FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wroblewski, EE Norman, PJ Rudicell, RS Ramirez, MA Hahn, BH Pusey, AE Parham, P AF Wroblewski, Emily E. Norman, Paul J. Rudicell, Rebecca S. Ramirez, Miguel A. Hahn, Beatrice H. Pusey, Anne E. Parham, Peter TI Major histocompatibility complex (MHC) variation in a population of wild chimpanzees. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract CT 82nd Annual Meeting of the American-Association-of-Physical-Anthropologists CY APR 09-13, 2013 CL Knoxville, TN SP Amer Assoc Phys Anthropologists C1 [Wroblewski, Emily E.; Norman, Paul J.; Parham, Peter] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Rudicell, Rebecca S.] NIH, Vaccine Res Ctr, Bethesda, MD USA. [Ramirez, Miguel A.; Hahn, Beatrice H.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Pusey, Anne E.] Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2013 VL 150 SU 56 SI SI BP 296 EP 296 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 132BR UT WOS:000318043202494 ER PT J AU Zhou, JJ Feigenbaum, L Yee, C Song, HB Yates, C AF Zhou, Jianjun Feigenbaum, Lionel Yee, Carole Song, Hongbin Yates, Clayton TI Mouse Prostate Epithelial Luminal Cells Lineage Originate in the Basal Layer Where the Primitive Stem/Early Progenitor Cells Reside: Implications for Identifying Prostate Cancer Stem Cells SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID INTRAEPITHELIAL NEOPLASIA; EXPRESSION; IDENTIFICATION; INITIATION; CARCINOMA; LEADS AB Prostate stem cells are thought to be responsible for generation of all prostate epithelial cells and for tissue maintenance. The lineage relationship between basal and luminal cells in the prostate is not well clarified. We developed a mouse model to trace cell fate and a mouse model with a slowly cycling cell label to provide insight into this question. The results obtained indicate that putative mouse prostate stem cells are likely to reside in the basal layer. C1 [Zhou, Jianjun; Yates, Clayton] Tuskegee Univ, Dept Biol, Tuskegee, AL 36088 USA. [Zhou, Jianjun; Yates, Clayton] Tuskegee Univ, Ctr Canc Res, Tuskegee, AL 36088 USA. [Zhou, Jianjun; Song, Hongbin] Acad Mil Med Sci, Inst Dis Control & Prevent, Beijing 100071, Peoples R China. [Feigenbaum, Lionel] NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp Frederick, Frederick, MD 21702 USA. [Yee, Carole] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Song, HB (reprint author), Acad Mil Med Sci, Inst Dis Control & Prevent, Beijing 100071, Peoples R China. EM hongbinsong@263.net; cyates@tuskegee.edu FU NIH/RCMI [G12 RR03059-21A1]; NIH/NCI [U54 CA118623]; Department of Defense [PC120913]; National Natural Science Foundation of China [81070969, 81171554]; Beijing Municipal Natural Science Foundation [7102126] FX The authors would like to provide a special honor to the late Jonathan C. Vogel, who was directly involved in this work. His guidance was instrumental. This work was supported by Grants G12 RR03059-21A1 (NIH/RCMI) [CY], U54 CA118623 (NIH/NCI) [CY]; a Department of Defense Grant, PC120913 [CY]; the National Natural Science Foundation of China (no. 81070969 and no. 81171554); and the Beijing Municipal Natural Science Foundation (no. 7102126). NR 18 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 913179 DI 10.1155/2013/913179 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 162MO UT WOS:000320269400001 ER PT J AU Handelsman, Y Oral, EA Bloomgarden, ZT Brown, RJ Chan, JL Einhorn, D Garber, AJ Garg, A Garvey, WT Grunberger, G Henry, RR Lavin, N Tapiador, CD Weyer, C AF Handelsman, Yehuda Oral, Elif A. Bloomgarden, Zachary T. Brown, Rebecca J. Chan, Jean L. Einhorn, Daniel Garber, Alan J. Garg, Abhimanyu Garvey, W. Timothy Grunberger, George Henry, Robert R. Lavin, Norman Tapiador, Carmen D. Weyer, Christian TI THE CLINICAL APPROACH TO THE DETECTION OF LIPODYSTROPHY - AN AACE CONSENSUS STATEMENT SO ENDOCRINE PRACTICE LA English DT Editorial Material ID FAMILIAL PARTIAL LIPODYSTROPHY; LEPTIN-REPLACEMENT THERAPY; SEIP CONGENITAL LIPODYSTROPHY; LONG-TERM EFFICACY; OF-THE-LITERATURE; DUNNIGAN VARIETY; GENERALIZED LIPODYSTROPHY; ADIPOSE-TISSUE; DERANGEMENTS; ADIPONECTIN C1 [Handelsman, Yehuda] Metab Inst Amer, Tarzana, CA 91356 USA. [Oral, Elif A.] Univ Michigan, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA. [Bloomgarden, Zachary T.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Brown, Rebecca J.] NIH, Bethesda, MD 20892 USA. [Chan, Jean L.; Weyer, Christian] Amylin Pharmaceut Inc, Res & Dev, San Diego, CA USA. [Einhorn, Daniel] Scripps Whittier Diabet Inst, La Jolla, CA USA. [Garber, Alan J.] Baylor Coll Med, Houston, TX 77030 USA. [Garg, Abhimanyu] UT Southwestern Med Ctr, Dallas, TX USA. [Garvey, W. Timothy] Univ Alabama Birmingham, UAB Diabet Res & Training Ctr, Birmingham, AL USA. [Grunberger, George] Grunberger Diabet Inst, Bloomfield Hills, MI USA. [Henry, Robert R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Lavin, Norman] Weight Control & Metab Ctr, Tarzana, CA USA. [Tapiador, Carmen D.] East Tennessee Childrens Hosp, Pediat Endocrinol Clin, Knoxville, TN USA. RP Handelsman, Y (reprint author), Metab Inst Amer, 18372 Clark St,212, Tarzana, CA 91356 USA. EM yhandelsman@pacbell.net OI Oral, Elif/0000-0002-9171-1144 FU NIDDK NIH HHS [P60 DK079626, R01 DK088114] NR 31 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JAN-FEB PY 2013 VL 19 IS 1 BP 107 EP 116 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 154JL UT WOS:000319671000023 PM 23435042 ER PT J AU Aaronson, MN AF Aaronson, Mark Neal TI Representing the Poor: Legal Advocacy and Welfare Reform During Reagan's Gubernatorial Years SO HASTINGS LAW JOURNAL LA English DT Article ID PUBLIC-INTEREST LAWYERS; SOCIAL-WELFARE; LAW; RIGHTS; CHALLENGE; ADVERSARY; CONFLICT; MOVEMENT; SYSTEM; WOMEN C1 [Aaronson, Mark Neal] Univ Chicago, Sch Law, Mandel Legal Aid Clin, Chicago, IL 60637 USA. [Aaronson, Mark Neal] Hartford Neighborhood Legal Serv, Hartford, CT USA. [Aaronson, Mark Neal] NIMH, Bethesda, MD 20892 USA. [Aaronson, Mark Neal] CUNY, Dept Polit Sci, New York, NY 10021 USA. RP Aaronson, MN (reprint author), Univ Chicago, Sch Law, Mandel Legal Aid Clin, Chicago, IL 60637 USA. NR 210 TC 0 Z9 0 U1 1 U2 1 PU UNIV CALIF PI SAN FRANCISCO PA HASTINGS COLLEGE LAW 200 MCALLISTER ST, SAN FRANCISCO, CA 94102 USA SN 0017-8322 J9 HASTINGS LAW J JI Hastings Law J. PY 2013 VL 64 SI SI BP 933 EP 1119 PG 187 WC Law SC Government & Law GA 154XN UT WOS:000319710100001 ER PT J AU Reddy, G Dreher, MR Rossmann, C Wood, BJ Haemmerich, D AF Reddy, Goutham Dreher, Matthew R. Rossmann, Christian Wood, Bradford J. Haemmerich, Dieter TI Cytotoxicity of hepatocellular carcinoma cells to hyperthermic and ablative temperature exposures: In vitro studies and mathematical modelling SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE Ablation; hyperthermia; modelling; thermal dose ID INTENSITY FOCUSED ULTRASOUND; RADIOFREQUENCY ABLATION; THERMAL THERAPY; BREAST-CANCER; TUMOR-CELLS; BONE-TUMORS; INJURY; LIVER; THERMOTOLERANCE; RADIOTHERAPY AB Purpose: Image-guided ablative therapies use temperatures greater than 45 degrees C to kill abnormal cells. There is limited published data of cell survival after ablative temperature exposures, which is of importance to predict ablation zone dimensions. The objective of this study was to determine and mathematically model survival of hepatocellular carcinoma cells following ablative temperature exposures (45-60 degrees C). Materials and methods: Hepatocellular carcinoma (HCC) cell lines were plated in 96-well plates, and heated between 45 and 60 degrees C for 0-32 min. Heating was applied by a rapid media exchange with heated Hank's balanced salt solution (HBSS) in a temperature-controlled water bath. Cell viability was determined by MTS assay. Survival data was modelled by the Arrhenius model, and the thermal isoeffective dose (TID) model where kinetic parameters were determined via non-linear optimisation. Results: Results suggest that the thermal dose based on cumulative equivalent minutes and parameters as used for hyperthermia exposures (<43 degrees C) is not applicable for ablative exposures. We found R = 0.72 for temperatures between 45-60 degrees C for the TID model. The Arrhenius parameters were frequency factor A = 3.25E43 1/s, and activation energy E-a = 281 kJ/mol. These parameters correlate well with a prior study in the same cell line, and with threshold temperatures for necrosis from in vivo studies. Conclusions: Our results suggest that standard TID model kinetic parameters based on hyperthermia studies, often also used at ablation temperatures, are not applicable at these higher temperatures for HCC cells. C1 [Reddy, Goutham; Dreher, Matthew R.; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Rossmann, Christian; Haemmerich, Dieter] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Haemmerich, Dieter] Clemson Univ, Dept Bioengn, Clemson, SC USA. RP Haemmerich, D (reprint author), Med Univ S Carolina, Dept Pediat Cardiol, 165 Ashley Ave,POB 250915, Charleston, SC 29425 USA. EM haemmerich@ieee.org OI Haemmerich, Dieter/0000-0003-1127-7024 FU US National Institutes of Health (NIH) [R01CA118990]; NIH Center for Interventional Oncology; NIH; National Center for Research Resources [C06 RR018823] FX This work was supported by US National Institutes of Health (NIH) grant R01CA118990 to D. H., and by the NIH Center for Interventional Oncology and NIH Intramural Research Program. The work was conducted in a facility constructed with support from the NIH, grant C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. The authors alone are responsible for the content and writing of the paper. NR 46 TC 8 Z9 8 U1 0 U2 6 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PY 2013 VL 29 IS 4 BP 318 EP 323 DI 10.3109/02656736.2013.792125 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 157ZZ UT WOS:000319939600006 PM 23738699 ER PT J AU Nishi, H Fong, JH Chang, C Teichmann, SA Panchenko, AR AF Nishi, Hafumi Fong, Jessica H. Chang, Christiana Teichmann, Sarah A. Panchenko, Anna R. TI Regulation of protein-protein binding by coupling between phosphorylation and intrinsic disorder: analysis of human protein complexes SO MOLECULAR BIOSYSTEMS LA English DT Article ID MOLECULAR RECOGNITION FEATURES; INTERACTION NETWORKS; STRUCTURAL BASIS; UNSTRUCTURED PROTEINS; PREDICTION; SCALE; STABILITY; DYNAMICS; SEQUENCE; DATABASE AB Phosphorylation offers a dynamic way to regulate protein activity, subcellular localization, and stability. The majority of signaling pathways involve an extensive set of protein-protein interactions, and phosphorylation is widely used to regulate protein-protein binding by affecting the stability, kinetics and specificity of interactions. Previously it was found that phosphorylation sites tend to be located on protein-protein binding interfaces and may orthosterically modulate the strength of interactions. Here we studied the effect of phosphorylation on protein binding in relation to intrinsic disorder for different types of human protein complexes with known structure of the binding interface. Our results suggest that the processes of phosphorylation, binding and disorder-order transitions are coupled to each other, with about one quarter of all disordered interface Ser/Thr/Tyr sites being phosphorylated. Namely, residue site disorder and interfacial states significantly affect the phosphorylation of serine and to a lesser extent of threonine. Tyrosine phosphorylation might not be directly associated with binding through disorder, and is often observed in ordered interface regions which are not predicted to be disordered in the unbound state. We analyze possible mechanisms of how phosphorylation might regulate protein-protein binding via intrinsic disorder, and specifically focus on how phosphorylation could prevent disorder-order transitions upon binding. C1 [Nishi, Hafumi; Fong, Jessica H.; Chang, Christiana; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Teichmann, Sarah A.] MRC Lab Mol Biol, Cambridge CB2 0QH, England. RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM panch@ncbi.nlm.nih.gov OI Nishi, Hafumi/0000-0002-0846-0330; Teichmann, Sarah/0000-0002-6294-6366 FU Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health; Medical Research