; GLYCOGEN-SYNTHASE KINASE-3; NEONATAL CHLORPYRIFOS EXPOSURE; INDUCED APOPTOTIC NEURODEGENERATION; DEPENDENT PROTEIN-KINASE; FETAL-ALCOHOL-SYNDROME; RAT CORTICAL-NEURONS; ALZHEIMERS-DISEASE; CACHE COUNTY; APOLIPOPROTEIN-E AB Considerable progress has been made over the past couple of decades concerning the molecular bases of neurobehavioral function and dysfunction. The field of neurobehavioral genetics is becoming mature. Genetic factors contributing to neurologic diseases such as Alzheimer's disease have been found and evidence for genetic factors contributing to other diseases such as schizophrenia and autism are likely. This genetic approach can also benefit the field of behavioral neurotoxicology. It is clear that there is substantial heterogeneity of response with behavioral impairments resulting from neurotoxicants. Many factors contribute to differential sensitivity, but it is likely that genetic variability plays a prominent role. Important discoveries concerning genetics and behavioral neurotoxicity are being made on a broad front from work with invertebrate and piscine mutant models to classic mouse knockout models and human epidemiologic studies of polymorphisms. Discovering genetic factors of susceptibility to neurobehavioral toxicity not only helps identify those at special risk, it also advances our understanding of the mechanisms by which toxicants impair neurobehavioral function in the larger population. This symposium organized by Edward Levin and Annette Kirshner, brought together researchers from the laboratories of Michael Aschner, Douglas Ruden, Ulrike Heberlein, Edward Levin and Kathleen Welsh-Bohmer conducting studies with Caenorhabditis elegans, Drosophila, fish, rodents and humans studies to determine the role of genetic factors in susceptibility to behavioral impairment from neurotoxic exposure. (C) 2009 Elsevier Inc. All rights reserved. C1 [Levin, Edward D.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Aschner, Michael; Helmcke, Kirsten] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Heberlein, Ulrike; Bartlett, Selena; Berger, Karen; Corl, Ammon B.; French, Rachael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ruden, Douglas] Wayne State Univ, Detroit, MI USA. [Chen, Lang] Univ Alabama, Birmingham, AL USA. [Hirsch, Helmut V. B.; Lnenicka, Greg; Possidente, Debra] SUNY Albany, Albany, NY 12222 USA. [Possidente, Bernard] Skidmore Coll, Saratoga Springs, NY 12866 USA. [Kirshner, Annette] NIEHS, Res Triangle Pk, NC 27709 USA. [Page, Grier P.] RTI Int, Stat & Epidemiol Unit, Atlanta, GA USA. RP Levin, ED (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3412, Durham, NC 27710 USA. EM edlevin@duke.edu RI Mavoa, Suzanne/B-5372-2010; Bartlett, Selena/J-1345-2012; Hayden, Kathleen/B-6442-2012 OI Bartlett, Selena/0000-0002-1741-3958; Hayden, Kathleen/0000-0002-7745-3513 FU NCI NIH HHS [R01 CA105349]; NIA NIH HHS [AG011380, AG028377, AG029336, AG11380, K01 AG029336, P30 AG028377, R01 AG011380]; NIAAA NIH HHS [AA010035, R01 AA010035]; NIEHS NIH HHS [P42 ES010356, ES010356, P30 ES006639, P30 ES06639, P42 ES010356-090006, R01 ES010563, R01 ES010563-09, R01 ES012933, R01 ES10563] NR 176 TC 17 Z9 17 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2009 VL 30 IS 5 BP 741 EP 753 DI 10.1016/j.neuro.2009.07.014 PG 13 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 513AC UT WOS:000271292900002 PM 19647018 ER PT J AU Kraft, AD McPherson, CA Harry, GJ AF Kraft, Andrew D. McPherson, Christopher A. Harry, G. Jean TI Heterogeneity of microglia and TNF signaling as determinants for neuronal death or survival SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 25th International Neurotoxicology Conference CY OCT 12-16, 2008 CL Rochester, NY DE Microglia; Neuroinflammation; Hippocampus; Trimethyltin; TNF alpha; TNF receptors ID TUMOR-NECROSIS-FACTOR; CENTRAL-NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; TRAUMATIC BRAIN-INJURY; EXPERIMENTAL AUTOIMMUNE NEURITIS; FACTOR RECEPTOR P75; KAPPA-B ACTIVATION; FACTOR-ALPHA; PARKINSONS-DISEASE; CELL-DEATH AB Microglia do not constitute a single, uniform cell population, but rather comprise cells with varied phenotypes, some which are beneficial and others that may require active regulatory control. Thus, gaining a better understanding of the heterogeneity of resident microglia responses will contribute to any interpretation regarding the impact of any such response in the brain. Microglia are the primary source of the pro-inflammatory cytokine, tumor necrosis factor (TNF) that can initiate various effects through the activation of membrane receptors. The TNF p55 receptor contains a death domain and activation normally leads to cellular apoptosis; however, under specific conditions, receptor activation can also lead to the activation of NF-kappa B and contribute to cell survival. These divergent outcomes have been linked to receptor localization with receptor internalization leading to cell death and membrane localization supporting cell survival. A second TNF receptor, TNF p75 receptor, is normally linked to cell growth and survival, however, it can cooperate with the p55 receptor and contribute to cell death. Thus, while an elevation in TNF alpha in the brain is often considered an indicator of microglia activation and neuroinflammation, a number of factors come into play to determine the final outcome. Data are reviewed demonstrating that heterogeneity in morphological response of microglia and the expression of TNF alpha and TNF receptors are critical in identifying and characterizing neurotoxic events as they relate to neuroinflammation, neuronal damage and in stimulating neuroprotection. Published by Elsevier Inc. C1 [Kraft, Andrew D.; McPherson, Christopher A.; Harry, G. Jean] NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Neurotoxicol Grp, Mol Toxicol Lab, NIH,Dept Hlth & Human Serv, POB 12233,MD C1-04, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov FU Intramural NIH HHS [ZIA ES021164-14, ZIA ES101623-08] NR 132 TC 40 Z9 44 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2009 VL 30 IS 5 BP 785 EP 793 DI 10.1016/j.neuro.2009.07.001 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 513AC UT WOS:000271292900008 PM 19596372 ER PT J AU Reitzel, LR Costello, TJ Mazas, CA Vidrine, JI Businelle, MS Kendzor, DE Li, YS Cofta-Woerpel, L Wetter, DW AF Reitzel, Lorraine R. Costello, Tracy J. Mazas, Carlos A. Vidrine, Jennifer I. Businelle, Michael S. Kendzor, Darla E. Li, Yisheng Cofta-Woerpel, Ludmila Wetter, David W. TI Response to Dr. DiFranza's letter SO NICOTINE & TOBACCO RESEARCH LA English DT Letter ID TOBACCO DEPENDENCE; SMOKING; WITHDRAWAL; SMOKERS; CHIPPERS C1 [Reitzel, Lorraine R.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440, Houston, TX 77230 USA. [Li, Yisheng] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77230 USA. [Cofta-Woerpel, Ludmila] Univ Texas MD Anderson Canc Ctr, NCI, Canc Informat Serv, Houston, TX 77230 USA. [Cofta-Woerpel, Ludmila] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77230 USA. RP Reitzel, LR (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440, POB 301402, Houston, TX 77230 USA. EM Lrreitze@mdanderson.org RI Reitzel, Lorraine/A-4843-2014; OI Kendzor, Darla/0000-0002-7947-7981; Wetter, David/0000-0002-6366-0108; Kendzor, Darla/0000-0002-7273-1916; Businelle, Michael/0000-0002-9038-2238; Reitzel, Lorraine/0000-0002-7165-5720; Costello, Tracy/0000-0001-6138-2450; LI, Yisheng/0000-0001-9847-8544 NR 6 TC 0 Z9 0 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD SEP PY 2009 VL 11 IS 9 BP 1124 EP 1125 DI 10.1093/ntr/ntp131 PG 2 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 483ZQ UT WOS:000269012700014 ER PT J AU Saneyoshi, H Mazzini, S Avino, A Portella, G Gonzalez, C Orozco, M Marquez, VE Eritja, R AF Saneyoshi, Hisao Mazzini, Stefania Avino, Anna Portella, Guillem Gonzalez, Carlos Orozco, Modesto Marquez, Victor E. Eritja, Ramon TI Conformationally rigid nucleoside probes help understand the role of sugar pucker and nucleobase orientation in the thrombin-binding aptamer SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LOCKED-NUCLEIC-ACID; DNA APTAMER; CARBOCYCLIC NUCLEOSIDES; MOLECULAR SIMULATION; QUADRUPLEX DNA; NEPLANOCIN-C; FORCE-FIELD; AB-INITIO; ANALOGS; D(GGTTGGTGTGGTTGG) AB Modified thrombin-binding aptamers carrying 2'-deoxyguanine (dG) residues with locked North-or South-bicyclo[3.1.0] hexane pseudosugars were synthesized. Individual 2'-deoxyguanosines at positions dG5, dG10, dG14 and dG15 of the aptamer were replaced by these analogues where the North/anti and South/syn conformational states were confined. It was found that the global structure of the DNA aptamer was, for the most part, very accommodating. The substitution at positions 5, 10 and 14 with a locked South/syn-dG nucleoside produced aptamers with the same stability and global structure as the innate, unmodified one. Replacing position 15 with the same South/syn-dG nucleoside induced a strong destabilization of the aptamer, while the antipodal North/anti-dG nucleoside was less destabilizing. Remarkably, the insertion of a North/anti-dG nucleoside at position 14, where both pseudosugar conformation and glycosyl torsion angle are opposite with respect to the native structure, led to the complete disruption of the G-tetraplex structure as detected by NMR and confirmed by extensive molecular dynamics simulations. We conclude that conformationally locked bicyclo[3.1.0] hexane nucleosides appear to be excellent tools for studying the role of key conformational parameters that are critical for the formation of a stable, antiparallel G-tetrad DNA structures. C1 [Avino, Anna; Eritja, Ramon] CIBER BBN Networking Ctr Bioengn Biomat & Nanomed, CSIC, IQAC, Inst Biomed Res, E-08028 Barcelona, Spain. [Mazzini, Stefania] Univ Milan, DISMA, I-20133 Milan, Italy. [Portella, Guillem; Orozco, Modesto] Inst Biomed Res, Joint IRB BSC Program Computat Biol, E-08028 Barcelona, Spain. [Portella, Guillem; Orozco, Modesto] Barcelona Supercomp Ctr, Barcelona 08034, Spain. [Portella, Guillem; Orozco, Modesto] Univ Barcelona, Dept Biochem, E-08028 Barcelona, Spain. [Gonzalez, Carlos] CSIC, Inst Quim Fis Rocasolano, E-28006 Madrid, Spain. [Saneyoshi, Hisao; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Eritja, R (reprint author), CIBER BBN Networking Ctr Bioengn Biomat & Nanomed, CSIC, IQAC, Inst Biomed Res, Baldiri Reixac 15, E-08028 Barcelona, Spain. EM marquezv@mail.nih.giv; recgma@cid.csic.es RI eritja, ramon/B-5613-2008; Portella, Guillem/G-2275-2014; Gonzalez, Carlos/A-4734-2013; Avino, Anna/N-5223-2015; OI eritja, ramon/0000-0001-5383-9334; Portella, Guillem/0000-0002-9380-6753; Gonzalez, Carlos/0000-0001-8796-1282; Avino, Anna/0000-0003-3047-738X; Orozco Lopez, Modesto/0000-0002-8608-3278 FU Spanish Ministry of Education [BFU2007-63287, NAN2004-09415-C05-5, BIO2006-01602, CTQ200768014-C02-02]; Generalitat de Catalunya [2005/SGR/00693, 2006PIV00028]; Instituto de Salud Carlos III [CB06/01/ 0019]; National Institute of Bioinformatics; Marcelino Botin foundation; COST project [G4-net, MP0802]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; FUNMOL [FP7-NMP-213382-2] FX Spanish Ministry of Education [BFU2007-63287, NAN2004-09415-C05-5, BIO2006-01602, CTQ200768014- C02-02, Consolider Escience Project]; the Generalitat de Catalunya [2005/SGR/00693, 2006PIV00028]; the Instituto de Salud Carlos III [CIBER-BBN, CB06/01/ 0019]; the National Institute of Bioinformatics, the Marcelino Botin foundation, the COST project (G4-net, MP0802), and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Funding for open access charge: FUNMOL, FP7-NMP-213382-2. NR 65 TC 22 Z9 23 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2009 VL 37 IS 17 BP 5589 EP 5601 DI 10.1093/nar/gkp598 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516UP UT WOS:000271569100001 PM 19620215 ER PT J AU Chepelev, I Wei, G Tang, QS Zhao, KJ AF Chepelev, Iouri Wei, Gang Tang, Qingsong Zhao, Keji TI Detection of single nucleotide variations in expressed exons of the human genome using RNA-Seq SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTOME AB Whole-genome resequencing is still a costly method to detect genetic mutations that lead to altered forms of proteins and may be associated with disease development. Since the majority of disease-related single nucleotide variations (SNVs) are found in protein-coding regions, we propose to identify SNVs in expressed exons of the human genome using the recently developed RNA-Seq technique. We identify 12 176 and 10 621 SNVs, respectively, in Jurkat T cells and CD4(+) T cells from a healthy donor. Interestingly, our data show that one copy of the TAL-1 proto-oncogene has a point mutation in 3' UTR and only the mutant allele is expressed in Jurkat cells. We provide a comprehensive dataset for further understanding the cancer biology of Jurkat cells. Our results indicate that this is a cost-effective and efficient strategy to systematically identify SNVs in the expressed regions of the human genome. C1 [Chepelev, Iouri; Wei, Gang; Tang, Qingsong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov RI Wei, Gang/A-3291-2011 FU NIH; National Heart, Lung and Blood Institute FX The Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. Funding for open access charge: The Intramural Research Program of the National Institutes of Health. NR 9 TC 78 Z9 81 U1 4 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP PY 2009 VL 37 IS 16 AR e106 DI 10.1093/nar/gkp507 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 516UO UT WOS:000271569000031 PM 19528076 ER PT J AU Byrd-Williams, CE Strother, ML Kelly, LA Huang, TTK AF Byrd-Williams, Courtney E. Strother, Myra L. Kelly, Louise A. Huang, Terry T. K. TI Dietary fiber and associations with adiposity and fasting insulin among college. students with plausible dietary reports SO NUTRITION LA English DT Article DE Diet; Glucose; Body composition; Adults; Health; Food habits ID PHYSICAL-ACTIVITY QUESTIONNAIRE; FOOD FREQUENCY QUESTIONNAIRES; DOUBLY LABELED WATER; BODY-MASS INDEX; ENERGY-INTAKE; GENDER-DIFFERENCES; US ADULTS; ATHEROSCLEROSIS RISK; DIABETES-MELLITUS; UNITED-STATES AB Objective: We examined dietary fiber intake, food sources of dietary fiber, and relation of dietary fiber to body composition and metabolic parameters in college students with plausible dietary reports. Methods: Students (18-24 y of age) provided data on anthropometry, fasting blood chemistries, and body composition (bioelectric impedance). Diet and physical activity were assessed with the Diet History Questionnaire and the International Physical Activity Questionnaire. Plausible dietary reporters were identified (+/- 1 SD cutoffs for reported energy intake as a percentage of predicted energy requirement). Multiple regression analyses were conducted with the total (n = 298) and plausible (n = 123) samples, adjusting for age, race, sex, smoking status, physical activity, energy intake, and fat-free mass (where applicable). Results: Food sources of dietary fiber were similar in men and women. In the plausible sample compared with the total sample, dietary fiber was more strongly associated with fat mass (beta = -0.24, P < 0.001), percentage of body fat (beta = -0.23, P < 0.001), body mass index (beta = -0.11, P < 0.01), waist circumference (beta = -0.67, P < 0.05), and fasting insulin (beta = -0.15, P < 0.001). When the effect of sex was investigated, dietary fiber was inversely related to fasting insulin and fat mass in men and women and inversely related to percentage of body fat, body mass index, and waist circumference in men only (P < 0.05). Conclusion: Inclusion of implausible dietary reports may result in spurious or weakened diet-health associations. Dietary fiber is negatively associated with fasting insulin levels in men and women and consistently associated with adiposity measurements in men. Published by Elsevier Inc. C1 [Huang, Terry T. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Byrd-Williams, Courtney E.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Strother, Myra L.] Univ Kansas, Student Hlth Serv, Lawrence, KS 66045 USA. [Kelly, Louise A.] Calif Lutheran Univ, Dept Exercise Sci, Thousand Oaks, CA USA. RP Huang, TTK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. EM huangter@mail.nih.gov FU NCI NIH HHS [T32 CA009492, T32 CA 09492, T32 CA009492-23] NR 55 TC 6 Z9 7 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD SEP PY 2009 VL 25 IS 9 BP 896 EP 904 DI 10.1016/j.nut.2009.02.003 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 485RH UT WOS:000269140900004 PM 19403267 ER PT J AU Komlodi-Pasztor, E Trostel, S Sackett, D Poruchynsky, M Fojo, T AF Komlodi-Pasztor, E. Trostel, S. Sackett, D. Poruchynsky, M. Fojo, T. TI Impaired p53 binding to importin: a novel mechanism of cytoplasmic sequestration identified in oxaliplatin-resistant cells SO ONCOGENE LA English DT Article DE nuclear localization; mutant p53; platinum resistance ID WILD-TYPE P53; NUCLEAR-LOCALIZATION SIGNALS; COLORECTAL ADENOCARCINOMA; SUBCELLULAR-LOCALIZATION; N-MYC; PROTEIN; ACCUMULATION; GENE; NEUROBLASTOMA; AMPLIFICATION AB Previous studies have described one nuclear localization signal (NLSI) in p53 and speculated on two additional sites termed NLSII and NLSIII. Drug-resistant KB cells selected with cisplatin or oxaliplatin were found to have increased p53 levels and in oxaliplatin-selected cells, a larger p53 predominantly in the cytoplasm. In oxaliplatin-selected cells a single nucleotide deletion in the sequence-encoding amino acid 382, part of NLSIII, resulted in a frame shift and a 420 amino acid protein (p53(420)). We investigated explanations for the cytoplasmic sequestration of p53(420) while assessing the role, if any, of NLSII and NLSIII in p53 nuclear import. We found that neither NLSII nor NLSIII are essential for p53 nuclear localization. Furthermore, we confirmed p53(420) is able to tetramerize, transactivate a p21 promoter, bind dynein and that the reduced nuclear accumulation is not a consequence of increased p53 nuclear export. However, the association of p53(420) with importin-beta, essential for nuclear import, was significantly impaired. We conclude that despite sequence similarity to consensus NLSs neither NLSII nor NLSIII have roles in p53 nuclear transport. We also identified impaired association with importin as a novel mechanism of p53 cytoplasmic sequestration that impairs nuclear transport rendering cells functionally deficient in p53. Oncogene (2009) 28, 3111-3120; doi: 10.1038/onc.2009.166; published online 6 July 2009 C1 [Komlodi-Pasztor, E.; Trostel, S.; Poruchynsky, M.; Fojo, T.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Sackett, D.] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Komlodi-Pasztor, E (reprint author), NCI, Med Oncol Branch, NIH, 9000 Rockville Pike,B10 R13N260, Bethesda, MD 20892 USA. EM komlodie@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 37 TC 10 Z9 10 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP PY 2009 VL 28 IS 35 BP 3111 EP 3120 DI 10.1038/onc.2009.166 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 490QC UT WOS:000269515100003 PM 19581934 ER PT J AU Izzotti, A D'Agostini, F Larghero, P Cartiglia, C Travaini, G Balansky, R Steele, VE De Flora, S AF Izzotti, Alberto D'Agostini, Francesco Larghero, Patrizia Cartiglia, Cristina Travaini, Giorgia Balansky, Roumen Steele, Vernon E. De Flora, Silvio TI Upregulation of stem cell antigen-1 in the lung of neonatal mice exposed to environmental cigarette smoke SO ONCOLOGY REPORTS LA English DT Article DE stem cell antigen-1; environmental cigarette smoke; neonatal mice; lung carcinogenesis ID MOUSE LUNG; N-ACETYLCYSTEINE; IN-VITRO; LIVER; SUSCEPTIBILITY; LIGHT; LIFE; ENDOTHELIUM; EXPRESSION; BIRTH AB Mice are particularly susceptible to carcinogens when exposure starts early in life. We evaluated the expression of stein cell antigen-1 (Sca-1) gene in the lung of variously aged CD-I mice, either untreated or exposed to environmental cigarette smoke (ECS) and/or to a light source. Sca-1 expression progressively decreased with age. The expression Sca-1 gene and the amount of Sca-1 protein, which was exclusively localized in endothelial cells of the pulmonary vasculature, were significantly upregulated in mice exposed either to ECS or ECS plus light throughout the weaning period, starting at birth. These findings may contribute to explain the high vulnerability of mouse lung early in life. C1 [Izzotti, Alberto; D'Agostini, Francesco; Larghero, Patrizia; Cartiglia, Cristina; Travaini, Giorgia; Balansky, Roumen; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Balansky, Roumen] Natl Oncol Ctr, Sofia 1756, Bulgaria. [Steele, Vernon E.] NCI, Rockville, MD USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it OI izzotti, alberto/0000-0002-8588-0347 FU U.S. National Cancer Institute [N01-CN53301]; Bulgarian Ministry of Education and Science FX This study was supported by the U.S. National Cancer Institute (contract N01-CN53301) and Bulgarian Ministry of Education and Science. NR 31 TC 6 Z9 6 U1 0 U2 1 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD SEP PY 2009 VL 22 IS 3 BP 469 EP 474 DI 10.3892/or_00000458 PG 6 WC Oncology SC Oncology GA 480KY UT WOS:000268734600004 PM 19639190 ER PT J AU Conway, DI Hashibe, M Boffetta, P Wunsch-Filho, V Muscat, J La Vecchia, C Winn, DM AF Conway, David I. Hashibe, Mia Boffetta, Paolo Wunsch-Filho, Victor Muscat, Joshua La Vecchia, Carlo Winn, Deborah M. CA INHANCE Consortium TI Enhancing epidemiologic research on head and neck cancer: INHANCE - The international head and neck cancer epidemiology consortium SO ORAL ONCOLOGY LA English DT Editorial Material ID ORAL-CANCER; ALCOHOL-DRINKING; POOLED ANALYSIS; METAANALYSIS; RISK; CONSUMPTION; SMOKING C1 [Conway, David I.] Univ Glasgow, Fac Med, Sch Dent, Glasgow, Lanark, Scotland. [Conway, David I.] NHS NSS ISD, Edinburgh, Midlothian, Scotland. [Hashibe, Mia; Boffetta, Paolo; INHANCE Consortium] Int Agcy Res Canc Genet & Epidemiol Cluster, Lifestyle Environm & Canc Grp, F-69008 Lyon, France. [Wunsch-Filho, Victor] Univ Sao Paulo, Sao Paulo, Brazil. [Muscat, Joshua] Penn State Coll Med, Hershey, PA USA. [La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Milan, Italy. [Winn, Deborah M.] NCI, Bethesda, MD 20892 USA. RP Conway, DI (reprint author), Univ Glasgow, Fac Med, Sch Dent, Glasgow, Lanark, Scotland. EM boffetta@iarc.fr RI Wunsch Filho, Victor/C-4475-2012; OI La Vecchia, Carlo/0000-0003-1441-897X NR 18 TC 51 Z9 54 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD SEP PY 2009 VL 45 IS 9 BP 743 EP 746 DI 10.1016/j.oraloncology.2009.02.007 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 488CM UT WOS:000269326700011 PM 19442571 ER PT J AU Whitcomb, BW Schisterman, EF Perkins, NJ Platt, RW AF Whitcomb, Brian W. Schisterman, Enrique F. Perkins, Neil J. Platt, Robert W. TI Quantification of collider-stratification bias and the birthweight paradox SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE collider-stratification bias; birthweight; directed acyclic graphs; neonatal nortality ID PERINATAL-MORTALITY; CAUSAL DIAGRAMS; INFANT-MORTALITY; ADJUSTMENT; TIME; CURVES; MODELS AB The 'birthweight paradox' describes the phenomenon whereby birthweight-specific mortality curves cross when stratified on other exposures, most notably cigarette smoking. The paradox has been noted widely in the literature and numerous explanations and corrections have been suggested. Recently, causal diagrams have been used to illustrate the possibility for collider-stratification bias in models adjusting for birthweight. When two variables share a common effect, stratification on the variable representing that effect induces a statistical relation between otherwise independent factors. This bias has been proposed to explain the birthweight paradox. Causal diagrams may illustrate sources of bias, but are limited to describing qualitative effects. In this paper, we provide causal diagrams that illustrate the birthweight paradox and use a simulation study to quantify the collider-stratification bias under a range of circumstances. Considered circumstances include exposures with and without direct effects on neonatal mortality, as well as with and without indirect effects acting through birthweight on neonatal mortality. The results of these simulations illustrate that when the birthweight-mortality relation is subject to substantial uncontrolled confounding, the bias on estimates of effect adjusted for birthweight may be sufficient to yield opposite causal conclusions, i.e. a factor that poses increased risk appears protective. Effects on stratum-specific birthweight-mortality curves were considered to illustrate the connection between collider-stratification bias and the crossing of the curves. The simulations demonstrate the conditions necessary to give rise to empirical evidence of the paradox. C1 [Whitcomb, Brian W.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. [Whitcomb, Brian W.; Schisterman, Enrique F.; Perkins, Neil J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, NIH, Bethesda, MD USA. [Platt, Robert W.] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Whitcomb, BW (reprint author), Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, 408 Arnold House,715 N Pleasant St, Amherst, MA 01003 USA. EM bwhitcomb@schoolph.umass.edu RI Platt, Robert/G-5847-2012; OI Perkins, Neil/0000-0002-6802-4733; Platt, Robert/0000-0002-5981-8443; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Chercheur-boursier award; Fonds de la Recherche en Sante du Quebec FX Brian Whitcomb, Neil Perkins and Enrique Schisterman are supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Robert Platt is supported by a Chercheur-boursier award, and by core support to the Montreal Children's Hospital Research Institute, from the Fonds de la Recherche en Sante du Quebec. The authors would like to thank Drs Miguel Hernan and Sonia Hernandez-Diaz for their helpful suggestions on a previous version of this paper and are grateful to the editor and referees for their insightful comments. NR 32 TC 37 Z9 37 U1 3 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD SEP PY 2009 VL 23 IS 5 BP 394 EP 402 DI 10.1111/j.1365-3016.2009.01053.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 479LA UT WOS:000268659600001 PM 19689488 ER PT J AU Schisterman, EF Whitcomb, BW Mumford, SL Platt, RW AF Schisterman, Enrique F. Whitcomb, Brian W. Mumford, Sunni L. Platt, Robert W. TI Z-scores and the birthweight paradox SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE birthweight; birthweight paradox; simulation; directed acyclic graphs; z-scores ID STANDARDIZED REGRESSION-COEFFICIENTS; PERINATAL-MORTALITY; INFANT-MORTALITY; GESTATIONAL-AGE; CAUSAL DIAGRAMS; UNITED-STATES; EXCHANGEABILITY; IDENTIFIABILITY; ADJUSTMENT; BIAS AB Investigators have long puzzled over the observation that low-birthweight babies of smokers tend to fare better than low-birthweight babies of non-smokers. Similar observations have been made with regard to factors other than smoking status, including socio-economic status, race and parity. Use of standardised birthweights, or birthweight z-scores, has been proposed as an approach to resolve the crossing of the curves that is the hallmark of the so-called birthweight paradox. In this paper, we utilise directed acyclic graphs, analytical proofs and an extensive simulation study to consider the use of z-scores of birthweight and their effect on statistical analysis. We illustrate the causal questions implied by inclusion of birthweight in statistical models, and illustrate the utility of models that include birthweight or z-scores to address those questions. Both analytically and through a simulation study we show that neither birthweight nor z-score adjustment may be used for effect decomposition. The z-score approach yields an unbiased estimate of the total effect, even when collider-stratification would adversely impact estimates from birthweight-adjusted models; however, the total effect could have been estimated more directly with an unadjusted model. The use of z-scores does not add additional information beyond the use of unadjusted models. Thus, the ability of z-scores to successfully resolve the paradoxical crossing of mortality curves is due to an alteration in the causal parameter being estimated (total effect), rather than adjustment for confounding or effect decomposition or other factors. C1 [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA. [Mumford, Sunni L.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Platt, Robert W.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov RI Platt, Robert/G-5847-2012; OI Platt, Robert/0000-0002-5981-8443; Schisterman, Enrique/0000-0003-3757-641X FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Fonds de la Recherche en Sante du Quebec (FRSQ), FX The authors thank Dr Miguel Hernan and Dr Sonia Hernandez-Diaz for their valuable comments. We are also grateful to the editor and referees for their helpful comments which improved this paper. This research was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Robert W. Platt is a Chercheur-boursier of the Fonds de la Recherche en Sante du Quebec (FRSQ), and is a member of the Research Institute of the McGill University Health Centre, which is supported in part by the FRSQ. NR 35 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD SEP PY 2009 VL 23 IS 5 BP 403 EP 413 DI 10.1111/j.1365-3016.2009.01054.x PG 11 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 479LA UT WOS:000268659600002 PM 19689489 ER PT J AU Schisterman, EF Whitcomb, BW AF Schisterman, Enrique F. Whitcomb, Brian W. TI Reply to Commentaries: Biology and methodology - the quest for parsimonious models of a complex reality SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material ID BIRTH-WEIGHT; MORTALITY C1 [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MS USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7803, Bethesda, MD 20892 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU Intramural NIH HHS [Z01 HD008761-05] NR 14 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD SEP PY 2009 VL 23 IS 5 BP 421 EP 423 DI 10.1111/j.1365-3016.2009.01052.x PG 3 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 479LA UT WOS:000268659600005 PM 21423833 ER PT J AU O'Meara, WP Lang, T AF O'Meara, W. P. Lang, T. TI Malaria vaccine trial endpoints - bridging the gaps between trial design, public health and the next generation of vaccines SO PARASITE IMMUNOLOGY LA English DT Review DE malaria; vaccine; clinical trial; endpoint; efficacy ID PLASMODIUM-FALCIPARUM MALARIA; CLINICAL CASE DEFINITIONS; HIGHLY ENDEMIC AREA; TRANSMISSION INTENSITY; PYROGENIC THRESHOLD; SOUTHERN TANZANIA; AFRICAN CHILDREN; RANDOMIZED-TRIAL; EFFICACY; INFECTION AB P>A recent working group convened by the World Health Organization recommended that time to first or only episode of clinical malaria should be used to evaluate vaccine efficacy in phase III trials. However, calculating vaccine efficacy based on this endpoint misses important aspects of malaria disease and transmission. Here, we discuss the gaps that this approach leaves in predicting the potential public health impact of a vaccine and the challenges faced by vaccine trial designers. We examine the implications of current vaccine trial design on effectiveness studies and the next generation of malaria vaccines. C1 [O'Meara, W. P.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Lang, T.] Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Clin Vaccinol, Oxford, England. RP O'Meara, WP (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM wendypomeara@gmail.com NR 49 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD SEP PY 2009 VL 31 IS 9 BP 574 EP 581 DI 10.1111/j.1365-3024.2009.01144.x PG 8 WC Immunology; Parasitology SC Immunology; Parasitology GA 480TS UT WOS:000268760300009 PM 19691560 ER PT J AU Goode, TD Haywood, SH Wells, N Rhee, K AF Goode, Tawara D. Haywood, Sonja Harris Wells, Nora Rhee, Kyu TI Family-centered, Culturally, and Linguistically Competent Care: Essential Components of the Medical Home SO PEDIATRIC ANNALS LA English DT Article ID CHILDREN; LANGUAGE; ASTHMA; NEEDS C1 [Goode, Tawara D.] Georgetown Univ, Med Ctr, Ctr Child & Human Dev, Natl Ctr Cultural Competence, Washington, DC 20007 USA. [Haywood, Sonja Harris] Case Western Reserve Univ, Dept Family Med, Div Res, Cleveland, OH 44106 USA. [Wells, Nora] Natl Ctr Family Profess Partnerships, Lexington, MA USA. [Rhee, Kyu] NIH, Off Innovat & Progrom Coordinat, Natl Ctr Minor Hlth & Hlth Dispar, Bethesda, MD 20892 USA. RP Goode, TD (reprint author), Georgetown Univ, Med Ctr, Ctr Child & Human Dev, Natl Ctr Cultural Competence, 3300 Whitehaven St,NW,Suite 3300, Washington, DC 20007 USA. EM tdg2@georgetown.edu FU NCRR NIH HHS [KL2 RR024990] NR 32 TC 6 Z9 6 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD SEP PY 2009 VL 38 IS 9 BP 505 EP 512 DI 10.3928/00904481-20090820-04 PG 8 WC Pediatrics SC Pediatrics GA 492FJ UT WOS:000269640000008 PM 19772237 ER PT J AU Mbulaiteye, SM Biggar, RJ Bhatia, K Linet, MS Devesa, SS AF Mbulaiteye, Sam M. Biggar, Robert J. Bhatia, Kishor Linet, Martha S. Devesa, Susan S. TI Sporadic Childhood Burkitt Lymphoma Incidence in the United States During 1992-2005 SO PEDIATRIC BLOOD & CANCER LA English DT Article DE epidemiology; HIV/AIDS; non-Hodgkin lymphoma; pediatric cancer ID EPSTEIN-BARR-VIRUS; SOCIOECONOMIC-STATUS; HODGKINS-LYMPHOMA; CANCER; CHILDREN; EPIDEMIOLOGY; LEUKEMIA; MALARIA; DISEASE; ANTIBODIES AB Background. The risk factors and co-factors for sporadic childhood BL are unknown. We investigated demographic and age-specific characteristics of childhood BL (0-14 years) in the U.S. Procedure. BL age-standardized incidence rates (2000 U.S. standard population), were calculated using data obtained from 12 registries in the NCI's Surveillance, Epidemiology, and End Results program for cases diagnosed from 1992 to 2005. Incidence rate ratios and 95% confidence intervals (95% CI) were calculated by gender, age-group, race, ethnicity, calendar-year period, and registry. Results. Of 296 cases identified, 56% were diagnosed in lymph nodes, 21% in abdominal organs, not including retroperitoneal lymph nodes, 14% were Burkitt cell leukemia, and 9%) on face/head structures. The male-to-female case ratio was highest for facial/head tumors (25:1) and lowest for Burkitt cell leukemia (1.6:1). BL incidence rate was 2.5 (95% CI 2.3-2.8) cases per million person-years and was higher among boys than girls (3.9 vs. 1.1, P<0.001) and higher among Whites and Asians/Pacific Islanders than among Blacks (2.8 and 2.9 vs. 1.2, respectively, P<0.001). By ethnicity, BL incidence was higher among non-Hispanic Whites than Hispanic Whites (3.2 vs. 2.0, P=0.002). Age-specific incidence rate for BL peaked by age 3-5 years (3.4 cases per million), then stabilized or declined with increasing age, but it did not vary with calendar-year or registry area. Conclusions. Our results indicate that early childhood exposures, male-sex, and White race may be risk factors for sporadic childhood BL in the United States. Pediatr Blood Cancer 2009;53:366-370. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Mbulaiteye, Sam M.; Biggar, Robert J.; Bhatia, Kishor] NCI, Infect & Immunoepidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Biggar, Robert J.] LV Prasad Eye Inst, Hyderabad, Andhra Pradesh, India. [Linet, Martha S.] NCI, Radiat Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Devesa, Susan S.] NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S,Rm 7080, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU Intramural Research Program of the National Cancer Institute; National Institutes of Health; Department of Health and Human Services [N02-CP-31003, N01-CO-12400] FX Grant sponsor: Intramural Research Program of the National Cancer Institute; Grant sponsor: National Institutes of Health; Grant sponsor: Department of Health and Human Services, Grant numbers: N02-CP-31003, N01-CO-12400. NR 32 TC 29 Z9 30 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 366 EP 370 DI 10.1002/pbc.22047 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200015 PM 19434731 ER PT J AU Fitzhugh, CD Wise, B Baird, K Tsokos, M Helman, L Mackall, C Savage, SA Warren, KE AF Fitzhugh, Courtney D. Wise, Barbara Baird, Kristin Tsokos, Maria Helman, Lee Mackall, Crystal Savage, Sharon A. Warren, Katherine E. TI Secondary Supratentorial Primitive Neuroectodermal Tumor Following Treatment of Childhood Osteosarcoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE genetic predisposition syndromes; osteosarcoma; primitive neuroectodermal tumor ID CANCER SURVIVOR; MIC2 EXPRESSION; EWING SARCOMA; NEOPLASMS; EXPERIENCE AB A 16-year-old Caucasian male was diagnosed with a primitive neuroectodermal tumor (PNET) 5 years following the diagnosis of nonmetastatic osteosarcoma of the left proximal humerus. The patient was initially treated with standard chemotherapy and limb salvage resection for osteosarcoma. Nine months after the completion of therapy, lie developed lung metastases for which he underwent surgical resection and received additional chemotherapy. Almost 5 years after the osteosarcoma diagnosis, the patient was diagnosed with a supratentorial PNET, which represents the first known case reported in a patient with osteosarcoma. Pediatr Blood Cancer 2009;53: 496-498. Published 2009 Wiley-Liss, Inc.(dagger) C1 [Fitzhugh, Courtney D.; Wise, Barbara; Baird, Kristin; Helman, Lee; Mackall, Crystal; Warren, Katherine E.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Tsokos, Maria] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room IW 3940, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU NIH, National Cancer Institute, Center for Cancer Research and Division of Cancer Epidemiology and Genetics FX We would like to thank Dr. Christine Mueller and Ms. June Peters, National Cancer Institute and Ms. Ann Carr, Westat, Inc., for their assistance in genetic counseling. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and Division of Cancer Epidemiology and Genetics. The views expressed do not necessarily represent the views of the National Institutes of Health or the United States Government. NR 20 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 496 EP 498 DI 10.1002/pbc.22074 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200043 PM 19434734 ER PT J AU Keshelava, N Houghton, PJ Morton, CL Lock, RB Carol, H Keir, ST Maris, JM Reynolds, CP Gorlick, R Kolb, EA Wu, J Smith, MA AF Keshelava, Nino Houghton, Peter J. Morton, Christopher L. Lock, Richard B. Carol, Hernan Keir, Stephen T. Maris, John M. Reynolds, C. Patrick Gorlick, Richard Kolb, E. Anders Wu, Jianrong Smith, Malcolm A. TI Initial Testing (Stage 1) of Vorinostat (SAHA) by the Pediatric Preclinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE developmental therapeutics; preclinical testing; vorinostat ID T-CELL LYMPHOMA; HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; INDUCED APOPTOSIS; IN-VITRO; PHASE-I; NEUROBLASTOMA; EXPRESSION; TRIAL; MEDULLOBLASTOMA AB Vorinostat, a histone deacetylase inhibitor, was evaluated against the in vitro and in vivo childhood solid tumor and leukemia models in the Pediatric Preclinical Testing Program (PPTP). In vitro testing was performed by the DIMSCAN cytotoxicity assay. In vivo, vorinostat was administered intraperitoneally to mice bearing xenografts. Vorinostat demonstrated 2-log cell growth inhibitory activity in vitro, but generally at concentrations not Sustainable in the clinic, No objective responses were observed for any of the Solid tumor or acute lymphoblastic leukemia xenografts. Preclinical Studies with appropriate drug combinations may provide direction for further clinical evaluations of vorinostat against selected pediatric cancers. Pediatr Blood Cancer 2009;53: 505-508. (C) 2009 Wiley-Liss, Inc. C1 [Keshelava, Nino] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Houghton, Peter J.; Morton, Christopher L.; Wu, Jianrong] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Lock, Richard B.; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Reynolds, C. Patrick] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Keshelava, N (reprint author), Childrens Hosp Los Angeles, 4650 W Sunset Blvd, Los Angeles, CA 90027 USA. EM nkeshelava@chla.usc.edu RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX This work was supported by NO1-CM-42216, CA21765, and CA108786 from the National Cancer Institute and used vorinostat provided by Merck. In addition to the authors, the report represents work contributed by the following: Sherry Ansher, Catherine A. Billups, Joshua Courtright, Edward Favours, Henry S. Friedman, Debbie Payne-Turner, Charles Stopford, Mayamin Tajbakhsh, Chandra Tucker, Joe Zeidner, Ellen Zhang, and Jian Zhang. Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children's Hospital. NR 20 TC 33 Z9 35 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 505 EP 508 DI 10.1002/pbc.21988 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200046 PM 19418547 ER PT J AU Morton, CL Houghton, PJ Gorlick, R Kolb, EA Lock, R Carol, H Keir, ST Reynolds, CP Kang, MH Maris, JM Billups, C Smith, MA AF Morton, Christopher L. Houghton, Peter J. Gorlick, Richard Kolb, E. Anders Lock, Richard Carol, Hernan Keir, Stephen T. Reynolds, C. Patrick Kang, Min H. Maris, John M. Billups, Catherine Smith, Malcolm A. TI Initial Testing of Aplidin by the Pediatric Pre-Clinical Testing Program SO PEDIATRIC BLOOD & CANCER LA English DT Article DE aplidin; developmental therapeutics; pre-clinical testing ID CANCER MODELS; IN-VIVO; CYTOTOXICITY; ACTIVATION; APOPTOSIS; CELLS AB Aplidin was tested in vitro at concentrations ranging from from 0.1 nM to 1.0 mu M and in vivo at a dose of 0.6 mg/kg administered intraperitoneally on an every 4 days x 3-schedule that was repeated at day 21. In vitro, Aplidin was most active against acute lymphoblastic leukemia (ALL) cell lines. In vivo, Aplidin induced significant differences in EFS distribution in 12 of 28 (43%) solid tumor models and 2 of 6 evaluable ALL models. Aplidin showed potent in vitro activity and induced significant in vivo tumor growth inhibition in some xenografts, but did not induce tumor regressions. Pediatr Blood Cancer 2009;53: 509-512. (C) 2009 Wiley-Liss, Inc. C1 [Morton, Christopher L.; Houghton, Peter J.; Billups, Catherine] St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. [Gorlick, Richard] Childrens Hosp Montefiore, Dept Pediat, Bronx, NY USA. [Kolb, E. Anders] Alfred I DuPont Hosp Children, Dept Pediat Hematol & Oncol, Wilmington, DE USA. [Lock, Richard; Carol, Hernan] Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. [Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA. [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Ctr Canc, Lubbock, TX 79430 USA. [Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. [Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Houghton, PJ (reprint author), St Jude Childrens Hosp, Dept Mol Pharmacol, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM peter.houghton@stjude.org RI Houghton, Peter/E-3265-2011; Carol, Hernan/F-5750-2013; Lock, Richard/G-4253-2013; OI Carol, Hernan/0000-0002-9443-8032; Reynolds, C. Patrick/0000-0002-2827-8536 FU National Cancer Institute [NO1-CM-42216, CA21765, CA108786] FX This work was supported by NO1-CM-42216, CA21765, and CA108786 from the National Cancer Institute and used Aplidin supplied by PharrnaMar. In addition to the authors represents work contributed by the following: Sherry Ansher, Ingrid Boehm, Joshua Courtright, Mila Dolotin, Edward Favours, Henry S. Friedman, Min Kang, Debbie Payne-Turner, Charles Stopford, Chandra Tucker, Amy E. Watkins, Jianrong Wu, Joe Zeidner, Ellen Zhang, and Jian Zhang. Children's Cancer Institute Australia for Medical Research is affiliated with the University of New South Wales and Sydney Children's Hospital. NR 13 TC 11 Z9 11 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD SEP PY 2009 VL 53 IS 3 BP 509 EP 512 DI 10.1002/pbc.21976 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 476LT UT WOS:000268443200047 PM 19418543 ER PT J AU Reis, JP von Muhlen, D Miller, ER Michos, ED Appel, LJ AF Reis, Jared P. von Muehlen, Denise Miller, Edgar R., III Michos, Erin D. Appel, Lawrence J. TI Vitamin D Status and Cardiometabolic Risk Factors in the United States Adolescent Population SO PEDIATRICS LA English DT Article DE cardiovascular; children; dietary supplements ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; PARATHYROID-HORMONE LEVELS; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; SERUM 25-HYDROXYVITAMIN-D; INCIDENT HYPERTENSION; INSULIN SENSITIVITY; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION AB OBJECTIVE: Evidence on the association of vitamin D with cardiovascular risk factors in youth is very limited. We examined whether low serum vitamin D levels (25-hydroxyvitamin D [25(OH) D]) are associated with cardiovascular risk factors in US adolescents aged 12 to 19 years. METHODS: We conducted a cross-sectional analysis of 3577 fasting, nonpregnant adolescents without diagnosed diabetes who participated in the 2001-2004 National Health and Nutrition Examination Survey. Cardiovascular risk factors were measured using standard methods and de. ned according to age-modified Adult Treatment Panel III definitions. RESULTS: Mean 25(OH) D was 24.8 ng/mL; it was lowest in black (15.5 ng/mL), intermediate in Mexican American (21.5 ng/mL), and highest in white (28.0 ng/mL) adolescents (P < .001 for each pairwise comparison). Low 25(OH) D levels were strongly associated with overweight status and abdominal obesity (P for trend < .001 for both). After adjustment for age, gender, race/ethnicity, BMI, socioeconomic status, and physical activity, 25(OH) D levels were inversely associated with systolic blood pressure (P = .02) and plasma glucose concentrations (P = .01). The adjusted odds ratio (95% confidence interval) for those in the lowest (<15 ng/mL) compared with the highest quartile (> 26 ng/mL) of 25(OH) D for hypertension was 2.36 (1.33-4.19); for fasting hyperglycemia it was 2.54 (1.01-6.40); for low high-density lipoprotein cholesterol it was 1.54 (0.99-2.39); for hypertriglyceridemia it was 1.00 (0.49-2.04); and for metabolic syndrome it was 3.88 (1.57-9.58). CONCLUSIONS: Low serum vitamin D in US adolescents is strongly associated with hypertension, hyperglycemia, and metabolic syndrome, independent of adiposity. Pediatrics 2009; 124: e371-e379 C1 [Reis, Jared P.; Miller, Edgar R., III; Appel, Lawrence J.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [von Muehlen, Denise] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Michos, Erin D.] Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA. RP Reis, JP (reprint author), NHLBI, Div Prevent & Populat Sci, 6701 Rockledge Dr,Suite 10197, Bethesda, MD 20892 USA. EM reisjp@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute [T32 HL07024] FX Dr Reis was supported by a grant from the National Heart, Lung, and Blood Institute (grant T32 HL07024). NR 53 TC 146 Z9 155 U1 0 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2009 VL 124 IS 3 BP E371 EP E379 DI 10.1542/peds.2009-0213 PG 9 WC Pediatrics SC Pediatrics GA 488XH UT WOS:000269383100024 PM 19661053 ER PT J AU Akolkar, B Karp, R Kimmel, PL McKeon, C Rasooly, RS AF Akolkar, Beena Karp, Robert Kimmel, Paul L. McKeon, Catherine Rasooly, Rebekah S. TI Fostering translation of genetics research: an NIDDK perspective SO PERSONALIZED MEDICINE LA English DT Article DE complex disease; gene therapy; genetics; Mendelian genetics; NIH; translation ID GENOME-WIDE ASSOCIATION; STAGE RENAL-DISEASE; CYSTIC-FIBROSIS; AFRICAN-AMERICANS; THERAPY; LOCI; RISK; INTERVENTIONS; COMPLICATIONS; GENES AB The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) part of the NIH, supports a large and varied portfolio of genetic research grants and contracts. As a funding agency, the NIDDK aims to support research that can be translated into discoveries that help to reduce the burden of genetic diseases. Except for the major advances in diagnostics for Mendelian diseases and a few disease-specific therapies, there has only been modest clinical benefit from the investment in human genetics research. For genetically complex, multifactorial diseases, including many of the common diseases in the USA, the risk genes are harder to find than for Mendelian diseases, and translation seems even further off. How can NIDDK make its investment in human genetics research pay off? This report describes the challenges in human genetics research and NIDDK's fivefold funding strategy to support science that will eventually lead to meaningful translation. C1 [Kimmel, Paul L.] NIDDK, NIH, Bethesda, MD 20817 USA. EM rasoolyr@mail.nih.gov OI Rasooly, Rebekah/0000-0002-6357-5528 NR 45 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD SEP PY 2009 VL 6 IS 5 BP 579 EP 588 DI 10.2217/PME.09.41 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507MS UT WOS:000270858900015 ER PT J AU Miller, FG Colloca, L Kaptchuk, TJ AF Miller, Franklin G. Colloca, Luana Kaptchuk, Ted J. TI THE PLACEBO EFFECT illness and interpersonal healing SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LOW-BACK-PAIN; DOCTOR-PATIENT-RELATIONSHIP; IRRITABLE-BOWEL-SYNDROME; CLINICAL-TRIALS; PARKINSONS-DISEASE; ULCERATIVE-COLITIS; POWERFUL PLACEBO; ALTERNATIVE MEDICINE; INDUCED ANALGESIA AB The placebo effect has been a source of fascination, irritation, and confusion within biomedicine over the past 60 years. Although scientific investigation has accelerated in the past decade, with particular attention to neurobiological mechanisms, there has been a dearth of attention to developing a general theory of the placebo effect. In this article, we attempt to address this gap. To set the stage, we review evidence relating to the reality and clinical significance of the placebo effect. Next we investigate the scope and limits of the placebo effect by examining the hypothesis that the placebo effect operates predominantly by modifying the experience and perceptions of illness symptoms, such as pain, anxiety, and fatigue, rather than by modifying the pathophysiology of disease. Based on this background, we characterize the placebo effect as a form of interpersonal healing, as distinct from spontaneous natural healing and from technological healing dependent on physiologically active pharmaceuticals or procedures. Finally, we argue that research on the placebo effect has the potential to revitalize the art of medicine. C1 [Miller, Franklin G.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Colloca, Luana] Univ Turin, Sch Med, Dept Neurosci, I-10124 Turin, Italy. [Kaptchuk, Ted J.] Harvard Univ, Sch Med, Osher Res Ctr, Cambridge, MA 02138 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov FU NIH (FGM) [K24 AT004095]; Regione Piemonte (LC); National Center for Complementary and Alternative Medicine FX The authors thank Howard Brody, Reidar Lie, and four anonymous reviewers for helpful comments on previous versions of this paper. Research for this paper was supported by the Intramural Research Program of the Clinical Center, NIH (FGM), a grant by Regione Piemonte (LC), and NIH grant No. K24 AT004095 from the National Center for Complementary and Alternative Medicine (TJK). NR 100 TC 75 Z9 79 U1 3 U2 24 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 0031-5982 EI 1529-8795 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD FAL PY 2009 VL 52 IS 4 BP 518 EP 539 PG 22 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 518IR UT WOS:000271685200003 PM 19855122 ER PT J AU Laje, G Allen, AS Akula, N Manji, H Rush, AJ McMahon, FJ AF Laje, Gonzalo Allen, Andrew S. Akula, Nirmala Manji, Husseini Rush, A. John McMahon, Francis J. TI Genome-wide association study of suicidal ideation emerging during citalopram treatment of depressed outpatients SO PHARMACOGENETICS AND GENOMICS LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the American-Society-of-Human-Genetics CY OCT 23-27, 2007 CL San Diego, CA SP Amer Soc Human Genet DE antidepressant; citalopram; genome-wide; major depression; pharmacogenetics; selective serotonin reuptake inhibitor; STAR*D; treatment-emergent suicidal ideation ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; MAJOR DEPRESSION; RATING-SCALE; SYMPTOMATOLOGY; ADOLESCENTS; RATIONALE AB Objectives Suicidal ideation is an uncommon but worrisome symptom than can emerge during antidepressant treatment. We have described earlier the association between treatment-emergent suicidal ideation (TESI) and markers in genes encoding glutamate receptor subunits GRIK2 and GRIA3. The present genome-wide association study was conducted to identify additional genetic markers associated with TESI that may help identify individuals at high risk who may benefit from closer monitoring, alternative treatments, and/or specialty care. Methods A clinically representative cohort of outpatients with nonpsychotic major depressive disorder enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were treated with citalopram under a standard protocol for up to 14 weeks. DNA samples from 90 White participants who developed TESI and a sex-matched and race-matched equal number of treated participants who denied any suicidal ideas were genotyped with 109365 single nucleotide polymorphisms on the Illumina's Human-1 BeadChip. Results One marker was found to be associated with TESI in this sample at the experiment-wide adjusted P less than 0.05 level (marker rs1 1628713, allelic P=6.2 x 10(-7), odds ratio=4.7, permutation P=0.01). A second marker was associated at the experiment-wide adjusted P=0.06 level (rs10903034, allelic P=3.02 x 10(-6), odds ratio=2.7, permutation P=0.06). These markers reside within the genes PAPLN and IL28RA, respectively. PAPLN encodes papilin, a protoglycan-like sulfated glycoprotein. IL28RA encodes an interleukin receptor. Conclusion Together with our earlier report, these findings may shed light on the biological basis of TESI and may help identify patients at increased risk of this potentially serious adverse event Pharmacogenetics and Genomics 19:666-674 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Laje, Gonzalo; Akula, Nirmala; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Manji, Husseini] NIMH, Lab Mol Pathophysiol Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Allen, Andrew S.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Dallas, TX 75390 USA. [Rush, A. John] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. RP Laje, G (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Dept Hlth & Human Serv, 35 Convent Dr,Rm 1A207, Bethesda, MD 20892 USA. EM gonzalo.laje@nih.gov RI Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Rush, Augustus/0000-0003-2004-2382; McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS [Z99 MH999999]; NHLBI NIH HHS [K25 HL077663]; NIMH NIH HHS [N01MH90003]; PHS HHS [1K25-077663] NR 28 TC 51 Z9 56 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD SEP PY 2009 VL 19 IS 9 BP 666 EP 674 DI 10.1097/FPC.0b013e32832e4bcd PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 494KD UT WOS:000269810700002 PM 19724244 ER PT J AU Reddy, AJ Kleeberger, SR AF Reddy, Anita J. Kleeberger, Steven R. TI Genetic polymorphisms associated with acute lung injury SO PHARMACOGENOMICS LA English DT Review DE acute respiratory distress syndrome; ARDS; association study; genetical genomics; genome-wide association studies; GWAS; haplotype; translational investigation ID RESPIRATORY-DISTRESS-SYNDROME; ANGIOTENSIN-CONVERTING ENZYME; GENOME-WIDE ASSOCIATION; COLONY-ENHANCING FACTOR; TUMOR-NECROSIS-FACTOR; PLASMINOGEN-ACTIVATOR INHIBITOR-1; INSERTION DELETION POLYMORPHISM; ENDOTHELIAL GROWTH-FACTOR; CHAIN-KINASE GENE; PROTEIN-B GENE AB Acute lung injury and acute respiratory distress syndrome are the result of intense inflammation in the lungs leading to respiratory failure. The causes of acute lung injury/acute respiratory distress syndrome are numerous (e.g., pneumonia, sepsis and trauma) but the reasons why certain individuals develop lung injury in response to these stimuli and others do not are not well understood. There is ample evidence in the literature that gene-host and gene-environment interactions may play a large role in the morbidity and mortality associated with this syndrome. In this review, we initially discuss methods for identification of candidate acute lung injury/acute respiratory distress syndrome susceptibility genes using a number of model systems including in vitro cell systems and inbred mice. We then describe examples of polymorphisms in genes that have been associated with the pathogenesis of acute lung injury/acute respiratory distress syndrome in human case-control studies. Systematic bench to bedside approaches to understand the genetic contribution to acute lung injury/acute respiratory distress syndrome have provided important insight to this complex disease and continuation of these investigations could lead to the development of novel prevention or intervention strategies. C1 [Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Reddy, Anita J.] Cleveland Clin Hlth Syst, Resp Inst, Cleveland, OH USA. RP Kleeberger, SR (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,Rm D240, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov FU Intramural NIH HHS [ZIA ES100512-08] NR 115 TC 15 Z9 15 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD SEP PY 2009 VL 10 IS 9 BP 1527 EP 1539 DI 10.2217/PGS.09.89 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507MQ UT WOS:000270858700019 PM 19761373 ER PT J AU Ernst, M Romeo, RD Andersen, SL AF Ernst, Monique Romeo, Russell D. Andersen, Susan L. TI Neurobiology of the development of motivated behaviors in adolescence: A window into a neural systems model SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT Conference on Pharmacology Biochemistry and Behavior CY JAN, 2008 CL Morzine, FRANCE DE Striatum; Amygdala; Prefrontal cortex; Appetitive; Aversive; Ontogeny; Dopamine; Motivation; Nucleus accumbens; Decision-making; Steroids; Puberty ID DOPAMINE-RECEPTOR OVERPRODUCTION; TESTOSTERONE NEGATIVE FEEDBACK; MEDIAL PREFRONTAL CORTEX; FOCAL CORTICAL ACTIVITY; AGE-RELATED-CHANGES; NUCLEUS-ACCUMBENS; DENTATE GYRUS; POSTNATAL-DEVELOPMENT; ADRENAL-STEROIDS; DECISION-MAKING AB Adaptive motivated behaviors are at the core of a successful life. Conversely, perturbed motivated behaviors are the hallmark of psychiatric disorders. Based on the notion that most psychopathology is developmental in nature, understanding the neural mechanisms that control motivated behavior across development and in psychopathology is a critical step for preventing and treating psychiatric diseases. This review focuses on adolescence, which is the critical developmental period that determines the successful passage into adulthood. We first present a heuristic neural systems model of motivated behavior (triadic model) that integrates neuroscience theories and the emerging body of functional neuroimaging work on the neurodevelopment of motivated behavior. As a key feature of adolescence, social reorientation is particularly emphasized through the presentation of a parallel model of social integration processing network. Although not yet integrated in the triadic model, pubertal changes and their possible contribution to adolescent motivated behavior are reviewed. Similarly, given its central role in motivated actions, the dopamine system is discussed from the perspective of animal studies dedicated to changes of this system across adolescence. This review reveals vast gaps in knowledge about the neurobiology of motivated behavior in normally developing individuals, which makes the translation to psychopathology only tentative. However, it provides clear directions for future research. Published by Elsevier Inc. C1 [Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Romeo, Russell D.] Columbia Univ Barnard Coll, Dept Psychol, New York, NY 10027 USA. [Romeo, Russell D.] Neurosci & Behav Program, New York, NY 10027 USA. [Andersen, Susan L.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, 15K N Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov; rromeo@barnard.edu; andersen@dbrp.mclean.org NR 146 TC 117 Z9 119 U1 2 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD SEP PY 2009 VL 93 IS 3 SI SI BP 199 EP 211 DI 10.1016/j.pbb.2008.12.013 PG 13 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 475UD UT WOS:000268385900002 PM 19136024 ER PT J AU Schmitt, AG Hall, FS Perona, M Ortega, G Hofmann, M Sora, I Uhl, GR Riederer, P Lesch, KP Gerlach, M Grunblatt, E AF Schmitt, A. G. Hall, F. S. Perona, M. Ortega, G. Hofmann, M. Sora, I Uhl, G. R. Riederer, P. Lesch, K. P. Gerlach, M. Gruenblatt, E. TI Stress and methylphenidate treatment, both modulate neuronal activity in an animal model for ADHD SO PHARMACOPSYCHIATRY LA English DT Meeting Abstract CT 26th Symposium of the Association-of-Neuropsychopharmacology-and-Pharmacopsychiatry (AGNP) CY OCT 07-10, 2009 CL Munich, GERMANY SP Assoc Neuropsychopharmacol & Pharmacopsychiat C1 [Schmitt, A. G.; Ortega, G.; Hofmann, M.; Riederer, P.; Lesch, K. P.; Gruenblatt, E.] Univ Wurzburg, Clin Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany. [Hall, F. S.; Perona, M.; Uhl, G. R.] Natl Inst Drug Abuse, Intramural Res Program, Bethesda, MD 20892 USA. [Sora, I] NIH, DHHS, Baltimore, MD USA. [Gerlach, M.] Tohoku Univ, Dept Neurosci, Grad Sch Med, Sendai, Miyagi 980, Japan. Univ Wurzburg, Clin Child & Adolescence Psychiat, Wurzburg, Germany. RI Grunblatt, Edna/A-6762-2016; Hall, Frank/C-3036-2013 OI Grunblatt, Edna/0000-0001-8505-7265; Hall, Frank/0000-0002-0822-4063 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD SEP PY 2009 VL 42 IS 5 MA A148 BP 240 EP 241 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 503BS UT WOS:000270507200159 ER PT J AU Rodriguez, IR Fliesler, SJ AF Rodriguez, Ignacio R. Fliesler, Steven J. TI Photodamage Generates 7-keto- and 7-hydroxycholesterol in the Rat Retina via a Free Radical-mediated Mechanism SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; LIGHT-INDUCED DAMAGE; CELL-DEATH; OXYSTEROL FORMATION; LIPID-PEROXIDATION; OUTER SEGMENT; IN-VIVO; CHOLESTEROL; IRON; 7-KETOCHOLESTEROL AB Albino Sprague-Dawley rats are known to undergo photoreceptor degeneration after exposure to constant light, but the molecular mechanism(s) by which the photoreceptors degenerate is not fully understood. We hypothesized that cytotoxic oxysterols are generated in situ in the retina under such conditions and may be involved in the degenerative mechanism. Thus, photodamaged and control rat retinas were analyzed for oxysterols by liquid chromatography mass spectroscopy. Elevated levels of two known cytotoxic oxysterols, 7-ketocholesterol (7KCh) and 7 alpha beta-hydroxycholesterol (7HCh), were found in the photodamaged retinas, at levels six-fold and 50-fold greater, respectively, than those found in non photodamaged controls. Notably, two key intermediates, 5,6 alpha,beta-epoxycholesterol (5,6-epoxyCh) and 7 alpha beta-hydroperoxy-cholesterol, were also identified, indicating that the formation of 7KCh and 7HCh is mediated by a free radical mechanism. By immunohistochemistry, 7KCh was localized to the ganglion cell layer, photoreceptor inner segments and retinal pigment epithelium (RPE), which coincides with the localization of ferritin in the retina. Exposure of a mixture of ferritin and low-density lipoprotein to intense white light in vitro produced similar oxysterol species as seen in vivo. We propose that the increased levels of 7KCh and 7HCh, especially in photoreceptor inner segments and RPE, may arise due to ferritin-catalyzed reactions and may be important contributors to the photoreceptor degeneration observed in photodamaged rats. C1 [Rodriguez, Ignacio R.] NEI, Retinal Cell & Mol Biol Lab, Sect Mech Retinal Dis, NIH, Bethesda, MD 20892 USA. [Fliesler, Steven J.] Vet Adm Western New York Healthcare Syst, Res Serv, Buffalo, NY USA. [Fliesler, Steven J.] SUNY Buffalo, Dept Ophthalmol, Buffalo, NY 14260 USA. [Fliesler, Steven J.] SUNY Buffalo, Dept Biochem, Buffalo, NY 14260 USA. RP Rodriguez, IR (reprint author), NEI, Retinal Cell & Mol Biol Lab, Sect Mech Retinal Dis, NIH, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov FU National Eye Institute intramural research program; U.S.P.H.S. [EY007361]; departmental Challenge Grant from Research to Prevent Blindness; Research to Prevent Blindness Senior Scientific Investigator Award FX The authors thank Dr. Ernesto F. Moreira for performing the 7KCh immunohistochemistry. This work was supported by the National Eye Institute intramural research program (I.R.R.), by U.S.P.H.S. grant EY007361 (S.J.F.) and by a departmental Challenge Grant from Research to Prevent Blindness (S.J.F.). S.J.F. is the recipient of a Research to Prevent Blindness Senior Scientific Investigator Award. NR 39 TC 17 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2009 VL 85 IS 5 BP 1116 EP 1125 DI 10.1111/j.1751-1097.2009.00568.x PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 489YT UT WOS:000269463700009 PM 19500292 ER PT J AU Bilski, PJ Risek, B Chignell, CF Schrader, WT AF Bilski, Piotr J. Risek, Boris Chignell, Colin F. Schrader, William T. TI Photocytotoxicity of the Fluorescent Nonsteroidal Androgen Receptor Ligand TDPQ SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET MOLECULAR-OXYGEN; PHOTODYNAMIC THERAPY; ROSE-BENGAL; CARBOSTYRIL DERIVATIVES; CATIONIC SURFACTANT; BIOLOGICAL-ACTIVITY; PROTEIN DAMAGE; AGONIST; CELLS; PROSTATE AB 1,2,3,4-tetrahydro-2,2-dimethyl-6-(trifluoromethyl)-8-pyridono[5,6-g]quinoline (TDPQ), a selective nonsteroidal androgen receptor (AR) ligand, is a fluorescent compound. We characterized its spectral properties in comparison with the structural precursor carbostyril 151 (C151) and with its racemic structural isomer 4-ethyl-1,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridino[5,6-g]quinoline (ETPQ). The absorption maximum in CH(3)CN of either TDPQ or ETPQ is 400 nm whereas that of C151 is 350 nm. The fluorescence lifetimes (tau) and quantum yields (phi(f)) in CH(3)CN are typical of fluorescent dyes: TDPQ (4.2 ns, 0.8) and ETPQ (4.6 ns, 0.76). C151 showed lower tau and phi(f) of 0.2 ns and 0.02, respectively. TDPQ can function as a fluorescent label at (sub)micromolar concentrations. We detected TDPQ fluorescence in human breast tumor cells using confocal microscopy. While the fluorescence maxima of the compounds were solvent insensitive, the phi(f) for ETPQ decreased in aqueous solutions regardless of the presence of albumin or DNA. The phi(f) of TDPQ was less affected. The quantum yield of singlet oxygen ((1)O(2)) photosensitization (phi(so)) by TDPQ and ETPQ was about 7% in CH(3)CN, sufficient to induce photocytotoxicity. TDPQ was photocytotoxic in AR-positive MDA-MB-453 breast cancer cells but not in AR-negative MDA-MB-231 cells. The combination of AR selectivity with photocytotoxicity makes TDPQ a promising candidate for selective targeting of AR-positive cells during photodynamic therapy. C1 [Bilski, Piotr J.; Chignell, Colin F.] Natl Inst Environm Hlth Sci, Pharmacol Lab, NIH, Res Triangle Pk, NC USA. [Risek, Boris; Schrader, William T.] Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. RP Bilski, PJ (reprint author), Natl Inst Environm Hlth Sci, Pharmacol Lab, NIH, Res Triangle Pk, NC USA. EM bilski@niehs.nih.gov FU NIH; NIEHS FX This research was supported by the Intramural Research Program of the NIH, NIEHS. The authors thank Mr. B. Karriker for assistance during fluorescence measurements and Mr. J.M. Reece for confocal microscopy. NR 45 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2009 VL 85 IS 5 BP 1225 EP 1232 DI 10.1111/j.1751-1097.2009.00575.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 489YT UT WOS:000269463700023 PM 19496989 ER PT J AU Adib, AB AF Adib, Artur B. TI Algorithms for Brownian first-passage-time estimation SO PHYSICAL REVIEW E LA English DT Article DE Brownian motion; lattice theory; probability; stochastic processes ID DYNAMICS AB A class of algorithms in discrete space and continuous time for Brownian first-passage-time estimation is considered. A simple algorithm is derived that yields exact mean first-passage times (MFPTs) for linear potentials in one dimension, regardless of the lattice spacing. When applied to nonlinear potentials and/or higher spatial dimensions, numerical evidence suggests that this algorithm yields MFPT estimates that either outperform or rival Langevin-based (discrete time and continuous space) estimates. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Adib, AB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM adiba@mail.nih.gov FU NIH; NIDDK FX The author would like to thank Attila Szabo for fruitful comments and suggestions. This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 14 TC 0 Z9 0 U1 1 U2 5 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD SEP PY 2009 VL 80 IS 3 AR 036706 DI 10.1103/PhysRevE.80.036706 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 501LN UT WOS:000270383500082 PM 19905245 ER PT J AU Mamasakhlisov, YS Todd, BA Badasyan, AV Mkrtchyan, AV Morozov, VF Parsegian, VA AF Mamasakhlisov, Yevgeni Sh. Todd, Brian A. Badasyan, Artem V. Mkrtchyan, Anna V. Morozov, Vladimir F. Parsegian, V. Adrian TI DNA stretching and multivalent-cation-induced condensation SO PHYSICAL REVIEW E LA English DT Article ID HELIX-COIL TRANSITION; PHASE TRANSITIONS; HYDRATION FORCES; ATTRACTION; MOLECULES; AGGREGATION; ELASTICITY; SPERMIDINE; BINDING; IONS AB Motivated by measurements on stretched double-stranded DNA in the presence of multivalent cations, we develop a statistical mechanical model for the compaction of an insoluble semiflexible polymer under tension. Using a mean-field approach, we determine the order of the extended-to-compact transition and provide an interpretation for the magnitude and interval of tensions over which compaction takes place. In the simplest thermodynamic limit of an infinitely long homogeneous polymer, compaction is a first-order transition that occurs at a single value of tension. For finite length chains or for heterogeneous polymers, the transition progresses over an interval of tension. Our theory provides an interpretation for the result of single-molecule experiments in terms of microscopic parameters such as persistence length and free energy of condensation. C1 [Mamasakhlisov, Yevgeni Sh.; Badasyan, Artem V.; Mkrtchyan, Anna V.; Morozov, Vladimir F.] Yerevan State Univ, Dept Mol Phys, Yerevan 375025, Armenia. [Todd, Brian A.] Purdue Univ, Dept Phys, W Lafayette, IN 47901 USA. [Parsegian, V. Adrian] NIH, Bethesda, MD 20892 USA. RP Mamasakhlisov, YS (reprint author), Yerevan State Univ, Dept Mol Phys, 1 Al Manougian Str, Yerevan 375025, Armenia. RI Badasyan, Artem/H-9907-2012 OI Badasyan, Artem/0000-0003-0563-5403 FU Intramural Research Program; NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX V. F. M., Y. Sh. M., and A. V. B. thankfully acknowledge the LPSB/NICHD/NIH for hospitality during short-term visits when part of this paper was written. A. V. B. acknowledges the support from a PRIN-COFIN 2007 grant. This work was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 38 TC 9 Z9 9 U1 3 U2 17 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD SEP PY 2009 VL 80 IS 3 AR 031915 DI 10.1103/PhysRevE.80.031915 PG 9 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 501LM UT WOS:000270383400114 PM 19905154 ER PT J AU Grey, CP Tycko, R AF Grey, Clare P. Tycko, Robert TI Solid-state NMR in biological and materials physics SO PHYSICS TODAY LA English DT Article ID ANGLE-SPINNING NMR; AMYLOID FIBRILS; SPECTROSCOPY; RESONANCE; BATTERIES C1 [Grey, Clare P.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Grey, Clare P.] Univ Cambridge, Cambridge, England. [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Grey, CP (reprint author), SUNY Stony Brook, Stony Brook, NY 11794 USA. NR 18 TC 7 Z9 7 U1 2 U2 9 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0031-9228 J9 PHYS TODAY JI Phys. Today PD SEP PY 2009 VL 62 IS 9 BP 44 EP 49 PG 6 WC Physics, Multidisciplinary SC Physics GA 493UA UT WOS:000269762400024 ER PT J AU Zou, C Lehti-Shiu, MD Thibaud-Nissen, F Prakash, T Buell, CR Shiu, SH AF Zou, Cheng Lehti-Shiu, Melissa D. Thibaud-Nissen, Francoise Prakash, Tanmay Buell, C. Robin Shiu, Shin-Han TI Evolutionary and Expression Signatures of Pseudogenes in Arabidopsis and Rice SO PLANT PHYSIOLOGY LA English DT Article ID LINEAGE-SPECIFIC EXPANSION; MESSENGER-RNA STABILITY; HOMOLOGOUS CODING GENE; RECEPTOR-LIKE KINASES; PROCESSED PSEUDOGENES; HUMAN GENOME; DUPLICATE GENES; LARGE-SCALE; IDENTIFICATION; TRANSCRIPTION AB Pseudogenes (Psi) are nonfunctional genomic sequences resembling functional genes. Knowledge of Psi s can improve genome annotation and our understanding of genome evolution. However, there has been relatively little systemic study of Psi s in plants. In this study, we characterized the evolution and expression patterns of Psi s in Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa). In contrast to animal Psi s, many plant Psi s experienced much stronger purifying selection. In addition, plant Psi s experiencing stronger selective constraints tend to be derived from relatively ancient duplicates, suggesting that they were functional for a relatively long time but became Psi s recently. Interestingly, the regions 5' to the first stops in the Psi s have experienced stronger selective constraints compared with 3' regions, suggesting that the 5' regions were functional for a longer period of time after the premature stops appeared. We found that few Psi s have expression evidence, and their expression levels tend to be lower compared with annotated genes. Furthermore, Psi s with expressed sequence tags tend to be derived from relatively recent duplication events, indicating that Psi expression may be due to insufficient time for complete degeneration of regulatory signals. Finally, larger protein domain families have significantly more Psi s in general. However, while families involved in environmental stress responses have a significant excess of Psi s, transcription factors and receptor-like kinases have lower than expected numbers of Psi s, consistent with their elevated retention rate in plant genomes. Our findings illustrate peculiar properties of plant Psi s, providing additional insight into the evolution of duplicate genes and benefiting future genome annotation. C1 [Zou, Cheng; Lehti-Shiu, Melissa D.; Buell, C. Robin; Shiu, Shin-Han] Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA. [Zou, Cheng] Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA. [Thibaud-Nissen, Francoise] J Craig Venter Inst, Rockville, MD 20850 USA. [Thibaud-Nissen, Francoise] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Prakash, Tanmay] Novi High Sch, Novi, MI 48375 USA. RP Shiu, SH (reprint author), Michigan State Univ, Dept Plant Biol, E Lansing, MI 48824 USA. EM shius@msu.edu OI Shiu, Shin-Han/0000-0001-6470-235X FU National Science Foundation [DBI 0638591, MCB 0749634] FX This work was supported by the National Science Foundation (grant nos. DBI 0638591 and MCB 0749634 to S.-H. S.). NR 67 TC 47 Z9 48 U1 2 U2 7 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD SEP PY 2009 VL 151 IS 1 BP 3 EP 15 DI 10.1104/pp.109.140632 PG 13 WC Plant Sciences SC Plant Sciences GA 490RS UT WOS:000269522200001 PM 19641029 ER PT J AU Liu, J Sun, YD Drubin, DG Oster, GF AF Liu, Jian Sun, Yidi Drubin, David G. Oster, George F. TI The Mechanochemistry of Endocytosis SO PLOS BIOLOGY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; MEMBRANE CURVATURE; COATED PITS; BAR-DOMAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; ACTIN CYTOSKELETON; VESICLE FORMATION; PLASMA-MEMBRANE; MULTIPLE STAGES; IMAGING ACTIN AB Endocytic vesicle formation is a complex process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane. Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear. That is, how the proper temporal and spatial coordination of endocytic events is achieved and what drives vesicle scission are not known. Drawing upon detailed knowledge from experiments in yeast, we develop the first integrated mechanochemical model that quantitatively recapitulates the temporal and spatial progression of endocytic events leading to vesicle scission. The central idea is that membrane curvature is coupled to the accompanying biochemical reactions. This coupling ensures that the process is robust and culminates in an interfacial force that pinches off the vesicle. Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells. The combination of experiments and theory in this work suggest a unified mechanism for endocytic vesicle formation across eukaryotes. C1 [Liu, Jian; Sun, Yidi; Drubin, David G.; Oster, George F.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Liu, J (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM drubin@berkeley.edu; goster@nature.berkeley.edu RI Liu, Jian/C-6755-2011 FU National Institutes of General Medical Sciences [1 R01 GM 50399, 1 R01 GM 42759]; National Science Foundation [DMS 0414039] FX This work was supported by National Institutes of General Medical Sciences grants 1 R01 GM 50399 and 1 R01 GM 42759 to DGD. GFO was supported by National Science Foundation grant DMS 0414039. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 110 Z9 110 U1 1 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD SEP PY 2009 VL 7 IS 9 AR e1000204 DI 10.1371/journal.pbio.1000204 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 507AF UT WOS:000270820800017 PM 19787029 ER PT J AU Guo, J Hall, KD AF Guo, Juen Hall, Kevin D. TI Estimating the Continuous-Time Dynamics of Energy and Fat Metabolism in Mice SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DIET-INDUCED OBESITY; PROTEIN; REQUIREMENTS; ANIMALS; BALANCE; GROWTH; MODEL; PIGS AB The mouse has become the most popular organism for investigating molecular mechanisms of body weight regulation. But understanding the physiological context by which a molecule exerts its effect on body weight requires knowledge of energy intake, energy expenditure, and fuel selection. Furthermore, measurements of these variables made at an isolated time point cannot explain why body weight has its present value since body weight is determined by the past history of energy and macronutrient imbalance. While food intake and body weight changes can be frequently measured over several weeks (the relevant time scale for mice), correspondingly frequent measurements of energy expenditure and fuel selection are not currently feasible. To address this issue, we developed a mathematical method based on the law of energy conservation that uses the measured time course of body weight and food intake to estimate the underlying continuous-time dynamics of energy output and net fat oxidation. We applied our methodology to male C57BL/6 mice consuming various ad libitum diets during weight gain and loss over several weeks and present the first continuous-time estimates of energy output and net fat oxidation rates underlying the observed body composition changes. We show that transient energy and fat imbalances in the first several days following a diet switch can account for a significant fraction of the total body weight change. We also discovered a time-invariant curve relating body fat and fat-free masses in male C57BL/6 mice, and the shape of this curve determines how diet, fuel selection, and body composition are interrelated. C1 [Guo, Juen; Hall, Kevin D.