Council, UK [U105161047] FX This work was supported by the Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health. This work was partially supported by the Medical Research Council, UK, (MRC file reference number U105161047). NR 53 TC 20 Z9 20 U1 0 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2013 VL 9 IS 7 BP 1620 EP 1626 DI 10.1039/c3mb25514j PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 157FU UT WOS:000319882200008 PM 23364837 ER PT J AU Lobkovsky, AE Wolf, YI Koonin, EV AF Lobkovsky, Alexander E. Wolf, Yuri I. Koonin, Eugene V. TI Quantifying the similarity of monotonic trajectories in rough and smooth fitness landscapes SO MOLECULAR BIOSYSTEMS LA English DT Article ID DNA-BINDING MOLECULES; SECONDARY STRUCTURES; ASEXUAL POPULATIONS; PROTEIN EVOLUTION; ADAPTATION; DYNAMICS; RECOGNITION; PATHWAYS; MODELS; RNA AB When selection is strong and mutations are rare, evolution can be thought of as an uphill trajectory in a rugged fitness landscape. In this context the fitness landscape is a directed acyclic graph in which nodes are genotypes and edges lead from lower to higher fitness genotypes that differ by a single mutation. Because the space of genotypes is vastly multi-dimensional, classification of fitness landscapes is challenging. Many proposed summary characteristics of fitness landscapes attempt to quantify biologically relevant and intuitive notions such as roughness or peak accessibility in alternative ways. Here we explore, in different types of landscapes, the behavior of the recently introduced mean path divergence which quantifies the degree of similarity among evolutionary trajectories with the same endpoints. We find that monotonic trajectories in empirical and model fitness landscapes are significantly more constrained, with low median path divergence, than those in purely additive landscapes. By contrast, transcription factor sequence specificity (aptamer binding affinity) landscapes are markedly smoother and allow substantial variability in monotonic paths that can be greater than that in fully additive landscapes. We propose that the smoothness of the specificity landscapes is a consequence of the simple dependence of the transcription factor binding affinity on the aptamer sequence in contrast to the complex sequence-fitness mapping in folding landscapes. C1 [Lobkovsky, Alexander E.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU DHHS (National Institutes of Health, National Library of Medicine) FX The authors' research is supported by the intramural funds of the DHHS (National Institutes of Health, National Library of Medicine). The authors wish to thank Dr Devesh Bhimsaria and Prof. Aseem Ansari for providing the DNA aptamer binding data. NR 34 TC 3 Z9 3 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2013 VL 9 IS 7 BP 1627 EP 1631 DI 10.1039/c3mb25553k PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 157FU UT WOS:000319882200009 PM 23460358 ER PT J AU Lee, SM Tsai, DH Hackley, VA Brechbiel, MW Cook, RF AF Lee, Sang-Min Tsai, De-Hao Hackley, Vincent A. Brechbiel, Martin W. Cook, Robert F. TI Surface-engineered nanomaterials as X-ray absorbing adjuvant agents for Auger-mediated chemo-radiation SO NANOSCALE LA English DT Article ID COATED GOLD NANOPARTICLES; COMPUTED-TOMOGRAPHY; LOW-ENERGY; CANCER; DELIVERY; PH; ENHANCEMENT; ADSORPTION; COMPLEXES; ELECTRONS AB We report a prototype approach to formulate gold nanoparticle-based X-ray absorbing agents through surface-engineering of a cisplatin pharmacophore with modified polyacrylate. The resulting agents exhibit both chemo-therapeutic potency to cancer cells and Auger-mediated secondary electron emission, showing great potential to improve the therapeutic efficacy of chemo-radiation. C1 [Lee, Sang-Min; Tsai, De-Hao; Hackley, Vincent A.; Cook, Robert F.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Lee, Sang-Min; Brechbiel, Martin W.] NCI, NIH, Bethesda, MD 20892 USA. RP Cook, RF (reprint author), NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM robert.cook@nist.gov OI Hackley, Vincent/0000-0003-4166-2724 FU National Research Council; National Institute of Standards and Technology (NIST); National Institutes of Health (NIH) FX This work was performed while S.-M. Lee held a National Research Council Postdoctoral Research Fellowship jointly with the National Institute of Standards and Technology (NIST) and National Institutes of Health (NIH). The authors thank Drs Jacek Capala and Kwon Joong Yong at NIH, Dr Tae Joon Cho for internal review at NIST, and Dr Jiwen Zheng at the Food and Drug Administration for TEM analyses. NR 40 TC 8 Z9 8 U1 1 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 12 BP 5252 EP 5256 DI 10.1039/c3nr00333g PG 5 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 155NX UT WOS:000319756200009 PM 23657262 ER PT J AU Campbell, MR Karaca, M Adamski, KN Chorley, BN Wang, XT Bell, DA AF Campbell, Michelle R. Karaca, Mehmet Adamski, Kelly N. Chorley, Brian N. Wang, Xuting Bell, Douglas A. TI Novel Hematopoietic Target Genes in the NRF2-Mediated Transcriptional Pathway SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID ANTIOXIDANT-RESPONSIVE ELEMENT; OXIDATIVE-STRESS-RESPONSE; CUL3-BASED E3 LIGASE; ERYTHROID-DIFFERENTIATION; C57BL/6J MICE; EXPRESSION PROFILES; HEMOLYTIC-ANEMIA; NETWORK ANALYSIS; SMALL-INTESTINE; BINDING-SITES AB Nuclear factor- (erythroid-derived 2) like 2 (NFE2L2, NRF2) is a key transcriptional activator of the antioxidant response pathway and is closely related to erythroid transcription factor NFE2. Under oxidative stress, NRF2 heterodimerizes with small Maf proteins and binds cis-acting enhancer sequences found near oxidative stress response genes. Using the dietary isothiocyanate sulforaphane (SFN) to activate NRF2, chromatin immunoprecipitation sequencing (ChIP-seq) identified several hundred novel NRF2-mediated targets beyond its role in oxidative stress. Activated NRF2 bound the antioxidant response element (ARE) in promoters of several known and novel target genes involved in iron homeostasis and heme metabolism, including known targets FTL and FTH1, as well as novel binding in the globin locus control region. Five novel NRF2 target genes were chosen for followup: AMBP, ABCB6, FECH, HRG-1 (SLC48A1), and TBXAS1. SFN-induced gene expression in erythroid K562 and lymphoid cells were compared for each target gene. NRF2 silencing showed reduced expression in lymphoid, lung, and hepatic cells. Furthermore, stable knockdown of NRF2 negative regulator KEAP1 in K562 cells resulted in increased NQO1, AMBP, and TBXAS1 expression. NFE2 binding sites in K562 cells revealed similar binding profiles as lymphoid NRF2 sites in all potential NRF2 candidates supporting a role for NRF2 in heme metabolism and erythropoiesis. C1 [Campbell, Michelle R.; Karaca, Mehmet; Adamski, Kelly N.; Chorley, Brian N.; Wang, Xuting; Bell, Douglas A.] NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Chorley, Brian N.] US EPA, Res Triangle Pk, NC 27709 USA. [Bell, Douglas A.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Bell, DA (reprint author), NIEHS, Environm Genom Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bell1@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health [Z01-ES-100475-11] FX Authors would like to thank Drs. Ngome L. Makia and Sailesh Surapureddi of NIEHS for helpful suggestions, discussion and review. This work was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health (Z01-ES-100475-11). NR 66 TC 9 Z9 9 U1 2 U2 6 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR 120305 DI 10.1155/2013/120305 PG 12 WC Cell Biology SC Cell Biology GA 157XD UT WOS:000319931700001 ER PT J AU Eisenhofer, G Lattke, P Herberg, M Siegert, G Qin, N Darr, R Hoyer, J Villringer, A Prejbisz, A Januszewicz, A Remaley, A Martucci, V Pacak, K Ross, HA Sweep, FCGJ Lenders, JWM AF Eisenhofer, Graeme Lattke, Peter Herberg, Maria Siegert, Gabriele Qin, Nan Daerr, Roland Hoyer, Jana Villringer, Arno Prejbisz, Aleksander Januszewicz, Andrzej Remaley, Alan Martucci, Victoria Pacak, Karel Ross, H. Alec Sweep, Fred C. G. J. Lenders, Jacques W. M. TI Reference intervals for plasma free metanephrines with an age adjustment for normetanephrine for optimized laboratory testing of phaeochromocytoma SO ANNALS OF CLINICAL BIOCHEMISTRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; BIOCHEMICAL-DIAGNOSIS; URINARY METANEPHRINES; CATECHOLAMINES; TUMORS; METHOXYTYRAMINE; PARAGANGLIOMAS; METADRENALINES; METABOLITES AB Background: Measurements of plasma normetanephrine and metanephrine provide a useful diagnostic test for phaeochromocytoma, but this depends on appropriate reference intervals. Upper cut-offs set too high compromise diagnostic sensitivity, whereas set too low, false-positives are a problem. This study aimed to establish optimal reference intervals for plasma normetanephrine and metanephrine. Methods: Blood samples were collected in the supine position from 1226 subjects, aged 5-84 y, including 116 children, 575 normotensive and hypertensive adults and 535 patients in whom phaeochromocytoma was ruled out. Reference intervals were examined according to age and gender. Various models were examined to optimize upper cut-offs according to estimates of diagnostic sensitivity and specificity in a separate validation group of 3888 patients tested for phaeochromocytoma, including 558 with confirmed disease. Results: Plasma metanephrine, but not normetanephrine, was higher (P < 0.001) in men than in women, but reference intervals did not differ. Age showed a positive relationship (P < 0.0001) with plasma normetanephrine and a weaker relationship (P = 0.021) with metanephrine. Upper cut-offs of reference intervals for normetanephrine increased from 0.47 nmol/L in children to 1.05 nmol/L in subjects over 60 y. A curvilinear model for age-adjusted compared with fixed upper cut-offs for normetanephrine, together with a higher cut-off for metanephrine (0.45 versus 0.32 nmol/L), resulted in a substantial gain in diagnostic specificity from 88.3% to 96.0% with minimal loss in diagnostic sensitivity from 93.9% to 93.6%. Conclusions: These data establish age-adjusted cut-offs of reference intervals for plasma normetanephrine and optimized cut-offs for metanephrine useful for minimizing false-positive results. C1 [Eisenhofer, Graeme; Lattke, Peter; Siegert, Gabriele; Qin, Nan] Univ Hosp Dresden, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany. [Eisenhofer, Graeme; Daerr, Roland] Univ Hosp Dresden, Dept Med 3, D-01307 Dresden, Germany. [Herberg, Maria] Univ Hosp Dresden, Inst Med Informat & Biometry, D-01307 Dresden, Germany. [Hoyer, Jana; Villringer, Arno] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, D-04103 Leipzig, Germany. [Prejbisz, Aleksander; Januszewicz, Andrzej] Inst Cardiol, Dept Hypertens, PL-04628 Warsaw, Poland. [Remaley, Alan] NICHHD, Dept Lab Med, NIH, Bethesda, MD 20892 USA. [Martucci, Victoria; Pacak, Karel] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Ross, H. Alec; Sweep, Fred C. G. J.] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 GA Nijmegen, Netherlands. [Lenders, Jacques W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands. RP Eisenhofer, G (reprint author), Univ Dresden, Div Clin Neurochem, Inst Clin Chem & Lab Med, Fetscherstr 74, D-01307 Dresden, Germany. EM Graeme.Eisenhofer@uniklinikum-dresden.de RI Sweep, C.G.J./H-8096-2014; Lenders, J.W.M./L-4487-2015; Ross, H.A./L-4613-2015 FU Deutsche Forschungsgesellschaft [EI855/1/1]; Institute of Cardiology, Warsaw, Poland [2.21/VII/12]; intramural programme of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by the Deutsche Forschungsgesellschaft (EI855/1/1), the Institute of Cardiology, Warsaw, Poland (Grant no: 2.21/VII/12) and the intramural programme of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 38 TC 23 Z9 24 U1 0 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0004-5632 J9 ANN CLIN BIOCHEM JI Ann. Clin. Biochem. PD JAN PY 2013 VL 50 IS 1 BP 62 EP 69 DI 10.1258/acb.2012.012066 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 150MR UT WOS:000319395500011 PM 23065528 ER PT J AU Quick, V Corda, KW Chamberlin, B Schaffner, DW Byrd-Bredbenner, C AF Quick, Virginia Corda, Kirsten W. Chamberlin, Barbara Schaffner, Donald W. Byrd-Bredbenner, Carol TI Ninja Kitchen to the rescue Evaluation of a food safety education game for middle school youth SO BRITISH FOOD JOURNAL LA English DT Article DE Video games; Food safety; Hygiene; Individual behaviour; Middle schools; Attitudes; Self-efficacy; Intentions; Serious games; Kitchen; Cooking ID BEHAVIOR-CHANGE; ADOLESCENTS; KNOWLEDGE; STUDENTS; MODEL; DIET AB Purpose - The purpose of this paper is to assess the effect of Ninja Kitchen, a food safety educational video game, on middle school students' food safety knowledge, psychographic characteristics, and usual and intended behaviors. Design/methodology/approach - The experimental group (n = 903) completed the following activities about one week apart from each other: pretest, played the game, posttest, and follow-up test. The control group (n = 365) completed the same activities at similar intervals but did not have access to the game until after the follow-up test. Findings - Linear mixed-effects models, controlling for gender, grade, and geographic location revealed significant time by group effects for knowledge of safe cooking temperatures for animal proteins and danger zone hazard prevention, and usual produce washing behaviors. Pairwise comparisons, adjusted for multiple comparisons, indicated that after playing the game, the experimental group felt more susceptible to foodborne illness, had stronger attitudes toward the importance of handling food safely and handwashing, had greater confidence in their ability to practice safe food handling, and had greater intentions to practice handwashing and safe food handling. Teachers and students found the game highly acceptable. Originality/value - The game has the potential to promote positive food safety behaviors among youth, in a fun and educational format. C1 [Quick, Virginia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Bethesda, MD USA. [Corda, Kirsten W.] Univ Texas San Antonio, Dept Hlth & Kinesiol, San Antonio, TX USA. [Chamberlin, Barbara] New Mexico State Univ, Media Prod Dept, Las Cruces, NM 88003 USA. [Schaffner, Donald W.] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08903 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. RP Byrd-Bredbenner, C (reprint author), Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. EM bredbenner@aesop.rutgers.edu RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU USDA, National Food Safety Initiative [2007-51110-03813] FX The research is supported by USDA, National Food Safety Initiative 2007-51110-03813. NR 45 TC 6 Z9 6 U1 2 U2 23 PU EMERALD GROUP PUBLISHING LIMITED PI BINGLEY PA HOWARD HOUSE, WAGON LANE, BINGLEY BD16 1WA, W YORKSHIRE, ENGLAND SN 0007-070X J9 BRIT FOOD J JI Br. Food J. PY 2013 VL 115 IS 5 BP 686 EP 699 DI 10.1108/00070701311331481 PG 14 WC Food Science & Technology SC Food Science & Technology GA 153WM UT WOS:000319633200005 ER PT J AU Trusko, B Thorne, J Jabs, D Belfort, R Dick, A Gangaputra, S Nussenblatt, R Okada, A Rosenbaum, J AF Trusko, B. Thorne, J. Jabs, D. Belfort, R. Dick, A. Gangaputra, S. Nussenblatt, R. Okada, A. Rosenbaum, J. CA Standardization Uveitis Nomenclatu TI The Standardization of Uveitis Nomenclature (SUN) Project Development of a Clinical Evidence Base Utilizing Informatics Tools and Techniques SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Classification criteria; uveitis; Delphi technique; nominal group techniques; standardized terminology AB Background: Given the recent increased focus on evidence-based medicine, it is critical that diseases and syndromes have accurate and complete descriptions, including standardized and widely accepted terminologies. Standardizing these descriptions and terminologies is necessary to develop tools such as computerized data entry forms and classification criteria. This need is especially true for diseases that are relatively uncommon, such as uveitis. Objectives: To develop a standardized and internationally accepted terminology for the field of uveitis. Methods: The Standardization of Uveitis Nomenclature (SUN) Working Group (WG) is an international group of 79 uveitis experts from 18 countries and 62 clinical centers. Initial terminology was developed utilizing a "modified" green field approach, which was enhanced through web-based surveys and teleconferences via a "modified" Delphi technique. Terms were mapped provisionally into ontologic dimensions for each syndrome. The Working Group then met and utilized nominal group techniques as a formalized method of finalizing the mappings. Results: Mapping of terms into dimensions to describe 28 major uveitic diseases was confirmed using nominal group techniques (achieving super-majority consensus) for each of the diseases at a meeting of the entire WG. Conclusions: The SUN WG utilized an informatics-based approach to develop a standardized and internationally accepted terminology for the uveitides. C1 [Trusko, B.; Jabs, D.] Mt Sinai Sch Med, New York, NY 10029 USA. [Thorne, J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Belfort, R.] Univ Fed Sao Paulo, Dept Ophthalmol, Sao Paulo, Brazil. [Dick, A.] Univ Bristol, Bristol, Avon, England. [Gangaputra, S.] Univ Wisconsin, Madison, WI USA. [Nussenblatt, R.] NEI, NIH, Bethesda, MD 20892 USA. [Okada, A.] Kyorin Eye Ctr, Tokyo, Japan. [Rosenbaum, J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Trusko, B (reprint author), Mt Sinai Sch Med, 1 Gustave L Levy Pl,Box 1183, New York, NY 10029 USA. EM brett.trusko@mssm.edu FU NEI NIH HHS [R01 EY026593] NR 13 TC 8 Z9 9 U1 0 U2 7 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2013 VL 52 IS 3 BP 259 EP 265 DI 10.3414/ME12-01-0063 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 154XY UT WOS:000319711200009 PM 23392263 ER PT J AU Rao, CV Patlolla, JMR Cooma, I Kawamori, T Steele, VE AF Rao, Chinthalapally V. Patlolla, Jagan M. R. Cooma, Indrani Kawamori, Toshihiko Steele, Vernon E. TI Prevention of Familial Adenomatous Polyp Development in APC(min) Mice and Azoxymethane-Induced Colon Carcinogenesis in F344 Rats by-3 Fatty Acid Rich Perilla Oil SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID RECTAL CELL-PROLIFERATION; ALPHA-LINOLENIC ACID; ABERRANT CRYPT FOCI; FISH-OIL; CANCER PREVENTION; PHOSPHOLIPASE-C; TUMOR PROMOTION; DIETARY-FAT; COX-2; CHEMOPREVENTION AB The present study explored the preventive effects of perilla oil, rich in -linolenic acid, in rodent models of colon tumorigenesis. Six-week-old male F344 rats were fed diets containing 5% corn oil or 10 or 20% perilla oil. Colonic aberrant crypt foci (ACF) were induced by azoxymethane (AOM) and colonic ACF were evaluated. In familial adenomatous polyposis mode, APC(min) mice fed with 20% corn oil or perilla oil for 80days and intestines were evaluated for polyps. Multiple colonic mucosal and polyp samples were assayed for the expression and activity of cyclooxygenase COX-isoforms. Dietary perilla oil produced a dose-dependent inhibition of AOM-induced colonic ACF formation (by 3553%, P < 0.010.005) and reduced the number of foci with 4 crypts/focus (by 3850%, P < 0.010.001) in F344 rats. Dietary perilla oil significantly inhibited development of small intestinal (>69%, P < 0.0001) and colon tumors (>52%, P < 0.03) in APC(min) mice. Administration of perilla oil produced lower levels of type-2 prostaglandins (3853%) from COX-activities in polyps of APC(min) mice. These observations demonstrate that dietary perilla oil rich in -3 fatty acids possesses preventive activity against intestinal neoplastic lesions, both in FAP in genetically-predisposed tissues, as well as against chemically induced preneoplastic lesions in the colon. C1 [Rao, Chinthalapally V.; Patlolla, Jagan M. R.; Cooma, Indrani] PC Stephenson Canc Ctr, Hem Onc Sect, Dept Med, Ctr Canc Prevent & Drug Dev, Oklahoma City, OK USA. [Kawamori, Toshihiko] Univ Honolulu, Dept Pathol, Honlulu, HI USA. [Kawamori, Toshihiko] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Steele, Vernon E.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Rao, CV (reprint author), Univ Oklahoma, Hlth Sci Ctr, Ctr Canc Prevent & Drug Dev, 975 NE 10th St,BRC 1203, Oklahoma City, OK 73104 USA. EM cv-rao@ouhsc.edu FU National Cancer Institute [N01CN-53300]; Kerley Cade Endowed Chair FX We do not have any financial conflicts. We want to thank University of Oklahoma Health Sciences Center Rodent Barrier Facility staff. We also want to thank Dr. Julie Sando for valuable suggestions and editorial help and acknowledge support from the National Cancer Institute, N01CN-53300, and Kerley Cade Endowed Chair. NR 35 TC 0 Z9 0 U1 0 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PD JAN 1 PY 2013 VL 65 SU 1 SI SI BP 54 EP 60 DI 10.1080/01635581.2013.785009 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 152DP UT WOS:000319511100007 PM 23682783 ER PT S AU Duffield, JS Lupher, M Thannickal, VJ Wynn, TA AF Duffield, Jeremy S. Lupher, Mark Thannickal, Victor J. Wynn, Thomas A. BE Abbas, AK Galli, SJ Howley, PM TI Host Responses in Tissue Repair and Fibrosis SO ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 8 SE Annual Review of Pathology-Mechanisms of Disease LA English DT Review; Book Chapter DE myofibroblast; pericyte; fibrotic disease; fibrocyte ID IDIOPATHIC PULMONARY-FIBROSIS; SERUM-AMYLOID-P; TUMOR-NECROSIS-FACTOR; RENAL INTERSTITIAL FIBROSIS; TO-MESENCHYMAL TRANSITION; HEPATIC STELLATE CELLS; COLONY-STIMULATING FACTOR; LATE APOPTOTIC CELLS; FC-GAMMA RECEPTORS; LIVER FIBROSIS AB Myofibroblasts accumulate in the spaces between organ structures and produce extracellular matrix (ECM) proteins, including collagen I. They are the primary "effector" cells in tissue remodeling and fibrosis. Previously, leukocyte progenitors termed fibrocytes and myofibroblasts generated from epithelial cells through epithelial-to-mesenchymal transition (EMT) were considered the primary sources of ECM-producing myofibroblasts in injured tissues. However, genetic fate mapping experiments suggest that mesenchyme-derived cells, known as resident fibroblasts, and pericytes are the primary precursors of scarforming myofibroblasts, whereas epithelial cells, endothelial cells, and myeloid leukocytes contribute to fibrogenesis predominantly by producing key fibrogenic cytokines and by promoting cell-to-cell communication. Numerous cytokines derived from T cells, macrophages, and other myeloid cell populations are important drivers of myofibroblast differentiation. Monocyte-derived cell populations are key regulators of the fibrotic process: They act as a brake on the processes driving fibrogenesis, and they dismantle and degrade established fibrosis. We discuss the origins, modes of activation, and fate of myofibroblasts in various important fibrotic diseases and describe how manipulation of macrophage activation could help ameliorate fibrosis. C1 [Duffield, Jeremy S.] Univ Washington, Div Nephrol, Ctr Lung Biol, Seattle, WA 98019 USA. [Duffield, Jeremy S.] Univ Washington, Div Nephrol, Inst Stem Cell & Regenerat Med, Seattle, WA 98019 USA. [Lupher, Mark] Promedior Inc, Malvern, PA 19355 USA. [Thannickal, Victor J.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, NIH, Bethesda, MD 20877 USA. [Wynn, Thomas A.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20877 USA. RP Duffield, JS (reprint author), Univ Washington, Div Nephrol, Ctr Lung Biol, Seattle, WA 98019 USA. EM twynn@niaid.nih.gov FU Intramural NIH HHS [ZIA AI000829-15, ZIA AI001019-06]; NHLBI NIH HHS [HL067967, HL107181, P50 HL107181, R01 HL067967]; NIDDK NIH HHS [DK84077, DK87389, DK93493, P30 DK017047, R01 DK084077, R01 DK093493, RC1 DK087389] NR 249 TC 145 Z9 148 U1 8 U2 71 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1553-4006 BN 978-0-8243-4308-8 J9 ANNU REV PATHOL-MECH JI Annu. Rev. Pathol.-Mech Dis. PY 2013 VL 8 BP 241 EP 276 DI 10.1146/annurev-pathol-020712-163930 PG 36 WC Pathology SC Pathology GA BEX15 UT WOS:000318483400010 PM 23092186 ER PT B AU Pearl, PL AF Pearl, Phillip L. BA Pearl, PL BF Pearl, PL TI Inherited Metabolic Epilepsies: The Top 10 Diagnoses You Cannot Afford to Miss SO INHERITED METABOLIC EPILESPSIES LA English DT Article; Book Chapter ID DEFICIENCY; BRAIN C1 [Pearl, Phillip L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pearl, Phillip L.] George Washington Univ, Sch Med, Washington, DC USA. [Pearl, Phillip L.] Columbian Coll Arts & Sci, Washington, DC USA. [Pearl, Phillip L.] NINDS, Clin Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Pearl, PL (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-25-3 PY 2013 BP 1 EP 13 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA BEW84 UT WOS:000318448600001 ER PT B AU Alduligan, MS Pearl, PL AF Alduligan, Mona S. Pearl, Phillip L. BA Pearl, PL BF Pearl, PL TI Electroencephalography in the Metabolic Epilepsies SO INHERITED METABOLIC EPILESPSIES LA English DT Article; Book Chapter ID INFANTILE NEUROAXONAL DYSTROPHY; SYRUP-URINE-DISEASE; CHERRY-RED SPOT; PROGRESSIVE MYOCLONUS EPILEPSIES; ALPHA-NEURAMINIDASE DEFICIENCY; NEURONAL CEROID-LIPOFUSCINOSIS; PYRIDOXINE-DEPENDENT EPILEPSY; INBORN-ERRORS; METACHROMATIC LEUKODYSTROPHY; SYNTHASE DEFICIENCY C1 [Alduligan, Mona S.] Childrens Natl Med Ctr, Div Clin Neurophysiol, Washington, DC 20010 USA. [Alduligan, Mona S.] Minist Hlth, Dept Pediat Neurol, Riyadh, Saudi Arabia. [Pearl, Phillip L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pearl, Phillip L.] George Washington Univ, Sch Med, Washington, DC USA. [Pearl, Phillip L.] Columbian Coll Arts & Sci, Washington, DC USA. [Pearl, Phillip L.] NINDS, Clin Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Alduligan, MS (reprint author), Childrens Natl Med Ctr, Div Clin Neurophysiol, Washington, DC 20010 USA. NR 114 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-25-3 PY 2013 BP 39 EP 67 PG 29 WC Clinical Neurology SC Neurosciences & Neurology GA BEW84 UT WOS:000318448600004 ER PT B AU Parikh, S Wolfe, LA Gropman, AL AF Parikh, Sumit Wolfe, Lynne A. Gropman, Andrea L. BA Pearl, PL BF Pearl, PL TI Mitochondrial Diseases and Epilepsy SO INHERITED METABOLIC EPILESPSIES LA English DT Article; Book Chapter ID DNA-POLYMERASE-GAMMA; N-ACETYL ASPARTATE; MOLECULAR-FEATURES; STATUS EPILEPTICUS; OXIDATIVE STRESS; MUTATIONS CAUSE; CHILDREN; DISORDERS; DYSFUNCTION; POLG1 C1 [Parikh, Sumit] Cleveland Clin, Div Neurol, Sect Neurogenet & Metab, Cleveland, OH 44106 USA. [Wolfe, Lynne A.] NHGRI, Undiagnosed Disorders Program, NIH, Bethesda, MD 20892 USA. [Gropman, Andrea L.] George Washington Univ Hlth Sci, Childrens Natl Med Ctr, Dept Neurol, Washington, DC USA. RP Parikh, S (reprint author), Cleveland Clin, Div Neurol, Sect Neurogenet & Metab, Cleveland, OH 44106 USA. NR 44 TC 0 Z9 0 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-25-3 PY 2013 BP 137 EP 144 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA BEW84 UT WOS:000318448600010 ER PT B AU Pearl, PL Jakobs, C Gibson, KM AF Pearl, Phillip L. Jakobs, Cornelis Gibson, K. Michael BA Pearl, PL BF Pearl, PL TI Disorders of GABA Metabolism and Epilepsy SO INHERITED METABOLIC EPILESPSIES LA English DT Article; Book Chapter ID SEMIALDEHYDE DEHYDROGENASE-DEFICIENCY; GAMMA-HYDROXYBUTYRIC ACID; MICE DEFICIENT; SSADH DEFICIENCY; TRANSAMINASE DEFICIENCY; INHERITED DISORDERS; ABSENCE SEIZURES; VIGABATRIN; CHILDREN; BRAIN C1 [Pearl, Phillip L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pearl, Phillip L.] George Washington Univ, Sch Med, Washington, DC USA. [Pearl, Phillip L.] Columbian Coll Arts & Sci, Washington, DC USA. [Pearl, Phillip L.] NINDS, Clin Epilepsy Branch, NIH, Bethesda, MD 20892 USA. [Jakobs, Cornelis] Vrje Univ Med Ctr, Dept Pediat, Metab Lab, Amsterdam, Netherlands. [Jakobs, Cornelis] Vrje Univ Med Ctr, Dept Clin Chem, Metab Lab, Amsterdam, Netherlands. [Gibson, K. Michael] Michigan Technol Univ, Dept Biol Sci, Houghton, MI 49931 USA. RP Pearl, PL (reprint author), Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 45 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-25-3 PY 2013 BP 167 EP 178 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA BEW84 UT WOS:000318448600013 ER PT B AU Pinto, AL Pearl, PL AF Pinto, Anna Lecticia Pearl, Phillip L. BA Pearl, PL BF Pearl, PL TI Clinical Approach to Inherited Metabolic Epilepsies CONCLUSIONS SO INHERITED METABOLIC EPILESPSIES LA English DT Editorial Material; Book Chapter C1 [Pinto, Anna Lecticia] Boston Childrens Hosp, Boston, MA USA. [Pearl, Phillip L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pearl, Phillip L.] George Washington Univ, Sch Med, Washington, DC USA. [Pearl, Phillip L.] Columbian Coll Arts & Sci, Washington, DC USA. [Pearl, Phillip L.] NINDS, Clin Epilepsy Branch, NIH, Bethesda, MD 20892 USA. RP Pinto, AL (reprint author), Boston Childrens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-25-3 PY 2013 BP 335 EP 337 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA BEW84 UT WOS:000318448600028 ER PT J AU Steuerwald, AJ Parsons, PJ Arnason, JG Chen, Z Peterson, CM Louis, GMB AF Steuerwald, Amy J. Parsons, Patrick J. Arnason, John G. Chen, Zhen Peterson, C. Matthew Louis, Germaine M. Buck TI Trace element analysis of human urine collected after administration of Gd-based MRI contrast agents: characterizing spectral interferences using inorganic mass spectrometry SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID ICP-MS; SELENIUM SUPPLEMENTATION; GADOLINIUM; QUADRUPOLE; PLATINUM; SERUM; CELL; OPTIMIZATION; STABILITY; COMPLEX AB Analysis of human urine is commonly used in biomonitoring studies to assess exposure to essential (e. g., Cu, Zn, Se) and non-essential (Pb, Cd, Pt) trace elements. These data are also used in epidemiological studies to evaluate potential associations between trace element exposure and various health outcomes within a population. Today most trace element analyses are typically performed using quadrupole-based inductively coupled plasma mass spectrometry (Q-ICP-MS). However, there is always the potential for spectral interferences with Q-ICP-MS instrumentation, especially when analyzing human specimens that may contain medications and other exogenous substances. Moreover, such xenobiotics may be unknown to the investigators. In a recent study focusing on environmental exposures and endometriosis: Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO Study), urine specimens (n = 619) were collected from participating women upon enrollment into the study or prior to surgery or pelvic magnetic resonance imaging (MRI), and analyzed for 21 trace elements by Q-ICP-MS. Here we report on some anomalous results observed for Se and Pt with elevated concentrations up to several orders of magnitude greater than what might be expected based on established reference intervals. Further investigations using Sector Field (SF-) ICP-MS instrumentation led to identification of doubly charged and polyatomic gadolinium (Gd) species traced to a Gd-based contrast agent that was administered to some subjects just prior to urine collection. Specifically, interferences from Gd2+ and several minor polyatomics were identified as interferences on all of the major isotopes of Se including Se-74, Se-76, Se-77, Se-78, Se-80, and Se-82. While trace amounts of Pt were present in the urine, a number of Gd-containing polyatomic species were also evident as major interferences on all isotopes of Pt (Pt-190, Pt-192, Pt-194, Pt-195, Pt-196, and Pt-198), including Gd-chlorides, Gd-argides, and Gd-oxides. These observations underscore the importance of considering potential isobaric interferences when interpreting unusual trace element results for clinical specimens. C1 [Steuerwald, Amy J.; Parsons, Patrick J.; Arnason, John G.] New York State Dept Hlth, Wadsworth Ctr, Lab Inorgan & Nucl Chem, Albany, NY 12201 USA. [Steuerwald, Amy J.; Parsons, Patrick J.; Arnason, John G.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12201 USA. [Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Peterson, C. Matthew] Univ Utah, Sch Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Salt Lake City, UT 84132 USA. [Peterson, C. Matthew] Univ Utah, Nano Inst Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. RP Parsons, PJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Lab Inorgan & Nucl Chem, POB 509, Albany, NY 12201 USA. EM pjp03@health.state.ny.us OI Parsons, Patrick/0000-0001-9133-875X; Buck Louis, Germaine/0000-0002-1774-4490 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health [NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02] FX This work was funded in part by the Intramural Research Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (contracts NO1-DK-6-3428; NO1-DK-6-3427; 10001406-02). NR 39 TC 4 Z9 4 U1 1 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0267-9477 EI 1364-5544 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PY 2013 VL 28 IS 6 BP 821 EP 830 DI 10.1039/c3ja30331d PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 144MR UT WOS:000318944300004 PM 27397951 ER PT J AU Paisan-Ruiz, C Lewis, PA Singleton, AB AF Paisan-Ruiz, Coro Lewis, Patrick A. Singleton, Andrew B. TI LRRK2: Cause, Risk, and Mechanism SO JOURNAL OF PARKINSONS DISEASE LA English DT Review DE LRRK2; associated phenotype; disease risk; biology; future challenges; Parkinson's disease; parkinsonism; genetics ID REPEAT KINASE 2; FAMILIAL PARKINSONS-DISEASE; AUTOSOMAL-DOMINANT PARKINSONISM; GENOME-WIDE ASSOCIATION; G2019S MUTATION CARRIERS; GENE LRRK2; CHINESE POPULATION; ALPHA-SYNUCLEIN; GTP-BINDING; ROC DOMAIN AB In 2004 it was first shown that mutations in LRRK2 can cause Parkinson's disease. This initial discovery was quickly followed by the observation that a single particular mutation is a relatively common cause of Parkinson's disease across varied populations. Further genetic investigation has revealed a variety of genetic ties to Parkinson's disease across this gene. These include common alleles with quite broad effects on risk, likely through both alterations at the protein sequence level, and in the context of expression. A great deal of functional characterization of LRRK2 and disease-causing mutations in this protein has occurred over the last 9 years, and considerable progress has been made. Particular attention has been paid to the kinase activity of LRRK2 as a therapeutic target, and while it is no means certain that this is viable target it is likely that this hypothesis will be tested in clinical trials sooner rather than later. We believe that the future goals for LRRK2 research are, while challenging, relatively clear and that the next 10 years of research promises to be perhaps more exciting than the last. C1 [Paisan-Ruiz, Coro] Icahn Sch Med Mt Sinai, Dept Neurol Psychiat & Genet & Genom Sci, New York, NY USA. [Paisan-Ruiz, Coro] Icahn Sch Med Mt Sinai, Friedman Brain & Mindich Child Hlth & Dev Inst, New York, NY USA. [Lewis, Patrick A.] UCL, Dept Mol Neurosci, UCL Inst Neurol, London, England. [Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading, Berks, England. [Singleton, Andrew B.