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Guo, J (reprint author), NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA. EM kevinh@niddk.nih.gov RI Hall, Kevin/F-2383-2010 FU NIH/NIDDK FX This work was supported by the Intramural Research Program of the NIH/NIDDK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 23 Z9 23 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD SEP PY 2009 VL 5 IS 9 AR e1000511 DI 10.1371/journal.pcbi.1000511 PG 7 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 506TV UT WOS:000270800100016 PM 19763167 ER PT J AU De Muyt, A Pereira, L Vezon, D Chelysheva, L Gendrot, G Chambon, A Laine-Choinard, S Pelletier, G Mercier, R Nogue, F Grelon, M AF De Muyt, Arnaud Pereira, Lucie Vezon, Daniel Chelysheva, Liudmila Gendrot, Ghislaine Chambon, Aurelie Laine-Choinard, Sandrine Pelletier, Georges Mercier, Raphael Nogue, Fabien Grelon, Mathilde TI A High Throughput Genetic Screen Identifies New Early Meiotic Recombination Functions in Arabidopsis thaliana SO PLOS GENETICS LA English DT Article ID DOUBLE-STRAND BREAK; CHROMOSOME SYNAPSIS; SCHIZOSACCHAROMYCES-POMBE; TOPOISOMERASE-VI; YEAST MEIOSIS; INTERHOMOLOG RECOMBINATION; MOLECULAR CHARACTERIZATION; SACCHAROMYCES-CEREVISIAE; HOMOLOG JUXTAPOSITION; SISTER CHROMATIDS AB Meiotic recombination is initiated by the formation of numerous DNA double-strand breaks (DSBs) catalysed by the widely conserved Spo11 protein. In Saccharomyces cerevisiae, Spo11 requires nine other proteins for meiotic DSB formation; however, unlike Spo11, few of these are conserved across kingdoms. In order to investigate this recombination step in higher eukaryotes, we took advantage of a high-throughput meiotic mutant screen carried out in the model plant Arabidopsis thaliana. A collection of 55,000 mutant lines was screened, and spo11-like mutations, characterised by a drastic decrease in chiasma formation at metaphase I associated with an absence of synapsis at prophase, were selected. This screen led to the identification of two populations of mutants classified according to their recombination defects: mutants that repair meiotic DSBs using the sister chromatid such as Atdmc1 or mutants that are unable to make DSBs like Atspo11-1. We found that in Arabidopsis thaliana at least four proteins are necessary for driving meiotic DSB repair via the homologous chromosomes. These include the previously characterised DMC1 and the Hop1-related ASY1 proteins, but also the meiotic specific cyclin SDS as well as the Hop2 Arabidopsis homologue AHP2. Analysing the mutants defective in DSB formation, we identified the previously characterised AtSPO11-1, AtSPO11-2, and AtPRD1 as well as two new genes, AtPRD2 and AtPRD3. Our data thus increase the number of proteins necessary for DSB formation in Arabidopsis thaliana to five. Unlike SPO11 and (to a minor extent) PRD1, these two new proteins are poorly conserved among species, suggesting that the DSB formation mechanism, but not its regulation, is conserved among eukaryotes. C1 [De Muyt, Arnaud; Pereira, Lucie; Vezon, Daniel; Chelysheva, Liudmila; Gendrot, Ghislaine; Chambon, Aurelie; Laine-Choinard, Sandrine; Pelletier, Georges; Mercier, Raphael; Nogue, Fabien; Grelon, Mathilde] INRA, Inst Jean Pierre Bourgin, Genet & Ameliorat Plantes Stn, UR 254, F-78026 Versailles, France. RP De Muyt, A (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. EM grelon@versailles.inra.fr RI mercier, Raphael/L-1497-2016 OI Nogue, Fabien/0000-0003-0619-4638; mercier, Raphael/0000-0001-6508-6608 FU ANR (Agence Nationale pour la Recherche, Genoplante) [GNP05040G, ANR07-BLAN-0215] FX This work was funded by the ANR ( Agence Nationale pour la Recherche, Genoplante GNP05040G: Comerec1 and ANR07-BLAN-0215: Copath). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 77 TC 53 Z9 54 U1 4 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2009 VL 5 IS 9 AR e1000654 DI 10.1371/journal.pgen.1000654 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 506ZG UT WOS:000270817800017 PM 19763177 ER PT J AU Kawauchi, S Calof, AL Santos, R Lopez-Burks, ME Young, CM Hoang, MP Chua, A Lao, TT Lechner, MS Daniel, JA Nussenzweig, A Kitzes, L Yokomori, K Hallgrimsson, B Lander, AD AF Kawauchi, Shimako Calof, Anne L. Santos, Rosaysela Lopez-Burks, Martha E. Young, Clint M. Hoang, Michelle P. Chua, Abigail Lao, Taotao Lechner, Mark S. Daniel, Jeremy A. Nussenzweig, Andre Kitzes, Leonard Yokomori, Kyoko Hallgrimsson, Benedikt Lander, Arthur D. TI Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl(+/-) Mouse, a Model of Cornelia de Lange Syndrome SO PLOS GENETICS LA English DT Article ID SISTER-CHROMATID COHESION; BRACHMANN-DELANGE SYNDROME; ENHANCER-BLOCKING ACTIVITY; CONGENITAL HEART-DISEASE; MICE LACKING; NIPPED-B; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; CONTROL REGION; OPHTHALMOLOGIC FINDINGS AB Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75-80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only similar to 30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl(+/-) mice and in individuals with CdLS. C1 [Kawauchi, Shimako; Calof, Anne L.; Santos, Rosaysela; Young, Clint M.; Kitzes, Leonard] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. [Kawauchi, Shimako; Calof, Anne L.; Santos, Rosaysela; Lopez-Burks, Martha E.; Young, Clint M.; Hoang, Michelle P.; Chua, Abigail; Lander, Arthur D.] Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92717 USA. [Kawauchi, Shimako; Calof, Anne L.; Kitzes, Leonard] Univ Calif Irvine, Ctr Hearing Res, Irvine, CA USA. [Calof, Anne L.; Lander, Arthur D.] Univ Calif Irvine, Ctr Complex Biol Syst, Irvine, CA USA. [Lopez-Burks, Martha E.; Hoang, Michelle P.; Chua, Abigail; Lander, Arthur D.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Lao, Taotao; Lechner, Mark S.] Drexel Univ, Dept Biosci & Biotechnol, Philadelphia, PA 19104 USA. [Daniel, Jeremy A.; Nussenzweig, Andre] NCI, NIH, Bethesda, MD 20892 USA. [Yokomori, Kyoko] Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. [Hallgrimsson, Benedikt] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada. RP Kawauchi, S (reprint author), Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA. EM alcalof@uci.edu; adlander@uci.edu RI Lander, Arthur/C-9008-2011; Calof, Anne/A-8644-2013; Hallgrimsson, Benedikt/A-9616-2008; Daniel, Jeremy/S-4729-2016 OI Calof, Anne/0000-0003-3676-2499; Hallgrimsson, Benedikt/0000-0002-7192-9103; Daniel, Jeremy/0000-0002-1981-5571 FU NIH [P01HD052860, R21HD050538]; Cornelia de Lange Syndrome Foundation; University of California Irvine; University of California Irvine NIH Minority Science Program [GM 55245] FX This work was supported by grants from the NIH (P01HD052860 to ADL and ALC; R21HD050538 to MSL); the Cornelia de Lange Syndrome Foundation; and the Center for Hearing Research at the University of California Irvine. RS was supported by the University of California Irvine NIH Minority Science Program ( GM 55245). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 134 TC 105 Z9 106 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2009 VL 5 IS 9 AR e1000650 DI 10.1371/journal.pgen.1000650 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 506ZG UT WOS:000270817800014 PM 19763162 ER PT J AU Westmoreland, J Ma, WJ Yan, Y Van Hulle, K Malkova, A Resnick, MA AF Westmoreland, Jim Ma, Wenjian Yan, Yan Van Hulle, Kelly Malkova, Anna Resnick, Michael A. TI RAD50 Is Required for Efficient Initiation of Resection and Recombinational Repair at Random, gamma-Induced Double-Strand Break Ends SO PLOS GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE MRE11; DNA-DAMAGE CHECKPOINT; HOMOLOGOUS RECOMBINATION; CHROMOSOME REARRANGEMENTS; DEINOCOCCUS-RADIODURANS; OVERLAPPING FUNCTIONS; BUDDING YEAST; SGS1; EXO1; NUCLEASES AB Resection of DNA double-strand break (DSB) ends is generally considered a critical determinant in pathways of DSB repair and genome stability. Unlike for enzymatically induced site-specific DSBs, little is known about processing of random "dirty-ended'' DSBs created by DNA damaging agents such as ionizing radiation. Here we present a novel system for monitoring early events in the repair of random DSBs, based on our finding that single-strand tails generated by resection at the ends of large molecules in budding yeast decreases mobility during pulsed field gel electrophoresis (PFGE). We utilized this "PFGE-shift'' to follow the fate of both ends of linear molecules generated by a single random DSB in circular chromosomes. Within 10 min after gamma-irradiation of G2/M arrested WT cells, there is a near-synchronous PFGE-shift of the linearized circular molecules, corresponding to resection of a few hundred bases. Resection at the radiation-induced DSBs continues so that by the time of significant repair of DSBs at 1 hr there is about 1-2 kb resection per DSB end. The PFGE-shift is comparable in WT and recombination-defective rad52 and rad51 strains but somewhat delayed in exo1 mutants. However, in rad50 and mre11 null mutants the initiation and generation of resected ends at radiation-induced DSB ends is greatly reduced in G2/M. Thus, the Rad50/Mre11/Xrs2 complex is responsible for rapid processing of most damaged ends into substrates that subsequently undergo recombinational repair. A similar requirement was found for RAD50 in asynchronously growing cells. Among the few molecules exhibiting shift in the rad50 mutant, the residual resection is consistent with resection at only one of the DSB ends. Surprisingly, within 1 hr after irradiation, double-length linear molecules are detected in the WT and rad50, but not in rad52, strains that are likely due to crossovers that are largely resection- and RAD50-independent. C1 [Westmoreland, Jim; Ma, Wenjian; Yan, Yan; Resnick, Michael A.] Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, NIH, Res Triangle Pk, NC USA. [Van Hulle, Kelly; Malkova, Anna] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA. RP Westmoreland, J (reprint author), Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, NIH, Res Triangle Pk, NC USA. EM resnick@niehs.nih.gov RI Ma, Wenjian/C-1071-2012 FU NIEHS (NIH, DHHS) [1 Z01 ES065073]; [1R01GM084242-01] FX This work was supported by grant 1R01GM084242-01 (AM) and the Intramural Research Program of the NIEHS (NIH, DHHS) under project 1 Z01 ES065073 (MAR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 65 TC 27 Z9 28 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD SEP PY 2009 VL 5 IS 9 AR e1000656 DI 10.1371/journal.pgen.1000656 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 506ZG UT WOS:000270817800018 PM 19763170 ER PT J AU Dawson, L Zarin, DA Emanuel, EJ Friedman, LM Chaudhari, B Goodman, SN AF Dawson, Liza Zarin, Deborah A. Emanuel, Ezekiel J. Friedman, Lawrence M. Chaudhari, Bimal Goodman, Steven N. TI Considering Usual Medical Care in Clinical Trial Design SO PLOS MEDICINE LA English DT Editorial Material ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIALS; VOLUME-REDUCTION SURGERY; GYNECOLOGIC-ONCOLOGY-GROUP; DISTRESS-SYNDROME TRIALS; ADVANCED OVARIAN-CANCER; MULTIMODAL TREATMENT; NATIONAL-INSTITUTE; STAGE-III; PACLITAXEL C1 [Dawson, Liza] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Zarin, Deborah A.] NIH, ClinicalTrials Gov, Natl Lib Med, Bethesda, MD 20892 USA. [Emanuel, Ezekiel J.] NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Chaudhari, Bimal] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. [Goodman, Steven N.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. RP Dawson, L (reprint author), NIAID, Div Aids, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dawsonl@niaid.nih.gov OI Chaudhari, Bimal/0000-0002-0115-949X NR 48 TC 18 Z9 19 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD SEP PY 2009 VL 6 IS 9 AR e1000111 DI 10.1371/journal.pmed.1000111 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 506ZH UT WOS:000270818100004 PM 19787044 ER PT J AU Bennett, AE Narayan, K Shi, D Hartnell, LM Gousset, K He, HF Lowekamp, BC Yoo, TS Bliss, D Freed, EO Subramaniam, S AF Bennett, Adam E. Narayan, Kedar Shi, Dan Hartnell, Lisa M. Gousset, Karine He, Haifeng Lowekamp, Bradley C. Yoo, Terry S. Bliss, Donald Freed, Eric O. Subramaniam, Sriram TI Ion-Abrasion Scanning Electron Microscopy Reveals Surface-Connected Tubular Conduits in HIV-Infected Macrophages SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLASMA-MEMBRANE; IN-VITRO; CELL; TYPE-1; RESERVOIR; TOMOGRAPHY; GENERATION; ENDOSOMES; LYSOSOMES AB HIV-1-containing internal compartments are readily detected in images of thin sections from infected cells using conventional transmission electron microscopy, but the origin, connectivity, and 3D distribution of these compartments has remained controversial. Here, we report the 3D distribution of viruses in HIV-1-infected primary human macrophages using cryo-electron tomography and ion-abrasion scanning electron microscopy (IA-SEM), a recently developed approach for nanoscale 3D imaging of whole cells. Using IA-SEM, we show the presence of an extensive network of HIV-1-containing tubular compartments in infected macrophages, with diameters of,150-200 nm, and lengths of up to,5 mm that extend to the cell surface from vesicular compartments that contain assembling HIV-1 virions. These types of surface-connected tubular compartments are not observed in T cells infected with the 29/31 KE Gag-matrix mutant where the virus is targeted to multi-vesicular bodies and released into the extracellular medium. IA-SEM imaging also allows visualization of large sheet-like structures that extend outward from the surfaces of macrophages, which may bend and fold back to allow continual creation of viral compartments and virion-lined channels. This potential mechanism for efficient virus trafficking between the cell surface and interior may represent a subversion of pre-existing vesicular machinery for antigen capture, processing, sequestration, and presentation. C1 [Bennett, Adam E.; Narayan, Kedar; Shi, Dan; Hartnell, Lisa M.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gousset, Karine; Freed, Eric O.] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. [He, Haifeng] FEI Co, Hillsboro, OR USA. [Lowekamp, Bradley C.; Yoo, Terry S.; Bliss, Donald] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Bennett, AE (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ss1@nih.gov OI Gousset, Karine/0000-0002-0988-2332 FU National Cancer Institute; NIH FX This work was entirely supported by funds from the intramural program of the National Cancer Institute, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 87 Z9 88 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2009 VL 5 IS 9 AR e1000591 DI 10.1371/journal.ppat.1000591 PG 10 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 506VO UT WOS:000270804900007 PM 19779568 ER PT J AU Mascola, JR AF Mascola, John R. TI The Cat and Mouse of HIV-1 Antibody Escape SO PLOS PATHOGENS LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; SUBTYPE-C INFECTION; NEUTRALIZING ANTIBODIES; TYPE-1 INFECTION; PERSISTENT INFECTION; RESPONSES; EMERGENCE; EVOLUTION; VARIANTS C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jmascola@nih.gov NR 36 TC 7 Z9 7 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2009 VL 5 IS 9 AR e1000592 DI 10.1371/journal.ppat.1000592 PG 2 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 506VO UT WOS:000270804900002 PM 19763273 ER PT J AU Pastrana, DV Tolstov, YL Becker, JC Moore, PS Chang, Y Buck, CB AF Pastrana, Diana V. Tolstov, Yanis L. Becker, Juergen C. Moore, Patrick S. Chang, Yuan Buck, Christopher B. TI Quantitation of Human Seroresponsiveness to Merkel Cell Polyomavirus SO PLOS PATHOGENS LA English DT Article ID KIDNEY-TRANSPLANT RECIPIENTS; BK VIRUS; MEDIATED NEUTRALIZATION; JC VIRUS; CARCINOMA; INFECTION; ANTIBODY; CANCER; SV40; DNA AB Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p<0.0001). Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection. C1 [Pastrana, Diana V.; Buck, Christopher B.] NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. [Tolstov, Yanis L.; Moore, Patrick S.; Chang, Yuan] Univ Pittsburgh, Inst Canc, Mol Virol Program, Pittsburgh, PA USA. [Becker, Juergen C.] Univ Clin Wurzburg, Dept Dermatol Venerol & Allergy, Wurzburg, Germany. RP Pastrana, DV (reprint author), NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. EM buckc@nih.gov RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011; OI Moore, Patrick/0000-0002-8132-858X; Buck, Christopher/0000-0003-3165-8094 FU NIH [CA136363, CA120726]; Center for Cancer Research; NCI Director's Intramural Innovation; Al Copeland Foundation; University of Pittsburgh EXPLORER; University of Pittsburgh Catalyst FX This work was funded in part by the Intramural Research Program of the NIH, with support from the Center for Cancer Research and the NCI Director's Intramural Innovation Award Program. This work was supported in part by awards from the Al Copeland Foundation, the University of Pittsburgh EXPLORER program, and NIH grants CA136363 and CA120726. YT was supported in part through a fellowship from the University of Pittsburgh Catalyst Program, and YC and PSM are funded as American Cancer Society Professors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 116 Z9 117 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD SEP PY 2009 VL 5 IS 9 AR e1000578 DI 10.1371/journal.ppat.1000578 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 506VO UT WOS:000270804900025 PM 19750217 ER PT J AU Kotlan, B Stroncek, DF Marincola, FM AF Kotlan, Beatrix Stroncek, David F. Marincola, Francesco M. TI Turning laboratory findings into therapy: a marathon goal that has to be reached SO POLSKIE ARCHIWUM MEDYCYNY WEWNETRZNEJ-POLISH ARCHIVES OF INTERNAL MEDICINE LA English DT Article DE obstacles; opportunities; therapy; translational medicine; translational research ID CYTOKINE FLOW-CYTOMETRY; TRANSLATIONAL RESEARCH; BIOMARKER DISCOVERY; TUMOR-MARKERS; CANCER; MELANOMA; WORKSHOP; SCIENCE; TISSUE; CRYOPRESERVATION AB The mission of translational research involves difficult tasks to be accomplished for its ultimate goal, i.e. the introduction of novel, effective therapeutic strategies in the clinic to diminish human suffering and cure life-threatening diseases. Translational research (also referred to as translational medicine) facilitates the translation of investment in biomedical research into successful medical treatment. This includes the transfer of diagnostic and therapeutic advances by proving their efficacy in large evidence-based trials. Through the study of humans novel insights about disease are brought back to the laboratory to identify new, observation-based strategies. This "two-way road" ("bench to bedside and bedside to bench") process includes formulating guidelines for drug development and principles for new therapeutic strategies; initiating clinical investigations that provide the biological basis for new therapies, and related clinical trials; defining therapeutic targets and clinical endpoints. It requires a systematic approach beginning with specimen sampling, patient data collection, laboratory investigations, data analysis, preclinical testing, clinical trials, treatment efficacy monitoring, and finally the evaluation of therapeutic result. The marathon well symbolizes the enormous efforts undertaken by clinicians, scientists, regulators, ethicists, patient advocates, drug developers, and others, coordinately attempting to overcome obstacles along this road toward the final "marathon goal in medicine". C1 [Marincola, Francesco M.] NIH, Chief Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Human Immunol, Bethesda, MD 20892 USA. [Kotlan, Beatrix] Natl Inst Oncol, Ctr Surg & Mol Tumor Pathol, Budapest, Hungary. [Stroncek, David F.] NIH, Chief Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Chief Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Human Immunol, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fmarincola@mail.cc.nih.gov FU American and Hungarian Fulbright [120610]; Hungarian OTKA [T048933]; Scientific Healthcare Committee FX The work was supported by the American and Hungarian Fulbright Grant No120610, the Hungarian OTKA T048933 and Scientific Healthcare Committee Grants. We thank Dr Balazs Banky for additional suggestions related to sample collection. NR 64 TC 2 Z9 2 U1 0 U2 0 PU MEDYCYNA PRAKTYCZNA PI KRAKOW PA UL KRAKOWSKA 41, KRAKOW, 31-066, POLAND SN 0032-3772 J9 POL ARCH MED WEWN JI Pol. Arch. Med. Wewn. PD SEP PY 2009 VL 119 IS 9 BP 586 EP 593 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 498XY UT WOS:000270180500011 PM 19776705 ER PT J AU Korde, LA Gadalla, SM AF Korde, Larissa A. Gadalla, Shahinaz M. TI Cancer Risk Assessment for the Primary Care Physician SO PRIMARY CARE LA English DT Article DE Cancer risk; Risk assessment; Genetics; Family history; Environmental risk factors; Lifestyle ID BILATERAL PROPHYLACTIC MASTECTOMY; HEREDITARY COLORECTAL-CANCER; SURGICAL ADJUVANT BREAST; MUTATION CARRIERS; PROSTATE-CANCER; FAMILY-HISTORY; BRCA2 MUTATION; OVARIAN-CANCER; LYNCH-SYNDROME; TOBACCO USE AB Cancer is the second leading cause of death in the United States. Cancer risk assessment can be divided into two major categories: assessment of familial or genetic risk and assessment of environmental factors that may be causally related to cancer. Identification of individuals with a suspected heritable cancer syndrome can lead to additional evaluation and to interventions that can substantially decrease cancer risk. Special attention should also be paid to potentially modifiable cancer risk factors in the course of advising primary care patients regarding a healthy lifestyle. Clinical guidelines, targeting both genetic and modifiable cancer risk factors, are available and can facilitate the application of these health care principles in the primary care setting. C1 [Korde, Larissa A.; Gadalla, Shahinaz M.] NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. [Gadalla, Shahinaz M.] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA. RP Korde, LA (reprint author), NCI, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,Room 7030, Rockville, MD 20852 USA. EM kordel@mail.nih.gov FU Intramural NIH HHS [Z01 CP010144-09] NR 84 TC 2 Z9 2 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD SEP PY 2009 VL 36 IS 3 BP 471 EP + DI 10.1016/j.pop.2009.04.006 PG 19 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 485PL UT WOS:000269135800005 PM 19616151 ER PT J AU Chu, C Lugovtsev, V Golding, H Betenbaugh, M Shiloach, J AF Chu, Chia Lugovtsev, Vladimir Golding, Hana Betenbaugh, Michael Shiloach, Joseph TI Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anchorage-independent; hemagglutinin; sialyltransferase; vaccine ID SCALE MICROCARRIER CULTURE; CYCLE PROGRESSION; CATIONIZED FERRITIN; HIGH GROWTH; B VIRUSES; VACCINES; EXPRESSION; ADHESION; VERO; GANGLIOSIDES AB MDCK cells are currently being considered as an alternative to embryonated eggs for influenza virus propagation and hemagglutinin ( HA) production intended for vaccine manufacturing. MDCK cells were found suitable for the virus production but their inability to grow in suspension burdens the process of scale up and hence their production capability. Anchorage-dependent MDCK cells were converted to anchorage-independent cells, capable of growing in suspension as a result of transfection with the human siat7e gene (ST6GaINac V). This gene was previously identified as having an important role in cellular adhesion when the transcriptions of genes from anchorage-dependent and anchorage-independent HeLa cells were compared. Unlike the parental MDCK cells, the siat7e-expressing cells were capable of growing in shake flasks as suspension cultures, achieving maximum concentration of 7 x 10(5) cells/mL while keeping close to 100% viability throughout the growth phase. In production experiments, the siat7e-expressing cells were infected with the Influenza B/Victoria/504/2000 strain. It was determined that the cell-derived viruses retained similar antigenic properties as those obtained from egg-derived viruses and their nucleotide sequences were identical. The specific production of hemagglutinin (expressed in hemagglutination units per 106 cells) from the siat7e-expressing cells was approximately 20 times higher than the specific production from the parental MDCK cells. If this suspension process scales up, the production potential of HA from 10 L of siat7e-expressing cells at a concentration of 106 cells/mL would be equivalent to the amount of HA obtained from 10,000 embryonated eggs. C1 [Chu, Chia; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA. [Chu, Chia; Betenbaugh, Michael] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Lugovtsev, Vladimir; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Core Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM yossi@nih.gov RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health FX We thank Dr. Bruce Raaka for his assistance with the FACS measurements and Dr. Pratik Jaluria for his communications on technical aspects of the experiments and formulation of the manuscript. This work was supported by the Intramural program at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health. NR 37 TC 27 Z9 29 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14802 EP 14807 DI 10.1073/pnas.0905912106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000015 PM 19706449 ER PT J AU Vu, VV Emerson, JP Martinho, M Kim, YS Munck, E Park, MH Que, L AF Vu, Van V. Emerson, Joseph P. Martinho, Marlene Kim, Yeon Sook Muenck, Eckard Park, Myung Hee Que, Lawrence, Jr. TI Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O-2 with a nonheme diiron center SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DOHH; peroxo intermediate; eIF5A; oxygen activation ID X-RAY-ABSORPTION; METHANE MONOOXYGENASE HYDROXYLASE; REDUCTASE PROTEIN R2; RIBONUCLEOTIDE REDUCTASE; PEROXO INTERMEDIATE; OXYGEN ACTIVATION; AMINO-ACID; PEROXODIFERRIC INTERMEDIATE; POSTTRANSLATIONAL SYNTHESIS; FERROXIDASE REACTION AB Deoxyhypusine hydroxylase is the key enzyme in the biosynthesis of hypusine containing eukaryotic translation initiation factor 5A (eIF5A), which plays an essential role in the regulation of cell proliferation. Recombinant human deoxyhypusine hydroxylase (hDOHH) has been reported to have oxygen- and iron-dependent activity, an estimated iron/holoprotein stoichiometry of 2, and a visible band at 630 nm responsible for the blue color of the as-isolated protein. EPR, Mossbauer, and XAS spectroscopic results presented herein provide direct spectroscopic evidence that hDOHH has an antiferromagnetically coupled diiron center with histidines and carboxylates as likely ligands, as suggested by mutagenesis experiments. Resonance Raman experiments show that its blue chromophore arises from a (mu-1,2-peroxo) diiron(III) center that forms in the reaction of the reduced enzyme with O-2, so the peroxo form of hDOHH is unusually stable. Nevertheless we demonstrate that it can carry out the hydroxylation of the deoxyhypusine residue present in the eIF5A substrate. Despite a lack of sequence similarity, hDOHH has a nonheme diiron active site that resembles both in structure and function those found in methane and toluene monooxygenases, bacterial and mammalian ribonucleotide reductases, and stearoyl acyl carrier protein Delta(9)-desaturase from plants, suggesting that the oxygen- activating diiron motif is a solution arrived at by convergent evolution. Notably, hDOHH is the only example thus far of a human hydroxylase with such a diiron active site. C1 [Kim, Yeon Sook; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Vu, Van V.; Emerson, Joseph P.; Que, Lawrence, Jr.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Vu, Van V.; Emerson, Joseph P.; Que, Lawrence, Jr.] Univ Minnesota, Ctr Met Biocatalysis, Minneapolis, MN 55455 USA. [Martinho, Marlene; Muenck, Eckard] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. RP Park, MH (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mhpark@nih.gov; larryque@umn.edu RI Vu, Van/B-2098-2010 FU National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH); NIH [GM38767, EB-001475]; Vietnam Education Foundation; U. S. Department of Energy FX This work was supported in part by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health (NIH), and by NIH Grants GM38767 (to L. Q.) and EB-001475 (to E. M.) and a Vietnam Education Foundation Fellowship (to V. V. V.). XAS data were collected on Beamline X3B at the National Synchrotron Radiation Light Source and Beamline 9-3 at the Stanford Synchrotron Radiation Lightsource, both of which are supported by the U. S. Department of Energy and NIH. We thank Mr. Erik R. Farquhar and Mr. Jonathan R. Frisch for experimental and writing assistance. NR 53 TC 51 Z9 52 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14814 EP 14819 DI 10.1073/pnas.0904553106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000017 PM 19706422 ER PT J AU Tu, C Zhou, XM Tropea, JE Austin, BP Waugh, DS Court, DL Ji, XH AF Tu, Chao Zhou, Xiaomei Tropea, Joseph E. Austin, Brian P. Waugh, David S. Court, Donald L. Ji, Xinhua TI Structure of ERA in complex with the 3 ' end of 16S rRNA: Implications for ribosome biogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GTPase; KH domain; 30S ribosomal subunit ID GTP-BINDING PROTEIN; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; RAS PROTEINS; KH DOMAIN; SUBUNIT; KSGA; TRANSLATION; ACTIVATION; SEQUENCE AB ERA, composed of an N-terminal GTPase domain followed by an RNA-binding KH domain, is essential for bacterial cell viability. It binds to 16S rRNA and the 30S ribosomal subunit. However, its RNA-binding site, the functional relationship between the two domains, and its role in ribosome biogenesis remain unclear. We have determined two crystal structures of ERA, a binary complex with GDP and a ternary complex with a GTP-analog and the (1531)AUCACCUCCUUA(1542) sequence at the 3' end of 16S rRNA. In the ternary complex, the first nine of the 12 nucleotides are recognized by the protein. We show that GTP binding is a prerequisite for RNA recognition by ERA and that RNA recognition stimulates its GTP-hydrolyzing activity. Based on these and other data, we propose a functional cycle of ERA, suggesting that the protein serves as a chaperone for processing and maturation of 16S rRNA and a checkpoint for assembly of the 30S ribosomal subunit. The AUCA sequence is highly conserved among bacteria, archaea, and eukaryotes, whereas the CCUCC, known as the anti-Shine-Dalgarno sequence, is conserved in noneukaryotes only. Therefore, these data suggest a common mechanism for a highly conserved ERA function in all three kingdoms of life by recognizing the AUCA, with a "twist" for noneukaryotic ERA proteins by also recognizing the CCUCC. C1 [Tu, Chao; Zhou, Xiaomei; Tropea, Joseph E.; Austin, Brian P.; Waugh, David S.; Court, Donald L.; Ji, Xinhua] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Tu, Chao/D-3637-2009; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Drs. M. Bubunenko, X. Chen, Y. Gu, and W. Guo for help and Drs. M. Bubunenko, J. Strathern, and A. Wlodawer for reading the manuscript. Diffraction data were collected at X9B, NSLS, Brookhaven National Laboratory and 22- BM (SER-CAT), APS, Argonne National Laboratory. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 40 TC 34 Z9 36 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14843 EP 14848 DI 10.1073/pnas.0904032106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000022 PM 19706445 ER PT J AU Salipante, SJ Mealiffe, ME Wechsler, J Krem, MM Liu, YJ Namkoong, S Bhagat, G Kirchhoff, T Offit, K Lynch, H Wiernik, PH Roshal, M McMaster, ML Tucker, M Fromm, JR Goldin, LR Horwitz, MS AF Salipante, Stephen J. Mealiffe, Matthew E. Wechsler, Jeremy Krem, Maxwell M. Liu, Yajuan Namkoong, Shinae Bhagat, Govind Kirchhoff, Tomas Offit, Kenneth Lynch, Henry Wiernik, Peter H. Roshal, Mikhail McMaster, Mary Lou Tucker, Margaret Fromm, Jonathan R. Goldin, Lynn R. Horwitz, Marshall S. TI Mutations in a gene encoding a midbody kelch protein in familial and sporadic classical Hodgkin lymphoma lead to binucleated cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; cytokinesis ID TUMOR-SUPPRESSOR GENE; CUL3-BASED E3 LIGASE; NASOPHARYNGEAL CARCINOMA; CHROMOSOME 3P; BREAST-CANCER; AURORA-B; CYTOKINESIS; IDENTIFICATION; DISEASE; LOCALIZATION AB Classical Hodgkin lymphoma (cHL) is a malignancy of B-cell origin in which the neoplastic cells, known as "Reed-Sternberg'' (RS) cells, are characteristically binucleated. Here we describe a family where multiple individuals developing cHL have inherited a reciprocal translocation between chromosomes 2 and 3. The translocation disrupts KLHDC8B, an uncharacterized gene from a region (3p21.31) previously implicated in lymphoma and related malignancies, resulting in its loss of expression. We tested KLHDC8B as a candidate gene for cHL and found that a 5'-UTR polymorphism responsible for decreasing its translational expression is associated with cHL in probands from other families with cHL and segregates with disease in those pedigrees. In one of three informative sporadic cases of cHL, we detected loss of heterozygosity (LOH) for KLHDC8B in RS cells, but not reactive T lymphocytes, purified from a malignant lymph node. KLHDC8B encodes a protein predicted to contain seven kelch repeat domains. KLHDC8B is expressed during mitosis, where it localizes to the midbody structure connecting cells about to separate during cytokinesis, and it is degraded after cell division. Depletion of KLHDC8B through RNA interference leads to an increase in binucleated cells, implicating its reduced expression in the formation of cHL's signature RS cell. C1 [Wechsler, Jeremy; Horwitz, Marshall S.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. [Salipante, Stephen J.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Mealiffe, Matthew E.; Liu, Yajuan; Namkoong, Shinae] Univ Washington, Sch Med, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Krem, Maxwell M.] Univ Washington, Sch Med, Med Oncol Program, Seattle, WA 98195 USA. [Roshal, Mikhail; Fromm, Jonathan R.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. [Bhagat, Govind] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. [Kirchhoff, Tomas; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Clin Canc Genet Lab, New York, NY 10021 USA. [Lynch, Henry] Creighton Univ, Sch Med, Dept Prevent Med, Omaha, NE 68178 USA. [Wiernik, Peter H.] New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY 10466 USA. [McMaster, Mary Lou; Tucker, Margaret; Goldin, Lynn R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Horwitz, MS (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. EM horwitz@u.washington.edu RI Tucker, Margaret/B-4297-2015; OI Bhagat, Govind/0000-0001-6250-048X; Kirchhoff, Tomas/0000-0002-9055-2364 FU University of Washington Medical Scientist Training Program; National Institutes of Health [F30AG030316]; Doris Duke Charitable Foundation Clinical Scientist Development Award; Fred Hutchinson/UW Cancer Consortium's Cancer Center Support; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics [N02-CP-55506] FX We thank participating families, W. Raskind and J. Wolff for EBV transformation of lymphoblasts, H. Massa and B. Trask for instruction in FISH, and T. Drumheller for case referral. This work was supported by the University of Washington Medical Scientist Training Program and National Institutes of Health Grant F30AG030316 (to S. J. S.); Doris Duke Charitable Foundation Clinical Scientist Development Award (M. E. M.); Fred Hutchinson/UW Cancer Consortium's Cancer Center Support Grant (M. S. H.); and Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and contract N02-CP-55506 (to M. L. M., M. T., and L. R. G.). NR 40 TC 22 Z9 23 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 1 PY 2009 VL 106 IS 35 BP 14920 EP 14925 DI 10.1073/pnas.0904231106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490EM UT WOS:000269481000035 PM 19706467 ER PT J AU Nair, SG Adams-Deutsch, T Epstein, DH Shaham, Y AF Nair, Sunila G. Adams-Deutsch, Tristan Epstein, David H. Shaham, Yavin TI The neuropharmacology of relapse to food seeking: Methodology, main findings, and comparison with relapse to drug seeking SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Diet; Extinction; Food reward; Self-administration; Food cues; Reinstatement; Relapse; Review; Stress ID CORTICOTROPIN-RELEASING-FACTOR; CONDITIONED PLACE PREFERENCE; CUE-INDUCED REINSTATEMENT; COCAINE-INDUCED REINSTATEMENT; STRESS-INDUCED REINSTATEMENT; PRIMING-INDUCED REINSTATEMENT; VENTRAL TEGMENTAL AREA; MELANIN-CONCENTRATING HORMONE; SELF-ADMINISTRATION BEHAVIOR; CB1 RECEPTOR ANTAGONIST AB Relapse to old, unhealthy eating habits is a major problem in human dietary treatments. The mechanisms underlying this relapse are unknown. Surprisingly, until recently this clinical problem has not been systematically studied in animal models. Here, we review results from recent studies in which a reinstatement model (commonly used to study relapse to abused drugs) was employed to characterize the effect of pharmacological agents on relapse to food seeking induced by either food priming (non-contingent exposure to small amounts of food), cues previously associated with food, or injections of the pharmacological stressor yohimbine. We also address methodological issues related to the use of the reinstatement model to study relapse to food seeking, similarities and differences in mechanisms underlying reinstatement of food seeking versus drug seeking, and the degree to which the reinstatement procedure provides a suitable model for studying relapse in humans. We conclude by discussing implications for medication development and future research. We offer three tentative conclusions: (1) The neuronal mechanisms of food-priming- and cue-induced reinstatement are likely different from those of reinstatement induced by the pharmacological stressor yohimbine. (2) The neuronal mechanisms of reinstatement of food seeking are possibly different from those of ongoing food-reinforced operant responding. (3) The neuronal mechanisms underlying reinstatement of food seeking overlap to some degree with those of reinstatement of drug seeking. Published by Elsevier Ltd. C1 [Shaham, Yavin] NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. [Epstein, David H.] NIDA, Clin Pharmacol & Therapeut Res Branch, IRP, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM Yshaham@intra.nida.nih.gov RI shaham, yavin/G-1306-2014 FU National Institute on Drug Abuse; Intramural Research Program FX Research was supported by the National Institute on Drug Abuse, Intramural Research Program. We thank Drs. Richard Rothman, Michael Baumann, and Richard Beninger for helpful comments and discussions. NR 353 TC 72 Z9 74 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD SEP PY 2009 VL 89 IS 1 BP 18 EP 45 DI 10.1016/j.pneurobio.2009.05.003 PG 28 WC Neurosciences SC Neurosciences & Neurology GA 496ZE UT WOS:000270018500002 PM 19497349 ER PT J AU Newmark, JL AF Newmark, Jill L. TI Face to Face with HISTORY SO PROLOGUE-QUARTERLY OF THE NATIONAL ARCHIVES AND RECORDS ADMINISTRATION LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD USA. RP Newmark, JL (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL ARCHIVES RECORDS ADMINISTRATION PI WASHINGTON PA TRUST FUND BOARD, WASHINGTON, DC 20408 USA SN 0033-1031 J9 PROLOGUE JI Prologue PD FAL PY 2009 VL 41 IS 3 BP 22 EP 25 PG 4 WC History SC History GA 509SS UT WOS:000271039300005 ER PT J AU Godlewski, G Offertaler, L Wagner, JA Kunos, G AF Godlewski, Grzegorz Offertaler, Laszlo Wagner, Jens A. Kunos, George TI Receptors for acylethanolamides-GPR55 and GPR119 SO PROSTAGLANDINS & OTHER LIPID MEDIATORS LA English DT Review DE G protein-coupled receptor; Lipid ligand; Cannabinoid ID PROTEIN-COUPLED RECEPTOR; ENDOTHELIAL CANNABINOID RECEPTOR; ISOLATED MESENTERIC-ARTERY; GLUCAGON-LIKE PEPTIDE-1; ARACHIDONOYL L-SERINE; ABNORMAL-CANNABIDIOL; BRAIN CONSTITUENT; PPAR-ALPHA; INSULIN-SECRETION; GLYCEMIC CONTROL AB Acylethanolamides are lipid substances widely distributed in the body, generated from a membrane phospholipid precursor, N-acylphosphatidylethanolamine (NAPE). The recent identification of arachidonoyl ethanolamide (anandamide or AEA) as an endogenous cannabinoid ligand has focused attention on acylethanolamides, which has further increased with the Subsequent identification of related additional acylethanolamides with signaling function, Such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Most of the biological functions of anandamide are mediated by the two G protein-coupled cannabinoid receptors identified to date, CB(1) and CB(2), with the transient receptor potential vanilloid-1 receptor being an additional potential target. There has been increasing pharmacological evidence for the existence of additional cannabinoid receptors, with the orphan G protein-coupled receptor GPR55 being the most actively scrutinized, and is one of the subjects of this review. The other receptor reviewed here is GPR119, which can recognize OEA and PEA. These two acylethanolamides, although structurally related to anandamide, do not interact with classical cannabinoid receptors. Instead, they have high affinity for the nuclear receptor PPAR alpha, which is believed to mediate many of their biological effects. Published by Elsevier Inc. C1 [Godlewski, Grzegorz; Offertaler, Laszlo; Wagner, Jens A.; Kunos, George] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Godlewski, G (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM godlewskig@mail.nih.gov FU Intramural NIH HHS [Z01 AA000351-07] NR 75 TC 83 Z9 91 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-8823 J9 PROSTAG OTH LIPID M JI Prostaglandins Other Lipid Mediat. PD SEP PY 2009 VL 89 IS 3-4 BP 105 EP 111 DI 10.1016/j.prostaglandins.2009.07.001 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506LU UT WOS:000270777100008 PM 19615459 ER PT J AU Clemens, JQ Calhoun, EA Litwin, MS McNaughton-Collins, M Dunn, RL Crowley, EM Landis, JR AF Clemens, J. Q. Calhoun, E. A. Litwin, M. S. McNaughton-Collins, M. Dunn, R. L. Crowley, E. M. Landis, J. R. CA Urologic Pelvic Pain Collaborative TI Rescoring the NIH chronic prostatitis symptom index: nothing new SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE chronic pelvic pain syndrome; questionnaire; psychometrics ID INSTITUTES-OF-HEALTH; PELVIC PAIN SYNDROME; VERSION; RELIABILITY; VALIDATION; VALIDITY AB The National Institutes of Health-chronic prostatitis symptom index (NIH-CPSI) is a commonly used 13-item questionnaire for the assessment of symptom severity in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). For each item, score ranges are 0-1 (6 items), 0-3 (2 items), 0-5 (3 items), 0-6 (1 item) and 0-10 (1 item). This scoring system is straightforward, but items with wider score ranges are de facto weighted more, which could adversely affect the performance characteristics of the questionnaire. We rescored the NIH-CPSI so that equal weights were assigned to each item, and compared the performance of the standard and rescored questionnaires using the original validation dataset. Both the original and revised versions of the scoring algorithm discriminated similarly among groups of men with CP (n = 151), benign prostatic hyperplasia (n = 149) and controls (n = 134). The internal consistency of the questionnaire was slightly better with the revised scoring, but values with the standard scoring were sufficiently high (Cronbach's >= 0.80). We conclude that although the rescored NIH-CPSI provides better face validity than the standard scoring algorithm, it requires additional calculation efforts and yields only marginal improvements in performance. Prostate Cancer and Prostatic Diseases (2009) 12, 285-287; doi: 10.1038/pcan.2009.22; published online 2 June 2009 C1 [Clemens, J. Q.; Dunn, R. L.] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI 48109 USA. [Calhoun, E. A.] Univ Illinois, Sch Publ Hlth, Dept Hlth Policy & Adm, Chicago, IL 60612 USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Urol, Los Angeles, CA 90024 USA. [McNaughton-Collins, M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Crowley, E. M.; Landis, J. R.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Urologic Pelvic Pain Collaborative] NIDDK, Bethesda, MD USA. RP Clemens, JQ (reprint author), Univ Michigan, Med Ctr, Dept Urol, 1500 E Med Ctr Dr,Taubman Ctr 3875, Ann Arbor, MI 48109 USA. EM qclemens@umich.edu RI Landis, J. Richard/A-9330-2010 FU NIDDK FX This study was funded by NIDDK. NR 12 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2009 VL 12 IS 3 BP 285 EP 287 DI 10.1038/pcan.2009.22 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 490FD UT WOS:000269483200013 PM 19488065 ER PT J AU Calhoun, EA Clemens, JQ Litwin, MS Walker-Corkery, E Markossian, T Kusek, JW McNaughton-Collins, M AF Calhoun, E. A. Clemens, J. Q. Litwin, M. S. Walker-Corkery, E. Markossian, T. Kusek, J. W. McNaughton-Collins, M. CA Chronic Prostatitis Collaborative TI Primary care physician practices in the diagnosis, treatment and management of men with chronic prostatitis/chronic pelvic pain syndrome SO PROSTATE CANCER AND PROSTATIC DISEASES LA English DT Article DE chronic prostatitis; primary care physicians; survey; practice patterns ID SYMPTOM INDEX; PREVALENCE; COMMUNITY; QUESTIONNAIRE; UROLOGISTS AB To describe practice patterns of primary care physicians (PCPs) for the diagnosis, treatment and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we surveyed 556 PCPs in Boston, Chicago, and Los Angeles (RR = 52%). Only 62% reported ever seeing a patient like the one described in the vignette. In all, 16% were ` not at all' familiar with CP/CPPS, and 48% were ` not at all' familiar with the National Institutes of Health classification scheme. PCPs reported practice patterns regarding CP/CPPS, which are not supported by evidence. Although studies suggest that CP/CPPS is common, many PCPs reported little or no familiarity, important knowledge deficits and limited experience in managing men with this syndrome. Prostate Cancer and Prostatic Diseases (2009) 12, 288-295; doi: 10.1038/pcan.2009.9; published online 7 April 2009 C1 [Walker-Corkery, E.; McNaughton-Collins, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Internal Med Div, Boston, MA 02114 USA. [Calhoun, E. A.; Markossian, T.] Univ Illinois, Sch Publ Hlth, Div Hlth Policy & Adm, Chicago, IL USA. [Clemens, J. Q.] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Urol, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Litwin, M. S.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. [Kusek, J. W.] NIDDK, NIH, Bethesda, MD USA. RP McNaughton-Collins, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Internal Med Div, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mmcnaughtoncollins@partners.org FU National Institutes of Health [U01 DK65187, DK 65277, DK 65257] FX The authors thank all the participating primary care physicians for making this study possible. This research was funded by Grants (U01 DK65187, DK 65277, and DK 65257) from the National Institutes of Health, which had no other role in the design or conduct of the study, or preparation of the manuscript. NR 27 TC 7 Z9 7 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1365-7852 J9 PROSTATE CANCER P D JI Prostate Cancer Prostatic Dis. PD SEP PY 2009 VL 12 IS 3 BP 288 EP 295 DI 10.1038/pcan.2009.9 PG 8 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 490FD UT WOS:000269483200014 PM 19350050 ER PT J AU Damjanovic, A Garcia-Moreno, B Brooks, BR AF Damjanovic, Ana Garcia-Moreno, Bertrand Brooks, Bernard R. TI Self-guided Langevin dynamics study of regulatory interactions in NtrC SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE self-guided Langevin dynamics; allostery; conformational transitions; NtrC ID PROTEIN SECONDARY STRUCTURE; TERMINAL RECEIVER DOMAIN; MOLECULAR-DYNAMICS; PK(A) CALCULATIONS; STRUCTURAL BASIS; PHOSPHORYLATION; SIMULATIONS; TRANSITION; PATHWAYS; PROGRAM AB Multiple self-guided Langevin dynamics (SGLD) simulations were performed to examine structural and dynamical properties of the receiver domain of nitrogen regulatory protein C (NtrC(r)). SGLD and MD simulations of the phosphorylated active form structure suggest a mostly stable but broad structural ensemble of this protein. The finite difference Poisson-Boltzmann calculations of the pK(a) values of the active site residues suggest an increase in the pK(a) of His-84 on phosphorylation of Asp-54. In SGLD simulations of the phosphorylated active form with charged His-84, the average position of the regulatory helix alpha 4 is found closer to the starting structure than in simulations with the neutral His-84. To model the transition pathway, the phosphate group was removed from the simulations. After 7 ns of simulations, the regulatory helix at alpha 4 was found approximately halfway between positions in the NMR structures of the active and inactive forms. Removal of the phosphate group stimulated loss of helix alpha 4, suggesting that the pathway of conformational transition may involve partial unfolding mechanism. The study illustrates the potential utility of the SGLD method in studies of the coupling between ligand binding and conformational transitions. C1 [Damjanovic, Ana; Garcia-Moreno, Bertrand] Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA. [Damjanovic, Ana; Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD USA. RP Damjanovic, A (reprint author), Johns Hopkins Univ, Dept Biophys, Baltimore, MD 21218 USA. EM ad@jhu.edu FU NHLBI [Z01 HL001050]; NIH [R01 GM061597] FX Grant sponsors: NIH, NHLBI; Grant; number: Z01 HL001050; Grant sponsor: NIH; Grant number: R01 GM061597. NR 39 TC 24 Z9 24 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD SEP PY 2009 VL 76 IS 4 BP 1007 EP 1019 DI 10.1002/prot.22439 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 481VD UT WOS:000268839400017 PM 19384996 ER PT J AU Chen, XL Hunt, D Cushman, SW Hess, S AF Chen, Xiaoli Hunt, Desmond Cushman, Samuel W. Hess, Sonja TI Proteomic characterization of thiazolidinedione regulation of obese adipose secretome in Zucker obese rats SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE High-throughput proteomics; Insulin resistance; Secreted proteome ID NECROSIS-FACTOR-ALPHA; PROMOTES INSULIN-RESISTANCE; SUBCUTANEOUS ADIPOCYTES; TISSUE; INFLAMMATION; PIOGLITAZONE; ROSIGLITAZONE; ASSOCIATION; LIPOCALIN-2; MACROPHAGES AB Signaling molecules released by adipose tissue have been implicated in inflammation, adipocyte dysfunction and systemic insulin resistance. In this study, we used 2-D LC-MS/MS and quantitative proteomics approaches to characterize the obese adipose secretory proteins that are responsive to the thiazolidinediones class of PPAR-gamma agonizts. We first showed the differential secretion profiling between obese and lean adipose tissue; 87 proteins were detected from the conditioned medium of adipose tissue of Zucker obese rats compared with 31 from lean rats. A total of 57 proteins comprising immune factors, inflammatory molecules, collagens, proteases, and extracellular matrix proteins were detected from obese, but not lean adipose tissue. More importantly, a quantitative proteomics approach using 180 proteolytic labeling allowed quantification of the difference in the secretion levels of 77 proteins, and thiazolidinediones treatment suppressed the secretion of most of the obese adipose tissue secretome, thus resembling a lean tissue. We have demonstrated an application of identifying the obese adipose secretome and characterizing the regulation of adipose secretion in obesity and insulin resistance. Our data provide the first evidence of changes in adipose secretion in obesity at a global level and show that such changes are correlated with systemic insulin resistance. C1 [Chen, Xiaoli] Univ Minnesota Twin Cities, Dept Food Sci & Nutr, St Paul, MN 55108 USA. [Hunt, Desmond; Cushman, Samuel W.] NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD USA. [Hess, Sonja] CALTECH, Proteome Explorat Lab, Pasadena, CA 91125 USA. RP Chen, XL (reprint author), Univ Minnesota Twin Cities, Dept Food Sci & Nutr, 1334 Eckles Ave, St Paul, MN 55108 USA. EM xlchen@umn.edu FU NIDDK FX This work was supported by the intramural research program of NIDDK. Experiments by SH were conducted at the Proteomics and Mass Spectrometry Facility, NIDDK. NR 38 TC 13 Z9 14 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD SEP PY 2009 VL 3 IS 9 BP 1099 EP 1111 DI 10.1002/prca.200900026 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 500VL UT WOS:000270333600008 PM 21137009 ER PT J AU Beesdo, K Knappe, S Pine, DS AF Beesdo, Katja Knappe, Susanne Pine, Daniel S. TI Anxiety and Anxiety Disorders in Children and Adolescents: Developmental Issues and Implications for DSM-V SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review DE Anxiety; Assessment; Diagnosis; Boundaries; Onset; Course; Outcome ID NATIONAL COMORBIDITY SURVEY; SUBSTANCE USE DISORDERS; PROSPECTIVE-LONGITUDINAL-COMMUNITY; COMMON MENTAL-DISORDERS; MAJOR DEPRESSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PARTLY DIFFERENT ENVIRONMENTS; R PSYCHIATRIC-DISORDERS; ALCOHOL-USE DISORDERS; 1ST 3 DECADES AB This review summarizes findings on the epidemiology and etiology of anxiety disorders among children and adolescents including separation anxiety disorder, specific phobia, social phobia, agoraphobia, panic disorder, and generalized anxiety disorder, also highlighting critical aspects of diagnosis, assessment, and treatment. Childhood and adolescence is the core risk phase for the development of anxiety symptoms and syndromes, ranging from transient mild symptoms to full-blown anxiety disorders. This article critically reviews epidemiological evidence covering prevalence, incidence, course, and risk factors. The core challenge in this age span is the derivation of developmentally more sensitive assessment methods. Identification of characteristics that could serve as solid predictors for onset, course, and outcome will require prospective designs that assess a wide range of putative vulnerability and risk factors. This type of information is important for improved early recognition and differential diagnosis as well as prevention and treatment in this age span. C1 [Beesdo, Katja; Knappe, Susanne] Tech Univ Dresden, Fac Sci, Dept Psychol, Inst Clin Psychol & Psychotherapy, D-01187 Dresden, Germany. [Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Beesdo, K (reprint author), Tech Univ Dresden, Fac Sci, Dept Psychol, Inst Clin Psychol & Psychotherapy, Chemnitzer Str 46, D-01187 Dresden, Germany. EM Katja.Beesdo@tu-dresden.de RI Beesdo-Baum, Katja/A-5793-2012; Knappe, Susanne/J-3626-2013 FU Intramural NIH HHS [ZIA MH002780-09, ZIA MH002781-09, ZIA MH002782-09] NR 158 TC 275 Z9 286 U1 26 U2 136 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2009 VL 32 IS 3 BP 483 EP + DI 10.1016/j.psc.2009.06.002 PG 44 WC Psychiatry SC Psychiatry GA 499HH UT WOS:000270208500003 PM 19716988 ER PT J AU Roy-Byrne, PP Joesch, JM Wang, PS Kessler, RC AF Roy-Byrne, Peter P. Joesch, Jutta M. Wang, Philip S. Kessler, Ronald C. TI Low Socioeconomic Status and Mental Health Care Use Among Respondents With Anxiety and Depression in the NCS-R SO PSYCHIATRIC SERVICES LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; UNITED-STATES; SURVEY REPLICATION; HURRICANE-KATRINA; ECONOMIC-CRISIS; SOUTH-KOREA; DISORDERS; SERVICES; IMPACT; INEQUALITIES AB Objective: This study sought to determine whether previously reported poor outcomes among patients of low socioeconomic status who have depression and anxiety could result from not receiving mental health treatment or from receiving minimally adequate treatment. Methods: The study sample consisted of 1,772 participants in the National Comorbidity Survey Replication (NCS-R) who met criteria for a mood or anxiety disorder. Bivariate and multivariate logistic regression analyses were used to examine associations between education, income, and assets and receipt of treatment and quality of treatment (minimally adequate treatment) for mood and anxiety disorders in sectors with the capacity to deliver evidence-based treatments (the general medical and mental health specialty sectors). Multivariate analyses controlled for age, gender, race-ethnicity, marital status, health insurance, and urbanicity. Results: Age, gender, marital status, and race-ethnicity were strong and fairly consistent predictors of mental health services use, with some modest variations by sector. In contrast, in bivariate and multivariate analyses, education, income, and assets were minimally related to use of mental health care and to receipt of minimally adequate care in both general medical and mental health specialty sectors. Conclusions: Socioeconomic status does not appear to play a major role in determining aspects of treatment for depression and anxiety disorders. Poor outcomes of depressed and anxious patients with low socioeconomic status may be due to differences in quality of care beyond the minimally adequate level assessed in this study or to factors unrelated to quality of care that could counteract effective treatments, such as the presence of ongoing chronic stress. (Psychiatric Services 60: 1190-1197, 2009) C1 [Roy-Byrne, Peter P.; Joesch, Jutta M.] Univ Washington, Sch Med, Harborview Med Ctr, Dept Psychiat, Seattle, WA 98104 USA. [Roy-Byrne, Peter P.; Joesch, Jutta M.] Harborview Med Ctr, Ctr Healthcare Improvement Addict Mental Illness, Seattle, WA USA. [Wang, Philip S.] NIMH, Bethesda, MD 20892 USA. [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Roy-Byrne, PP (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, Dept Psychiat, 325 9th Ave,Box 359911, Seattle, WA 98104 USA. EM roybyrne@u.washington.edu FU Bristol-Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Pharmaceuticals; Pfizer; Sanofi-Aventis FX Dr. Kessler has been a consultant for GlaxoSmithKline, Kaiser Permanente, Pfizer, Sanofi-Aventis, Shire Pharmaceuticals, and Wyeth-Ayerst; has served on advisory boards for Eli Lilly and Company and Wyeth-Ayerst; and has received research support for epidemiological studies from Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals, Pfizer, and Sanofi-Aventis. NR 33 TC 28 Z9 30 U1 0 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD SEP PY 2009 VL 60 IS 9 BP 1190 EP 1197 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 489RD UT WOS:000269438700007 PM 19723733 ER PT J AU Nestadt, G Di, CZ Riddle, MA Grados, MA Greenberg, BD Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Pinto, A Knowles, JA Piacentini, J Pauls, DL Bienvenu, OJ Wang, Y Liang, KY Samuels, JF Roche, KB AF Nestadt, G. Di, C. Z. Riddle, M. A. Grados, M. A. Greenberg, B. D. Fyer, A. J. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Pinto, A. Knowles, J. A. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Wang, Y. Liang, K. Y. Samuels, J. F. Roche, K. Bandeen TI Obsessive-compulsive disorder: subclassification based on co-morbidity SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Latent class; OCD; subtypes ID OCD COLLABORATIVE GENETICS; AFFECTED SIBLING PAIRS; SYMPTOM DIMENSIONS; TOURETTE-SYNDROME; LATENT STRUCTURE; ANXIETY; COMORBIDITY; FAMILY; MODELS; DEPRESSION AB Background. Obsessive-compulsive disorder (OCD) is probably an etiologically heterogeneous condition. Many patients manifest other psychiatric syndromes. This study investigated the relationship between OCD and co-morbid conditions to identify subtypes. Method. Seven hundred and six individuals with OCD were assessed in the OCD Collaborative Genetics Study (OCGS). Multi-level latent class analysis was conducted based on the presence of eight co-morbid psychiatric conditions [generalized anxiety disorder (GAD), major depression, panic disorder (PD), separation anxiety disorder (SAD), tics, mania, somatization disorders (Som) and grooming disorders (GrD)]. The relationship of the derived classes to specific clinical characteristics was investigated. Results. Two and three classes of OCD syndromes emerge from the analyses. The two-class solution describes lesser and greater co-morbidity classes and the more descriptive three-class solution is characterized by: (1) an OCD simplex class, in which major depressive disorder (MDD) is the most frequent additional disorder; (2) an OCD co-morbid tic-related class, in which tics are prominent and affective syndromes are considerably rarer; and (3) an OCD co-morbid affective-related class in which PD and affective syndromes are highly represented. The OCD co-morbid tic-related class is predominantly male and characterized by high conscientiousness. The OCD co-morbid affective-related class is predominantly female, has a young age at onset, obsessive-compulsive personality disorder (OCPD) features, high scores on the 'taboo' factor of OCD symptoms, and low conscientiousness. Conclusions. OCD can be classified into three classes based on co-morbidity. Membership within a class is differentially associated with other clinical characteristics. These classes, if replicated, should have important implications for research and clinical endeavors. C1 [Nestadt, G.; Riddle, M. A.; Grados, M. A.; Cullen, B.; Bienvenu, O. J.; Wang, Y.; Samuels, J. F.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Di, C. Z.; Liang, K. Y.; Roche, K. Bandeen] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21287 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Dept Psychiat & Human Behav, Brown Med Sch, Providence, RI 02906 USA. [Fyer, A. J.; Pinto, A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. [McCracken, J. T.; Piacentini, J.; Pauls, D. L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA. [Rauch, S. L.] Harvard Univ, Sch Med, Boston, MA USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Knowles, J. A.] Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Health [R01-MH-50214, K23-MH-64543]; NIH/NCRR/OPD-GCRC [RR00052] FX We thank the many families participating in the study, Drs D. Housman, K. Merikangas, A. Pulver and A. Wilson for consultation, and clinicians and coordinators at each site. This work was funded by National Institute of Health grants R01-MH-50214, K23-MH-64543 and NIH/NCRR/OPD-GCRC RR00052. NR 44 TC 41 Z9 43 U1 4 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD SEP PY 2009 VL 39 IS 9 BP 1491 EP 1501 DI 10.1017/S0033291708004753 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 486CP UT WOS:000269173400009 PM 19046474 ER PT J AU Keil, A Freund, AM AF Keil, Andreas Freund, Alexandra M. TI Changes in the Sensitivity to Appetitive and Aversive Arousal Across Adulthood SO PSYCHOLOGY AND AGING LA English DT Article DE emotion; ratings; valence; arousal; International Affective Picture System ID SELF-ASSESSMENT MANNEQUIN; OLDER-ADULTS; EMOTIONAL REACTIVITY; ATTENTIONAL BLINK; IMPLICIT THEORIES; NEGATIVITY BIAS; AGE-DIFFERENCES; YOUNGER ADULTS; MEMORY; PICTURES AB In 2 cross-sectional studies, the authors examined age-related differences in the evaluation of emotional stimuli in 2 community samples, with participants ranging in age from young to older adulthood (18-81 years old). Pictures of the International Affective Picture System were used in Study 1, and written verbs were used in Study 2. Participants rated these stimuli along the 2 major affective dimensions of hedonic valence and emotional arousal, thus yielding a 2-dimensional affective space for each participant. Young adults showed the expected pattern of 2 distinct clusters of stimuli in this space, representing increasing pleasantness (appetitive activation) and unpleasantness (aversive activation) with increasing emotional arousal. In contrast, for older adults, emotional valence and arousal ratings were linearly related: Low-arousing stimuli were rated as most pleasant, and high-arousing stimuli were rated as most unpleasant. When regressed on age, these changes revealed a gradual decrease of appetitive activation (i.e., the relationship between pleasure and arousal) across adulthood and a linear increase in aversive activation (i.e., the relationship between displeasure and arousal). These results extend previous work on emotional development, adding information as to the role of emotional intensity for affective experience in different age groups. C1 [Keil, Andreas] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Keil, Andreas] Univ Florida, NIMH, Ctr Study Emot & Attent, Gainesville, FL 32611 USA. [Freund, Alexandra M.] Univ Zurich, Dept Psychol, Zurich, Switzerland. RP Keil, A (reprint author), Univ Florida, Dept Psychol, POB 112766, Gainesville, FL 32611 USA. EM akeil@ufl.edu RI Keil, Andreas/F-9427-2011 OI Keil, Andreas/0000-0002-4064-1924 NR 61 TC 41 Z9 41 U1 2 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 2009 VL 24 IS 3 BP 668 EP 680 DI 10.1037/a0016969 PG 13 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 495YX UT WOS:000269933600015 PM 19739923 ER PT J AU Lockenhoff, CE Terracciano, A Costa, PT AF Loeckenhoff, Corinna E. Terracciano, Antonio Costa, Paul T., Jr. TI Five-Factor Model Personality Traits and the Retirement Transition: Longitudinal and Cross-Sectional Associations SO PSYCHOLOGY AND AGING LA English DT Article DE retirement; personality traits; five-factor model; longitudinal; aging ID EPIDEMIOLOGIC CATCHMENT-AREA; WORK EXPERIENCES; JOB-PERFORMANCE; NATURAL-HISTORY; FOLLOW-UP; SATISFACTION; HEALTH; METAANALYSIS; STABILITY; BEHAVIOR AB The authors examined associations between 5-factor personality traits and retirement in a diverse community sample. Longitudinal analyses (n = 367) compared personality trajectories of participants who remained employed and participants who retired. Personality at baseline did not predict future retirement, but compared to participants who remained employed, retirees increased in Agreeableness and decreased in Activity, a facet of Extraversion. In cross-sectional analyses among retirees (n = 144), those low in Neuroticism and high in Extraversion reported higher retirement satisfaction, and those high in Extraversion reported higher postretirement activity levels. Findings suggest that the trait perspective contributes to the understanding of the retirement process. C1 [Loeckenhoff, Corinna E.; Terracciano, Antonio; Costa, Paul T., Jr.] NIA, Lab Personal & Cognit, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Lockenhoff, CE (reprint author), Cornell Univ, Dept Human Dev, G35 Martha Van Rensselaer Hall, Ithaca, NY 14853 USA. EM cel72@cornell.edu RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712; Loeckenhoff, Corinna/0000-0003-1605-1323 FU Intramural NIH HHS [Z01 AG000183-19, Z01 AG000184-19, Z99 AG999999, ZIA AG000183-22, ZIA AG000183-23, ZIA AG000197-03, ZIA AG000197-04]; NIMH NIH HHS [R01 MH050616, K23 MH064543, K23 MH064543-01A2, MH 47447, MH50616, MH64543, R01 MH047447] NR 46 TC 21 Z9 22 U1 2 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 2009 VL 24 IS 3 BP 722 EP 728 DI 10.1037/a0015121 PG 7 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 495YX UT WOS:000269933600020 PM 19739928 ER PT J AU Corrigall, WA AF Corrigall, William A. TI Hypocretin mechanisms in nicotine addiction: evidence and speculation SO PSYCHOPHARMACOLOGY LA English DT Review DE Hypocretin; Nicotine; Addiction; VTA; Pontine; Thalamus; Thalamocortical; Amygdala; Prefrontal cortex ID VENTRAL TEGMENTAL AREA; GAMMA-AMINOBUTYRIC-ACID; MIDBRAIN DOPAMINE NEURONS; RESTING TOBACCO SMOKERS; RAT PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; BRAIN REWARD AREAS; PARAVENTRICULAR NUCLEUS; ACETYLCHOLINE-RECEPTORS; DRUG-ADDICTION AB The hypocretin/orexin system has been implicated in arousal mechanisms, sleep, and sleep disorders, including narcolepsy, and more recently in drug addiction. Theoretically, hypocretin (hcrt) mechanisms appear to be potential substrates for nicotine addiction: arousal and attentional mechanisms influence use and withdrawal symptoms, and hcrt systems overlap anatomically with a number of brain regions associated with nicotine addiction. This review summarizes the studies that have examined hcrt mechanisms in the effects of nicotine and describes hcrt innervation of, and effects in, several brain regions implicated in nicotine addiction. The review speculates on the possible mechanisms by which hcrt may contribute to nicotine addiction in these regions, with the objective of encouraging research in this area. In a small literature, both experimenter-administered and self-administered nicotine have been shown to elicit or depend on hcrt signaling. However, although untested in experimental designs, there is compelling evidence that hcrt mechanisms in the ventral tegmental area, the pontine region, thalamocortical circuits, the prefrontal cortex, and the amygdala could have a broad influence on nicotine addiction. Evidence reviewed leads to the conclusion that hcrt mechanisms could mediate several dimensions of nicotine addiction, including a multi-faceted regulation of mesocorticolimbic dopaminergic function, but beyond dopaminergic mechanisms, hcrt could influence nicotine use and relapse during abstinence through broadly based arousal/attentional effects. These speculative ideas need to be examined experimentally; the potential gains are a more thorough understanding of the pathophysiology of nicotine addiction, and the discovery of novel targets for the development of pharmacotherapeutics. C1 [Corrigall, William A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Corrigall, William A.] Minneapolis Med Res Fdn Inc, Minneapolis, MN USA. [Corrigall, William A.] NIDA, NIH, Bethesda, MD 20892 USA. RP Corrigall, WA (reprint author), Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. EM corri040@umn.edu NR 195 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2009 VL 206 IS 1 BP 23 EP 37 DI 10.1007/s00213-009-1588-2 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 484AQ UT WOS:000269015700002 PM 19529922 ER PT J AU Bossert, JM Wihbey, KA Pickens, CL Nair, SG Shaham, Y AF Bossert, Jennifer M. Wihbey, Kristina A. Pickens, Charles L. Nair, Sunila G. Shaham, Yavin TI Role of dopamine D-1-family receptors in dorsolateral striatum in context-induced reinstatement of heroin seeking in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE Conditioned cues; Dopamine; Dorsal striatum; Drug environment; Extinction; Heroin self-administration; Opiates; Reinstatement; SCH 23390; Ventral striatum ID NUCLEUS-ACCUMBENS CORE; COCAINE-SEEKING; PREFRONTAL CORTEX; DORSAL STRIATUM; INDUCED RELAPSE; DRUG SEEKING; EFFERENT PROJECTIONS; BASOLATERAL AMYGDALA; ALCOHOL-SEEKING; RENEWAL AB In humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of D-1-family receptors in lateral or medial accumbens shell, but not accumbens core. In this study, we further characterized the role of striatal D-1-family receptors in context-induced reinstatement by assessing the effect of dorsolateral or dorsomedial injections of the D-1-family receptor antagonist SCH 23390 on this reinstatement. Rats were trained to self-administer heroin (0.05-0.10 mg/kg per infusion) for 12 days; drug infusions were paired with a discrete tone-light cue. Subsequently, heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a nondrug context. During reinstatement tests under extinction conditions, the D-1-family receptor antagonist SCH 23390 (0.3-1.0 A mu g per side) was injected into the dorsolateral or dorsomedial striatum prior to exposure to heroin self-administration context or the nondrug (extinction) context. We then used a disconnection procedure to examine whether D-1-family receptors in the dorsolateral striatum and lateral accumbens shell jointly or independently support context-induced reinstatement. Dorsolateral but not dorsomedial SCH 23390 injections attenuated context-induced reinstatement of heroin seeking. SCH 23390 injections into the dorsolateral striatum of one hemisphere and lateral accumbens shell of the other hemisphere were ineffective. Results indicate that dorsolateral striatum D-1-family dopamine receptors are critical for context-induced reinstatement of heroin seeking. Results also suggest that D-1-receptor-mediated dopamine transmission in the dorsolateral striatum and lateral accumbens shell independently support this reinstatement. C1 [Bossert, Jennifer M.; Wihbey, Kristina A.; Pickens, Charles L.; Nair, Sunila G.; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov RI Pickens, Charles/E-8984-2010; shaham, yavin/G-1306-2014 FU National Institute on Drug Abuse FX The work was supported by the Intramural Research Program of the National Institute on Drug Abuse. We thank Makeda Carroll for the technical assistance and Drs. Geoff Schoenbaum, Satoshi Ikemoto, and Stefanie Geisler for the excellent comments regarding data interpretation and neuroanatomy. NR 50 TC 39 Z9 40 U1 2 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD SEP PY 2009 VL 206 IS 1 BP 51 EP 60 DI 10.1007/s00213-009-1580-x PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 484AQ UT WOS:000269015700004 PM 19506837 ER PT J AU Achat-Mendes, C Platt, DM Newman, AH Spealman, RD AF Achat-Mendes, Cindy Platt, Donna M. Newman, Amy H. Spealman, Roger D. TI The dopamine D3 receptor partial agonist CJB 090 inhibits the discriminative stimulus but not the reinforcing or priming effects of cocaine in squirrel monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE D3 receptor partial agonist; CJB 090; Cocaine discrimination; Cocaine-primed reinstatement of cocaine-seeking; Cocaine self-administration; Food-maintained behavior ID ABUSE THERAPEUTIC AGENTS; DRUG-ASSOCIATED STIMULI; SEEKING BEHAVIOR; D-3 DOPAMINE; INDUCED REINSTATEMENT; TARGETED DISRUPTION; NUCLEUS-ACCUMBENS; RHESUS-MONKEYS; ANIMAL-MODELS; HUMAN BRAIN AB Dopamine D3 receptor mechanisms have been implicated in the abuse-related behavioral effects of cocaine. The purpose of this study was to investigate the effects of the D3 receptor partial agonist CJB 090 on the discriminative stimulus, reinforcing and priming effects of cocaine in squirrel monkeys. Complementary studies were conducted to compare CJB 090's effects on food-maintained behavior and species-typical unconditioned behaviors. Monkeys were trained to: (1) discriminate cocaine from saline using a two-lever choice procedure, (2) self-administer cocaine on a second-order fixed-interval, fixed-ratio schedule of i.v. drug injection, or (3) self-administer food on a comparable second-order schedule of food delivery. A final group of monkeys served in quantitative observational studies of unconditioned behaviors. In cocaine discrimination studies, pretreatment with CJB 090 significantly attenuated cocaine's discriminative stimulus effects. CJB 090 also significantly attenuated the partial cocaine-like stimulus effects of the preferential D3 receptor agonist PD 128907 but not the preferential D2 receptor agonist sumanirole. CJB 090 did not attenuate either self-administration of cocaine or cocaine-induced reinstatement of extinguished drug-seeking at a dose that reduced responding maintained by food. CJB 090 did not induce scratching or biting (species-typical effects of D2/3 receptor agonists) or catalepsy (typical effect of D2/3 receptor antagonists). The results provide no evidence that CJB 090 reduced either the reinforcing or priming effects of cocaine but do suggest that CJB 090, acting via a D3 receptor mechanism, antagonized the discriminative stimulus effects of cocaine at a dose that did not induce adverse side effects. C1 [Achat-Mendes, Cindy; Platt, Donna M.; Spealman, Roger D.] Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurosci, Southborough, MA 01772 USA. [Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD USA. RP Achat-Mendes, C (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Neurosci, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. EM Cindy_Achat-Mendes@hms.harvard.edu FU United States Public Health Service Grants [DA011054, DA017700, NIDA-IRP, RR00168] FX This work was supported by United States Public Health Service Grants DA011054, DA017700, NIDA-IRP and RR00168. NR 49 TC 15 Z9 15 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 SEP PY 2009 VL 206 IS 1 BP 73 EP 84 DI 10.1007/s00213-009-1581-9 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 484AQ UT WOS:000269015700006 PM 19513698 ER PT J AU Rea, M Caria, A Kullmann, S Braun, C Canova, C Belardinelli, MO Gentilomo, A Birbaumer, N AF Rea, Massimiliano Caria, Andrea Kullmann, Stephanie Braun, Christoph Canova, Carlos Belardinelli, Marta Olivetti Gentilomo, Adriano Birbaumer, Niels TI THE INFLUENCE OF AVERSIVE FACES ON PROSPECTIVE MEMORY: AN EVENT-RELATED FMRI STUDY SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 21-24, 2009 CL Berlin, GERMANY SP Soc Psychophysiol Res DE prospective memory; event-related fmri design C1 [Rea, Massimiliano; Caria, Andrea; Kullmann, Stephanie; Canova, Carlos; Birbaumer, Niels] Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. [Rea, Massimiliano; Belardinelli, Marta Olivetti; Gentilomo, Adriano] Univ Roma La Sapienza, Rome, Italy. [Caria, Andrea] Univ Trent, Dept Cognit Sci & Educ, Trento, Italy. [Braun, Christoph] Univ Trent, Ctr Mind Brain Sci, CiMEC, Trento, Italy. [Birbaumer, Niels] NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. RI Braun, Christoph/E-4561-2010; Braun, Christoph/J-4160-2014 OI Braun, Christoph/0000-0002-7836-4010; Braun, Christoph/0000-0002-7836-4010 NR 0 TC 0 Z9 0 U1 0 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 PD SEP PY 2009 VL 46 BP S144 EP S144 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NR UT WOS:000269744700820 ER PT J AU Schmitz, A Merikangas, KR Grillon, C AF Schmitz, Anja Merikangas, Kathleen R. Grillon, Christian TI ANXIOUS RESPONSE TO PREDICTABLE AND UNPREDICTABLE AVERSIVE EVENTS IN CHILDREN SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract CT 49th Annual Meeting of the Society-for-Psychophysiological-Research CY OCT 21-24, 2009 CL Berlin, GERMANY SP Soc Psychophysiol Res DE startle; anxiety; predictability C1 [Schmitz, Anja; Merikangas, Kathleen R.; Grillon, Christian] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 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 PD SEP PY 2009 VL 46 BP S157 EP S157 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 493NR UT WOS:000269744700895 ER PT J AU Dittfeld, C Dietrich, A Peickert, S Hering, S Baumann, M Grade, M Ried, T Kunz-Schughart, LA AF Dittfeld, Claudia Dietrich, Antje Peickert, Susann Hering, Sandra Baumann, Michael Grade, Marian Ried, Thomas Kunz-Schughart, Leoni A. TI CD133 expression is not selective for tumor-initiating or radioresistant cell populations in the CRC cell lines HCT-116 SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Cancer stem/tumor-initiating cells (CSC/TIC); Colorectal carcinoma (CRC) cell lines; HCT-116; 2-D culture; 3-D culture; Radioresponse ID CANCER STEM-CELLS; HEPATOCELLULAR-CARCINOMA CELLS; COLORECTAL-CANCER; COLON-CANCER; STEM/PROGENITOR CELLS; PROGENITOR CELLS; PLASMA-MEMBRANE; BRAIN-TUMORS; IDENTIFICATION; MARKER AB Background and purpose: CD133 is controversially discussed as putative (surrogate) marker for cancer stem/tumor-initiating cell populations (CSC/TIC) in epithelial tumors including colorectal carcinomas (CRCs). We studied CD133 expression in established CRC cell lines and examined in vitro behavior, radioresponse and in vivo tumor formation of CD133(+/-) subpopulations of one cell line of interest. Materials and methods: Ten CRC cell lines were analyzed for CD133 expression using flow cytometry and Western blotting. CD133(+) and CD133(-) HCT-116 subpopulations were separated by FACS and studied in 2-D and 3-D culture and colony formation assays after irradiation. Subcutaneous xenograft formation was monitored in NMRI (nu/nu) mice. Results and conclusions: CRC cell lines could be classified into three groups: (i) CD133(-), (ii) CD133(+) and (iii) those with two distinct CD133(+) and CD133(-) subpopulations. Isolated CD133(+/-) HCT-116 subpopulations were studied relative to the original fraction. No difference was found in 2-D growth, spheroid formation or radioresponse in vitro. Also, tumor formation and growth rate did not differ for the sorted subpopulations. However, a subset of xenografts originated from CD133(-) HCT-116 showed a striking enrichment in the CD133(+) fraction. Our data show that CD133 expression is not selective for sphere forming, tumor-initiating or radioresistant subpopulations in the HCT-116 CRC cell lines. This implies that CD133 cannot be regarded as a CSC/TIC marker in all CRC cell lines and that functional measurements Of tumor formation have to generally accompany CSC/TIC-directed mechanistic or therapeutic studies. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 353-361 C1 [Kunz-Schughart, Leoni A.] Tech Univ Dresden, Fac Med Carl Gustav Carus, OncoRay Ctr Radiat Res Oncol, D-01307 Dresden, Germany. [Hering, Sandra] Tech Univ Dresden, Inst Legal Med, D-01307 Dresden, Germany. [Baumann, Michael] Univ Hosp Dresden, Dept Radiat Oncol, Dresden, Germany. [Grade, Marian] Univ Med Goettingen, Dept Gen & Visceral Surg, Gottingen, Germany. [Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA. RP Kunz-Schughart, LA (reprint author), Tech Univ Dresden, Fac Med Carl Gustav Carus, OncoRay Ctr Radiat Res Oncol, Fetscherstr 74,PF 86, D-01307 Dresden, Germany. EM leoni.kunz-schughart@oncoray.de FU German Federal Ministry of Education and Research (BMBF) [O1ZZ0502]; German Research Foundation [KU 971/7-1, GR 3376/2-1, KFO 179]; BMBF FX The authors gratefully acknowledge the excellent technical assistance of Ms. Marit Wondrak and Ms. Melanie Huether. This work was supported in part by the German Federal Ministry of Education and Research (BMBF) through Grant O1ZZ0502 and the German Research Foundation (DFG) through Grants KU 971/7-1 and GR 3376/2-1, and the KFO 179. OncoRay is funded by the BMBF in the program "Center for Innovation Competence". NR 69 TC 31 Z9 31 U1 2 U2 7 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 SEP PY 2009 VL 92 IS 3 BP 353 EP 361 DI 10.1016/j.radonc.2009.06.034 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 502OQ UT WOS:000270470200010 PM 19699546 ER PT J AU Kerner, JF Hall, KL AF Kerner, Jon F. Hall, Kara L. TI Research Dissemination and Diffusion Translation Within Science and Society SO RESEARCH ON SOCIAL WORK PRACTICE LA English DT Article DE translation; diffusion; dissemination; research; practice; policy ID KNOWLEDGE TRANSLATION; IMPLEMENTATION AB In moving health and social service programs from planning into action, it is essential to understand the extent to which the knowledge gained from research should influence the actions taken by organizations and agencies that provide services (e.g., government, nongovernment organizations [NGOs]). The complexity of the challenges in translating lessons learned from science into different service settings, as well as into public policy, requires a multifaceted approach to accelerate the integration of research with practice. In this paper, the relationship between science and service is examined within the contexts of the scientific, health practice, and policy communities largely from a public sector perspective within the United States. C1 [Kerner, Jon F.] NCI, Div Canc Control & Populat Sci, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Kerner, JF (reprint author), NCI, Div Canc Control & Populat Sci, NIH, US Dept HHS, 6130 Execut Blvd EPN 6142, Bethesda, MD 20892 USA. EM kernerj@mail.nih.gov NR 40 TC 21 Z9 21 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7315 J9 RES SOCIAL WORK PRAC JI Res. Soc. Work. Pract. PD SEP PY 2009 VL 19 IS 5 BP 519 EP 530 DI 10.1177/1049731509335585 PG 12 WC Social Work SC Social Work GA 484XS UT WOS:000269084200003 ER PT J AU Sun, YQ Sundaram, R Zhao, YC AF Sun, Yanqing Sundaram, Rajeshwari Zhao, Yichuan TI Empirical Likelihood Inference for the Cox Model with Time-dependent Coefficients via Local Partial Likelihood SO SCANDINAVIAN JOURNAL OF STATISTICS LA English DT Article DE empirical likelihood; empirical processes; Gaussian multiplier calibration; local partial likelihood; pointwise and simultaneous confidence regions; bands; proportional hazards model; strong approximations ID ADDITIVE RISK MODEL; CENSORED-DATA; REGRESSION-MODEL; CONFIDENCE BANDS; SEMIPARAMETRIC ANALYSIS; SURVIVAL PROBABILITIES; TRANSFORMATION MODELS; LINEAR-MODELS; INTERVALS AB The Cox model with time-dependent coefficients has been studied by a number of authors recently. In this paper, we develop empirical likelihood (EL) pointwise confidence regions for the time-dependent regression coefficients via local partial likelihood smoothing. The EL simultaneous confidence bands for a linear combination of the coefficients are also derived based on the strong approximation methods. The EL ratio is formulated through the local partial log-likelihood for the regression coefficient functions. Our numerical studies indicate that the EL pointwise/simultaneous confidence regions/bands have satisfactory finite sample performances. Compared with the confidence regions derived directly based on the asymptotic normal distribution of the local constant estimator, the EL confidence regions are overall tighter and can better capture the curvature of the underlying regression coefficient functions. Two data sets, the gastric cancer data and the Mayo Clinic primary biliary cirrhosis data, are analysed using the proposed method. C1 [Sun, Yanqing] Univ N Carolina, Dept Math & Stat, Charlotte, NC 28223 USA. [Sundaram, Rajeshwari] NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Zhao, Yichuan] Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. RP Sun, YQ (reprint author), Univ N Carolina, Dept Math & Stat, Charlotte, NC 28223 USA. EM yasun@uncc.edu OI Sundaram, Rajeshwari/0000-0002-6918-5002 FU NSF [DMS-0604576]; NIH [5 RO1 AI054165-05]; Intramural research program of NIH; NSA [H98230-07-1-0002] FX The authors would like to thank the Editor, Associate Editor and the referee for their very helpful comments and suggestions. The. first author's research work was partially supported by NSF grant DMS-0604576 and NIH grant 5 RO1 AI054165-05. The second author's research was supported by Intramural research program of NIH. The third author's research work was partially supported by NSA grant H98230-07-1-0002. NR 49 TC 8 Z9 8 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0303-6898 J9 SCAND J STAT JI Scand. J. Stat. PD SEP PY 2009 VL 36 IS 3 BP 444 EP 462 DI 10.1111/j.1467-9469.2008.00634.x PG 19 WC Statistics & Probability SC Mathematics GA 483SP UT WOS:000268988600005 ER PT J AU Woods, SW Addington, J Cadenhead, KS Cannon, TD Cornblatt, BA Heinssen, R Perkins, DO Seidman, LJ Tsuang, MT Walker, EF McGlashan, TH AF Woods, Scott W. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. Cornblatt, Barbara A. Heinssen, Robert Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. McGlashan, Thomas H. TI Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study SO SCHIZOPHRENIA BULLETIN LA English DT Article DE prodrome; risk syndrome; psychosis; schizophrenia; schizotypy ID ULTRA-HIGH-RISK; NATIONAL COMORBIDITY SURVEY; DYSBINDIN GENE DTNBP1; DIAGNOSTIC STABILITY; 1ST-EPISODE PSYCHOSIS; BIPOLAR-DISORDER; SCHIZOPHRENIA PRODROME; PREDICTIVE-VALIDITY; AT-RISK; COMPREHENSIVE ASSESSMENT AB Treatment and prevention studies over the past decade have enrolled patients believed to be at risk for future psychosis. These patients were considered at risk for psychosis by virtue of meeting research criteria derived from retrospective accounts of the psychosis prodrome. This study evaluated the diagnostic validity of the prospective "prodromal risk syndrome" construct. Patients assessed by the Structured Interview for Prodromal Syndromes as meeting criteria of prodromal syndromes (n = 377) from the North American Prodrome Longitudinal Study were compared with normal comparison (NC, n = 196), help-seeking comparison (HSC, n = 198), familial high-risk (FHR, n = 40), and schizotypal personality disorder (SPD, n = 49) groups. Comparisons were made on variables from cross-sectional demographic, symptom, functional, comorbid diagnostic, and family history domains of assessment as well as on follow-up outcome. Prodromal risk syndrome patients as a group were robustly distinguished from NC subjects across all domains and distinguished from HSC subjects and from FHR subjects on most measures in many of these domains. Adolescent and young adult SPD patients, while distinct from prodromal patients on definitional grounds, were similar to prodromals on multiple measures, consistent with SPD in young patients possibly being an independent risk syndrome for psychosis. The strong evidence of diagnostic validity for the prodromal risk syndrome for first psychosis raises the question of its evaluation for inclusion in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). C1 [Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, PRIME Prodromal Res Clin, New Haven, CT 06519 USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Heinssen, Robert] NIMH, Div Adult Translat Res, Schizophrenia Spectrum Disorders Res Program, Bethesda, MD 20892 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Woods, SW (reprint author), Yale Univ, Sch Med, Dept Psychiat, PRIME Prodromal Res Clin, 34 Pk St, New Haven, CT 06519 USA. EM scott.woods@yale.edu FU National Institute of Mental Health [U01 MH066160, U01 MH066134, R01 MH60720, K24 MH76191, R01 MH065079, R01 MH061523, U01 MH066069, P50 MH064065, R01 MH065562, P50 MH080272, R21MH075027, RO1MH062066, K05MH01654]; Donaghue Foundation; Eli Lilly and Co FX National Institute of Mental Health (U01 MH066160 to S. W. W., U01 MH066134 to J. A., R01 MH60720 and K24 MH76191 to K. S. C., R01 MH065079 to T. D. C., R01 MH061523 to B. A. C., U01 MH066069 and P50 MH064065 to D. O. P., R01 MH065562 and P50 MH080272 to L. J. S., R21MH075027 to M. T. T., RO1MH062066 to E. F. W., K05MH01654 to T. H. M.); Donaghue Foundation (to S. W. W.); Eli Lilly and Co (study HGGF to T. H. M., J. A., D. O. P.). NR 98 TC 207 Z9 213 U1 4 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2009 VL 35 IS 5 BP 894 EP 908 DI 10.1093/schbul/sbp027 PG 15 WC Psychiatry SC Psychiatry GA 486PY UT WOS:000269210700011 PM 19386578 ER PT J AU Miller, R Ream, G McCormack, J Gunduz-Bruce, H Sevy, S Robinson, D AF Miller, Rachel Ream, Geoffrey McCormack, Joanne Gunduz-Bruce, Handan Sevy, Serge Robinson, Delbert TI A prospective study of cannabis use as a risk factor for non-adherence and treatment dropout in first-episode schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Adherence; Dropout; Cannabis; First episode; Substance abuse; Compliance ID 1ST EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC MEDICATION ADHERENCE; EARLY PSYCHOSIS PROGRAM; SCHIZOAFFECTIVE DISORDER; UNTREATED PSYCHOSIS; EARLY INTERVENTION; SUBSTANCE MISUSE; FOLLOW-UP; PREDICTORS; DURATION AB Introduction: Although several studies have reported on cannabis use and adherence for first episode of psychosis patients, the findings remain unclear as to whether cannabis use is a risk factor for poor adherence in young people with first-episode schizophrenia. This study was designed to follow patients' use of cannabis and adherence in a naturalistic setting during the first 12 months of treatment. It examines whether cannabis use is a risk factor for two distinct types of non-adherence: non-adherence to medication and treatment dropout. Methods: Participants were 112 first-episode schizophrenia patients of diverse backgrounds a two community hospitals, enrolled in a study of differential effectiveness of two second generation antipsychotic medications. Multiple indicators were used to assess cannabis use and adherence to medication. Patients were encouraged to continue in the study even after period of treatment refusal or change from study to standardized medication. Study hypotheses were tested using Cox proportional hazards models with cannabis use as a time-varying covariate. Results: After 12 months, 23 had dropped out and 37 had at some point been non-adherent to medication. Of 34 participants who used cannabis during treatment, 32 had a prior diagnosis of cannabis abuse/dependence and 30 were male. Independently of age, race, socioeconomic status, gender, site, and medication assignment, cannabis use significantly increased hazard of non-adherence by a factor of 2.4 (p<.001) and hazard of dropout by a factor of 6.4 (p =.034) Conclusion: Results indicate that cannabis use is a risk factor for non-adherence to medication and dropout from treatment. Treatment for first-episode schizophrenia may be more effective if providers address the issue of cannabis use with patients throughout the early years of treatment, especially for those with existing cannabis abuse/dependence. Published by Elsevier B.V. C1 [Miller, Rachel; McCormack, Joanne; Gunduz-Bruce, Handan; Sevy, Serge; Robinson, Delbert] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA. [Ream, Geoffrey] Adelphi Univ, Garden City, NY 11530 USA. [Miller, Rachel] NIMH, Bethesda, MD 20892 USA. [Gunduz-Bruce, Handan] Yale Univ, Sch Med, New Haven, CT 06511 USA. RP Miller, R (reprint author), NIMH, 10 Ctr Dr,Bldg 10,Room 3B24, Bethesda, MD 20892 USA. EM mrachel@mail.nih.gov; ream@adelphi.edu; jMcCorma@lij.edu; hg68@email.med.yale.edu; ssevy@lij.edu; Robinson@lij.edu OI Ream, Geoffrey/0000-0003-1149-9495 FU NCRR NIH HHS [M01 RR018535, RR018535-01]; NIDA NIH HHS [5 T32 DA07233-22, K23 DA015541, T32 DA007233]; NIMH NIH HHS [MH41960, MH60004, R01 MH060004, R01 MH060004-05] NR 36 TC 37 Z9 38 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2009 VL 113 IS 2-3 BP 138 EP 144 DI 10.1016/j.schres.2009.04.018 PG 7 WC Psychiatry SC Psychiatry GA 492CD UT WOS:000269630800003 PM 19481424 ER PT J AU Klejbor, I Kucinski, A Wersinger, SR Corso, T Spodnik, JH Dziewiatkowski, J Morys, J Hesse, RA Rice, KC Miletich, R Stachowiak, EK Stachowiak, MK AF Klejbor, Ilona Kucinski, Aaron Wersinger, Scott R. Corso, Thomas Spodnik, Jan H. Dziewiatkowski, Jerzy Morys, Janusz Hesse, Renae A. Rice, Kenner C. Miletich, Robert Stachowiak, Ewa K. Stachowiak, Michal K. TI Serotonergic hyperinnervation and effective serotonin blockade in an FGF receptor developmental model of psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE FGF receptor-1; Midbrain dopamine neurons; 5-HT2A receptor; Atypical antipsychotics; Sensory gating; Social interaction ID FIBROBLAST-GROWTH-FACTOR; MIDBRAIN DOPAMINE NEURONS; VENTRAL TEGMENTAL AREA; SUBSTANTIA-NIGRA; SCHIZOPHRENIC-PATIENTS; CELL-PROLIFERATION; PROGENITOR CELLS; CEREBRAL-CORTEX; MESSENGER-RNA; RAT-BRAIN AB The role of fibroblast growth factor receptors (FGFR) in normal brain development has been well-documented in transgenic and knock-out mouse models. Changes in FGF and its receptors have also been observed in schizophrenia and related developmental disorders. The current study examines a transgenic th(tk-)/th(tk-) mouse model with FGF receptor signaling disruption targeted to dopamine (DA) neurons, resulting in neurodevelopmental, anatomical, and biochemical alterations similar to those observed in human schizophrenia. We show in th(tk-)/th(tk-) mice that hypoplastic development of DA systems induces serotonergic hyperinnervation of midbrain DA nuclei, demonstrating the co-developmental relationship between DA and 5-HT systems. Behaviorally, th(tk-)/th(tk-) mice displayed impaired sensory gaiting and reduced social interactions correctable by atypical antipsychotics (AAPD) and a specific 5-HT2A antagonist, M100907. The adult onset of neurochemical and behavioral deficits was consistent with the postpubertal time course of psychotic symptoms in schizophrenia and related disorders. The spectrum of abnormalities observed in th(tk-)/th(tk-) mice and the ability of AAPD to correct the behavioral deficits consistent with human psychosis suggests that midbrain 5-HT-2A-controlling systems are important loci of therapeutic action. These results may provide further insight into the complex multi-neurotransmitter etiology of neurodevelopmental diseases such autism, bipolar disorder, Asperger's Syndrome and schizophrenia. (C) 2009 Elsevier B.V. All rights reserved. C1 [Klejbor, Ilona; Kucinski, Aaron; Corso, Thomas; Stachowiak, Ewa K.; Stachowiak, Michal K.] SUNY Buffalo, Dept Pathol & Anat Sci, Buffalo, NY 14214 USA. [Klejbor, Ilona; Spodnik, Jan H.; Dziewiatkowski, Jerzy; Morys, Janusz; Stachowiak, Michal K.] Med Univ Gdansk, Dept Anat & Neurobiol, Gdansk, Poland. [Wersinger, Scott R.; Hesse, Renae A.] SUNY Buffalo, Dept Psychol, Buffalo, NY 14214 USA. [Miletich, Robert] SUNY Buffalo, Dept Nucl Med, Buffalo, NY 14214 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Bethesda, MD USA. [Rice, Kenner C.] NIAAA, Bethesda, MD USA. [Corso, Thomas] Lake Erie Coll Osteopath Med, Dept Biochem, Erie, PA 16509 USA. RP Stachowiak, MK (reprint author), SUNY Buffalo, Dept Pathol & Anat Sci, 3435 Main St,206A Farber Hall, Buffalo, NY 14214 USA. EM mks4@buffalo.edu FU University at Buffalo FX We grateful for funding from University at Buffalo (two IRDF grants) which supported this study and EKS for participating in part as a volunteer. NR 80 TC 14 Z9 14 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP PY 2009 VL 113 IS 2-3 BP 308 EP 321 DI 10.1016/j.schres.2009.06.006 PG 14 WC Psychiatry SC Psychiatry GA 492CD UT WOS:000269630800025 PM 19570652 ER PT J AU Segars, JH Aagaard-Tillery, KM AF Segars, James H., Jr. Aagaard-Tillery, Kjersti M. TI Epigenetics in Reproduction PREFACE SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Editorial Material C1 [Segars, James H., Jr.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. [Aagaard-Tillery, Kjersti M.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. RP Segars, JH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 3 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD SEP PY 2009 VL 27 IS 5 BP 349 EP 350 DI 10.1055/s-0029-1237422 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 489SW UT WOS:000269443800001 PM 19711244 ER PT J AU Dupont, C Armant, DR Brenner, CA AF Dupont, Catherine Armant, D. Randall Brenner, Carol A. TI Epigenetics: Definition, Mechanisms and Clinical Perspective SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Epigenetics; X-chromosome inactivation; imprinting; transgenerational inheritance ID X-CHROMOSOME INACTIVATION; EARLY MAMMALIAN DEVELOPMENT; DNA METHYLTRANSFERASE; IMPRINTED GENES; PREIMPLANTATION EMBRYOS; OOCYTE GROWTH; HUMAN-CELLS; CYTOSINE METHYLATION; HISTONE ACETYLATION; DOSAGE COMPENSATION AB A vast array of successive epigenetic modifications ensures the creation of a healthy individual. Crucial epigenetic reprogramming events occur during germ cell development and early embryogenesis in mammals. As highlighted by the large offspring syndrome with in vitro conceived ovine and bovine animals, any disturbance during germ cell development or early ernbryogenesis has the potential to alter epigenetic reprogramming. Therefore the complete array of human assisted reproductive technology (ART), starting from ovarian hormonal stimulation to embryo uterine transfer, could have a profound impact on the epigenetic state of human in vitro produced individuals. Although some investigators have suggested an increased incidence of epigenetic abnormalities in in vitro conceived children, other researchers have refuted these allegations. To date, multiple reasons can be hypothesized why irrefutable epigenetic alterations as a result of ART have not been demonstrated yet. C1 [Brenner, Carol A.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Detroit, MI 48201 USA. [Dupont, Catherine; Brenner, Carol A.] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA. [Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Brenner, CA (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, 275 E Hancock St, Detroit, MI 48201 USA. EM cbrenner@med.wayne.edu OI Armant, D. Randall/0000-0001-5904-9325 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health, DHHS [1R03HD046553, 1R21RR021881, RO1HD045966]; Reproductive Biology and Medicine Branch, NICHD FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS (1R03HD046553, 1R21RR021881, and RO1HD045966, and the Reproductive Biology and Medicine Branch, NICHD). NR 92 TC 65 Z9 73 U1 7 U2 32 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD SEP PY 2009 VL 27 IS 5 BP 351 EP 357 DI 10.1055/s-0029-1237423 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 489SW UT WOS:000269443800002 PM 19711245 ER PT J AU Grace, KS Sinclair, KD AF Grace, Kristen S. Sinclair, Kevin D. TI Assisted Reproductive Technology, Epigenetics, and Long-Term Health: A Developmental Time Bomb Still Ticking SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Artificial reproductive techniques; imprinting; embryogenesis; in vitro culture; prenatal development ID IN-VITRO CULTURE; ADVANCED UTERINE ENVIRONMENT; CELL NUCLEAR TRANSFER; DNA METHYLATION; EMBRYO CULTURE; GENE-EXPRESSION; FETAL-GROWTH; IMPRINTED GENES; PREIMPLANTATION EMBRYOS; MAMMALIAN DEVELOPMENT AB Live birthrates following assisted reproduction account for 1 to 3% of pregnancies in developed countries, and these figures seem set to rise. Concerns regarding the safe use of assisted reproductive technology (ART) for the treatment of infertility have been voiced for several years, yet, to date, the vast majority of children conceived using these techniques are apparently normal. Controversy surrounding reports of epigenetic alterations to genomic imprinting following human ART in recent years has fueled the ongoing debate. In contrast, both the incidence and severity of such anomalies are more apparent following ART in comparative animal species. The reasons for this are not known. By and large, the confounding effects of infertility and advanced maternal age do not apply to animal studies, which report better pregnancy rates following embryo transfer. Perhaps the incidence of imprinting disorders is increased when procedures such as ovarian stimulation, in vitro maturation, or both are used in conjunction with extended periods of embryo culture; this frequently occurs in animal but rarely in human ART. The focus of attention on imprinting, however, may have served to distract the scientific community from more Subtle epigenetic modifications to nonimprinted loci in gametes and the preimplantation embryo, with health-related consequences that do not manifest until adulthood. Accumulating evidence from animal studies indicates that such effects, not yet apparent in human subjects, exist; and this may ultimately transpire to be the true developmental legacy of human ART. This article discusses these issues in the context of epigenetic and developmental abnormalities following ART in animals. C1 [Sinclair, Kevin D.] Univ Nottingham, Sch Biosci, Ctr Reprod & Early Life, Loughborough LE12 5RD, Leics, England. [Grace, Kristen S.] Natl Inst Diabet Digest & Kidney Dis, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. RP Sinclair, KD (reprint author), Univ Nottingham, Sch Biosci, Ctr Reprod & Early Life, Sutton Bonington Campus, Loughborough LE12 5RD, Leics, England. EM kevin.Sinclair@nottingham.ac.uk OI Sinclair, Kevin/0000-0002-6375-215X NR 77 TC 63 Z9 65 U1 8 U2 27 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD SEP PY 2009 VL 27 IS 5 BP 409 EP 416 DI 10.1055/s-0029-1237429 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 489SW UT WOS:000269443800008 PM 19711251 ER PT J AU Owen, CM Segars, JH AF Owen, Carter M. Segars, James H., Jr. TI Imprinting Disorders and Assisted Reproductive Technology SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE Assisted reproductive technology; ART; imprinting disorders; nongenomic inheritance; loss of maternal methylation; DNA methylation; BWS; AS ID BECKWITH-WIEDEMANN-SYNDROME; IN-VITRO FERTILIZATION; SILVER-RUSSELL-SYNDROME; INTRACYTOPLASMIC SPERM INJECTION; ANGELMAN-SYNDROME; CHILDREN BORN; RETINOBLASTOMA; GENE; DEFECTS; RISK AB Worldwide use of assisted reproductive technology (ART) accounts for all estimated 1 to 3% of births. Since 2002, a series of reports have suggested all increased risk of imprinting disorders (Beckwith-Wiedemann syndrome and Angelman syndrome) in children conceived by ART. Definitive conclusions are difficult to substantiate due to the rarity of imprinting disorders and the variability in ART protocols. Despite these limitations, there is biological plausibility for alteration in nongenomic inheritance caused by ART. Animal studies have shown that ART procedures can alter normal imprinting, specifically DNA methylation patterns. Collectively, studies suggest an association between ART and loss of maternal methylation. More recent reports examined a possible association between ART and global hypomethylation of DNA. Three other imprinting disorders (Silver-Russell syndrome, maternal hypomethylation syndrome, and retinoblastoma) have also been implicated, but there is insufficient evidence to establish an association of these syndromes with ART. Based on current evidence, the absolute risk of imprinting disorders after ART remains small and does not warrant routine screening. Large prospective studies are needed to better understand the risks associated with imprinting disorders, imprinting defects, and ART. C1 [Owen, Carter M.; Segars, James H., Jr.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. [Owen, Carter M.] NIH, Clin Res Training Program, Ctr Clin, Bethesda, MD 20892 USA. RP Segars, JH (reprint author), Bldg 10,CRC,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov OI Owen, Carter Monique/0000-0002-5012-2706 FU National Institute of Child Health and Human Development; National Institutes of Health, Bethesda, Maryland; NIH; Pfizer, Inc FX Supported in part by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Carter Owen was supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer, Inc. via a grant to the Foundation for NIH from Pfizer, Inc. NR 59 TC 45 Z9 48 U1 0 U2 10 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD SEP PY 2009 VL 27 IS 5 BP 417 EP 428 DI 10.1055/s-0029-1237430 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 489SW UT WOS:000269443800009 PM 19711252 ER PT J AU Mabley, JG Pacher, P Murthy, KGK Williams, W Southan, GJ Salzman, AL Szabo, C AF Mabley, Jon G. Pacher, Pal Murthy, Kanneganti G. K. Williams, William Southan, Garry J. Salzman, Andrew L. Szabo, Csaba TI THE NOVEL INOSINE ANALOGUE INO-2002 EXERTS AN ANTI-INFLAMMATORY EFFECT IN A MURINE MODEL OF ACUTE LUNG INJURY SO SHOCK LA English DT Article DE Adenosine; cytokines; inflammation; inosine; lung; purine ID RESPIRATORY-DISTRESS-SYNDROME; LOW-DOSE STREPTOZOTOCIN; DIABETIC MOUSE MODELS; ADP-RIBOSE POLYMERASE; NITRIC-OXIDE; INFLAMMATORY CYTOKINES; PERSISTENT ELEVATION; REPERFUSION INJURY; IMPROVES SURVIVAL; ENDOTOXIC-SHOCK AB Endogenous purines, including inosine, have been shown to exert immunomodulatory and antiinflammatory effects in a variety of disease models. The dosage of inosine required for these effects has been shown to be between 200 and 600 mg kg(-1) because of the rapid metabolism of inosine in vivo. The aim of this study was to determine whether a metabolic resistant purine analog, [NO-2002, exerts anti-inflammatory effects in an animal model of acute respiratory distress syndrome. Mice challenged with intratracheal LIPS (50 mu g) were treated with INO-2002 (30 or 100 mg kg(-1), i.p.) in divided doses at either 1 and 12 h or at 5 and 16 h. After 24 h, bronchoalveolar lavage fluid was obtained to measure leukocyte infiltration by myeloperoxidase levels, lung edema by protein levels, and proinflammatory chemokine (macrophage inflammatory protein 1 alpha) and cytokine (TNF-alpha, IL-1, and IL-6) levels. INO-2002 (30 and 100 mg kg(-1)) reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by bronchoalveolar lavage fluid reduction in levels of myeloperoxidase and protein. INO-2002 also downregulated expression of the proinflammatory mediators macrophage inflammatory protein 1 alpha, TNF-alpha, IL-1, and IL-6. Delaying the start of treatment by 5 h after LPS administration affected the potency of INO-2002 protective effects, with 100 but not 30 mg kg(-1) having anti-inflammatory effects. The inosine analog INO-2002 largely suppressed LPS-induced inflammation in vivo at doses lower than those needed for the naturally occurring purine inosine. These data support the proposal that purine analogs, resistant to metabolic breakdown, may represent a useful addition to the therapy of acute respiratory distress syndrome. C1 [Mabley, Jon G.] Univ Brighton, Sch Pharm & Biomol Sci, Brighton BN2 4GJ, E Sussex, England. [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. [Murthy, Kanneganti G. K.; Williams, William; Southan, Garry J.; Salzman, Andrew L.] Inotek Pharmaceut Corp, Beverly, MA USA. [Szabo, Csaba] Univ Texas Med Branch, Dept Anesthesiol, Galveston, TX USA. RP Mabley, JG (reprint author), Univ Brighton, Sch Pharm & Biomol Sci, Cockcroft Bldg,Lewes Rd, Brighton BN2 4GJ, E Sussex, England. EM j.g.Mabley@brighton.ac.uk RI Mabley, Jon/D-2296-2010; Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU National Institutes of Health [RO1GM60915] FX This study was supported, in part. by the NR 38 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD SEP PY 2009 VL 32 IS 3 BP 258 EP 262 DI 10.1097/SHK.0b013e31819c3414 PG 5 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 486UU UT WOS:000269226000005 PM 19174745 ER PT J AU Maas, MB Furie, KL Lev, MH Ay, H Singhal, AB Greer, DM Harris, GJ Halpern, E Koroshetz, WJ Smith, WS AF Maas, Matthew B. Furie, Karen L. Lev, Michael H. Ay, Hakan Singhal, Aneesh B. Greer, David M. Harris, Gordon J. Halpern, Elkan Koroshetz, Walter J. Smith, Wade S. TI National Institutes of Health Stroke Scale Score Is Poorly Predictive of Proximal Occlusion in Acute Cerebral Ischemia SO STROKE LA English DT Article DE acute stroke; angiography; CT; scales ID DIFFUSION-WEIGHTED MRI; HYPERACUTE STROKE; NIHSS SCORE; TIME WINDOW; THROMBOLYSIS; PERFUSION; THERAPY; MANAGEMENT; PATIENT; BRAIN AB Background and Purpose-Multimodal imaging is gaining an important role in acute stroke. The benefit of obtaining additional clinically relevant information must be weighed against the detriment of increased cost, delaying time to treatment, and adverse events such as contrast-induced nephropathy. Use of National Institutes of Health Stroke Scale (NIHSS) score to predict a proximal arterial occlusion (PO) is suggested by several case series as a viable method of selecting cases appropriate for multimodal imaging. Methods-Six hundred ninety-nine patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke were dichotomized according to the presence of a PO, including a subgroup of 177 subjects with middle cerebral artery M1 occlusion. Results-The median NIHSS score of patients found to have a PO was higher than the overall median (9 versus 5, P < 0.0001). The median NIHSS score of patients with middle cerebral artery M1 occlusion was 14. NIHSS score >= 10 had 81% positive predictive value for PO but only 48% sensitivity with the majority of subjects with PO presenting with lower NIHSS scores. All patients with NIHSS score >= 2 would need to undergo angiographic imaging to detect 90% of PO. Conclusions-High NIHSS score correlates with the presence of a proximal arterial occlusion in patients presenting with acute cerebral ischemia. No NIHSS score threshold can be applied to select a subgroup of patients for angiographic imaging without failing to capture the majority of cases with clinically important occlusive lesions. The finding of minimal clinical deficits should not deter urgent angiographic imaging in otherwise appropriate patients suspected of acute stroke. (Stroke. 2009;40:2988-2993.) C1 [Maas, Matthew B.; Furie, Karen L.; Singhal, Aneesh B.; Greer, David M.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Maas, MB (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM mmaas@partners.org FU Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; National Institutes of Health [P50NS051343] FX Supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392. M. B. M. is supported by National Institutes of Health grant P50NS051343. NR 20 TC 55 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 2988 EP 2993 DI 10.1161/STROKEAHA.109.555664 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300010 PM 19608992 ER PT J AU Maas, MB Lev, MH Ay, H Singhal, AB Greer, DM Smith, WS Harris, GJ Halpern, E Kemmling, A Koroshetz, WJ Furie, KL AF Maas, Matthew B. Lev, Michael H. Ay, Hakan Singhal, Aneesh B. Greer, David M. Smith, Wade S. Harris, Gordon J. Halpern, Elkan Kemmling, Andre Koroshetz, Walter J. Furie, Karen L. TI Collateral Vessels on CT Angiography Predict Outcome in Acute Ischemic Stroke SO STROKE LA English DT Article DE acute stroke; angiography; collateral; outcomes ID SOURCE IMAGES; BLOOD-FLOW; INFARCT; BRAIN; TIME; MRI AB Background and Purpose-Despite the abundance of emerging multimodal imaging techniques in the field of stroke, there is a paucity of data demonstrating a strong correlation between imaging findings and clinical outcome. This study explored how proximal arterial occlusions alter flow in collateral vessels and whether occlusion or extent of collaterals correlates with prehospital symptoms of fluctuation and worsening since onset or predict in-hospital worsening. Methods-Among 741 patients enrolled in a prospective cohort study involving CT angiographic imaging in acute stroke, 134 cases with proximal middle cerebral artery occlusion and 235 control subjects with no occlusions were identified. CT angiography was used to identify occlusions and grade the extent of collateral vessels in the sylvian fissure and leptomeningeal convexity. History of symptom fluctuation or progressive worsening was obtained on admission. Results-Prehospital symptoms were unrelated to occlusion or collateral status. In cases, 37.5% imaged within 1 hour were found to have diminished collaterals versus 12.1% imaged at 12 to 24 hours (P=0.047). No difference in worsening was seen between cases and control subjects with adequate collaterals, but cases with diminished sylvian and leptomeningeal collaterals experienced greater risk of worsening compared with control subjects measured either by admission to discharge National Institutes of Health Stroke Scale increase >= 1 (55.6% versus 16.6%, P=0.001) or >= 4 (44.4% versus 6.4%, P=0.001). Conclusion-Most patients with proximal middle cerebral artery occlusion rapidly recruit sufficient collaterals and follow a clinical course similar to patients with no occlusions, but a subset with diminished collaterals is at high risk for worsening. (Stroke. 2009;40:3001-3005.) C1 [Maas, Matthew B.; Singhal, Aneesh B.; Greer, David M.; Furie, Karen L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lev, Michael H.; Ay, Hakan; Harris, Gordon J.; Halpern, Elkan; Kemmling, Andre] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Koroshetz, Walter J.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Maas, MB (reprint author), 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM mmaas@partners.org FU Agency for Healthcare Research and Quality [R01 HS11392]; National Institutes of Health [P50NS051343] FX Supported by Agency for Healthcare Research and Quality grant AHRQ R01 HS11392. M. B. M. supported by National Institutes of Health grant P50NS051343. NR 14 TC 110 Z9 117 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP 3001 EP 3005 DI 10.1161/STROKEAHA.109.552513 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300012 PM 19590055 ER PT J AU Masdeu, JC Wolfson, L AF Masdeu, Joseph C. Wolfson, Leslie TI White Matter Lesions Predispose to Falls in Older People SO STROKE LA English DT Letter C1 [Masdeu, Joseph C.] NIH, Bethesda, MD 20892 USA. [Wolfson, Leslie] Univ Connecticut, Ctr Hlth, Dept Neurol, Framingham, MA USA. RP Masdeu, JC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2009 VL 40 IS 9 BP E546 EP E546 DI 10.1161/STROKEAHA.109.558122 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 487BB UT WOS:000269244300053 PM 19628802 ER PT J AU Shi, YB AF Shi, Yun-Bo TI Dual Functions of Thyroid Hormone Receptors in Vertebrate Development: The Roles of Histone-Modifying Cofactor Complexes SO THYROID LA English DT Review ID XENOPUS-LAEVIS METAMORPHOSIS; RETINOIC ACID RECEPTORS; ACTION IN-VIVO; BETA-A GENE; AMPHIBIAN METAMORPHOSIS; EMBRYONIC-DEVELOPMENT; POSTEMBRYONIC DEVELOPMENT; COREPRESSOR COMPLEX; TRANSCRIPTIONAL REPRESSION; PROTEIN METHYLTRANSFERASE AB Thyroid hormone (TH) receptor (TR) plays critical roles in vertebrate development. Transcription studies have shown that TR activates or represses TH-inducible genes by recruiting coactivators or corepressors in the presence or absence of TH, respectively. However, the developmental roles of these TR cofactors remain largely unexplored. Frog metamorphosis is totally dependent on TH and mimics the postembryonic period in mammalian development during which TH levels are also high. We have previously proposed a dual function model for TR in the development of the anuran Xenopus laevis. That is, unliganded TR recruits corepressors to TH-inducible genes in premetamorphic tadpoles to repress these genes and prevent premature metamorphic changes and subsequently, when TH becomes available, liganded TR recruits coactivators to activate these same genes, leading to metamorphosis. Over the years, we and others have used molecular and genetic approaches to demonstrate the importance of the dual functions of TR in Xenopus laevis. In particular, unliganded TR has been shown to recruit histone deacetylase-containing corepressor complexes in premetamorphic tadpoles to control metamorphic timing. In contrast, metamorphosis requires TH-bound TR to recruit coactivator complexes containing histone acetyltransferases and methyltransferases to activate transcription. Furthermore, the concentrations of coactivators appear to regulate the rate of metamorphic progression. Studies in mammals also suggest that the dual function model for TR is conserved across vertebrates. C1 NICHHD, Lab Gene Regulat & Dev, Program Cell Regulat & Dev,PCRM, Sect Mol Morphogenesis,NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, Program Cell Regulat & Dev,PCRM, Sect Mol Morphogenesis,NIH, Bldg 18 T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU Intramural Research Program of National Institute of Child Health and Human Development; National Institutes of Health FX I would like to thank Dr. D. Buchholz and current members inmylaboratory for comments on the manuscript. The work in the author's laboratory has been supported by the Intramural Research Program of National Institute of Child Health and Human Development, National Institutes of Health. NR 112 TC 41 Z9 41 U1 1 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD SEP PY 2009 VL 19 IS 9 BP 987 EP 999 DI 10.1089/thy.2009.0041 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491KP UT WOS:000269577900011 PM 19678741 ER PT J AU Cohen, SM Storer, RD Criswell, KA Doerrer, NG Dellarco, VL Pegg, DG Wojcinski, ZW Malarkey, DE Jacobs, AC Klaunig, JE Swenberg, JA Cook, JC AF Cohen, Samuel M. Storer, Richard D. Criswell, Kay A. Doerrer, Nancy G. Dellarco, Vicki L. Pegg, David G. Wojcinski, Zbigniew W. Malarkey, David E. Jacobs, Abigail C. Klaunig, James E. Swenberg, James A. Cook, Jon C. TI Hemangiosarcoma in Rodents: Mode-of-Action Evaluation and Human Relevance SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT International Workshop on Hemangiosarcoma in Rodents - Mode-of-Action Evaluation and Human Relevance CY DEC 04-05, 2008 CL Arlington, VA SP ILSI, Hlth & Environm Sci Inst DE hemangiosarcoma; angiogenesis; endothelial cells; endothelial precursor cells; mode of action; human relevance; PPAR agonists ID ACTIVATED-RECEPTOR-GAMMA; ENDOTHELIAL PROGENITOR CELLS; ERUPTIVE CHERRY ANGIOMAS; ADIPOSE-TISSUE MASS; GROWTH-FACTOR; DIFFERENTIAL EXPRESSION; CANINE HEMANGIOSARCOMA; CHUVASH POLYCYTHEMIA; UNCOUPLING PROTEIN; VASCULAR TUMORS AB Although rarely occurring in humans, hemangiosarcomas (HS) have become important in evaluating the potential human risk of several chemicals, including industrial, agricultural, and pharmaceutical agents. Spontaneous HS arise frequently in mice, less commonly in rats, and frequently in numerous breeds of dogs. This review explores knowledge gaps and uncertainties related to the mode of action (MOA) for the induction of HS in rodents, and evaluates the potential relevance for human risk. For genotoxic chemicals (vinyl chloride and thorotrast), significant information is available concerning the MOA. In contrast, numerous chemicals produce HS in rodents by nongenotoxic, proliferative mechanisms. An overall framework is presented, including direct and indirect actions on endothelial cells, paracrine effects in local tissues, activation of bone marrow endothelial precursor cells, and tissue hypoxia. Numerous obstacles are identified in investigations into the MOA for mouse HS and the relevance of the mouse tumors to humans, including lack of identifiable precursor lesions, usually late occurrence of the tumors, and complexities of endothelial biology. This review proposes a working MOA for HS induced by nongenotoxic compounds that can guide future research in this area. Importantly, a common MOA appears to exist for the nongenotoxic induction of HS, where there appears to be a convergence of multiple initiating events (e.g., hemolysis, decreased respiration, adipocyte growth) leading to either dysregulated angiogenesis and/or erythropoiesis that results from hypoxia and macrophage activation. These later events lead to the release of angiogenic growth factors and cytokines that stimulate endothelial cell proliferation, which, if sustained, provide the milieu that can lead to HS formation. C1 [Doerrer, Nancy G.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. [Cohen, Samuel M.] Univ Nebraska Med Ctr, Omaha, NE 68198 USA. [Storer, Richard D.] Merck Res Labs, West Point, PA 19486 USA. [Criswell, Kay A.; Cook, Jon C.] Pfizer Inc, Groton, CT 06340 USA. [Dellarco, Vicki L.] US EPA, Washington, DC 20460 USA. [Malarkey, David E.] Michigan Technol & Res Inst, Ann Arbor, MI 48104 USA. [Wojcinski, Zbigniew W.] Fulcrum Pharma Dev Inc, Ann Arbor, MI 48103 USA. [Malarkey, David E.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Jacobs, Abigail C.] US FDA, Silver Spring, MD 20993 USA. [Klaunig, James E.] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. [Swenberg, James A.] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM ndoerrer@hesiglobal.org NR 99 TC 39 Z9 41 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 4 EP 18 DI 10.1093/toxsci/kfp131 PG 15 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200002 PM 19525443 ER PT J AU Yanagiba, Y Ito, Y Kamijima, M Gonzalez, FJ Nakajima, T AF Yanagiba, Yukie Ito, Yuki Kamijima, Michihiro Gonzalez, Frank J. Nakajima, Tamie TI Octachlorostyrene Induces Cytochrome P450, UDP-glucuronosyltransferase, and Sulfotransferase via the Aryl Hydrocarbon Receptor and Constitutive Androstane Receptor SO TOXICOLOGICAL SCIENCES LA English DT Article DE aryl hydrocarbon receptor; constitutive androstendione receptor; octachlorostyrene ID PREGNANE-X RECEPTOR; ORGANOCHLORINE PESTICIDES; INDUCTION; RAT; METABOLISM; SAMPLES; GENES; LIVER; CAR; XENOBIOTICS AB Octachlorostyrene (OCS) is a byproduct produced in the process of synthesis of chlorinated compounds. There are some reports concerning environmental contamination by OCS, but few on the toxicological effects on human. Drug-metabolizing enzymes may play an important role in toxicity through metabolic activation or deactivation of OCS. In this study, we investigated whether OCS influences these enzymes using wild-type and aryl hydrocarbon receptor (Ahr)-null mice; AhR regulates cytochrome P450 (CYP) 1A, UDP-glucuronosyltransferase (UGT), or sulfotransferase (SULT). Both mouse lines were treated with OCS (0, 32, and 64 mu mol/kg) for 4 days by gavage. As a reference, the mice were treated with 20 mg/kg 3-methylcholanthrene (3MC) for 4 days. OCS treatment increased the expression of CYP 1A1 and CYP1A2 mRNA and ethoxyresorfin O-deethylase activity only in the wild-type mice, similar to that of the AhR activator 3MC. OCS treatment increased expression of UGT1A6 and SULT 1A1 mRNA and their associated enzyme activities only in Ahr-null mice, whereas 3MC still influenced these enzymes only in wild-type mice. OCS induced constitutive androstane receptor (CAR) only in Ahr-null mice, and the target gene CYP2B10 mRNA was induced more strongly in Ahr-null mice than in wild-type mice. 3MC slightly induced CYP2B10 mRNA only in the wild-type mice. These results suggest that CAR is involved in regulation of the UGT and SULT genes by OCS. Thus, OCS may regulate CYP1A via AhR, whereas it controls UGT1A6 and SULT1A via CAR. C1 [Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, Nagoya, Aichi 4668550, Japan. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Nakajima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM tnasu23@med.nagoya-u.ac.jp RI Ito, Yuki/C-3698-2008 FU Japan Society for the Promotion of Science [B 14370121, 17390169, 20390171] FX Grants-in Aid for Scientific Research (B 14370121, 17390169, and 20390171) from the Japan Society for the Promotion of Science. NR 27 TC 11 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 19 EP 26 DI 10.1093/toxsci/kfp130 PG 8 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200003 PM 19525444 ER PT J AU Gopee, NV Roberts, DW Webb, P Cozart, CR Siitonen, PH Latendresse, JR Warbitton, AR Yu, WW Colvin, VL Walker, NJ Howard, PC AF Gopee, Neera V. Roberts, Dean W. Webb, Peggy Cozart, Christy R. Siitonen, Paul H. Latendresse, John R. Warbitton, Alan R. Yu, William W. Colvin, Vicki L. Walker, Nigel J. Howard, Paul C. TI Quantitative Determination of Skin Penetration of PEG-Coated CdSe Quantum Dots in Dermabraded but not Intact SKH-1 Hairless Mouse Skin SO TOXICOLOGICAL SCIENCES LA English DT Article DE quantum dots; nanoscale materials; dermabrasion ID SILVER NANOPARTICLES; MURINE MODEL; RAT SKIN; PROTEIN; FULLERENES; NANOTECHNOLOGY; NANOMATERIALS; PARTICLES; STABILITY; EXPOSURE AB Many cosmetics, sunscreens, and other consumer products are reported to contain nanoscale materials. The possible transdermal absorption of nanoscale materials and the long-term consequences of the absorption have not been determined. We used polyethylene glycol coated cadmium selenide (CdSe) core quantum dots (QD; 37 nm diameter) to evaluate the penetration of nanoscale material into intact, tape stripped, acetone treated, or dermabraded mouse skin. QD were suspended in an oil-in-water emulsion (approximately 9 mu M) and the emulsion was applied at 2 mg/cm(2) to mouse dorsal skin pretreated as follows: intact; tape stripped to remove the stratum corneum; acetone pretreated; dermabraded to remove stratum corneum and epidermis. QD penetration into the skin was monitored in sentinel organs (liver and regional draining lymph nodes) using inductively coupled plasma mass spectrometry analysis of cadmium (from the CdSe QD). No consistent cadmium elevation was detected in the sentinel organs of mice with intact, acetone pretreated, or tape-stripped skin at 24- and 48-h post-QD application; however, in dermabraded mice, cadmium elevations were detected in the lymph nodes and liver. QD accumulation (as cadmium) in the liver was approximately 2.0% of the applied dose. The passing of QD through the dermabraded skin was confirmed using confocal fluorescence microscopy. These results suggest that transdermal absorption of nanoscale materials depends on skin barrier quality, and that the lack of an epidermis provided access to QD penetration. Future dermal risk assessments of nanoscale materials should consider key barrier aspects of skin and its overall physiologic integrity. C1 [Howard, Paul C.] US FDA, Div Biochem Toxicol, Natl Toxicol Program, Ctr Phototoxicol,Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Latendresse, John R.; Warbitton, Alan R.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Yu, William W.; Colvin, Vicki L.] Rice Univ, Ctr Biol & Environm Nanotechnol, Houston, TX 77005 USA. [Walker, Nigel J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Howard, PC (reprint author), US FDA, Div Biochem Toxicol, Natl Toxicol Program, Ctr Phototoxicol,Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 110, Jefferson, AR 72079 USA. EM Paul.Howard@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU U. S. Food & Drug Administration [IAG 224-93-001]; National Institute of Environmental Health Sciences (NIEHS); National Institutes of Health (NIH) [2 P20 RR 16460]; Intramural Research Program of the NIEHS/NIH; NIH/NCRR [1 S10 RR 19395]; LSM [510] FX Interagency agreement (IAG 224-93-001) between the U. S. Food & Drug Administration and the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), and in part by the Intramural Research Program of the NIEHS/NIH; and University of Arkansas for Medical Sciences Digital and Confocal Microscopy Laboratory supported by NIH Grant (2 P20 RR 16460) (L. Cornett, PI, INBRE, Partnerships for Biomedical Research in Arkansas) and NIH/NCRR Grant (1 S10 RR 19395) (R. Kurten, PI, "Zeiss LSM 510 META Confocal Microscope System''). NR 56 TC 58 Z9 59 U1 3 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 37 EP 48 DI 10.1093/toxsci/kfp139 PG 12 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200005 PM 19574408 ER PT J AU Zuo, PJ Qu, W Cooper, RN Goyer, RA Diwan, BA Waalkes, MP AF Zuo, Peijun Qu, Wei Cooper, Ryan N. Goyer, Robert A. Diwan, Bhalchandra A. Waalkes, Michael P. TI Potential Role of alpha-Synuclein and Metallothionein in Lead-Induced Inclusion Body Formation SO TOXICOLOGICAL SCIENCES LA English DT Article DE lead; inclusion bodies; alpha-synuclein; metallothionein; MT-null ID PARKINSONS-DISEASE; EXPOSURE; PROTEIN; SENSITIVITY; TOXICITY; BODIES; HYPOTHESIS; CADMIUM; CELLS; MICE AB Lead (Pb) produces aggresome-like inclusion bodies (IBs) in target cells as a toxic response. Our prior work shows metallothionein (MT) is required for this process. We used MT-I/II double knockout (MT-null) and parental wild-type (WT) cell lines to further explore the formation process of Pb-induced IBs. Unlike WT cells, MT-null cells did not form IBs after Pb exposure. Western blot of cytosol showed soluble MT protein in WT cells was lost during Pb exposure as IBs formed. Transfection of MT-I into MT-null cells allowed IBs formation after Pb exposure. Considering Pb-induced IBs may be like disease-related aggresomes, which often contain alpha-synuclein (Scna), we investigated Scna expression in cells capable (WT) and incapable (MT-null) of producing IBs after Pb exposure. Scna protein showed poor basal expression in MT-null cells. Pb exposure increased Scna expression only in WT cells. MT transfection increased Scna transcript to WT levels. In WT or MT-transfected MT-null cells, Pb-induced Scna expression rapidly increased and then decreased over 48 h as Pb-induced IBs were formed. A direct interaction between Scna and MT was confirmed ex vivo by antibody pulldown assay where the proteins coprecipitated with an antibody to MT. Pb exposure caused increased colocalization of MT and Scna proteins with time only in WT cells. In WT mice after chronic Pb exposure Scna was localized in renal cells containing forming IBs, whereas MT-null mice did not form IBs. Thus, Scna could be component of Pb-induced IBs and, with MT, may play a role in IBs formation. C1 [Zuo, Peijun; Qu, Wei; Cooper, Ryan N.; Goyer, Robert A.; Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Diwan, Bhalchandra A.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU National Cancer Institute; National Institutes of Health [NO1-CO-12400] FX Federal funds from the National Cancer Institute, National Institutes of Health, under contract (NO1-CO-12400). NR 29 TC 14 Z9 14 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2009 VL 111 IS 1 BP 100 EP 108 DI 10.1093/toxsci/kfp132 PG 9 WC Toxicology SC Toxicology GA 483WM UT WOS:000269002200011 PM 19542206 ER PT J AU Wehbe, RM Yau, Y Wesley, R Bolan, CD Leitman, SF AF Wehbe, R. M. Yau, Y. Wesley, R. Bolan, C. D. Leitman, S. F. TI Risk of Total Joint Arthroplasty in Patients with C282Y-Homozygous Hemochromatosis SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Wehbe, R. M.; Yau, Y.; Leitman, S. F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Bolan, C. D.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wesley, R.] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM wehber@mail.cc.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 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 SEP PY 2009 VL 49 BP 14A EP 14A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200036 ER PT J AU Schmid, P von Zabern, I Scharberg, EA Wagner, FF Flegel, WA AF Schmid, P. von Zabern, I. Scharberg, E. A. Wagner, F. F. Flegel, W. A. TI Amino Acid Substitutions Encoding JAL (RH48) and JAHK (RH53) Do Not Induce Expression of these Antigens by RhD SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Schmid, P.] Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany. [von Zabern, I.] German Red Cross DRK, Blood Donor Serv Baden Wurttemberg Hessen, Ulm, Germany. [Scharberg, E. A.] German Red Cross DRK, Blood Donor Serv Baden Wurttemberg Hessen, Baden Baden, Germany. [Wagner, F. F.] German Red Cross DRK, Blood Donor Serv NSTOB, Springe, Germany. [Flegel, W. A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM schmidp@cc.nih.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 16A EP 16A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200041 ER PT J AU Cable, RG Glynn, SA Gottschall, JL Kiss, JE Mast, AE Murphy, EL Simon, TL Sacher, RA Fang, J Wright, DJ AF Cable, R. G. Glynn, S. A. Gottschall, J. L. Kiss, J. E. Mast, A. E. Murphy, E. L. Simon, T. L. Sacher, R. A. Fang, J. Wright, D. J. TI Predicting Iron Deficiency in Blood Donors SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Cable, R. G.] Amer Red Cross, Blood Serv, Northeast Div, Farmington, CT 20892 USA. [Glynn, S. A.] NHLBI, Bethesda, MD 20850 USA. [Simon, T. L.; Fang, J.; Wright, D. J.] WESTAT Corp, Rockville, MD 53233 USA. [Gottschall, J. L.; Mast, A. E.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI USA. [Kiss, J. E.] LifeSource, Inst Transfus Med, Pittsburgh, PA USA. [Murphy, E. L.] Blood Ctr Pacific, San Francisco, CA USA. [Sacher, R. A.] Univ Cincinnati, Acad Hlth Ctr, Hoxworth Blood Ctr, Cincinnati, OH USA. EM cabler@usa.redcross.org 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 40A EP 41A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200104 ER PT J AU Cable, RG Mast, AE Glynn, SA Gottschall, JL Kiss, JE Lee, T Busch, MP Murphy, EL Sacher, RA Carrick, DM Wright, DJ AF Cable, R. G. Mast, A. E. Glynn, S. A. Gottschall, J. L. Kiss, J. E. Lee, T. Busch, M. P. Murphy, E. L. Sacher, R. A. Carrick, D. M. Wright, D. J. TI Human Transferrin G277S Polymorphism is Not a Useful Predictor of Blood Donor Iron Deficiency SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Cable, R. G.] Blood Serv, Amer Red Cross, Northeast Div, Farmington, CT USA. [Carrick, D. M.; Wright, D. J.] WESTAT Corp, Rockville, MD 20850 USA. [Glynn, S. A.] NHLBI, Bethesda, MD 20892 USA. [Mast, A. E.; Gottschall, J. L.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA. [Kiss, J. E.] LifeSource Blood Serv, Inst Transfus Med, Pittsburgh, PA USA. [Lee, T.; Busch, M. P.; Murphy, E. L.] Blood Syst Res Inst, San Francisco, CA USA. [Sacher, R. A.] Univ Cincinnati, Acad Hlth Ctr, Hoxworth Blood Ctr, Cincinnati, OH USA. EM cabler@usa.redcross.org NR 0 TC 0 Z9 0 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 SEP PY 2009 VL 49 BP 41A EP 41A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200107 ER PT J AU Norris, PJ Glynn, SA Todd, DS Likos, AM Heitman, JW Collins, CS Linnen, JM Busch, MP AF Norris, P. J. Glynn, S. A. Todd, D. S. Likos, A. M. Heitman, J. W. Collins, C. S. Linnen, J. M. Busch, M. P. TI Assessment for Influenza A Virus in Blood Donors SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Norris, P. J.; Heitman, J. W.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Norris, P. J.; Busch, M. P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Glynn, S. A.] NHLBI, Bethesda, MD 20892 USA. [Todd, D. S.] Westat Corp, Rockville, MD USA. [Likos, A. M.] Ctr Dis Control & Prevent, DVRD, NCID, Atlanta, GA USA. [Collins, C. S.; Linnen, J. M.] Gen Probe Inc, San Diego, CA USA. EM pnorris@bloodsystems.org NR 0 TC 0 Z9 0 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 SEP PY 2009 VL 49 BP 43A EP 43A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200108 ER PT J AU Bryant, BJ Wehbe, RM Yau, Y Arceo, SM Hopkins, JA Leitman, SF AF Bryant, B. J. Wehbe, R. M. Yau, Y. Arceo, S. M. Hopkins, J. A. Leitman, S. F. TI Effect of Body Position on Donor Deferral Rates Due to Low Fingerstick Hemoglobin SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Bryant, B. J.] Univ Texas Med Branch, Blood Bank, Galveston, TX USA. [Wehbe, R. M.; Yau, Y.; Arceo, S. M.; Hopkins, J. A.; Leitman, S. F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. EM bbryant@utmb.edu 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 60A EP 60A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200150 ER PT J AU Leitman, SF Yau, Y Belak, M Matthews, C Min, K AF Leitman, S. F. Yau, Y. Belak, M. Matthews, C. Min, K. TI Unstimulated Mononuclear Cell Collection in Healthy Donors: Comparison of Two Continuous-Flow Apheresis Devices SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Leitman, S. F.; Yau, Y.; Belak, M.; Matthews, C.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Min, K.] Fenwal Inc, Lake Zurich, IL USA. EM sleitman@nih.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 77A EP 78A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200196 ER PT J AU Rosiello, K Johnson, S Clibourn, D Klein, HG AF Rosiello, K. Johnson, S. Clibourn, D. Klein, H. G. TI Spray Dried Plasma: An Alternative to Fresh Frozen Plasma SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Rosiello, K.; Johnson, S.; Clibourn, D.] Velico Med, Beverly, MA USA. [Klein, H. G.] NIH, Bethesda, MD 20892 USA. EM keithr@krossengineering.com 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 80A EP 80A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200203 ER PT J AU Daniel-Johnson, JA Sheldon, S Lee-Stroka, H Tran, MT Quillen, K AF Daniel-Johnson, J. A. Sheldon, S. Lee-Stroka, H. Tran, M. T. Quillen, K. TI Universal Platelet Screening for High-Titer Anti-A and Anti-B in a Hospital-Based Donor Center Detects a Significant Prevalence of High Titer Group O and A Units SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Daniel-Johnson, J. A.; Sheldon, S.; Lee-Stroka, H.; Tran, M. T.] NIH, Bethesda, MD 20892 USA. [Quillen, K.] Boston Univ, Med Ctr, Boston, MA USA. EM danieljohnsonj@cc.nih.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 116A EP 116A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200293 ER PT J AU Sheldon, S Lee-Stroka, H Tran, MT Quillen, K AF Sheldon, S. Lee-Stroka, H. Tran, M. T. Quillen, K. TI A Simple Screening Procedure to Reduce the Risk of Hemolysis from Minor ABO-Incompatible Apheresis Platelets SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Sheldon, S.; Lee-Stroka, H.; Tran, M. T.; Quillen, K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. EM ssheldon@cc.nih.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 116A EP 117A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200294 ER PT J AU von Zabern, I Wagner, FF Hanna, D Moulds, JM Flegel, WA AF von Zabern, I. Wagner, F. F. Hanna, D. Moulds, J. M. Flegel, W. A. TI Clinical Relevance of D category IV Comprising Phylogenetically Heterogeneous Alleles SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [von Zabern, I.] Inst Clin Transfus Med & Immunogenet Ulm, Ulm, Germany. [Wagner, F. F.] German Red Cross DRK Blood Donor Serv NSTOB, Springe, Germany. [Hanna, D.; Moulds, J. M.] LifeShare Blood Ctr, Shreveport, LA USA. [Flegel, W. A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. EM ingeborg.von-zabern@uni-ulm.de NR 0 TC 1 Z9 1 U1 0 U2 0 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 SEP PY 2009 VL 49 BP 119A EP 119A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200301 ER PT J AU Khuu, HM Chen, P Frodigh, S Procter, JL Childs, R Stroncek, DF AF Khuu, H. M. Chen, P. Frodigh, S. Procter, J. L. Childs, R. Stroncek, D. F. TI Natural Killer Cell Culture Loss Due to Incubator Failure SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Khuu, H. M.; Chen, P.; Frodigh, S.; Procter, J. L.; Stroncek, D. F.] NIH, Bethesda, MD 20892 USA. [Childs, R.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA. EM hkhuu@mail.cc.nih.gov 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 180A EP 180A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200471 ER PT J AU Kleinman, SH Endres, RO Carrick, DM Steele, WR Wright, DJ Norris, PJ Busch, MP Glynn, SA Kakaiya, R Triulzi, DJ AF Kleinman, S. H. Endres, R. O. Carrick, D. M. Steele, W. R. Wright, D. J. Norris, P. J. Busch, M. P. Glynn, S. A. Kakaiya, R. Triulzi, D. J. TI Correlation of HLA Antibody Detected by Single-Antigen and Multiple-Antigen Bead Assays SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Endres, R. O.] Blood Syst Lab, HLA Lab, Tempe, AZ USA. [Kleinman, S. H.; Carrick, D. M.; Steele, W. R.; Wright, D. J.] Westat Corp, Rockville, MD USA. [Kakaiya, R.; Triulzi, D. J.] Inst Transfus Med, Pittsburgh, PA USA. [Glynn, S. A.] NHLBI, DBDR TMCT, Bethesda, MD 20892 USA. [Kleinman, S. H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Norris, P. J.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Norris, P. J.; Busch, M. P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kakaiya, R.] LifeSource Blood Svcs, Glenview IL, San Francisco, CA USA. EM skleinman@shaw.ca 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 190A EP 190A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200499 ER PT J AU Hassell, PJ Minchinton, RM Stroncek, DF Schuller, RM Fung, Y AF Hassell, P. J. Minchinton, R. M. Stroncek, D. F. Schuller, R. M. Fung, Y. TI Anti-HNA-2a Antibodies Implicated in TRALI and ANN Demonstrate Serological Variability and Different Epitope Preferences SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Hassell, P. J.; Minchinton, R. M.; Fung, Y.] Australian Red Cross Blood Serv, Brisbane, Qld, Australia. [Stroncek, D. F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Schuller, R. M.] Amer Red Cross, Midamer Blood Serv Div, Neutrophil & Platelet Immunol Lab, St Paul, MN USA. EM phassell@arcbs.redcross.org.au RI Fung, Yoke Lin/F-2778-2010 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 198A EP 198A PG 1 WC Hematology SC Hematology GA 490XU UT WOS:000269542200521 ER PT J AU Kassalow, N Wood, D Gee, AP McKenna, DH Kadidlo, D Whiteside, TL Griffin, DL Mondoro, TH Wagner, EL Reed, W AF Kassalow, N. Wood, D. Gee, A. P. McKenna, D. H. Kadidlo, D. Whiteside, T. L. Griffin, D. L. Mondoro, T. H. Wagner, E. L. Reed, W. TI Educational Program for Cell Therapy: A Review of Efforts Sponsored by the Production Assistance for Cellular Therapies (PACT) Group SO TRANSFUSION LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-of-Blood-Banks CY OCT 24-27, 2009 CL New Orleans, LA SP Amer Assoc Blood Banks C1 [Kassalow, N.; Wood, D.] EMMES Corp, Rockville, MD USA. [Gee, A. P.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [McKenna, D. H.; Kadidlo, D.] Univ Minnesota, Mol & Cellular Therapeut Facil, St Paul, MN 55108 USA. [Whiteside, T. L.; Griffin, D. L.] Univ Pittsburgh, Pittsburgh, PA USA. [Mondoro, T. H.; Wagner, E. L.] NHLBI, Bethesda, MD 20892 USA. [Reed, W.] Amer Red Cross, Oakland, CA USA. EM nkassalow@emmes.com 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 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2009 VL 49 BP 274A EP 275A PG 2 WC Hematology SC Hematology GA 490XU UT WOS:000269542200720 ER PT J AU Bugert, P Scharberg, EA Geisen, C von Zabern, I Flegel, WA AF Bugert, Peter Scharberg, Erwin A. Geisen, Christof von Zabern, Inge Flegel, Willy A. TI RhCE protein variants in Southwestern Germany detected by serologic routine testing SO TRANSFUSION LA English DT Article ID MOLECULAR-BASIS; TRANSFUSION SAFETY; BLACK INDIVIDUALS; ANTIGEN RH48; AMINO-ACIDS; RHD GENE; EXPRESSION; ALLELE; PHENOTYPES; JAL AB BACKGROUND: Variant RHCE alleles with diminished expression of C, c, E, and e antigens have been described and indicate the genetic diversity of this gene locus in several populations. In this study the molecular background of variant RhCE antigens identified by standard serologic routine testing in German blood donors and patients was determined. STUDY DESIGN AND METHODS: Samples from blood donors and patients were routinely analyzed for RhCE phenotype using the PK7200 analyzer with two sets of monoclonal anti-C, -c, -E, and -e reagents. Samples with confirmed variant RhCE antigens were analyzed by nucleotide sequencing of the 10 RHCE exons. A multiplex polymerase chain reaction with sequence-specific priming (PCR-SSP) method was established for rapid typing of the rare RHCE alleles. RESULTS: We identified 43 samples with serologic RhCE variants. Molecular analysis revealed variant RHCE alleles in 34 samples. Altogether 22 RHCE alleles were detected; 10 have not been published before. Twenty alleles harbored distinct single-nucleotide substitutions, 18 of which encoded amino acid changes and 2 of which occurred in noncoding regions. Two samples represented RHCE-D-CE hybrid alleles involving different segments of the RHCE Exon 5. A multiplex PCR-SSP screening for 17 RHCE alleles was negative in 1344 samples of the DNA bank GerBS. The cumulative phenotype frequency was estimated between 1 in 488 (0.20%) and 1 in 8449 (0.012%). CONCLUSION: Single-amino-acid substitutions were the molecular basis for variant RhCE antigen expression in most samples. Nucleotide substitutions in RHCE exons were excluded as possible mechanism of diminished RhCE antigen expression in one-fifth of the serologically identified samples. C1 German Red Cross Blood Donor Serv, Baden Wurttemberg Hessen, Germany. Univ Heidelberg, Inst Transfus Med & Immunol, Med Fac Mannheim, D-6900 Heidelberg, Germany. Inst Transfus Med & Immunohematol, Baden Baden, Germany. Inst Transfus Med & Immunohematol, Frankfurt, Germany. Univ Hosp Ulm, Inst Transfus Med, Ulm, Germany. Inst Clin Transfus Med & Immunogenet, Ulm, Germany. RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM flegelwa@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 35 TC 12 Z9 14 U1 0 U2 0 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 SEP PY 2009 VL 49 IS 9 BP 1793 EP 1802 DI 10.1111/j.1537-2995.2009.02220.x PG 10 WC Hematology SC Hematology GA 489AM UT WOS:000269391800005 PM 19453980 ER PT J AU Triulzi, DJ Kleinman, S Kakaiya, RM Busch, MP Norris, PJ Steele, WR Glynn, SA Hillyer, CD Carey, P Gottschall, JL Murphy, EL Rios, JA Ness, PM Wright, DJ Carrick, D Schreiber, GB AF Triulzi, Darrell J. Kleinman, Steven Kakaiya, Ram M. Busch, Michael. P. Norris, Philip J. Steele, Whitney R. Glynn, Simone A. Hillyer, Christopher D. Carey, Patricia Gottschall, Jerome L. Murphy, Edward L. Rios, Jorge A. Ness, Paul M. Wright, David J. Carrick, Danielle Schreiber, George B. CA Retrovirus Epidemiology Donor Stud TI The effect of previous pregnancy and transfusion on HLA alloimmunization in blood donors: implications for a transfusion-related acute lung injury risk reduction strategy SO TRANSFUSION LA English DT Article ID LEUKOCYTE ANTIGEN ANTIBODIES; PREVALENCE; PATHOGENESIS; COMPONENTS; RECIPIENTS; TRALI AB BACKGROUND: Antibodies to human leukocyte antigens (HLA) in donated blood have been implicated as a cause of transfusion-related acute lung injury (TRALI). A potential measure to reduce the risk of TRALI includes screening plateletpheresis donors for HLA antibodies. The prevalence of HLA antibodies and their relationship to previous transfusion or pregnancy in blood donors was determined. STUDY DESIGN AND METHODS: A total of 8171 volunteer blood donors were prospectively recruited by six US blood centers from December 2006 to May 2007. Donors provided a detailed history of pregnancy and transfusion and a sample for HLA Class I and II antibody testing by multiantigen bead flow analysis. RESULTS: A total of 8171 donors were enrolled; 7920 (96.9%) had valid HLA antibody test results and 7841 (99%) of those had complete pregnancy and transfusion information. The prevalence of any HLA antibody was similar in nontransfused (n = 1138) and transfused (n = 895) men, 1.0% versus 1.7% (p = 0.16). HLA antibodies were detected in 17.3% of all female donors (n = 5834) and in 24.4% of those with a history of previous pregnancy (n = 3992). The prevalence of HLA antibodies increased in women with greater numbers of pregnancy: 1.7% (zero), 11.2% (one), 22.5% (two), 27.5% (three), and 32.2% (four or more pregnancies; p < 0.0001). CONCLUSION: HLA Class I and Class II antibodies are detectable at low prevalence in male donors regardless of transfusion and in female donors without known immunizing events. The prevalence of HLA antibodies increases significantly with more pregnancies. These data will allow blood centers to estimate the impact of HLA antibody testing as a potential TRALI risk reduction measure. C1 [Triulzi, Darrell J.] Inst Transfus Med, Pittsburgh, PA 15213 USA. Blood Syst Res Inst, San Francisco, CA USA. Blood Ctr Pacific, San Francisco, CA USA. NHLBI, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. Hoxworth Blood Ctr, Cincinnati, OH USA. Blood Ctr Wisconsin, Milwaukee, WI USA. Amer Red Cross, New England Reg, Dedham, MA USA. WESTAT Corp, Rockville, MD 20850 USA. RP Triulzi, DJ (reprint author), Inst Transfus Med, 3636 Blvd Allies, Pittsburgh, PA 15213 USA. EM dtriulzi@itxm.org OI Carey, Patricia/0000-0001-8706-280X FU NHLBI NIH HHS [HHSN268200517181C, N01 HB047168, N01 HB047169, N01 HB047170, N01 HB047171, N01 HB047172, N01 HB047174, N01 HB047175, N01HB47168, N01HB47169, N01HB47170, N01HB47171, N01HB47172, N01HB47174, N01HB47175, N01HB57181] NR 28 TC 134 Z9 142 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 SEP PY 2009 VL 49 IS 9 BP 1825 EP 1835 DI 10.1111/j.1537-2995.2009.02206.x PG 11 WC Hematology SC Hematology GA 489AM UT WOS:000269391800009 PM 19453983 ER PT J AU Daniel-Johnson, J Leitman, S Klein, H Alter, H Lee-Stroka, A Scheinberg, P Pantin, J Quillen, K AF Daniel-Johnson, Jennifer Leitman, Susan Klein, Harvey Alter, Harvey Lee-Stroka, Agnes Scheinberg, Phillip Pantin, Jeremy Quillen, Karen TI Probiotic-associated high-titer anti-B in a group A platelet donor as a cause of severe hemolytic transfusion reactions SO TRANSFUSION LA English DT Article ID ACUTE INTRAVASCULAR HEMOLYSIS; APHERESIS PLATELETS; DOUBLE-BLIND; BACTERIA; VACCINE; TRIAL AB BACKGROUND: Hemolytic transfusion reactions (HTRs) can occur with transfusion of platelets (PLTs) containing ABO-incompatible plasma. Reported cases have involved group O donors. Two cases of PLT-mediated HTRs associated with the same group A plateletpheresis component, collected from a donor taking high doses of probiotics are reported. CASE REPORT: Case 1 was a 40-year-old 69-kg group B stem cell transplant patient who received one-half of a group A plateletpheresis component. Severe back pain occurred 10 minutes into the transfusion, accompanied by anemia and hyperbilirubinemia. Case 2 was a 5-year-old 26-kg group B male with aplastic anemia who received the other half of the same plateletpheresis component, volume reduced to 37 mL. Syncope occurred immediately after the transfusion, with laboratory evidence of hemolysis a few hours later. RESULTS: Serologic investigation of posttransfusion samples from both patients revealed positive direct antiglobulin tests: C3d only for Case 1 and immunoglobulin (Ig) G and C3d for Case 2; the eluates contained anti-B. The group A donor's anti-B titer was 16,384 at saline and IgG phases. Donor lookback revealed that the donor had donated 134 apheresis PLTs over many years. For 3 years, he had intermittently taken probiotics; 3 weeks before the index donation, he began taking three tablets of probiotics every day. Lookback of prior group B recipients uncovered a case of acute hemolysis that was not recognized at the time. The solubilized probiotic inhibited anti-B in vitro. CONCLUSION: Non-group O PLT donors can have high-titer anti-A or anti-B that might mediate HTRs, and probiotic ingestion in blood donors represents a novel mechanism of stimulating high-titer anti-B. C1 NHLBI, NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Quillen, K (reprint author), 88 E Newton St,H-3600, Boston, MA 02118 USA. EM kq@bu.edu OI Quillen, Karen/0000-0002-4243-0864; Pantin, Jeremy/0000-0001-7536-0623; Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS [ZIA CL002122-02] NR 16 TC 23 Z9 26 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 SEP PY 2009 VL 49 IS 9 BP 1845 EP 1849 DI 10.1111/j.1537-2995.2009.02208.x PG 5 WC Hematology SC Hematology GA 489AM UT WOS:000269391800011 PM 19453987 ER PT J AU Bryant, BJ Hopkins, JA Arceo, SM Leitman, SF AF Bryant, Barbara J. Hopkins, Julie A. Arceo, Sarah M. Leitman, Susan F. TI Evaluation of low red blood cell mean corpuscular volume in an apheresis donor population SO TRANSFUSION LA English DT Article ID IRON-DEFICIENCY ANEMIA; BETA-THALASSEMIC TRAIT; DISCRIMINATION INDEXES; DISTRIBUTION WIDTH; SCREENING-TESTS; MICROCYTOSIS; DIFFERENTIATION; DIAGNOSIS; MCV AB BACKGROUND: Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (<80 fL) in the presence of an acceptable hemoglobin (Hb; >= 12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed. METHODS: Predonation samples for CBC were obtained from 1162 consecutive apheresis donors. Donors with a MCV of less than 80 fL were evaluated by CBC, iron studies (ferritin, serum iron, transferrin, percentage of transferrin saturation), and hemoglobin (Hb) electrophoresis. Iron deficiency was defined as a ferritin value below the reference range. Beta chain Hb variants were determined by Hb electrophoresis. Alpha thalassemia trait was presumed if the red blood cell (RBC) count was elevated, no variant Hbs were detected, and the iron studies were within normal ranges. RESULTS: In a 19-month period, 33 of 1162 apheresis donors had low MCV values. Iron deficiency was present in 64%; 49% had isolated iron deficiency and 15% had iron deficiency plus hemoglobinopathy. Hemoglobinopathy without concomitant iron deficiency was found in the remaining 36%. CONCLUSION: Iron deficiency is present in the majority of apheresis donors with repeatedly low MCV values and Hb levels of 12.5 g/dL or more. Hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy. Low MCV values should be investigated to determine if iron replacement therapy is indicated. C1 [Bryant, Barbara J.; Hopkins, Julie A.; Arceo, Sarah M.; Leitman, Susan F.] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Bryant, BJ (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711, Bethesda, MD 20892 USA. EM bryantb2@cc.nih.gov FU Intramural NIH HHS [Z01 CL002117-02] NR 25 TC 7 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 SEP PY 2009 VL 49 IS 9 BP 1971 EP 1976 DI 10.1111/j.1537-2995.2009.02207.x PG 6 WC Hematology SC Hematology GA 489AM UT WOS:000269391800026 PM 19453988 ER PT J AU Powers, MLE Lublin, D Eby, C Leitman, SF Dynis, M Despotis, GJ AF Powers, Michelle L. E. Lublin, Douglas Eby, Charles Leitman, Susan F. Dynis, Marian Despotis, George J. TI Safety concerns related to use of unapproved needles for accessing implantable venous access devices SO TRANSFUSION LA English DT Letter C1 [Powers, Michelle L. E.; Lublin, Douglas; Eby, Charles; Despotis, George J.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. [Eby, Charles] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Dynis, Marian] Barnes Jewish Hosp, Apheresis Dept, St Louis, MO 63110 USA. [Despotis, George J.] Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63110 USA. RP Powers, MLE (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. EM gdespotis@path.wustl.edu FU Intramural NIH HHS [Z99 CL999999] NR 2 TC 0 Z9 0 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 SEP PY 2009 VL 49 IS 9 BP 2008 EP 2009 PG 3 WC Hematology SC Hematology GA 489AM UT WOS:000269391800033 PM 19735506 ER PT J AU Goldstein, RZ Craig, AD Bechara, A Garavan, H Childress, AR Paulus, MP Volkow, ND AF Goldstein, Rita Z. Craig, A. D. (Bud) Bechara, Antoine Garavan, Hugh Childress, Anna Rose Paulus, Martin P. Volkow, Nora D. TI The Neurocircuitry of Impaired Insight in Drug Addiction SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; SELF-AWARENESS; INTEROCEPTIVE AWARENESS; ALCOHOL-CONSUMPTION; COCAINE ADDICTION; DECISION-MAKING; LIMBIC ACTIVATION; NEURAL ACTIVATION; COGNITIVE CONTROL AB More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such 'denial' might instead reflect dysfunction of brain networks subserving insight and self-awareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (l) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug-related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction. C1 [Goldstein, Rita Z.] Brookhaven Natl Lab, Ctr Translat Neuroimaging, Upton, NY 11973 USA. [Craig, A. D. (Bud)] Barrow Neurol Inst, Atkinson Res Lab, Phoenix, AZ 85013 USA. [Bechara, Antoine] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Garavan, Hugh] Trinity Coll Dublin, Sch Psychol, Dublin 2, Ireland. [Garavan, Hugh] Trinity Coll Dublin, Inst Neurosci, Dublin 2, Ireland. [Garavan, Hugh] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. [Childress, Anna Rose] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Paulus, Martin P.] Univ Calif San Diego, Dept Psychiat, Lab Biol Dynam & Theoret Med, La Jolla, CA 92037 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Ctr Translat Neuroimaging, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA. EM rgoldstein@bnl.gov FU National Institute on Drug Abuse [1R01DA023579, R21DA02062, R01DA023051, DA014100]; Barrow Neurological Foundation FX The contribution of Steven J. Grant, Division of Clinical Neuroscience and Behavioral Research, National Institute on Drug Abuse, who reviewed and edited this manuscript is gratefully acknowledged. This manuscript is based on the symposium `Functional Neuroimaging Evidence for a Brain Network Underlying Impaired Insight Into Illness in Drug Addiction' chaired by RZG and co-chaired by SJG at the 2008 annual meeting of the Society for Neuroscience, Washington DC. The preparation of this manuscript was supported by grants from the National Institute on Drug Abuse (to RZG: 1ROlDA023579 and R21DA02062; to AB: RO1DA023051; to HG: DA014100) and the Barrow Neurological Foundation (to ADC). NR 80 TC 230 Z9 236 U1 12 U2 59 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 SEP PY 2009 VL 13 IS 9 BP 372 EP 380 DI 10.1016/j.tics.2009.06.004 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 506GW UT WOS:000270764100006 PM 19716751 ER PT J AU Giorgobiani, E Babuadze, G Chanturia, G Chitadze, N Sacks, D Lawyer, P Kamhawi, S AF Giorgobiani, E. Babuadze, G. Chanturia, G. Chitadze, N. Sacks, D. Lawyer, P. Kamhawi, S. TI Epidemiological and entomological survey of visceral leishmaniasis focus in Tbilisi, Georgia SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Meeting Abstract C1 [Giorgobiani, E.; Babuadze, G.; Chanturia, G.; Chitadze, N.] Natl Ctr Dis Control Malaria & Other Protozoonosi, Tbilisi, Rep of Georgia. [Sacks, D.; Lawyer, P.; Kamhawi, S.] NIAID, NIH, Parasit Dis Lab, 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 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD SEP PY 2009 VL 14 BP 60 EP 60 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 487HZ UT WOS:000269264000174 ER PT J AU Goldman, RC Laughon, BE AF Goldman, Robert C. Laughon, Barbara E. TI Discovery and validation of new antitubercular compounds as potential drug leads and probes SO TUBERCULOSIS LA English DT Article DE High-throughput screening; Tuberculosis; Chemical probes; Drug development; Mycobacteria ID GENE-DISRUPTED MICE; MYCOBACTERIUM-TUBERCULOSIS; IN-VIVO; SOUTH-AFRICA; 1,4-DI-N-OXIDE; DERIVATIVES; VITRO; ASSAY; MODEL; TB AB Increasing multidrug resistance in Mycobacterium tuberculosis continues to diminish the number of effective drugs available for treatment of active tuberculosis. Although there are four new products (representing three new chemical classes) in clinical development, an active, robust pipeline of new chemical entities is critical to discovery of medicines to dramatically improve or shorten length of therapy via new mechanisms of action. In the absence of major pharmaceutical industry activity in tuberculosis drug development, the National Institute of Allergy and Infectious Diseases (NIAID) has supported the development of a high throughput screen for growth inhibitors of M. tuberculosis using a chemically diverse commercial library, a compound library available through the NIH Roadmap, Molecular Libraries Screening Center Network, and other compound sources. The rationale for these screens and suggested approaches for follow-up studies to identify compounds for advanced preclinical studies and as chemical probes of critical functions in M. tuberculosis, are discussed. Published by Elsevier Ltd. C1 [Goldman, Robert C.] NIAID, DHHS, NIH,TB Leprasy & Other Mycobacterial Dis Sect, Div Microbiol & Infect Dis,Resp Dis Branch, Bethesda, MD 20892 USA. [Laughon, Barbara E.] NIAID, DHHS, NIH, Div Microbiol & Infect Dis,Off Director, Bethesda, MD 20892 USA. RP Goldman, RC (reprint author), NIAID, DHHS, NIH,TB Leprasy & Other Mycobacterial Dis Sect, Div Microbiol & Infect Dis,Resp Dis Branch, 6610 Rockledge Dr,Room 5083,MSC 6603, Bethesda, MD 20892 USA. EM rgoldman@niaid.nih.gov; blaughon@niaid.nih.gov FU Intramural NIH HHS [NIH0010636212]; PHS HHS [NIH0010636212] NR 19 TC 20 Z9 20 U1 1 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD SEP PY 2009 VL 89 IS 5 BP 331 EP 333 DI 10.1016/j.tube.2009.07.007 PG 3 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 513QY UT WOS:000271339500002 PM 19716767 ER PT J AU Ananthan, S Faaleolea, ER Goldman, RC Hobrath, JV Kwong, CD Laughon, BE Maddry, JA Mehta, A Rasmussen, L Reynolds, RC Secrist, JA Shindo, N Showe, DN Sosa, MI Suling, WJ White, EL AF Ananthan, Subramaniam Faaleolea, Ellen R. Goldman, Robert C. Hobrath, Judith V. Kwong, Cecil D. Laughon, Barbara E. Maddry, Joseph A. Mehta, Alka Rasmussen, Lynn Reynolds, Robert C. Secrist, John A., III Shindo, Nice Showe, Dustin N. Sosa, Melinda I. Suling, William J. White, E. Lucile TI High-throughput screening for inhibitors of Mycobacterium tuberculosis H37Rv SO TUBERCULOSIS LA English DT Review DE TAACF; Antitubercular; High-throughput screening methods; Medicinal chemistry analysis; Medicinally relevant chemical library ID DRUG-RESISTANT TUBERCULOSIS; POTENTIAL ANTITUBERCULOSIS AGENTS; RING-SUBSTITUTED QUINOLINES; UDP-GALACTOPYRANOSE MUTASE; MEFLOQUINE-BASED LIGANDS; CELL-WALL BIOSYNTHESIS; PLATE-BASED SCREEN; IN-VITRO; MULTIDRUG-RESISTANT; 1,4-NAPHTHOQUINONE DERIVATIVES AB There is an urgent need for the discovery and development of new antitubercular agents that target new biochemical pathways and treat drug resistant forms of the disease. One approach to addressing this need is through high-throughput screening of medicinally relevant libraries against the whole bacterium in order to discover a variety of new, active scaffolds that will stimulate new biological research and drug discovery. Through the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (www.taacf.org), a large, medicinally relevant chemical library was screened against M. tuberculosis strain H37Rv. The screening methods and a medicinal chemistry analysis of the results are reported herein. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Ananthan, Subramaniam; Hobrath, Judith V.; Kwong, Cecil D.; Maddry, Joseph A.; Mehta, Alka; Rasmussen, Lynn; Reynolds, Robert C.; Secrist, John A., III; Shindo, Nice; Sosa, Melinda I.; Suling, William J.; White, E. Lucile] So Res Inst, Birmingham, AL 35205 USA. [Faaleolea, Ellen R.; Showe, Dustin N.] So Res Inst, Frederick, MD 21701 USA. [Goldman, Robert C.; Laughon, Barbara E.] NIAID, DHHS, NIH,Therapeut Res Program,Complicat & Coinfect Br, Div Acquired Immunodeficiency Syndrome, Bethesda, MD USA. RP Ananthan, S (reprint author), So Res Inst, 2000 9th Ave S, Birmingham, AL 35205 USA. EM ananthan@southernresearch.org; faaleolea@southernresearch.org; rgoldman@niaid.nih.gov; hobrath@southernresearch.org; kwong@southernresearch.org; blaughon@niaid.nih.gov; maddry@southernresearch.org; mehta@southernresearch.org; rasmussen@southernresearch.org; reynolds@southernresearch.org; secrist@southernresearch.org; shindo@southernresearch.org; showe@southernresearch.org; sosa@southernresearch.org; suling@southernresearch.org; white@southernresearch.org FU [N01-AI-95364]; [N01-AI-15449] FX This work was supported by contracts N01-AI-95364 (JAS) and N01-AI-15449 (ELW). The complete data sets for the HTS campaign will be deposited in PubChem. The authors thank Dr. Scott Franzblau who generously provided us with his protocol for the Alamar Blue M. tuberculosis assay at the beginning of this program. The authors are appreciative of the assistance of Sara McKellip, Nicole Kushner and Kristen Southworth in running the H37Rv screen, Anna Manouvakhova for assistance in the data analysis and Shuang Feng for the statistical analyses. NR 138 TC 152 Z9 155 U1 2 U2 28 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD SEP PY 2009 VL 89 IS 5 BP 334 EP 353 DI 10.1016/j.tube.2009.05.008 PG 20 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 513QY UT WOS:000271339500003 PM 19758845 ER PT J AU Maddry, JA Ananthan, S Goldman, RC Hobrath, JV Kwong, CD Maddox, C Rasmussen, L Reynolds, RC Secrist, JA Sosa, MI White, EL Zhang, W AF Maddry, Joseph A. Ananthan, Subramaniam Goldman, Robert C. Hobrath, Judith V. Kwong, Cecil D. Maddox, Clinton Rasmussen, Lynn Reynolds, Robert C. Secrist, John A., III Sosa, Melinda I. White, E. Lucile Zhang, Wei TI Antituberculosis activity of the molecular libraries screening center network library SO TUBERCULOSIS LA English DT Article DE MLSCN; TAACF; Antitubercular; High-throughput screening; Medicinal chemistry analysis; Small molecule chemical library; Tuberculosis ID RESISTANT MYCOBACTERIUM-TUBERCULOSIS; ANTIBACTERIAL ACTIVITY; DERIVATIVES; AGENTS; IDENTIFICATION; INHIBITORS AB There is an urgent need for the discovery and development of new antitubercular agents that target novel biochemical pathways and treat drug-resistant forms of the disease. One approach to addressing this need is through high-throughput screening of drug-like small molecule libraries against the whole bacterium in order to identify a variety of new, active scaffolds that will stimulate additional biological research and drug discovery. Through the Molecular Libraries Screening Center Network, the NIAID Tuberculosis Antimicrobial Acquisition and Coordinating Facility tested a 215,110-compound library against Mycobacterium tuberculosis strain H37Rv. A medicinal chemistry survey of the results from the screening campaign is reported herein. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Maddry, Joseph A.; Ananthan, Subramaniam; Hobrath, Judith V.; Kwong, Cecil D.; Maddox, Clinton; Rasmussen, Lynn; Reynolds, Robert C.; Secrist, John A., III; Sosa, Melinda I.; White, E. Lucile; Zhang, Wei] So Res Inst, Birmingham, AL 35205 USA. [Goldman, Robert C.] NIAID, DHHS, NIH,TB Leprosy & Other Mycobacterial Dis Sect, Div Microbiol & Infect Dis,Resp Dis Branch, Bethesda, MD USA. RP Maddry, JA (reprint author), So Res Inst, 2000 9th Ave S, Birmingham, AL 35205 USA. EM maddry@southernresearch.org; ananthan@southernresearch.org; rgoldman@niaid.nih.gov; hobrath@southernresearch.org; kwong@southernresearch.org; maddox@southernresearch.org; rasmussen@southernresearch.org; reynolds@southernresearch.org; secrist@southernresearch.org; sosa@southernresearch.org; white@southernresearch.org; zhangw@southernresearch.org FU National Institutes of Health [1U54-HG-003917]; Southern Research Molecular Libraries Screening Center; NIH TAACF [N01-AI-95364] FX The screening of this assay was supported by National Institutes of Health grant 1U54-HG-003917, Southern Research Molecular Libraries Screening Center. The data analysis was supported by the NIH TAACF contract, N01-AI-95364. The complete data sets for the HTS campaign have been deposited in PubChem (http://pubchem.ncbi.nlm.nih.gov/; assay AIDs 1332 and 1626). The authors thank Dr. Scott Franzblau who provided his protocol for the alamarBlue M. tuberculosis assay at the beginning of the TAACF program, which was adapted for the MLSCN assay. We also thank Dr. William J. Suling for his assistance and insight during the analysis, and Ms. Sara McKellip for her assistance with the assay. NR 32 TC 91 Z9 92 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD SEP PY 2009 VL 89 IS 5 BP 354 EP 363 DI 10.1016/j.tube.2009.07.006 PG 10 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 513QY UT WOS:000271339500004 PM 19783214 ER PT J AU Harford, JB Edwards, BK Nandakumar, A Ndom, P Capocaccia, R Coleman, MP AF Harford, Joe B. Edwards, Brenda K. Nandakumar, Ambakumar Ndom, Paul Capocaccia, Riccardo Coleman, Michel P. CA ICCC 3 Session A Grp TI Cancer control-planning and monitoring population-based systems SO TUMORI LA English DT Article; Proceedings Paper CT 3rd International Cancer Control Congress CY NOV 08-11, 2009 CL Cernobbio, ITALY DE ICCC-3; cancer control-planning; international collaboration ID BURDEN; CARE AB Cancer is a growing global health issue, and many countries are in-prepared to deal with their current cancer burden let alone the increased burden looming on the horizon. Growing and aging populations are projected to result in dramatic increases in cancer cases and cancer deaths particularly in low- and middle-income countries. It is imperative that planning begin now to deal not only with those cancers already occurring but also with the larger numbers expected in the future. Unfortunately, such planning is hampered, because the magnitude of the burden of cancer in many countries is poorly understood owing to lack of surveillance and monitoring systems for cancer risk factors and for the documentation of cancer incidence, survival and mortality. Moreover, the human resources needed to fight cancer effectively are often limited or lacking. Cancer diagnosis and cancer care services are also inadequate in low- and middle-income countries. Late-stage presentation of cancers is very common in these settings resulting in less potential for cure and more need for symptom management. Palliative care services are grossly inadequate in low- and middle-income countries, and many cancer patients die unnecessarily painful deaths. Many of the challenges faced by low- and middle-income countries have been at least partially addressed by higher income countries. Experiences from around the world are reviewed to highlight the issues and showcase some possible solutions. C1 [Harford, Joe B.] NCI, Off Int Affairs, Bethesda, MD 20892 USA. [Nandakumar, Ambakumar] ICMR, Natl Canc Registry Program India, Bangalore, Karnataka, India. [Ndom, Paul] Gen Hosp Yaounde, Oncol Serv, Yaounde, Cameroon. [Capocaccia, Riccardo] Ist Super Sanita, I-00161 Rome, Italy. [Coleman, Michel P.] London Sch Hyg & Trop Med, London WC1, England. RP Harford, JB (reprint author), NCI, Off Int Affairs, EPN100, Bethesda, MD 20892 USA. EM harfordj@nih.gov RI Baili, Paolo/J-7422-2016; Sant, Milena/D-2362-2017; Di Salvo, Francesca/E-2840-2017; OI Baili, Paolo/0000-0003-0335-2418; Sant, Milena/0000-0002-4148-8597; Di Salvo, Francesca/0000-0003-2537-081X; Coleman, Michel/0000-0001-8940-3807; Micheli, Andrea/0000-0002-4558-4754; Tiro, Jasmin/0000-0001-8300-0441 FU Cancer Research UK [11700] NR 26 TC 10 Z9 11 U1 3 U2 7 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD SEP-OCT PY 2009 VL 95 IS 5 BP 568 EP 578 PG 11 WC Oncology SC Oncology GA 529AV UT WOS:000272489000002 PM 19999948 ER PT J AU Ramsey, SD Zeliadt, SB Arora, NK Potosky, AL Blough, DK Hamilton, AS Van Den Eeden, SK Oakley-Girvan, I Penson, DF AF Ramsey, Scott D. Zeliadt, Steven B. Arora, Neeraj K. Potosky, Arnold L. Blough, David K. Hamilton, Ann S. Van Den Eeden, Stephen K. Oakley-Girvan, Ingrid Penson, David F. TI Access to Information Sources and Treatment Considerations Among Men With Local Stage Prostate Cancer SO UROLOGY LA English DT Article ID EDUCATION MATERIALS; SEEKING BEHAVIORS; NEEDS; PREFERENCES; CARCINOMA; PARTNERS; DECISION; INTERNET AB OBJECTIVES To determine the role of information sources in the treatment decision-making process of men diagnosed with local stage prostate cancer. Diagnosed men have access to a large number of information sources about therapy, including print and broadcast media, the Internet, books, and friends with the disease. METHODS Prospective survey of men with local stage prostate cancer in 3 geographically separate regions was carried out. Most men were surveyed after diagnosis but before starting therapy. RESULTS On average, men with local prostate cancer consulted nearly 5 separate sources of information before treatment. The most common source of information was the patient's physician (97%), followed by lay-literature (pamphlets, videos) (76%), other health professionals (71%), friends with prostate cancer (67%), and the Internet (58%). Most men rated the Sources they consulted as helpful. Consulting the Internet was associated with considering more treatment options. Several information sources were significantly associated with considering particular treatments, but the magnitude of association was small in relation to patient age, comorbidity, and Gleason score. More than 70% of men stated that they were considering or planning only one type of therapy. CONCLUSIONS Men with local stage prostate cancer consult a wide range of information sources. Nonphysician information sources appear to influence their treatment considerations, but to a smaller degree than clinical factors. UROLOGY 74: 509-516, 2009. (C) 2009 Elsevier Inc. C1 [Ramsey, Scott D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Canc Control Program, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Kaiser Permanente, Div Res, Oakland, CA USA. No Calif Canc Cctr, Fremont, CA USA. Univ So Calif, Dept Urol, Norris Canc Ctr, Los Angeles, CA USA. Univ So Calif, Dept Prevent Med, Norris Canc Ctr, Los Angeles, CA 90089 USA. RP Ramsey, SD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-B232, Seattle, WA 98109 USA. EM sramsey@fhcrc.org FU National Cancer Institute [N01-PC-35142, N01-PC-35139, N01-PC-35136]; Cancer Surveillance System; Fred Hutchinson Cancer Research Center [N01-PC-35142] FX Supported by the National Cancer Institute contracts N01-PC-35142, N01-PC-35139, and N01-PC-35136 and by the Cancer Surveillance System of the Fred Hutchinson Cancer Research Center, which is funded by Contract No. N01-PC-35142 from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute with additional support from the Fred Hutchinson Cancer Research Center and the State of Washington. NR 25 TC 18 Z9 18 U1 1 U2 1 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 SEP PY 2009 VL 74 IS 3 BP 509 EP 515 DI 10.1016/j.urology.2009.01.090 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 499GU UT WOS:000270207100011 PM 19589564 ER PT J AU Narfstrom, K David, V Jarret, O Beatty, J Barrs, V Wilkie, D O'Brien, S Menotti-Raymond, M AF Narfstrom, Kristina David, Victor Jarret, Oswald Beatty, Julia Barrs, Vanessa Wilkie, David O'Brien, Stephen Menotti-Raymond, Marilyn TI Retinal degeneration in the Abyssinian and Somali cat (rdAc): correlation between genotype and phenotype and rdAc allele frequency in two continents SO VETERINARY OPHTHALMOLOGY LA English DT Article DE allele frequency; cat; degeneration; hereditary; photoreceptor; retina ID ROD-CONE DEGENERATION; JOUBERT-SYNDROME; CENTROSOMAL PROTEIN; ATROPHY; MUTATIONS; CEP290; ELECTRORETINOGRAM; DISORDERS AB Objective To characterize hereditary retinal degeneration in the Abyssinian cat (rdAc) in a recently established closed colony segregating for the rdAc mutation, and evaluate possible differences in the age of onset and progression of disease phenotype since the initial description of rdAc 25 years ago. The sample size of an earlier study was increased in order to determine the allele frequency in Abyssinian and Somali cats on a worldwide basis. Animals studied Twenty rdAc affected cats from the closed animal facility, 87 Abyssinian and Somali cats for study of genotype-phenotype concordance, and DNA from 131 Abyssinian and Somali cats from Scandinavia, the UK and Australia for evaluation of the rdAc allele frequency. Procedures DNA was extracted from blood and buccal swabs using commercially available kits, followed by genotyping. Ophthalmic examinations were performed in the USA and Sweden by two board-certified veterinary ophthalmologists. Results A greater variation in the age of onset and progression of the disease was observed compared to that previously described. An excellent correlation between genotype and phenotype was observed. A population genetic survey revealed that the rdAc allele is in moderate abundance in the Abyssinian breed in Europe and Australia. Surprisingly, homozygosity for the mutant allele was observed in a Siamese cat with ophthalmoscopic findings similar to those originally described for affected rdAc individuals. Conclusions Alertness to the potential of rdAc is needed on the part of the veterinary ophthalmology community, not only in Abyssinian and Somali cats but possibly also in other related cat breeds. C1 [Narfstrom, Kristina] Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA. [David, Victor; O'Brien, Stephen; Menotti-Raymond, Marilyn] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Jarret, Oswald] Univ Glasgow, Inst Comparat Med, Fac Vet Med, Glasgow G61 1QH, Lanark, Scotland. [Beatty, Julia; Barrs, Vanessa] Univ Sydney, Fac Vet Sci, Sydney, NSW 2006, Australia. [Wilkie, David] Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA. RP Narfstrom, K (reprint author), Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA. EM narfstromk@missouri.edu RI Barrs, Vanessa/K-3755-2012 FU National Cancer Institute; National Institutes of Health; Grousbeck Family Foundation FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Funds from the Grousbeck Family Foundation are gratefully acknowledged. NR 34 TC 5 Z9 5 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1463-5216 J9 VET OPHTHALMOL JI Vet. Ophthalmol. PD SEP-OCT PY 2009 VL 12 IS 5 BP 285 EP 291 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 493BV UT WOS:000269709000002 PM 19751487 ER PT J AU Knoper, RC Ferrarone, J Yan, YH Lafont, BAR Kozak, CA AF Knoper, Ryan C. Ferrarone, John Yan, Yuhe Lafont, Bernard A. R. Kozak, Christine A. TI Removal of either N-glycan site from the envelope receptor binding domain of Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor usage SO VIROLOGY LA English DT Article DE Mouse ecotropic gammaretrovirus; CAT-1 retrovirus receptor; Gammaretrovirus envelope glycosylation sites; Retrovirus entry ID MURINE LEUKEMIA-VIRUS; LINKED GLYCOSYLATION SITES; AMINO-ACID TRANSPORTER; PRECURSOR POLYPROTEIN; RETROVIRUS INFECTION; MUTATIONAL ANALYSIS; MAMMALIAN-CELLS; HOST-RANGE; PROTEIN; GLYCOPROTEIN AB Three N-linked glycosylation sites were removed from the envelope glycoproteins of Friend, Moloney, and AKV mouse ecotropic gammaretroviruses: gs1 and gs2, in the receptor binding domain; and gs8, in a region implicated in post-binding cell fusion. Mutants were tested for their ability to infect rodent cells expressing 4 CAT-1 receptor variants. Three mutants (Mo-gs1, Mo-gs2, and Fr-gs1) infect NIH 3T3 and rat XC cells, but are severely restricted in Mus dunni cells and Lec8, a Chinese hamster cell line susceptible to ecotropic virus. This restriction is reproduced in ferret cells expressing M. dunni dCAT-1, but not in cells expressing NIH 3T3 mCAT-1. Virus binding assays, pseudotype assays, and the use of glycosylation inhibitors further suggest that restriction is primarily due to receptor polymorphism and, in M. dunni cells, to glycosylation of cellular Proteins. Virus envelope glycan size or type does not affect infectivity. Thus, host range variation due to N-glycan deletion is receptor variant-specific, cell-specific, virus type-specific, and glycan site-specific. Published by Elsevier Inc. C1 [Kozak, Christine A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Kozak, CA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 329,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA. EM ckozak@niaid.nih.gov RI Lafont, Bernard/B-7236-2014 FU Intramural Research Program of the NIH, MAID FX We thank Qingping Liu for expert technical assistance and Alicia Buckler-White for the sequencing. NR 37 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2009 VL 391 IS 2 BP 232 EP 239 DI 10.1016/j.virol.2009.06.015 PG 8 WC Virology SC Virology GA 486ZD UT WOS:000269238700010 PM 19584017 ER PT J AU Sashihara, J Burbelo, PD Savoldo, B Pierson, TC Cohen, JI AF Sashihara, Junji Burbelo, Peter D. Savoldo, Barbara Pierson, Theodore C. Cohen, Jeffrey I. TI Human antibody titers to Epstein-Barr Virus (EBV) gp350 correlate with neutralization of infectivity better than antibody titers to EBV gp42 using a rapid flow cytometry-based EBV neutralization assay SO VIROLOGY LA English DT Article DE Epstein-Barr virus; Antibody-mediated neutralization; Herpesvirus; Glycoprotein 350; Glycoprotein 42; Transformation ID ENVELOPE GLYCOPROTEIN GP340; GREEN FLUORESCENT PROTEIN; HUMAN LYMPHOCYTES-B; HLA CLASS-II; COTTONTOP TAMARINS; MONOCLONAL-ANTIBODY; MEMBRANE ANTIGEN; C3D RECEPTOR; MEDIATED NEUTRALIZATION; EPITHELIAL-CELLS AB Measurement of neutralizing antibodies to Epstein-Barr virus (EBV) is important for evaluation of candidate vaccines. The Current neutralization assay is based on antibody inhibition of EBV transformation of B cells and requires 6 weeks to perform. We developed a rapid, quantitative flow cytometry assay and show that neutralizing antibody titers measured by the new assay strongly correlate with antibody titers in the standard transformation-based assay. Antibodies to EBV gp350 and gp42 have been shown to block infection of B cells by EBV. Using new assays to quantify antibodies to these glycoproteins, we show for the first time that human plasma contains high titers of antibody to gp42; these titers correlate with neutralization of EBV infectivity or transformation. Furthermore, we show that antibody titers to EBV gp350 Correlate incite strongly with neutralization than antibody titers to gp42. These assays Should be useful in accessing antibody responses to candidate EBV vaccines. Published by Elsevier Inc. C1 [Sashihara, Junji; Cohen, Jeffrey I.] NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Burbelo, Peter D.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Savoldo, Barbara] Methodist Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Savoldo, Barbara] Texas Childrens Hosp, Houston, TX 77030 USA. [Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10,Rm 11N234, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases; National Institute of Dental and Craniofacial Research; Japan Herpesvirus Infection Forum FX This work was supported by the intramural research programs of the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research. J.S. was partially supported by the Japan Herpesvirus Infection Forum. We thank Henri-Jacques Delecluse and Bill Sugden for the 293/2089 cells, Lindsey Hutt-Fletcher for anti-gp42 monoclonal antibody, Yo Hoshino for help with statistics, and Qingxue Li for reviewing the manuscript. NR 49 TC 31 Z9 31 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2009 VL 391 IS 2 BP 249 EP 256 DI 10.1016/j.virol.2009.06.013 PG 8 WC Virology SC Virology GA 486ZD UT WOS:000269238700012 PM 19584018 ER PT J AU Fujii, K Munshi, UM Ablan, SD Demirov, DG Soheilian, F Nagashima, K Stephen, AG Fisher, RJ Freed, EO AF Fujii, Ken Munshi, Utpal M. Ablan, Sherimay D. Demirov, Dimiter G. Soheilian, Ferri Nagashima, Kunio Stephen, Andrew G. Fisher, Robert J. Freed, Eric O. TI Functional role of Alix in HIV-1 replication SO VIROLOGY LA English DT Article DE HIV-1; Retrovirus; Assembly; Endosomal sorting; ESCRT; Alix; Gag; Virus budding ID IMMUNODEFICIENCY-VIRUS TYPE-1; LATE-BUDDING DOMAINS; PARTICLE-PRODUCTION; PROTEIN; TSG101; RELEASE; RETROVIRUS; BINDING; ESCRT; VPR AB Retroviral Gag proteins encode small peptide motifs known as late domains that promote the release of virions from infected cells by interacting directly with host cell factors. Three types of retroviral late domains, with core sequences P(T/S)AP, YPX(n)L, and PPPY, have been identified. HIV-1 encodes a primary P(T/S)AP-type late domain and an apparently secondary late domain sequence of the YPX(n)L type. The P(T/S)AP and YPX(n)L motifs, interact with the endosomal sorting factors Tsg101 and Alix, respectively. Although biochemical and structural studies support a direct binding between HIV-1 p6 and Alix, the physiological role of Alix in HIV-1 biology remains undefined. To elucidate the function of the p6-Alix interaction in HIV-1 replication, we introduced a series of mutations in the p6 Alix binding site and evaluated the effects on virus particle production and virus replication in a range of cell types, including physiologically relevant primary T cells and macrophages. We also examined the effects of the Alix binding site mutations on virion morphogenesis and single-cycle virus infectivity. We determined that the p6-Alix interaction plays an important role in HIV-1 replication and observed a particularly severe impact of Alix binding site mutations when they were combined with mutational inactivation of the Tsg101 binding site. Published by Elsevier Inc. C1 [Fujii, Ken; Munshi, Utpal M.; Ablan, Sherimay D.; Demirov, Dimiter G.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. [Soheilian, Ferri; Nagashima, Kunio] NCI, Electron Microscope Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] NCI, Prot Chem Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. RP Freed, EO (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA. EM efreed@nih.gov FU Center for Cancer Research; National Cancer Institute, NIH [N01-CO-12400]; Intramural AIDS Targeted Antiviral Program FX We thank members of the Freed laboratory for helpful discussion and critical review of the manuscript. Purification of Alix V protein was performed by the Protein Expression Laboratory, SAIC, NCI-Frederick. HIV-Ig was obtained through the NIH AIDS Research and Reference Reagent Program. This research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH, and by the Intramural AIDS Targeted Antiviral Program. This project was funded in part with federal funds from the National Cancer institute, NIH, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 53 TC 39 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2009 VL 391 IS 2 BP 284 EP 292 DI 10.1016/j.virol.2009.06.016 PG 9 WC Virology SC Virology GA 486ZD UT WOS:000269238700016 PM 19596386 ER PT J AU Azimzadeh, AM Kelishadi, SS Ezzelarab, M Singh, AK Stoddard, T Zhang, TS Burdorf, L Avon, C Laaris, A Cheng, XF Ayares, D Horvath, KA Corcoran, PC Mohiuddin, MM Cooper, DKC Barth, RN Pierson, RN AF Azimzadeh, Agnes M. Kelishadi, Sean S. Ezzelarab, Mohammed Singh, Avnesh K. Stoddard, Tiffany Zhang, Tianshu Burdorf, Lars Avon, Christopher Laaris, Amal Cheng, Xiang-fei Ayares, David Horvath, Keith A. Corcoran, P. C. Mohiuddin, Muhammad M. Cooper, David K. C. Barth, Rolf N. Pierson, Richard N. TI Early graft failure of gtko pig organs in baboons is reduced by hCPRP expression SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Azimzadeh, Agnes M.; Kelishadi, Sean S.; Stoddard, Tiffany; Zhang, Tianshu; Burdorf, Lars; Avon, Christopher; Laaris, Amal; Cheng, Xiang-fei; Barth, Rolf N.; Pierson, Richard N.] Univ Maryland, Baltimore, MD 21201 USA. [Ezzelarab, Mohammed; Cooper, David K. C.] Univ Pittsburgh, Starzl Transplant Inst, Pittsburgh, PA USA. [Singh, Avnesh K.; Horvath, Keith A.; Corcoran, P. C.; Mohiuddin, Muhammad M.] NHLBI, NIH, Cardiothorac Res Program, Bethesda, MD 20892 USA. [Ayares, David] Revivicor, Blacksburg, VA USA. RI Barth, Rolf/B-2542-2014; Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 356 EP 356 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500198 ER PT J AU Mohiuddin, MM Singh, AK Corcoran, PC Azimzadeh, AM Ayares, D Hoyt, RF Carrier, C Thomas, ML Pierson, RN Horvath, KA AF Mohiuddin, Muhammad M. Singh, Avneesh K. Corcoran, Philip C. Azimzadeh, Agnes M. Ayares, David Hoyt, Robert F. Carrier, Charles Thomas, Marvin L. Pierson, Richard N. Horvath, Keith A. TI B cell depletion by anti CD20 prolongs GalKO.hCD46 pig heterotopic cardiac xenograft survival in baboons SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Mohiuddin, Muhammad M.; Singh, Avneesh K.; Corcoran, Philip C.; Hoyt, Robert F.; Carrier, Charles; Horvath, Keith A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Azimzadeh, Agnes M.; Pierson, Richard N.] Univ Maryland, Sch Med, Baltimore, MD USA. [Azimzadeh, Agnes M.; Pierson, Richard N.] Univ Maryland, Baltimore VAMC, Baltimore, MD USA. [Thomas, Marvin L.] NIH, DVR, ORS, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 357 EP 357 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500201 ER PT J AU Mohiuddin, MM Singh, AK Seavey, C Horvath, KA AF Mohiuddin, Muhammad M. Singh, Avneesh K. Seavey, Caleb Horvath, Keith A. TI Ex-vivo expanded CD4+CD25+treg cells inhibit the proliferation of B cells SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Mohiuddin, Muhammad M.; Singh, Avneesh K.; Seavey, Caleb; Horvath, Keith A.] NHLBI, NIH, CSRP, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X 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 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 362 EP 363 PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500219 ER PT J AU Horvath, KA Corcoran, PC Singh, AK Hoyt, RF Thomas, T Carrier, C Mohiuddin, MM AF Horvath, Keith A. Corcoran, Philip C. Singh, Avneesh K. Hoyt, Robert F. Thomas, Tom Carrier, Charles Mohiuddin, Muhammad M. TI Telemetry is an effective means to evaluate transplanted heart function in experimental heterotopic cardiac xenotransplantation SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Horvath, Keith A.; Corcoran, Philip C.; Singh, Avneesh K.; Hoyt, Robert F.; Carrier, Charles; Mohiuddin, Muhammad M.] NHLBI, NIH, CSRP, Bethesda, MD 20892 USA. [Thomas, Tom] NIH, DVR, ORS, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X 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 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 380 EP 380 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500273 ER PT J AU Corcoran, PC Horvath, KA Singh, AK Hoyt, RF Thomas, ML Mohiuddin, MM AF Corcoran, Philip C. Horvath, Keith A. Singh, Avneesh K. Hoyt, Robert F. Thomas, Marvin L. Mohiuddin, Muhammad M. TI Surgical and non surgical complications of a pig to baboon xenotransplantation model SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Pancreas-and-Islet-Transplant-Association/International-Xe notransplantation-Association CY OCT 12-16, 2009 CL Venice, ITALY SP Int Pancreas & Islet Transplant Assoc, Int Xenotransplantat Assoc C1 [Corcoran, Philip C.; Horvath, Keith A.; Singh, Avneesh K.; Hoyt, Robert F.; Mohiuddin, Muhammad M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Thomas, Marvin L.] NIH, DVR, ORS, Bethesda, MD USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X 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 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP-OCT PY 2009 VL 16 IS 5 BP 429 EP 429 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 502CA UT WOS:000270430500443 ER PT J AU Simons-Morton, B Chen, RS AF Simons-Morton, Bruce Chen, Rusan TI Peer and Parent Influences on School Engagement Among Early Adolescents SO YOUTH & SOCIETY LA English DT Article DE social influences; latent growth modeling; school adjustment ID GROWTH CURVE ANALYSES; MIDDLE SCHOOL; SUBSTANCE USE; ACADEMIC-ACHIEVEMENT; FRIENDS INFLUENCE; PROBLEM BEHAVIOR; ADJUSTMENT; MOTIVATION; STUDENTS; COMPETENCE AB Students who are not motivated and do not try to do well are unlikely to achieve consistent with their abilities. This research assesses the relationships over time between school engagement and parenting practices and peer affiliation among sixth to ninth graders using latent growth models. Participants included 2,453 students recruited from seven public middle schools who were assessed five times between fall of sixth and ninth grades as part of a program evaluation study. School engagement and adjustment declined somewhat, whereas substance use, conduct problems, and problem-behaving friends increased and authoritative parenting practices declined. The significant, positive, over-time associations between school engagement and parent involvement, expectations, and monitoring were fully mediated by growth in problem-behaving friends. School adjustment mediated the relationship between school engagement and parent expectations. Findings suggest that authoritative parenting practices may foster school engagement directly and indirectly by discouraging affiliation with problem-behaving friends and facilitating school adjustment. C1 [Simons-Morton, Bruce] NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Chen, Rusan] Georgetown Univ, Ctr New Designs Learning & Scholarship, Washington, DC 20057 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 FU Intramural NIH HHS [Z01 HD002110-16, Z99 HD999999] NR 64 TC 63 Z9 64 U1 6 U2 31 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0044-118X J9 YOUTH SOC JI Youth Soc. PD SEP PY 2009 VL 41 IS 1 BP 3 EP 25 DI 10.1177/0044118X09334861 PG 23 WC Social Issues; Social Sciences, Interdisciplinary; Sociology SC Social Issues; Social Sciences - Other Topics; Sociology GA 475UU UT WOS:000268388100001 PM 19888349 ER PT J AU Soman, G Yang, XY Jiang, HG Giardina, S Vyas, V Mitra, G Yovandich, J Creekmore, SP Waldmann, TA Quinones, O Alvord, WG AF Soman, Gopalan Yang, Xiaoyi Jiang, Hengguang Giardina, Steve Vyas, Vinay Mitra, George Yovandich, Jason Creekmore, Stephen P. Waldmann, Thomas A. Quinones, Octavio Alvord, W. Gregory TI MTS dye based colorimetric CTLL-2 cell proliferation assay for product release and stability monitoring of Interleukin-15: Assay qualification, standardization and statistical analysis SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Cell proliferation assay; IL-15; Assay qualification; R statistical language and environment; Statistical analysis ID ACTIVATED KILLER-CELLS; FLUOROMETRIC ASSAY; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; GROWTH-FACTOR; BETA-CHAIN; T-CELLS; IL-15; LYMPHOKINE; CYTOKINES AB A colorimetric cell proliferation assay using soluble tetrazolium salt [(CellTiter 96 (R) Aqueous One Solution) cell proliferation reagent, containing the (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and an electron coupling reagent phenazine ethosulfate], was optimized and qualified for quantitative determination of IL-15 dependent CTLL-2 cell proliferation activity. An in-house recombinant Human (rHu)IL-15 reference lot was standardized (IU/mg) against an international reference standard. Specificity of the assay for IL-15 was documented by illustrating the ability of neutralizing anti-IL-15 antibodies to block the product specific CTLL-2 cell proliferation and the lack of blocking effect with anti-IL-2 antibodies. Under the defined assay conditions, the linear dose-response concentration range was between 0.04 and 0.17 ng/ml of the rHuIL-15 produced in-house and 0.5-3.0 IU/ml for the international standard. Statistical analysis of the data was performed with the use of scripts written in the R Statistical Language and Environment utilizing a four-parameter logistic regression fit analysis procedure. The overall variation in the ED(50) values for the in-house reference standard from 55 independent estimates performed over the period of 1 year was 12.3% of the average. Excellent intra-plate and within-day/inter-plate consistency was observed for all four parameter estimates in the model. Different preparations of rHuIL-15 showed excellent intra-plate consistency in the parameter estimates corresponding to the lower and upper asymptotes as well as to the 'slope' factor at the mid-point. The ED(50) values showed statistically significant differences for different lots and for control versus stressed samples. Three R-scripts improve data analysis capabilities allowing one to describe assay variations, to draw inferences between data sets from formal statistical tests, and to set up improved assay acceptance criteria based on comparability and consistency in the four parameters of the model. The assay is precise, accurate and robust and can be fully validated. Applications of the assay were established including process development support, release of the rHuIL-15 product for pre-clinical and clinical studies, and for monitoring storage stability. (C) 2009 Elsevier B.V. All rights reserved. C1 [Soman, Gopalan] NCI, Bioanalyt Dev Lab, Biopharmaceut Dev Program, SAIC Frederick Inc,Dept Proc Analyt, Frederick, MD 21702 USA. [Yovandich, Jason; Creekmore, Stephen P.] NCI, Biol Resources Branch, Frederick, MD 21702 USA. [Waldmann, Thomas A.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Soman, G (reprint author), NCI, Bioanalyt Dev Lab, Biopharmaceut Dev Program, SAIC Frederick Inc,Dept Proc Analyt, Frederick, MD 21702 USA. EM somang@mail.nih.gov FU NCI NIH HHS [HHSN2612008000016C, N01 CO012400, N01-CO-12400, N01CO12400]; PHS HHS [HHSN2612008000016C] NR 42 TC 16 Z9 17 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG 31 PY 2009 VL 348 IS 1-2 BP 83 EP 94 DI 10.1016/j.jim.2009.07.010 PG 12 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 496TN UT WOS:000270001600010 PM 19646987 ER PT J AU Tomasi, D Wang, GJ Wang, RL Backus, W Geliebter, A Telang, F Jayne, MC Wong, C Fowler, JS Volkow, ND AF Tomasi, Dardo Wang, Gene-Jack Wang, Ruiliang Backus, Walter Geliebter, Allan Telang, Frank Jayne, Millar C. Wong, Christopher Fowler, Joanna S. Volkow, Nora D. TI Association of Body Mass and Brain Activation during Gastric Distention: Implications for Obesity SO PLOS ONE LA English DT Article AB Background: Gastric distention (GD), as it occurs during meal ingestion, signals a full stomach and it is one of the key mechanisms controlling food intake. Previous studies on GD showed lower activation of the amygdala for subjects with higher body mass index (BMI). Since obese subjects have dopaminergic deficits that correlate negatively with BMI and the amygdala is innervated by dopamine neurons, we hypothesized that BMI would correlate negatively with activation not just in the amygdala but also in other dopaminergic brain regions (midbrain and hypothalamus). Methodology/Principal Findings: We used functional magnetic resonance imaging (fMRI) to evaluate brain activation during GD in 24 healthy subjects with BMI range of 20-39 kg/m(2). Using multiple regression and cross-correlation analyses based on a family-wise error corrected threshold P = 0.05, we show that during slow GD to maximum volumes of 500 ml and 700 ml subjects with increased BMI had increased activation in cerebellum and left posterior insula, and decreased activation of dopaminergic (amygdala, midbrain, hypothalamus, thalamus) and serotonergic (pons) brain regions and anterior insula, regions that were functionally interconnected with one another. Conclusions: The negative correlation between BMI and BOLD responses to gastric distention in dopaminergic (midbrain, hypothalamus, amygdala, thalamus) and serotonergic (pons) brain regions is consistent with disruption of dopaminergic and serotonergic signaling in obesity. In contrast the positive correlation between BMI and BOLD responses in posterior insula and cerebellum suggests an opposing mechanism that promotes food intake in obese subjects that may underlie their ability to consume at once large food volumes despite increasing gastric distention. RP Tomasi, D (reprint author), NIAAA, NIH, Bethesda, MD USA. EM tomasi@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [5-M01-RR-10710, M01 RR010710]; NIAAA NIH HHS [Y1AA3009, R01 AA009481, R01AA09481]; NIDA NIH HHS [R01 DA006278, R01 DA006891, R01DA006278, R01DA006891]; NIDDK NIH HHS [R01 DK054318, R01 DK054318-01A1, R01 DK054318-02, R01 DK054318-03, R01 DK080153, R01 DK080153-01A2, R01 DK080153-02, R01 DK080153-03, R01 DK080153-04, R56 DK080153, R56 DK080153-01A1] NR 73 TC 22 Z9 22 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 31 PY 2009 VL 4 IS 8 AR e6847 DI 10.1371/journal.pone.0006847 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 489JH UT WOS:000269415900019 PM 19718256 ER PT J AU Abdala, APL Rybak, IA Smith, JC Zoccal, DB Machado, BH St-John, WM Paton, JFR AF Abdala, A. P. L. Rybak, I. A. Smith, J. C. Zoccal, D. B. Machado, B. H. St-John, W. M. Paton, J. F. R. TI Multiple pontomedullary mechanisms of respiratory rhythmogenesis SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Review DE Retrotrapezoid nuclei; Botzinger complex; Abdominal nerve ID BRAIN-STEM PREPARATION; RETROTRAPEZOID NUCLEUS; GLYCINERGIC INHIBITION; RHYTHM GENERATION; NEWBORN RATS; IN-VIVO; NEURONS; NETWORK; MEDULLA; INSPIRATION AB Mammalian central pattern generators producing rhythmic movements exhibit robust but flexible behavior. However, brainstem network architectures that enable these features are not well understood. Using precise sequential transections through the pons to medulla, it was observed that there was compartmentalization of distinct rhythmogenic mechanisms in the ponto-medullary respiratory network, which has rostro-caudal organization. The eupneic 3-phase respiratory pattern was transformed to a 2-phase and then to a 1-phase pattern as the network was physically reduced. The pons, the retrotrapezoid nucleus and glycine mediated inhibition are all essential for expression of the 3-phase rhythm. The 2-phase rhythm depends on inhibitory interactions (reciprocal) between Botzinger and pre-Botzinger complexes, whereas the 1-phase-pattern is generated within the pre-Botzinger complex and is reliant on the persistent sodium current. In conditions of forced expiration, the RTN region was found to be essential for the expression of abdominal late expiratory activity. However, it is unknown whether the RTN generates or simply relays this activity. Entrained with the central respiratory network is the sympathetic nervous system, which exhibits patterns of discharge coupled with the respiratory cycle (in terms of both gain and phase of coupling) and dysfunctions in this coupling appear to underpin pathological conditions. In conclusion, the respiratory network has rhythmogenic capabilities at multiple levels of network organization, allowing expression of motor patterns specific for various physiological and pathophysiological respiratory behaviors. (C) 2009 Elsevier B.V. All rights reserved. C1 [Abdala, A. P. L.; Paton, J. F. R.] Univ Bristol, Sch Med Sci, Bristol Heart Inst, Dept Physiol & Pharmacol, Bristol BS8 1TD, Avon, England. [Rybak, I. A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Smith, J. C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Zoccal, D. B.; Machado, B. H.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Physiol, BR-14049 Ribeirao Preto, Brazil. [St-John, W. M.] Dartmouth Hitchcock Med Ctr, Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03755 USA. RP Paton, JFR (reprint author), Univ Bristol, Sch Med Sci, Bristol Heart Inst, Dept Physiol & Pharmacol, Univ Walk, Bristol BS8 1TD, Avon, England. EM julian.f.r.paton@bristol.ac.uk RI Abdala, Ana Paula/G-9104-2014; Zoccal, Daniel/I-9467-2012; OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913 FU National Institutes of Health (NIH); British Heart Foundation; Royal Society Wolfson Research Merit Award FX The support of the National Institutes of Health (NIH) and British Heart Foundation is acknowledged. JFRP is the recipient of a Royal Society Wolfson Research Merit Award. NR 34 TC 41 Z9 42 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD AUG 31 PY 2009 VL 168 IS 1-2 BP 19 EP 25 DI 10.1016/j.resp.2009.06.011 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 498OF UT WOS:000270150300004 PM 19540366 ER PT J AU Bugge, TH Antalis, TM Wu, QY AF Bugge, Thomas H. Antalis, Toni M. Wu, Qingyu TI Type II Transmembrane Serine Proteases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; FACTOR ACTIVATOR INHIBITOR-1B; PROSTATE-CANCER PROGRESSION; EPITHELIAL SODIUM-CHANNEL; CELL-SURFACE; GENE FUSION; PLASMINOGEN-ACTIVATOR; MATRIPTASE-2 TMPRSS6; FUNCTIONAL-ANALYSIS; IRON-DEFICIENCY AB Analysis of genome and expressed sequence tag data bases at the turn of the millennium unveiled a new protease family named the type II transmembrane serine proteases (TTSPs) in a Journal of Biological Chemistry minireview (Hooper, J. D., Clements, J. A., Quigley, J. P., and Antalis, T. M. (2001) J. Biol. Chem. 276, 857-860). Since then, the number of known TTSPs has more than doubled, and more importantly, our understanding of the physiological functions of individual TTSPs and their contribution to human disease has greatly increased. Progress has also been made in identifying molecular substrates and endogenous inhibitors. This minireview summarizes the current knowledge of the rapidly advancing TTSP field. C1 [Bugge, Thomas H.] NIH, Proteases & Tissue Remodeling Sect, NIDCR, Bethesda, MD 20892 USA. [Antalis, Toni M.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Antalis, Toni M.] Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. [Wu, Qingyu] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA. [Wu, Qingyu] Cleveland Clin, Lerner Res Inst, Dept Nephrol, Cleveland, OH 44195 USA. RP Bugge, TH (reprint author), NIH, Proteases & Tissue Remodeling Sect, NIDCR, Bldg 10, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU National Institutes of Health Intramural Program; National Institutes of Health [CA098369, HL084387, HL089298]; Mary Kay Ash Charitable Foundation [075-07] FX This work was supported, in wholeor in part, by the National Institutes of Health Intramural Program (to T. H. B.) and National Institutes of Health Grants CA098369 and HL084387 (to T. M. A.) and HL089298 (to Q. W.). This work was also supported by the Mary Kay Ash Charitable Foundation (075-07). This is the sixth article in the Thematic Minireview Series on Proteolytic Enzymes. The first article was published in the November 7, 2008 issue; the second and third articles were published in the May 22, 2009 issue; and the fourth and fifth articles were published in the July 31, 2009 issue. This minireview will be reprinted in the 2009 Minireview Compendium, which will be available in January, 2010. NR 61 TC 104 Z9 105 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23177 EP 23181 DI 10.1074/jbc.R109.021006 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000001 PM 19487698 ER PT J AU Griffon, N Jin, WJ Petty, TJ Millar, J Badellino, KO Saven, JG Marchadier, DH Kempner, ES Billheimer, J Glick, JM Rader, DJ AF Griffon, Nathalie Jin, Weijin Petty, Thomas J. Millar, John Badellino, Karen O. Saven, Jeffery G. Marchadier, Dawn H. Kempner, Ellis S. Billheimer, Jeffrey Glick, Jane M. Rader, Daniel J. TI Identification of the Active Form of Endothelial Lipase, a Homodimer in a Head-to-Tail Conformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; HUMAN HEPATIC LIPASE; RADIATION INACTIVATION; HEPARIN-BINDING; PROTEIN STRUCTURES; PANCREATIC LIPASE; SUBSTRATE-SPECIFICITY; CHIMERIC LIPASE; CATALYTIC SITE; HDL METABOLISM AB Endothelial lipase (EL) is a member of a subfamily of lipases that act on triglycerides and phospholipids in plasma lipoproteins, which also includes lipoprotein lipase and hepatic lipase. EL has a tropism for high density lipoprotein, and its level of phospholipase activity is similar to its level of triglyceride lipase activity. Inhibition or loss-of-function of EL in mice results in an increase in high density lipoprotein cholesterol, making it a potential therapeutic target. Although hepatic lipase and lipoprotein lipase have been shown to function as homodimers, the active form of EL is not known. In these studies, the size and conformation of the active form of EL were determined. Immunoprecipitation experiments suggested oligomerization. Ultracentrifugation experiments showed that the active form of EL had a molecular weight higher than the molecular weight of a simple monomer but less than a dimer. A construct encoding a covalent head-to-tail homodimer of EL (EL-EL) was expressed and had similar lipolytic activity to EL. The functional molecular weights determined by radiation inactivation were similar for EL and the covalent homodimer EL-EL. We previously showed that EL could be cleaved by proprotein convertases, such as PC5, resulting in loss of activity. In cells overexpressing PC5, the covalent homodimeric EL-EL appeared to be more stable, with reduced cleavage and conserved lipolytic activity. A comparative model obtained using other lipase structures suggests a structure for the head-to-tail EL homodimer that is consistent with the experimental findings. These data confirm the hypothesis that EL is active as a homodimer in head-to-tail conformation. C1 [Griffon, Nathalie; Jin, Weijin; Millar, John; Marchadier, Dawn H.; Billheimer, Jeffrey; Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Griffon, Nathalie; Jin, Weijin; Millar, John; Marchadier, Dawn H.; Billheimer, Jeffrey; Rader, Daniel J.] Univ Penn, Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA. [Glick, Jane M.] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Kempner, Ellis S.] NIAMS, NIH, Bethesda, MD 20892 USA. [Petty, Thomas J.; Saven, Jeffery G.] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Badellino, Karen O.] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. RP Rader, DJ (reprint author), Univ Penn, Sch Med, Inst Translat Med & Therapeut, Cardiovasc Inst, 654 BRBII-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM rader@mail.med.upenn.edu RI Petty, Tom/A-6758-2011 OI Petty, Tom/0000-0002-4007-6515 FU NHLBI [HL55323] FX This work was supported, in whole or in part, by National Institutes of Health Grant HL55323 from the NHLBI (to D.J.R.). NR 47 TC 21 Z9 24 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23322 EP 23330 DI 10.1074/jbc.M109.037002 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000017 PM 19567873 ER PT J AU Park, JW Mieyal, JJ Rhee, SG Chock, PB AF Park, Ji Won Mieyal, John J. Rhee, Sue Goo Chock, P. Boon TI Deglutathionylation of 2-Cys Peroxiredoxin Is Specifically Catalyzed by Sulfiredoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYSTEINE-SULFINIC ACID; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; MAMMALIAN PEROXIREDOXIN; REDUCE PEROXIDES; ACTIVE-SITE; GLUTATHIONYLATION; THIOREDOXIN; PROTEINS; IDENTIFICATION AB Reversible protein glutathionylation plays a key role in cellular regulation and cell signaling and protects protein thiols from hyperoxidation. Sulfiredoxin (Srx), an enzyme that catalyzes the reduction of Cys-sulfinic acid derivatives of 2-Cys peroxiredoxins (2-Cys Prxs), has been shown to catalyze the deglutathionylation of actin. We show that deglutathionylation of 2-Cys Prx, a family of peroxidases, is specifically catalyzed by Srx. Using the ubiquitously expressed member of 2-Cys Prx, Prx I, we revealed the following. (i) Among its four Cys residues, Cys(52), Cys(83), and Cys(173) can be glutathionylated in vitro. Deglutathionylation with Cys mutants showed that Cys(83) and Cys(173) were preferentially catalyzed by Srx, with glutathionylated Srx as the reaction intermediate, whereas glutaredoxin I was more favorable for deglutathionylating Cys(52). (ii) Studies using site-directed mutagenesis coupled with binding and deglutathionylation activities revealed that Pro(174) and Pro(179) of Prx I and Tyr(92) of Srx are essential for both activities. Furthermore, relative to glutaredoxin I, Srx exhibited negligible deglutathionylation activity for glutathionylated cysteine and glutathionylated BSA. These results indicate that Srx is specific for deglutathionylating Prx I due to its favorable affinity for Prx I. To assess the biological relevance of these observations, we showed that Prx I is glutathionylated in A549 and HeLa cells under modest levels of H(2)O(2). In addition, the level of glutathionylated Prx I was substantially elevated in small interfering RNA-mediated Srx-knocked down cells, whereas the reverse was observed in Srx-overexpressing cells. However, glutathionylation of Prx V, not known to bind to Srx, was not affected by the change in Srx expression levels. C1 [Rhee, Sue Goo] Ewha Womans Univ, Ctr Cell Signaling Res, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Park, Ji Won; Chock, P. Boon] NHLBI, Biochem Lab, Biochem & Biophys Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Mieyal, John J.] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. [Mieyal, John J.] Louis B Stokes Cleveland Vet Affairs Med Res Ctr, Cleveland, OH 44106 USA. RP Rhee, SG (reprint author), Ewha Womans Univ, Ctr Cell Signaling Res, Div Life & Pharmaceut Sci, 210 Sci Ctr Bldg,Block C,Dae Hyun Dong 11, Seoul 120750, South Korea. EM rheesg@ewha.ac.kr; chockp@mail.nih.gov FU National Institutes of Health [2 PO1 AG 15885]; NHLBI; Intramural Research Program; Brain Korea21; Korean Science and Engineering Foundation; Department of Veterans Affairs FX This work was supported, in whole or in part, by the National Institutes of Health, NHLBI, Intramural Research Program and by National Institutes of Health Research Grant 2 PO1 AG 15885 (to J.J.M.). This study was also supported in part by a Brain Korea21 grant (to J.W.P.), by BioR and D Program grants of Korean Science and Engineering Foundation (to S. G. R.), and by a Merit Review research grant from the Department of Veterans Affairs (to J.J.M.). NR 39 TC 62 Z9 64 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23364 EP 23374 DI 10.1074/jbc.M109.021394 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000021 PM 19561357 ER PT J AU Li, YJ Bolderson, E Kumar, R Muniandy, PA Xue, YT Richard, DJ Seidman, M Pandita, TK Khanna, KK Wang, WD AF Li, Yongjiang Bolderson, Emma Kumar, Rakesh Muniandy, Parameswary A. Xue, Yutong Richard, Derek J. Seidman, Michael Pandita, Tej K. Khanna, Kum Kum Wang, Weidong TI hSSB1 and hSSB2 Form Similar Multiprotein Complexes That Participate in DNA Damage Response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPLICATION PROTEIN-A; SINGLE-STRANDED-DNA; BLOOMS-SYNDROME PROTEIN; RNA-POLYMERASE-II; TOPOISOMERASE-I; FANCONI-ANEMIA; RAD52 PROTEIN; BINDING; REPAIR; STABILITY AB hSSB1 (human single strand DNA-binding protein 1) has been shown to participate in homologous recombination (HR)dependent repair of DNA double strand breaks (DSBs) and ataxia telangiectasia-mutated (ATM)-mediated checkpoint pathways. Here we present evidence that hSSB2, a homolog of hSSB1, plays a role similar to hSSB1 in DNA damage-response pathways. This was evidenced by findings that hSSB2-depleted cells resemble hSSB1-depleted cells in hypersensitivity to DNA-damaging reagents, reduced efficiency in HR-dependent repair of DSBs, and defective ATM-dependent phosphorylation. Notably, hSSB1 and hSSB2 form separate complexes with two identical proteins, INTS3 and hSSBIP1 (C9ORF80). Cells depleted of INTS3 and hSSBIP1 also exhibited hypersensitivity to DNA damage reagents, chromosomal instability, and reduced ATM-dependent phosphorylation. hSSBIP1 was rapidly recruited to laser-induced DSBs, a feature also similar to that reported for hSSB1. Depletion of INTS3 decreased the stability of hSSB1 and hSSBIP1, suggesting that INTS3 may provide a scaffold to allow proper assembly of the hSSB complexes. Thus, our data demonstrate that hSSB1 and hSSB2 form two separate complexes with similar structures, and both are required for efficient HR-dependent repair of DSBs and ATM-dependent signaling pathways. C1 [Li, Yongjiang; Xue, Yutong; Wang, Weidong] NIA, Genet Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Muniandy, Parameswary A.; Seidman, Michael] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Bolderson, Emma; Richard, Derek J.; Khanna, Kum Kum] Queensland Inst Med Res, Signal Transduct Lab, Brisbane, Qld 4029, Australia. [Kumar, Rakesh; Pandita, Tej K.] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. RP Wang, WD (reprint author), 251 Bayview Blvd,Rm 10B113, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov RI Bolderson, Emma/B-8743-2013; OI Richard, Derek/0000-0002-4839-8471 FU National Institutes of Health [Z01: AG000657-09]; National Institute on Aging and National Institutes of Health [CA123232, CA129537]; National Health and Medical Research Council of Australia FX This work was supported, in whole or in part, by National Institutes of Health Grant Z01: AG000657-09 from the Intramural Research Program of the National Institute on Aging and National Institutes of Health Grants CA123232 and CA129537 (to T. K. P.). This work was also supported by a grant from the National Health and Medical Research Council of Australia (to K. K. K.). NR 29 TC 54 Z9 61 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23525 EP 23531 DI 10.1074/jbc.C109.039586 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000037 PM 19605351 ER PT J AU Deng, Y Guo, Y Watson, H Au, WC Shakoury-Elizeh, M Basrai, MA Bonifacino, JS Philpott, CC AF Deng, Yi Guo, Yan Watson, Hadiya Au, Wei-Chun Shakoury-Elizeh, Minoo Basrai, Munira A. Bonifacino, Juan S. Philpott, Caroline C. TI Gga2 Mediates Sequential Ubiquitin-independent and Ubiquitin-dependent Steps in the Trafficking of ARN1 from the trans-Golgi Network to the Vacuole SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-BINDING PROTEINS; EPSIN-RELATED PROTEINS; SACCHAROMYCES-CEREVISIAE; FERRICHROME TRANSPORTER; MULTIVESICULAR BODY; STRUCTURAL BASIS; SORTING-SIGNAL; ENTH DOMAIN; YEAST; RECOGNITION AB In Saccharomyces cerevisiae, ARN1 encodes a transporter for the uptake of ferrichrome, an important nutritional source of iron. In the absence of ferrichrome, Arn1p is sorted directly from the trans-Golgi network (TGN) to the vacuolar lumen via the vacuolar protein-sorting pathway. Arn1p is mis-sorted to the plasma membrane in cells lacking Gga2p, a monomeric clathrin-adaptor protein involved in vesicular transport from the TGN. Although Ggas have been characterized as ubiquitin receptors, we show here that ubiquitin binding by Gga2 was not required for the TGN-to-endosome trafficking of Arn1, but it was required for subsequent sorting of Arn1 into the multivesicular body. In a ubiquitin-binding mutant of Gga2, Arn1p accumulated on the vacuolar membrane in a ubiquitinated form. The yeast epsins Ent3p and Ent4p were also involved in TGN-to-vacuole sorting of Arn1p. Amino-terminal sequences of Arn1p were required for vacuolar protein sorting, as mutation of ubiquitinatable lysine residues resulted in accumulation on the vacuolar membrane, and mutation of either a THN or YGL sequence resulted in mis-sorting to the plasma membrane. These studies suggest that Gga2 is involved in sorting at both the TGN and multivesicular and that the first step can occur without ubiquitin binding. C1 [Deng, Yi; Guo, Yan; Shakoury-Elizeh, Minoo; Philpott, Caroline C.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Watson, Hadiya; Bonifacino, Juan S.] Eunice Kennedy Shriver NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Au, Wei-Chun; Basrai, Munira A.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), Bldg 10,Rm 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov OI Bonifacino, Juan S./0000-0002-5673-6370 FU National Institutes of Health Intramural Research Programs of the NIDDK; Eunice Kennedy Shriver NICHD; NCI FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Programs of the NIDDK (to Y.D., Y.G., M.S.-E., and C.C.P.), the Eunice Kennedy Shriver NICHD (to H.W.and J.S.B.), and the NCI (to W.-C.A.and M.B.). NR 54 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 28 PY 2009 VL 284 IS 35 BP 23830 EP 23841 DI 10.1074/jbc.M109.030015 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 486EZ UT WOS:000269180000066 PM 19574226 ER PT J AU Yang, Y Aisa, HA Ito, Y AF Yang, Yi Aisa, Haji Akber Ito, Yoichiro TI Mathematical model of computer-programmed intermittent dual countercurrent chromatography applied to hydrostatic and hydrodynamic equilibrium systems SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Programmed intermittent dual countercurrent chromatography; Mathematical model; Spiral tube assembly; Toroidal coil countercurrent chromatography; Sliding valve; Hydrostatic and hydrodynamic equilibrium systems ID PURIFICATION; SEPARATION AB Dual high-speed countercurrent chromatography (dual CCC) literally permits countercurrent flow of two immiscible solvent phases continuously through the coiled column for separation of solutes according to their partition coefficients. Application of this technique has been successfully demonstrated by separation of analytes by gas-liquid and liquid-liquid two-phase systems. However, the method cannot be directly applied to the system with a set of coiled columns connected in series, since the countercurrent process is interrupted at the junction between the columns. However, this problem can be solved by intermittent dual CCC by eluting each phase alternately through the opposite ends of the separation column. This mode of application has an advantage over the conventional dual CCC in that the method can be applied to all types of CCC systems including hydrostatic equilibrium systems such as toroidal coil CCC and centrifugal partition chromatography. Recently, the application of this method to high-speed CCC (hydrodynamic system) has been demonstrated for separation of natural products by Hewitson et al. using a set of conventional multilayer coil separation columns connected in series. Here, we have developed a mathematical model for this intermittent dual CCC system to predict retention time of the analytes, and using a simplified model system the validity of the model is justified by a series of basic studies on both hydrodynamic and hydrostatic CCC systems with a computer-programmed single sliding valve. The present method has been successfully applied to spiral tube assembly high-speed CCC (hydrodynamic system) and toroidal coil CCC (hydrostatic system) for separation of DNP-amino acid samples with two biphasic solvent systems composed of hexane-ethyl acetate-methanol-0.1 M hydrochloric acid (1:11:1 and 4:5:4:5,v/v). Published by Elsevier B.V. C1 [Yang, Yi; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Yang, Yi; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China. [Yang, Yi] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China. RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 18 TC 25 Z9 26 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 28 PY 2009 VL 1216 IS 35 BP 6310 EP 6318 DI 10.1016/j.chroma.2009.07.015 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 488TE UT WOS:000269372200007 PM 19640542 ER PT J AU Krishna, S Orosz, L Sneppen, K Adhya, S Semsey, S AF Krishna, Sandeep Orosz, Laszlo Sneppen, Kim Adhya, Sankar Semsey, Szabolcs TI Relation of Intracellular Signal Levels and Promoter Activities in the gal Regulon of Escherichia coli SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE transcription; signal integration; regulatory network; gal regulon; computational biology ID INCOHERENT FEEDFORWARD LOOP; REGULATORY NETWORK; GLUCOSE INHIBITION; ADENYLATE-CYCLASE; INPUT FUNCTIONS; TRANSCRIPTION; DNA; INDUCER; OPERON; REPRESSOR AB Transcription of many genes is regulated by combinations of multiple signals. In Escherichia coli, combinatorial control is typical in the case of operons related to utilization of different sugars in the absence of glucose. To understand regulation of the transport and metabolic pathways in the galactose system, we measured activities of the six gal regulon promoters simultaneously, using an in vitro transcription system containing purified components. Input functions were computed on the basis of the experimental measurements. We observed four different shapes of input functions. From the results, we can conclude that the structure of the regulatory network is insufficient for the determination of signal integration. It is the actual structure of the promoter and regulatory region, the mechanism of transcription regulation, and the interplay between transcription factors that shape the input function to be suitable for adaptation. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Orosz, Laszlo; Semsey, Szabolcs] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. [Krishna, Sandeep; Sneppen, Kim] Niels Bohr Inst, Ctr Models Life, DK-2100 Copenhagen, Denmark. [Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Semsey, S (reprint author), Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. EM semseys@yahoo.com RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495; Sneppen, Kim/0000-0001-9820-3567 FU NIH; European Community Framework Program [OTKA PD75496]; Danish National Research Foundation; Hungarian Academy of Sciences FX We thank our colleagues in the laboratory for various inputs into the project, in particular Thomas Soares and Mofang Liu for purification of HU and CRP, and Takacsne Botond Judit for technical assistance. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by a Marie Curie Intemational Reintegration Grant within the 6th European Community Framework Program, by OTKA PD75496, and by the Danish National Research Foundation. S. S. is grateful for the Jinos Bolyai fellowship of the Hungarian Academy of Sciences. NR 34 TC 12 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 28 PY 2009 VL 391 IS 4 BP 671 EP 678 DI 10.1016/j.jmb.2009.06.043 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 489ZO UT WOS:000269466100002 PM 19559028 ER PT J AU Cao, L Xu, XL Bunting, SF Liu, J Wang, RH Cao, LYL Wu, JJ Peng, TN Chen, JJ Nussenzweig, A Deng, CX Finkel, T AF Cao, Liu Xu, Xioaling Bunting, Samuel F. Liu, Jie Wang, Rui-Hong Cao, Longyue L. Wu, J. Julie Peng, Tie-Nan Chen, Junjie Nussenzweig, Andre Deng, Chu-Xia Finkel, Toren TI A Selective Requirement for 53BP1 in the Biological Response to Genomic Instability Induced by Brca1 Deficiency SO MOLECULAR CELL LA English DT Article ID ONCOGENE-INDUCED SENESCENCE; DNA-DAMAGE; CELLULAR SENESCENCE; TUMOR SUPPRESSION; MICE LACKING; P53; TUMORIGENESIS; CANCER; ACTIVATION; APOPTOSIS AB The molecular pathways leading from genomic instability to cellular senescence and/or cell death remain incompletely characterized. Using mouse embryonic fibroblasts with constitutively increased DNA damage due to the absence of the full-length form of the tumor suppressor Brca1 (Brca1(Delta 11/Delta 11)), we show that deletion of p53 binding protein 1 (53BP1) selectivity abrogates senescence and cell death stimulated by reduced Brca1 activity. Furthermore, the embryonic lethality induced by Brca1 mutation can be alleviated by 53BP1 deletion. Adult Brca1(Delta 11/Delta 11)53BP1(-/-) manifest constitutively high levels of genomic instability, yet age relatively normally, with a surprisingly low incidence of overall tumor formation. Together, these in vitro and in vivo data suggest that 53BP1 is specifically required for the development of premature senescence and apoptosis induced by Brca1 deficiency. These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging. C1 [Cao, Liu; Liu, Jie; Cao, Longyue L.; Wu, J. Julie; Finkel, Toren] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Cao, Liu; Xu, Xioaling; Wang, Rui-Hong; Cao, Longyue L.; Deng, Chu-Xia] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Bunting, Samuel F.; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Peng, Tie-Nan] Jilin Univ, Stomatol Coll, Dept Oral & Maxillofacial Surg, Changchun 130041, Jilin Province, Peoples R China. [Chen, Junjie] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. RP Cao, L (reprint author), NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. EM liu.cao@nih.gov; chuxiad@bdg10.niddk.nih.gov; finkelt@nih.gov RI deng, chuxia/N-6713-2016 FU Ellison Medical Foundation FX We are grateful to N. Motoyama for the generous gift of Chk2-/- mice. This work was supported by NIH Intramural funds and a grant from the Ellison Medical Foundation (T.F.). NR 38 TC 129 Z9 130 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG 28 PY 2009 VL 35 IS 4 BP 534 EP 541 DI 10.1016/j.molcel.2009.06.037 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 489PK UT WOS:000269432600016 PM 19716796 ER PT J AU Samoshkin, A Arnaoutov, A Jansen, LET Ouspenski, I Dye, L Karpova, T McNally, J Dasso, M Cleveland, DW Strunnikov, A AF Samoshkin, Alexander Arnaoutov, Alexei Jansen, Lars E. T. Ouspenski, Ilia Dye, Louis Karpova, Tatiana McNally, James Dasso, Mary Cleveland, Don W. Strunnikov, Alexander TI Human Condensin Function Is Essential for Centromeric Chromatin Assembly and Proper Sister Kinetochore Orientation SO PLOS ONE LA English DT Article ID MITOTIC CHROMOSOME ARCHITECTURE; MAMMALIAN TISSUE-CELLS; AURORA-B; MICROTUBULE ATTACHMENT; HISTONE H3; SACCHAROMYCES-CEREVISIAE; MEROTELIC ATTACHMENT; STRUCTURAL INTEGRITY; INNER CENTROMERE; REGULATES MCAK AB Condensins I and II in vertebrates are essential ATP-dependent complexes necessary for chromosome condensation in mitosis. Condensins depletion is known to perturb structure and function of centromeres, however the mechanism of this functional link remains elusive. Depletion of condensin activity is now shown to result in a significant loss of loading of CENP-A, the histone H3 variant found at active centromeres and the proposed epigenetic mark of centromere identity. Absence of condensins and/or CENP-A insufficiency produced a specific kinetochore defect, such that a functional mitotic checkpoint cannot prevent chromosome missegregation resulting from improper attachment of sister kinetochores to spindle microtubules. Spindle microtubule-dependent deformation of both inner kinetochores and the HEC1/Ndc80 microtubule-capturing module, then results in kinetochore separation from the Aurora B pool and ensuing reduced kinase activity at centromeres. Moreover, recovery from mitosis-inhibition by monastrol revealed a high incidence of merotelic attachment that was nearly identical with condensin depletion, Aurora B inactivation, or both, indicating that the Aurora B dysfunction is the key defect leading to chromosome missegregation in condensin-depleted cells. Thus, beyond a requirement for global chromosome condensation, condensins play a pivotal role in centromere assembly, proper spatial positioning of microtubule-capturing modules and positioning complexes of the inner centromere versus kinetochore plates. RP Samoshkin, A (reprint author), NICHHD, Unit Chromosome Struct & Funct, NICHD, LGRD, Bethesda, MD 20892 USA. EM strunnik@mail.nih.gov OI Strunnikov, Alexander/0000-0002-9058-2256; Jansen, Lars/0000-0002-2158-0345; Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM074150, GM074150] NR 61 TC 46 Z9 46 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 28 PY 2009 VL 4 IS 8 AR e6831 DI 10.1371/journal.pone.0006831 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 489JG UT WOS:000269415800015 PM 19714251 ER PT J AU Kadan-Lottick, NS Brouwers, P Breiger, D Kaleita, T Dziura, J Liu, HB Chen, L Nicoletti, M Stork, L Bostrom, B Neglia, JP AF Kadan-Lottick, Nina S. Brouwers, Pim Breiger, David Kaleita, Thomas Dziura, James Liu, Haibei Chen, Lu Nicoletti, Megan Stork, Linda Bostrom, Bruce Neglia, Joseph P. TI A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia SO BLOOD LA English DT Article ID LONG-TERM SURVIVORS; ACUTE LYMPHOCYTIC-LEUKEMIA; COGNITIVE SEQUELAE; NEUROPSYCHOLOGICAL SEQUELAE; CRANIAL IRRADIATION; MENINGEAL LEUKEMIA; CANCER GROUP; SCHOOL-AGE; CHEMOTHERAPY; THERAPY AB In previous clinical trials of childhood acute lymphoblastic leukemia (ALL), dexamethasone resulted in higher event-free survival rates than prednisone, presumably due to greater central nervous system penetration. Dexamethasone's association with long-term neurocognitive toxicity is unknown. In this multisite study, we measured neurocognitive functioning in 92 children with standard-risk ALL, 1 to 9.99 years at diagnosis, at a mean of 9.8 years after randomization to prednisone (n = 41) or dexamethasone (n = 51) on Children's Cancer Group (CCG) 1922. No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age, sex, and time since diagnosis. The exception was that patients receiving dexamethasone scored one-third of a standard deviation worse on word reading (98.8 +/- 1.7 vs 104.9 +/- 1.8; P = .02). There were no group differences in the distribution of test scores or the parents' report of neurologic complications, psychotropic drug use, and special education. Further analyses suggested for the dexamethasone group, older age of diagnosis was associated with worse neurocognitive functioning; for the prednisone group, younger age at diagnosis was associated with worse functioning. In conclusion, our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid randomization. This study is registered with http://www.clinicaltrials.gov under NCT00085176. (Blood. 2009;114:1746-1752) C1 [Kadan-Lottick, Nina S.; Nicoletti, Megan] Yale Univ, Sch Med, New Haven, CT USA. [Kadan-Lottick, Nina S.; Nicoletti, Megan] Yale Canc Ctr, New Haven, CT USA. [Brouwers, Pim] Texas Childrens Canc Ctr, Houston, TX USA. [Brouwers, Pim] NIMH, Rockville, MD 20857 USA. [Breiger, David] Univ Washington, Sch Med, Seattle, WA USA. [Kaleita, Thomas] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Dziura, James; Liu, Haibei] Yale Ctr Clin Invest, New Haven, CT USA. [Chen, Lu] Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. [Stork, Linda] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bostrom, Bruce] Childrens Hosp & Clin, Minneapolis, MN USA. [Neglia, Joseph P.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Kadan-Lottick, NS (reprint author), 333 Cedar St LMP 2073,POB 208064, New Haven, CT 06520 USA. EM nina.kadan-lottick@yale.edu FU NCI NIH HHS [U10 CA98543, U10 CA98413, U10 CA95861, U10 CA095861, U10 CA098413, U10 CA098543]; NCRR NIH HHS [KL2 RR024138] NR 36 TC 39 Z9 41 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1746 EP 1752 DI 10.1182/blood-2008-12-186502 PG 7 WC Hematology SC Hematology GA 488WI UT WOS:000269380600009 PM 19546477 ER PT J AU Klebanoff, CA Yu, ZY Hwang, LN Palmer, DC Gattinoni, L Restifo, NP AF Klebanoff, Christopher A. Yu, Zhiya Hwang, Leroy N. Palmer, Douglas C. Gattinoni, Luca Restifo, Nicholas P. TI Programming tumor-reactive effector memory CD8(+) T cells in vitro obviates the requirement for in vivo vaccination SO BLOOD LA English DT Article ID ANTITUMOR-ACTIVITY; ADOPTIVE TRANSFER; TRANSFER THERAPY; METASTATIC MELANOMA; CANCER REGRESSION; DENDRITIC CELLS; STEM-CELLS; EX-VIVO; IMMUNOTHERAPY; EXPANSION AB Naive and memory CD8(+) T cells can undergo programmed activation and expansion in response to a short T-cell receptor stimulus, but the extent to which in vitro programming can qualitatively substitute for an in vivo antigen stimulation remains unknown. We show that self-/tumor-reactive effector memory CD8(+) T cells (T(EM)) programmed in vitro either with peptide-pulsed antigen-presenting cells or plate-bound anti-CD3/anti-CD28 embark on a highly stereotyped response of in vivo clonal expansion and tumor destruction nearly identical to that of vaccine-stimulated TEM cells. This programmed response was associated with an interval of antigen-independent interferon-gamma (IFN-gamma) release that facilitated the dynamic expression of the major histocompatibility complex class I restriction element H-2D(b) on responding tumor cells, leading to recognition and subsequent tumor lysis. Delaying cell transfer for more than 24 hours after stimulation or infusion of cells deficient in IFN-gamma entirely abrogated the benefit of the programmed response, whereas transfer of cells unable to respond to IFN-gamma had no detriment to antitumor immunity. These findings extend the phenomenon of a programmable effector response to memory CD8(+) T cells and have major implications for the design of current adoptive-cell transfer trials. (Blood. 2009;114:1776-1783) C1 [Klebanoff, Christopher A.; Yu, Zhiya; Hwang, Leroy N.; Palmer, Douglas C.; Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Klebanoff, Christopher A.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20817 USA. RP Klebanoff, CA (reprint author), NCI, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM klebanoc@mail.nih.gov; restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/D-9581-2011; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU National Cancer Institute, National Institutes of Health; Howard Hughes Medical Institute FX This study was done in partial fulfillment of a PhD in Biochemistry (to D. C. P.) at The George Washington University, Washington, DC. NR 56 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1776 EP 1783 DI 10.1182/blood-2008-12-192419 PG 8 WC Hematology SC Hematology GA 488WI UT WOS:000269380600013 PM 19561320 ER PT J AU Greenwell-Wild, T Vazquez, N Jin, WW Rangel, Z Munson, PJ Wahl, SM AF Greenwell-Wild, Teresa Vazquez, Nancy Jin, Wenwen Rangel, Zoila Munson, Peter J. Wahl, Sharon M. TI Interleukin-27 inhibition of HIV-1 involves an intermediate induction of type I interferon SO BLOOD LA English DT Article ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; LEUKOCYTE PROTEASE INHIBITOR; INNATE ANTIVIRAL RESPONSE; IL-27 GENE-EXPRESSION; NF-KAPPA-B; GASTROINTESTINAL-TRACT; ENTRY INHIBITORS; ALPHA-INTERFERON; FAMILY PROTEINS AB Infection of CD4(+) chemokine coreceptor(+) targets by HIV is aided and abetted by the proficiency of HIV in eliminating or neutralizing host cell-derived defensive molecules. Among these innate protective molecules, a family of intracellular apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminases, is constitutively expressed but inactivated by HIV viral infectivity factor. The ability of interferon-alpha (IFN-alpha) to augment cytidine deaminases offered the possibility that the balance between virus and target cell might be altered in favor of the host. Further characterization of transcriptional profiles induced by IFN-alpha using microarrays, with the intention to identify and dissociate retroviral countermaneuvers from associated toxicities, revealed multiple molecules with suspected antiviral activity, including IL-27. To establish whether IFN-alpha toxicity might be sidestepped through the use of downstream IL-27 against HIV, we examined whether IL-27 directly regulated cytidine deaminases. Although IL-27 induces APOBECs, it does so in a delayed fashion. Dissecting the underlying regulatory events uncovered an initial IL-27 dependent induction of IFN-alpha and/or IFN-beta, which in turn, induces APOBEC3, inhibited by IFN-alpha/beta receptor blockade. In addition to macrophages, the IL-27-IFN-alpha connection is operative in CD4(+) T cells, consistent with an IFN-alpha-dependent pathway underlying host cell defense to HIV. (Blood. 2009;114:1864-1874) C1 [Wahl, Sharon M.] NIDCR, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. [Rangel, Zoila; Munson, Peter J.] NIH, Ctr Informat Technol, Div Computat Biosci, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, NIH, Oral Infect & Immun Branch, Bldg 30,Room 320,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. EM smwahl@dir.nidcr.nih.gov FU National Institutes of Health; National Institute of Dental; Craniofacial Research FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Dental and Craniofacial Research. NR 50 TC 40 Z9 41 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1864 EP 1874 DI 10.1182/blood-2009-03-211540 PG 11 WC Hematology SC Hematology GA 488WI UT WOS:000269380600023 PM 19556424 ER PT J AU Anong, WA Franco, T Chu, HY Weis, TL Devlin, EE Bodine, DM An, XL Mohandas, N Low, PS AF Anong, William A. Franco, Taina Chu, Haiyan Weis, Tahlia L. Devlin, Emily E. Bodine, David M. An, Xiuli Mohandas, Narla Low, Philip S. TI Adducin forms a bridge between the erythrocyte membrane and its cytoskeleton and regulates membrane cohesion SO BLOOD LA English DT Article ID SPECTRIN-ACTIN BINDING; HEREDITARY SPHEROCYTOSIS; GLYCOPHORIN-C; CELL MEMBRANE; CYTOPLASMIC DOMAIN; HEMOLYTIC-ANEMIA; ANKYRIN-BINDING; ALPHA-ADDUCIN; PROTEIN 4.1; BAND-3 AB The erythrocyte membrane skeleton is the best understood cytoskeleton. Because its protein components have homologs in virtually all other cells, the membrane serves as a fundamental model of biologic membranes. Modern textbooks portray the membrane as a 2-dimensional spectrin-based membrane skeleton attached to a lipid bilayer through 2 linkages: band 3-ankyrin-beta-spectrin and glycophorin C-protein 4.1-beta-spectrin.(1-7) Although evidence supports an essential role for the first bridge in regulating membrane cohesion, rupture of the glycophorin C-protein 4.1 interaction has little effect on membrane stability.(8) We demonstrate the existence of a novel band 3 adducin-spectrin bridge that connects the spectrin/actin/protein 4.1 junctional complex to the bilayer. As rupture of this bridge leads to spontaneous membrane fragmentation, we conclude that the band 3-adducin spectrin bridge is important to membrane stability. The required relocation of part of the band 3 population to the spectrin/actin junctional complex and its formation of a new bridge with adducin necessitates a significant revision of accepted models of the erythrocyte membrane. (Blood. 2009; 114: 1904-1912) C1 [Anong, William A.; Franco, Taina; Chu, Haiyan; Weis, Tahlia L.; Low, Philip S.