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA. RP Singleton, AB (reprint author), NIA, Mol Genet Sect, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM Singleta@mail.nih.gov RI Paisan-Ruiz, Coro/C-2912-2009; Lewis , Patrick/C-3674-2009; OI Lewis, Patrick/0000-0003-4537-0489 FU Parkinson's UK research fellow [F1002]; Michael J. Fox Foundation; Wellcome Trust/MRC Joint Call in Neurodegeneration award [WT089698]; National Institute of Neurological Disorders and Stroke of the National Institutes of Health [R01NS079388]; Intramural Research Program of the National Institute on Aging, National Institutes of Health, part of the Department of Health and Human Services [ZO1 AG000949-07, ZO1 AG000958-10] FX P.A.L. is a Parkinson's UK research fellow (grant F1002) and thanks the Michael J. Fox Foundation for generous research support. This work was supported in part by the Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to the UK Parkinson's Disease Consortium (UKPDC) whose members are from the UCL Institute of Neurology, the University of Sheffield and the MRC Protein Phosphorylation Unit at the University of Dundee. This work was supported in part by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS079388 to C.P.R. This work is supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, part of the Department of Health and Human Services; project numbers ZO1 AG000949-07 and ZO1 AG000958-10. NR 180 TC 18 Z9 20 U1 0 U2 17 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 2 BP 85 EP 103 DI 10.3233/JPD-130192 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 149SE UT WOS:000319340700001 PM 23938341 ER PT J AU Djamshidian, A O'Sullivan, SS Foltynie, T Aviles-Olmos, I Limousin, P Noyce, A Zrinzo, L Lees, AJ Averbeck, BB AF Djamshidian, Atbin O'Sullivan, Sean S. Foltynie, Thomas Aviles-Olmos, Iciar Limousin, Patricia Noyce, Alastair Zrinzo, Ludvic Lees, Andrew J. Averbeck, Bruno B. TI Dopamine Agonists Rather than Deep Brain Stimulation Cause Reflection Impulsivity in Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Deep brain stimulation; neuropsychology; Parkinson's disease ID SUBTHALAMIC NUCLEUS STIMULATION; DECISION-MAKING; PREVALENCE; MEDICATION; BEHAVIORS; IMPROVES AB 4 Background: Dopamine agonist therapy is the main risk factor for impulse control disorders in Parkinson's disease (PD). However, it is unclear whether bilateral deep brain stimulation of the subthalamic nucleus also causes impairment in decision making. Objectives: To assess the role of dopamine agonist therapy and deep brain stimulation on reflection impulsivity in non-demented patients with PD. Methods: We recruited 61 PD patients, 20 treated with L-dopa in combination with a dopamine agonist, 14 taking L-dopa monotherapy, a further 16 PD patients with bilateral subthalamic nucleus deep brain stimulation treated with L-dopa in combination with a dopamine agonist, and 11 PD patients with bilateral subthalamic nucleus deep brain stimulation taking L-dopa but not a dopamine agonist. Results were compared with 18 healthy controls. Patients who had evidence of impulsive compulsive behaviour were excluded. Reflection impulsivity was assessed with the beads task, which is a validated information sampling task. Results: All patients treated with a dopamine agonist gathered significantly less information and made more irrational decisions than all other groups regardless of whether they had surgical treatment. Conclusions: Our results imply that dopamine agonist therapy but not deep brain stimulation leads to "reflection impulsivity" in PD. C1 [Djamshidian, Atbin; O'Sullivan, Sean S.; Noyce, Alastair; Lees, Andrew J.] Univ London, Dept Mol Neurosci, London, England. [Djamshidian, Atbin; O'Sullivan, Sean S.; Noyce, Alastair; Lees, Andrew J.] Univ London, Reta Lila Weston Inst Neurol Studies, London, England. [Foltynie, Thomas; Aviles-Olmos, Iciar; Limousin, Patricia; Zrinzo, Ludvic; Averbeck, Bruno B.] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disord, London, England. [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49 Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov RI Lees, Andrew/A-6605-2009; O'Sullivan, Sean/C-9333-2012; OI O'Sullivan, Sean/0000-0002-0583-7956; Zrinzo, Ludvic/0000-0002-6013-4946 FU Reta Lila Weston Institute for Neurological Studies; TEVA Pharmaceuticals; Parkinson's UK; Cure Parkinson's Trust; European Union; National Institute of Health Research; PSP Association; Reta Lila Howard Foundation; Wellcome; Intramural research program of the NIH FX This study was funded by the Reta Lila Weston Institute for Neurological Studies.; Atbin Djamshidian received funding from TEVA Pharmaceuticals to attend the Movement disorders congress in Dublin 2012. Sean O'Sullivan received honoraria from Britannia Pharmaceuticals, Teva, Lundbeck. Thomas Foltynie received honoraria from Abbott, St Jude Medical, Data Monitoring Committee for Oxford Biomedical and grants from Parkinson's UK, Cure Parkinson's Trust and European Union FP7. Iciar Aviles-Olmos reports no disclosures. Patricia Limousin has received honoraria from industry (Medtronic and St Jude Medical) and for invited talks. Alastair Noyce received funding and travel support from the National Institute of Health Research and grants from the Parkinson's UK, National Institute of Health Research; consultancy: Elan Pharmaceuticals. Ludvic Zrinzo has received honoraria from industry (Medtronic and St Jude Medical) and for invited talks. Andrew Lees is a consultant for Genus, received honoraria from Novartis, Teva, Meda, Boehringer Ingelheim, GSK, Ipsen, Lundbeck, Allergan, Orion, grants from the PSP Association, Weston Trust - The Reta Lila Howard Foundation. Bruno Averbeck received grants from Wellcome, and the Intramural research program of the NIH. NR 33 TC 13 Z9 13 U1 1 U2 9 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 2 BP 139 EP 144 DI 10.3233/JPD-130178 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 149SE UT WOS:000319340700003 PM 23938343 ER PT J AU Rothman, SM Griffioen, KJ Vranis, N Ladenheim, B Cong, WN Cadet, JL Haran, J Martin, B Mattson, MP AF Rothman, Sarah M. Griffioen, Kathleen J. Vranis, Neil Ladenheim, Bruce Cong, Wei-na Cadet, Jean-Lud Haran, Jamie Martin, Bronwen Mattson, Mark P. TI Neuronal Expression of Familial Parkinson's Disease A53T alpha-Synuclein Causes Early Motor Impairment, Reduced Anxiety and Potential Sleep Disturbances in Mice SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; alpha-synuclein; hypothalamus; dopamine; circadian; stride length; anxiety; sleep; serotonin ID ELEVATED-PLUS-MAZE; TRANSGENIC MICE; DOPAMINE TRANSPORTER; LEWY BODIES; BEHAVIOR; DYSFUNCTION; NEURODEGENERATION; DEPRESSION; SEROTONIN; DISORDER AB Background: Mutations in the human alpha-synuclein gene lead to early-onset Parkinson's disease (PD); however, phenotypes of alpha-synuclein mutant mice vary depending upon the promoter driving transgene expression. Objective: The goal of this study was to characterize behavior and neurochemical alterations in mice expressing mutant (A53T) human alpha-synuclein, controlled by a neuron-specific Thy-1 promoter. Our data provide important additional phenotypic and biochemical characterization of a previously generated model of PD. Methods: A53T (SNCA) and wild type (WT) littermate mice were evaluated for motor function (rotarod and stride length) and anxiety (elevated plus maze and open field) every 2 weeks. At 24 weeks mice were evaluated in a Comprehensive Lab Animal Monitoring System (CLAMS). A separate cohort of mice were euthanized at 12, 24 and 36 weeks for immunoblot analysis of alpha-synuclein, dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum, and hypothalamic serotonin and metabolites were measured. Results: SNCA mice display significant motor deficits at 14-18 weeks of age compared to WT mice, which progress over time. CLAMS analysis revealed an increase in activity during the dark phase and a reduction in overall estimated sleep time for SNCA mice compared to WT consistent with clinical reports of sleep abnormalities in PD. A transient change in the levels of DAT appeared at 12 weeks in the striatum and serotonin levels were also altered in the hypothalamus at this time point. Conclusions: This PD model displays consistent and clinically relevant motor and sleep phenotypes. Anxiety phenotypes are consistent with other alpha-synuclein based PD models yet incongruous with typical clinical symptoms. Early increases in serotonin levels potentially explain reductions in anxiety behaviors and sleep. C1 [Rothman, Sarah M.; Griffioen, Kathleen J.; Vranis, Neil; Haran, Jamie; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Ladenheim, Bruce; Cadet, Jean-Lud] NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH, Baltimore, MD USA. [Cong, Wei-na; Martin, Bronwen] NIA, Clin Invest Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, SM (reprint author), NIA, Neurosci Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM srothman02@gmail.com FU Intramural Research Program of the NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. The authors thank Catherine Crews and Charles Reitz for assistance with management of mouse colonies. NR 49 TC 9 Z9 11 U1 6 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1877-7171 J9 J PARKINSON DIS JI J. Parkinsons Dis. PY 2013 VL 3 IS 2 BP 215 EP 229 DI 10.3233/JPD-120130 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 149SE UT WOS:000319340700012 PM 23938351 ER PT J AU Amara, SG AF Amara, Susan G. TI A new take on uptake: neurotransmitter transporters & the cellular mechanisms of amphetamine action SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Amara, Susan G.] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 30P EP 30P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000086 ER PT J AU Hayashi, T AF Hayashi, Teruo TI The molecular function of the sigma-1 receptor SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Hayashi, Teruo] Seiwakai Nishikawa Hosp, Hamada, Shimane 6970052, Japan. [Hayashi, Teruo] Natl Inst Drug Abuse, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 33P EP 33P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000096 ER PT J AU Mori, T Hayashi, T Shibasaki, M Su, TP Suzuki, T AF Mori, Tomohisa Hayashi, Teruo Shibasaki, Masahiro Su, Tsung-Ping Suzuki, Tsutomu TI Involvement of sigma-1 receptor chaperone on the cytoprotective effects and neuroplasticity against dopamine SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Mori, Tomohisa; Shibasaki, Masahiro; Suzuki, Tsutomu] Hoshi Univ, Sch Pharmaceut Sci, Dept Toxicol, Shinagawa Ku, Tokyo 1428501, Japan. [Mori, Tomohisa; Hayashi, Teruo; Su, Tsung-Ping] NIDA, NIH, Baltimore, MD 21224 USA. [Hayashi, Teruo] Seiwakai Nishikawa Hosp, Hamada 6970052, Japan. NR 0 TC 0 Z9 0 U1 1 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 33P EP 33P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000098 ER PT J AU Tanahashi, Y Unno, T Matsuyama, H Kitazawa, T Yamada, M Wess, J Seiichi, K AF Tanahashi, Yasuyuki Unno, Toshihiro Matsuyama, Hayato Kitazawa, Takio Yamada, Masahisa Wess, Jurgen Seiichi, Komori TI Muscarinic regulation of ATP sensitive K+ channels in mouse ileal smooth muscles SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Tanahashi, Yasuyuki] Kyoto Sangyo Univ, Fac Life Sci, Pharmacol Lab, Kita Ku, Kamigamo, Kyoto 6038555, Japan. [Unno, Toshihiro; Matsuyama, Hayato; Seiichi, Komori] Gifu Univ, Fac Appl Biol Sci, Lab Pharmacol, Gifu 5011193, Japan. [Kitazawa, Takio] Rakuno Gakuen Univ, Sch Vet Med, Dept Vet Sci, Ebetsu, Hokkaido 0698501, Japan. [Yamada, Masahisa] Okinawa Inst Sci & Technol, Common Resources Grp, Okinawa 9040412, Japan. [Wess, Jurgen] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 168P EP 168P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000585 ER PT J AU Unno, T Katsurada, T Matsuyama, H Tanahashi, Y Kitazawa, T Yamada, M Wess, Y AF Unno, Toshihiro Katsurada, Taisuke Matsuyama, Hayato Tanahashi, Yasuyuki Kitazawa, Takio Yamada, Masahisa Wess, Yurgen TI Involvement of M-2 or M-3 muscarinic receptor-coupled signalling molecules in the activation of muscarinic cation channels in mouse ileal smooth muscle cells SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Unno, Toshihiro; Katsurada, Taisuke; Matsuyama, Hayato] Gifu Univ, Dept Vet Med, Gifu 5011193, Japan. [Tanahashi, Yasuyuki] Kyoto Sangyo Univ, Dept Anim Med Sci, Kita Ku, Kyoto 6038555, Japan. [Kitazawa, Takio] Rakuno Gakuen Univ, Dept Vet Med, Ebetsu, Hokkaido 0698501, Japan. [Yamada, Masahisa] Okinawa Inst Sci Tech, Common Resources Grp, Onnason, Okinawa 9040412, Japan. [Wess, Yurgen] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 230P EP 230P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000830 ER PT J AU Yoshikawa, M Murayama, C Cotrim, A Hirayama, R Furusawa, Y Bruce, B AF Yoshikawa, Masanobu Murayama, Chieko Cotrim, Ana Hirayama, Ryo-ichi Furusawa, Yoshiya Bruce, Baum TI D-methionine as a protector for irradiation-induced oral mucositis or salivary glands dysfunction SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 86th Annual Meeting of the Japanese-Pharmacological-Society CY MAR 21-23, 2013 CL Fukuoka, JAPAN SP Japanese Pharmacol Soc C1 [Yoshikawa, Masanobu; Murayama, Chieko] Tokai Univ, Sch Med, Dept Clin Pharmacol, Isehara, Kanagawa 2591143, Japan. [Cotrim, Ana; Bruce, Baum] NIH NIDCR, Bethesda, MD USA. [Hirayama, Ryo-ichi; Furusawa, Yoshiya] NIRS, Inage Ku, Chiba, Japan. RI Furusawa, Yoshiya/A-4487-2012 OI Furusawa, Yoshiya/0000-0003-4213-7331 NR 0 TC 0 Z9 0 U1 0 U2 3 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2013 VL 121 SU 1 BP 250P EP 250P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151WL UT WOS:000319491000911 ER PT J AU Bio, DS Soeiro-de-Souza, MG Otaduy, MCG Machado-Vieira, R Moreno, RA AF Bio, Danielle Soares Soeiro-de-Souza, Marcio Gerhardt Garcia Otaduy, Maria Concepcion Machado-Vieira, Rodrigo Moreno, Ricardo Alberto TI The impact of limbic system morphology on facial emotion recognition in bipolar I disorder and healthy controls SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE bipolar disorder; social cognition; facial emotion recognition ID HUMAN CEREBRAL-CORTEX; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; MAGNETIC-RESONANCE IMAGES; MAJOR DEPRESSIVE DISORDER; TEMPORAL-LOBE STRUCTURES; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; GEOMETRICALLY ACCURATE; PREFRONTAL CORTEX; COORDINATE SYSTEM AB Introduction: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) subjects during all mood states. This study aims to investigate the impact of limbic system morphology on FER scores in BD subjects and healthy controls. Material and methods: Thirty-nine euthymic BD I (type I) subjects and 40 healthy controls were subjected to a battery of FER tests and examined with 3D structural imaging of the amygdala and hippocampus. Results: The volume of these structures demonstrated a differential pattern of influence on FER scores in BD subjects and controls. In our control sample, larger left and right amygdala demonstrated to be associated to less recognition of sadness faces. In BD group, there was no impact of amygdala volume on FER but we observed a negative impact of the left hippocampus volume in the recognition of happiness while the right hippocampus volume positively impacted on the scores of happiness. Conclusion: Our results indicate that amygdala and hippocampus volumes have distinct effects on FER in BD subjects compared to controls. Knowledge of the neurobiological basis of the illness may help to provide further insights on the role of treatments and psychosocial interventions for BD. Further studies should explore how these effects of amygdala and hippocampus volumes on FER are associated with social networks and social network functioning. C1 [Bio, Danielle Soares; Soeiro-de-Souza, Marcio Gerhardt; Moreno, Ricardo Alberto] Univ Sao Paulo, Sch Med, Mood Disorders Unit, Sao Paulo, Brazil. [Garcia Otaduy, Maria Concepcion] Univ Sao Paulo, Sch Med, Inst Radiol, Dept & Inst Psychiat, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD USA. RP Moreno, RA (reprint author), Inst Psiquiatria, Dr Ovidio Pires de Campos 785,3rd Floor,North Win, BR-05403010 Sao Paulo, Brazil. EM ricardoalbertomoreno@gmail.com RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU Sao Paulo Research Foundation (Fundo de Apoio a Pesquisa do Estado de Sao Paulo - FAPESP) FX The Sao Paulo Research Foundation (Fundo de Apoio a Pesquisa do Estado de Sao Paulo - FAPESP) financed this research. The authors report no other conflicts of interest in this work. NR 66 TC 1 Z9 1 U1 5 U2 13 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2013 VL 9 BP 743 EP 751 DI 10.2147/NDT.S41896 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 148PT UT WOS:000319258700001 PM 23723706 ER PT J AU Lubega, M Musenze, IA Joshua, G Dhafa, G Badaza, R Bakwesegha, CJ Reynolds, SJ AF Lubega, Muhamadi Musenze, Ibrahim A. Joshua, Gukiina Dhafa, George Badaza, Rose Bakwesegha, Christopher J. Reynolds, Steven J. TI Sex inequality, high transport costs, and exposed clinic location: reasons for loss to follow-up of clients under prevention of mother-to-child HIV transmission in eastern Uganda a qualitative study SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE mother-to-child transmission; HIV; Uganda; sex inequality ID ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; HEALTH-CARE; ADHERENCE; EXPERIENCES; DISCLOSURE; BARRIERS; STIGMA; GENDER; WOMEN AB Background: In Iganga, Uganda, 45% of women who tested HIV-positive during antenatal care between 2007 and 2010 were lost to follow-up (LTFU). We explored reasons for LTFU during prevention of mother-to-child transmission (PMTCT) from a client perspective in eastern Uganda, where antiretroviral therapy (ART) awareness is presumably high. Methods: Seven key informant interviews and 20 in-depth interviews, including both clients who had been retained under PMTCT care and those LTFU during PMTCT were held. Ten focus-group discussions involving a total of 112 participants were also conducted with care-takers/relatives of the PMTCT clients. Content analysis was performed to identify recurrent themes. Results: Our findings indicate that LTFU during PMTCT in eastern Uganda was due to sex inequality, high transport costs to access the services, inadequate posttest counseling, lack of HIV status disclosure, and the isolated/exposed location of the ART clinic, which robs the clients of their privacy. Conclusion: There is a need for approaches that empower women with social capital, knowledge, and skills to influence health-seeking practices. There is also a need to train low-ranking staff and take PMTCT services closer to the clients at the lower-level units to make them affordable and accessible to rural clients. Posttest counseling should be improved to enable PMTCT clients to appreciate the importance of PMTCT services through increasing the number of staff in antenatal care to match the client numbers for improved quality. The counseling should emphasize HIV status disclosure to partners and encourage partner escort for antenatal care visits for further counseling. The exposed and isolated ART clinic should be integrated with the other regular outpatient services to reduce the labeling stigma. C1 [Lubega, Muhamadi] Iganga Dist Adm, Dist Hlth Off, Iganga, Uganda. [Lubega, Muhamadi; Joshua, Gukiina; Dhafa, George] Busoga Univ, Res Inst, Iganga, Uganda. [Lubega, Muhamadi; Musenze, Ibrahim A.; Badaza, Rose; Bakwesegha, Christopher J.] Busoga Univ, Sch Grad Studies & Res, Iganga, Uganda. [Lubega, Muhamadi; Reynolds, Steven J.] NIH NIAID, ICER Amer Embassy, Kampala, Uganda. RP Lubega, M (reprint author), NIH NIAID, ICER Amer Embassy, POB 7007, Kampala, Uganda. EM dlmuhamadi@yahoo.co.uk FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Busoga University School of Graduate Studies FX This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and Busoga University School of Graduate Studies. NR 47 TC 9 Z9 9 U1 0 U2 11 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2013 VL 7 BP 447 EP 454 DI 10.2147/PPA.S19327 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 148SL UT WOS:000319267500001 PM 23737663 ER PT B AU Hallett, M Karp, B AF Hallett, Mark Karp, Barbara BE Alter, KA Hallett, M Karp, B Lungu, C TI Pharmacology and Physiology SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM TOXIN TREATMENT; A INJECTION; NEUROTOXINS C1 [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. [Karp, Barbara] NINDS, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Med Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 2 EP 8 PG 7 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600001 ER PT B AU Lungu, C Hallett, M AF Lungu, Codrin Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Toxin Handling, Reconstitution, and Dilution SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN; SPASMODIC TORTICOLLIS; FACIAL AESTHETICS; MUSCLE; RECOMMENDATIONS; BIOCHEMISTRY C1 [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Lungu, C (reprint author), NINDS, Human Motor Control Sect, Div Intramural Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 10 EP 13 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600002 ER PT B AU Karp, B Hallett, M AF Karp, Barbara Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Focal Dystonia of the Upper Extremity SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter C1 [Karp, Barbara] NINDS, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Karp, B (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 16 EP 19 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600003 ER PT B AU Karp, B Hallett, M AF Karp, Barbara Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Truncal Dystonia and Other Truncal Dyskinesias SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; BOTULINUM TOXIN; PARKINSONS-DISEASE; CAMPTOCORMIA C1 [Karp, Barbara] NINDS, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Karp, B (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 20 EP 23 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600004 ER PT B AU Lungu, C Hallett, M AF Lungu, Codrin Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Cervical Dystonia SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID DEEP BRAIN-STIMULATION; TOXIN TYPE-B; BOTULINUM TOXIN; SPASMODIC TORTICOLLIS; DOUBLE-BLIND; EFFICACY; SAFETY; MULTICENTER; POPULATION; INJECTIONS C1 [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Lungu, C (reprint author), NINDS, Human Motor Control Sect, Div Intramural Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 24 EP 27 PG 4 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600005 ER PT B AU Lungu, C Hallett, M AF Lungu, Codrin Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Hemifacial Spasm SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID DOPA-RESPONSIVE DYSTONIA; LOWER-EXTREMITY DYSTONIA; LOWER-LIMB DYSTONIA; BOTULINUM TOXIN; TORSION DYSTONIA; ONSET; DISORDERS; EPIDEMIOLOGY; SPASTICITY; MOVEMENTS C1 [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Lungu, C (reprint author), NINDS, Human Motor Control Sect, Div Intramural Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 28 EP 35 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600006 ER PT B AU Alter, KE Nahab, FB AF Alter, Katharine E. Nahab, Fatta B. BE Alter, KA Hallett, M Karp, B Lungu, C TI Lower Limb Dystonia SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID MODIFIED ASHWORTH SCALE; RESEARCH ARM TEST; CEREBRAL-PALSY; 1ST-EVER STROKE; TIME-COURSE; SPASTICITY; CHILDREN; MUSCLE; MANAGEMENT; REFLEXES C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurosci, Miami, FL 33136 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 48 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 30 EP 45 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600008 ER PT B AU Alter, KE Nahab, FB AF Alter, Katharine E. Nahab, Fatta B. BE Alter, KA Hallett, M Karp, B Lungu, C TI Upper Motor Neuron Syndromes SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID HEMIFACIAL SPASM; FACIAL-NERVE; DECOMPRESSION; EFFICACY C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Nahab, Fatta B.] Univ Miami, Miller Sch Med, Dept Neurosci, Miami, FL 33136 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 36 EP 37 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600007 ER PT B AU Lungu, C Hallett, M AF Lungu, Codrin Hallett, Mark BE Alter, KA Hallett, M Karp, B Lungu, C TI Hyperhidrosis SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN-A; AXILLARY HYPERHIDROSIS C1 [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. [Hallett, Mark] NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. RP Lungu, C (reprint author), NINDS, Human Motor Control Sect, Div Intramural Res, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 46 EP 47 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600009 ER PT B AU Alter, KE Bohart, Z Lungu, C AF Alter, Katharine E. Bohart, Zachary Lungu, Codrin BE Alter, KA Hallett, M Karp, B Lungu, C TI Botulinum Toxin Therapy for the Treatment of Sialorrhea SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID AMYOTROPHIC-LATERAL-SCLEROSIS; PARKINSONS-DISEASE; DOUBLE-BLIND; CEREBRAL-PALSY; CHILDREN; TRIAL; INJECTIONS; UPDATE C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Bohart, Zachary] Braintree Rehabil Hosp, Spast Program, Braintree, MA USA. [Alter, Katharine E.] Braintree Rehabil Hosp, Neurorehabil Clin, Braintree, MA USA. [Bohart, Zachary] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Lungu, Codrin] NINDS, Human Motor Control Sect, Div Intramural Res, Bethesda, MD 20892 USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 48 EP 53 PG 6 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600010 ER PT B AU Alter, KE Skurow, SM AF Alter, Katharine E. Skurow, Steven M. BE Alter, KA Hallett, M Karp, B Lungu, C TI Instrumentation and Knobology SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID THORACIC OUTLET SYNDROME; BOTULINUM-TOXIN-A; CEREBRAL-PALSY; INJECTION TECHNIQUES; ULTRASOUND; SONOGRAPHY; MUSCLES; BLIND C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Skurow, Steven M.] Terason Ultrasound, Burlington, MA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 35 TC 3 Z9 3 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 84 EP 107 PG 24 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600012 ER PT B AU Alter, KE Munin, MC Skurow, SM AF Alter, Katharine E. Munin, Michael C. Skurow, Steven M. BE Alter, KA Hallett, M Karp, B Lungu, C TI Ultrasound for Procedural Guidance: Scanning-Techniques and Tips SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN; CEREBRAL-PALSY; NERVE BLOCK; INJECTION; CHILDREN C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Munin, Michael C.