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Devlin, Emily E.; Bodine, David M.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [An, Xiuli; Mohandas, Narla] New York Blood Ctr, Physiol Lab, New York, NY USA. RP Low, PS (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA. EM plow@purdue.edu OI Low, Philip/0000-0001-9042-5528 FU National Institutes of Health [GM24417-29] FX This work was supported by National Institutes of Health Grant GM24417-29. NR 50 TC 74 Z9 74 U1 3 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 27 PY 2009 VL 114 IS 9 BP 1904 EP 1912 DI 10.1182/blood-2009-02-203216 PG 9 WC Hematology SC Hematology GA 488WI UT WOS:000269380600028 PM 19567882 ER PT J AU McNeil, BD Wu, LG AF McNeil, Benjamin D. Wu, Ling-Gang TI Location Matters: Synaptotagmin Helps Place Vesicles Near Calcium Channels SO NEURON LA English DT Editorial Material ID CENTRAL SYNAPSE; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; CA2+; CALYX; DEPENDENCE AB Positioning releasable vesicles near voltage-gated calcium channels may ensure transmitter release upon calcium influx. Disruption of vesicle positioning may underlie short-term synaptic depression. However, how this positioning is achieved is unclear. In this issue of Neuron, Young and Neher find that synaptotagmin 2 helps to align readily releasable vesicles near calcium channels at nerve terminals. C1 [McNeil, Benjamin D.; Wu, Ling-Gang] NINDS, Bethesda, MD 20892 USA. RP Wu, LG (reprint author), NINDS, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI McNeil, Benjamin/0000-0001-7545-3598 FU Intramural NIH HHS [Z01 NS003009-05, Z01 NS003009-04] NR 15 TC 3 Z9 3 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 27 PY 2009 VL 63 IS 4 BP 419 EP 421 DI 10.1016/j.neuron.2009.08.001 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 491HV UT WOS:000269570400001 PM 19709623 ER PT J AU Lauer, MS AF Lauer, Michael S. TI Elements of Danger -- The Case of Medical Imaging. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID DISEASE C1 NHLBI, Bethesda, MD 20892 USA. RP Lauer, MS (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 5 TC 80 Z9 81 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 27 PY 2009 VL 361 IS 9 BP 841 EP 843 DI 10.1056/NEJMp0904735 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 487XV UT WOS:000269312700001 PM 19710480 ER PT J AU Hoenerhoff, MJ Chu, I Barkan, D Liu, ZY Datta, S Dimri, GP Green, JE AF Hoenerhoff, M. J. Chu, I. Barkan, D. Liu, Z-y Datta, S. Dimri, G. P. Green, J. E. TI BMI1 cooperates with H-RAS to induce an aggressive breast cancer phenotype with brain metastases SO ONCOGENE LA English DT Article DE BMI1; H-RAS; breast cancer; metastasis ID MAMMARY EPITHELIAL-CELLS; STEM-CELLS; CARCINOMA; MYC; TUMORIGENESIS; TRASTUZUMAB; EXPRESSION; APOPTOSIS; THERAPY; RENEWAL AB B-lymphoma Moloney murine leukaemia virus insertion region-1 (BMI1) is a member of the polycomb group of transcription repressors, which functions in stem cell maintenance and oncogenesis through the inhibition of the INK4A/ARF tumour suppressor locus. Overexpression of BMI1 is associated with poor prognosis in several human cancers, including breast cancer. We have previously shown that BMI1 collaborates with H-RAS to induce transformation of MCF10A human mammary epithelial cells through dysregulation of multiple growth pathways independent of the INK4A/ARF locus. In this study, we show that BMI1 collaborates with H-RAS to promote increased proliferation, invasion and resistance to apoptosis in vitro, and an increased rate of spontaneous metastases from mammary fat pad xenografts including novel metastases to the brain. Furthermore, in collaboration with H-RAS, BMI1 induced fulminant metastatic disease in the lung using a tail vein model of haematogenous spread through accelerated cellular proliferation and inhibition of apoptosis. Finally, we show that knockdown of BMI1 in several established breast cancer cell lines leads to decreased oncogenic behaviour in vitro and in vivo. In summary, BMI1 collaborates with H-RAS to induce an aggressive and metastatic phenotype with the unusual occurrence of brain metastasis, making it an important target for diagnosis and treatment of aggressive breast cancer. Oncogene (2009) 28, 3022-3032; doi:10.1038/onc.2009.165; published online 22 June 2009 C1 [Hoenerhoff, M. J.; Chu, I.; Barkan, D.; Liu, Z-y; Green, J. E.] NCI, Transgen Oncogenesis Grp, Lab Canc Biol & Genet, NIH, Bethesda, MD 20982 USA. [Datta, S.; Dimri, G. P.] Northwestern Univ, N Shore Univ Hlth Syst Res Inst, Feinberg Sch Med, Div Canc Biol, Evanston, IL USA. [Datta, S.; Dimri, G. P.] Northwestern Univ, N Shore Univ Hlth Syst Res Inst, Feinberg Sch Med, Dept Med, Evanston, IL USA. RP Green, JE (reprint author), NCI, Transgen Oncogenesis Grp, Lab Canc Biol & Genet, NIH, 37 Convent Dr,Bldg 37,Room 4054, Bethesda, MD 20982 USA. EM jegreen@nih.gov FU NIH; Center for Cancer Research; National Cancer Institute [RO1CA 094150] FX We are grateful to Max Wicha for providing the shRNA lentiviral constructs, George Dunn, Asa Dorsey and Gail McMullen for animal care, Zi-ayo Liu for lentiviral transductions and Suresh Arya for advice on lentiviral preparation, and Aleksandra Michalowski and the NIH Biostatisitics Branch for assistance with statistical analysis. This work was supported in part by the Intramural Program of the NIH, Center for Cancer Research, National Cancer Institute and by RO1CA 094150 (GD). NR 31 TC 61 Z9 62 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 27 PY 2009 VL 28 IS 34 BP 3022 EP 3032 DI 10.1038/onc.2009.165 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 487ZU UT WOS:000269319000002 PM 19543317 ER PT J AU Ferrari, PF Bonini, L Fogassi, L AF Ferrari, P. F. Bonini, L. Fogassi, L. TI From monkey mirror neurons to primate behaviours: possible 'direct' and 'indirect' pathways SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Review DE imitation; motor cognition; development ID CHIMPANZEES PAN-TROGLODYTES; VENTRAL PREMOTOR CORTEX; CHILDREN HOMO-SAPIENS; PRIMARY MOTOR CORTEX; SOCIAL COGNITION; MACAQUE MONKEY; FUNCTIONAL-ORGANIZATION; GRASP REPRESENTATIONS; IMITATION RECOGNITION; VISUAL RESPONSES AB The discovery of mirror neurons (MNs), deemed to be at the basis of action understanding, could constitute the potential solution to the 'correspondence problem' between one's own and others' action that is crucial for of imitative behaviours. However, it is still to be clarified whether, and how, several imitative phenomena, differing in terms of complexity and cognitive effort, could be explained within a unified framework based on MNs. Here we propose that MNs could differently contribute to distinct imitative behaviours by means of two anatomo-functional pathways, subjected to changes during development. A 'direct mirror pathway', directly influencing the descending motor output, would be responsible for neonatal and automatic imitation. This proposal is corroborated by some new behavioural evidences provided here. During development, the increased control of voluntary movements and the capacity to efficiently suppress automatic motor activation during action observation assign to the core MNs regions essentially perceptuo-cognitive functions. These functions would be exploited by an 'indirect mirror pathway' from the core regions of the MN system to prefrontal cortex. This latter would play a key role in parsing, storing and organizing motor representations, allowing the emergence of more efficient and complex imitative behaviours such as response facilitation and true imitation. C1 [Ferrari, P. F.] Univ Parma, Dipartimento Biol Evolut & Funz, I-43100 Parma, Italy. [Ferrari, P. F.; Bonini, L.; Fogassi, L.] Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. [Ferrari, P. F.] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Fogassi, L.] Univ Parma, Dipartimento Psicol, I-43100 Parma, Italy. RP Ferrari, PF (reprint author), Univ Parma, Dipartimento Biol Evolut & Funz, Via Usberti 11-A, I-43100 Parma, Italy. EM pierfrancesco.ferrari@unipr.it FU European Program Neurocom [12738. 2005-2008]; MIUR (Cofin) [2004057380]; Division of Intramural research, National Institute of Child Health and Human Development, NIH FX This work was supported by European Program Neurocom no. 12738. 2005-2008, MIUR (Cofin) no. 2004057380 and Division of Intramural research, National Institute of Child Health and Human Development, NIH. We thank Annika Paukner and Fausto Caruana for their useful comments on an earlier version of the manuscript. NR 114 TC 71 Z9 72 U1 1 U2 19 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD AUG 27 PY 2009 VL 364 IS 1528 BP 2311 EP 2323 DI 10.1098/rstb.2009.0062 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 472ID UT WOS:000268122900003 PM 19620103 ER PT J AU Cohen, H Parekh, P Sercan, Z Kotekar, A Weissman, JD Singer, DS AF Cohen, Helit Parekh, Palak Sercan, Zeynep Kotekar, Aparna Weissman, Jocelyn D. Singer, Dinah S. TI In Vivo Expression of MHC Class I Genes Depends on the Presence of a Downstream Barrier Element SO PLOS ONE LA English DT Article AB Regulation of MHC class I gene expression is critical to achieve proper immune surveillance. In this work, we identify elements downstream of the MHC class I promoter that are necessary for appropriate in vivo regulation: a novel barrier element that protects the MHC class I gene from silencing and elements within the first two introns that contribute to tissue specific transcription. The barrier element is located in intergenic sequences 39 to the polyA addition site. It is necessary for stable expression in vivo, but has no effect in transient transfection assays. Accordingly, in both transgenic mice and stably transfected cell lines, truncation of the barrier resulted in transcriptional gene silencing, increased nucleosomal density and decreased histone H3K9/K14 acetylation and H3K4 di-methylation across the gene. Significantly, distinct sequences within the barrier element govern anti-silencing and chromatin modifications. Thus, this novel barrier element functions to maintain transcriptionally permissive chromatin organization and prevent transcriptional silencing of the MHC class I gene, ensuring it is poised to respond to immune signaling. RP Cohen, H (reprint author), NIH, Expt Immunol Branch, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA. EM Dinah.singer@nih.gov RI Parekh, Palak/B-7042-2015 OI Parekh, Palak/0000-0001-9201-5194 FU Intramural NIH HHS NR 65 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 26 PY 2009 VL 4 IS 8 AR e6748 DI 10.1371/journal.pone.0006748 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 488FQ UT WOS:000269335000007 PM 19707598 ER PT J AU Makarova, KS Wolf, YI van der Oost, J Koonin, EV AF Makarova, Kira S. Wolf, Yuri I. van der Oost, John Koonin, Eugene V. TI Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements SO BIOLOGY DIRECT LA English DT Article ID MESSENGER-RNA TARGETS; SILENCING COMPLEX; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; ARCHAEOGLOBUS-FULGIDUS; COMPARATIVE GENOMICS; HISTONE DEACETYLASE; AEOLICUS ARGONAUTE; REGULATORY RNAS; SLICER ACTIVITY AB Background: In eukaryotes, RNA interference (RNAi) is a major mechanism of defense against viruses and transposable elements as well of regulating translation of endogenous mRNAs. The RNAi systems recognize the target RNA molecules via small guide RNAs that are completely or partially complementary to a region of the target. Key components of the RNAi systems are proteins of the Argonaute-PIWI family some of which function as slicers, the nucleases that cleave the target RNA that is base-paired to a guide RNA. Numerous prokaryotes possess the CRISPR-associated system (CASS) of defense against phages and plasmids that is, in part, mechanistically analogous but not homologous to eukaryotic RNAi systems. Many prokaryotes also encode homologs of Argonaute-PIWI proteins but their functions remain unknown. Results: We present a detailed analysis of Argonaute-PIWI protein sequences and the genomic neighborhoods of the respective genes in prokaryotes. Whereas eukaryotic Ago/PIWI proteins always contain PAZ (oligonucleotide binding) and PIWI (active or inactivated nuclease) domains, the prokaryotic Argonaute homologs (pAgos) fall into two major groups in which the PAZ domain is either present or absent. The monophyly of each group is supported by a phylogenetic analysis of the conserved PIWI-domains. Almost all pAgos that lack a PAZ domain appear to be inactivated, and the respective genes are associated with a variety of predicted nucleases in putative operons. An additional, uncharacterized domain that is fused to various nucleases appears to be a unique signature of operons encoding the short (lacking PAZ) pAgo form. By contrast, almost all PAZ-domain containing pAgos are predicted to be active nucleases. Some proteins of this group (e. g., that from Aquifex aeolicus) have been experimentally shown to possess nuclease activity, and are not typically associated with genes for other (putative) nucleases. Given these observations, the apparent extensive horizontal transfer of pAgo genes, and their common, statistically significant over-representation in genomic neighborhoods enriched in genes encoding proteins involved in the defense against phages and/or plasmids, we hypothesize that pAgos are key components of a novel class of defense systems. The PAZ-domain containing pAgos are predicted to directly destroy virus or plasmid nucleic acids via their nuclease activity, whereas the apparently inactivated, PAZ-lacking pAgos could be structural subunits of protein complexes that contain, as active moieties, the putative nucleases that we predict to be co-expressed with these pAgos. All these nucleases arepredicted to be DNA endonucleases, so it seems most probable that the putative novel phage/plasmid-defense system targets phage DNA rather than mRNAs. Given that in eukaryotic RNAi systems, the PAZ domain binds a guide RNA and positions it on the complementary region of the target, we further speculate that pAgos function on a similar principle (the guide being either DNA or RNA), and that the uncharacterized domain found in putative operons with the short forms of pAgos is a functional substitute for the PAZ domain. Conclusion: The hypothesis that pAgos are key components of a novel prokaryotic immune system that employs guide RNA or DNA molecules to degrade nucleic acids of invading mobile elements implies a functional analogy with the prokaryotic CASS and a direct evolutionary connection with eukaryotic RNAi. The predictions of the hypothesis including both the activities of pAgos and those of the associated endonucleases are readily amenable to experimental tests. Reviewers: This article was reviewed by Daniel Haft, Martijn Huynen, and Chris Ponting. C1 [Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [van der Oost, John] Wageningen Univ, Microbiol Lab, Dept Agrotechnol & Food Sci, NL-6703 HB Wageningen, Netherlands. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM makarova@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; john.vanderoost@wur.nl; koonin@ncbi.nlm.nih.gov FU DHHS FX KSM, YIW and EVK are supported by intramural funds of the DHHS (National Library of Medicine, National Institutes of Health) NR 77 TC 62 Z9 64 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD AUG 25 PY 2009 VL 4 AR 29 DI 10.1186/1745-6150-4-29 PG 15 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 499MB UT WOS:000270223300002 PM 19706170 ER PT J AU Pagani, JH Rosen, JB AF Pagani, Jerome H. Rosen, Jeffrey B. TI The medial hypothalamic defensive circuit and 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) induced fear: Comparison of electrolytic and neurotoxic lesions SO BRAIN RESEARCH LA English DT Article DE Trimethylthiazoline; Predator odor; Conditioned fear; Anterior hypothalamus; Ventromedial hypothalamus; Dorsal premammillary nucleus ID DORSAL PREMAMMILLARY NUCLEUS; STRIA TERMINALIS; BED NUCLEUS; FOX ODOR; VENTROMEDIAL HYPOTHALAMUS; CONDITIONED FEAR; PREDATOR ODOR; UNCONDITIONED FEAR; CAT ODOR; PERIAQUEDUCTAL GRAY AB The neural circuits for unconditioned fear to predator odors (e.g., cat fur odor, trimethylthiazoline, TMT) are not well delineated. A putative neural circuit for predator odor fear, the medial hypothalamic defensive circuit (MHDC), consisting of the anterior hypothalamic (AHN), ventromedial hypothalamic (VMH) and dorsal premammillary nuclei (PMd), has been proposed. Electrolytic and ibotenic acid lesions of the PMd have been shown to reduce unconditioned fear in rats presented with either a cat or cat odor. Whether the PMd, AHN and VMH are involved in unconditioned fear to another predator odor derived from fox feces, 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), has not been explored. The present study compared the effects of electrolytic and neurotoxic lesions of MHDC nuclei in rats on unconditioned fear to TMT and shock-induced contextually conditioned fear, as measured by freezing. Electrolytic lesions of the PMd did not reduce TMT-induced freezing, but diminished post-shock and shock-induced contextually conditioned freezing, suggesting a role for the PMd in contextually conditioned fear. In contrast, electrolytic lesions of the AHN and VMH reduced freezing to TMT while not affecting conditioned fear. However, neither NMDA lesions of the AHN nor ibotenic acid lesions of the VMH reduced freezing in shock-induced conditioned or TMT-induced unconditioned fear paradigms. The data suggest that fibers passing through the AHN and VMH, and not cells in the MHDC, mediate unconditioned freezing to the predator odor TMT. (C) 2009 Elsevier B.V. All rights reserved. C1 [Pagani, Jerome H.; Rosen, Jeffrey B.] Univ Delaware, Dept Psychol, Newark, DE 19716 USA. RP Pagani, JH (reprint author), NIMH, Sect Neural Gene Express, Bldg 49,Room 5A51, Bethesda, MD 20892 USA. NR 75 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 25 PY 2009 VL 1286 BP 133 EP 146 DI 10.1016/j.brainres.2009.06.062 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 488VI UT WOS:000269378000016 PM 19559688 ER PT J AU Cook, MB Chow, WH Devesa, SS AF Cook, M. B. Chow, W-H Devesa, S. S. TI Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977-2005 SO BRITISH JOURNAL OF CANCER LA English DT Article DE adenocarcinoma; squamous cell; oesophagus; incidence; SEER program; trends ID GASTROESOPHAGEAL-REFLUX DISEASE; BODY-MASS INDEX; BARRETTS-ESOPHAGUS; GASTRIC CARDIA; VEGETABLE INTAKE; RACIAL GROUPS; REGISTRY DATA; ADENOCARCINOMA; RISK; METAANALYSIS AB BACKGROUND: In the United States, the rates and temporal trends of oesophageal cancer overall and for the two predominant histologic types-adenocarcinoma (ADC) and squamous cell carcinoma (SCC)-differ between Blacks and Whites, but little is known with regard to the patterns among Asians/ Pacific Islanders or Hispanics. METHODS: Using the Surveillance, Epidemiology, and End Results programme data, we analysed oesophageal cancer incidence patterns by race, sex, and histologic type for the period 1977-2005. RESULTS: Total oesophageal cancer incidence has been increasing among Whites only; the rates among all other race groups have declined. Moreover, rates among White men surpassed those among Blacks in 2004. Oesophageal SCC rates have been decreasing among virtually all racial/ethnic groups; rates among Hispanic and Asian/Pacific Islander men have been intermediate to those of Blacks and Whites, with rates among women being lower than those among Blacks or Whites. The ADC rates among Hispanic men may be rising, akin to the historical trends among Whites and Blacks. The sex ratios for these cancers also varied markedly. CONCLUSIONS: These observations may provide clues for aetiological research. British Journal of Cancer ( 2009) 101, 855-859. doi:10.1038/sj.bjc.6605246 www.bjcancer.com Published online 11 August 2009 (C) 2009 Cancer Research UK C1 [Cook, M. B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20852 USA. RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS Suite 550,Room 5012, Bethesda, MD 20852 USA. EM cookmich@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural Program of the National Cancer Institute; National Institutes of Health, Department of Health and Human Services FX We thank the SEER Program staff across the country and here at NCI for their invaluable data, and John Lahey of IMS, Inc., David Check of BB, DCEG, and Danny Carreon of HREB, DCEG for figure development. Intramural Program of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services funded the work. NR 50 TC 162 Z9 167 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 25 PY 2009 VL 101 IS 5 BP 855 EP 859 DI 10.1038/sj.bjc.6605246 PG 5 WC Oncology SC Oncology GA 487XW UT WOS:000269312800016 PM 19672254 ER PT J AU Ko, SU Ling, SM Winters, J Ferrucci, L AF Ko, Seung Uk Ling, Shari M. Winters, Joshua Ferrucci, Luigi TI Age-related mechanical work expenditure during normal walking: The Baltimore Longitudinal Study of Aging SO JOURNAL OF BIOMECHANICS LA English DT Article DE Mechanical work expenditure; Walking speed; Gait phase; Medial-lateral stability ID KINETIC VARIABLES; JOINT TORQUES; GAIT; PATTERNS; ADULTS; OSTEOARTHRITIS; GENERATION; SPEED; ANKLE; YOUNG AB The aim of this cross-sectional study was to delineate age-associated kinematic and kinetic gait patterns of normal walking, and to test the hypothesis that older adults exhibit gait patterns that reduce generative mechanical work expenditures (MWEs). We studied 52 adult Baltimore Longitudinal Study of Aging participants (means age 72 +/- 9, from 60 to 92 years) who could walk 4m unaided. Three-dimensional kinematic and kinetic parameters assessed during rotation-defined gait periods were used to estimate MWEs for the rotation of lower extremities about the medial-lateral (ML) and anterior-posterior (AP) axes of proximal joints, which represent MWEs in the AP and ML sides, respectively. Relationships between gait parameters and age were examined using regression analysis with adjustments for walking speed, sex, height, and weight. Older age was associated with slower self-selected walking speed (p < 0.001), shorter stride length (p < 0.001), and greater propensity of landing flat-footed (p = 0.003). With older age, hip generative MWE for thigh rotation was lower about the AP axis (hip abduction and adduction) during stance (p = 0.010) and higher about the ML axis (hip extension and flexion) during late stance (p<0.001). Knee absorptive MWE for shank rotation about the AP axis (knee abduction and adduction) during early stance was also lower with older age (p < 0.003). These age-related gait patterns may represent a compensatory effort to maintain balance and may also reflect mobility limitations. Published by Elsevier Ltd. C1 [Ko, Seung Uk; Ling, Shari M.; Winters, Joshua; Ferrucci, Luigi] NIA, Clin Res Branch, Harbor Hosp, Baltimore, MD 21225 USA. RP Ko, SU (reprint author), NIA, Clin Res Branch, Harbor Hosp, 3001 S Hanover St, Baltimore, MD 21225 USA. EM kos2@mail.nih.gov RI Agaliotis, Maria/G-5334-2012 FU NIH; National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the National Institute on Aging. NR 23 TC 25 Z9 26 U1 1 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD AUG 25 PY 2009 VL 42 IS 12 BP 1834 EP 1839 DI 10.1016/j.jbiomech.2009.05.037 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 493KB UT WOS:000269734200004 PM 19646705 ER PT J AU Wilson, NA Sheehan, FT AF Wilson, Nicole A. Sheehan, Frances T. TI Dynamic in vivo 3-dimensional moment arms of the individual quadriceps components SO JOURNAL OF BIOMECHANICS LA English DT Article DE Knee; Modeling; Moment arm; Patella; Patellofemoral pain; Kinematics ID KNEE EXTENSOR MECHANISM; PATELLOFEMORAL PAIN; PATELLAR TENDON; TIBIOFEMORAL KINEMATICS; CEREBRAL-PALSY; LEG MUSCLES; JOINT; FORCE; ORIENTATIONS; BIOMECHANICS AB The purpose of this study was to provide the first in vivo 3-dimensional (3D) measures of knee extensor moment arms, measured during dynamic volitional activity. The hypothesis was that the vastus lateralis (VL) and vastus medialis (VM) have significant off-axis moment arms compared to the central quadriceps components. After obtaining informed consent, three 3D dynamic cine phase contrast (PC) MRI sets (x,y,z velocity and anatomic images) were acquired from 22 subjects during active knee flexion and extension. Using a sagittal-oblique and two coronal-oblique imaging planes, the origins and insertions of each quadriceps muscle were identified and tracked through each time frame by integrating the cine-PC velocity data. The moment arm (MA) and relative moment (RM, defined as the cross product of the tendon line-of-action and a line connecting the line-of-action with the patellar center of mass) were calculated for each quadriceps component. The tendencies of the VM and VL to produce patellar tilt were evenly balanced. Interestingly, the magnitude of RM-P(Spin) for the VM and VL is approximately four times greater than the magnitude of RM-P(Tilt) for the same muscles suggesting that patellar spin may play a more important role in patellofemoral kinematics than previously thought. Thus, a force imbalance that leads to excessive lateral tilt, such as VM weakness in patellofemoral pain syndrome, would produce excessive negative spin (positive spin: superior patellar pole rotates laterally) and to a much greater degree. This would explain the increased negative spin found in recent studies of patellar maltracking. Assessing the contribution of each quadriceps component in three dimensions provides a more complete understanding of muscle functionality. Published by Elsevier Ltd. C1 [Wilson, Nicole A.; Sheehan, Frances T.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Sheehan, FT (reprint author), NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bldg 10,CRC RM 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009; Wilson, Nicole/C-4049-2008 OI Wilson, Nicole/0000-0002-0844-1885 FU NIH; Clinical Center at the NIH FX This research was supported by the Intramural Research Program of the NIH, and the Clinical Center at the NIH. We thank Abrahm Behnam, Jacqueline Feenster, Bonnie Damaska, and the Diagnostic Radiology Department at the National Institutes of Health for their support and research time. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Institutes of Health or the US Public Health Service. NR 41 TC 15 Z9 15 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD AUG 25 PY 2009 VL 42 IS 12 BP 1891 EP 1897 DI 10.1016/j.jbiomech.2009.05.011 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 493KB UT WOS:000269734200012 PM 19515373 ER PT J AU Luo, W Stanhope, SJ Sheehan, FT AF Luo, Weidong Stanhope, Steven J. Sheehan, Frances T. TI Using two palpable measurements improves the subject-specific femoral modeling SO JOURNAL OF BIOMECHANICS LA English DT Article DE Scaling; Magnetic resonance imaging; Femur ID ANTHROPOMETRIC SCALING METHOD; TOTAL HIP-ARTHROPLASTY; BONE; ANATOMY AB Subject-specific musculoskeletal models are essential to biomedical research and clinical applications, such as customized joint replacement, computer-aided surgical planning, gait analysis and automated segmentation. Generating these models from CT or magnetic resonance imaging (MRI) is time and resource intensive, requiring special skills. Therefore, in many studies individual bone models are approximated by scaling a generic template. Thus, the primary goal of this study was to determine a set of clinically available parameters (palpable measures and demographic data) that could improve the prediction of femoral dimensions, as compared to predicting these variables using uniform scaling based on palpable length. Similar to previous non-homogenous anthropometric scaling methods, the non-homogenous scaling method proposed in this study improved the prediction over uniform scaling of five key femoral measures. Homogenous scaling forces all dimensions of an object to be scaled equally, whereas non-homogenous scaling allows the dimensions to be scaled independently. The largest improvement was in femoral depth, where the coefficient of determination (r(2)) improved from 0.22 (homogenous) to 0.60 (non-homogeneous). In general, the major advantage of this non-homogenous scaling method is its ability to support the accurate and rapid generation of subject-specific femoral models since all parameters can be collected clinically, without imaging or invasive methods. Published by Elsevier Ltd. C1 [Luo, Weidong; Sheehan, Frances T.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Luo, Weidong] Catholic Univ Amer, Dept Phys, Washington, DC 20064 USA. [Stanhope, Steven J.] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE USA. [Stanhope, Steven J.] Univ Delaware, Dept Mech Engn, Newark, DE USA. RP Sheehan, FT (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 FU NIH, CC; NICHD FX The Authors wish to thank Tom Kepple for providing data for this study. We also thank Bonnie Damaska, Susan O'Connell, Jere McLucas and the Diagnostic Radiology Department at the National Institutes of Health for their support and research time. Any opinions, findings and conclusions or recommendations expressed in this material are those of the author and do not necessarily reflect the views of the National Institutes of Health or the US Public Health Service. This research was supported in part by the Intramural Research Program of the NIH, CC and NICHD. The NIH did not have any involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; nor in the decision to submit the manuscript for publication. NR 15 TC 4 Z9 4 U1 4 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD AUG 25 PY 2009 VL 42 IS 12 BP 2000 EP 2005 DI 10.1016/j.jbiomech.2009.05.006 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 493KB UT WOS:000269734200028 PM 19520371 ER PT J AU Tsivgoulis, G Alexandrov, AV Wadley, VG Unverzagt, FW Go, RCP Moy, CS Kissela, B Howard, G AF Tsivgoulis, G. Alexandrov, A. V. Wadley, V. G. Unverzagt, F. W. Go, R. C. P. Moy, C. S. Kissela, B. Howard, G. TI Association of higher diastolic blood pressure levels with cognitive impairment SO NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; CENTRAL OBESITY; PULSE PRESSURE; FOLLOW-UP; DEMENTIA; HYPERTENSION; PERFORMANCE; POPULATION; OLDER; RISK AB Background: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. Methods: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women > 45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of <= 4 on 6-Item Screener) after adjusting for demographic and environmental characteristics, cardiovascular risk factors, depressive symptoms, and current use of any antihypertensive medication. Results: Higher DBP levels were associated with impaired cognitive status after adjusting for demographic and environmental characteristics, risk factors, depressive symptoms, and antihypertensive medications. An increment of 10 mm Hg in DBP was associated with a 7% (95% confidence interval [CI] 1%-14%, p = 0.0275) higher odds of cognitive impairment. No independent association was identified between impaired cognitive status and SBP (odds ratio [OR] 1.02, 95% CI 0.99-1.06) or PP (OR 0.99, 95% CI 0.95-1.04). There was no evidence of nonlinear relationships between any of the BP components and impaired cognitive status. There was no interaction between age and the relationship of impaired cognitive status with SBP (p = 0.827), DBP (p = 0.133), or PP (p = 0.827) levels. Conclusions: Higher diastolic blood pressure was cross-sectionally and independently associated with impaired cognitive status in this large, geographically dispersed, race-and sex-balanced sample of stroke-free individuals. Neurology (R) 2009; 73: 589-595 C1 [Tsivgoulis, G.; Alexandrov, A. V.] Univ Alabama, Comprehens Stroke Ctr, Birmingham, AL 35294 USA. [Wadley, V. G.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Go, R. C. P.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Howard, G.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Tsivgoulis, G.] Democritus Univ Thrace, Univ Hosp Alexandroupolis, Dept Neurol, Komotini, Greece. [Unverzagt, F. W.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Moy, C. S.] NINDS, NIH, Bethesda, MD 20892 USA. [Kissela, B.] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. RP Tsivgoulis, G (reprint author), Univ Alabama, Comprehens Stroke Ctr, RWUH M226,1530 3rd Ave S, Birmingham, AL 35294 USA. EM tsivgoulisgiorg@yahoo.gr OI Alexandrov, Andrei V/0000-0001-8871-1023; Kissela, Brett/0000-0002-9773-4013 FU NIH [R01 AG026096, U01 NR004508, R01 AG09956, P30 AG10133, NIH-NINDS R-01 NS30678, NIH-NINDS R-01 NS039987, NINDS NS41588, NINDS NS38384, NINDS NS038529, NHLBI HL77100, NINDS NS34789]; Indiana University [ITRAC 23-87539 (PI)]; American Cancer Society [RSGPB04-089-01-PBP]; NINDS [U01NS04588] FX Dr. Tsivgoulis, Dr. Alexandrov, Dr. Wadley, and Dr. Moy report no disclosures. Dr. Unverzagt serves as consultant for Eli Lilly and Co.; and receives research support from the NIH [R01 AG026096 (PI), U01 NR004508 (PI), R01 AG09956 (Co-PI), P30 AG10133 (Co-PI)], Indiana University [ITRAC 23-87539 (PI)], and the American Cancer Society [RSGPB04-089-01-PBP (Co-PI)]. Dr. Go receives research support from the NINDS [U01NS04588 (Coinvestigator)]. Dr. Kissela has received speaker honoraria from Boehringer-Ingelheim and Allergan; receives research support from the NIH [NIH-NINDS R-01 NS30678 (Multiple PI), NIH-NINDS R-01 NS039987 (Site PI and Member of Executive Committee), NIH-NINDS U-01 NS041588 (Member of Executive Committee)]; and has served as an expert witness in medicolegal cases related to stroke. Dr. Howard serves on a scientific advisory board for Bayer Healthcare; serves as a Section Editor for Stroke and on the editorial board of American Society of Hypertension; and receives research support from Amgen and the NIH [NINDS NS41588 (PI), NINDS NS38384 (Co-PI of Coordinating Center), NIAMS AR02247 (Co-PI), NICHD HD39939 (Co-PI), NINDS NS038529 (Coinvestigator), NHLBI HL77100 (Coinvestigator), and NINDS NS34789 (Coinvestigator)]. NR 39 TC 51 Z9 54 U1 6 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 25 PY 2009 VL 73 IS 8 BP 589 EP 595 DI 10.1212/WNL.0b013e3181b38969 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 486SW UT WOS:000269219200005 PM 19704077 ER PT J AU Chen, B Thurber, KR Shewmaker, F Wickner, RB Tycko, R AF Chen, Bo Thurber, Kent R. Shewmaker, Frank Wickner, Reed B. Tycko, Robert TI Measurement of amyloid fibril mass-per-length by tilted-beam transmission electron microscopy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Alzheimer's disease; molecular structure; prions; solid state NMR ID BETA-SHEET STRUCTURE; HET-S PRION; NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; IN-VITRO; SACCHAROMYCES-CEREVISIAE; WEIGHT DETERMINATION; PIN+ PRION; PROTEIN; YEAST AB We demonstrate that accurate values of mass-per-length (MPL), which serve as strong constraints on molecular structure, can be determined for amyloid fibrils by quantification of intensities in dark-field electron microscope images obtained in the tilted-beam mode of a transmission electron microscope. MPL values for fibrils formed by residues 218-289 of the HET-s fungal prion protein, for 2-fold- and 3-fold-symmetric fibrils formed by the 40-residue beta-amyloid peptide, and for fibrils formed by the yeast prion protein Sup35NM are in good agreement with previous results from scanning transmission electron microscopy. Results for fibrils formed by the yeast prion protein Rnq1, for which the MPL value has not been previously reported, support an in-register parallel beta-sheet structure, with one Rnq1 molecule per 0.47-nm beta-sheet repeat spacing. Since tilted-beam dark-field images can be obtained on many transmission electron microscopes, this work should facilitate MPL determination by a large number of research groups engaged in studies of amyloid fibrils and similar supramolecular assemblies. C1 [Chen, Bo; Thurber, Kent R.; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Shewmaker, Frank; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov RI Chen, Bo/F-3573-2015 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health. We thank Dr. D. Eric Anderson of NIDDK for mass spectrometry of Rnq1 prion domain fibrils, and Prof. Gerald Stubbs and Dr. Amy Kendall of Vanderbilt University for providing TMV. NR 38 TC 53 Z9 54 U1 4 U2 37 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14339 EP 14344 DI 10.1073/pnas.0907821106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100033 PM 19706519 ER PT J AU Dulev, S de Renty, C Mehta, R Minkov, I Schwob, E Strunnikov, A AF Dulev, Stanimir de Renty, Christelle Mehta, Rajvi Minkov, Ivan Schwob, Etienne Strunnikov, Alexander TI Essential global role of CDC14 in DNA synthesis revealed by chromosome underreplication unrecognized by checkpoints in cdc14 mutants SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA replication; genome; rDNA; RFA2; SWI6; importins ID REPLICATION PROTEIN-A; S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; YEAST RDNA; NUCLEOLAR SEGREGATION; MITOTIC TRANSMISSION; POLYMERASE-EPSILON; NUCLEAR EXPORT; BUDDING YEAST; TRANSCRIPTION AB The CDC14 family of multifunctional evolutionarily conserved phosphatases includes major regulators of mitosis in eukaryotes and of DNA damage response in humans. The CDC14 function is also crucial for accurate chromosome segregation, which is exemplified by its absolute requirement in yeast for the anaphase segregation of nucleolar organizers; however the nature of this essential pathway is not understood. Upon investigation of the rDNA nondisjunction phenomenon, it was found that cdc14 mutants fail to complete replication of this locus. Moreover, other late-replicating genomic regions (10% of the genome) are also underreplicated in cdc14 mutants undergoing anaphase. This selective genome-wide replication defect is due to dosage insufficiency of replication factors in the nucleus, which stems from two defects, both contingent on the reduced CDC14 function in the preceding mitosis. First, a constitutive nuclear import defect results in a drastic dosage decrease for those replication proteins that are regulated by nuclear transport. Particularly, essential RPA subunits display both lower mRNA and protein levels, as well as abnormal cytoplasmic localization. Second, the reduced transcription of MBF and SBF-controlled genes in G1 leads to the reduction in protein levels of many proteins involved in DNA replication. The failure to complete replication of late replicons is the primary reason for chromosome nondisjunction upon CDC14 dysfunction. As the genome-wide slow-down of DNA replication does not trigger checkpoints [Lengronne A, Schwob E (2002) Mol Cell 9: 1067-1078], CDC14 mutations pose an overwhelming challenge to genome stability, both generating chromosome damage and undermining the checkpoint control mechanisms. C1 [Dulev, Stanimir; Mehta, Rajvi; Strunnikov, Alexander] NICHHD, NIH, Bethesda, MD 20892 USA. [de Renty, Christelle; Schwob, Etienne] Univ Montpellier 2, Inst Mol Genet, Ctr Natl Rech Sci, Unite Mixte Rech 5535, F-34293 Montpellier, France. [Dulev, Stanimir; Minkov, Ivan] Paisij Hilendarski Univ Plovdiv, BG-4000 Plovdiv, Bulgaria. RP Strunnikov, A (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM strunnik@mail.nih.gov RI Schwob, Etienne/H-4678-2015; OI Schwob, Etienne/0000-0002-9369-6419; Minkov, Ivan/0000-0001-9331-353X; Strunnikov, Alexander/0000-0002-9058-2256 FU Institut National du Cancer ( INCa); Association pour la Recherche sur le Cancer ( ARC) FX We thank A. Amon, S. Brill, M. Nomura, E. Schiebel, I. Dawid, and G. Brush for research materials; R. Woodgate, M. Lichten, and D. Gordenin for critical comments; and N. Sghir for help on DNA combing experiments. E. S. acknowledges Association pour la Recherche sur le Cancer ( ARC) and Institut National du Cancer ( INCa) for financial support. NR 65 TC 20 Z9 21 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14466 EP 14471 DI 10.1073/pnas.0900190106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100055 PM 19666479 ER PT J AU Miyaji, M Kortum, RL Surana, R Li, WM Woolard, KD Simpson, RM Samelson, LE Sommers, CL AF Miyaji, Michihiko Kortum, Robert L. Surana, Rishi Li, Wenmei Woolard, Kevin D. Simpson, R. Mark Samelson, Lawrence E. Sommers, Connie L. TI Genetic evidence for the role of Erk activation in a lymphoproliferative disease of mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Bam32; LAT; lymphoproliferation; T cells ID T-CELL DEVELOPMENT; ADAPTER PROTEINS; ANTIGEN RECEPTOR; RAS ACTIVATION; LAT; MUTATION; PATHWAY; BAM32; LINKS; TOLERANCE AB Germline mutation of the linker for activation of T cells (LAT) gene at the phospholipase C-gamma 1 (PLC-gamma 1)-binding site leads to a fatal lymphoproliferative disease in mice. The hyperactivated T cells that develop in these mice have defective T-cell antigen receptor (TCR)-induced calcium flux but enhanced mitogen-activated protein kinase (MAPK) activation. We used genetic analysis to investigate genes whose products might suppress MAPK activation and lymphoproliferative disease in LAT mutant mice. B-lymphocyte adaptor molecule of 32 kDa (Bam32) is a known mediator of MAPK activation in B cells. We recently reported that in CD4(+) T cells, Bam32 deficiency decreased MAPK activation and specifically extracellular-signal-regulated kinase (Erk) signaling, following TCR stimulation. By crossing the Bam32 null mutation onto the LAT knock-in background, we found that the Bam32 null mutation delayed the onset and decreased the severity of lymphoproliferative disease in LAT knock-in mice. The pulmonary lymphocyte infiltration seen in LAT knock-in mice was also markedly decreased in double-mutant mice. Additionally, Erk activation was diminished in LAT knock-in Bam32 knockout CD4(+) T cells. To more accurately determine the role of Erk in this delay of lymphoproliferative disease, we also bred a transgenic, hypersensitive Erk allele (the Erk2 sevenmaker mutant) onto the LAT knock-in Bam32 knockout double-mutant background. These triple transgenic mice demonstrated a role for Erk activation in lymphoproliferative disease caused by the LAT knock-in mutation. C1 [Miyaji, Michihiko; Kortum, Robert L.; Surana, Rishi; Li, Wenmei; Samelson, Lawrence E.; Sommers, Connie L.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Woolard, Kevin D.; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM connies@helix.nih.gov FU National Cancer Institute (NCI) Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Cancer Institute (NCI) Center for Cancer Research. We thank Barbara J. Taylor of the NCI Flow Cytometry Core Facility for help with cell sorting, Michel Nussenzweig of Rockefeller University for providing Bam32 knockout mice, and Stephen Hedrick of the University of California, San Diego (UCSD) for providing Erk2 transgenic mice. NR 34 TC 18 Z9 18 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14502 EP 14507 DI 10.1073/pnas.0903894106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100061 PM 19667175 ER PT J AU Matsumoto, T Wang, PY Ma, WZ Sung, HJ Matoba, S Hwang, PM AF Matsumoto, Takumi Wang, Ping-yuan Ma, Wenzhe Sung, Ho Joong Matoba, Satoaki Hwang, Paul M. TI Polo-like kinases mediate cell survival in mitochondrial dysfunction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell cycle; respiration; sco2 ID HUMAN CANCER-CELLS; GENE; P53; CHECKPOINT; PLK1; POLO-LIKE-KINASE-2; PROLIFERATION; MALIGNANCIES; KNOCKOUTS; SNK/PLK2 AB Cancer cells often display defects in mitochondrial respiration, thus the identification of pathways that promote cell survival under this metabolic state may have therapeutic implications. Here, we report that the targeted ablation of mitochondrial respiration markedly increases expression of Polo-like kinase 2 (PLK2) and that it is required for the in vitro growth of these nonrespiring cells. Furthermore, we identify PLK2 as a kinase that phosphorylates Ser-137 of PLK1, which is sufficient to mediate this survival signal. In vivo, knockdown of PLK2 in an isogenic human cell line with a modest defect in mitochondrial respiration eliminates xenograft formation, indicating that PLK2 activity is necessary for growth of cells with compromised respiration. Our findings delineate a mitochondrial dysfunction responsive cell cycle pathway critical for determining cancer cell outcome. C1 [Matsumoto, Takumi; Wang, Ping-yuan; Ma, Wenzhe; Sung, Ho Joong; Hwang, Paul M.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. [Matoba, Satoaki] Kyoto Prefectural Univ Med, Kyoto 6028566, Japan. RP Hwang, PM (reprint author), NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov FU Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH); Japan Society for the Promotion of Science FX We thank N. Raghavachari and X. Xu of the National Heart, Lung, and Blood Institute (NHLBI) microarray core for technical assistance, L. Samsel for cell sorting, P. Dagur for calcium measurements, J. G. Kang for technical support, and T. Finkel for helpful suggestions and critical reading of this manuscript. This work was supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), and a postdoctoral fellowship to T. Matsumoto from the Japan Society for the Promotion of Science. NR 36 TC 28 Z9 28 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14542 EP 14546 DI 10.1073/pnas.0904229106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100068 PM 19706541 ER PT J AU Barr, CS Dvoskin, RL Gupte, M Sommer, W Sun, H Schwandt, ML Lindell, SG Kasckow, JW Suomi, SJ Goldman, D Higley, JD Heilig, M AF Barr, Christina S. Dvoskin, Rachel L. Gupte, Manisha Sommer, Wolfgang Sun, Hui Schwandt, Melanie L. Lindell, Stephen G. Kasckow, John W. Suomi, Stephen J. Goldman, David Higley, J. Dee Heilig, Markus TI Functional CRH variation increases stress-induced alcohol consumption in primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE corticotropin-releasing factor; CRH promoter ID CORTICOTROPIN-RELEASING HORMONE; RECEPTOR ANTAGONIST; REARING CONDITION; RHESUS MACAQUES; GENE-EXPRESSION; BEHAVIOR; ETHANOL; BRAIN; AXIS; NEUROENDOCRINE AB Corticotropin-releasing factor (CRF), encoded by the CRH gene, is a key integrator of stress responses, and, as such, CRH gene variation may contribute to individual differences in susceptibility to stress-related pathology. In rhesus macaques, a single nucleotide polymorphism (SNP) is found within the CRH promoter (-248C -> T). Here, we assessed whether this variant influenced stress responding and, because increased CRF system activity drives alcohol drinking in rodents, we examined whether it predicted voluntary alcohol consumption as a function of prior stress exposure. Using a hypothalamic nuclear extract, we showed that the -248 T allele resulted in increased DNA protein interactions relative to the C allele. In vitro, the T allele resulted in CRH promoter activity that was higher following both stimulation with forskolin and treatment with dexamethasone. Endocrine and behavioral responses to social separation stress (release of ACTH and cortisol, and suppression of environmental exploration, respectively) were higher among carriers of the T allele, particularly among those exposed to early adversity in the form of peer rearing. We also found that T allele carriers with a history of early life adversity consumed more alcohol in a limited-access paradigm. Our data suggest that CRH promoter variation that confers increased stress reactivity increases the risk for alcohol use disorders in stress-exposed individuals. C1 [Barr, Christina S.; Dvoskin, Rachel L.; Gupte, Manisha; Sommer, Wolfgang; Sun, Hui; Schwandt, Melanie L.; Lindell, Stephen G.; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Gupte, Manisha; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Kasckow, John W.] Univ Pittsburgh, Med Ctr, VA Pittsburgh Hlth Care Syst MIRECC & Behav Hlth, Pittsburgh, PA 15206 USA. [Kasckow, John W.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. RP Barr, CS (reprint author), NIAAA, NIH, Lab Clin & Translat Studies, Anim Ctr, POB 529, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov RI Goldman, David/F-9772-2010; Schwandt, Melanie/L-9866-2016; OI Goldman, David/0000-0002-1724-5405; Holmes, Manisha/0000-0002-4262-0764 FU National Alliance for Research on Schizophrenia and Depression; NIAAA; NICHD FX We thank Karen Smith, MLS, for assistance in the preparation of this manuscript and the research and animal care staff at the Institutes on Alcohol Abuse and Alcoholism (NIAAA), National Institute of Child Health and Human Development (NICHD), and National Institutes of Health Animal Center for their assistance in data collection. This work was funded by National Alliance for Research on Schizophrenia and Depression and the NIAAA and NICHD intramural programs. NR 46 TC 47 Z9 47 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14593 EP 14598 DI 10.1073/pnas.0902863106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100077 PM 19706546 ER PT J AU Sun, MK Hongpaisan, J Alkon, DL AF Sun, Miao-Kun Hongpaisan, Jarin Alkon, Daniel L. TI Postischemic PKC activation rescues retrograde and anterograde long-term memory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bryostatin; protein kinase C; stroke therapy; synaptogenesis ID PROTEIN-KINASE-C; ACUTE ISCHEMIC-STROKE; ALZHEIMERS-DISEASE; CELL-DEATH; IN-VIVO; BRYOSTATIN-1; TRIALS; SYNAPTOGENESIS; NEURONS; FUTURE AB Therapeutics for cerebral ischemia/hypoxia, which often results in ischemic stroke in humans, are a global unmet medical need. Here, we report that bryostatin-1, a highly potent protein kinase C (PKC) activator, interrupts pathophysiological molecular cascades and apoptosis triggered by cerebral ischemia/hypoxia, enhances neurotrophic activity, and induces synaptogenesis in rats. This postischemic therapeutic approach is further shown to preserve learning and memory capacity even 4 months later as well as long-term memory induced before the ischemic event. Our results of electromicroscopic and immunohistochemical analyses of neuronal and synaptic ultra-structure are consistent with a PKC-mediated synaptic remodeling and repair process that confers long-lasting preservation of spatial learning and memory before and after the cerebral ischemic/hypoxic event, suggesting a previously undescribed therapeutic modality for cerebral ischemia/hypoxia and ischemic stroke. C1 [Sun, Miao-Kun; Hongpaisan, Jarin; Alkon, Daniel L.] W Virginia Univ, Blanchette Rockefeller Neurosci Inst, Morgantown, WV 26505 USA. [Hongpaisan, Jarin] Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Sun, MK (reprint author), W Virginia Univ, Blanchette Rockefeller Neurosci Inst, Morgantown, WV 26505 USA. EM mksun@brni-jhu.org NR 24 TC 41 Z9 44 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP 14676 EP 14680 DI 10.1073/pnas.0907842106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100091 PM 19667190 ER PT J AU Redd, AD Quinn, TC AF Redd, Andrew D. Quinn, Thomas C. TI Reply to Lester et al.: Microbial translocation and HIV pathogenesis in Africa SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID ACTIVATION C1 [Redd, Andrew D.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM tquinn@jhmi.edu RI Redd, Andrew/D-1802-2010 NR 5 TC 1 Z9 1 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 25 PY 2009 VL 106 IS 34 BP E90 EP E90 DI 10.1073/pnas.0907977106 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487SF UT WOS:000269295100002 ER PT J AU Grillet, N Kazmierczak, P Xiong, W Schwander, M Reynolds, A Sakaguchi, H Tokita, J Kachar, B Muller, U AF Grillet, Nicolas Kazmierczak, Piotr Xiong, Wei Schwander, Martin Reynolds, Anna Sakaguchi, Hirofumi Tokita, Joshua Kachar, Bechara Mueller, Ulrich TI The Mechanotransduction Machinery of Hair Cells SO SCIENCE SIGNALING LA English DT Article ID USHER-SYNDROME; TIP-LINK; CADHERIN-23; HARMONIN; PROTEINS; COMPLEX; PROTOCADHERIN-15; TRANSDUCTION; MECHANISMS; MUTATIONS AB Mechanotransduction, the conversion of mechanical force into an electrochemical signal, allows living organisms to detect touch, hear, register movement and gravity, and sense changes in cell volume and shape. Hair cells in the vertebrate inner ear are mechanoreceptor cells specialized for the detection of sound and head movement. Each hair cell contains, at the apical surface, rows of stereocilia that are connected by extracellular filaments to form an exquisitely organized bundle. Mechanotransduction channels, localized near the tips of the stereocilia, are gated by the gating spring, an elastic element that is stretched upon stereocilia deflection and mediates rapid channel opening. Components of the mechanotransduction machinery in hair cells have been identified and several are encoded by genes linked to deafness in humans, which indicates that defects in the mechanotransduction machinery are the underlying cause of some forms of hearing impairment. C1 [Grillet, Nicolas; Kazmierczak, Piotr; Xiong, Wei; Schwander, Martin; Reynolds, Anna; Mueller, Ulrich] Scripps Res Inst, Dept Cell Biol, Inst Childhood & Neglected Dis, La Jolla, CA 92037 USA. [Sakaguchi, Hirofumi; Tokita, Joshua; Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, Lab Cell Struct & Dynam, Bethesda, MD 20892 USA. RP Muller, U (reprint author), Scripps Res Inst, Dept Cell Biol, Inst Childhood & Neglected Dis, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM umueller@scripps.edu RI Wang, Shirong/G-1698-2011; Xiong, Wei/A-6170-2012 FU NIDCD NIH HHS [R01 DC007704] NR 21 TC 6 Z9 7 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD AUG 25 PY 2009 VL 2 IS 85 AR pt5 DI 10.1126/scisignal.285pt5 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 569MW UT WOS:000275602200003 PM 19706872 ER PT J AU Mulkidjanian, AY Galperin, MY AF Mulkidjanian, Armen Y. Galperin, Michael Y. TI On the origin of life in the Zinc world. 2. Validation of the hypothesis on the photosynthesizing zinc sulfide edifices as cradles of life on Earth SO BIOLOGY DIRECT LA English DT Review ID TRANSFER-RNA-SYNTHETASE; TETRAHYMENA RIBOZYME REACTION; UNIVERSAL COMMON ANCESTOR; ELECTRON-DEFICIENT ALKENES; ENZYME INFORMATION-SYSTEM; METALLO-BETA-LACTAMASE; GREEN SULFUR BACTERIA; BLACK SMOKER CHIMNEY; MINIMAL-GENE-SET; GROUP-I RIBOZYME AB Background: The accompanying article (A.Y. Mulkidjanian, Biology Direct 4: 26) puts forward a detailed hypothesis on the role of zinc sulfide (ZnS) in the origin of life on Earth. The hypothesis suggests that life emerged within compartmentalized, photosynthesizing ZnS formations of hydrothermal origin (the Zn world), assembled in sub-aerial settings on the surface of the primeval Earth. Results: If life started within photosynthesizing ZnS compartments, it should have been able to evolve under the conditions of elevated levels of Zn2+ ions, byproducts of the ZnS-mediated photosynthesis. Therefore, the Zn world hypothesis leads to a set of testable predictions regarding the specific roles of Zn2+ ions in modern organisms, particularly in RNA and protein structures related to the procession of RNA and the "evolutionarily old" cellular functions. We checked these predictions using publicly available data and obtained evidence suggesting that the development of the primeval life forms up to the stage of the Last Universal Common Ancestor proceeded in zinc-rich settings. Testing of the hypothesis has revealed the possible supportive role of manganese sulfide in the primeval photosynthesis. In addition, we demonstrate the explanatory power of the Zn world concept by elucidating several points that so far remained without acceptable rationalization. In particular, this concept implies a new scenario for the separation of Bacteria and Archaea and the origin of Eukarya. Conclusion: The ability of the Zn world hypothesis to generate non-trivial veritable predictions and explain previously obscure items gives credence to its key postulate that the development of the first life forms started within zinc-rich formations of hydrothermal origin and was driven by solar UV irradiation. This concept implies that the geochemical conditions conducive to the origin of life may have persisted only as long as the atmospheric CO2 pressure remained above ca. 10 bar. This work envisions the first Earth biotopes as photosynthesizing and habitable areas of porous ZnS and MnS precipitates around primeval hot springs. Further work will be needed to provide details on the life within these communities and to elucidate the primordial (bio) chemical reactions. Reviewers: This article was reviewed by Arcady Mushegian, Eugene Koonin, and Patrick Forterre. For the full reviews, please go to the Reviewers' reports section. C1 [Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. [Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119991, Russia. [Galperin, Michael Y.] Natl Inst Hlth, 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; galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Deutsche Forschungsgemeinschaft; Volkswagen Foundation; National Library of Medicine at the National Institutes of Health FX Valuable discussions with Drs. V. V. Aleshin, J. F. Allen, A. V. Bogachev, D. A. Cherepanov, W. F. Doolittle, M. Eigen, R. B. Gennis, E. V. Koonin, K. S. Makarova, W. Martin, W. Nitschke, A. W. Rutherford, M. J. Russell, V. P. Skulachev, R. Thauer, N. E. Voskoboynikova, R. J. P. Williams, Y. I. Wolf, and G. Z. Yusupova are greatly appreciated. This study was supported by grants to AYM from the Deutsche Forschungsgemeinschaft and the Volkswagen Foundation and by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health (MYG). This manuscript is dedicated to the memory of Leslie E. Orgel. NR 335 TC 26 Z9 27 U1 2 U2 32 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD AUG 24 PY 2009 VL 4 AR 27 DI 10.1186/1745-6150-4-27 PG 37 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 499MA UT WOS:000270223200001 PM 19703275 ER PT J AU Jung, G Titus, MA Hammer, JA AF Jung, Goeh Titus, Margaret A. Hammer, John A., III TI The Dictyostelium type V myosin MyoJ is responsible for the cortical association and motility of contractile vacuole membranes SO JOURNAL OF CELL BIOLOGY LA English DT Article ID FUNCTION IN-VIVO; UNCONVENTIONAL MYOSIN; MELANOSOME TRANSPORT; FLUORESCENT PROTEIN; H+-ATPASE; DISCOIDEUM; DYNAMICS; COMPLEX; CELLS; DICYOSTELIUM AB The contractile vacuole (CV) complex in Dictyostelium is a tubulovesicular osmoregulatory organelle that exhibits extensive motility along the actin-rich cortex, providing a useful model for investigating myosin-dependent membrane transport. Here, we show that the type V myosin myoJ localizes to CV membranes and is required for efficient osmoregulation, the normal accumulation of CV membranes in the cortex, and the conversion of collapsed bladder membranes into outwardly radiating cortical CV tubules. Complementation of myoJ-null cells with a version of myoJ containing a shorter lever arm causes these radiating tubules to move at a slower speed, confirming myoJ's role in translocating CV membranes along the cortex. MyoJ-null cells also exhibit a dramatic concentration of CV membranes around the microtubule-organizing center. Consistently, we demonstrate that CV membranes also move bi-directionally on microtubules between the cortex and the centrosome. Therefore, myoJ cooperates with plus and minus end-directed microtubule motors to drive the normal distribution and dynamics of the CV complex in Dictyostelium. C1 [Jung, Goeh; Hammer, John A., III] NHLBI, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. [Titus, Margaret A.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Hammer, JA (reprint author), NHLBI, Lab Cell Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov FU National Science Foundation FX M.A. Titus was supported by the National Science Foundation. NR 29 TC 16 Z9 16 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD AUG 24 PY 2009 VL 186 IS 4 BP 555 EP 570 DI 10.1083/jcb.200810147 PG 16 WC Cell Biology SC Cell Biology GA 489RH UT WOS:000269439200012 PM 19687255 ER PT J AU Avondoglio, D Scott, T Kil, WJ Sproull, M Tofilon, PJ Camphausen, K AF Avondoglio, Dane Scott, Tamalee Kil, Whoon Jong Sproull, Mary Tofilon, Philip J. Camphausen, Kevin TI High throughput evaluation of gamma-H2AX SO RADIATION ONCOLOGY LA English DT Article ID STRAND BREAK REPAIR; HISTONE H2AX; RADIOSENSITIZATION; INHIBITION; EXPRESSION; CELLS AB The DNA double-strand break (DSB) is the primary lethal lesion after therapeutic radiation. Thus, the development of assays to detect and to quantitate these lesions could have broad preclinical and clinical impact. Phosphorylation of histone H2AX to form gamma-H2AX is a known marker for irradiation-induced DNA DSBs. However, the first generation assay involves the use of immunofluorescent staining of gamma-H2AX foci. This assay is time consuming, operator dependent and is not scalable for high throughput assay development. Thus, we sought to develop a new assay using a high throughput electrochemiluminescent platform from Mesoscale Discovery Systems to quantify gamma-H2AX levels. The results show that our assay utilizes significantly less time and labor, has greater intra-assay reproducibility and has a greater dynamic range of gamma-H2AX versus irradiation dose. C1 [Avondoglio, Dane; Scott, Tamalee; Sproull, Mary; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Tofilon, Philip J.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM avondogd@mail.nih.gov; scottta@mail.nih.gov; kilwh@mail.nih.gov; sproullm@mail.nih.gov; philip.tofilon@moffitt.org; camphauk@mail.nih.gov NR 13 TC 21 Z9 22 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PD AUG 24 PY 2009 VL 4 AR 31 DI 10.1186/1748-717X-4-31 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 498LJ UT WOS:000270141600001 PM 19703306 ER PT J AU Lim, JB Kim, HO Jeong, SH Ha, JE Jang, S Lee, SG Lee, K Stroncek, D AF Lim, Jong-Baeck Kim, Hyun Ok Jeong, Seok Hoon Ha, Joo Eun Jang, Sunphil Lee, Sang-Guk Lee, Kyungwon Stroncek, David TI Identification of HLA-A*2402-restricted HCMV immediate early-1 (IE-1) epitopes as targets for CD8+HCMV-specific cytotoxic T lymphocytes SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID STEM-CELL TRANSPLANTATION; ALLOGENEIC BONE-MARROW; HUMAN CYTOMEGALOVIRUS; ADOPTIVE TRANSFER; DENDRITIC CELLS; COMMON TARGETS; PEPTIDE MOTIFS; CMV INFECTION; RESPONSES; PP65 AB Background: To identify novel HLA-A*2402-restricted human cytomegalovirus ( HCMV) immediate early-1 (IE-1) epitopes for adoptive immunotherapy, we explored 120 overlapping 15-amino acid spanning IE-1. Methods: These peptides were screened by measuring the frequency of polyclonal CD8+ T cells producing intracellular interferon-gamma (IFN-gamma) using flow cytometry and the epitopes were validated with a HCMV-infected target Cr release cytotoxicity assay. Results: Initial screening was performed with 12 mini-pools of 10 consecutive peptides made from 120 overlapping peptides15-amino acids in length that spanned IE-1. When peripheral blood mononuclear cells (PBMCs) from HLA-A*2402 HCMV-seropositive donors were sensitized with each of the 12 mini-pools, mini-pools 1 and 2 induced the highest frequency of CD8+ cytotoxic T lymphocytes (CTLs) producing IFN-gamma. When PBMCs were stimulated with each of the twenty peptides belonging to mini-pools 1 and 2, peptides IE-1(1-15)MESSAKRKMDPDNPD and IE-1(5-19)AKRKMDPDNPDEGPS induced the greatest quantities of IFN-gamma production and cytotoxicity of HLA-matched HCMV-infected fibroblasts. To determine the exact HLA-A*2402- restricted epitopes within the two IE-1 proteins, we synthesized a total of twenty-one overlapping 9- or 10 amino acid peptides spanning IE-1(1-15) and IE-1(5-19). Peptide IE-1(3-12)SSAKRKMDPD induced the greatest quantities of IFN-gamma production and target cell killing by CD8+ CTLs. Conclusion: HCMV IE-1(3-12)SSAKRKMDPD is a HLA-A*2402- restricted HCMV IE-1 epitope that can serve as a common target for CD8+ HCMV-specific CTLs. C1 [Stroncek, David] NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Lim, Jong-Baeck; Kim, Hyun Ok; Jeong, Seok Hoon; Ha, Joo Eun; Jang, Sunphil; Lee, Sang-Guk; Lee, Kyungwon] Yonsei Univ, Coll Med, Dept Lab Med, Seoul, South Korea. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM jlim@yumc.yonsei.ac.kr; hyunok1019@yumc.yonsei.ac.kr; kscpjsh@yumc.yonsei.ac.kr; 522win@hanmail.net; sunjfeel@yumc.yonsei.ac.kr; COMFORTER6@yumc.yonsei.ac.kr; leekcp@cc.nih.gov; dstroncek@cc.nih.gov FU National Core Research Center for Nanomedical Technology [R15-2004024-01001-0] FX This work was supported by KOSEF through the National Core Research Center for Nanomedical Technology (R15-2004024-01001-0). NR 33 TC 6 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD AUG 23 PY 2009 VL 7 AR 72 DI 10.1186/1479-5876-7-72 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 495DP UT WOS:000269870800001 PM 19698161 ER PT J AU Tekola, F Bull, S Farsides, B Newport, MJ Adeyemo, A Rotimi, CN Davey, G AF Tekola, Fasil Bull, Susan Farsides, Bobbie Newport, Melanie J. Adeyemo, Adebowale Rotimi, Charles N. Davey, Gail TI Impact of social stigma on the process of obtaining informed consent for genetic research on podoconiosis: a qualitative study SO BMC MEDICAL ETHICS LA English DT Article ID NON-FILARIAL ELEPHANTIASIS; BIOMEDICAL-RESEARCH; KENYAN COAST; SOUTHERN ETHIOPIA; COMMUNITY VOICES; TRUST; MEMBERS; FAMILY; MODEL; TRIAL AB Background: The consent process for a genetic study is challenging when the research is conducted in a group stigmatized because of beliefs that the disease is familial. Podoconiosis, also known as 'mossy foot', is an example of such a disease. It is a condition resulting in swelling of the lower legs among people exposed to red clay soil. It is a very stigmatizing problem in endemic areas of Ethiopia because of the widely held opinion that the disease runs in families and is untreatable. The aim of this study was to explore the impact of social stigma on the process of obtaining consent for a study on the genetics of podoconiosis in Southern Ethiopia. Methods: We adapted a rapid assessment tool validated in The Gambia. The methodology was qualitative involving focus-group discussions (n = 4) and in-depth interviews ( n = 25) with community members, fieldworkers, researchers and staff of the Mossy Foot Treatment and Prevention Association (MFTPA) working on prevention and treatment of podoconiosis. Results: We found that patients were afraid of participation in a genetic study for fear the study might aggravate stigmatization by publicizing the familial nature of the disease. The MFTPA was also concerned that discussion about the familial nature of podoconiosis would disappoint patients and would threaten the trust they have in the organization. In addition, participants of the rapid assessment stressed that the genetic study should be approved at family level before prospective participants are approached for consent. Based on this feedback, we developed and implemented a consent process involving community consensus and education of fieldworkers, community members and health workers. In addition, we utilized the experience and established trust of the MFTPA to diminish the perceived risk. Conclusion: The study showed that the consent process developed based on issues highlighted in the rapid assessment facilitated recruitment of participants and increased their confidence that the genetic research would not fuel stigma. Therefore, investigators must seek to assess and address risks of research from prospective participants' perspectives. This involves understanding the issues in the society, the culture, community dialogues and developing a consent process that takes all these into consideration. C1 [Tekola, Fasil; Davey, Gail] Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia. [Tekola, Fasil; Farsides, Bobbie; Newport, Melanie J.] Brighton & Sussex Med Sch, Falmer, Sussex, England. [Tekola, Fasil; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Bull, Susan] Univ Oxford, Div Publ Hlth & Primary Care, Ethox Ctr, Oxford OX1 2JD, England. RP Tekola, F (reprint author), Univ Addis Ababa, Sch Publ Hlth, Addis Ababa, Ethiopia. EM fasiltekola@yahoo.com; susan.bull@well.ox.ac.uk; B.Farsides@bsms.ac.uk; M.J.Newport@bsms.ac.uk; adeyemoa@mail.nih.gov; rotimic@mail.nih.gov; nerurkar@ethionet.et OI Davey, Gail/0000-0003-2796-7468; Adeyemo, Adebowale/0000-0002-3105-3231; Tekola-Ayele, Fasil/0000-0003-4194-9370 FU Wellcome Trust, UK [079791] FX We would like to acknowledge the Mossy Foot Treatment and Prevention Association in Ethiopia for organizing logistics for the fieldwork, and all participants for devoting their time for discussion. We are endebted to Ashenafi Debebe for doing all interviews with the community in Wolaitigna. The study was funded by the Wellcome Trust, UK, project grant 079791. The funding body had no direct role in the study design; the collection, analysis and interpretation of data; or the writing or submission of this paper for publication. NR 36 TC 41 Z9 41 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6939 J9 BMC MED ETHICS JI BMC Med. Ethics PD AUG 22 PY 2009 VL 10 AR 13 DI 10.1186/1472-6939-10-13 PG 10 WC Ethics; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Biomedical Social Sciences GA 507EQ UT WOS:000270834700001 PM 19698115 ER PT J AU Parks, AR Li, ZP Shi, QJ Owens, RM Jin, MM Peters, JE AF Parks, Adam R. Li, Zaoping Shi, Qiaojuan Owens, Roisin M. Jin, Moonsoo M. Peters, Joseph E. TI Transposition into Replicating DNA Occurs through Interaction with the Processivity Factor SO CELL LA English DT Article ID BETA-SLIDING-CLAMP; POLYMERASE-III HOLOENZYME; ESCHERICHIA-COLI; TN7 TRANSPOSITION; SACCHAROMYCES-CEREVISIAE; PROTEIN INTERACTIONS; BACILLUS-SUBTILIS; MISMATCH-REPAIR; DELTA-SUBUNIT; RECOGNITION AB The bacterial transposon Tn7 directs transposition into actively replicating DNA by a mechanism involving the transposon-encoded protein TnsE. Here we show that TnsE physically and functionally interacts with the processivity factor of the DNA replication machinery in vivo and in vitro. Our work establishes an in vitro TnsABC+E transposition reaction reconstituted from purified proteins and target DNA structures. Using the in vitro reaction we confirm that the processivity factor specifically reorders TnsE-mediated transposition events on target DNAs in a way that matches the bias with active DNA replication in vivo. The TnsE interaction with an essential and conserved component of the replication machinery, and a DNA structure reveals a mechanism by which Tn7, and probably other elements, selects target sites associated with DNA replication. C1 [Parks, Adam R.; Li, Zaoping; Shi, Qiaojuan; Peters, Joseph E.] Cornell Univ, Dept Microbiol, Ithaca, NY 14853 USA. [Owens, Roisin M.; Jin, Moonsoo M.] Cornell Univ, Dept Biomed Engn, Ithaca, NY 14853 USA. RP Peters, JE (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA. EM jep48@cornell.edu RI Jin, Moonsoo/D-6128-2011; OI Peters, Joseph/0000-0001-8309-3297; Owens, Roisin/0000-0001-7856-2108 FU National Institutes of Health [R01 GM069508] FX This work was supported by National Institutes of Health grant R01 GM069508. We thank Mark Sutton and Bik Tye for strains and plasmids and helpful discussions. We also thank Eric Alani, Bik Tye, Jeff Roberts, and the members of the Peters laboratory for comments on the manuscript. NR 62 TC 31 Z9 32 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD AUG 21 PY 2009 VL 138 IS 4 BP 685 EP 695 DI 10.1016/j.cell.2009.06.011 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 485WS UT WOS:000269156100011 PM 19703395 ER PT J AU Luka, Z Mudd, SH Wagner, C AF Luka, Zigmund Mudd, S. Harvey Wagner, Conrad TI Glycine N-Methyltransferase and Regulation of S-Adenosylmethionine Levels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID FOLATE-BINDING-PROTEIN; METHYL-GROUP DEFICIENCY; KNOCKOUT MOUSE MODEL; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; COOPERATIVE BINDING; CRYSTAL-STRUCTURES; PROSTATE-CANCER; METABOLISM; PHOSPHORYLATION AB Methylation is a major biological process. It has been shown to be important in formation of compounds such as phosphatidylcholine, creatine, and many others and also participates in epigenetic effects through methylation of histones and DNA. The donor of methyl groups for almost all cellular methylation reactions is S-adenosylmethionine. It seems that the level of S-adenosylmethionine must be regulated in response to developmental stages and metabolic changes, and the enzyme glycine N-methyltransferase has been shown to play a major role in such regulation in mammals. This minireview will focus on the latest discoveries in the elucidation of the mechanism of that regulation. C1 [Luka, Zigmund; Wagner, Conrad] Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA. [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Wagner, C (reprint author), Vanderbilt Univ, Med Ctr, Dept Biochem, Nashville, TN 37232 USA. EM conrad.wagner@vanderbilt.edu FU National Institutes of Health [R01 DK15289, DK080010]; Department of Veterans Affairs FX This work was supported, in whole or in part, by National Institutes of Health Grants R01 DK15289 and DK080010 and by a merit revue award from the Department of Veterans Affairs. This minireview will be reprinted in the 2009 Minireview Compendium, which will be available in January, 2010. NR 43 TC 66 Z9 68 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 2009 VL 284 IS 34 BP 22507 EP 22511 DI 10.1074/jbc.R109.019273 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 483KG UT WOS:000268963100002 PM 19483083 ER PT J AU Zheng, B Han, M Bernier, M Zhang, XH Meng, F Miao, SB He, M Zhao, XM Wen, JK AF Zheng, Bin Han, Mei Bernier, Michel Zhang, Xin-hua Meng, Fang Miao, Sui-bing He, Ming Zhao, Xin-ming Wen, Jin-kun TI Kruppel-like Factor 4 Inhibits Proliferation by Platelet-derived Growth Factor Receptor beta-mediated, Not by Retinoic Acid Receptor alpha-mediated, Phosphatidylinositol 3-Kinase and ERK Signaling in Vascular Smooth Muscle Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE ACTIVATION; EXPRESSION IN-VIVO; HEART LIM PROTEIN; GENE-EXPRESSION; ANGIOTENSIN-II; TISSUE TRANSGLUTAMINASE; TRANSCRIPTION FACTORS; NEOINTIMA FORMATION; INDUCED APOPTOSIS; EMERGING ROLE AB Proliferation inhibition of vascular smooth muscle cells (VSMCs) is governed by the activity of a transcription factor network. Kruppel-like factor 4 (Klf4), retinoic acid receptor (RAR alpha), and platelet-derived growth factor receptor (PDGFR) are expressed in VSMCs and are components of such a network. However, the relationship among them in the regulation of VSMC proliferation remains unknown. Here, we investigated the mechanisms whereby Klf4 mediates the growth inhibitory effects in VSMCs through RAR alpha and PDGFR beta. We demonstrated that Klf4 directly binds to the 5' regulatory region of RAR alpha, down-regulates RAR alpha expression, and specifically inhibits RAR alpha-mediated phosphatidylinositol 3-kinase (PI3K) and ERK signaling in cultured VSMCs induced by the synthetic retinoid Am80. Of particular interest, Klf4 inhibits RAR alpha and PDGFR beta expression while blocking PI3K and ERK signaling induced by Am80 and PDGF-BB, respectively. The anti-proliferative effects of Klf4 on neointimal formation depend largely on PDGFR-mediated PI3K signaling without involvement of the RAR alpha-activated signaling pathways. These findings provide a novel mechanism for signal suppression and growth inhibitory effects of Klf4 in VSMCs. Moreover, the results of this study suggest that Klf4 is one of the key mediators of retinoid actions in VSMCs. C1 [Zheng, Bin; Han, Mei; Zhang, Xin-hua; Meng, Fang; Miao, Sui-bing; He, Ming; Zhao, Xin-ming; Wen, Jin-kun] Hebei Med Univ, Dept Biochem & Mol Biol, Shijiazhuang 050017, Peoples R China. [Bernier, Michel] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Wen, JK (reprint author), Hebei Med Univ, Dept Biochem & Mol Biol, 361 Zhongshan E Rd, Shijiazhuang 050017, Peoples R China. EM wjk@hebmu.edu.cn RI Cheng, Yunhui/A-5668-2010; OI Bernier, Michel/0000-0002-5948-368X FU NIA, National Institutes of Health; Major State Basic Research Development Program of China [2008CB517402]; National Natural Science Foundation of People's Republic of China [30770787, 30670845, 30871272]; Chinese Ministry of Education [206016]; Hebei Natural Science Foundation of People's Republic of China [C2007000831, C2009001541] FX This work was supported, in whole or in part, by the Intramural Research Program of the NIA, National Institutes of Health. This work was also supported by Program for Major State Basic Research Development Program of China Grant 2008CB517402, National Natural Science Foundation of People's Republic of China Grants 30770787, 30670845, and 30871272, Key Project of Chinese Ministry of Education Grant 206016, and Hebei Natural Science Foundation of People's Republic of China Grants C2007000831 and C2009001541. NR 50 TC 32 Z9 38 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 2009 VL 284 IS 34 BP 22773 EP 22785 DI 10.1074/jbc.M109.026989 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 483KG UT WOS:000268963100031 PM 19531492 ER PT J AU Kohli, RM Abrams, SR Gajula, KS Maul, RW Gearhart, PJ Stivers, JT AF Kohli, Rahul M. Abrams, Shaun R. Gajula, Kiran S. Maul, Robert W. Gearhart, Patricia J. Stivers, James T. TI A Portable Hot Spot Recognition Loop Transfers Sequence Preferences from APOBEC Family Members to Activation-induced Cytidine Deaminase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; IN-VIVO; CRYSTAL-STRUCTURE; MUTATION SPECTRA; ENZYME APOBEC3G; AID; SPECIFICITY; GENOME; DOMAIN AB Enzymes of the AID/APOBEC family, characterized by the targeted deamination of cytosine to generate uracil within DNA, mediate numerous critical immune responses. One family member, activation-induced cytidine deaminase ( AID), selectively introduces uracil into antibody variable and switch regions, promoting antibody diversity through somatic hyper-mutation or class switching. Other family members, including APOBEC3F and APOBEC3G, play an important role in retroviral defense by acting on viral reverse transcripts. These enzymes are distinguished from one another by targeting cytosine within different DNA sequence contexts; however, the reason for these differences is not known. Here, we report the identification of a recognition loop of 9-11 amino acids that contributes significantly to the distinct sequence motifs of individual family members. When this recognition loop is grafted from the donor APOBEC3F or 3G proteins into the acceptor scaffold of AID, the mutational signature of AID changes toward that of the donor proteins. These loop-graft mutants of AID provide useful tools for dissecting the biological impact of DNA sequence preferences upon generation of antibody diversity, and the results have implications for the evolution and specialization of the AID/APOBEC family. C1 [Kohli, Rahul M.; Gajula, Kiran S.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Abrams, Shaun R.; Stivers, James T.] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Maul, Robert W.; Gearhart, Patricia J.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Stivers, JT (reprint author), 733 N Broadway, Baltimore, MD 21205 USA. EM jstivers@jhmi.edu RI Gajula, Kiran/F-5813-2010; OI Maul, Robert/0000-0002-6958-8514; Kohli, Rahul/0000-0002-7689-5678 FU National Institutes of Health [GM056834-13]; NIA, National Institutes of Health FX This work was supported, in whole or in part, by National Institutes of Health Grant GM056834-13 (to J.T.S.) and by the Intramural Research Program of the NIA, National Institutes of Health. NR 43 TC 61 Z9 61 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 21 PY 2009 VL 284 IS 34 BP 22898 EP 22904 DI 10.1074/jbc.M109.025536 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 483KG UT WOS:000268963100043 PM 19561087 ER PT J AU Ludek, OR Schroeder, GK Liao, C Russ, PL Wolfenden, R Marquez, VE AF Ludek, Olaf R. Schroeder, Gottfried K. Liao, Chenzhong Russ, Pamela L. Wolfenden, Richard Marquez, Victor E. TI Synthesis and Conformational Analysis of Locked Carbocyclic Analogues of 1,3-Diazepinone Riboside, a High-Affinity Cytidine Deaminase Inhibitor SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID TRANSITION-STATE ANALOG; CAMBRIDGE STRUCTURAL DATABASE; RING-CLOSING METATHESIS; ADENOSINE-DEAMINASE; CRYSTAL-STRUCTURE; NUCLEOSIDE ANALOGS; OLEFIN METATHESIS; POTENT INHIBITORS; N-ALKYLATION; ISOMERIZATION AB Cytidine deaminase (CDA) catalyzes the deamination of cytidine via a hydrated transition-state intermediate that results from the nucleophilic attack of zinc-bound water at the active site. Nucleoside analogues where the leaving NH(3) group is replaced by a proton and prevent conversion of the transition state to product are very potent inhibitors of the enzyme. However, stable carbocyclic versions of these analogues are less effective as the role of the ribose in facilitating formation of hydrated species is abolished. The discovery that a 1,3-diazepinone riboside (4) operated as a tight-binding inhibitor of CDA independent of hydration provided the opportunity to study novel inhibitors built as conformationally locked, carbocyclic 1,3-diazepinone nucleosides to determine the enzyme's conformational preference for a specific form of sugar pucker. This work describes the synthesis of two target bicyclo[3.1.0]hexane nucleosides, locked as north (5) and south (6) conformers, as well as a flexible analogue (7) built with a cyclopentane ring. The seven-membered 1,3-diazepinone ring in all the three targets was built from the corresponding benzoyl-protected carbocyclic bis-allyl ureas by ring-closing metathesis. The results demonstrate CDA's binding preference for a south sugar pucker in agreement with the high-resolution crystal structures of other CDA inhibitors bound at the active site. C1 [Ludek, Olaf R.; Liao, Chenzhong; Russ, Pamela L.; Marquez, Victor E.] NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. [Schroeder, Gottfried K.; Wolfenden, Richard] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM marquezv@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; [GM-18325] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by Grant No, GM-18325 (D.W. and G.K.S.). NR 52 TC 7 Z9 7 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD AUG 21 PY 2009 VL 74 IS 16 BP 6212 EP 6223 DI 10.1021/jo901127a PG 12 WC Chemistry, Organic SC Chemistry GA 482RV UT WOS:000268907300053 PM 19618900 ER PT J AU Pawelczyk, E Jordan, EK Balakumaran, A Chaudhry, A Gormley, N Smith, M Lewis, BK Childs, R Robey, PG Frank, JA AF Pawelczyk, Edyta Jordan, Elaine K. Balakumaran, Arun Chaudhry, Aneeka Gormley, Nicole Smith, Melissa Lewis, Bobbi K. Childs, Richard Robey, Pamela G. Frank, Joseph A. TI In Vivo Transfer of Intracellular Labels from Locally Implanted Bone Marrow Stromal Cells to Resident Tissue Macrophages SO PLOS ONE LA English DT Article AB Intracellular labels such as dextran coated superparamagnetic iron oxide nanoparticles (SPION), bromodeoxyuridine (BrdU) or green fluorescent protein (GFP) are frequently used to study the fate of transplanted cells by in vivo magnetic resonance imaging or fluorescent microscopy. Bystander uptake of labeled cells by resident tissue macrophages (TM) can confound the interpretation of the presence of intracellular labels especially during direct implantation of cells, which can result in more than 70% cell death. In this study we determined the percentages of TM that took up SPION, BrdU or GFP from labeled bone marrow stromal cells (BMSCs) that were placed into areas of angiogenesis and inflammation in a mouse model known as Matrigel (TM) plaque perfusion assay. Cells recovered from digested plaques at various time points were analyzed by fluorescence microscopy and flow cytometry. The analysis of harvested plaques revealed 5% of BrdU(+), 5-10% of GFP(+) and 5-15% of dextran(+) macrophages. The transfer of the label was not dependent on cell dose or viability. Collectively, this study suggests that care should be taken to validate donor origin of cells using an independent marker by histology and to assess transplanted cells for TM markers prior to drawing conclusions about the in vivo behavior of transplanted cells. RP Pawelczyk, E (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM pawelczyke@cc.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 47 TC 61 Z9 63 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 21 PY 2009 VL 4 IS 8 AR e6712 DI 10.1371/journal.pone.0006712 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487JB UT WOS:000269267600004 PM 19696933 ER PT J AU Parker, HG VonHoldt, BM Quignon, P Margulies, EH Shao, S Mosher, DS Spady, TC Elkahloun, A Cargill, M Jones, PG Maslen, CL Acland, GM Sutter, NB Kuroki, K Bustamante, CD Wayne, RK Ostrander, EA AF Parker, Heidi G. VonHoldt, Bridgett M. Quignon, Pascale Margulies, Elliott H. Shao, Stephanie Mosher, Dana S. Spady, Tyrone C. Elkahloun, Abdel Cargill, Michele Jones, Paul G. Maslen, Cheryl L. Acland, Gregory M. Sutter, Nathan B. Kuroki, Keiichi Bustamante, Carlos D. Wayne, Robert K. Ostrander, Elaine A. TI An Expressed Fgf4 Retrogene Is Associated with Breed-Defining Chondrodysplasia in Domestic Dogs SO SCIENCE LA English DT Article ID GENE DUPLICATION; GENOME; EVOLUTION; ACHONDROPLASIA; MUTATIONS; ELEMENTS; DNA AB Retrotransposition of processed mRNAs is a common source of novel sequence acquired during the evolution of genomes. Although the vast majority of retroposed gene copies, or retrogenes, rapidly accumulate debilitating mutations that disrupt the reading frame, a small percentage become new genes that encode functional proteins. By using a multibreed association analysis in the domestic dog, we demonstrate that expression of a recently acquired retrogene encoding fibroblast growth factor 4 (fgf4) is strongly associated with chondrodysplasia, a short-legged phenotype that defines at least 19 dog breeds including dachshund, corgi, and basset hound. These results illustrate the important role of a single evolutionary event in constraining and directing phenotypic diversity in the domestic dog. C1 [Parker, Heidi G.; Quignon, Pascale; Shao, Stephanie; Mosher, Dana S.; Spady, Tyrone C.; Elkahloun, Abdel; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [VonHoldt, Bridgett M.; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Margulies, Elliott H.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Cargill, Michele] Affymetrix Corp, Santa Clara, CA 95051 USA. [Jones, Paul G.] WALTHAM Ctr Pet Nutr, Melton Mowbray LE14 4RT, Leics, England. [Maslen, Cheryl L.] Oregon Hlth & Sci Univ, Div Cardiovasc Med, Portland, OR 97239 USA. [Acland, Gregory M.] Cornell Univ, James A Baker Inst Anim Hlth, Ithaca, NY 14853 USA. [Acland, Gregory M.; Sutter, Nathan B.] Cornell Univ, Coll Vet Med, Ithaca, NY 14853 USA. [Kuroki, Keiichi] Univ Missouri, Comparat Orthopaed Lab, Columbia, MO 65211 USA. [Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU NSF [0733033, 516310]; NIH [5R01EY006855, 1R24GM082910, 1R01GM83606] FX Funded by NSF grants 0733033 (R.K.W.) and 516310 (C.D.B.) and NIH grants 5R01EY006855 and 1R24GM082910 (G.M.A.) and 1R01GM83606 (C.D.B.). NR 33 TC 128 Z9 129 U1 3 U2 43 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 AUG 21 PY 2009 VL 325 IS 5943 BP 995 EP 998 DI 10.1126/science.1173275 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487AN UT WOS:000269242800046 PM 19608863 ER PT J AU Ahmadzadeh, M Johnson, LA Heemskerk, B Wunderlich, JR Dudley, ME White, DE Rosenberg, SA AF Ahmadzadeh, Mojgan Johnson, Laura A. Heemskerk, Bianca Wunderlich, John R. Dudley, Mark E. White, Donald E. Rosenberg, Steven A. TI Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired SO BLOOD LA English DT Article ID CHRONIC VIRAL-INFECTION; IL-7 RECEPTOR; LYMPHOCYTE-ACTIVATION; PROGRAMMED DEATH-1; MELANOMA LESIONS; CD127 EXPRESSION; B7-H1 EXPRESSION; EXHAUSTION; AUTOIMMUNITY; IMMUNITY AB Tumor antigen-aspecific T cells are found within melanomas, yet tumors continue to grow. Although the tumor microenvironment is thought to influence the suppression of tumor-reactive T cells, the underlying mechanisms for this T-cell dysfunction are not clear. Here, we report that the majority of tumor infiltrating T lymphocytes (TIL), including MART-1/Melan-A melanoma antigen-aspecific CD8 T cells, predominantly expressed PD-1, in contrast to T cells in normal tissues and peripheral blood T lymphocytes (PBL). PD-1(+) TIL expressed CTLA-4 and Ki-67, markers that were not expressed by PD-1(+) TIL and T cells in the normal tissues and PBL. Moreover, PD-1(+) TIL were primarily HLA-DR+ and CD127(-), in contrast to PD-1(+) TIL. Effector cytokine production by PD-1(+) TIL was impaired compared with PD-1(+) TIL and PBL. Collectively, the phenotypic and functional characterizations of TIL revealed a significantly higher frequency and level of PD-1 expression on TIL compared with normal tissue T-cell infiltrates and PBL, and PD-1 expression correlated with an exhausted phenotype and impaired effector function. These findings suggest that the tumor microenvironment can lead to up-regulation of PD-1 on tumor-reactive T cells and contribute to impaired antitumor immune responses. (Blood. 2009; 114: 1537-1544) C1 [Ahmadzadeh, Mojgan; Johnson, Laura A.; Heemskerk, Bianca; Wunderlich, John R.; Dudley, Mark E.; White, Donald E.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC Bldg,Rm 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM mojgan_ahmadzadeh@nih.gov; sar@nih.gov RI Heemskerk, Bianca/C-4635-2012; Johnson, Laura/H-4861-2013 NR 42 TC 412 Z9 424 U1 8 U2 38 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 20 PY 2009 VL 114 IS 8 BP 1537 EP 1544 DI 10.1182/blood-2008-12-195792 PG 8 WC Hematology SC Hematology GA 488WF UT WOS:000269380300015 PM 19423728 ER PT J AU Geldmacher, C Metzler, IS Tovanabutra, S Asher, TE Gostick, E Ambrozak, DR Petrovas, C Schuetz, A Ngwenyama, N Kijak, G Maboko, L Hoelscher, M McCutchan, F Price, DA Douek, DC Koup, RA AF Geldmacher, Christof Metzler, Ian S. Tovanabutra, Sodsai Asher, Tedi E. Gostick, Emma Ambrozak, David R. Petrovas, Constantinos Schuetz, Alexandra Ngwenyama, Njabulo Kijak, Gustavo Maboko, Leonard Hoelscher, Michael McCutchan, Francine Price, David A. Douek, Daniel C. Koup, Richard A. TI Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ORIGINAL ANTIGENIC SIN; LYMPHOCYTE RESPONSES; IMMUNE ESCAPE; DISEASE PROGRESSION; PRIMARY INFECTION; TYPE-1 INFECTION; HIV; GAG; VIREMIA AB Human immunodeficiency virus-1 sub-types A and C differ in the highly conserved Gag-TL9 epitope at a single amino acid position. Similarly, the TL9 presenting human leukocyte antigen (HLA) class I molecules B42 and B81 differ only at 6 amino acid positions. Here, we addressed the influence of such minor viral and host genetic variation on the TL9-specific CD8 T-cell response. The clonotypic characteristics of CD8 T-cell populations elicited by subtype A or subtype C were distinct, and these responses differed substantially with respect to the recognition and selection of TL9 variants. Irrespective of the presenting HLA class I molecule, CD8 T-cell responses elicited by subtype C exhibited largely comparable TL9 variant cross-recognition properties, expressed T-cell receptors that used almost exclusively the TRBV 12-3 gene, and selected for predictable patterns of viral variation within TL9. In contrast, subtype A elicited TL9-specific CD8 T-cell populations with completely different, more diverse TCRBV genes and did not select for viral variants. Moreover, TL9 variant cross-recognition properties were extensive in B81(+) subjects but limited in B42(+) subjects. Thus, minor viral and host genetic polymorphisms can dramatically alter the immunologic and virologic outcome of an epitope-specific CD8 T-cell response. (Blood. 2009; 114: 1553-1562) C1 [Geldmacher, Christof; Ambrozak, David R.; Petrovas, Constantinos; Ngwenyama, Njabulo; Koup, Richard A.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Metzler, Ian S.; Asher, Tedi E.; Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Tovanabutra, Sodsai; Schuetz, Alexandra; Kijak, Gustavo; McCutchan, Francine] US Mil HIV Res Program, Rockville, MD USA. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales. [Schuetz, Alexandra; Maboko, Leonard] Referral Hosp, Natl Inst Med Res Mbeya, Med Res Programme, Mbeya, Tanzania. [Hoelscher, Michael] Klinikum Univ Munich, Dept Infect Dis & Trop Med, Munich, Germany. RP Geldmacher, C (reprint author), Univ Munich, Inst Trop Med & Infect Dis, Georgenstr 5, D-80802 Munich, Germany. EM geldmacher@lrz.uni-muenchen.de RI Hoelscher, Michael/D-3436-2012; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU European Commission; DG XII; INCO-DC [ICA-CT-2002-10048]; Henry M. Jackson Foundation; US Department of Defense; National Institutes of Health intramural program FX The authors thank Alasdair Leslie for providing the HLA B*4201 and HLA B*8101 heavy chain plasmids.; D. A. P. is a Medical Research Council (United Kingdom) Senior Clinical Fellow. Sample collection was supported by the European Commission, DG XII, INCO-DC (grant ICA-CT-2002-10048), and funding for analysis was provided by a cooperative agreement between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the US Department of Defense. This research was performed as a part of the National Institutes of Health intramural program.; The views and opinions expressed herein do not necessarily reflect those of the US Army or the Department of Defense. NR 51 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 20 PY 2009 VL 114 IS 8 BP 1553 EP 1562 DI 10.1182/blood-2009-02-206193 PG 10 WC Hematology SC Hematology GA 488WF UT WOS:000269380300017 PM 19542300 ER PT J AU Salvucci, O Maric, D Economopoulou, M Sakakibara, S Merlin, S Follenzi, A Tosato, G AF Salvucci, Ombretta Maric, Dragan Economopoulou, Matina Sakakibara, Shuhei Merlin, Simone Follenzi, Antonia Tosato, Giovanna TI EphrinB reverse signaling contributes to endothelial and mural cell assembly into vascular structures SO BLOOD LA English DT Article ID SMOOTH-MUSCLE; CARDIOVASCULAR DEVELOPMENT; TYROSINE PHOSPHORYLATION; TRANSMEMBRANE LIGANDS; LENTIVIRAL-VECTORS; KINASE PATHWAY; FACTOR-I; ANGIOGENESIS; RECEPTOR; EPHB4 AB EphrinB transmembrane ligands and their cognate EphB receptor tyrosine kinases regulate vascular development through bidirectional cell-to-cell signaling, but little is known about the role of EphrinB during postnatal vascular remodeling. We report that EphrinB is a critical mediator of postnatal pericyte-to-endothelial cell assembly into vascular structures. This function is dependent upon extracellular matrix-supported cell-to-cell contact, engagement of EphrinB by EphB receptors expressed on another cell, and Src-dependent phosphorylation of the intracytoplasmic domain of EphrinB. Phosphorylated EphrinB marks angiogenic blood vessels in the developing and hypoxic retina, the wounded skin, and tumor tissue, and is detected at contact points between endothelial cells and pericytes. Furthermore, inhibition of EphrinB activity prevents proper assembly of pericytes and endothelial cells into vascular structures. These results reveal a role for EphrinB signaling in orchestrating pericyte/endothelial cell assembly, and suggest that therapeutic targeting of EphrinB may prove useful for disrupting angiogenesis when it contributes to disease. (Blood. 2009; 114: 1707-1716) C1 [Salvucci, Ombretta; Economopoulou, Matina; Sakakibara, Shuhei; Tosato, Giovanna] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Maric, Dragan] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. [Merlin, Simone; Follenzi, Antonia] Univ Piemonte Orientale, Sch Med, Dept Med Sci, Novara, Italy. [Follenzi, Antonia] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Dept Pathol, New York, NY USA. RP Salvucci, O (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, 37 Covent Dr,Rm 4134, Bethesda, MD 20892 USA. EM salvucco@mail.nih.gov OI Follenzi, Antonia/0000-0001-9780-300X FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX We thank Susan Garfield for confocal microscopy imaging; Lucy Sierra for technical support; and Drs Ira Daar, Triantafyllos Chavakis, Peter McCormick, Marta Segarra, Paola Gasperini, Stuart H. Yuspa, and Doug Lowy for their help on various aspects of this work.; This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 52 TC 63 Z9 65 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD AUG 20 PY 2009 VL 114 IS 8 BP 1707 EP 1716 DI 10.1182/blood-2008-12-192294 PG 10 WC Hematology SC Hematology GA 488WF UT WOS:000269380300034 PM 19411631 ER PT J AU Panchal, RG Bradfute, SB Peyser, BD Warfield, KL Ruthel, G Lane, D Kenny, TA Anderson, AO Raschke, WC Bavari, S AF Panchal, Rekha G. Bradfute, Steven B. Peyser, Brian D. Warfield, Kelly L. Ruthel, Gordon Lane, Douglas Kenny, Tara A. Anderson, Arthur O. Raschke, William C. Bavari, Sina TI Reduced Levels of Protein Tyrosine Phosphatase CD45 Protect Mice from the Lethal Effects of Ebola Virus Infection SO CELL HOST & MICROBE LA English DT Article ID T-CELL RESPONSES; HEMORRHAGIC-FEVER; MOUSE MODEL; GUINEA-PIGS; EXPRESSION; PATHOGENESIS; REGULATOR; KINASE; FAMILY; IMMUNODEFICIENCY AB Ebola virus (EBOV) infection of humans is a lethal but accidental dead-end event. Understanding resistance to EBOV in other species may help establish the basis of susceptibility differences among its hosts. Although rodents are resistant to EBOV, a murine-adapted variant is lethal when injected intraperitoneally into mice. We find that mice expressing reduced levels of the tyrosine phosphatase CD45 are protected against EBOV, whereas wild-type, CD45-deficient, or enzymatically inactive CD45-expressing mice succumbed to infection. Protection was dependent on CD8(+) T cells and interferon gamma. Reduced CD45-expressing mice retained greater control of gene expression and immune cell proliferation following EBOV infection, which contributed to reduced apoptosis, enhanced viral clearance, and increased protection against the virus. Together, these findings suggest that host susceptibility to EBOV is dependent on the delicate balance of immune homeostasis, which, as demonstrated here, can be determined by the levels of a single regulator. C1 [Panchal, Rekha G.; Bradfute, Steven B.; Peyser, Brian D.; Warfield, Kelly L.; Ruthel, Gordon; Anderson, Arthur O.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Lane, Douglas; Kenny, Tara A.] NCI, SAIC Frederick Inc, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. [Raschke, William C.] Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. [Raschke, William C.] Virogenics Inc, Del Mar, CA 92104 USA. RP Panchal, RG (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA. EM rekha.panchal@amedd.army.mil; sina.bavad@amedd.army.mil OI Peyser, Brian/0000-0002-3455-5181 FU Defense Threat Reduction Agency; National Institute for Allergy and Infectious Diseases [R43 A1055102]; National Cancer Institute, National Institutes of Health [N01-CO-12400]; National Cancer Institute FX We thank Christine Mach, Sean Van Tongeren, Jay Wells, and Meagan Cooper for technical support and Dr. Javad Amen for critical review of the manuscript. This project has been funded by the Defense Threat Reduction Agency (to R.G.P. and S.B.) and the National Institute for Allergy and Infectious Diseases (grant R43 A1055102 to W.C.R.). This project has been funded, in whole or in part, with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported, in part, by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. We would like to thank Oak Ridge Institute for Science and Engineering for participating in the Postgraduate Research Program at the U.S. Army Medical Research and Materiel Command. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. NR 45 TC 13 Z9 13 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD AUG 20 PY 2009 VL 6 IS 2 BP 162 EP 173 DI 10.1016/j.chom.2009.07.003 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 487JK UT WOS:000269268900008 PM 19683682 ER PT J AU Inskip, PD Robison, LL Stovall, M Smith, SA Hammond, S Mertens, AC Whitton, JA Diller, L Kenney, L Donaldson, SS Meadows, AT Neglia, JP AF Inskip, Peter D. Robison, Leslie L. Stovall, Marilyn Smith, Susan A. Hammond, Sue Mertens, Ann C. Whitton, John A. Diller, Lisa Kenney, Lisa Donaldson, Sarah S. Meadows, Anna T. Neglia, Joseph P. TI Radiation Dose and Breast Cancer Risk in the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HODGKINS-DISEASE; YOUNG-WOMEN; 2ND MALIGNANCY; NEOPLASMS; CHEMOTHERAPY; RADIOTHERAPY; ADOLESCENCE; COHORT AB Purpose The purpose of this study was to quantify the risk of breast cancer in relation to radiation dose and chemotherapy among survivors of childhood cancer. Methods We conducted a case-control study of breast cancer in a cohort of 6,647 women who were 5-year survivors of childhood cancer and who were treated during 1970 through 1986. One hundred twenty patients with histologically confirmed breast cancer were identified and were individually matched to four selected controls on age at initial cancer and time since initial cancer. Medical physicists estimated radiation dose to the breast tumor site and ovaries on the basis of medical records. Results The odds ratio for breast cancer increased linearly with radiation dose, and it reached 11-fold for local breast doses of approximately 40 Gy relative to no radiation (P for trend < .0001). Risk associated with breast irradiation was sharply reduced among women who received 5 Gy or more to the ovaries (P = .002). The excess odds ratio per Gy was 0.36 for those who received ovarian doses less than 5 Gy and was 0.06 for those who received higher doses. Radiation-related risk did not vary significantly by age at exposure. Borderline significantly elevated risks were seen for doxorubicin, dactinomycin, dacarbazine, and carmustine. Conclusion Results confirm the radiation sensitivity of the breast in girls age 10 to 20 years but do not demonstrate a strong effect of age at exposure within this range. Irradiation of the ovaries at doses greater than 5 Gy seems to lessen the carcinogenic effects of breast irradiation, most likely by reducing exposure of radiation-damaged breast cells to stimulating effects of ovarian hormones. C1 [Inskip, Peter D.] NCI, NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Ohio State Univ, Sch Med, Nationwide Childrens Hosp, Dept Pathol, Columbus, OH 43210 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Inskip, PD (reprint author), NCI, NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7052, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov FU NCI NIH HHS [U24 CA055727] NR 23 TC 97 Z9 97 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 3901 EP 3907 DI 10.1200/JCO.2008.20.7738 PG 7 WC Oncology SC Oncology GA 484RG UT WOS:000269064300007 PM 19620485 ER PT J AU Goedert, JJ AF Goedert, James J. CA Rockville Merkel Cell Carcinoma Gr TI Merkel Cell Carcinoma: Recent Progress and Current Priorities on Etiology, Pathogenesis, and Clinical Management SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POLYOMAVIRUS; SKIN; VIRUS; IDENTIFICATION; INFECTION; BIOPSY; CANCER; GENE; LUNG AB Purpose To expedite improved understanding, diagnosis, treatment, and prevention of Merkel cell carcinoma (MCC), a rare malignancy of cutaneous neuroendocrine cells that has a 28% 2-year mortality rate. Methods This article summarizes a workshop that discussed the state-of-the-art research and priorities for research on MCC and on a new human polyomavirus (ie, MCPyV) recently discovered in 80% of MCC tumors. Results Normal Merkel cells are widely distributed in the epidermis near the end of nerve axons and may function as mechanoreceptors or chemoreceptors. Malignant MCC cells typically stain for cytokeratin 20 as well as for other epithelial and neuroendocrine markers. MCC subtypes, which are based on histology, on cell line growth properties, and on gene expression profiles, have been reported but have not been linked to prognosis. Clinical management has been empiric. MCPyV is clonally integrated at various sites in the human genome of MCC tumors, with truncating mutations in the viral, large T antigen gene that interrupt viral replication. MCPyV seroprevalence may be high, as with previously known human polyomaviruses. MCC risk is increased 11-fold with AIDS and with other cell-mediated immune deficiencies, B-cell neoplasms, and ultraviolet radiation exposure. Conclusion Development and validation of a range quantitative polymerase chain reaction and serologic assays for detection of MCPyV, as well as an infectious clone of the virus, would clarify the fundamental biology, natural history, and epidemiology of the virus, of MCC, and of other diseases. Contingent on standardized histologic diagnosis and staging of MCC, consortia are needed to clarify the risks and benefits of sentinel lymph node biopsy, adjuvant radiation therapy, and salvage therapies; consortia are needed also for epidemiologic studies of MCC etiology. C1 [Goedert, James J.; Rockville Merkel Cell Carcinoma Gr] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7068, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU National Institutes of Health (NIH); National Cancer Institute, NIH FX Supported in part by the Office of Rare Diseases, National Institutes of Health (NIH); the Office of HIV and AIDS Malignancies, National Cancer Institute, NIH; and the Intramural Research Program, National Cancer Institute, NIH. NR 37 TC 61 Z9 62 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 20 PY 2009 VL 27 IS 24 BP 4021 EP 4026 DI 10.1200/JCO.2009.22.6605 PG 6 WC Oncology SC Oncology GA 484RG UT WOS:000269064300025 ER PT J AU Satyanarayana, A Kaldis, P AF Satyanarayana, A. Kaldis, P. TI Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms SO ONCOGENE LA English DT Review DE cell cycle; cyclin; Cdk; DNA damage; meiosis; knockout mouse ID RNA-POLYMERASE-II; DEPENDENT KINASES; PROTEIN-KINASE; ACTIVATING KINASE; S-PHASE; RETINOBLASTOMA PROTEIN; EMBRYONIC LETHALITY; IN-VIVO; SUBCELLULAR-LOCALIZATION; CENTROSOME DUPLICATION AB After a decade of extensive work on gene knockout mouse models of cell-cycle regulators, the classical model of cell-cycle regulation was seriously challenged. Several unexpected compensatory mechanisms were uncovered among cyclins and Cdks in these studies. The most astonishing observation is that Cdk2 is dispensable for the regulation of the mitotic cell cycle with both Cdk4 and Cdk1 covering for Cdk2's functions. Similar to yeast, it was recently discovered that Cdk1 alone can drive the mammalian cell cycle, indicating that the regulation of the mammalian cell cycle is highly conserved. Nevertheless, cell-cycle-independent functions of Cdks and cyclins such as in DNA damage repair are still under investigation. Here we review the compensatory mechanisms among major cyclins and Cdks in mammalian cell-cycle regulation. Oncogene (2009) 28, 2925-2939; doi:10.1038/onc.2009.170; published online 29 June 2009 C1 [Kaldis, P.] IMCB, Lab Cell Div & Canc, Singapore 138673, Singapore. [Satyanarayana, A.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), IMCB, Lab Cell Div & Canc, 61 Biopolis Dr,Proteos,3-10B, Singapore 138673, Singapore. EM satya@ncifcrf.gov; kaldis@imcb.a-star.edu.sg RI Kaldis, Philipp/G-2714-2010; ASTAR, IMCB/E-2320-2012 OI Kaldis, Philipp/0000-0002-7247-7591; FU A*STAR of Singapore (PK); NIH; National Cancer Institute; Center for Cancer Research FX We thank Kaldis lab members for discussions and support. This research was supported by A*STAR of Singapore (PK) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (AS). NR 123 TC 275 Z9 289 U1 5 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 20 PY 2009 VL 28 IS 33 BP 2925 EP 2939 DI 10.1038/onc.2009.170 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 485SA UT WOS:000269142800001 PM 19561645 ER PT J AU Huaman, MC Mullen, GED Long, CA Mahanty, S AF Huaman, Maria Cecilia Mullen, Gregory E. D. Long, Carole A. Mahanty, Siddhartha TI Plasmodium falciparum apical membrane antigen 1 vaccine elicits multifunctional CD4 cytokine-producing and memory T cells SO VACCINE LA English DT Article DE Plasmodium falciparum apical membrane; antigen 1 (PfAMA1); Multifunctional T-cell responses; Central and effector memory T cells ID BLOOD-STAGE VACCINE; MALARIA VACCINE; FUNCTIONAL-HETEROGENEITY; LEISHMANIA-MAJOR; CLINICAL-TRIAL; T(H)1 CELLS; IFN-GAMMA; IN-VIVO; RESPONSES; PROTECTION AB The Plasmodium falciparum apical membrane antigen I (AMA1) is a leading vaccine candidate and was tested for safety and immunogenicity in human Phase I Clinical Trials. PBMC from vaccine recipients were analyzed by flow cytometric methods to determine the nature of T-cell responses and AMA1-reactive memory T cells. Both CD4 and CD8 T cells produced a number of cytokines following AMA1 re-stimulation, with IL-5-producing cells at the highest frequency, consistent with a Th2 bias. The relative frequency of multifunctional cells synthesizing Th1 cytokines IFN-gamma, IL-2 and TNF-alpha changed after each vaccination. Interestingly, median fluorescence intensity measurements revealed that cells producing more than one cytokine contributed greater quantities of each cytokine than cell populations that produced each of the cytokines alone. AMA1 vaccination also elicited the development of memory cell populations, and both central and effector memory T cells were identified concurrently after the AMA1 vaccination. The detailed profile of multifunctional T-cell responses to AMA1 presented here will advance our ability to assess the immunogenicity of human malarial vaccines. Published by Elsevier Ltd. C1 [Huaman, Maria Cecilia] NIAID, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20892 USA. RP Huaman, MC (reprint author), NIAID, Lab Malaria & Vector Res, Malaria Vaccine Dev Branch, NIH, 12735 Twinbrook Pkwy,Twinbrook 3, Rockville, MD 20892 USA. EM huamanc@niaid.nih.gov OI Mahanty, Siddhartha/0000-0003-1068-0524 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The Intramural Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health supported this study. NR 44 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 20 PY 2009 VL 27 IS 38 BP 5239 EP 5246 DI 10.1016/j.vaccine.2009.06.066 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 484UB UT WOS:000269071900014 PM 19591795 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Polymorphism of Alzheimer's A beta(17-42) (p3) Oligomers: The Importance of the Turn Location and Its Conformation SO BIOPHYSICAL JOURNAL LA English DT Article ID BETA-AMYLOID PEPTIDE; SOLID-STATE NMR; MOLECULAR-DYNAMICS SIMULATIONS; ATOMIC-FORCE MICROSCOPY; PARTICLE MESH EWALD; A-BETA; FIBRIL FORMATION; IN-VITRO; PRION STRAINS; POTENTIAL FUNCTIONS AB A beta(17-42) (so-called p3) amyloid is detected in vivo in the brains of individuals with Alzheimer's disease or Down's syndrome. We investigated the polymorphism of A beta(17-42) oligomers based on experimental data from steady-state NMR measurements, electron microscopy, two-dimensional hydrogen exchange, and mutational studies, using all-atom molecular-dynamics simulation with explicit solvent. We assessed the structural stability and the populations. Our results suggest that conformational differences in the U-turn of A beta(17-42) lead to polymorphism in beta-sheet registration and retention of an ordered beta-strand organization at the termini. Further, although the parallel A beta(17-42) oligomer organization is the most stable of the conformers investigated here, different antiparallel A beta(17-42) organizations are also stable and compete with the parallel architectures, presenting a polymorphic population. In this study we propose that 1), the U-turn conformation is the primary factor leading to polymorphism in the assembly of A beta(17-42) Oligomers, and is also coupled to oligomer growth; and 2), both parallel A beta(17-42) Oligomers and an assembly of A beta(17-42) oligomers that includes both parallel and antiparallel organizations contribute to amyloid fibril formation. Finally, since a U-turn motif generally appears in amyloids formed by full proteins or long fragments, and since to date these have been shown to exist only in parallel architectures, our results apply to a broad range of oligomers and fibrils. C1 [Ma, Buyong; Nussinov, Ruth] NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. EM ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [NO1-CO-12400]; Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This project was funded in whole or in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract number NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 88 TC 51 Z9 52 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG 19 PY 2009 VL 97 IS 4 BP 1168 EP 1177 DI 10.1016/j.bpj.2009.05.042 PG 10 WC Biophysics SC Biophysics GA 485HV UT WOS:000269112800028 PM 19686665 ER PT J AU Nielsen, JA Lau, P Maric, D Barker, JL Hudson, LD AF Nielsen, Joseph A. Lau, Pierre Maric, Dragan Barker, Jeffery L. Hudson, Lynn D. TI Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis SO BMC NEUROSCIENCE LA English DT Article ID DEVELOPING CEREBRAL-CORTEX; FIBROBLAST-GROWTH-FACTOR; NEURAL STEM-CELLS; GENE-EXPRESSION; BRAIN; DIFFERENTIATION; REPRESSION; FOREBRAIN; MIGRATION; NEOCORTEX AB Background: Cortical development is a complex process that includes sequential generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the developing cortex. To identify the individual microRNAs (miRNAs) and mRNAs that may regulate the genetic network guiding the earliest phase of cortical development, the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 were analyzed. Results: Neuronal progenitors were purified from telencephalic dissociates by a positive-selection strategy featuring surface labeling with tetanus-toxin and cholera-toxin followed by fluorescence-activated cell sorting. Microarray analyses revealed the fractions of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors at the beginning of cortical development. Nearly half of the dynamically expressed miRNAs were negatively correlated with the expression of their predicted target mRNAs. Conclusion: These data support a regulatory role for miRNAs during the transition from neuronal progenitors into the earliest differentiating cortical neurons. In addition, by supplying a robust data set in which miRNA and mRNA profiles originate from the same purified cell type, this empirical study may facilitate the development of new algorithms to integrate various "-omics" data sets. C1 [Nielsen, Joseph A.; Lau, Pierre; Hudson, Lynn D.] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. [Nielsen, Joseph A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Maric, Dragan; Barker, Jeffery L.] NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, JA (reprint author), NINDS, Sect Dev Genet, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM joseph.nielsen@fda.hhs.gov; laup@ninds.nih.gov; maricd@ninds.nih.gov; jeffery.barker@nih.hhs.gov; hudsonl1@od.nih.gov FU NINDS FX We thank Dr. Abdel Elkahloun (NHGRI) and his staff for carrying out the microarray hybridization, washing and scanning. This research was supported by the Intramural Research Program of the NINDS. NR 42 TC 39 Z9 41 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD AUG 19 PY 2009 VL 10 AR 98 DI 10.1186/1471-2202-10-98 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 491EO UT WOS:000269560600001 PM 19689821 ER PT J AU Gonzalez-Suarez, I Redwood, AB Perkins, SM Vermolen, B Lichtensztejin, D Grotsky, DA Morgado-Palacin, L Gapud, EJ Sleckman, BP Sullivan, T Sage, J Stewart, CL Mai, S Gonzalo, S AF Gonzalez-Suarez, Ignacio Redwood, Abena B. Perkins, Stephanie M. Vermolen, Bart Lichtensztejin, Daniel Grotsky, David A. Morgado-Palacin, Lucia Gapud, Eric J. Sleckman, Barry P. Sullivan, Teresa Sage, Julien Stewart, Colin L. Mai, Sabine Gonzalo, Susana TI Novel roles for A-type lamins in telomere biology and the DNA damage response pathway SO EMBO JOURNAL LA English DT Article DE A-type lamins; DNA damage response; genomic instability; nuclear organization; telomeres ID RNA-POLYMERASE-II; REPEAT-CONTAINING RNA; STRAND BREAK REPAIR; MAMMALIAN TELOMERES; NUCLEAR LAMINS; HEMATOLOGIC MALIGNANCIES; RETINOBLASTOMA PROTEIN; EPIGENETIC REGULATION; HUMAN FIBROBLASTS; C CONTAINS AB A-type lamins are intermediate filament proteins that provide a scaffold for protein complexes regulating nuclear structure and function. Mutations in the LMNA gene are linked to a variety of degenerative disorders termed laminopathies, whereas changes in the expression of lamins are associated with tumourigenesis. The molecular pathways affected by alterations of A-type lamins and how they contribute to disease are poorly understood. Here, we show that A-type lamins have a key role in the maintenance of telomere structure, length and function, and in the stabilization of 53BP1, a component of the DNA damage response (DDR) pathway. Loss of A-type lamins alters the nuclear distribution of telomeres and results in telomere shortening, defects in telomeric heterochromatin, and increased genomic instability. In addition, A-type lamins are necessary for the processing of dysfunctional telomeres by non-homologous end joining, putatively through stabilization of 53BP1. This study shows new functions for A-type lamins in the maintenance of genomic integrity, and suggests that alterations of telomere biology and defects in DDR contribute to the pathogenesis of lamin-related diseases. The EMBO Journal (2009) 28, 2414-2427. doi:10.1038/emboj.2009.196; Published online 23 July 2009 C1 [Gonzalo, Susana] Washington Univ, Sch Med, Dept Radiat Oncol, Radiat & Canc Biol Div, St Louis, MO 63108 USA. [Gonzalez-Suarez, Ignacio; Redwood, Abena B.; Perkins, Stephanie M.; Grotsky, David A.; Morgado-Palacin, Lucia; Gonzalo, Susana] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63108 USA. [Vermolen, Bart] Univ Twente, Fac Sci & Technol, Biophys Engn Grp, Enschede, Netherlands. [Lichtensztejin, Daniel; Mai, Sabine] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada. [Gapud, Eric J.; Sleckman, Barry P.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63108 USA. [Sullivan, Teresa; Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. [Sage, Julien] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Sage, Julien] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Stewart, Colin L.] Inst Med Biol, Singapore, Singapore. RP Gonzalo, S (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, Radiat & Canc Biol Div, 4511 Forest Pk, St Louis, MO 63108 USA. EM sgonzalo@radonc.wustl.edu RI Mai, Sabine/E-5667-2017 OI Mai, Sabine/0000-0002-5797-2201 FU American Cancer Society; Radiation Oncology Department at Washington University FX We thank S Stewart, J Zhang and J Roti-Roti of Washington University and J Davie of Manitoba Institute of Cell Biology for helpful discussions. We are grateful to T de Lange for providing TRF2Delta B Delta M retroviral vector, D Hodzig for providing shLmna and shLucif vectors, and B Kennedy for the gift of lamins A/C expressing vectors. We thank A Searleman, L Revollo, K Chiappinelli, P Ramachandan, E Peterson, and C Franz for their contributions during their laboratory rotation. We are grateful to T Whitehead for his help with statistical analyses. CancerCare Manitoba Foundation supported the study carried out at the SM lab. Research in the laboratory of SG was supported by an institutional research grant from American Cancer Society, an Alzheimer's Disease Research Centre Pilot Grant, and Start-Up funds provided by the Radiation Oncology Department at Washington University. NR 70 TC 104 Z9 108 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 19 PY 2009 VL 28 IS 16 BP 2414 EP 2427 DI 10.1038/emboj.2009.196 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 484UX UT WOS:000269074400010 PM 19629036 ER PT J AU Hodges, MR Wehner, M Aungst, J Smith, JC Richerson, GB AF Hodges, Matthew R. Wehner, Mackenzie Aungst, Jason Smith, Jeffrey C. Richerson, George B. TI Transgenic Mice Lacking Serotonin Neurons Have Severe Apnea and High Mortality during Development SO JOURNAL OF NEUROSCIENCE LA English DT Article ID INFANT-DEATH-SYNDROME; RESPIRATORY RHYTHM GENERATOR; CHRONIC INTERMITTENT HYPOXIA; C-FOS EXPRESSION; BRAIN-STEM; RAPHE NEURONS; SUBSTANCE-P; MEDULLARY RAPHE; NEONATAL-RATS; 5-HT NEURONS AB Central serotonin (5-HT) neurons modulate many vital brain functions, including respiratory control. Whether breathing depends critically on 5-HT neurons, or whether their influence is excitatory or inhibitory, remains controversial. Here we show that neonatal Lmx1b(flox/flox;ePet-Cre/+) mice (also called Lmx1b(f/f/p) mice), which selectively lack serotonin neurons, display frequent and severe apnea lasting as long as 55 s. This was associated with a marked decrease in ventilation to less than one-half of normal. These respiratory abnormalities were most severe during the postnatal period, markedly improving by the time the pups were 2-4 weeks old. Despite the severe breathing dysfunction, many of these mice survived, but there was a high perinatal mortality, and those that survived had a decrease in growth rate until the age at which the respiratory defects resolved. Consistent with these in vivo observations, respiratory output was markedly reduced in isolated brainstem-spinal cord preparations from neonatal Lmx1b(f/f/p) mice and completely blocked in perfused brain preparations from neonatal rats treated with selective antagonists of 5-HT(2A) and neurokinin 1 (NK-1) receptors. The ventilatory deficits in neonatal Lmx1b(f/f/p) mice were reversed in vitro and in vivo with agonists of 5-HT(2A) and/or NK-1 receptors. These results demonstrate that ventilatory output in the neonatal period is critically dependent on serotonin neurons, which provide excitatory drive to the respiratory network via 5-HT(2A) and NK-1 receptor activation. These findings provide insight into the mechanisms of sudden infant death syndrome, which has been associated with abnormalities of 5-HT neurons and of cardiorespiratory control. C1 [Hodges, Matthew R.; Wehner, Mackenzie; Richerson, George B.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Hodges, Matthew R.; Wehner, Mackenzie; Richerson, George B.] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. [Aungst, Jason; Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. [Richerson, George B.] Vet Adm Med Ctr, West Haven, CT 06516 USA. RP Hodges, MR (reprint author), Yale Univ, Sch Med, Dept Neurol, LCI 704, New Haven, CT 06520 USA. EM matthew.hodges@yale.edu FU Parker B. Francis Foundation; National Institute of Child Health and Human Development; Bumpus Foundation; Veterans Affairs Medical Center; Intramural Research Program of the National Institute of Neurological Disorders and Stroke-National Institutes of Health FX This work was supported by the Parker B. Francis Foundation ( M. R. H.), the National Institute of Child Health and Human Development, the Bumpus Foundation, and Veterans Affairs Medical Center ( G. B. R.) and the Intramural Research Program of the National Institute of Neurological Disorders and Stroke-National Institutes of Health (J.A. and J.C.S.). NR 54 TC 87 Z9 87 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 19 PY 2009 VL 29 IS 33 BP 10341 EP 10349 DI 10.1523/JNEUROSCI.1963-09.2009 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 484YQ UT WOS:000269087300017 PM 19692608 ER PT J AU Tu, B Gu, ZL Shen, JX Lamb, PW Yakel, JL AF Tu, Bin Gu, Zhenglin Shen, Jian-xin Lamb, Patricia W. Yakel, Jerrel L. TI Characterization of a Nicotine-Sensitive Neuronal Population in Rat Entorhinal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Review ID LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; ACETYLCHOLINE-RECEPTOR CHANNELS; HIPPOCAMPAL CA1 INTERNEURONS; IN-SITU HYBRIDIZATION; LAYER-V NEURONS; DENTATE GYRUS; ACH RECEPTORS; INTRINSIC CONNECTIONS; ALLOSTERIC MODULATOR AB The entorhinal cortex (EC) is a part of the hippocampal complex that is essential to learning and memory, and nicotine affects memory by activating nicotinic acetylcholine receptors (nAChRs) in the hippocampal complex. However, it is not clear what types of neurons in the EC are sensitive to nicotine and whether they play a role in nicotine-induced memory functions. Here, we have used voltage-sensitive dye imaging methods to locate the neuronal populations responsive to nicotine in entorhino-hippocampal slices and to clarify which nAChR subtypes are involved. In combination with patch-clamp methods, we found that a concentration of nicotine comparable to exposure during smoking depolarized neurons in layer VI of the EC (ECVI) by acting through the non-alpha 7 subtype of nAChRs. Neurons in the subiculum (Sb; close to the deep EC layers) also contain nicotine-sensitive neurons, and it is known that Sb neurons project to the ECVI. When we recorded evoked EPSCs (eEPSCs) from ECVI neurons while stimulating the Sb near the CA1 region, a low dose of nicotine not only enhanced synaptic transmission ( by increasing eEPSC amplitude) but also enhanced plasticity by converting tetanus stimulation-induced short-term potentiation to long-term potentiation; nicotine enhanced synaptic transmission and plasticity of ECVI synapses by acting on both the alpha 7 and non-alpha 7 subtypes of nAChRs. Our data suggest that ECVI neurons are important regulators of hippocampal function and plasticity during smoking. C1 [Tu, Bin; Gu, Zhenglin; Shen, Jian-xin; Lamb, Patricia W.; Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, US Dept HHS, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institutes of Health - National Institute of Environmental Health Sciences. We are grateful to Drs. David Armstrong, J. Victor Nadler, Serena Dudek, and Christian Erxleben for providing valuable suggestions in experiments and in the writing of this manuscript. NR 105 TC 28 Z9 28 U1 2 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 19 PY 2009 VL 29 IS 33 BP 10436 EP 10448 DI 10.1523/JNEUROSCI.2580-09.2009 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 484YQ UT WOS:000269087300028 PM 19692619 ER PT J AU Davis, AM Berg, JM AF Davis, Alisa M. Berg, Jeremy M. TI Homodimerization and Heterodimerization of Minimal Zinc(II)-Binding-Domain Peptides of T-Cell Proteins CD4, CD8 alpha, and Lck SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID IMMUNOLOGICAL SYNAPSE; CYTOPLASMIC TAIL; ZINC-DEFICIENCY; TYROSINE KINASE; P56(LCK); BINDING; SPECIFICITY; EXPRESSION; GENERATION; RESOLUTION AB Metal-mediated protein oligomerization is an emerging mode of protein-protein interaction. The C-terminal cytosolic domains of T-cell coreceptors CD4 and CD8 alpha form zinc-bridged. heterodimers with the N-terminal region of the kinase Lck, with each protein contributing two cysteinate ligands to the complex. Using size exclusion chromatography, H-1 NMR, and UV/visible absorption spectroscopy with cobalt(II) as a spectroscopic probe, we demonstrate that small peptides derived from these regions form metal-bridged heterodimers but also homodimers, in contrast to previous reports. The Lck-CD4 and Lck-CD8 alpha cobalt(II)-bridged heterodimer complexes are more stable than the corresponding (Lck)(2)cobalt(II) complex by factors of 11 +/- 4 and 22 +/- 9, respectively. These studies were aided by the discovery that cobalt(II) complexes with a cobalt(II)(-Cys-X-X-Cys-)(-Cys-X-Cys-) chromophore show unusual optical spectra with one component of the visible d-d ((4)A(2)-to-T-4(1)(P)). transition red-shifted and well separated from the other components. These results provide insights into the basis of specificity of metal-bridged complex formation and on the potential biological significance of metal-bridged homodimers in T-cells. C1 [Davis, Alisa M.; Berg, Jeremy M.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Berg, JM (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM bergj@mail.nih.gov OI Berg, Jeremy/0000-0003-3022-0963 FU NIH Intramural Program through the National Institute of Diabetes and Diabetes and Kidney Diseases and the National Institute of General Medical Sciences FX This work was supported by the NIH Intramural Program through the National Institute of Diabetes and Diabetes and Kidney Diseases and the National Institute of General Medical Sciences. This was completed as part of the Graduate Partnership Program with the Johns Hopkins University Program in Molecular Biophysics. We thank Christopher Jaroniec, Jinfa Ying, Beat Vogeli, and Ananya Majumdar for assistance with acquiring NMR spectra, and Drs. Peter Kim and Barbara Amman for useful discussions. NR 30 TC 8 Z9 8 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 EI 1520-5126 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD AUG 19 PY 2009 VL 131 IS 32 BP 11492 EP 11497 DI 10.1021/ja9028928 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 488VU UT WOS:000269379200053 PM 19624124 ER PT J AU Fox, E Citrin, D Balis, FM AF Fox, Elizabeth Citrin, Deborah Balis, Frank M. TI The Legacy of Cancer Therapy in Children SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HIGH-RISK NEUROBLASTOMA; 13-CIS-RETINOIC ACID; CHILDHOOD-CANCER; SURVIVORS C1 [Fox, Elizabeth] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Balis, Frank M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 10-CRC,1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM foxb@mail.nih.gov NR 11 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 19 PY 2009 VL 101 IS 16 BP 1105 EP 1107 DI 10.1093/jnci/djp238 PG 3 WC Oncology SC Oncology GA 484XY UT WOS:000269084800004 PM 19648512 ER PT J AU Baker, SG AF Baker, Stuart G. TI Improving the Biomarker Pipeline to Develop and Evaluate Cancer Screening Tests SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CUMULATIVE RISK; CLINICAL-TRIALS; MARKERS; DESIGN; CLASSIFICATION; MICROARRAYS; STANDARDS AB The biomarker pipeline to develop and evaluate cancer screening tests has three stages: identification of promising biomarkers for the early detection of cancer, initial evaluation of biomarkers for cancer screening, and definitive evaluation of biomarkers for cancer screening. Statistical and biological issues to improve this pipeline are discussed. Although various recommendations, such as identifying cases based on clinical symptoms, keeping biomarker tests simple, and adjusting for postscreening noise, have been made previously, they are not widely known. New recommendations include more frequent specimen collection to help identify promising biomarkers and the use of the paired availability design with interval cases (symptomatic cancers detected in the interval after screening) for initial evaluation of biomarkers for cancer screening. C1 NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, EPN 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 33 TC 20 Z9 21 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 19 PY 2009 VL 101 IS 16 BP 1116 EP 1119 DI 10.1093/jnci/djp186 PG 4 WC Oncology SC Oncology GA 484XY UT WOS:000269084800008 PM 19574417 ER PT J AU Chaturvedi, AK Madeleine, MM Biggar, RJ Engels, EA AF Chaturvedi, Anil K. Madeleine, Margaret M. Biggar, Robert J. Engels, Eric A. TI Risk of Human Papillomavirus-Associated Cancers Among Persons With AIDS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; SQUAMOUS INTRAEPITHELIAL LESIONS; HIV-INFECTED PERSONS; ANAL CANCER; NATURAL-HISTORY; POSITIVE WOMEN; UNITED-STATES; CELL COUNT; ADULTS AB Background Although risk of human papillomavirus (HPV)-associated cancers of the anus, cervix, oropharynx, penis, vagina, and vulva is increased among persons with AIDS, the etiologic role of immunosuppression is unclear and incidence trends for these cancers over time, particularly after the introduction of highly active antiretroviral therapy in 1996, are not well described. Methods Data on 499 230 individuals diagnosed with AIDS from January 1, 1980, through December 31, 2004, were linked with cancer registries in 15 US regions. Risk of in situ and invasive HPV-associated cancers, compared with that in the general population, was measured by use of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). We evaluated the relationship of immunosuppression with incidence during the period of 4-60 months after AIDS onset by use of CD4 T-cell counts measured at AIDS onset. Incidence during the 4-60 months after AIDS onset was compared across three periods (1980-1989, 1990-1995, and 1996-2004). All statistical tests were two-sided. Results Among persons with AIDS, we observed statistically significantly elevated risk of all HPV-associated in situ ( SIRs ranged from 8.9, 95% CI = 8.0 to 9.9, for cervical cancer to 68.6, 95% CI = 59.7 to 78.4, for anal cancer among men) and invasive ( SIRs ranged from 1.6, 95% CI = 1.2 to 2.1, for oropharyngeal cancer to 34.6, 95% CI = 30.8 to 38.8, for anal cancer among men) cancers. During 1996-2004, low CD4 T-cell count was associated with statistically significantly increased risk of invasive anal cancer among men (relative risk [RR] per decline of 100 CD4 T cells per cubic millimeter = 1.34, 95% CI = 1.08 to 1.66, P = .006) and non-statistically significantly increased risk of in situ vagina or vulva cancer (RR = 1.52, 95% CI = 0.99 to 2.35, P = .055) and of invasive cervical cancer (RR = 1.32, 95% CI = 0.96 to 1.80, P = .077). Among men, incidence (per 100 000 person-years) of in situ and invasive anal cancer was statistically significantly higher during 1996-2004 than during 1990-1995 (61% increase for in situ cancers, 18.3 cases vs 29.5 cases, respectively; RR = 1.71, 95% CI = 1.24 to 2.35, P < .001; and 104% increase for invasive cancers, 20.7 cases vs 42.3 cases, respectively; RR = 2.03, 95% CI = 1.54 to 2.68, P < .001). Incidence of other cancers was stable over time. Conclusions Risk of HPV-associated cancers was elevated among persons with AIDS and increased with increasing immunosuppression. The increasing incidence for anal cancer during 1996-2004 indicates that prolonged survival may be associated with increased risk of certain HPV-associated cancers. C1 [Chaturvedi, Anil K.; Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Madeleine, Margaret M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. [Biggar, Robert J.] State Serum Inst, Copenhagen, Denmark. RP Chaturvedi, AK (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU National Cancer Institute, National Institutes of Health FX Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 41 TC 204 Z9 206 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 19 PY 2009 VL 101 IS 16 BP 1120 EP 1130 DI 10.1093/jnci/djp205 PG 11 WC Oncology SC Oncology GA 484XY UT WOS:000269084800009 PM 19648510 ER PT J AU Darash-Yahana, M Gillespie, JW Hewitt, SM Chen, YYK Maeda, S Stein, I Singh, SP Bedolla, RB Peled, A Troyer, DA Pikarsky, E Karin, M Farber, JM AF Darash-Yahana, Merav Gillespie, John W. Hewitt, Stephen M. Chen, Yun-Yun K. Maeda, Shin Stein, Ilan Singh, Satya P. Bedolla, Roble B. Peled, Amnon Troyer, Dean A. Pikarsky, Eli Karin, Michael Farber, Joshua M. TI The Chemokine CXCL16 and Its Receptor, CXCR6, as Markers and Promoters of Inflammation-Associated Cancers SO PLOS ONE LA English DT Article AB Clinical observations and mouse models have suggested that inflammation can be pro-tumorigenic. Since chemokines are critical in leukocyte trafficking, we hypothesized that chemokines play essential roles in inflammation-associated cancers. Screening for 37 chemokines in prostate cancer cell lines and xenografts revealed CXCL16, the ligand for the receptor CXCR6, as the most consistently expressed chemokine. Immunohistochemistry and/or immunofluorescence and confocal imaging of 121 human prostate specimens showed that CXCL16 and CXCR6 were co-expressed, both on prostate cancer cells and adjacent T cells. Expression levels of CXCL16 and CXCR6 on cancer cells correlated with poor prognostic features including high-stage and high-grade, and expression also correlated with post-inflammatory changes in the cancer stroma as revealed by loss of alpha-smooth muscle actin. Moreover, CXCL16 enhanced the growth of CXCR6-expressing cancer and primary CD4 T cells. We studied expression of CXCL16 in an additional 461 specimens covering 12 tumor types, and found that CXCL16 was expressed in multiple human cancers associated with inflammation. Our study is the first to describe the expression of CXCL16/CXCR6 on both cancer cells and adjacent T cells in humans, and to demonstrate correlations between CXCL16 and CXCR6 vs. poor both prognostic features and reactive changes in cancer stoma. Taken together, our data suggest that CXCL16 and CXCR6 may mark cancers arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through direct effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes. RP Darash-Yahana, M (reprint author), NIAID, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM meravd@hadassah.org.il; jfarber@niaid.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS NR 53 TC 59 Z9 63 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 19 PY 2009 VL 4 IS 8 AR e6695 DI 10.1371/journal.pone.0006695 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 487IY UT WOS:000269267300011 PM 19690611 ER PT J AU Goldbach-Mansky, R Wilson, M Fleischmann, R Olsen, N Silverfield, J Kempf, P Kivitz, A Sherrer, Y Pucino, F Csako, G Costello, R Pham, TH Snyder, C van der Heijde, D Tao, XL Wesley, R Lipsky, PE AF Goldbach-Mansky, Raphaela Wilson, Mildred Fleischmann, Roy Olsen, Nancy Silverfield, Joel Kempf, Phillip Kivitz, Alan Sherrer, Yvonne Pucino, Frank Csako, Gyorgy Costello, Rene Pham, Tuyet Hang Snyder, Christopher van der Heijde, Desiree Tao, Xuelian Wesley, Robert Lipsky, Peter E. TI Comparison of Tripterygium wilfordii Hook F Versus Sulfasalazine in the Treatment of Rheumatoid Arthritis A Randomized Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; NF-KAPPA-B; DOUBLE-BLIND; TRIPTOLIDE; DISEASE; METHOTREXATE; LEFLUNOMIDE; INHIBITOR; EFFICACY; EXTRACT AB Background: Extracts of the medicinal plant Tripterygium wilfordii Hook F (TwHF) have been used in China for centuries to treat a spectrum of inflammatory diseases. Objective: To compare the benefits and side effects of TwHF extract with those of sulfasalazine for the treatment of active rheumatoid arthritis. Design: Randomized, controlled trial. A computer-generated code with random, permuted blocks was used to assign treatment. Setting: 2 U. S. academic centers (National Institutes of Health, Bethesda, Maryland, and University of Texas, Dallas, Texas) and 9 rheumatology subspecialty clinics (in Dallas and Austin, Texas; Tampa and Fort Lauderdale, Florida; Arlington, Virginia; Duncanville, Pennsylvania; Wheaton and Greenbelt, Maryland; and Lansing, Michigan). Patients: 121 patients with active rheumatoid arthritis and 6 or more painful and swollen joints. Intervention: TwHF extract, 60 mg 3 times daily, or sulfasalazine, 1 g twice daily. Patients could continue stable doses of oral prednisone or nonsteroidal anti-inflammatory drugs but had to stop taking disease-modifying antirheumatic drugs at least 28 days before randomization. Measurements: The primary outcome was the rate of achievement of 20% improvement in the American College of Rheumatology criteria (ACR 20) at 24 weeks. Secondary end points were safety; radiographic scores of joint damage; and serum levels of interleukin-6, cholesterol, cortisol, and adrenocorticotropic hormone. Results: Outcome data were available for only 62 patients at 24 weeks. In a mixed-model analysis that imputed data for patients who dropped out, 65.0% (95% CI, 51.6% to 76.9%) of the TwHF group and 32.8% (CI, 21.3% to 46.0%) of the sulfasalazine group met the ACR 20 response criteria (P = 0.001). Patients receiving TwHF also had significantly higher response rates for ACR 50 and ACR 70 in mixed-model analyses. Analyses of only completers showed similar significant differences between the treatment groups. Significant improvement was demonstrated in all individual components of the ACR response, including the Health Assessment Questionnaire disability score. Interleukin-6 levels rapidly and significantly decreased in the TwHF group. Although not statistically significant, radiographic progression was lower in the TwHF group. The frequency of adverse events was similar in both groups. Limitations: Only 62% and 41% of patients continued receiving TwHF extract and sulfasalazine, respectively, during the 24 weeks of the study. Long-term outcome data were not collected on participants who discontinued treatment. Conclusion: In patients who continued treatment for 24 weeks and could also use stable oral prednisone and nonsteroidal anti-inflammatory drugs, attainment of the ACR 20 response criteria was significantly greater with TwHF extract than with sulfasalazine. C1 [Goldbach-Mansky, Raphaela] NIAMSD, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Metroplex Clin Res Ctr, Dallas, TX USA. Tampa Med Grp, Tampa, FL USA. Arthrit Ctr, Ft Lauderdale, FL USA. Arthrit Clin No Virginia, Arlington, VA USA. Altoona Ctr Clin Res, Duncanville, PA USA. Leiden Univ, Med Ctr, Leiden, Netherlands. RP Goldbach-Mansky, R (reprint author), NIAMSD, NIH, US Dept Hlth & Human Serv, Bldg 10,Room 6D-47B,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov FU National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Phytomedics FX By the Intramural Research Program of the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and Phytomedics. NR 43 TC 97 Z9 112 U1 0 U2 6 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 18 PY 2009 VL 151 IS 4 BP 229 EP W51 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 484IW UT WOS:000269038900002 PM 19687490 ER PT J AU Sczepanski, JT Jacobs, AC Van Houten, B Greenberg, MM AF Sczepanski, Jonathan T. Jacobs, Aaron C. Van Houten, Bennett Greenberg, Marc M. TI Double-Strand Break Formation during Nucleotide Excision Repair of a DNA Interstrand Cross-Link SO BIOCHEMISTRY LA English DT Article ID DAMAGE; BLEOMYCIN; RADIATION; PSORALEN; LESION; SITE; INDUCTION; MECHANISM; OXIDATION; COMPLEX AB The DNA interstrand cross-link (ICL) resulting from the C4'-oxidized abasic site (C4-AP) is a unique clustered lesion comprised of a cross-link adjacent to a nick. The ICL is a Substrate for the UvrABC nucleotide excision repair system. The strand containing the nick is preferentially incised.. but the nick influences the cleavage sites. Moreover, in approximately 15% of the molecules, the strand opposite the nick is incised, resulting in a more toxic double-strand break. This is the first example in which an interstrand cross-link is converted by nucleotide excision misrepair into a more deleterious double-strand break. C1 [Sczepanski, Jonathan T.; Jacobs, Aaron C.; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. [Van Houten, Bennett] NIEHS, NIH, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Sczepanski, JT (reprint author), Johns Hopkins Univ, Dept Chem, 3400 N Charles St, Baltimore, MD 21218 USA. RI Sczepanski, Jonathan/N-8719-2015 OI Sczepanski, Jonathan/0000-0002-9275-2597 FU National Institute of General Medical Sciences [GM-063028]; Johns Hopkins University; National Institute of Environmental Health Sciences, National Institutes of Health FX M.M.G. is grateful for support from the National Institute of General Medical Sciences (Grant GM-063028). J.T.S. thanks Johns Hopkins University for a Sonneborn Fellowship. B.V.H. was supported by intramural funds from the National Institute of Environmental Health Sciences, National Institutes of Health. NR 20 TC 33 Z9 34 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 18 PY 2009 VL 48 IS 32 BP 7565 EP 7567 DI 10.1021/bi901006b PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480GK UT WOS:000268720300001 PM 19606890 ER PT J AU Abraham, SJ Nolet, RP Calvert, RJ Anderson, LM Gaponenko, V AF Abraham, Sherwin J. Nolet, Ryan P. Calvert, Richard J. Anderson, Lucy M. Gaponenko, Vadim TI The Hypervariable Region of K-Ras4B Is Responsible for Its Specific Interactions with Calmodulin SO BIOCHEMISTRY LA English DT Article ID RAS-BINDING DOMAIN; K-RAS; AKT ACTIVATION; H-RAS; COMPLEX; TARGET; EXPRESSION; CA2+/CALMODULIN; TUMORIGENESIS; FIBROBLASTS AB K-Ras4B belongs to the family of p21 Ras GTPases, which play all important role in cell proliferation, survival, and motility. The p21 Ras proteins, such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras, share 85% sequence homology and activate very similar signaling pathways. Only the C-terminal hypervariable regions differ significantly. A growing body of literature demonstrates that each Ras isoform possesses unique functions in normal physiological processes as well as in pathogenesis. One of the central questions in the field of Ras biology is how these very Similar proteins achieve such remarkable specificity in protein-protein interactions that regulate signal transduction pathways. Here we explore specific binding of K-Ras4B to calmodulin. Using NMR techniques and isothermal titration calorimetry, we demonstrate that the hypervariable region of K-Ras4B contributes in a major way to the interaction with calmodulin, while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding. The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca(2+)-loaded calmodulin With micromolar affinity, while the GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal domain or calmodulin. C1 [Abraham, Sherwin J.; Nolet, Ryan P.; Gaponenko, Vadim] Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. [Calvert, Richard J.; Anderson, Lucy M.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Calvert, Richard J.] US FDA, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Gaponenko, V (reprint author), Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. EM vadimg@uic.edu FU American Cancer Society [ACS 08-14]; U.S. Department of Health and Human Services FX Supported by the American Cancer Society, Illinois Division Grant ACS 08-14 (to.G.), and the U.S. Department of Health and Human Services. NR 34 TC 24 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 18 PY 2009 VL 48 IS 32 BP 7575 EP 7583 DI 10.1021/bi900769j PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480GK UT WOS:000268720300003 PM 19583261 ER PT J AU Crowe, A Huang, WW Ballatore, C Johnson, RL Hogan, AML Huang, R Wichterman, J McCoy, J Huryn, D Auld, DS Smith, AB Inglese, J Trojanowski, JQ Austin, CP Brunden, KR Lee, VMY AF Crowe, Alex Huang, Wenwei Ballatore, Carlo Johnson, Ronald L. Hogan, Anne-Marie L. Huang, Ruili Wichterman, Jennifer McCoy, Joshua Huryn, Donna Auld, Douglas S. Smith, Amos B., III Inglese, James Trojanowski, John Q. Austin, Christopher P. Brunden, Kurt R. Lee, Virginia M. -Y. TI Identification of Aminothienopyridazine Inhibitors of Tau Assembly by Quantitative High-Throughput Screening SO BIOCHEMISTRY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEIN; FIBRILLIZATION IN-VITRO; ALZHEIMERS-DISEASE; NEURODEGENERATIVE TAUOPATHIES; PHOSPHORYLATED-TAU; PURIFIED TUBULIN; AGGREGATION; IMPAIRMENTS; DISORDERS; FILAMENTS AB Inclusions comprised of fibrils of the microtubule- (MT-) associated protein tau are found in the brains of those with Alzheimer's disease (AD) and other neurodegenerative tauopathies. The pathology that is observed in these diseases is believed to result from the formation of toxic tau oligomers or fibrils and/or from the loss of normal tau function due to its sequestration into insoluble deposits. Hence, small molecules that prevent tau oligomerization and/or fibrillization might have therapeutic value. Indeed, examples of such compounds have been published, but nearly all have properties that render them unsuitable as drug candidates. For these reasons, we conducted quantitative high-throughput screening (qHTS) of similar to 292000 compounds to identify drug-like inhibitors of tau assembly. The fibrillization of a truncated tau fragment that contains Four MT-binding domains was monitored in an assay that employed complementary thioflavin T fluorescence and fluorescence polarization methods. Previously described classes of inhibitors as well as new scaffolds were identified, including novel aminothienopyridazines (ATPZs). A number of ATPZ analogues were synthesized, and structure-activity relationships were defined. Further characterization of representative ATPZ compounds showed they do not interfere with tau-mediated MT assembly, and they are significantly more effective at preventing the fibrillization of tau than the A beta(1-42) peptide which forms AD senile plaques. Thus, the ATPZ molecules described here represent a novel class of tau assembly inhibitors that merit further development for testing in animal models of AD-like tau pathology. C1 [Crowe, Alex; Ballatore, Carlo; Trojanowski, John Q.; Brunden, Kurt R.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. [Crowe, Alex; Ballatore, Carlo; Trojanowski, John Q.; Brunden, Kurt R.; Lee, Virginia M. -Y.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Ballatore, Carlo; Hogan, Anne-Marie L.; Huryn, Donna; Smith, Amos B., III] Univ Penn, Sch Arts & Sci, Dept Chem, Philadelphia, PA 19104 USA. [Huang, Wenwei; Johnson, Ronald L.; Huang, Ruili; Wichterman, Jennifer; McCoy, Joshua; Auld, Douglas S.; Inglese, James; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Brunden, KR (reprint author), Univ Penn, Sch Med, Inst Aging, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. EM kbrunden@upenn.edu RI Brunden, Kurt/D-1994-2009; OI Huryn, Donna/0000-0001-5542-4968 FU National Institutes of Health [PO1 AG09215, P30 AG10124, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG17586, P01 AG19724, P01 NS-044233, UO1 AG24904]; Marian S. Ware Alzheimer Program, NIH Roadmap for Medical Research; Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This work was supported by grants from the National Institutes of Health (PO 1 AG09215, P30 AG10124, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG17586, P01 AG19724. P01 NS-044233, UO1 AG24904). the Marian S. Ware Alzheimer Program, NIH Roadmap for Medical Research, and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 61 TC 55 Z9 56 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 18 PY 2009 VL 48 IS 32 BP 7732 EP 7745 DI 10.1021/bi9006435 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 480GK UT WOS:000268720300020 PM 19580328 ER PT J AU Im, YJ Wollert, T Boura, E Hurley, JH AF Im, Young Jun Wollert, Thomas Boura, Evzen Hurley, James H. TI Structure and Function of the ESCRT-II-III Interface in Multivesicular Body Biogenesis SO DEVELOPMENTAL CELL LA English DT Article ID ENDOSOME-ASSOCIATED COMPLEX; ESCHERICHIA-COLI; GLUE DOMAIN; PROTEIN; MACHINERY; YEAST; VPS4; RECOGNITION; MODEL; MECHANISMS AB The ESCRT-II-ESCRT-III interaction coordinates the sorting of ubiquitinated cargo with the budding and scission of intralumenal vesicles into multivesicular bodies. The interacting regions of these complexes were mapped to the second winged helix domain of human ESCRT-II subunit VPS25 and the first helix of ESCRT-III subunit VPS20. The crystal structure of this complex was determined at 2.0 angstrom resolution. Residues involved in structural interactions explain the specificity of ESCRT-II for Vps20, and are critical for cargo sorting in vivo. ESCRT-II directly activates ESCRT-III-driven vesicle budding and scission in vitro via these structural interactions. VPS20 and ESCRT-II bind membranes with nanomolar affinity, explaining why binding to ESCRT-II is dispensable for the recruitment of Vps20 to membranes. Docking of the ESCRT-II-VPS20(2) supercomplex reveals a convex membrane-binding surface, suggesting a hypothesis for negative membrane curvature induction in the nascent intralumenal vesicle. C1 [Im, Young Jun; Wollert, Thomas; Boura, Evzen; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov RI Boura, Evzen/I-2626-2012; Boura, Evzen/G-5275-2014; OI Wollert, Thomas/0000-0001-9732-4789 FU U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; NIH; NIDDK; IATAP FX We thank Boris Baibakov for assistance with microscopy, Jurrien Dean and Jennifer Lippincott-Schwartz for use of their microscopes, Will Prinz for providing yeast strains and discussions, Adriana Rojas for help with crystallographic data collection, Ethan Tyler for producing Movie S1, and the SER-CAT staff for user support at the Advanced Photon Source (APS). Use of the APS was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No.W-31-109-Eng-38. This research was supported by NIH intramural support, NIDDK and IATAP. T.W. is an EMBO long-term fellow. NR 47 TC 55 Z9 56 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG 18 PY 2009 VL 17 IS 2 BP 234 EP 243 DI 10.1016/j.devcel.2009.07.008 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 485QM UT WOS:000269138600013 PM 19686684 ER PT J AU Goss, AM Tian, Y Tsukiyama, T Cohen, ED Zhou, D Lu, MM Yamaguchi, TP Morrisey, EE AF Goss, Ashley M. Tian, Ying Tsukiyama, Tadasuke Cohen, Ethan David Zhou, Diane Lu, Min Min Yamaguchi, Terry P. Morrisey, Edward E. TI Wnt2/2b and beta-Catenin Signaling Are Necessary and Sufficient to Specify Lung Progenitors in the Foregut SO DEVELOPMENTAL CELL LA English DT Article ID ENHANCER-BINDING PROTEIN; LIVER GROWTH; WNT SIGNALS; MORPHOGENESIS; GENE; EPITHELIUM; PROLIFERATION; SPECIFICATION; DELETION; CELLS AB Patterning of the primitive foregut promotes appropriate organ specification along its anterior-posterior axis. However, the molecular pathways specifying foregut endoderm progenitors are poorly understood. We show here that Wnt2/2b signaling is required to specify lung endoderm progenitors within the anterior foregut. Embryos lacking Wnt2/2b expression exhibit complete lung agenesis and do not express Nkx2.1, the earliest marker of the lung endoderm. In contrast, other foregut endoderm-derived organs, including the thyroid, liver, and pancreas, are correctly specified. The phenotype observed is recapitulated by an endoderm-restricted deletion of beta-catenin, demonstrating that Wnt2/2b signaling through the canonical Writ pathway is required to specify lung endoderm progenitors within the foregut. Moreover, activation of canonical Wnt/beta-catenin signaling results in the reprogramming of esophagus and stomach endoderm to a lung endoderm progenitor fate. Together, these data reveal that canonical Wnt2/2b signaling is required for the specification of lung endoderm progenitors in the developing foregut. C1 [Goss, Ashley M.; Tian, Ying; Cohen, Ethan David; Zhou, Diane; Lu, Min Min; Morrisey, Edward E.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Goss, Ashley M.; Morrisey, Edward E.] Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Tian, Ying; Cohen, Ethan David; Zhou, Diane; Lu, Min Min; Morrisey, Edward E.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Tsukiyama, Tadasuke; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA. [Morrisey, Edward E.] Univ Penn, Inst Regenerat Med, Philadelphia, PA 19104 USA. RP Morrisey, EE (reprint author), Univ Penn, Dept Med, Philadelphia, PA 19104 USA. EM emorrise@mail.med.upenn.edu RI Tsukiyama, Tadasuke/D-7589-2012 FU American Heart Association; National Institutes of Health (NIH) [HL075215, HL087825]; NIH, National Cancer Institute FX A.M.G. was, supported by an American Heart Association Predoctoral fellowship, and Y.T. and E.D.C. were supported by American Heart Association Postdoctoral fellowships. This work was support by funding from the National Institutes of Health (NIH) to E.E.M. (HL075215 and HL087825). This research was supported by the Intramural Research Program of the NIH, National Cancer Institute (T.P.Y.). The authors would like to thank the animal care personnel in the Animal Services Unit of the John Morgan Animal Facility at the University of Pennsylvania for help with animal husbandry. NR 40 TC 152 Z9 157 U1 7 U2 21 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG 18 PY 2009 VL 17 IS 2 BP 290 EP 298 DI 10.1016/j.devcel.2009.06.005 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 485QM UT WOS:000269138600018 PM 19686689 ER PT J AU Palmer, JR Herbst, AL Noller, KL Boggs, DA Troisi, R Titus-Ernstoff, L Hatch, EE Wise, LA Strohsnitter, WC Hoover, RN AF Palmer, Julie R. Herbst, Arthur L. Noller, Kenneth L. Boggs, Deborah A. Troisi, Rebecca Titus-Ernstoff, Linda Hatch, Elizabeth E. Wise, Lauren A. Strohsnitter, William C. Hoover, Robert N. TI Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study SO ENVIRONMENTAL HEALTH LA English DT Article ID TESTICULAR DYSGENESIS; SEXUAL DEVELOPMENT; PRENATAL EXPOSURE; EARLY-PREGNANCY; HORMONE LEVELS; CRYPTORCHIDISM; INUTERO; TESTIS; MALES; RISK AB Background: Diethylstilbestrol ( DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results. Methods: In data from a collaborative follow-up of three U. S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth. Results: Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11(th) week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes. Conclusion: These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years. C1 [Palmer, Julie R.; Boggs, Deborah A.; Wise, Lauren A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Herbst, Arthur L.] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. [Noller, Kenneth L.; Strohsnitter, William C.] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. [Troisi, Rebecca; Hoover, Robert N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Troisi, Rebecca; Titus-Ernstoff, Linda] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Troisi, Rebecca; Titus-Ernstoff, Linda] Dartmouth Med Sch, Dept Pediat, Lebanon, NH USA. [Hatch, Elizabeth E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Palmer, JR (reprint author), Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. EM jpalmer@bu.edu; alherbst@babies.bsd.uchicago.edu; knoller@tuftsmedicalcenter.org; dboggs@slone.bu.edu; troisir@mail.nih.gov; Linda.T.Titus-Ernstoff@Dartmouth.EDU; eehatch@bu.edu; lwise@slone.bu.edu; wstrohsnitter@tuftsmedicalcenter.org; hooverr@exchange.nih.gov OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 FU National Cancer Institute of the United States [N01-CP-21168, N01-CP-51017, N01CP-021289, N01-CP-55507] FX Funding was provided by contracts N01-CP-21168, N01-CP-51017, N01CP-021289, and N01-CP-55507 from the National Cancer Institute of the United States. NR 24 TC 50 Z9 52 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-069X J9 ENVIRON HEALTH-GLOB JI Environ. Health PD AUG 18 PY 2009 VL 8 AR 37 DI 10.1186/1476-069X-8-37 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 494AN UT WOS:000269781600002 PM 19689815 ER PT J AU Chen, KQ Huang, J Liu, Y Gong, WH Cui, YH Wang, JM AF Chen, Keqiang Huang, Jian Liu, Ying Gong, Wanghua Cui, Youhong Wang, Ji Ming TI Synergy of TRIF-dependent TLR3 and MyD88-dependent TLR7 in up-regulating expression of mouse FPR2, a promiscuous G-protein-coupled receptor, in microglial cells SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE TLR3; TLR7; Cooperation; Microglia; mFPR2 ID DOUBLE-STRANDED-RNA; TOLL-LIKE RECEPTOR-3; CENTRAL-NERVOUS-SYSTEM; FORMYL PEPTIDE RECEPTOR-2; NF-KAPPA-B; DENDRITIC CELLS; MONOCLONAL-ANTIBODY; ALZHEIMERS-DISEASE; ACTIVATION; COOPERATION AB Human G-protein-coupled formyl peptide receptor-like 1 and its mouse homologue formyl peptide receptor 2 mediate the chemotactic activity of a variety of pathogen and host-derived peptides, including amyloid 1342, a key causative factor in Alzheimer's disease (AD). Here, we found that polyinosine-polycytidylic acid (Poly(I:C)), which is a specific TLR3 ligand, and Imiquimod (R837), which is a specific TLR7 ligand, when used alone, each increased MAPK-dependent functional mFPR2 expression in microglial cells, and the combination of Poly(I:C) and R837 exhibited additive effect by enhancing the level Of I kappa B-alpha phosphorylation. Our results indicated that RNA virus infection may actively participate in the pathogenic processes of brain inflammation and neurodegenerative diseases by TLR3- and TLR7-mediated TRIF-dependent and MyD88-dependent signaling pathways. Published by Elsevier B.V. C1 [Chen, Keqiang; Huang, Jian; Liu, Ying; Wang, Ji Ming] NCI, Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Chen, Keqiang] Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 200030, Peoples R China. [Huang, Jian; Cui, Youhong] Third Mil Med Univ, Chongqing, Peoples R China. [Gong, Wanghua] NCI, SAIC Frederick, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Ctr Canc Res, Mol Immunoregulat Lab, Canc & Inflammat Program, Bldg 560,Room 31-76, Frederick, MD 21702 USA. EM wangji@mail.nih.gov FU National Cancer Institute; National Institutes of Health [NO1-CO-12400] FX The authors thank Dr. J. J. Oppenheim for critically reviewing the manuscript, and Ms. C. Lamb and Ms. C. Magers for secretarial assistance. We also thank S. Bauchiero, R. Matthai and K. Noer of CCR, NCI-Frederick, for flow cytometry analyses. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The research was also supported in part by the Intramural Research Program of the NCI, NIH. NR 41 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD AUG 18 PY 2009 VL 213 IS 1-2 BP 69 EP 77 DI 10.1016/j.jneuroim.2009.05.018 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 491HD UT WOS:000269568500009 PM 19559490 ER PT J AU Kim, YC Wikstrom, M Hummer, G AF Kim, Young C. Wikstrom, Marten Hummer, Gerhard TI Kinetic gating of the proton pump in cytochrome c oxidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bioenergetics; biological machines; kinetic master equation; respiration ID HEME-COPPER OXIDASES; ELECTRON-TRANSFER REACTIONS; PARACOCCUS-DENITRIFICANS; COUPLED PROTON; OXYGEN ACTIVATION; CATALYTIC CYCLE; TRANSLOCATION; MECHANISM; REDUCTION; MODEL AB Cytochrome c oxidase (CcO), the terminal enzyme of the respiratory chain, reduces oxygen to water and uses the released energy to pump protons across a membrane. Here, we use kinetic master equations to explore the energetic and kinetic control of proton pumping in CcO. We construct models consistent with thermodynamic principles, the structure of CcO, experimentally known proton affinities, and equilibrium constants of intermediate reactions. The resulting models are found to capture key properties of CcO, including the midpoint redox potentials of the metal centers and the electron transfer rates. We find that coarse-grained models with two proton sites and one electron site can pump one proton per electron against membrane potentials exceeding 100 mV. The high pumping efficiency of these models requires strong electrostatic couplings between the proton loading (pump) site and the electron site (heme a), and kinetic gating of the internal proton transfer. Gating is achieved by enhancing the rate of proton transfer from the conserved Glu-242 to the pump site on reduction of heme a, consistent with the predictions of the water-gated model of proton pumping. The model also accounts for the phenotype of D-channel mutations associated with loss of pumping but retained turnover. The fundamental mechanism identified here for the efficient conversion of chemical energy into an electro-chemical potential should prove relevant also for other molecular machines and novel fuel-cell designs. C1 [Kim, Young C.; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Wikstrom, Marten] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki, Finland. [Wikstrom, Marten] Univ Helsinki, Biocentrum Helsinki, FI-00014 Helsinki, Finland. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Institutes of Health; Academy of Finland; Biocentrum Helsinki; Sigrid Juselius Foundation FX Y.C.K and G.H. were supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. M. W. was supported by grants from the Academy of Finland, Biocentrum Helsinki, and the Sigrid Juselius Foundation. NR 48 TC 47 Z9 47 U1 1 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 13707 EP 13712 DI 10.1073/pnas.0903938106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700017 PM 19666617 ER PT J AU McGlinchey, RP Shewmaker, F McPhie, P Monterroso, B Thurber, K Wickner, RB AF McGlinchey, Ryan P. Shewmaker, Frank McPhie, Peter Monterroso, Begona Thurber, Kent Wickner, Reed B. TI The repeat domain of the melanosome fibril protein Pmel17 forms the amyloid core promoting melanin synthesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SOLID-STATE NMR; BETA-SHEET STRUCTURE; NUCLEAR-MAGNETIC-RESONANCE; PRION-INDUCING DOMAIN; PINK-EYED DILUTION; HET-S PRION; IN-VITRO; PARALLEL; ORGANIZATION; PH AB Pmel17 is a melanocyte protein necessary for eumelanin deposition 1 in mammals and found in melanosomes in a filamentous form. The luminal part of human Pmel17 includes a region (RPT) with 10 copies of a partial repeat sequence, pt.e.gttp.qv., known to be essential in vivo for filament formation. We show that this RPT region readily forms amyloid in vitro, but only under the mildly acidic conditions typical of the lysosome-like melanosome lumen, and the filaments quickly become soluble at neutral pH. Under the same mildly acidic conditions, the Pmel filaments promote eumelanin formation. Electron diffraction, circular dichroism, and solid-state NMR studies of Pmel17 filaments show that the structure is rich in beta sheet. We suggest that RPT is the amyloid core domain of the Pmel17 filaments so critical for melanin formation. C1 [McGlinchey, Ryan P.; Shewmaker, Frank; McPhie, Peter; Monterroso, Begona; Wickner, Reed B.] NIDDKD, Lab Biochem & Genent, NIH, Bethesda, MD 20892 USA. [Thurber, Kent] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genent, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Monterroso, Begona/J-9748-2014 OI Monterroso, Begona/0000-0003-2538-084X FU National Institute of Diabetes, Digestive and Kidney Diseases FX We thank Mickey Marks (University of Pennsylvania, Philadelphia) for clones of Pmel17, Eric Anderson for mass spectrometry work, Rob Tycko and Vince Hearing for fruitful discussions, and our colleagues for critical reading of the manuscript. This work was supported by the Intramural Program of the National Institute of Diabetes, Digestive and Kidney Diseases. NR 55 TC 55 Z9 57 U1 0 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 13731 EP 13736 DI 10.1073/pnas.0906509106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700021 PM 19666488 ER PT J AU Boyko, AR Boyko, RH Boyko, CM Parker, HG Castelhano, M Corey, L Degenhardt, JD Auton, A Hedimbi, M Kityo, R Ostrander, EA Schoenebeck, J Todhunter, RJ Jones, P Bustamante, CD AF Boyko, Adam R. Boyko, Ryan H. Boyko, Corin M. Parker, Heidi G. Castelhano, Marta Corey, Liz Degenhardt, Jeremiah D. Auton, Adam Hedimbi, Marius Kityo, Robert Ostrander, Elaine A. Schoenebeck, Jeffrey Todhunter, Rory J. Jones, Paul Bustamante, Carlos D. TI Complex population structure in African village dogs and its implications for inferring dog domestication history SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Canis familiaris; microsatellites; principal component analysis; single nucleotide polymorphisms ID MITOCHONDRIAL-DNA; DIVERSITY; ASSOCIATION; PROGRAM; ORIGIN; BREEDS; BALI AB High genetic diversity of East Asian village dogs has recently been used to argue for an East Asian origin of the domestic dog. However, global village dog genetic diversity and the extent to which semiferal village dogs represent distinct, indigenous populations instead of admixtures of various dog breeds has not been quantified. Understanding these issues is critical to properly reconstructing the timing, number, and locations of dog domestication. To address these questions, we sampled 318 village dogs from 7 regions in Egypt, Uganda, and Namibia, measuring genetic diversity >680 bp of the mitochondrial D-loop, 300 SNPs, and 89 microsatellite markers. We also analyzed breed dogs, including putatively African breeds (Afghan hounds, Basenjis, Pharaoh hounds, Rhodesian ridgebacks, and Salukis), Puerto Rican street dogs, and mixed breed dogs from the United States. Village dogs from most African regions appear genetically distinct from non-native breed and mixed-breed dogs, although some individuals cluster genetically with Puerto Rican dogs or United States breed mixes instead of with neighboring village dogs. Thus, African village dogs are a mosaic of indigenous dogs descended from early migrants to Africa, and non-native, breed-admixed individuals. Among putatively African breeds, Pharaoh hounds, and Rhodesian ridgebacks clustered with non-native rather than indigenous African dogs, suggesting they have predominantly non-African origins. Surprisingly, we find similar mtDNA haplotype diversity in African and East Asian village dogs, potentially calling into question the hypothesis of an East Asian origin for dog domestication. C1 [Boyko, Adam R.; Degenhardt, Jeremiah D.; Auton, Adam; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Boyko, Ryan H.; Boyko, Corin M.] Univ Calif Davis, Dept Anthropol, Davis, CA 95616 USA. [Boyko, Ryan H.; Boyko, Corin M.] Univ Calif Davis, Grad Grp Ecol, Davis, CA 95616 USA. [Parker, Heidi G.; Ostrander, Elaine A.; Schoenebeck, Jeffrey] NHGRI, NIH, Bethesda, MD 20892 USA. [Castelhano, Marta; Corey, Liz; Todhunter, Rory J.] Cornell Univ, Coll Vet Med, Dept Clin Sci & Med Genet Arch, Ithaca, NY 14853 USA. [Hedimbi, Marius] Univ Namibia, Dept Biol Sci, Windhoek, Namibia. [Kityo, Robert] Makerere Univ, Dept Zool, Kampala, Uganda. [Jones, Paul] Walthan Ctr Pet Nutr, Melton Mowbray LE14 4RT, Leics, England. RP Boyko, AR (reprint author), Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. EM arb83@cornell.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU Center for Vertebrate Genomics, Department of Clinical Sciences and Baker Institute of Animal Health, Cornell University; National Institutes of Health Center for Scientific Review; R24 research grant program; National Science Foundation [0516310]; Sloan Foundation FX We thank numerous volunteers and animal shelters for their assistance in gathering samples, including Leonard Kuwale, Ahmed Samaha, Kazhila Chinsembu, Animal Care in Egypt (Luxor), Animal Friends Shelter (Giza), Albergue de Animales Villa Michelle (Mayaguez), and Albergue La Gabriella (Ponce); Jason Mezey, Fengfei Wang, Katarzyna Bryc, and Andy Reynolds for their assistance with lab and computational resources; Bob Wayne, Niels Pedersen, Ben Sacks, Sarah Brown, and Peter Savolainen for helpful comments and discussion; and the intramural program of the National Human Genome Research Institute. This work supported by the Center for Vertebrate Genomics, Department of Clinical Sciences and Baker Institute of Animal Health, Cornell University; National Institutes of Health Center for Scientific Review and R24 research grant program; National Science Foundation Grant 0516310; and a Sloan Foundation research fellowship. NR 29 TC 73 Z9 76 U1 5 U2 66 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 13903 EP 13908 DI 10.1073/pnas.0902129106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700052 PM 19666600 ER PT J AU Simons, SB Escobedo, Y Yasuda, R Dudek, SM AF Simons, Stephen B. Escobedo, Yasmin Yasuda, Ryohei Dudek, Serena M. TI Regional differences in hippocampal calcium handling provide a cellular mechanism for limiting plasticity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CA2; hippocampus; synaptic plasticity ID LONG-TERM POTENTIATION; IQ-MOTIF PROTEINS; SYNAPTIC PLASTICITY; POSTSYNAPTIC CALCIUM; BLOCK INDUCTION; CALMODULIN; NEURONS; PEP-19; RAT; TRANSMISSION AB Although much is known about the mechanisms underlying synaptic plasticity, the cellular mechanisms that negatively regulate plasticity in some brain regions are considerably less studied. One region where neurons do not reliably express long-term potentiation (LTP) is the CA2 subfield of the hippocampus. Given the connection between synaptic plasticity and increases in postsynaptic [Ca(2+)], and that CA2 neurons express a large number of calcium-regulating proteins, we tested the hypothesis that the relative lack of LTP in CA2 results from differences in the calcium dynamics of these neurons. By measuring calcium-dependent fluorescence transients in dendritic spines, we show that CA2 neurons have smaller action potential-evoked intracellular Ca(2+) transients because of a higher endogenous Ca(2+)-buffering capacity and significantly higher rates of Ca(2+) extrusion when compared with CA1 and CA3 neurons. Perfusion with higher external [Ca(2+)] during induction restores LTP to CA2 neurons, suggesting that they possess the cellular machinery required for plasticity, but that the restriction of postsynaptic [Ca(2+)] limits its expression. Camstatin, an analogue of the calcium-modulating protein Pep-19 strongly expressed in CA2 neurons, blocked LTP and increased Ca(2+) extrusion in CA1 neurons, suggesting a role for extrusion in the regulation of plasticity in CA2. In agreement with this idea, we found that intracellular introduction of a PMCA pump inhibitor (carboxyeosin) allows for the induction of LTP in CA2 neurons. Our results indicate that regulation of postsynaptic [Ca(2+)] through modulation of extrusion and/or buffering regulates expression of LTP in CA2 and potentially other brain regions. C1 [Simons, Stephen B.; Dudek, Serena M.] NIEHS, Neurobiol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. [Escobedo, Yasmin; Yasuda, Ryohei] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. RP Dudek, SM (reprint author), NIEHS, Neurobiol Lab, Dept Hlth & Human Serv, NIH, 111 TW Alexander Dr,MD F2-04, Res Triangle Pk, NC 27709 USA. EM dudek@niehs.nih.gov RI Yasuda, Ryohei/E-7726-2011; OI Dudek, Serena M./0000-0003-4094-8368 FU National Institute of Health, National Institute of Environmental Health Science; National Institutes of Health [RO1MH080047] FX We thank Dr. Jim Putney for his helpful suggestions on the manuscript. This work was supported by the Intramural Research Program of the National Institute of Health, National Institute of Environmental Health Science, and by National Institutes of Health Grant RO1MH080047. NR 35 TC 44 Z9 44 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 14080 EP 14084 DI 10.1073/pnas.0904775106 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700082 PM 19666491 ER PT J AU Pelled, G Bergstrom, DA Tierney, PL Conroy, RS Chuang, KH Yu, D Leopold, DA Walters, JR Koretsky, AP AF Pelled, Galit Bergstrom, Debra A. Tierney, Patrick L. Conroy, Richard S. Chuang, Kai-Hsiang Yu, David Leopold, David A. Walters, Judith R. Koretsky, Alan P. TI Ipsilateral cortical fMRI responses after peripheral nerve damage in rats reflect increased interneuron activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE imaging; plasticity; somatosensory cortex; nerve injury; cortical interneurons ID CEREBRAL BLOOD-FLOW; NEURONAL-ACTIVITY; FUNCTIONAL MRI; SYNAPTIC ACTIVITY; FOREPAW STIMULATION; SENSORY CORTEX; BRAIN; SIGNALS; AREA; DEPRIVATION AB In the weeks following unilateral peripheral nerve injury, the deprived primary somatosensory cortex (SI) responds to stimulation of the ipsilateral intact limb as demonstrated by functional magnetic resonance imaging (fMRI) responses. The neuronal basis of these responses was studied by using high-resolution fMRI, in vivo electrophysiological recordings, and juxtacellular neuronal labeling in rats that underwent an excision of the forepaw radial, median, and ulnar nerves. These nerves were exposed but not severed in control rats. Significant bilateral increases of fMRI responses in SI were observed in denervated rats. In the healthy SI of the denervated rats, increases in fMRI responses were concordant with increases in local field potential (LFP) amplitude and an increased incidence of single units responding compared with control rats. In contrast, in the deprived SI, increases in fMRI responses were associated with a minimal change in LFP amplitude but with increased incidence of single units responding. Based on action potential duration, juxtacellular labeling, and immunostaining results, neurons responding to intact forepaw stimulation in the deprived cortex were identified as interneurons. These results suggest that the increases in fMRI responses in the deprived cortex reflect increased interneuron activity. C1 [Pelled, Galit; Conroy, Richard S.; Chuang, Kai-Hsiang; Koretsky, Alan P.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. [Bergstrom, Debra A.; Walters, Judith R.] Natl Inst Neurol Disorders & Stroke, Neurophysiol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. [Tierney, Patrick L.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Yu, David] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Leopold, David A.] NEI, Natl Inst Neurol Disorders & Stroke, NIMH,NIH, Lab Neuropsychol,Unit Cognit Neurophysiol & Imagi, Bethesda, MD 20892 USA. RP Pelled, G (reprint author), Johns Hopkins Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA. EM pelled@kennedykrieger.org RI Tierney, Patrick/E-5860-2010; Conroy, Richard/D-1979-2009; Koretsky, Alan/C-7940-2015; OI Conroy, Richard/0000-0002-8896-6090; Koretsky, Alan/0000-0002-8085-4756; Leopold, David/0000-0002-1345-6360; Chuang, Kai-Hsiang/0000-0002-8356-0657 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke FX We thank Dr. Steve Dodd and Ms. Nadia Bouraoud for assistance. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. NR 30 TC 36 Z9 37 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 18 PY 2009 VL 106 IS 33 BP 14114 EP 14119 DI 10.1073/pnas.0903153106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 484WE UT WOS:000269078700088 PM 19666522 ER PT J AU Wilson, AD AF Wilson, Aaron D. TI Homogenous electrocatalysts and activation of small molecules with the relevance to energy research SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wilson, Aaron D.] NCI, NIH, Bethesda, MD 20892 USA. EM aarondoylewilson@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 31-AEI BP 55 EP 55 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900054 ER PT J AU Eaton, WA AF Eaton, William A. TI Single molecule protein kinetics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Eaton, William A.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM eaton@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 125-BIOL BP 743 EP 743 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900655 ER PT J AU Qualley, DF Stewart-Maynard, KM Wang, F Mitra, M Gorelick, RJ Rouzina, I Williams, MC Musier-Forsyth, K AF Qualley, Dominic F. Stewart-Maynard, Kristen M. Wang, Fei Mitra, Mithun Gorelick, Robert J. Rouzina, Ioulia Williams, Mark C. Musier-Forsyth, Karin TI BIOL 155 - C-terminal domain regulates the nucleic acid chaperone activity of HTLV-1 NC via an electrostatic mechanism SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Qualley, Dominic F.] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. [Stewart-Maynard, Kristen M.] Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. [Wang, Fei; Williams, Mark C.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Mitra, Mithun] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. [Gorelick, Robert J.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Rouzina, Ioulia] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. [Musier-Forsyth, Karin] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA. EM dqualley@chemistry.ohio-state.edu; musier@chemistry.ohio-state.edu RI Mitra, Mithun/A-2133-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 155-BIOL BP 835 EP 835 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900747 ER PT J AU Basudhar, D Ridnour, LA Wink, DA Miranda, KM AF Basudhar, Debashree Ridnour, Lisa A. Wink, David A. Miranda, Katrina M. TI BIOL 14 - No-aspirin: Synthesis and study of chemical and biological properties SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Basudhar, Debashree; Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. [Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. EM basudhar@email.arizona.edu RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 14-BIOL BP 881 EP 881 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861900793 ER PT J AU Adams, KM Kaczmarek, P Lee, YC Keay, SK Barchi, JJ AF Adams, Kristie M. Kaczmarek, Piotr Lee, Yi-Chien Keay, Susan K. Barchi, Joseph J., Jr. TI CARB 48-Biophysical characterization and conformational analysis of antiproliferative factor (APF): A novel anticancer lead compound SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Barchi, Joseph J., Jr.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. [Keay, Susan K.] Univ Maryland, Sch Med, Baltimore VA Med Ctr, Baltimore, MD 21201 USA. EM adamskm@mail.nih.gov; pkaczmarek@ncifcrf.gov; leey@ncifcrf.gov; skeay@medicine.umaryland.edu; barchi@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 48-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902109 ER PT J AU Appella, DH AF Appella, Daniel H. TI Molecular designs for peptide nucleic acids in detection and multivalent platforms SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 62-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908370 ER PT J AU Appella, DH AF Appella, Daniel H. TI CARB 38-Multivalent binding oligomers to target TAR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 38-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902034 ER PT J AU Bahde, RJ Trenkle, WC AF Bahde, Robert J. Trenkle, William C. TI Controlled decomposition of azides under base mediated conditions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bahde, Robert J.; Trenkle, William C.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. EM bahder@mail.nih.gov; wtrenkle@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 263-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908597 ER PT J AU Bahta, M AF Bahta, Medhanit TI Development of inhibitors of the Yersinia pestis protein tyrosine phosphatase, YopH: Application of substrate activity screening SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bahta, Medhanit] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM bahtam@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 178-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907166 ER PT J AU Bhattacharyya, S Cheal, SM Hill, GC Griffiths, GL AF Bhattacharyya, Sibaprasad Cheal, Sarah M. Hill, G. Craig Griffiths, Gary L. TI ANYL 116-Radiometric metal binding assay to determine chelate to protein ratio: A comparative study between 57Co and 111In SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bhattacharyya, Sibaprasad] NCI, Appl & Dev Res Support Directorate, SAIC Frederick, NIH, Frederick, MD 21702 USA. [Cheal, Sarah M.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Hill, G. Craig] NCI, Clin Monitoring Res Program, SAIC Frederick Inc, NIH, Bethesda, MD 20892 USA. EM bhattacharyyas2@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 116-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901090 ER PT J AU Bolton, E AF Bolton, Evan TI Structure activity relationship analysis using PubChem SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bolton, Evan] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM bolton@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 37-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904315 ER PT J AU Boukari, H Silva, C Nossal, R Horkay, F AF Boukari, Hacene Silva, Candida Nossal, Ralph Horkay, Ferenc TI POLY 384-Probing macromolecular motion in polymeric and biopolymeric gels SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Boukari, Hacene] NIH, Program Phys Biol, Bethesda, MD 20892 USA. [Silva, Candida; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Nossal, Ralph] NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM boukarih@mail.nih.gov; silvaca@mail.nih.gov; horkay@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 384-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906105 ER PT J AU Bradley, JC Mirza, K Guha, R Lang, A Williams, A AF Bradley, Jean-Claude Mirza, Khalid Guha, Rajarshi Lang, Andrew Williams, A. TI CINF 15-Crowdsourcing nonaqueous solubility and synthesis using Open Notebook Science SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bradley, Jean-Claude; Mirza, Khalid] Drexel Univ, Dept Chem, Philadelphia, PA 19104 USA. [Guha, Rajarshi] NIH Chem Genom Ctr, Rockville, MD 20850 USA. [Lang, Andrew] Oral Roberts Univ, Dept Math, Tulsa, OK 74171 USA. [Williams, A.] ChemZoo Inc, Wake Forest, NC 27587 USA. EM bradlejc@drexel.edu; rajarshi.guha@gmail.com; gameshoncho@hotmail.com; antony.williams@chemspider.com NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 15-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902710 ER PT J AU Brinas, RP Sundgren, A Maetani, M Rittenhouse-Olson, K Sahoo, P Morey, S Houghton, A Barchi, JJ AF Brinas, Raymond P. Sundgren, Andreas Maetani, Micah Rittenhouse-Olson, Kate Sahoo, Padmini Morey, Susan Houghton, Amy Barchi, Joseph J., Jr. TI CARB 69-Multivalent presentation of tumor-associated carbohydrate antigen using gold nanoparticles as scaffold for immunotherapeutic applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brinas, Raymond P.; Sundgren, Andreas; Maetani, Micah] NCI, Med Chem Lab, Ft Detrick, MD 21702 USA. [Rittenhouse-Olson, Kate; Sahoo, Padmini; Morey, Susan; Houghton, Amy; Barchi, Joseph J., Jr.] SUNY Buffalo, Dept Clin Lab Sci, Sch Hlth Related Profess, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 69-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902100 ER PT J AU Brooks, BR AF Brooks, Bernard R. TI Examining protein dynamics and function using multiscale methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brooks, Bernard R.] NHLBI, NIH, Lab Computat Biol, Bethesda, MD 20892 USA. EM brb@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 61-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904220 ER PT J AU Brooks, PJ AF Brooks, Phillip J. TI TOXI 101-DNA adducts involved in xeroderma pigmentosum neurologic disease and in alcohol-related carcinogenesis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Brooks, Phillip J.] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. EM pjbrooks@dicbr.niaaa.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 101-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906780 ER PT J AU Bumb, A Dobson, PJ Regino, CAS Bernardo, M Baidoo, K Choyke, P Brechbiel, MW AF Bumb, Ambika Dobson, Peter J. Regino, Celeste A. S. Bernardo, Marcelino Baidoo, Kwamena Choyke, Peter Brechbiel, Martin W. TI Nanomedicine: Engineering of a tri-imageable nanoparticle for diagnostics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Bumb, Ambika] NCI, Radiat Oncol Branch, NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. [Dobson, Peter J.] Univ Oxford, Kidlington OX5 1PF, Oxon, England. [Regino, Celeste A. S.; Choyke, Peter] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA. [Bernardo, Marcelino] SAIC Frederick Inc, Imaging Phys, Lab Anim Sci Program, Bethesda, MD 20892 USA. EM bumba@mail.nih.gov; peter.dobson@begbroke.ox.ac.uk; reginoc@mail.nih.gov; bernardme@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 292-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000474 ER PT J AU Cai, LS Houlihan, B Peng, YY Liu, HL Pike, VW AF Cai, Lisheng Houlihan, Brenna Peng, Yi-Yuan Liu, Han-Liang Pike, Victor W. TI Highly efficient N-monomethylation of primary aryl amines in the synthesis of radioligands for amyloid imaging in Alzheimer's disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cai, Lisheng; Houlihan, Brenna] NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, Bethesda, MD 20892 USA. [Peng, Yi-Yuan; Liu, Han-Liang] Jiangxi Normal Univ, Dept Chem, Nanchang 330027, Peoples R China. [Pike, Victor W.] NIMH, Mol Imaging Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM cail@intra.nimh.nih.gov; houlihanb@mail.nih.gov; pikev@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 41-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907187 ER PT J AU Cai, LS Houlihan, B Tao, XC Dai, CY Cao, XJ Pike, VW AF Cai, Lisheng Houlihan, Brenna Tao, Xiaochun Dai, Chunya Cao, Xiongjie Pike, Victor W. TI Palladium-catalyzed aryl C-N bond formation in the synthesis of radioligands for amyloid imaging in Alzheimer's disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cai, Lisheng; Houlihan, Brenna] NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, Bethesda, MD 20892 USA. [Tao, Xiaochun; Dai, Chunya; Cao, Xiongjie] E China Univ Sci & Technol, Dept Chem, Lab Organometall Chem, Shanghai 200237, Peoples R China. [Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM cail@intra.nimh.nih.gov; houlihanb@mail.nih.gov; pikev@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 464-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907161 ER PT J AU Chatterjee, K Lin-Gibson, S Wallace, WE Young, MF Simon, CG AF Chatterjee, Kaushik Lin-Gibson, Sheng Wallace, William E. Young, Marian F. Simon, Carl G., Jr. TI Combinatorial screening of hydrogel properties for 3D cell culture: Effect of stiffness on encapsulated osteoblasts SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chatterjee, Kaushik; Lin-Gibson, Sheng; Wallace, William E.; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Young, Marian F.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM kaushik.chatterjee@nist.gov; sheng.lin-gibson@nist.gov; william.wallace@nist.gov; mayoung@mail.nih.gov; carl.simon@nist.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 200-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861905339 ER PT J AU Cho, TJ Zangmeister, RA MacCuspie, RI Patri, AK Hackley, VA AF Cho, Tae Joon Zangmeister, Rebecca A. MacCuspie, Robert I. Patri, Anil K. Hackley, Vincent A. TI COLL 365-Newkome type dendron stabilized gold nanoparticles: Syntheses, reactivity, and stability SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cho, Tae Joon; MacCuspie, Robert I.; Hackley, Vincent A.] NIST, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA. [Zangmeister, Rebecca A.] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. EM taejoon.cho@nist.gov; razang@nist.gov; robert.maccuspie@nist.gov; patria@mail.nih.gov; vince.hackley@nist.gov RI Zangmeister, Rebecca/D-6641-2017 OI Zangmeister, Rebecca/0000-0002-0540-6240 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 365-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903388 ER PT J AU Chun, JH Pike, VW AF Chun, Joong-Hyun Pike, Victor W. TI Synthesis of unsymmetrical diaryliodonium salts via in situ generated [hydroxy(tosyloxy)iodo] arenes as precursors for radiofluoridation studies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chun, Joong-Hyun; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM chunjoong@mail.nih.gov; pikev@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 816-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000603 ER PT J AU Clore, GM AF Clore, G. Marius TI Visualizing lowly-populated regions of the free energy landscape of macromolecular complexes by paramagnetic relaxation enhancement SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Clore, G. Marius] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM mariusc@mail.nih.gov NR 4 TC 0 Z9 0 U1 3 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 30-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904002 ER PT J AU Costanzi, S Vilar, S Karpiak, JD AF Costanzi, Stefano Vilar, Santiago Karpiak, Joel D. TI In silico analyses suggest the freedom of motion of the second extracellular loop as a requirement for the activation of the beta(2)-adrenergic receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Costanzi, Stefano; Vilar, Santiago; Karpiak, Joel D.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov; vilarvarelas@niddk.nih.gov; karpiakj@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 452-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907364 ER PT J AU Cushman, M Xiao, XS Ioanoviciu, A Morrell, A Nagarajan, M Song, YL Shao, ZY Kiselev, E Cinelli, MA Staker, B Burgin, AB Stewart, L Antony, S Kohlhagen, G Dexheimer, TS Pommier, Y AF Cushman, Mark Xiao, Xiangshu Ioanoviciu, Alexandra Morrell, Andrew Nagarajan, Muthukaman Song, Yunlong Shao, Zhi-Yu Kiselev, Evgeny Cinelli, Maris A. Staker, Bart Burgin, Alex B. Stewart, Lance Antony, Smitha Kohlhagen, Glenda Dexheimer, Thomas S. Pommier, Yves TI Design and synthesis of indenoisoquinoline topoisomerase I inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Cushman, Mark; Xiao, Xiangshu; Ioanoviciu, Alexandra; Morrell, Andrew; Nagarajan, Muthukaman; Song, Yunlong; Shao, Zhi-Yu; Kiselev, Evgeny; Cinelli, Maris A.] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Cushman, Mark; Xiao, Xiangshu; Ioanoviciu, Alexandra; Morrell, Andrew; Nagarajan, Muthukaman; Song, Yunlong; Shao, Zhi-Yu; Kiselev, Evgeny; Cinelli, Maris A.] Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. [Staker, Bart; Burgin, Alex B.; Stewart, Lance] deCODE Genet Inc, BioStruct Grp, DeCODE genet, Bainbridge Isl, WA 98110 USA. [Antony, Smitha; Kohlhagen, Glenda; Dexheimer, Thomas S.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM cushman@pharmacy.purdue.edu NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 322-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908716 ER PT J AU Darian, E Semenyuk, A Seidman, MM MacKerell, AD AF Darian, Eva Semenyuk, Andrey Seidman, Michael M. MacKerell, Alexander D., Jr. TI Effect of the nucleotide modification on the conformation and stability of the triple DNA formation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Darian, Eva; MacKerell, Alexander D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Semenyuk, Andrey] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Seidman, Michael M.] NIA, Lab Mol Gerontol, Sect Gene Targeting, Baltimore, MD 21224 USA. EM edarian@outerbanks.umaryland.edu; semenyuka@mail.nih.gov; seidmanm@grc.nia.nih.gov; alex@outerbanks.umaryland.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 234-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904201 ER PT J AU Das, A Zhou, YX Carter, RL Harden, TK Jacobson, KA AF Das, Arijit Zhou, Yixing Carter, Rhonda L. Harden, T. Kendall Jacobson, Kenneth A. TI Enhanced potency of nucleotide-dendrimer conjugates as agonists of the P2Y14 receptor: Multivalent effect in G protein-coupled receptor recognition SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Das, Arijit; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Zhou, Yixing; Carter, Rhonda L.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM dasarijit@niddk.nih.gov; kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 186-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907136 ER PT J AU Davis, M AF Davis, Myrtle TI Comparative toxicity of kinase inhibitors: Considerations for drug discovery and development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Davis, Myrtle] NCI, Chief Toxicol & Pharmacol Branch, Dev Therapeut Program, Rockville, MD 20852 USA. EM myrtledavis@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 589-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908306 ER PT J AU De Castro, S Kim, Y Gao, ZG Ijzerman, AP Jacobson, KA AF De Castro, Sonia Kim, Yoonkyung Gao, Zhan-Guo Ijzerman, Adriaan P. Jacobson, Kenneth A. TI Novel 2-and 4-substituted 1H-Imidazo[4,5-c]quinolin-4-amine derivatives as allosteric modulators of the A3 adenosine receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [De Castro, Sonia; Kim, Yoonkyung; Gao, Zhan-Guo] NIDDK, NIH, Bethesda, MD 20892 USA. [Ijzerman, Adriaan P.] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. EM soniadecastro@gmail.com; kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 173-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907039 ER PT J AU DeFusco, AA Ivanic, J Schmidt, MW Gordon, MS AF DeFusco, Albert A., III Ivanic, Joseph Schmidt, Michael W. Gordon, Mark S. TI Vertical excitations of nucleobases in solution SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [DeFusco, Albert A., III] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Ivanic, Joseph] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. [Schmidt, Michael W.; Gordon, Mark S.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Schmidt, Michael W.; Gordon, Mark S.] Iowa State Univ, Ames Lab USDOE, Ames, IA 50011 USA. EM albert@si.msg.chem.iastate.edu; jivanic@ncifcrf.gov; mike@si.msg.chem.iastate.edu; mark@si.msg.chem.iastate.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 414-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909041 ER PT J AU Dong, SW Hamel, E Beutler, JA Porco, JA AF Dong, Suwei Hamel, Ernest Beutler, John A. Porco, John A., Jr. TI Enantioselective synthesis of (+)-chamaecypanone C and analogs using a tandem retro-Diels-Alder/Diels-Alder cascade SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dong, Suwei; Porco, John A., Jr.] Boston Univ, Dept Chem, Boston, MA 02215 USA. [Dong, Suwei; Porco, John A., Jr.] Boston Univ, Ctr Chem Methodol & Lib Dev, Boston, MA 02215 USA. [Hamel, Ernest] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Beutler, John A.] NCI, Mol Targets Dev Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM swdong@bu.edu; porco@bu.edu RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 229-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908297 ER PT J AU Doroshow, JH AF Doroshow, James H. TI National Cancer Institute's Chemical Biology Consortium: An academic/public partnership for the discovery of novel cancer therapeutics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Doroshow, James H.] NCI, Div Canc Therapy & Diag, NIH, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 368-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908729 ER PT J AU Dunkers, JP Lee, HJ Matos, MA Pakstis, LM Taboas, JM Hudson, SD Cicerone, MT AF Dunkers, Joy P. Lee, Hae-Jeong Matos, Marvi A. Pakstis, Lisa M. Taboas, Juan M. Hudson, Steven D. Cicerone, Marcus T. TI Differences in PDMS modification affect laminin composition and smooth muscle cell response SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dunkers, Joy P.; Lee, Hae-Jeong; Matos, Marvi A.; Pakstis, Lisa M.; Hudson, Steven D.; Cicerone, Marcus T.] Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. [Taboas, Juan M.] Natl Inst Arthrit & Musculoskeletal Dis, Cartilage Biol & Orthoped Branch, Bethesda, MD 20892 USA. EM joy.dunkers@nist.gov; hae-jeong.lee@nist.gov; lisa.pakstis@nist.gov; taboasj@mail.nih.gov; steven.hudson@nist.gov; cicerone@nist.gov NR 0 TC 0 Z9 0 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 432-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861905441 ER PT J AU Edwankar, CR Edwankar, RV Zeilhofer, H Stables, JP Roth, BL Furtmuller, R Sieghart, W Cook, JM AF Edwankar, Chitra R. Edwankar, Rahul V. Zeilhofer, Hanns Stables, James P. Roth, Bryan L. Furtmueller, Roman Sieghart, Werner Cook, James M. TI New benzodiazepine-related agents to treat neuropathic pain SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Edwankar, Chitra R.; Edwankar, Rahul V.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA. [Zeilhofer, Hanns] Univ Zurich, Inst Pharmacol & Toxicol, ETH, Inst Pharmaceut Sci, CH-8057 Zurich, Switzerland. [Stables, James P.] NINDS, Epilepsy Branch, NIH, Rockville, MD 20852 USA. [Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Furtmueller, Roman] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria. [Sieghart, Werner] Med Univ, Brain Res Inst, A-1090 Vienna, Austria. [Cook, James M.] Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA. EM csawant@uwm.edu; edwankar@uwm.edu; zeilhofer@pharma.uzh.ch; bryan_roth@med.unc.edu; roman.furtmueller@meduniwien.ac.at; werner.sieghart@meduniwien.ac.at RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 169-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907366 ER PT J AU Edwankar, RV Edwankar, CR Stables, JP Roth, BL Furtmuller, R Sieghart, W Cook, JM AF Edwankar, Rahul V. Edwankar, Chitra R. Stables, James P. Roth, Bryan L. Furtmueller, Roman Sieghart, Werner Cook, James M. TI Novel nonsedative agents to treat epilepsy: Benzodiazepine-related ligands that do not develop tolerance SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Edwankar, Rahul V.; Edwankar, Chitra R.; Cook, James M.] Univ Wisconsin, Dept Chem & Biochem, Milwaukee, WI 53211 USA. [Stables, James P.] NINDS, Epilepsy Branch, NIH, Rockville, MD 20852 USA. [Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Furtmueller, Roman] Med Univ Vienna, Ctr Brain Res, A-1090 Vienna, Austria. [Sieghart, Werner] Med Univ, Brain Res Inst, A-1090 Vienna, Austria. EM edwankar@uwm.edu; csawant@uwm.edu; bryan_roth@med.unc.edu; roman.furtmueller@meduniwien.ac.at; werner.sieghart@meduniwien.ac.at; capncook@uwm.edu RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 99-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907363 ER PT J AU Englund, EA Appella, DH AF Englund, Ethan A. Appella, Daniel H. TI Gamma-substituted PNA oligomers in nonnucleic acid based molecular recognition SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Englund, Ethan A.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. EM englunde@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 24-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908643 ER PT J AU Fawzi, NL Doucleff, M Clore, GM AF Fawzi, Nicolas Lux Doucleff, Michaeleen Clore, G. Marius TI Paramagnetic relaxation enhancement NMR for the structural characterization of amyloid beta 40 and 42 oligomers in aqueous buffers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Fawzi, Nicolas Lux; Doucleff, Michaeleen; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM fawzin@niddk.nih.gov; doucleffm@niddk.nih.gov; clore@speck.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 141-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909556 ER PT J AU Filippov, IV Nicklaus, MC AF Filippov, Igor V. Nicklaus, Marc C. TI Optical structure recognition application SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Filippov, Igor V.] NCI Frederick, SAIC Frederick Inc, Med Chem Lab, Frederick, MD 21702 USA. [Nicklaus, Marc C.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM igorf@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 86-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904335 ER PT J AU Frank, JA Moats, R AF Frank, Joseph A. Moats, Rex TI Labeling of stem cells for detection by cellular MRI: CNS applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Frank, Joseph A.] NIH, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. [Moats, Rex] Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. EM jafrank@helix.nih.gov; moats@usc.edu RI Moats, Rex/F-5995-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 447-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000839 ER PT J AU Gildersleeve, JC AF Gildersleeve, Jeffrey C. TI Multidimensional carbohydrate microarrays for cancer research SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Gildersleeve, Jeffrey C.] NCI, Med Chem Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 66-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908146 ER PT J AU Grindrod, SC Suy, S Fallen, S Berry, D Toretsky, JA Kallakury, BVS Eto, M Bai, RL Hamel, E Brown, ML AF Grindrod, Scott C. Suy, Simeng Fallen, Shannon Berry, Deborah Toretsky, Jeffrey A. Kallakury, Bhashkar V. S. Eto, Masumi Bai, Ruoli Hamel, Ernest Brown, Milton L. TI Specific myosin light chain phosphatase inhibitors as potential therapeutic agents for human prostate cancer SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Grindrod, Scott C.; Suy, Simeng; Brown, Milton L.] Georgetown Univ, Med Ctr, Drug Discovery Program, Washington, DC 20057 USA. [Fallen, Shannon] Georgetown Univ, Med Ctr, Washington, DC 22057 USA. [Berry, Deborah] Georgetown Univ, Med Ctr, Dept Oncol, Dept Pathol,Georgetown Univ Hosp, Washington, DC 20057 USA. [Eto, Masumi] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Bai, Ruoli; Hamel, Ernest] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM scg36@georgetown.edu; suys@georgetown.edu; dlb82@georgetown.edu; mb544@georgetown.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 307-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907375 ER PT J AU Guha, R AF Guha, Rajarshi TI Crunching molecules and numbers in R SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Guha, Rajarshi] NIH, Chem Genom Ctr, Rockville, MD 20850 USA. EM rajarshi.guha@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 85-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904326 ER PT J AU Hajjo, R Fourches, D Roth, BR Tropsha, A AF Hajjo, Rima Fourches, Denis Roth, Bryan R. Tropsha, Alexander TI In silico strategies to identify novel 5-HT6 receptor ligands as potential anti-Alzheimer's and anti-obesity treatments SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hajjo, Rima; Fourches, Denis; Tropsha, Alexander] Univ N Carolina, Sch Pharm, Lab Mol Modeling, Chapel Hill, NC 27599 USA. [Roth, Bryan R.] Univ N Carolina, Sch Med, Dept Pharmacol, Natl Inst Mental Hlth,Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA. [Roth, Bryan R.] Univ N Carolina, Sch Med, Dept Pharmacol, Dept Biochem, Chapel Hill, NC 27599 USA. EM hajjo@email.unc.edu; fourches@email.unc.edu; bryan_roth@med.unc.edu; alex_tropsha@unc.edu RI Tropsha, Alexander/G-6245-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 38-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907040 ER PT J AU Hanson, PR AF Hanson, Paul R. TI Design and production of sultam libraries as potential small molecule therapeutic agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hanson, Paul R.] Univ Kansas, NIH Ctr Chem Methodol & Lib Dev, Dept Chem, Struct Biol Ctr, Lawrence, KS 66047 USA. EM phanson@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 587-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908706 ER PT J AU Hayashi, R Wang, DY Hara, T Durell, SR Jenkins, LM Appella, DH AF Hayashi, Ryo Wang, Deyun Hara, Toshiaki Durell, Stewart R. Jenkins, Lisa Miller Appella, Daniel H. TI Synthesis and inhibitory activities of tri-substituted triurea compounds as inhibitors of p53-binding to HDM2 and HDMX SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hayashi, Ryo; Hara, Toshiaki; Durell, Stewart R.; Jenkins, Lisa Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Deyun; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. EM hayashir@mail.nih.gov; wangdeyun@niddk.nih.gov; harato@mail.nih.gov; durells@mail.nih.gov; jenkins1@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 196-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908579 ER PT J AU Ho, PS Voth, AR Khuu, P AF Ho, P. Shing Voth, Andrea Regier Khuu, Patricia TI Energy-geometry relationships in biological halogen bonds: Applications to biomolecular engineering SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Voth, Andrea Regier] NIDDK, NIH, Bethesda, MD 20892 USA. [Khuu, Patricia] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. [Ho, P. Shing] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. EM shing.ho@colostate.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 59-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908046 ER PT J AU Horkay, F Lin, DC Dimitriadis, EK Horkayne-Szakaly, I Silva, C Basser, PJ AF Horkay, Ferenc Lin, David C. Dimitriadis, Emilios K. Horkayne-Szakaly, Iren Silva, Candida Basser, Peter J. TI BIOT 261-Biomechanical properties of cartilage proteoglycan assemblies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Horkay, Ferenc; Lin, David C.; Horkayne-Szakaly, Iren; Silva, Candida; Basser, Peter J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov; lindavid@mail.nih.gov; dimitria@helix.nih.gov; horkayi@mail.nih.gov; silvaca@mail.nih.gov; pjbasser@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 261-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901479 ER PT J AU Huang, WW Neumann, S Titus, SA Krause, G Kleinau, G Zheng, W Southall, NT Raaka, BM Inglese, J Thomas, CJ Gershengorn, MC Austin, CP AF Huang, Wenwei Neumann, Susanne Titus, Steven A. Krause, Gerd Kleinau, Gunnar Zheng, Wei Southall, Noel T. Raaka, Bruce M. Inglese, James Thomas, Craig J. Gershengorn, Marvin C. Austin, Christopher P. TI Discovery of 2,3-dihydroquinazolin-4-ones as novel TSHR agonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Huang, Wenwei; Zheng, Wei; Southall, Noel T.; Inglese, James; Thomas, Craig J.; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Neumann, Susanne; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. [Titus, Steven A.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Krause, Gerd; Kleinau, Gunnar] Leibniz Inst Mol Pharmacol, Berlin, Germany. EM huangwe@mail.nih.gov RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 164-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907144 ER PT J AU Ivanov, AA Tosh, DK Gao, ZG Chinn, M Jacobson, KA AF Ivanov, Andrei A. Tosh, Dilip K. Gao, Zhan-Guo Chinn, Moshe Jacobson, Kenneth A. TI Macromolecular ligands for G protein-coupled receptors: Biotin functionalized congeners complexed with streptavidin as agonist probes for the A(3) adenosine receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ivanov, Andrei A.; Tosh, Dilip K.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Chinn, Moshe] NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM andrei.aivanov@yahoo.com; toshd@niddk.nih.gov; ZhanguoG@intra.niddk.nih.gov; chinnmoshe@niddk.nih.gov; kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 410-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907223 ER PT J AU Jacobson, KA AF Jacobson, Kenneth A. TI Design of nucleoside and nucleotide receptor ligands as potential therapeutic agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 537-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908708 ER PT J AU Jang, BS Shin, IS Kim, H Yao, ZS Pastan, IH Paik, CH AF Jang, Beom-Su Shin, In Soo Kim, Hyungsub Yao, Zhengsheng Pastan, Ira H. Paik, Chang H. TI Effect of taxol and avastin on alpha(v)beta(3)-expression on angiogenic blood vessels assessed with indium-111 labeled RGD peptide SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jang, Beom-Su; Shin, In Soo; Kim, Hyungsub; Yao, Zhengsheng; Paik, Chang H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Pastan, Ira H.] NCI, NIH, Bethesda, MD 20892 USA. EM bsjang7@empal.com; ShinI@mail.nih.gov; kimh4@cc.nih.gov; yaozhe@cc.nih.gov; pastani@mail.nih.gov; CPaik@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 677-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000210 ER PT J AU Jiang, JK Ghoreschi, K Pesu, M Deflorian, F Costanzi, S O'Shea, JJ Thomas, CJ AF Jiang, Jian Kang Ghoreschi, Kamran Pesu, Marko Deflorian, Francesca Costanzi, Stefano O'Shea, John J. Thomas, Craig J. TI Investigating inhibitory activity of stereoisomers of CP-690,550 for Jak family and related kinases through biological assay and docking study SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jiang, Jian Kang; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Ghoreschi, Kamran; Pesu, Marko; O'Shea, John J.] NIAMS, Mol Immunol & Inflammat Dis Branch, NIH, Bethesda, MD 20892 USA. [Deflorian, Francesca; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM jiankangj@mail.nih.gov; stefanoc@mail.nih.gov; osheajo@mail.nih.gov RI Pesu, marko/L-6344-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 132-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907322 ER PT J AU Jiang, MS Michiel, D Yuan, JH Nelson, E Nellis, DF Perkins, S Warren, K Vyas, VV Yang, XY Soman, G Giardina, S Mitra, G Gilly, J Yovandich, J Creekmore, S Waldmann, T Zhu, JW AF Jiang, Man-Shiow Michiel, Dennis Yuan, Jin-Hui Nelson, Earl Nellis, David F. Perkins, Shelley Warren, Kelley Vyas, Vinay V. Yang, Xiaoyi Soman, Gopalan Giardina, Steve Mitra, George Gilly, John Yovandich, Jason Creekmore, Stephen Waldmann, Thomas Zhu, Jianwei TI BIOT 216-Purification of recombinant human Interleukin 15 by preparative reversed phase chromatography for clinical manufacturing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Jiang, Man-Shiow; Michiel, Dennis; Yuan, Jin-Hui; Nelson, Earl; Nellis, David F.; Perkins, Shelley; Warren, Kelley; Vyas, Vinay V.; Yang, Xiaoyi; Soman, Gopalan; Giardina, Steve; Mitra, George; Gilly, John; Zhu, Jianwei] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA. [Yovandich, Jason; Creekmore, Stephen] NCI, Biol Resources Branch, Frederick, MD 21702 USA. [Waldmann, Thomas] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM mjiang@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 216-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901502 ER PT J AU Kelley, JA Blonder, J Sumpter, TL Veenstra, TD Phillips, LR AF Kelley, James A. Blonder, Josip Sumpter, Terry L. Veenstra, Timothy D. Phillips, Lawrence R. TI CHED 58-Continuing education in chemistry for the nonchemist: Development of a mass spectrometry tutorial series for biomedical researchers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kelley, James A.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Blonder, Josip; Veenstra, Timothy D.] SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. [Sumpter, Terry L.] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA. [Phillips, Lawrence R.] NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21702 USA. EM kelleyj@dc37a.nci.nih.gov; blonder@mail.ncifcrf.gov; sumptert@mail.nih.gov; veenstra@ncifcrf.gov; phillipl@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 58-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902515 ER PT J AU Kim, JH Deschamps, JR Jacobson, AE Rice, KC AF Kim, Jin-Hee Deschamps, Jeffrey R. Jacobson, Arthur E. Rice, Kenner C. TI New approach to the rac-(3R,6a5,11aS)-2-methyl-1,3,4,5,6,11a-hexahydro-2H-3,6a-methanobenzof uro[2,3-c]azocine-8-ol (c-oxide-bridged phenylmorphan) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kim, Jin-Hee; Jacobson, Arthur E.; Rice, Kenner C.] NIAAA, NIH, DHHS, Rockville, MD 20852 USA. [Kim, Jin-Hee; Jacobson, Arthur E.; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Rockville, MD 20852 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. EM jheeeee@gmail.com; aej@helix.nih.gov; kr21f@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 730-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908573 ER PT J AU Kim, S Cregar-Hernandez, L Moayeri, M McKasson, L Millis, SZ Margosiak, S Leppla, SH Johnson, AT AF Kim, Seongjin Cregar-Hernandez, Lynne Moayeri, Mahtab McKasson, Linda Millis, Sherri Z. Margosiak, Stephen Leppla, Stephen H. Johnson, Alan T. TI Anthrax lethal factor inhibitors: Synthesis and SAR of N-hydroxy-4-phenyl butanamide derivatives SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kim, Seongjin; McKasson, Linda; Johnson, Alan T.] PanThera Biopharma LLC, Dept Chem, Aiea, HI 96701 USA. [Cregar-Hernandez, Lynne; Millis, Sherri Z.; Margosiak, Stephen] PanThera Biopharma LLC, Dept Biosci, Aiea, HI 96701 USA. [Moayeri, Mahtab; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. EM skim@pantherabio.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 119-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907002 ER PT J AU Kim, SE Choi, WJ Stephen, AG Weidlich, IE Giubellino, A Liu, F Worthy, KM Bindu, L Fivash, MJ Nicklaus, MC Bottaro, D Fisher, RJ Burke, TR AF Kim, Sung-Eun Choi, Won Jun Stephen, Andrew G. Weidlich, Iwona E. Giubellino, Alessio Liu, Fa Worthy, Karen M. Bindu, Lakshman Fivash, Matthew J. Nicklaus, Marc C. Bottaro, Donald Fisher, Robert J. Burke, Terrence R., Jr. TI Development of peptoid-peptide hybrids as She SH2 domain - binding inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Stephen, Andrew G.; Worthy, Karen M.; Bindu, Lakshman; Fisher, Robert J.] SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. [Weidlich, Iwona E.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Giubellino, Alessio; Bottaro, Donald] NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Fivash, Matthew J.] NCI, Data Management Serv Inc, Frederick, MD 21702 USA. EM giubella@mail.nih.gov; liuf@ncifcrf.gov; mn1@helix.nih.gov; bottarod@mail.nih.gov; tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 138-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907213 ER PT J AU Kim, S Bolton, E Bryant, SH AF Kim, Sunghwan Bolton, Evan Bryant, Stephen H. TI CINF 29-Sphericity and oblate-prolate indices: 3D shape descriptors for fast shape comparison SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kim, Sunghwan; Bolton, Evan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM kimsungh@ncbi.nlm.nih.gov; bolton@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 29-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902699 ER PT J AU Klauda, JB Venable, R MacKerell, AD Pastor, RW AF Klauda, Jeffery B. Venable, Richard MacKerell, Alexander D., Jr. Pastor, Richard W. TI Improving the lipid force field of CHARMM: A quantum mechanical and experimental approach SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Klauda, Jeffery B.] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Venable, Richard; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [MacKerell, Alexander D., Jr.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. EM jbklauda@umd.edu; pastorr@nhlbi.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 350-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904054 ER PT J AU Kovac, PP AF Kovac, Pavol Pavol TI CARB 21-Conjugate vaccines from synthetic carbohydrate antigens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kovac, Pavol Pavol] NIDDK, LBC, Sect Carbohydrates, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 21-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902011 ER PT J AU Leapman, R Aronova, M Azari, A Zhang, GF Sousa, A AF Leapman, Richard Aronova, Maria Azari, Afrouz Zhang, Guofeng Sousa, Alioscka TI Developments in 3D nanoscale imaging of cells by electron tomography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Leapman, Richard; Aronova, Maria; Azari, Afrouz; Zhang, Guofeng; Sousa, Alioscka] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov; aronovaa@mail.nih.gov; sousaali@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 88-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909398 ER PT J AU LeClair, CA Skoumbourdis, AP Stefan, E Turjanski, AG Maguire, W Titus, SA Huang, RL Auld, DS Inglese, J Austin, CP Michnick, SW Xia, MH Thomas, CJ AF LeClair, Christopher A. Skoumbourdis, Amanda P. Stefan, Eduard Turjanski, Adrian G. Maguire, William Titus, Steven A. Huang, Ruili Auld, Douglas S. Inglese, James Austin, Christopher P. Michnick, Stephen W. Xia, Menghang Thomas, Craig J. TI Exploration and optimization of substituted triazolothiadiazines and triazolopyridazines as PDE4 inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [LeClair, Christopher A.; Skoumbourdis, Amanda P.; Maguire, William; Titus, Steven A.; Huang, Ruili; Auld, Douglas S.; Inglese, James; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Stefan, Eduard; Michnick, Stephen W.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. [Turjanski, Adrian G.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM leclairc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 357-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907347 ER PT J AU Lee, JH Liu, W Jordan, E Frank, JA Blumenthal, R AF Lee, Jae-Ho Liu, Wei Jordan, Elaine Frank, Joseph A. Blumenthal, Robert TI COLL 499-Electrostatically assembled complexes of fluorescent superparamagnetic iron oxide nanoparticles (FL SPIONs) and protamine sulfate for cell labeling SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lee, Jae-Ho; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Liu, Wei; Jordan, Elaine; Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. EM leejaeho@mail.nih.gov; jafrank@helix.nih.gov; blumenthalr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 499-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903377 ER PT J AU Lee, JH Frank, JA Puri, A Blumenthal, R AF Lee, Jae-Ho Frank, Joseph A. Puri, Anu Blumenthal, Robert TI COLL 191-Nanoparticle-triggered liposomal drug delivery for cancer imaging and treatment SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lee, Jae-Ho; Puri, Anu; Blumenthal, Robert] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Frank, Joseph A.] NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. EM leejaeho@mail.nih.gov; jafrank@helix.nih.gov; apuri@helix.nih.gov; blumenthalr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 191-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903362 ER PT J AU Li, JJ Sekiya, F Chock, PB Trenkle, WC AF Li, Jiaojie Sekiya, Fujio Chock, P. Boon Trenkle, William C. TI Development and preparation of a new fluorogenic IP3 bioprobe SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Li, Jiaojie; Trenkle, William C.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. [Sekiya, Fujio; Chock, P. Boon] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. EM jiaojie@niddk.nih.govl; sekiyaf@nhlbi.nih.gov; chockp@nhlbi.nih.gov; wtrenkle@niddk.nih NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 132-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908610 ER PT J AU Liao, CZ Lee, KS Nicklaus, MC AF Liao, Chenzhong Lee, Kyung S. Nicklaus, Marc C. TI Docking studies and molecular dynamics simulations of inhibitors of polo-like kinase 1 polo box domain: Implications for design of nonphosphopeptide ligands SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Liao, Chenzhong; Nicklaus, Marc C.] NCI, Med Chem Lab, Ctr Canc Res, NIH,DHHS, Frederick, MD 21702 USA. [Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. EM czliao@helix.nih.gov; kyunglee@mail.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 146-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907359 ER PT J AU Lin-Gibson, S Chatterjee, K Cooper, JA Wallace, WE Becker, ML Simon, CG Horkay, F AF Lin-Gibson, Sheng Chatterjee, Kaushik Cooper, James A. Wallace, William E. Becker, Matthew L. Simon, Carl G., Jr. Horkay, Ferenc TI POLY 31-PEG-hydrogels: Synthesis, characterization, and cell encapsulation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lin-Gibson, Sheng; Chatterjee, Kaushik; Cooper, James A.; Wallace, William E.; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Becker, Matthew L.] Univ Akron, Dept Polymer Sci, Akron, OH 44325 USA. [Horkay, Ferenc] NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM sheng.lin-gibson@nist.gov; kaushik.chatterjee@nist.gov; william.wallace@nist.gov; becker@uakron.edu; carl.simon@nist.gov; horkay@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 31-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906220 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, Jennifer TI Near molecule protein distribution and dynamics using photoactivatable fluorescent protein technology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lippincott-Schwartz, Jennifer] NICHHD, Cell Biol & Metab Program, Bethesda, MD 20817 USA. EM lippincj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 181-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909214 ER PT J AU Liu, F Stephen, AG Waheed, AA Freed, EO Fisher, RJ Burke, TR AF Liu, Fa Stephen, Andrew G. Waheed, Abdul A. Freed, Eric O. Fisher, Robert J. Burke, Terrence R., Jr. TI Macrocyclic peptide-peptoid hybrids designed as polyproline type II helix mimetics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Liu, Fa; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Stephen, Andrew G.; Fisher, Robert J.] SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. [Waheed, Abdul A.; Freed, Eric O.] HIV Drug Resistance Program, Virus Cell Interact Sect, Retroviral Replicat Lab, Frederick, MD 21702 USA. EM liuf@ncifcrf.gov; tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 412-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907237 ER PT J AU Lucas, HR Lee, JC AF Lucas, Heather R. Lee, Jennifer C. TI Insights into the primary copper(II) and copper(I) binding site of alpha-synuclein SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lucas, Heather R.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM lucash@nhlbi.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 68-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000229 ER PT J AU Malhotra, SV Pommier, Y Jun, JH Dexheimer, TS Gupta, S AF Malhotra, Sanjay V. Pommier, Yves Jun, Jung Ho Dexheimer, Thomas S. Gupta, Shalu TI Newly developed piperidinyl sulfamides as tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Malhotra, Sanjay V.; Jun, Jung Ho] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA. [Pommier, Yves; Dexheimer, Thomas S.; Gupta, Shalu] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. EM malhotrasa@mail.nih.gov; pommier@mail.nih.gov; junj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 538-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908700 ER PT J AU Malhotra, SV Pommier, Y Kumar, V Maddali, K Marchand, C Puri, A Yavlovich, A AF Malhotra, Sanjay V. Pommier, Yves Kumar, Vineet Maddali, Kasthuraiah Marchand, Christophe Puri, Anu Yavlovich, Amichai TI Ionic liquids: Potential inhibitors of HIV-1 integrase SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Malhotra, Sanjay V.; Kumar, Vineet] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA. [Pommier, Yves; Maddali, Kasthuraiah; Marchand, Christophe] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Puri, Anu; Yavlovich, Amichai] NCI, Membrane Struct & Funct Sect, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov; pommier@mail.nih.gov; kumarvin@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 289-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908698 ER PT J AU Maruoka, H Ko, H Tosh, DK Melman, A Carter, RL Costanzi, S Harden, TK Jacobson, KA AF Maruoka, Hiroshi Ko, Hyojin Tosh, Dilip K. Melman, Artem Carter, Rhonda L. Costanzi, Stefano Harden, T. Kendall Jacobson, Kenneth A. TI Selective P2Y6 receptor agonists: Extended phosphate and (S)-methanocarba ribonucleotide analogs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Maruoka, Hiroshi; Ko, Hyojin; Tosh, Dilip K.; Melman, Artem; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. [Carter, Rhonda L.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM maruokah@niddk.nih.gov; hyojinko@niddk.nih.gov; toshd@niddk.nih.gov; melmana@mail.nih.gov; stefanoc@mail.nih.gov; kajacobs@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 187-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907214 ER PT J AU Marzabadi, CH Talisman, J Khawam, F Stables, JP Roth, BL AF Marzabadi, Cecilia H. Talisman, Jamie Khawam, Fadi Stables, James P. Roth, Bryan L. TI Deoxy-sugar analogs for the treatment of epilepsy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Marzabadi, Cecilia H.; Talisman, Jamie; Khawam, Fadi] Seton Hall Univ, Dept Chem & Biochem, S Orange, NJ 07079 USA. [Stables, James P.] Natl Inst Neurol Disorders & Stroke, Epilepsy Branch, NIH, Rockville, MD 20852 USA. [Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. EM marzabce@shu.edu; talismja@shu.edu; bryan_roth@med.unc.edu RI Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 324-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907122 ER PT J AU Micklitsch, CM Appella, DH AF Micklitsch, Christopher M. Appella, Daniel H. TI DNA-templated crosslinking of PNA oligomers for DNA detection SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Micklitsch, Christopher M.; Appella, Daniel H.] NIDDK, Lab Biorgan Chem, DHHS, NIH, Bethesda, MD 20892 USA. EM micklitschc@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 48-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908660 ER PT J AU Miller, Y Ma, BY Nussinov, R AF Miller, Yifat Ma, Buyong Nussinov, Ruth TI Polymorphism in Alzheimer A-beta17-42 (p3): Insight into amyloid arrangements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Miller, Yifat] NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. [Ma, Buyong; Nussinov, Ruth] NCI FCRDC, Ctr Canc Res, Nanobiol Program, Basic Res Program,SAIC, Frederick, MD 21702 USA. EM millery@mail.nih.gov; mab@ncifcrf.gov RI Miller, Yifat/G-6776-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 312-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909114 ER PT J AU Moyer, BR Macaluso, A Homer, M Voigt, B Manning, RG Young, WS Cibulsky, S Prasher, JM Maidment, BW Hatchett, RJ AF Moyer, Brian R. Macaluso, Anthony Homer, Mary Voigt, Beryl Manning, Ronald G. Young, Wayne S. Cibulsky, Susan Prasher, Joanna M. Maidment, Bert W. Hatchett, Richard J. TI SCHB 29-Advanced development of medical countermeasures for use in chemical and nuclear/radiological public health emergencies: Small business opportunities SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Moyer, Brian R.; Macaluso, Anthony; Homer, Mary; Voigt, Beryl; Manning, Ronald G.; Young, Wayne S.; Cibulsky, Susan; Prasher, Joanna M.] US Dept Hlth & Human Serv, Washington, DC 20201 USA. [Maidment, Bert W.; Hatchett, Richard J.] NIH, Bethesda, MD 20892 USA. EM brian.moyer@hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 29-SCHB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906635 ER PT J AU Muus, U Lountos, GT Waugh, DS Burke, TR AF Muus, Ulrike Lountos, George T. Waugh, David S. Burke, Terrence R., Jr. TI Design of covalent inhibitors of Cdc25 phosphatases SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Muus, Ulrike; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Waugh, David S.] NCI, Macromol Crystallog Lab, CCR, NIH, Frederick, MD 21702 USA. EM umuus@ncifcrf.gov; waughd@ncifcrf.gov; tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 411-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907232 ER PT J AU Nandurdikar, RS Maciag, A Citro, ML Keefer, LK Saavedra, JE Chakrapani, H AF Nandurdikar, Rahul S. Maciag, Anna Citro, Michael L. Keefer, Larry K. Saavedra, Joseph E. Chakrapani, Harinath TI Structural analogs of O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K), an anticancer lead compound SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nandurdikar, Rahul S.; Keefer, Larry K.; Chakrapani, Harinath] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna; Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Citro, Michael L.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM nandurdikarr@mail.nih.gov; chakrah@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 293-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907250 ER PT J AU Nandurdikar, RS Maciag, A Chakrapani, H Citro, ML Saavedra, JE Keefer, LK AF Nandurdikar, Rahul S. Maciag, Anna Chakrapani, Harinath Citro, Michael L. Saavedra, Joseph E. Keefer, Larry K. TI O2-Glycosylated PROLI/NO prodrugs: Biocompatible nitric oxide donors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nandurdikar, Rahul S.; Chakrapani, Harinath] NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna; Saavedra, Joseph E.] SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. [Citro, Michael L.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM nandurdikarr@mail.nih.gov; chakrah@ncifcrf.gov; keefer@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 435-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907240 ER PT J AU Nguyen, TM Kim, SK Capala, J Lee, SB AF Nguyen, Thao M. Kim, Sung-Kyoung Capala, Jacek Lee, Sang Bok TI COLL 226-Template-synthesized multifunctional nanotube for targeting, imaging, and triggered drug releasing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Nguyen, Thao M.; Kim, Sung-Kyoung; Lee, Sang Bok] Univ Maryland, Dept Chem, College Pk, MD 20740 USA. [Capala, Jacek] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20878 USA. EM nguyent@umd.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 226-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903512 ER PT J AU O'Keefe, B Giomarelli, B Saucedo, C McCray, P Lear, C Olinger, E Palmer, KE Shattock, R McMahon, JB AF O'Keefe, Barry Giomarelli, Barbara Saucedo, Carrie McCray, Paul Lear, Calli Olinger, Eugene Palmer, Kenneth E. Shattock, Robin McMahon, James B. TI CARB 125-Potent antiviral activity of the lectin griffithsin SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [O'Keefe, Barry; Giomarelli, Barbara; Saucedo, Carrie; McMahon, James B.] NCI, Mol Targets Dev Program, NIH, CCR, Frederick, MD 21702 USA. [McCray, Paul] Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA. [Lear, Calli; Olinger, Eugene] USA, Div Virol, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Palmer, Kenneth E.] Univ Louisville, Dept Pharmacol & Toxicol, James Grahm Brown Canc Res Ctr, Louisville, KY 40202 USA. [Shattock, Robin] St Georges Univ London, Ctr Infect, Div Cellular & Mol Med, London, England. EM okeefe@ncifcrf.gov; kenneth.palmer@louisville.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 125-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902037 ER PT J AU Patri, AK AF Patri, Anil K. TI COLL 552-Cancer nanotechnology: Resources for clinical translation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Patri, Anil K.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick, Frederick, MD 21702 USA. EM patria@mail.nihgov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 552-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903448 ER PT J AU Peach, ML Nicklaus, MC AF Peach, Megan L. Nicklaus, Marc C. TI Molecular dynamics of second-shell interactions in zinc finger binding sites SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Peach, Megan L.] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Nicklaus, Marc C.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM mpeach@helix.nih.gov; mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 245-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904206 ER PT J AU Pepe, A Malhotra, SV AF Pepe, Antonella Malhotra, Sanjay V. TI Synthesis and biological evaluation of novel compounds containing fused bicyclic systems, including indolizidine and quinolizidine SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Pepe, Antonella; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA. EM pepea@mail.nih.gov; malhotrasa@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 760-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908266 ER PT J AU Petrik, AF Lee, JC AF Petrik, Amy F. Lee, Jennifer C. TI Tryptophan probes of ligand binding to ionotropic glutamate receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Petrik, Amy F.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM grimesa2@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 569-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909500 ER PT J AU Petrik, AF Jackson, MS Lee, JC AF Petrik, Amy F. Jackson, Mark S. Lee, Jennifer C. TI COLL 541--Synuclein-lipid interactions determined by fluorescence correlation spectroscopy: Can -synuclein feel the curves? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Petrik, Amy F.; Jackson, Mark S.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM grimesa2@mail.nih.gov; jacksonms@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 541-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903111 ER PT J AU Pfefferkorn, CM Lee, JC AF Pfefferkorn, Candace M. Lee, Jennifer C. TI Tryptophan probes of alpha-synuclein membrane binding SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM pfefferc@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 594-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909220 ER PT J AU Pfefferkorn, CM Petrik, AF Jackson, MS Lucas, HR Yap, TL Lee, JC AF Pfefferkorn, Candace M. Petrik, Amy F. Jackson, Mark S. Lucas, Heather R. Yap, Thai Leong Lee, Jennifer C. TI Conformational and dynamical probes of alpha-synuclein interaction with lipids, metals, and itself SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Pfefferkorn, Candace M.; Petrik, Amy F.; Jackson, Mark S.; Lucas, Heather R.; Yap, Thai Leong; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM pfefferc@mail.nih.gov; grimesa2@mail.nih.gov; jacksonms@mail.nih.gov; lucash@nhlbi.nih.gov; yap2@mail.nih.gov; leej4@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 98-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909223 ER PT J AU Pietsch, KE Yu, X Neels, JF Gong, JC Sturla, SJ AF Pietsch, Kathryn E. Yu, Xiang Neels, James F. Gong, Jiachang Sturla, Sham J. TI TOXI 61-Chemical aspects of acylfulvene bioactivation to a cytotoxic reactive intermediate SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Pietsch, Kathryn E.; Neels, James F.; Gong, Jiachang; Sturla, Sham J.] Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. [Yu, Xiang] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20814 USA. EM piet0123@umn.edu; yux@mail.nih.gov; sturl002@umn.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 61-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906764 ER PT J AU Poroikov, VV Filimonov, D Nicklaus, MC AF Poroikov, Vladimir V. Filimonov, Dmitry Nicklaus, Marc C. TI CINF 13-Public molecular databases: How can their value be increased by generation of additional data in silico? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Poroikov, Vladimir V.; Filimonov, Dmitry] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119121, Russia. [Nicklaus, Marc C.] NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM vladimir.poroikov@ibmc.msk.ru; dmitry.filimonov@ibmc.msk.ru; mn1@helix.nih.gov RI Poroikov, Vladimir/O-2769-2013 OI Poroikov, Vladimir/0000-0001-7937-2621 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 13-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902696 ER PT J AU Puri, A Yavlovich, A Singh, A Blumenthal, R AF Puri, Anu Yavlovich, Amichai Singh, Alok Blumenthal, Robert TI COLL 547-Design and development of a novel class of light-sensitive liposomes for sustained and triggered (localized) delivery of cancer therapeutics SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Yavlovich, Amichai] NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. [Singh, Alok] USN, Ctr Biomol Sci & Engn, Res Lab, Washington, DC 20375 USA. EM apuri@helix.nih.gov; asingh@cbmse.nrl.navy.mil; blumenthalr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 547-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903196 ER PT J AU Rai, G Sayed, A Lea, W Chakrapani, H Jadhav, A Keefer, LK Simeonov, A Maloney, DJ Williams, DL Thomas, CJ AF Rai, Ganesha Sayed, Ahmed Lea, Wendy Chakrapani, Harinath Jadhav, Ajit Keefer, Larry K. Simeonov, Anton Maloney, David J. Williams, David L. Thomas, Craig J. TI Structure-activity relationship and mechanistic studies on potential antischistosomal oxadiazole-2-oxides SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rai, Ganesha] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. [Sayed, Ahmed; Williams, David L.] Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. [Lea, Wendy; Jadhav, Ajit; Simeonov, Anton; Maloney, David J.; Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. [Chakrapani, Harinath] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Keefer, Larry K.] NCI FCRDC, Chem Carcinogen Lab, NCI Frederick, Canc Res & Dev Ctr, Frederick, MD 21702 USA. EM bantukallug@mail.nih.gov; keefer@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 347-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907340 ER PT J AU Rasaiah, JC Feng, GG Hummer, G AF Rasaiah, Jayendran C. Feng, Guogang Hummer, Gerhard TI Upper and lower bounds for the chemical potential SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rasaiah, Jayendran C.; Feng, Guogang] Univ Maine, Dept Chem, Orono, ME 04469 USA. [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM rasaiah@maine.edu; Guogang_Feng@umit.maine.edu; Gerhard.Hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 492-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909344 ER PT J AU Ravichandran, S AF Ravichandran, Sarangan TI TOXI 54-Identifying the common binding modes of flavonoids to cytochrome P450 3A4 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ravichandran, Sarangan] SAIC Frederick, Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. EM sravi@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 54-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906739 ER PT J AU Ravichandran, S AF Ravichandran, Sarangan TI Understanding how flavonoids provide protection to skin cells: A molecular modeling study SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Ravichandran, Sarangan] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. EM sravi@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 172-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904217 ER PT J AU Rosta, E Woodcock, HL Brooks, BR Hummer, G AF Rosta, Edina Woodcock, H. Lee, III Brooks, Bernard R. Hummer, Gerhard TI Artificial reaction coordinate "tunneling" in free energy calculations: The catalytic reaction of RNase H SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Rosta, Edina] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Woodcock, H. Lee, III; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM rosta@helix.nih.gov; hlwood@nih.gov; brb@nih.gov; Gerhard.Hummer@nih.gov RI Woodc, Henry/D-9275-2011; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 72-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904130 ER PT J AU Sanjayan, GJ AF Sanjayan, Gangadhar J. TI Novel conformationally ordered synthetic oligomers (foldamers) with hetero backbone SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sanjayan, Gangadhar J.] NIDDK, NIH, Bethesda, MD 20892 USA. EM sanjayangj@niddk.nih.gov RI sanjayan, Gangadhar/E-4789-2010 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 246-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908242 ER PT J AU Sczepanski, J Jacobs, A Van Houten, B Greenberg, MM AF Sczepanski, Jonathan Jacobs, Aaron Van Houten, Bennett Greenberg, Marc M. TI TOXI 85-Scope and mechanism of formation of interstrand crosslinks that give rise to double strand breaks upon nucleotide excision repair SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sczepanski, Jonathan; Jacobs, Aaron; Greenberg, Marc M.] Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. [Van Houten, Bennett] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM jons@jhu.edu; ajacobs@jhu.edu; vanhout1@niehs.nih.gov; mgreenberg@jhu.edu RI Sczepanski, Jonathan/N-8719-2015 OI Sczepanski, Jonathan/0000-0002-9275-2597 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 85-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906721 ER PT J AU Sheeley, DM AF Sheeley, Douglas M. TI ANYL 246-Mass spectrometry in translation: NCRR Biomedical Technology Research Centers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Sheeley, Douglas M.] Natl Ctr Res Resources, Div Biomed Technol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 246-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901356 ER PT J AU Shenoy, N Cheal, SM Dulcey, A Regino, CAS Shi, ZD Smith, VJ Sulima, A Vasalatiy, O Wu, HT Xu, BY Barbacow, K Cofiell, S Lamb, J Wilson, CM Griffiths, GL AF Shenoy, Nalini Cheal, Sarah M. Dulcey, Andres Regino, Celeste A. S. Shi, Zhen-Dan Smith, Valerie J. Sulima, Agnieszka Vasalatiy, Olga Wu, Haitao Xu, Biying Barbacow, Kyle Cofiell, Shannon Lamb, Jeffery Wilson, Colin M. Griffiths, Gary L. TI The imaging probe development center (IPDC): Facilitating the advancement of biomedical imaging research through production of molecular probes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Shenoy, Nalini; Cheal, Sarah M.; Dulcey, Andres; Shi, Zhen-Dan; Smith, Valerie J.; Sulima, Agnieszka; Vasalatiy, Olga; Wu, Haitao; Xu, Biying; Barbacow, Kyle; Cofiell, Shannon; Lamb, Jeffery; Wilson, Colin M.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Regino, Celeste A. S.] NCI, Mol Imaging Program, CCR, NIH, Bethesda, MD 20892 USA. EM shenoyn2@mail.nih.gov; reginoc@mail.nih.gov RI Shenoy, Nalini/O-2132-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 642-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000368 ER PT J AU Shinkre, BA Wang, QY Ye, YH Trenkle, WC AF Shinkre, Bidhan A. Wang, Qiuyan Ye, Yihong Trenkle, William C. TI Synthetic preparation and evaluation of eeyarestatin (EER1) analogs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Shinkre, Bidhan A.; Trenkle, William C.] NIDDK, Chem Biol Core Facil, NIH, Bethesda, MD 20892 USA. [Wang, Qiuyan; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM shinkreb@niddk.nih.gov; wangqiu@niddk.nih.gov; yihongy@niddk.nih.gov; wtrenkle@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 778-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908640 ER PT J AU Shtengel, G Galbraith, JA Galbraith, CG Lippincott-Schwartz, J Manley, S Sougrat, R Waterman, CM Kanchanawong, P Davidson, M Fetter, RD Hess, H AF Shtengel, Gleb Galbraith, James A. Galbraith, Catherine G. Lippincott-Schwartz, Jennifer Manley, Suliana Sougrat, Rachid Waterman, Clare M. Kanchanawong, Pankorn Davidson, Michael Fetter, Richard D. Hess, Harald TI Fluorescent protein based super-resolution in 3D with iPALM SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Shtengel, Gleb; Fetter, Richard D.; Hess, Harald] Janelia Farms, HHMI, Ashburn, VA 20147 USA. [Galbraith, James A.; Galbraith, Catherine G.; Lippincott-Schwartz, Jennifer; Manley, Suliana; Sougrat, Rachid; Waterman, Clare M.; Kanchanawong, Pankorn] NIH, Bethesda, MD 20892 USA. [Davidson, Michael] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Davidson, Michael] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. EM shtengelg@janelia.hhmi.org; fetterr@janelia.hhmi.org; hessh@janelia.hhmi.org RI Manley, Suliana/D-3818-2012 OI Manley, Suliana/0000-0002-4755-4778 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 59-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909358 ER PT J AU Silva, C Horkayne-Szakaly, I Lin, DC Basser, PJ Horkay, F AF Silva, Candida Horkayne-Szakaly, Iren Lin, David C. Basser, Peter J. Horkay, Ferenc TI POLY 193-Osmotic swelling behavior of bovine cartilage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Silva, Candida; Horkayne-Szakaly, Iren; Lin, David C.; Basser, Peter J.; Horkay, Ferenc] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Tissue Biophys & Biomimet, Program Phys Biol, NIH, Bethesda, MD 20892 USA. EM silvaca@mail.nih.gov; horkayi@mail.nih.gov; lindavid@mail.nih.gov; pjbasser@helix.nih.gov; horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 193-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861906101 ER PT J AU Smirnov, AV Rosales, T Davenport, L Xu, JH Combs, CA Knutson, JR AF Smirnov, Aleksandr V. Rosales, Tilman Davenport, Lesley Xu, Jianhua Combs, Christopher A. Knutson, Jay R. TI COLL 446-Unilamellar lipid vesicles as subcellular compartment models in advanced microscopic imaging (FLIM and CARS) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Combs, Christopher A.] NHLBI, Light Microscopy Facil, NIH, Bethesda, MD 20892 USA. [Davenport, Lesley] CUNY, Grad Ctr, Dept Chem, Brooklyn, NY 11210 USA. [Davenport, Lesley] CUNY, Brooklyn Coll, Brooklyn, NY 11210 USA. [Smirnov, Aleksandr V.; Rosales, Tilman; Xu, Jianhua; Knutson, Jay R.] NIH, Lab Mol Biophys, Bethesda, MD 20892 USA. EM avs@helix.nih.gov; avs@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 446-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861903545 ER PT J AU Soman, G Saptharshi, N Yang, XY Mancini, L Giardina, S Vyas, V Gilly, J Yovandich, J Creekmore, S Mitra, G AF Soman, Gopalan Saptharshi, Nirmala Yang, Xiaoyi Mancini, Luke Giardina, Steve Vyas, Vinay Gilly, John Yovandich, Jason Creekmore, Stephen Mitra, George TI BIOT 179-Protein conformation and biochemical stability of recombinant human IL-15 expressed in E.coli. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Soman, Gopalan; Saptharshi, Nirmala; Yang, Xiaoyi; Mancini, Luke; Giardina, Steve; Vyas, Vinay; Gilly, John; Mitra, George] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA. [Yovandich, Jason; Creekmore, Stephen] NCI, Biol Resources Branch, Frederick, MD 21702 USA. EM somang@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 179-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901446 ER PT J AU Subramaniam, S AF Subramaniam, Sriram TI Visualizing cells and viruses at molecular resolution with 3D electron microscopy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Subramaniam, Sriram] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM ss1@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 87-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909496 ER PT J AU Telu, S Simeon, FG Jenko, K Zoghbi, SS Innis, RB Pike, VW AF Telu, Sanjay Simeon, Fabrice G. Jenko, Kimberly Zoghbi, Sami S. Innis, Robert B. Pike, Victor W. TI Synthesis of a novel fluorescent aryloxyanilide TSPO ligand SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Telu, Sanjay; Simeon, Fabrice G.; Jenko, Kimberly; Zoghbi, Sami S.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. EM telus@mail.nih.gov; simeonf@mail.nih.gov; jenkok@mail.nih.gov; zoghbis@intra.nimh.nih.gov; innisr@intra.nimh.nih.gov; pikev@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 413-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907249 ER PT J AU Thakur, NM AF Thakur, Neil M. TI CINF 7-NIH public access policy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Thakur, Neil M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 7-CINF PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902733 ER PT J AU Thomas, CJ AF Thomas, Craig J. TI Bioactive small molecule discovery at the NIH chemical genomics center SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Thomas, Craig J.] NIH, NIH Chem Genom Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 8-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908124 ER PT J AU Thomas, JD Skeffington, L Hofer, T Rader, C Burke, TR AF Thomas, Joshua D. Skeffington, Lauren Hofer, Thomas Rader, Christoph Burke, Terrence R., Jr. TI Program and arm: Conferring tissue-specific cytotoxicity to Fc-drug conjugates SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Skeffington, Lauren; Hofer, Thomas; Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. EM josthom@ncifcrf.gov; raderc@mail.nih.gov; tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 409-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907217 ER PT J AU Tikhonova, I Costanzi, S AF Tikhonova, Irina Costanzi, Stefano TI Intrinsic mobility of rhodopsin photointermediates investigated by molecular dynamics simulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tikhonova, Irina; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM tikhonovai@niddk.nih.gov; stefanoc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 334-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904113 ER PT J AU Tosh, DK Chinn, M Ivanov, AA Gao, ZG Jacobson, KA AF Tosh, Dilip K. Chinn, Moshe Ivanov, Andrei A. Gao, Zhan-Guo Jacobson, Kenneth A. TI Functionalized congeners of A3 adenosine receptor-selective nucleosides SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tosh, Dilip K.; Ivanov, Andrei A.; Gao, Zhan-Guo] NIDDK, Mol Recognit Sect, NIDDK, NIH, Bethesda, MD 20892 USA. EM toshd@niddk.nih.gov; chinnmoshe@niddk.nihgov; andrei.aivanov@yahoo.com; ZhanguoG@intra.niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 174-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907059 ER PT J AU Tycko, R AF Tycko, Robert TI Structural characterization of amyloid fibrils by solid state NMR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 267-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909129 ER PT J AU Tycko, R Sciarretta, KL Cloe, A Orgel, JPRO Meredith, SC AF Tycko, Robert Sciarretta, Kimberly L. Cloe, Adam Orgel, Joseph P. R. O. Meredith, Stephen C. TI Structural examination of D23N-and Delta E22-A beta 40 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Sciarretta, Kimberly L.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. [Cloe, Adam; Meredith, Stephen C.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Orgel, Joseph P. R. O.] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. [Meredith, Stephen C.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. EM robertty@mail.nih.gov; ksciarretta@gmail.com; adamcloe@uchicago.edu; orgel@iit.edu; scmeredi@uchicago.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 314-PHYS PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861909128 ER PT J AU ul Hussan, SS Shah, AB Bewley, CA AF ul Hussan, Syed Shahzad Shah, Ali B. Bewley, Carole A. TI CARB 92-Structural specificity of gp120 carbohydrates for binding to HIV-fusion blocking cyanobacterial proteins determined by NMR and other biophysical techniques SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [ul Hussan, Syed Shahzad; Shah, Ali B.; Bewley, Carole A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM hussans@mail.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 92-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902136 ER PT J AU Vasalatiy, O Cheal, SM Wu, H Wu, WH Ungerleider, L Koretsky, AP Griffiths, GL AF Vasalatiy, Olga Cheal, S. M. Wu, H. Wu, W-H Ungerleider, L. Koretsky, A. P. Griffiths, Gary L. TI Synthesis and characterization of gadolinium-benzyl-DOTA-cholera toxin B conjugates for MRI brain circuitry studies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Vasalatiy, Olga; Cheal, S. M.; Wu, H.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD 20850 USA. [Wu, W-H; Koretsky, A. P.] NINDS, NIH, Bethesda, MD 20892 USA. [Ungerleider, L.] NIMH, NIH, Bethesda, MD 20892 USA. EM vasalatiyo@mail.nih.gov; cheals@mail.nih.gov; wuh3@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 638-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HZ UT WOS:000207862000472 ER PT J AU Vilar, S Ferino, G Costanzi, S AF Vilar, Santiago Ferino, Giulio Costanzi, Stefano TI On the applicability of homology models of G protein-coupled receptors to computer-aided drug discovery SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Vilar, Santiago; Ferino, Giulio; Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM vilarvarelas@niddk.nih.gov; ferinog@niddk.nih.gov; stefanoc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 252-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904174 ER PT J AU Vyas, V Michiel, D Nellis, D Burnette, A Jiang, MS Sumpter, TL Broadt, T Knapp, G Yang, XY Soman, G Shaban, S Roach, J Giardina, S Gilly, J Mitra, G Yovandich, J Creekmore, S Waldmann, T Zhu, JW AF Vyas, Vinay Michiel, Dennis Nellis, David Burnette, Andrew Jiang, Man-Shiow Sumpter, Terry L. Broadt, Trevor Knapp, George Yang, Xiaoyi Soman, Gopalan Shaban, Samir Roach, John Giardina, Steve Gilly, John Mitra, George Yovandich, Jason Creekmore, Stephen Waldmann, Thomas Zhu, Jianwei TI BIOT 396-Challenges to process development of rhIL-15 from Escherichia coli: RP-HPLC as a tool for process analytical technology SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Vyas, Vinay; Michiel, Dennis; Nellis, David; Burnette, Andrew; Jiang, Man-Shiow; Sumpter, Terry L.; Broadt, Trevor; Knapp, George; Yang, Xiaoyi; Soman, Gopalan; Shaban, Samir; Roach, John; Giardina, Steve; Gilly, John; Mitra, George; Zhu, Jianwei] SAIC Frederick Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA. [Yovandich, Jason; Creekmore, Stephen] NCI, Biol Resources Branch, DTP, Frederick, MD 21702 USA. [Waldmann, Thomas] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM vyasv@mail.nihgov; sumptert@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 396-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901477 ER PT J AU Wang, DY Appella, DH AF Wang, Deyun Appella, Daniel H. TI Multivalent binding oligomers for HIV TAR RNA recognition SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wang, Deyun] NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. EM wangdeyun@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 244-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908442 ER PT J AU Wang, K Golbraikh, A Roth, BL Tropsha, A AF Wang, Kun Golbraikh, Alexander Roth, Bryan L. Tropsha, Alexander TI QSAR modeling and knowledge discovery of a large unbalanced dataset of hERG K plus channel blockers and openers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Tropsha, Alexander] Univ N Carolina, Sch Pharm, Lab Mol Modeling, Chapel Hill, NC 27599 USA. EM kunwang@email.unc.edu; golbraik@email.unc.edu; bryan_roth@med.unc.edu; tropsha@email.unc.edu RI Tropsha, Alexander/G-6245-2014; Roth, Bryan/F-3928-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 259-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904294 ER PT J AU Watson, R Popelka-Filcoff, R Kramer-Marek, G Mackey, EA Spatz, RO Capala, J AF Watson, Russell Popelka-Filcoff, Rachel Kramer-Marek, Gabriela Mackey, Elizabeth A. Spatz, Rabia O. Capala, Jacek TI ANYL 96-Quantitation of gold in biological tissues using neutron activation analysis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Watson, Russell; Popelka-Filcoff, Rachel; Mackey, Elizabeth A.; Spatz, Rabia O.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Kramer-Marek, Gabriela; Capala, Jacek] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20878 USA. EM russell.watson@nist.gov; rachel.popelka-filcoff@nist.gov RI Popelka-Filcoff, Rachel/I-4546-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 96-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901088 ER PT J AU Wei, LY Malhotra, SV AF Wei, Linyi Malhotra, Sanjay V. TI Design, synthesis and structure-activity relationships (SARs) studies of novel 4-substituted-2-amino-pyrido[3,4-d]pyrimidin-8(7H)-one analogs as potential antitumor agents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wei, Linyi; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick, Frederick, MD 21702 USA. EM weil3@mail.nih.gov; malhotrasa@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 691-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908378 ER PT J AU Woodcock, HL Ghysels, A Shao, YH Kong, J Brooks, BR AF Woodcock, H. Lee, III Ghysels, An Shao, Yihan Kong, Jing Brooks, Bernard R. TI The evaluation of QM/MM full Hessian and some applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Woodcock, H. Lee, III; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Ghysels, An] Univ Ghent, Ctr Mol Modeling, B-9000 Ghent, Belgium. [Shao, Yihan; Kong, Jing] Q Chem Inc, Pittsburgh, PA 15213 USA. EM hlwood@nih.gov; yihan@q-chem.com; jkong@q-chem.com; brb@nih.gov RI Woodc, Henry/D-9275-2011; Ghysels, An/M-9095-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 345-COMP PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861904273 ER PT J AU Xu, Q Appella, D AF Xu, Qun Appella, Daniel TI Synthesis and evaluation of penta-substituted pyrrole derivatives as Wip 1 phosphatase inhibitors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Xu, Qun; Appella, Daniel] NIDDK, NIH, Bethesda, MD 20892 USA. EM xuqun@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 297-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908423 ER PT J AU Zhang, DM Zou, SG Sygula, A AF Zhang, Dongmao Zou, Sige Sygula, Andrzej TI ANYL 389-Ratiometric Raman spectroscopy of protein oxidative damage SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Dongmao; Sygula, Andrzej] Mississippi State Univ, Dept Chem, Hand Lab 1115, Mississippi State, MS 39762 USA. [Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM dz33@msstate.edu; zous@grc.nia.nih.gov; asygula@chemistry.msstate.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 389-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861901142 ER PT J AU Zhang, N Appella, DH AF Zhang, Ning Appella, Daniel H. TI Postsynthetic PNA-PNA ligation through CuAAC click reaction SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Ning] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, DHHS, Bethesda, MD 20892 USA. EM zhangning@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 71-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861908411 ER PT J AU Zhang, P Zou, MF Rodriguez, AL Conn, PJ Newman, AH AF Zhang, Peng Zou, Mu-Fa Rodriguez, Alice L. Conn, P. Jeffrey Newman, Amy H. TI Novel quinoline-based mGluR5 noncompetitive antagonists SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Peng; Zou, Mu-Fa; Newman, Amy H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Rodriguez, Alice L.; Conn, P. Jeffrey] Vanderbilt Univ, Med Ctr, Vanderbilt Program Drug Discovery, Dept Pharmacol, Nashville, TN 37232 USA. EM mzou@intra.nida.nih.gov RI Conn, Peter/D-7848-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 87-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907182 ER PT J AU Zhang, YL AF Zhang, Yalong TI CARB 121-Studies of the racemization of Tn-antigen containing glycopeptides via solid-phase peptide synthesis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Yalong] NCI, Med Chem Lab, Frederick, MD 21702 USA. EM zhangy7@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 121-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902114 ER PT J AU Zhang, YL AF Zhang, Yalong TI CARB 132-An array-based method to identify high affinity inhibitors for carbohydrate-binding proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhang, Yalong] NCI, Med Chem Lab, Frederick, MD 21702 USA. EM zhangy7@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 132-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861902113 ER PT J AU Zhao, XZ Maddali, K Vu, BC Marchand, C Hughes, SH Pommier, Y Burke, TR AF Zhao, Xue Zhi Maddali, Kasthuraiah Vu, B. Christie Marchand, Christophe Hughes, Stephen H. Pommier, Yves Burke, Terrence R., Jr. TI Examination of halogen substituent effects on HIV-1 integrase inhibitors derived from 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-ones and 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Med Chem Lab, CCR, NIH, Frederick, MD 21702 USA. [Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Vu, B. Christie; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, CCR, NIH, Frederick, MD 21702 USA. EM cvu@ncifcrf.gov; hughes@ncifcrf.gov; pommier@mail.nih.gov; tburke@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 111-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907220 ER PT J AU Zou, MF Cao, JJ Rodriguez, AL Conn, PJ Newman, AH AF Zou, Mu-Fa Cao, Jianjing Rodriguez, Alice L. Conn, P. Jeffrey Newman, Amy H. TI Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides as allosteric modulators of the mGluR5 receptor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Zou, Mu-Fa; Cao, Jianjing; Newman, Amy H.] Natl Inst Drug Abuse, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Rodriguez, Alice L.; Conn, P. Jeffrey] Vanderbilt Univ, Dept Pharmacol, Vanderbilt Program Drug Discovery, Med Ctr, Nashville, TN 37232 USA. EM mzou@intra.nida.nih.gov RI Conn, Peter/D-7848-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 16 PY 2009 VL 238 MA 75-MEDI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V16HY UT WOS:000207861907371 ER PT J AU Fox, CS Hwang, SJ Massaro, JM Lieb, K Vasan, RS O'Donnell, CJ Hoffmann, U AF Fox, Caroline S. Hwang, Shih-Jen Massaro, Joseph M. Lieb, Kathrin Vasan, Ramachandran S. O'Donnell, Christopher J. Hoffmann, Udo TI Relation of Subcutaneous and Visceral Adipose Tissue to Coronary and Abdominal Aortic Calcium (from the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; RISK-FACTORS; CARDIOVASCULAR-DISEASE; YOUNG-ADULTS; FOLLOW-UP; CALCIFICATION; OBESITY; PROGRESSION; COMMUNITY AB Body fat distribution might be differentially associated with subclinical cardiovascular disease. We examined whether the body mass index, waist circumference, and subcutaneous and visceral adipose tissue are associated with the prevalence of either coronary or abdominal aortic calcium in the Framingham Heart Study. Participants (n = 3,130, mean age 52 years, 49% women) free of clinical cardiovascular disease from the Framingham Heart Study underwent multidetector computed tomographic assessment to quantify the subcutaneous and visceral fat volume and coronary and abdominal aortic calcification. Coronary artery calcification and abdominal aortic calcium were examined in relation to the body mass index, waist circumference, subcutaneous adipose tissue, and visceral adipose tissue in age-, gender-, and multivariate-adjusted models. All measures of adiposity were associated with coronary aortic calcium in the age- and gender-adjusted models (all p <0.008). All relations were attenuated in the multivariate models (all p >0.14). The body mass index, waist circumference, and visceral adipose tissue (but not the subcutaneous adipose tissue) were associated with abdominal aortic calcification in the age- and gender-adjusted models (all p <0.012). However, all relations were attenuated in the multivariate models (all p >0.23). Similar findings were observed in the quartile-based analyses. In conclusion, the general measures of obesity and measures of central abdominal fat are related to the coronary aortic calcium and abdominal aortic calcium levels. However, these cross-sectional associations are attenuated by cardiovascular disease risk factors, possibly because they mediate the association between adiposity measures and subclinical cardiovascular disease. Published by Elsevier Inc. (Am J Cardiol 2009;104:543-547) C1 [Fox, Caroline S.; Hwang, Shih-Jen; Lieb, Kathrin; Vasan, Ramachandran S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. [O'Donnell, Christopher J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Massaro, Joseph M.] Sch Publ Hlth, Div Biostat, Boston, MA USA. [Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM foxca@nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung and Blood Institute's Framingham Heart Study, Bethesda, Maryland [N01-HC-25195]; National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland [2K24HL04334, R01-DK-080739] FX This work was supported by Grant N01-HC-25195 from the National Heart, Lung and Blood Institute's Framingham Heart Study, Bethesda, Maryland. Dr. Vasan was supported in part by Grants 2K24HL04334 and R01-DK-080739 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. NR 21 TC 27 Z9 30 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2009 VL 104 IS 4 BP 543 EP 547 DI 10.1016/j.amjcard.2009.04.019 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 488TJ UT WOS:000269372700016 PM 19660609 ER PT J AU Lieb, W Sullivan, LA Aragam, J Harris, TB Roubenoff, R Benjamin, EJ Vasan, RS AF Lieb, Wolfgang Sullivan, Lisa A. Aragam, Jayashri Harris, Tamara B. Roubenoff, Ronenn Benjamin, Emelia J. Vasan, Ramachandran S. TI Relation of Serum Leptin With Cardiac Mass and Left Atrial Dimension in Individuals > 70 Years of Age SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; HEART-FAILURE; BODY-WEIGHT; OBESITY; PLASMA; ECHOCARDIOGRAPHY; DYSFUNCTION; MYOCYTES; IMPACT AB Experimental evidence indicates that leptin-deficient animals develop left ventricular (LV) hypertrophy, but data relating circulating leptin levels to cardiac structure and function in subjects >70 years old are lacking. We related circulating leptin concentrations to echocardiographic measurements of cardiac structure and function in 432 participants of the community-based Framingham Heart Study (mean age 75 years, 67% women) who underwent echocardiography at a routine examination (approximately 4 years before leptin concentrations were assayed). In multivariable linear regression, logarithmically transformed gender-standardized leptin concentrations were related to the following echocardiographic measurements: LV mass, left atrial size, and fractional shortening (primary analysis); LV wall thickness and LV end-diastolic dimensions (the 2 components of LV mass); and transmitral early/late diastolic filling velocities (secondary analysis). Leptin concentrations were inversely associated with LV mass, LV wall thickness, and left atrial size (p <0.04 for all). The top gender-specific tertile of leptin was associated with an adjusted LV mass 16 g lower compared with the lowest tertile (p = 0.007 for trend across tertiles). Leptin levels were not associated with LV fractional shortening, transmitral early/late diastolic filling velocities, or LV end-diastolic diameter (p >0.16). In conclusion, our cross-sectional observations suggest a cardioprotective influence of leptin on LV remodeling consistent with experimental data and may provide insight into the potential role of leptin resistance as a mediator of obesity-associated cardiomyopathy. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:602-605) C1 [Lieb, Wolfgang; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. [Sullivan, Lisa A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Prevent Med Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Roubenoff, Ronenn] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. EM vasan@bu.edu RI Lieb, Wolfgang/C-1990-2012; OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU Framingham Heart Study [N01-HC-25195]; National Heart, Lung and Blood Institute, Bethesda, Maryland [6R01-NS 17950]; [2K24 HL04334]; [RO 1 HL080124]; [1RO1DK080739] FX This work was supported by Contract N01-HC-25195 through the Framingham Heart Study, Grants 2K24 HL04334, RO 1 HL080124, and 1RO1DK080739 to Dr. Vasan, and Grant 6R01-NS 17950 from the National Heart, Lung and Blood Institute, Bethesda, Maryland. Dr. Roubenoff is an employee of Biogen Idec, Inc., Cambridge, Massachusetts. NR 23 TC 17 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD AUG 15 PY 2009 VL 104 IS 4 BP 602 EP 605 DI 10.1016/j.amjcard.2009.04.026 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 488TJ UT WOS:000269372700026 PM 19660619 ER PT J AU Lynch, SM Vrieling, A Lubin, JH Kraft, P Mendelsohn, JB Hartge, P Canzian, F Steplowski, E Arslan, AA Gross, M Helzlsouer, K Jacobs, EJ LaCroix, A Petersen, G Zheng, W Albanes, D Amundadottir, L Bingham, SA Boffetta, P Boutron-Ruault, MC Chanock, SJ Clipp, S Hoover, RN Jacobs, K Johnson, KC Kooperberg, C Luo, JH Messina, C Palli, D Patel, AV Riboli, E Shu, XO Suarez, LR Thomas, G Tjonneland, A Tobias, GS Tong, E Trichopoulos, D Virtamo, J Ye, WM Yu, K Zeleniuch-Jacquette, A Bueno-de-Mesquita, HB Stolzenberg-Solomon, RZ AF Lynch, Shannon M. Vrieling, Alina Lubin, Jay H. Kraft, Peter Mendelsohn, Julie B. Hartge, Patricia Canzian, Federico Steplowski, Emily Arslan, Alan A. Gross, Myron Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Albanes, Demetrius Amundadottir, Laufey Bingham, Sheila A. Boffetta, Paolo Boutron-Ruault, Marie-Christine Chanock, Stephen J. Clipp, Sandra Hoover, Robert N. Jacobs, Kevin Johnson, Karen C. Kooperberg, Charles Luo, Juhua Messina, Catherine Palli, Domenico Patel, Alpa V. Riboli, Elio Shu, Xiao-Ou Rodriguez Suarez, Laudina Thomas, Gilles Tjonneland, Anne Tobias, Geoffrey S. Tong, Elissa Trichopoulos, Dimitrios Virtamo, Jarmo Ye, Weimin Yu, Kai Zeleniuch-Jacquette, Anne Bueno-de-Mesquita, H. Bas Stolzenberg-Solomon, Rachael Z. TI Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Congress-of-Epidemiology CY SEP 14-16, 2008 CL Tucson, AZ SP Amer Congress Epidemiol DE pancreas; pancreatic neoplasms; smoking; tobacco use cessation ID MODELING TOTAL EXPOSURE; LUNG-CANCER; RISK-FACTORS; METAANALYSIS; INTENSITY; TRIAL; MEN; PREVENTION; SHANGHAI; PATTERNS AB Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (>= 30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (>= 50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (>= 40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis. C1 [Lynch, Shannon M.] NCI, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Rockville, MD USA. [Vrieling, Alina; Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. [Lubin, Jay H.; Mendelsohn, Julie B.; Hartge, Patricia; Albanes, Demetrius; Amundadottir, Laufey; Chanock, Stephen J.; Hoover, Robert N.; Jacobs, Kevin; Thomas, Gilles; Tobias, Geoffrey S.; Yu, Kai; Stolzenberg-Solomon, Rachael Z.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Canzian, Federico] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Steplowski, Emily] Informat Management Serv Inc, Rockville, MD USA. [Arslan, Alan A.; Zeleniuch-Jacquette, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquette, Anne] NYU, Sch Med, Inst Canc, New York, NY USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Prevent Res Ctr, Minneapolis, MN 55455 USA. [Helzlsouer, Kathy] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Bingham, Sheila A.] Univ Cambridge, Ctr Nutr & Canc, MRC, Cambridge, England. [Boffetta, Paolo; Ye, Weimin] Int Agcy Res Canc, F-69372 Lyon, France. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Clipp, Sandra] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. [Jacobs, Kevin] Bioinformed Consulting Serv, Gaithersburg, MD USA. [Jacobs, Kevin] SAIC Frederick Inc, Natl Canc Inst Frederick, Adv Technol Program, Core Genotyping Facil, Frederick, MD USA. [Johnson, Karen C.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA. [Luo, Juhua] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Messina, Catherine] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Palli, Domenico] ISPP, Canc Res & Prevent Inst, Mol & Nutr Epidemiol Unit, Florence, Italy. [Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Rodriguez Suarez, Laudina] Hlth & Hlth Care Serv Council, Publ Hlth Directorate, Asturias, Spain. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Tong, Elissa] Univ Calif Davis, Div Gen Internal Med, Davis, CA 95616 USA. [Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. [Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Lynch, SM (reprint author), NCI, 6130 Execut Blvd,EPN 5121, Bethesda, MD 20892 USA. EM lynchs@mail.nih.gov RI Ye, Weimin/A-5939-2008; Boutron Ruault, Marie-Christine/G-3705-2013; Boutron, Marie-Christine/K-8168-2013; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Vrieling, Alina/A-2725-2016; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; PALLI, Domenico/0000-0002-5558-2437 FU British Heart Foundation; CCR NIH HHS [N01-RC-45035, N01RC37004]; Cancer Research UK; Intramural NIH HHS; Medical Research Council [, MC_U105630924]; NCI NIH HHS [N01-CN-25516, CA105069, CA73790, N01 CN045165, N01 CN25404, N01 CN25476, N01 CN25511, N01 CN25512, N01 CN25513, N01 CN25514, N01 CN25515, N01 CN25516, N01 CN25518, N01 CN25522, N01 CN25524, N01 CN75022, N01-CN-25404, N01-CN-25476, N01-CN-25511, N01-CN-25512, N01-CN-25513, N01-CN-25514, N01-CN-25515, N01-CN-25518, N01-CN-25522, N01-CN-25524, N01-CN-75022, P30 CA016087, P30CA016087, R01 CA070867, R01 CA082729, R01 CA098661, R01 CA105069, R01 CA70867, R01 CA82729, R01CA034588, R01CA098661, R37 CA070867]; NIA NIH HHS [5U01AG018033, U01 AG018033]; NIEHS NIH HHS [ES000260, P30 ES000260]; WHI NIH HHS [N01WH22110, N01WH24152, N01WH32100-2, N01WH32105-6, N01WH32108-9, N01WH32111-13, N01WH32115, N01WH32118-32119, N01WH32122, N01WH42107-26, N01WH42129-32, N01WH44221]; Wellcome Trust NR 32 TC 95 Z9 98 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2009 VL 170 IS 4 BP 403 EP 413 DI 10.1093/aje/kwp134 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 478KI UT WOS:000268586800001 PM 19561064 ER PT J AU Zhang, DM Jiang, DP Yanney, M Zou, S Sygula, A AF Zhang, Dongmao Jiang, Dongping Yanney, Michael Zou, Sige Sygula, Andrzej TI Ratiometric Raman spectroscopy for quantification of protein oxidative damage SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Raman; DCDR; Carbonyl; Protein oxidation; Protein modification; Biomolecule modification ID CARBONYL-MODIFIED PROTEINS; TANDEM MASS-SPECTROMETRY; AMINO-ACIDS; IDENTIFICATION; INSULIN; PHOSPHORYLATION; DERIVATIZATION; GLYCOSYLATION; MITOCHONDRIA; MICROARRAYS AB A novel ratiometric Raman spectroscopic (RMRS) method has been developed for quantitative determination of protein carbonyl levels. Oxidized bovine serum albumin (BSA) and oxidized lysozyme were used as model proteins to demonstrate this method. The technique involves conjugation of protein carbonyls with dinitrophenyl hydrazine (DNPH), followed by drop coating deposition Raman spectral acquisition (DCDR). The RMRS method is easy to implement because it requires only one conjugation reaction, uses a single spectral acquisition, and does not require sample calibration, Characteristic peaks from both protein and DNPH moieties are obtained in a single spectral acquisition, allowing the protein carbonyl level to be calculated from the peak intensity ratio. Detection sensitivity for the RMRS method is approximately 0.33 pmol carbonyl per measurement. Fluorescence and/or immunoassay-based techniques only detect a signal from the labeling molecule and, thus, yield no structural or quantitative information for the modified protein, whereas the RMRS technique allows protein identification and protein carbonyl quantification in a single experiment. (C) 2009 Elsevier Inc. All rights reserved. C1 [Zhang, Dongmao; Jiang, Dongping; Yanney, Michael; Sygula, Andrzej] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. [Zou, Sige] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Zhang, DM (reprint author), Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. EM dz33@msstate.edu FU Intramural NIH HHS [ZIA AG000366-02] NR 39 TC 9 Z9 10 U1 2 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 2009 VL 391 IS 2 BP 121 EP 126 DI 10.1016/j.ab.2009.05.019 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 465XP UT WOS:000267623600007 PM 19457432 ER PT J AU Dai, CL Liang, YJ Chen, LM Zhang, X Deng, WJ Su, XD Shi, Z Wu, CP Ashby, CR Akiyarna, S Ambudkar, SV Chen, ZS Fu, LW AF Dai, Chun-ling Liang, Yong-ju Chen, Li-ming Zhang, Xu Deng, Wen-jing Su, Xiao-dong Shi, Zhi Wu, Chung-pu Ashby, Charles R., Jr. Akiyarna, Shin-ichi Ambudkar, Suresh V. Chen, Zhe-sheng Fu, Li-wu TI Sensitization of ABCB1 overexpressing cells to chemotherapeutic agents by FG020326 via binding to ABCB1 and inhibiting its function SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE FG020326; Multidrug resistance; P-glycoprotein; ABC transporter; Chemosensitivity ID MEDIATED MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; DRUG-RESISTANCE; IN-VITRO; CANCER-CHEMOTHERAPY; REVERSAL; MDR; PHARMACOKINETICS; MODULATION; COMBINATION AB The effectiveness of chemotherapeutic treatment is usually limited by the overexpression of adenosine triphosphate binding cassette (ABC) transporters, which mediate multidrug resistance (MDR) by acting as efflux pumps to remove chemotherapeutic agents from MDR cancer cells. Thus, the inhibition of ABC transporters may represent a promising strategy to reverse MDR. This study was to characterize the actions of FG020326, a newly synthesized triaryl-substituted imidazole derivative, to reverse MDR in vitro and in vivo. FG020326 significantly potentiated the cytotoxicity of paclitaxel, doxorubicin, and vincristine in the ABCB1 (P-glycoprotein, P-gp) overexpressing cells KBv200 and MCF-7/adr, but not in the ABCB1 negative parental cell lines KB and MCF-7. However, FG020326 did not alter the cytotoxicity of the aforementioned drugs in ABCC1 (MRP1), ABCC4 (MRP4), ABCG2 (BCRP) and LRP overexpressing cell lines, KB-CV60, NIH3T3/MRP4-2, S1-MI-80 and SW1573/2R120, respectively. FG020326, following p.o. administration, was present in concentrations sufficient for reversal of MDR in mice. The co-administration of FG020326 with paclitaxel or vincristine significantly enhanced the antitumor activity of these drugs without significantly increasing toxicity in the mice bearing the KBv200 cell xenografts. In addition, FG020326, at concentrations that reversed MDR, did not significantly affect the activity of CYP3A4 or alter the pharmacokinetic profile of paclitaxel after co-administration with paclitaxel. FG020326 produced a significant concentration-dependent displacement of [H-3]azidopine and inhibition of efflux of drug from cells. Furthermore, FG020326 was co-localized with ABCB1 in cell membranes. Hence, FG020326 is characterized as a third generation MDR modulator that holds great promise for the treatment of cancer patients with ABCB1-mediated MDR. (C) 2009 Elsevier Inc. All rights reserved. C1 [Shi, Zhi; Ashby, Charles R., Jr.; Chen, Zhe-sheng] St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. [Dai, Chun-ling; Liang, Yong-ju; Chen, Li-ming; Zhang, Xu; Deng, Wen-jing; Su, Xiao-dong; Shi, Zhi; Fu, Li-wu] Sun Yat Sen Univ, State Key Lab Oncol S China, Ctr Canc, Guangzhou 510060, Peoples R China. [Wu, Chung-pu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Akiyarna, Shin-ichi] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Mol Oncol, Kagoshima 8908544, Japan. RP Chen, ZS (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. EM chenz@stjohns.edu; fulw@mail.sysu.edu.cn FU Chinese National Natural Sciences Foundation [30672407, 30600769]; Chinese Ministry of Education Doctor Foundation [20050558062]; John's University Faculty Start-Up Funding [C-0531]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX We thank Drs. S.E. Bates, and R.W. Robey (NCI, NIH) for S1 and S1-M1-80 cell lines; Dr. G.D. Kruh (Fox Chase Cancer Center, Philadelphia) for the cDNA of human ABCC4. We thank Yangmin (Mimi) Chen (Montgomery High School, New Jersey) for the editorial assistance. This work was supported by the grants from Chinese National Natural Sciences Foundation (No. 30672407 L.-W. Fu and No. 30600769 L.-M. Chen.), Chinese Ministry of Education Doctor Foundation (No. 20050558062 L.-W. Fu) and St. John's University Faculty Start-Up Funding (No. C-0531, Z.-S. Chen). Drs. C-P Wu and SV Ambudkar were supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 22 Z9 23 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 EI 1873-2968 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD AUG 15 PY 2009 VL 78 IS 4 BP 355 EP 364 DI 10.1016/j.bcp.2009.04.023 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 464TG UT WOS:000267529200005 PM 19410561 ER PT J AU Kumar, V Malhotra, SV AF Kumar, Vineet Malhotra, Sanjay V. TI Study on the potential anti-cancer activity of phosphonium and ammonium-based ionic liquids SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Ionic liquids; Anti-tumor; Anti-cancer; Cytotoxicity ID CELL-LINE HELA; CYTOTOXICITY; SCREEN AB The anti-cancer activity and cytotoxicity of phosphonium and ammonium-based ionic liquids (ILs) have been determined for the first time via NCI's in vitro 60 human tumor cell lines. The preliminary SAR showed that the chain length of alkyl substitution on the cations plays crucial role towards anti-tumor activity and cytotoxicity of these ionic liquids. In general, phosphonium-based ILs were found to be more active and less cytotoxic as compared to ammonium ILs. Cell line data and hollow fiber study has demonstrated the potential of ILs to be developed as therapeutic agent. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors would like to thank the NCI Developmental Therapeutics Program for 60 cell line screen of compounds described in this paper. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. NR 25 TC 38 Z9 39 U1 3 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 15 PY 2009 VL 19 IS 16 BP 4643 EP 4646 DI 10.1016/j.bmcl.2009.06.086 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 475KY UT WOS:000268358800025 PM 19615902 ER PT J AU Annunziata, CM Kotz, HL AF Annunziata, Christina M. Kotz, Herbert L. TI Uterine Papillary Serous Carcinoma A New Paradigm for Treatment? SO CANCER LA English DT Editorial Material ID ENDOMETRIAL CANCER; SURVIVAL; CHEMOTHERAPY; OVARIAN C1 [Annunziata, Christina M.; Kotz, Herbert L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Annunziata, CM (reprint author), NCI, Med Oncol Branch, Bldg 10,Room 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM annunzic@mail.nih.gov RI Annunziata, Christina/L-3219-2016 OI Annunziata, Christina/0000-0003-2033-6532 NR 13 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2009 VL 115 IS 16 BP 3594 EP 3596 DI 10.1002/cncr.24425 PG 3 WC Oncology SC Oncology GA 481DH UT WOS:000268786800002 PM 19452535 ER PT J AU Liu, YM Borchert, GL Donald, SP Diwan, BA Anver, M Phang, JM AF Liu, Yongmin Borchert, Gregory L. Donald, Steven P. Diwan, Bhalchandra A. Anver, Miriam Phang, James M. TI Proline Oxidase Functions as a Mitochondrial Tumor Suppressor in Human Cancers SO CANCER RESEARCH LA English DT Article ID P53-INDUCED GENE-6; CELL-METABOLISM; APOPTOSIS; HYDROXYLASES; OXYGEN; CHROMOSOME-22; EXPRESSION; HSNF5/INI1; MUTATIONS; GROWTH AB Tumor metabolism and bioenergetics have become important topics for cancer research and are promising targets for anticancer therapy. Although glucose serves as the main source of energy, proline, an alternative substrate, is important, especially during nutrient stress. Proline oxidase (POX), catalyzing the first step in proline catabolism, is induced by p53 and can regulate cell survival as well as mediate programmed cell death. in a mouse xenograft tumor model, we found that POX greatly reduced tumor formation by causing G(2) cell cycle arrest. Furthermore, immunohistochemical staining showed decreased POX expression in tumor tissues. Importantly, HIF-1 alpha signaling was impaired with POX expression due to the increased production of alpha-ketoglutarate, a critical substrate for prolyl hydroxylation and degradation of HIF-1 alpha. Combined with previous in vitro findings and reported clinical genetic associations, these new findings lead us to propose POX as a mitochondrial tumor suppressor and a potential target for cancer therapy. [Cancer Res 2009:69(16):6414-22] C1 [Liu, Yongmin; Borchert, Gregory L.; Diwan, Bhalchandra A.] Sci Applicat Int Corp Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA. [Anver, Miriam] Sci Applicat Int Corp Frederick Inc, Pathol Histotechnol Lab, Frederick, MD 21702 USA. [Donald, Steven P.; Phang, James M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Liu, YM (reprint author), Sci Applicat Int Corp Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA. EM yongminl@mail.nih.gov; phang@nciferf.gov FU NIH [HHSN261 200800001]; National Cancer Institute; Center for Cancer Research FX Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project also has been funded in part with Federal fluids from the National Cancer Institute, NIH under contract no. HHSN261 200800001. The content of this publication does riot necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. National Cancer Institute-Frederick is accredited by Association for Assessment and Accreditation of Laboratory Annual Care International and follows the Public Health Service Policy for the Care and Use of Laboratory Animals. Annual care was provided in accordance with the procedures outlined in tire "Guide for Care and Use of Laboratory Animals" (National Research Council; 1996; National Academy Press; Washington, D.C.). NR 44 TC 49 Z9 49 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6414 EP 6422 DI 10.1158/0008-5472.CAN-09-1223 PG 9 WC Oncology SC Oncology GA 484RI UT WOS:000269064600008 PM 19654292 ER PT J AU Edwards, RA Witherspoon, M Wang, KH Afrasiabi, K Pham, T Birnbaumer, L Lipkin, SM AF Edwards, Robert A. Witherspoon, Mavee Wang, Kehui Afrasiabi, Kambiz Pham, Trang Birnbaumer, Lutz Lipkin, Steven M. TI Epigenetic Repression of DNA Mismatch Repair by Inflammation and Hypoxia in Inflammatory Bowel Disease-Associated Colorectal Cancer SO CANCER RESEARCH LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MICROSATELLITE-INSTABILITY; COLON-CANCER; EXPERIMENTAL COLITIS; BETHESDA GUIDELINES; GENOMIC INSTABILITY; LYNCH-SYNDROME; MICE; GENE; EXPRESSION AB Sporadic human mismatch repair (MMR)-deficient colorectal cancers account for similar to 12.5% of all cases of colorectal cancer. MMR-deficient colorectal cancers are classically characterized by right-sided location, multifocality, mucinous histology, and lymphocytic infiltration. However, tumors in germ-line MMR-deficient mouse models lack these histopathologic features. Mice lacking the heterotrimeric G protein alpha subunit Gi alpha 2 develop chronic colitis and multifocal, right-sided cancers with mucinous histopathology, similar to human MMR-deficient colorectal cancer. Young Gi alpha 2(-/-) colonic epithelium has normal MMR expression but selectively loses MLH1 and consequently PMS2 expression following inflammation. Gi alpha 2(-/-) cancers have microsatellite instability. Mlh1 is epigenetically silenced not by promoter hypermethylation but by decreased histone acetylation. Chronically inflamed Gi alpha 2(-/-) colonic mucosa contains patchy hypoxia, with increased crypt expression of the hypoxia markers DEC-1 and BNIP3. Chromatin immunoprecipitation identified increased binding of the transcriptional repressor DEC-1 to the proximal Mlh1 promoter in hypoxic YAMC cells and colitic Gi alpha 2(-/-) crypts. Treating Gi alpha 2(-/-) mice with the histone deacetylase inhibitor suberoylanilide hydroxamic acid significantly decreased colitis activity and rescued MLH1 expression in crypt epithelial cells, which was associated with increased acetyl histone H3 levels and decreased DEC-1 binding at the proximal Mlh1 promoter, consistent with a histone deacetylase-dependent mechanism. These data link chronic hypoxic inflammation, epigenetic MMR protein down-regulation, development of MMR-deficient colorectal cancer, and the first mouse model of somatically acquired MMR-deficient colorectal cancer. [Cancer Res 2009;69(16):6423-9] C1 [Edwards, Robert A.; Wang, Kehui] Univ Calif Irvine, Dept Pathol, Irvine, CA 92697 USA. [Witherspoon, Mavee; Afrasiabi, Kambiz; Pham, Trang; Lipkin, Steven M.] Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. [Birnbaumer, Lutz] NIEHS, Lab Neurobiol Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Edwards, RA (reprint author), Univ Calif Irvine, Dept Pathol, D449 Med Sci 1, Irvine, CA 92697 USA. EM redwards@uci.edu; stl2012@med.cornell.edu FU NIH [K08 DK59816, R21 DK071591, Z01-ES101643] FX NIH grants K08 DK59816 and R21 DK071591 (R.A. Edwards) and CA98626 (S.M. Lipkin) laid Intramural Research program of the NIH Project Z01-ES101643. NR 49 TC 37 Z9 37 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6423 EP 6429 DI 10.1158/0008-5472.CAN-09-1285 PG 7 WC Oncology SC Oncology GA 484RI UT WOS:000269064600009 PM 19638594 ER PT J AU Vajdic, CM Falster, MO de Sanjose, S Martinez-Maza, O Becker, N Bracci, PM Melbye, M Smedby, KE Engels, EA Turner, J Vineis, P Costantini, AS Holly, EA Kane, E Spinelli, JJ La Vecchia, C Zheng, TZ Chiu, BCH Dal Maso, L Cocco, P Maynadie, M Foretova, L Staines, A Brennan, P Davis, S Severson, R Cerhan, JR Breen, EC Birmann, B Cozen, W Grulich, AE AF Vajdic, Claire M. Falster, Michael O. de Sanjose, Silvia Martinez-Maza, Otoniel Becker, Nikolaus Bracci, Paige M. Melbye, Mads Smedby, Karin Ekstrom Engels, Eric A. Turner, Jennifer Vineis, Paolo Costantini, Adele Seniori Holly, Elizabeth A. Kane, Eleanor Spinelli, John J. La Vecchia, Carlo Zheng, Tongzhang Chiu, Brian C-H. Dal Maso, Luigino Cocco, Pierluigi Maynadie, Marc Foretova, Lenka Staines, Anthony Brennan, Paul Davis, Scott Severson, Richard Cerhan, James R. Breen, Elizabeth C. Birmann, Brenda Cozen, Wendy Grulich, Andrew E. TI Atopic Disease and Risk of Non-Hodgkin Lymphoma: An InterLymph Pooled Analysis SO CANCER RESEARCH LA English DT Article ID FRANCISCO BAY AREA; MEDICAL HISTORY; SAN-FRANCISCO; HEMATOLOGICAL MALIGNANCIES; CANCER INCIDENCE; BIRTH-ORDER; ALLERGY; POPULATION; ASTHMA; WOMEN AB We performed a pooled analysis of data on atopic disease and risk of non-Hodgkin lymphoma (NHL) from 13 case-control studies, including 13,535 NHL cases and 16,388 controls. Self-reported atopic diseases diagnosed 2 years or more before NHL diagnosis (cases) or interview (controls) were analyzed. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were computed in two-stage random-effects or joint fixed-effects models, and adjusted for age, sex, and study center. When modeled individually, lifetime history of asthma, flay fever, specific allergy (excluding hay fever, asthma, and eczema), and food allergy were associated with a significant reduction in NHL, risk, and there was no association for eczema. When each atopic condition was included in the same model, reduced NHL risk was only associated with a history of allergy (OR, 0.80; 95% CI, 0.68-0.94) and reduced R-cell NHL risk was associated with history of hay fever (OR, 0.85; 95% CI, 0.77-0.95) and allergy (OR, 0.84; 95% CI, 0.76-0.93). Significant reductions in B-cell NHL risk were also observed individuals who were likely to be truly or highly atopic-those with hay fever, allergy, or asthma and at least one other atopic condition over their lifetime. The inverse associations were consistent for the diffuse large B-cell and follicular subtypes. Eczema was positively associated with lymphomas of the skin; misdiagnosis of lymphoma as eczema is likely, but progression of eczema to cutaneous lymphoma cannot be excluded. This Pooled study shows evidence of a modest but consistent reduction in the risk of B-cell NHL associated with atopy. [Cancer Res 2009;69(16):6482-9] C1 [Vajdic, Claire M.; Falster, Michael O.] Univ New S Wales, Canc Res Ctr, Prince Wales Clin Sch, Randwick, NSW 2031, Australia. [Falster, Michael O.; Grulich, Andrew E.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW 2052, Australia. [Turner, Jennifer] St Vincents Hosp, Dept Anat Pathol, Sydney, NSW 2010, Australia. [de Sanjose, Silvia] Inst Catala, Barcelona, Spain. [de Sanjose, Silvia] CIBER Epidemiol & Salud Publ, Barcelona, Spain. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Obstet & Gynecol, AIDS Inst, Los Angeles, CA 90024 USA. [Martinez-Maza, Otoniel] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, AIDS Inst, Los Angeles, CA 90024 USA. [Breen, Elizabeth C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Becker, Nikolaus] German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Smedby, Karin Ekstrom] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Smedby, Karin Ekstrom] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Costantini, Adele Seniori] Inst Study & Prevent Canc, Occupat & Environm Epidemiol Unit, Florence, Italy. [Kane, Eleanor] Univ York, Epidemiol & Genet Unit, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Spinelli, John J.] BC Canc Agcy, Canc Control Res Program, Vancouver, BC, Canada. [La Vecchia, Carlo] Univ Milan, Ist Ric Farmacol Mario Negro, Milan, Italy. [La Vecchia, Carlo] Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy. [Zheng, Tongzhang] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Chiu, Brian C-H.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Dal Maso, Luigino] Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy. [Cocco, Pierluigi] Univ Cagliari, Occupat Hlth Sect, Dept Publ Hlth, Cagliari, Italy. [Maynadie, Marc] Dijon Univ Hosp, Registry Hematol Malignancies Cote Or, Dijon, France. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic. [Staines, Anthony] Dublin City Univ, Sch Nursing, Dublin 9, Ireland. [Brennan, Paul] IARC, Lyon, France. [Davis, Scott] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Davis, Scott] Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. [Severson, Richard] Wayne State Univ, Sch Med, Dept Family Med, Detroit, MI USA. [Severson, Richard] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. [Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Birmann, Brenda] Harvard Univ, Sch Med, Boston, MA USA. [Birmann, Brenda] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Vajdic, CM (reprint author), Univ New S Wales, Canc Res Ctr, Prince Wales Clin Sch, Prince Wales Hosp, Level 1 S Wing Edmund Blacket Bldg, Randwick, NSW 2031, Australia. EM claire.vajdic@unsw.edu.au RI Maynadie, Marc/E-6271-2010; Spinelli, John/B-6210-2013; Martinez-Maza, Otoniel/B-2667-2009; de Sanjose Llongueras, Silvia/H-6339-2014; OI La Vecchia, Carlo/0000-0003-1441-897X; Falster, Michael/0000-0001-6444-7272; Martinez-Maza, Otoniel/0000-0003-1364-0675; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357; dal maso, luigino/0000-0001-6163-200X FU NCI NIH HHS [PC67010, CA104682, CA69269-02, CA87014, CA89745, CA92153, K07 CA115687, N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, PC65064, PC67008, PC67009, PC71105, R01 CA045614, R01 CA051086, R01 CA062006, R01 CA069269-02, R01 CA087014, R01 CA087014-01A1, R01 CA092153, R01 CA092153-01A2, R01 CA104682, R01 CA104682-01, R01 CA121195, R03 CA089745, R03 CA089745-01]; NIEHS NIH HHS [P42 ES004705]; Associazione Italiana per la Ricerca sul Cancro NR 51 TC 44 Z9 55 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6482 EP 6489 DI 10.1158/0008-5472.CAN-08-4372 PG 8 WC Oncology SC Oncology GA 484RI UT WOS:000269064600016 PM 19654312 ER PT J AU Wang, Z Zheng, M Li, ZC Li, RG Jia, LJ Xiong, XF Southall, N Wang, SM Xia, MH Austin, CP Zheng, W Xie, ZJ Sun, Y AF Wang, Zhen Zheng, Min Li, Zhichuan Li, Ruiguo Jia, Lijun Xiong, Xiufang Southall, Noel Wang, Shaomeng Xia, Menghang Austin, Christopher P. Zheng, Wei Xie, Zijian Sun, Yi TI Cardiac Glycosides Inhibit p53 Synthesis by a Mechanism Relieved by Src or MAPK Inhibition SO CANCER RESEARCH LA English DT Article ID LUNG-CANCER CELLS; RIBOSOMAL-PROTEIN L26; SMALL-MOLECULE; MUTANT P53; GROWTH-INHIBITION; TUMOR-SUPPRESSOR; BREAST-CANCER; ACTIVATES P53; APOPTOSIS; MDM2 AB p53 is regulated at multiple levels. We report here that p53, in multiple lines of human cancer cells, is down-regulated by cardiac glycoside drugs digoxin and ouabain, potent inhibitors of Na(+)/K(+)-ATPase. These drugs reduced the basal levels of p53 protein at nanomolar concentrations in a dose-, time-, and cancer cell line-dependent manner, but independent of p53 status of wild-type or mutant. The drugs also reduced the levels of p53 induced by its activators as well as p53 transfected into human cancer cells, regardless of its status. Interestingly, the drugs had no effect on endogenous p53 in two immortalized human cell lines. Mechanistically, p53 reduction occurred not at the mRNA levels but at the protein levels, as a result of reduced protein synthesis rather than enhanced degradation. The cellular sensitivity to drug-induced p53 reduction was not associated with the levels of alpha subunits of Na(+)/K(+)-ATPase in different cell lines. Although lowering extracellular K(+) did not reduce p53 as did ouabain and digoxin, it did potentiate both digoxin- and ouabain-induced p53 reduction in sensitive lines. Finally, p53 reduction seems to be triggered by activation of Src/mitogen-activated protein kinase (MAPK) signaling pathways upon drug binding to the Na(+)/K(+)-ATPase and can be completely blocked by the inhibitors of Src or MAP/ERK kinase. This is the first report that cardiac glycoside drugs, by initiating the Src/MAPK signaling pathways, reduce the p53 levels via inhibition of p53 protein synthesis. The drugs may be useful in the treatment of human cancers with a gain-of-function p53 mutation. [Cancer Res 2009;69(16):6556-64] C1 [Wang, Zhen; Zheng, Min; Li, Ruiguo; Jia, Lijun; Xiong, Xiufang; Sun, Yi] Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Li, Zhichuan; Xie, Zijian] Univ Toledo, Dept Physiol & Pharmacol, Toledo, OH 43606 USA. [Southall, Noel; Xia, Menghang; Austin, Christopher P.; Zheng, Wei] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Sun, Y (reprint author), Univ Michigan, Dept Radiat Oncol, Div Radiat & Canc Biol, Ctr Comprehens Canc, 4424B Med Sci 1,1301 Catherine St, Ann Arbor, MI 48109 USA. EM sunyi@umich.edu RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014 OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757 FU National Cancer Institute [CA111554, CA118762]; DOD concept Award [W81XWH-08-1-0539] FX National Cancer Institute grants CA111554 and CA118762 and DOD concept Award W81XWH-08-1-0539 (Y. Sun). NR 50 TC 53 Z9 59 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6556 EP 6564 DI 10.1158/0008-5472.CAN-09-0891 PG 9 WC Oncology SC Oncology GA 484RI UT WOS:000269064600025 PM 19679550 ER PT J AU Shanker, A Brooks, AD Jacobsen, KM Wine, JW Wiltrout, RH Yagita, H Sayers, TJ AF Shanker, Anil Brooks, Alan D. Jacobsen, Kristen M. Wine, John W. Wiltrout, Robert H. Yagita, Hideo Sayers, Thomas J. TI Antigen Presented by Tumors In vivo Determines the Nature of CD8(+) T-Cell Cytotoxicity SO CANCER RESEARCH LA English DT Article ID MURINE RENAL-CANCER; PERFORIN-DEFICIENT MICE; IFN-GAMMA; MEDIATED CYTOTOXICITY; FAS LIGAND; PATHWAYS; CTL; IMMUNOTHERAPY; ACTIVATION; REGRESSION AB The biological relevance of the perforin and Fas ligand (FasL) cytolytic pathways of CD8(+) T lymphocytes (CTL) for cancer immunotherapy is controversial. We investigated the importance of these pathways in a murine renal cell carcinoma expressing influenza viral hemagglutinin as a defined surrogate antigen (Renca-HA). Following Renca-HA injection, all FasL-dysfunctional FasL(gld/gld) mice (n = 54) died from Renca-HA tumors by day 62. By contrast, perforin(-/-) (51%; n = 45) and Fas(lpr/lpr) (55%; n = 51) mice remained tumor-free at day 360. Blocking FasL in vivo inhibited tumor rejection in these mice. Moreover, established Renca-RA tumors were cleared more efficiently by adoptively transferred HA(518-526)-specific T-cell receptor-transgenic CTL using FasL rather than perforin. Strikingly, a range of mouse tumor cells presenting low concentrations of immunogenic peptide were all preferentially lysed by the FasL but not the Pfp-mediated effector pathway of CTL, whereas at higher peptide concentrations, the preference in effector pathway usage by CTL was lost. Interestingly, a number of human renal cancer lines were also susceptible to FasL-mediated cytotoxicity. Therefore, the FasL cytolytic pathway may be particularly important for eradicating Fas-sensitive tumors presenting low levels of MHC class I-associated antigens following adoptive T-cell therapy. [Cancer Res 2009;69(16):6615-23] C1 [Shanker, Anil; Brooks, Alan D.; Jacobsen, Kristen M.; Wine, John W.; Wiltrout, Robert H.; Sayers, Thomas J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21702 USA. [Shanker, Anil; Brooks, Alan D.; Sayers, Thomas J.] NCI, Sci Applicat Int Corp Frederic Inc, Frederick, MD 21702 USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Bunkyo Ku, Tokyo 113, Japan. RP Shanker, A (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Bldg 560-31-33, Frederick, MD 21702 USA. EM shankera@mail.nih.gov; sayerst@mail.nih.gov RI Sayers, Thomas/G-4859-2015; OI Shanker, Anil/0000-0001-6372-3669 FU NIH [N01-CO-12400]; Center for Cancer Research, National Cancer institute, NIH FX This project has been funded in whole or in part with federal funds from the NCl, NIH under contract N01-CO-12400. The content of this publication does net necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part.) by the Intramural Research Program of the Center for Cancer Research, National Cancer institute, NIH. NR 34 TC 26 Z9 28 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6615 EP 6623 DI 10.1158/0008-5472.CAN-09-0685 PG 9 WC Oncology SC Oncology GA 484RI UT WOS:000269064600032 PM 19654302 ER PT J AU Wright, ME Albanes, D AF Wright, Margaret E. Albanes, Demetrius TI Comment Re: Vitamin E Transport Gene Variants and Prostate Cancer Response SO CANCER RESEARCH LA English DT Letter ID EXPRESSION; PROTEIN; CLONING; RISK C1 [Wright, Margaret E.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA. [Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wright, ME (reprint author), Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA. RI Albanes, Demetrius/B-9749-2015 NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2009 VL 69 IS 16 BP 6756 EP 6757 DI 10.1158/0008-5472.CAN-09-1739 PG 2 WC Oncology SC Oncology GA 484RI UT WOS:000269064600049 ER PT J AU Evans, DG Kalamarides, M Hunter-Schaedle, K Blakeley, J Allen, J Babovic-Vuskanovic, D Belzberg, A Bollag, G Chen, RH DiTomaso, E Golfinos, J Harris, G Jacob, A Kalpana, G Karajannis, M Korf, B Kurzrock, R Law, M McClatchey, A Packer, R Roehm, P Rubenstein, A Slattery, W Tonsgard, JH Welling, DB Widemann, B Yohay, K Giovannini, M AF Evans, D. Gareth Kalamarides, Michel Hunter-Schaedle, Kim Blakeley, Jaishri Allen, Jeffrey Babovic-Vuskanovic, Dusica Belzberg, Allan Bollag, Gideon Chen, Ruihong DiTomaso, Emmanuelle Golfinos, John Harris, Gordon Jacob, Abraham Kalpana, Ganjam Karajannis, Matthias Korf, Bruce Kurzrock, Razelle Law, Meng McClatchey, Andrea Packer, Roger Roehm, Pamela Rubenstein, Allan Slattery, William, III Tonsgard, James H. Welling, D. Bradley Widemann, Brigitte Yohay, Kaleb Giovannini, Marco TI Consensus Recommendations to Accelerate Clinical Trials for Neurofibromatosis Type 2 SO CLINICAL CANCER RESEARCH LA English DT Article ID VESTIBULAR-SCHWANNOMA; MENINGIOMA DEVELOPMENT; TUMOR-SUPPRESSOR; NF2; MUTATION; PATIENT; MERLIN; MOUSE; MRI; NF2/MERLIN AB Purpose: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder associated primarily with bilateral schwannomas seen on the superior vestibular branches of the eighth cranial nerves. Significant morbidity can result from surgical treatment of these tumors. Meningiomas, ependymomas, and other benign central nervous system tumors are also common in NF2. The lack of effective treatments for NF2 marks an unmet medical need. Experimental Design: Here, we provide recommendations from a workshop, cochaired by Drs. D. Gareth Evans and Marco Giovannini, of 36 international researchers, physicians, representatives of the biotechnology industry, and patient advocates on how to accelerate progress toward NF2 clinical trials. Results: Workshop participants reached a consensus that, based on current knowledge, the time is right to plan and implement NF2 clinical trials. Obstacles impeding NF2 clinical trials and how to address them were discussed, as well as the candidate therapeutic pipeline for NF2. Conclusions: Both phase 0 and phase 11 NF2 trials are near-term options for NF2 clinical trials. The number of NF2 patients in the population remains limited, and successful recruitment will require ongoing collaboration efforts between NF2 clinics. (Clin Cancer Res 2009;15(16):5032-9) C1 [Giovannini, Marco] House Ear Res Inst, Ctr Neural Tumor Res, Los Angeles, CA 90057 USA. [Evans, D. Gareth] St Marys Hosp, Manchester M13 0JH, Lancs, England. [Kalamarides, Michel] Hop Beaujon, APHP, Clichy, France. [Allen, Jeffrey; Golfinos, John; Karajannis, Matthias; Roehm, Pamela] NYU, New York, NY 10003 USA. [Law, Meng] Mt Sinai Sch Med, New York, NY USA. [Yohay, Kaleb] Cornell Univ, Med Ctr, New York, NY 10021 USA. [Blakeley, Jaishri; Belzberg, Allan] Johns Hopkins Univ, Baltimore, MD USA. [Babovic-Vuskanovic, Dusica] Mayo Clin, Rochester, MN USA. [Bollag, Gideon] Plexxikon Inc, Berkeley, CA USA. [DiTomaso, Emmanuelle; Harris, Gordon; McClatchey, Andrea] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Jacob, Abraham; Welling, D. Bradley] Ohio State Univ, Columbus, OH 43210 USA. [Kalpana, Ganjam] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Korf, Bruce] Univ Alabama, Birmingham, AL USA. [Kurzrock, Razelle] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Packer, Roger] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Tonsgard, James H.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. [Widemann, Brigitte] NCI, Bethesda, MD 20892 USA. RP Giovannini, M (reprint author), House Ear Res Inst, Ctr Neural Tumor Res, 2100 W 3rd St, Los Angeles, CA 90057 USA. EM mgiovannini@hei.org OI Yohay, Kaleb/0000-0001-5560-3392; Karajannis, Matthias/0000-0002-7151-6528; Evans, Gareth/0000-0002-8482-5784 FU Children's Tumor Foundation FX The NF2 Clinical Trials Consensus Workshop was convened and funded by the Children's Tumor Foundation. NR 36 TC 39 Z9 42 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5032 EP 5039 DI 10.1158/1078-0432.CCR-08-3011 PG 8 WC Oncology SC Oncology GA 484DX UT WOS:000269024900004 PM 19671848 ER PT J AU McCord, AM Jamal, M Williams, ES Camphausen, K Tofilon, PJ AF McCord, Amy M. Jamal, Muhammad Williams, Eli S. Camphausen, Kevin Tofilon, Philip J. TI CD133(+) Glioblastoma Stem-like Cells are Radiosensitive with a Defective DNA Damage Response Compared with Established Cell Lines SO CLINICAL CANCER RESEARCH LA English DT Article ID BRAIN-TUMORS; S-PHASE; H2AX PHOSPHORYLATION; IONIZING IRRADIATION; STRAND BREAKS; HISTONE H2AX; CANCER; RADIATION; REPAIR; INSTABILITY AB Purpose: CD133(+) glioblastoma tumor stem-like cells (TSC) have been defined as radioresistant. However, although previously classified relative to CD133(-) cells, the radiosensitivity of CD133(+) TSCs with respect to the standard glioblastoma model, established glioma cell lines, has not been determined. Therefore, to better understand the radio-response of this cancer stem cell, we have used established cell lines as a framework for defining their in vitro radioresponse. Experimental Design: The intrinsic radiosensitivity of CD133(+) TSC cultures and established glioma cell lines was determined by clonogenic assay. The TSCs and established cell lines were also compared in terms of DNA double-strand break (DSB) repair capacity and cell cycle checkpoint activation. Results: Based on clonogenic analysis, each of the six TSC cultures evaluated was more sensitive to radiation than the established glioma cell lines. Consistent with increased radiosensitivity, the DSB repair capacity as defined by neutral comet assay and yH2AX and Rad51 foci was significantly reduced in TSCs compared with the cell lines. Although G2 checkpoint activation was intact, in contrast to the cell lines, DNA synthesis was not inhibited in TSCs after irradiation, indicating the absence of the intra-S-phase checkpoint. Conclusions: These data indicate that the mechanisms through which CD133(+) TSCs respond to radiation are significantly different from those of the traditional glioblastoma in vitro model, established glioma cell lines. If TSCs play a critical role in glioblastoma treatment response, then such differences are likely to be of consequence in the development and testing of radiosensitizing agents. (Clin Cancer Res 2009;15(16):5145-53) C1 [McCord, Amy M.; Jamal, Muhammad; Williams, Eli S.; Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, Tampa, FL 33612 USA. [Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Tofilon, PJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, 12902 Magnolia Dr,SRB3 DRDIS, Tampa, FL 33612 USA. EM philip.tofilon@moffitt.org NR 36 TC 98 Z9 104 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5145 EP 5153 DI 10.1158/1078-0432.CCR-09-0263 PG 9 WC Oncology SC Oncology GA 484DX UT WOS:000269024900016 PM 19671863 ER PT J AU Jain, A McKnight, DA Fisher, LW Humphreys, EB Mangold, LA Partin, AW Fedarko, NS AF Jain, Alka McKnight, Dianalee A. Fisher, Larry W. Humphreys, Elizabeth B. Mangold, Leslie A. Partin, Alan W. Fedarko, Neal S. TI Small Integrin-Binding Proteins as Serum Markers for Prostate Cancer Detection SO CLINICAL CANCER RESEARCH LA English DT Article ID LINKED GLYCOPROTEINS SIBLINGS; ELEVATED PLASMA OSTEOPONTIN; COMPLEMENT-MEDIATED ATTACK; BONE SIALOPROTEIN; DENTIN MATRIX; PROGNOSTIC VALUE; SCREENING TRIAL; BREAST-CANCER; CELL-BINDING; EXPRESSION AB Purpose: The small integrin-binding ligand N-linked glycoprotein (SIBLING) gene family includes bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE), and osteopontin (OPN). Previous studies have separately reported elevated expression of BSP, OPN, or DSPP in prostate tumor paraffin sections. We hypothesized that SIBLINGs may be informative serum markers for subjects with prostate cancer. Methods: Expression levels of SIBLINGS in biopsies of normal tissue and tumors from prostate were determined by cDNA array and by immunohistochemical staining with monoclonal antibodies. Competitive ELISAs for measuring total BSP, DSPP, MEPE, and OPN were applied to a test group of 102 subjects with prostate cancer and 110 normal subjects and a validation group of 90 subjects. Results: BSP, DMP1, DSPP, and OPN exhibited elevated mRNA expression and protein levels in biopsies. BSP, DSPP, and OPN were elevated in serum from prostate cancer subjects, with serum DSPP exhibiting the greatest difference, yielding an area under the receiver operator characteristic curve value of 0.98. Serum BSP and OPN levels were significantly elevated only in late stages, whereas DSPP was significantly elevated at all stages. Optimal serum value cutoff points derived for BSP, OPN, and DSPP were applied as a validation test to a new group of 90 subjects and DSPP yielded a sensitivity of 90% and a specificity of 100%. Conclusion: Of the SIBLING gene family members, DSPP appears to be a strong candidate for use in serum assays for prostate cancer detection. (Clin Cancer Res 2009;15(16):5199-207) C1 [Jain, Alka; Fedarko, Neal S.] Johns Hopkins Univ, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. [Humphreys, Elizabeth B.; Mangold, Leslie A.; Partin, Alan W.] Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. [McKnight, Dianalee A.; Fisher, Larry W.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Fedarko, NS (reprint author), Room 5A-64 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM ndarko@jhmi.edu OI Fedarko, Neal/0000-0001-6055-6279 FU NIH [113865, 2U01 CA86323]; Department of Defense [W81XWH-04-1-0844]; Division of Intramural Research; National Institute of Dental and Craniofacial Research Intramural Research Program; NIH; Department of Health and Human Services FX NIH grants CA 113865 (N.S. Fedarko) and 2U01 CA86323 (A.W. Partin), Department of Defense grant W81XWH-04-1-0844 (N.S. Fedarko), and Division of Intramural Research, National Institute of Dental and Craniofacial Research Intramural Research Program, NIH, Department of Health and Human Services (L.W. Fisher). NR 46 TC 19 Z9 21 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5199 EP 5207 DI 10.1158/1078-0432.CCR-09-0783 PG 9 WC Oncology SC Oncology GA 484DX UT WOS:000269024900023 PM 19671866 ER PT J AU Badros, A Burger, AM Philip, S Niesvizky, R Kolla, SS Goloubeva, O Harris, C Zwiebel, J Wright, JJ Espinoza-Delgado, I Baer, MR Holleran, JL Egorin, MJ Grant, S AF Badros, Ashraf Burger, Angelika M. Philip, Sunita Niesvizky, Ruben Kolla, Sarah S. Goloubeva, Olga Harris, Carolynn Zwiebel, James Wright, John J. Espinoza-Delgado, Igor Baer, Maria R. Holleran, Julianne L. Egorin, Merrill J. Grant, Steven TI Phase I Study of Vorinostat in Combination with Bortezomib for Relapsed and Refractory Multiple Myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; T-CELL LYMPHOMA; FACTOR-KAPPA-B; REGULATES AGGRESOME FORMATION; PANCREATIC-CANCER CELLS; RESISTANCE CAM-DR; LEUKEMIA-CELLS; APOPTOSIS; PROTEASOME AB Purpose: Vorinostat, a histone deacetylase inhibitor, enhances cell death by the proteasome inhibitor bortezomib in vitro. We sought to test the combination clinically. Experimental Design: A phase I trial evaluated sequential dose escalation of bortezomib at 1 to 1.3 mg/m(2) i.v. on days 1, 4, 8, and 11 and vorinostat at 100 to 500 mg orally daily for 8 days of each 21-day cycle in relapsed/refractory multiple myeloma patients. Vorinostat pharmacokinetics and dynamics were assessed. Results: Twenty-three patients were treated. Patients had received a median of 7 prior regimens (range, 3-13), including autologous transplantation in 20, thalidomide in all 23, lenalidomide in 17, and bortezomib in 19, 9 of whom were bortezomib-refractory. Two patients receiving 500 mg vorinostat had prolonged QT interval and fatigue as dose-limiting toxicities. The most common grade >3 toxicities were myelo-suppression (n = 13), fatigue (n = 11), and diarrhea (n = 5). There were no drug-related deaths. Overall response rate was 42%, including three partial responses among nine bortezomib refractory patients. Vorinostat pharmacokinetics were nonlinear. Serum C(max) reached a plateau above 400 mg. Pharmacodynamic changes in CD-138+ bone marrow cells before and on day 11 showed no correlation between protein levels of NF-kappa B, I kappa B, acetylated tubulin, and p21CIP1 and clinical response. Conclusions: The maximum tolerated dose of vorinostat in our study was 400 mg daily for 8 days every 21 days, with bortezomib administered at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11. The promising antimyeloma activity of the regimen in refractory patients merits further evaluation. (Clin Cancer Res 2009;15(16):5250-7) C1 [Badros, Ashraf; Burger, Angelika M.; Philip, Sunita; Goloubeva, Olga; Harris, Carolynn; Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Niesvizky, Ruben] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Kolla, Sarah S.; Grant, Steven] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Zwiebel, James; Wright, John J.; Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Holleran, Julianne L.; Egorin, Merrill J.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Badros, A (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM Abadros@umm.edu FU NIH [MO-RR00071]; National Cancer Institute [N01-CO-124001, CA93783, CA 100866] FX NIH grant # MO-RR00071 and National Cancer Institute contract N01-CO-124001 (A. Badros), subcontract 25XS115-Task Order 2 (M. Egorin), and supported in part by CA93783 and CA 100866 IS. Grant). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 50 TC 150 Z9 156 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5250 EP 5257 DI 10.1158/1078-0432.CCR-08-2850 PG 8 WC Oncology SC Oncology GA 484DX UT WOS:000269024900029 PM 19671864 ER PT J AU Jackman, DM Miller, VA Cioffredi, LA Yeap, BY Janne, PA Riely, GJ Ruiz, MG Giaccone, G Sequist, LV Johnson, BE AF Jackman, David M. Miller, Vincent A. Cioffredi, Leigh-Anne Yeap, Beow Y. Jaenne, Pasi A. Riely, Gregory J. Ruiz, Marielle Gallegos Giaccone, Giuseppe Sequist, Lecia V. Johnson, Bruce E. TI Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non-Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOTHERAPY-NAIVE PATIENTS; PREVIOUSLY TREATED PATIENTS; SOUTHWEST-ONCOLOGY-GROUP; PHASE-II; BRONCHIOLOALVEOLAR-CARCINOMA; ACTIVATING MUTATIONS; GEFITINIB THERAPY; TYROSINE KINASE; EGFR MUTATIONS; GENE-MUTATIONS AB Purpose: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR-tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. Experimental Design: Chemotherapy-naive patients with advanced non-small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. Results: Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of first-line therapy with an EGFR-TKI. Conclusion: EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non-small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib. (Clin Cancer Res 2009;15(16):5267-73) C1 [Jackman, David M.; Cioffredi, Leigh-Anne; Jaenne, Pasi A.; Johnson, Bruce E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Jackman, David M.; Yeap, Beow Y.; Jaenne, Pasi A.; Sequist, Lecia V.; Johnson, Bruce E.] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Miller, Vincent A.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, Dept Med, Thorac Oncol Serv, New York, NY 10021 USA. [Ruiz, Marielle Gallegos] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Giaccone, Giuseppe] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Jackman, DM (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. EM djackman@partners.org RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU The American Society of Clinical Oncology (ASCO) Cancer Foundation Translational Research Professorship; NIH [5RO1 CA 114465-05]; International Association for the Study of Lung Cancer Fellowship; Alice and Stephen D. Cutler Investigator Fund FX The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 27 TC 233 Z9 249 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5267 EP 5273 DI 10.1158/1078-0432.CCR-09-0888 PG 7 WC Oncology SC Oncology GA 484DX UT WOS:000269024900031 PM 19671843 ER PT J AU Kreitman, RJ Hassan, R FitzGerald, DJ Pastan, I AF Kreitman, Robert J. Hassan, Raffit FitzGerald, David J. Pastan, Ira TI Phase I Trial of Continuous Infusion Anti-Mesothelin Recombinant Immunotoxin SS1P SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; ANTITUMOR-ACTIVITY; MONOCLONAL-ANTIBODY; MALIGNANT MESOTHELIOMA; ANTI-B4-BLOCKED RICIN; LUNG ADENOCARCINOMA; PANCREATIC CANCERS; TUMOR XENOGRAFTS; GENE-EXPRESSION; OVARIAN CANCERS AB Purpose: To conduct a phase I trial of recombinant immunotoxin SS1P given by continuous infusion in chemoresistant solid tumors expressing mesothelin. Experimental Design: Eligible patients had mesothelioma, ovarian, or pancreatic cancer, which was recurrent or unresectable despite standard therapy, and were mesothelin positive by immunohistochemistry. SS1P was given by continuous infusion for 10 days, and cycles could be repeated at 4-week intervals in the absence of neutralizing antibodies or progressive disease. Results: Twenty-four patients, five with peritoneal mesothelioma, nine with pleural mesothelioma, two with pleural-peritoneal mesothelioma, seven with ovarian carcinoma, and one with pancreatic carcinoma, received 4, 8, 12, 18, and 25 mu g/kg/d x 10. The maximum tolerated dose was 25 mu g/kg/d x 10, where one of six patients had dose-limiting toxicity due to reversible vascular leak syndrome. Immunogenicity was observed in 18 (75%) of 24 patients, and five (21%) received a second cycle. Constant plasma levels of SS1P were maintained for most of the 10-day infusion time, with median peak levels of up to 153 ng/mL. One patient had a partial response. Nonmajor responses included cessation of ascites and independence from paracentesis, resolution of masses by positron emission tomography, and improved pain and range of motion. Conclusions: As a single agent by continuous infusion, recombinant immunotoxin SS1P was well tolerated up to 25 mu g/kg/d x 10 and showed evidence of modest clinical activity. Continuous infusion showed no significant advantage over bolus dosing, and further clinical development of SS1P is proceeding by bolus dosing in combination with chemotherapy. (Clin Cancer Res 2009;15(16):5274-9) C1 [Kreitman, Robert J.; Hassan, Raffit; FitzGerald, David J.; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 5124B, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU NIH National Cancer Institute Center for Cancer Research Intramural Research Program FX The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 37 TC 109 Z9 109 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2009 VL 15 IS 16 BP 5274 EP 5279 DI 10.1158/1078-0432.CCR-09-0062 PG 6 WC Oncology SC Oncology GA 484DX UT WOS:000269024900032 PM 19671873 ER EF