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Skurow, Steven M.] Terason Ultrasound, Burlington, MA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 108 EP 123 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600013 ER PT B AU Alter, KE Nichols, S Skurow, SM AF Alter, Katharine E. Nichols, Steven Skurow, Steven M. BE Alter, KA Hallett, M Karp, B Lungu, C TI Chemodenervation: Ultrasound Characteristics of Relevant Tissues SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN-A; MUSCLE ULTRASOUND; SALIVARY-GLANDS; JOINT PAIN; INJECTION; DIAGNOSIS; CHILDREN C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Nichols, Steven] Mt Washington Pediat Hosp, Baltimore, MD USA. [Skurow, Steven M.] Terason Ultrasound, Burlington, MA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 124 EP 137 PG 14 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600014 ER PT B AU Alter, KE Munin, MC AF Alter, Katharine E. Munin, Michael C. BE Alter, KA Hallett, M Karp, B Lungu, C TI Comparing Guidance Techniques for Chemodenervation Procedures SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN-A; TIBIALIS POSTERIOR MUSCLE; THORACIC OUTLET SYNDROME; FOREARM FLEXOR MUSCLES; MOTOR ENTRY POINT; CEREBRAL-PALSY; ANATOMIC LOCALIZATION; ULTRASOUND GUIDANCE; NEEDLE PLACEMENT; GUIDED INJECTION C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Munin, Michael C.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 89 TC 3 Z9 3 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 138 EP 153 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600015 ER PT B AU Alter, KE Munin, MC AF Alter, Katharine E. Munin, Michael C. BE Alter, KA Hallett, M Karp, B Lungu, C TI US-Guided Neurotoxin (BoNT) Injections: Clinical Applications SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BOTULINUM-TOXIN-A; BENIGN PROSTATIC HYPERPLASIA; THORACIC OUTLET SYNDROME; FOREARM FLEXOR MUSCLES; CEREBRAL-PALSY; LATERAL EPICONDYLITIS; INITIAL-EXPERIENCE; PLANTAR FASCIITIS; ILIOPSOAS MUSCLE; DOUBLE-BLIND C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Munin, Michael C.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 75 TC 1 Z9 1 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 154 EP 169 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600016 ER PT B AU Alter, KE Lin, JL AF Alter, Katharine E. Lin, John L. BE Alter, KA Hallett, M Karp, B Lungu, C TI Ultrasound Guidance for Nerve and Motor Point Blocks SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter ID BRACHIAL-PLEXUS BLOCK; TIBIALIS POSTERIOR MUSCLE; ANATOMIC LOCALIZATION; INTRANEURAL INJECTION; REGIONAL ANESTHESIA; INFRACLAVICULAR BLOCK; BOTULINUM TOXIN; CEREBRAL-PALSY; ENTRY POINT; STIMULATION C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. [Lin, John L.] Emory Univ, Sch Med, Atlanta, GA USA. [Lin, John L.] Spinal Cord Med Shepherd Ctr, Atlanta, GA USA. RP Alter, KE (reprint author), Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD 21209 USA. NR 71 TC 3 Z9 3 U1 0 U2 1 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 170 EP 183 PG 14 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600017 ER PT B AU Wilson, NA Alter, KE AF Wilson, Nicole A. Alter, Katharine E. BE Alter, KA Hallett, M Karp, B Lungu, C TI Anatomic and Procedural Atlas SO ULTRASOUND-GUIDED CHEMODENERVATION PROCEDURES: TEXT AND ATLAS LA English DT Article; Book Chapter C1 [Alter, Katharine E.] Mt Washington Pediat Hosp, Rehabil Programs, Baltimore, MD USA. [Alter, Katharine E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-60-4 PY 2013 BP 185 EP 339 PG 155 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA BEX32 UT WOS:000318528600018 ER PT S AU Wickner, RB Fujimura, T Esteban, R AF Wickner, Reed B. Fujimura, Tsutomu Esteban, Rosa BE Ghabrial, SA TI Viruses and Prions of Saccharomyces cerevisiae SO ADVANCES IN VIRUS RESEARCH, VOL 86: MYCOVIRUSES SE Advances in Virus Research LA English DT Review; Book Chapter ID DOUBLE-STRANDED-RNA; L-A-VIRUS; EUKARYOTIC MESSENGER-RNA; POL FUSION PROTEIN; BIPARTITE 3'-CIS-ACTING SIGNAL; TRANSLATION INITIATION-FACTOR; RIBOSOMAL-SUBUNIT BIOGENESIS; BETA-SHEET STRUCTURE; COMPLEX IN-VIVO; HET-S PRION AB Saccharomyces cerevisiae has been a key experimental organism for the study of infectious diseases, including dsRNA viruses, ssRNA viruses, and prions. Studies of the mechanisms of virus and prion replication, virus structure, and structure of the amyloid filaments that are the basis of yeast prions have been at the forefront of such studies in these classes of infectious entities. Yeast has been particularly useful in defining the interactions of the infectious elements with cellular components: chromosomally encoded proteins necessary for blocking the propagation of the viruses and prions, and proteins involved in the expression of viral components. Here, we emphasize the L-A dsRNA virus and its killer-toxin-encoding satellites, the 205 and 235 ssRNA naked viruses, and the several infectious proteins (prions) of yeast. C1 [Wickner, Reed B.] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Fujimura, Tsutomu; Esteban, Rosa] Univ Salamanca, CSIC, Inst Biol Func & Genom, E-37008 Salamanca, Spain. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Esteban, Rosa/K-4356-2014; Fujimura, Tsutomu/K-5807-2014 OI Esteban, Rosa/0000-0001-6804-7209; Fujimura, Tsutomu/0000-0002-9457-6769 FU Intramural NIH HHS [ZIA DK024950-07] NR 154 TC 23 Z9 26 U1 0 U2 17 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3527 BN 978-0-12-394315-6 J9 ADV VIRUS RES JI Adv.Virus Res. PY 2013 VL 86 BP 1 EP 36 DI 10.1016/B978-0-12-394315-6.00001-5 PG 36 WC Virology SC Virology GA BEV07 UT WOS:000318253300002 PM 23498901 ER PT J AU Hadigan, C Edwards, E Rosenberg, A Purdy, JB Fleischman, E Howard, L Mican, JM Sampath, K Oyalowo, A Johnson, A Adler, A Rehm, C Smith, M Lai, L Kopp, JB AF Hadigan, Colleen Edwards, Elizabeth Rosenberg, Alice Purdy, Julia B. Fleischman, Estee Howard, Lilian Mican, JoAnn M. Sampath, Karmini Oyalowo, Akinbowale Johnson, Antoinette Adler, Alexandra Rehm, Catherine Smith, Margo Lai, Leon Kopp, Jeffrey B. TI Microalbuminuria in HIV Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE HIV infection; Microalbuminuria; Urinary albumin/creatinine ratio ID CHRONIC KIDNEY-DISEASE; INFECTED PATIENTS; METABOLIC SYNDROME; AIDS MORTALITY; RENAL-FUNCTION; TENOFOVIR; ALBUMINURIA; PREVALENCE; WOMEN; TELMISARTAN AB Background/Aims: Microalbuminuria is a marker for early kidney disease and cardiovascular risk. The purposes of this study were to determine the prevalence of microalbuminuria in an HIV-infected clinic population, to test the predictive value of a single urine albumin/creatinine ratio (ACR) to identify persistent microalbuminuria and to examine covariates of microalbuminuria. Methods: We conducted a prospective cohort study of HIV-infected subjects (n = 182) without proteinuria (urine protein/creatinine ratio >= 0.5 g/g), elevated serum creatinine, diabetes, or chronic inflammatory conditions. Subjects completed three research visits within 9 months. Microalbuminuria was defined as the geometric mean ACR of 25-355 mg/g for females and 17-250 mg/g for males. Results: The prevalence of microalbuminuria was 14%. The negative predictive value of a single urine ACR determination was 98%, whereas the positive predictive value was only 74%. Microalbuminuria was similar among Black (15%) and non-Black (14%) subjects (p = 0.8). Subjects with microalbuminuria were more likely to have hypertension (p = 0.02) and metabolic syndrome (p = 0.03). While duration of HIV infection and the level of HIV viremia were similar between groups, those with microalbuminuria were more likely to have a CD4 count <200 cells/mu l (p = 0.0003). In a multi-variate logistic regression analysis, the only significant independent predictors of microalbuminuria were low CD4 count (p = 0.018) and current ritonavir exposure (p = 0.04). Conclusion: The prevalence of microalbuminuria in an HIV-infected clinic population was similar to earlier reports, and was associated with hypertension and impaired immune function. A single normal ACR determination effectively excludes microalbuminuria, whereas an elevated ACR requires confirmation. C1 [Hadigan, Colleen; Edwards, Elizabeth; Fleischman, Estee; Rehm, Catherine] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Mican, JoAnn M.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Purdy, Julia B.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Howard, Lilian; Sampath, Karmini; Oyalowo, Akinbowale; Johnson, Antoinette; Adler, Alexandra; Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Rosenberg, Alice] SAIC Frederick Inc, Frederick, MD USA. [Smith, Margo; Lai, Leon] Washington Hosp Ctr, Dept Infect Dis, Washington, DC 20010 USA. RP Hadigan, C (reprint author), 10 Ctr Dr,Bldg 10,Rm 11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH Research Program of National Institute of Allergy and Infectious Disease; National Cancer Institute [HHSN261200800001E]; Intramural NIH Research Program of National Institute of Diabetes and Digestive and Kidney Diseases FX The study is registered in ClinicalTrials.gov (NCT00524992). This project has been funded through the Intramural NIH Research Programs of National Institute of Allergy and Infectious Disease and National Institute of Diabetes and Digestive and Kidney Diseases. It was also supported through the National Cancer Institute under Contract No. HHSN261200800001E. NR 30 TC 11 Z9 12 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2013 VL 37 IS 5 BP 443 EP 451 DI 10.1159/000350384 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 141CT UT WOS:000318703900006 PM 23615312 ER PT S AU Xie, F Eddy, EM Conti, M AF Xie, Fang Eddy, Edward M. Conti, Marco BE Marshall, WF TI Analysis of Signaling Pathways Controlling Flagellar Movements in Mammalian Spermatozoa SO CILIA, PT A SE Methods in Enzymology LA English DT Review; Book Chapter ID SOLUBLE ADENYLYL-CYCLASE; SPERM; CAMP; IDENTIFICATION; BICARBONATE; MOTILITY; CALCIUM; CELLS; BODY AB The mammalian sperm flagellum is an example of organelles where sensory and signaling functions are integrated with motility. Structurally related to other ciliary appendages, it has unique cytoskeletal structures that serve to assemble signaling complexes as well as components of metabolic pathways. Flagellar motility is regulated by signaling events that control sperm ion milieu, energy production, and classical second messenger-dependent phosphorylation cascades. Here, we will concentrate on the cAMP signaling pathway associated with flagellar motility. We will describe methods to analyze the properties of a unique adenylyl cyclase termed sAC (gene name Sacy,Adcy10), which plays an essential function in cAMP accumulation in spermatozoa. This soluble adenylyl cyclase (sAC) is a sensor for bicarbonate, pH, and Ca2+ and is likely involved in coupling energy homeostasis with signaling events. We will also describe methods to investigate the macromolecular complexes that bring together sAC and other signaling molecules. C1 [Xie, Fang; Conti, Marco] Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA. [Eddy, Edward M.] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. RP Conti, M (reprint author), Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA. EM contim@obgyn.ucsf.edu FU NICHD NIH HHS [HD31544, R01 HD031544] NR 29 TC 2 Z9 3 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-397945-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 524 BP 91 EP 104 DI 10.1016/B978-0-12-397945-2.00006-8 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BEV06 UT WOS:000318253200007 PM 23498736 ER PT S AU Ramamoorthy, S Cidlowski, JA AF Ramamoorthy, Sivapriya Cidlowski, John A. BE Maghnie, M Loche, S Cappa, M Ghizzoni, L Lorini, R TI Exploring the Molecular Mechanisms of Glucocorticoid Receptor Action from Sensitivity to Resistance SO HORMONE RESISTANCE AND HYPERSENSITIVITY: FROM GENETICS TO CLINICAL MANAGEMENT SE Endocrine Development LA English DT Proceedings Paper CT Meeting on Hormone Resistance and Hypersensitivity from Genetics to Clinical Management CY MAY 13-15, 2012 CL Genoa, ITALY ID SELECTIVE REGULATION; DOWN-REGULATION; MESSENGER-RNA; BETA; PHOSPHORYLATION; DEGRADATION; EXPRESSION; SEQUENCES; ISOFORMS; DISEASE AB Glucocorticoids regulate a variety of physiological processes, and are commonly used to treat disorders of inflammation, autoimmune diseases, and cancer. Glucocorticoid action is predominantly mediated through the classic glucocorticoid receptor (GR), but sensitivity to glucocorticoids varies among individuals, and even within different tissues from the same individual. The molecular basis of this phenomenon can be partially explained through understanding the process of generating bioavailable ligand and the molecular heterogeneity of the GR. The molecular mechanisms that regulate glucocorticoid action highlight the dynamic nature of hormone signaling and provide novel insights into genomic glucocorticoid actions and glucocorticoid sensitivity. Although glucocorticoids are highly effective for therapeutic purposes, long-term and/or high-dose glucocorticoid administration often leads to reduced glucocorticoid sensitivity or resistance. Here, we summarize our current understanding of the mechanisms that modulate glucocorticoid sensitivity and resistance with a focus on GR-mediated signaling. Copyright (C) 2013 S. Karger AG, Basel C1 [Ramamoorthy, Sivapriya; Cidlowski, John A.] NIEHS, NIH, Dept Hlth & Human Serv, Lab Signal Transduct, 111 TW Alexander Dr,MD F3 07, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, Lab Signal Transduct, 111 TW Alexander Dr,MD F3 07, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090057-13, Z01 ES090057-12] NR 28 TC 37 Z9 39 U1 0 U2 16 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-318-02267-4 J9 ENDOCR DEV JI Endocr. Dev. PY 2013 VL 24 BP 41 EP + DI 10.1159/000342502 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BFA76 UT WOS:000319026400005 PM 23392094 ER PT S AU Charmandari, E Kino, T Chrousos, GP AF Charmandari, Evangelia Kino, Tomoshige Chrousos, George P. BE Maghnie, M Loche, S Cappa, M Ghizzoni, L Lorini, R TI Primary Generalized Familial and Sporadic Glucocorticoid Resistance (Chrousos Syndrome) and Hypersensitivity SO HORMONE RESISTANCE AND HYPERSENSITIVITY: FROM GENETICS TO CLINICAL MANAGEMENT SE Endocrine Development LA English DT Proceedings Paper CT Meeting on Hormone Resistance and Hypersensitivity from Genetics to Clinical Management CY MAY 13-15, 2012 CL Genoa, ITALY ID LIGAND-BINDING DOMAIN; PRIMARY CORTISOL RESISTANCE; RECEPTOR N363S VARIANT; BODY-MASS INDEX; GENE-EXPRESSION; POINT MUTATION; ER22/23EK POLYMORPHISM; IN-VIVO; DIFFERENTIAL REGULATION; CLINICAL-IMPLICATIONS AB Familial or sporadic primary generalized glucocorticoid resistance or Chrousos syndrome is a rare genetic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids and a consequent hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis. Primary generalized glucocorticoid hypersensitivity (PGGH) represents the mirror image of the former, and is characterized by generalized, partial, target-tissue hypersensitivity to glucocorticoids, and compensatory hypoactivation of the HPA axis. The molecular basis of both conditions has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair the molecular mechanisms of hGR action and alter tissue sensitivity to glucocorticoids. This review summarizes the pathophysiology, molecular mechanisms and clinical aspects of Chrousos syndrome and PGGH. Copyright (C) 2013 S. Karger AG, Basel C1 [Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, GR-11527 Athens, Greece. [Charmandari, Evangelia; Chrousos, George P.] Biomed Res Fdn Acad Athens, Clin Res Ctr, Div Endocrinol & Metab, Athens, Greece. [Charmandari, Evangelia; Kino, Tomoshige; Chrousos, George P.] Natl Inst Hlth, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Unit Mol Hormone Act, Bethesda, MD USA. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, GR-11527 Athens, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS [ZIA HD008732-12] NR 68 TC 19 Z9 21 U1 1 U2 4 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1421-7082 BN 978-3-318-02267-4 J9 ENDOCR DEV JI Endocr. Dev. PY 2013 VL 24 BP 67 EP + DI 10.1159/000342505 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BFA76 UT WOS:000319026400007 PM 23392096 ER PT J AU Kim, JM Kosak, JP Kim, JK Kissling, G Germolec, DR Zeldin, DC Bradbury, JA Baek, SJ Eling, TE AF Kim, J. M. Kosak, J. P. Kim, J. K. Kissling, G. Germolec, D. R. Zeldin, D. C. Bradbury, J. A. Baek, S. J. Eling, T. E. TI NAG-1/GDF15 Transgenic Mouse Has Less White Adipose Tissue and a Reduced Inflammatory Response SO MEDIATORS OF INFLAMMATION LA English DT Article ID TGF-BETA SUPERFAMILY; COLON-CANCER; LEPTIN; MICE; ACTIVATION; EXPRESSION; CELLS; PROLIFERATION; TUMORIGENESIS; INHIBITORS AB NAG-1/GDF15 is a TGF-beta superfamily member with poorly characterized biological activity proposed to inhibit inflammatory cytokine production. Transgenic mice expressing human NAG-1/GDF15 (NAG-1(Tg/Lox)) are leaner with lower body weight and are resistant to chemically or genetically induced intestinal tumors. Because of the link between obesity, inflammation, and cancer, we examined whether these mice exhibit a reduced response to inflammatory stimuli. The NAG-1(Tg/Lox) mice had a reduced inflammatory response to LPS based on the serum levels of cytokines KC, IL-6, MCP-1, and TNF alpha. In contrast to literature reports and our in vivo results, NAG-1 did not inhibit LPS-induced cytokine expression in vitro in RAW264.7 cells, mouse peritoneal macrophages, or mouse liver Kupffer cells, suggesting that NAG-1/GDF15 does not directly inhibit LPS-induced inflammatory cytokine production. However, NAG-1(Tg/Lox) mice have less white adipose tissue, the major source of inflammatory adipokines including leptin. Basal and LPS-treated serum leptin and mRNA levels in the adipose tissue of NAG-1(Tg/Lox) mice were lower than those in WT mice. We propose that the reduced white adipose tissue and reduced leptin expression may be responsible, in part, for the reduced inflammatory response to LPS and the decrease in intestinal tumors observed in NAG-1(Tg/Lox) mice. C1 [Kim, J. M.; Kosak, J. P.; Kim, J. K.; Eling, T. E.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kim, J. M.] Korea Natl Inst Hlth, Div Struct & Funct Gen, Osong 363951, South Korea. [Kissling, G.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Germolec, D. R.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Zeldin, D. C.; Bradbury, J. A.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Baek, S. J.] Univ Tennessee, Coll Vet Med, Dept Biomed & Diagnost Sci, Knoxville, TN 37996 USA. [Eling, T. E.] Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, Res Triangle Pk, NC 27709 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU NIH, NIEHS Intramural Research Program [Z01 ES025043, Z01- ES010016-14] FX The authors thank Colleen Anna, NIEHS, and Kyung-Won Min for their excellent technical assistance, the staff of ILS for their support, and Nichelle Whitlock (University of Tennessee) for mouse genotyping. They also thank James Clark, NIEHS for his expertise performing the mouse liver perfusions. This research was supported, in part, by NIH, NIEHS Intramural Research Program: Projects (Zeldin) Z01 ES025043 and (Eling) Z01- ES010016-14. The current address of J. M. Kim is the Division of Structural and Functional Genomics at Korea National Institute of Health, Osong, Republic of Korea. NR 29 TC 4 Z9 4 U1 0 U2 7 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 0962-9351 J9 MEDIAT INFLAMM JI Mediat. Inflamm. PY 2013 AR 641851 DI 10.1155/2013/641851 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 147HE UT WOS:000319156500001 ER PT J AU Cho, HY Gladwell, W Yamamoto, M Kleeberger, SR AF Cho, Hye-Youn Gladwell, Wesley Yamamoto, Masayuki Kleeberger, Steven R. TI Exacerbated Airway Toxicity of Environmental Oxidant Ozone in Mice Deficient in Nrf2 SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED LUNG INFLAMMATION; DIESEL EXHAUST; NITRIC-OXIDE; TRANSCRIPTION FACTOR; GAMMA-TOCOPHEROL; OXIDATIVE STRESS; FACTOR-ALPHA; EXPOSURE; SUSCEPTIBILITY AB Ozone (O-3) is a strong oxidant in air pollution that has harmful effects on airways and exacerbates respiratory disorders. The transcription factor Nrf2 protects airways from oxidative stress through antioxidant response element-bearing defense gene induction. The present study was designed to determine the role of Nrf2 in airway toxicity caused by inhaled O-3 in mice. For this purpose, Nrf2-deficient (Nrf2(-/-)) and wild-type (Nrf2(+/+)) mice received acute and subacute exposures to O-3. Lung injury was determined by bronchoalveolar lavage and histopathologic analyses. Oxidation markers and mucus hypersecretion were determined by ELISA, and Nrf2 and its downstream effectors were determined by RT-PCR and/or Western blotting. Acute and subacute O-3 exposures heightened pulmonary inflammation, edema, and cell death more severely in Nrf2(-/-) mice than in Nrf2(+/+) mice. O-3 caused bronchiolar and terminal bronchiolar proliferation in both genotypes of mice, while the intensity of compensatory epithelial proliferation, bronchial mucous cell hyperplasia, bronchial mucous hypersecretion was greater in Nrf2(-/-) mice than in Nrf2(+/+) mice. Relative to Nrf2(+/+), O-3 augmented lung protein and lipid oxidation more highly in Nrf2(-/-) mice. Results suggest that Nrf2 deficiency exacerbates oxidative stress and airway injury caused by the environmental pollutant O-3. C1 [Cho, Hye-Youn; Gladwell, Wesley; Kleeberger, Steven R.] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Tohoku Univ, Grad Sch Med, Sendai, Miyagi 9808575, Japan. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov RI Yamamoto, Masayuki/A-4873-2010 FU Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services. This research was supported by the Intramural Research Program of the NIEHS, NIH, Department of Health and Human Services. O3 exposures were conducted at Alion Science and Technology Inc. The authors thank Dr. Daniel Morgan and Mr. Herman Price for coordinating the inhalation exposures. Drs. Donald Cook and Mike Fessler of the NIEHS provided excellent critical review of the paper. NR 55 TC 8 Z9 9 U1 1 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR 254069 DI 10.1155/2013/254069 PG 14 WC Cell Biology SC Cell Biology GA 147IB UT WOS:000319158900001 ER PT J AU Heiss, JD AF Heiss, J. D. TI The AAV-GDNF Clinical Trial for PD SO CELL TRANSPLANTATION LA English DT Meeting Abstract C1 [Heiss, J. D.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2013 VL 22 IS 5 BP 904 EP 904 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 139LX UT WOS:000318585300045 ER PT J AU Li, Q Schwender, H Louis, TA Fallin, MD Ruczinski, I AF Li, Qing Schwender, Holger Louis, Thomas A. Fallin, M. Daniele Ruczinski, Ingo TI Efficient Simulation of Epistatic Interactions in Case-Parent Trios SO HUMAN HEREDITY LA English DT Article DE Case-parent trios; Interactions; Single nucleotide polymorphisms; Haplotypes ID GENE-GENE INTERACTIONS; MULTIFACTOR DIMENSIONALITY REDUCTION; FAMILY-BASED ASSOCIATION; NEURAL-NETWORK ARCHITECTURE; QUANTITATIVE TRAIT LOCI; DISCORDANT SIB PAIRS; ENVIRONMENT INTERACTIONS; LINKAGE DISEQUILIBRIUM; LOGIC REGRESSION; RANDOM FORESTS AB Statistical approaches to evaluate interactions between single nucleotide polymorphisms (SNPs) and SNP-environment interactions are of great importance in genetic association studies, as susceptibility to complex disease might be related to the interaction of multiple SNPs and/or environmental factors. With these methods under active development, algorithms to simulate genomic data sets are needed to ensure proper type I error control of newly proposed methods and to compare power with existing methods. In this paper we propose an efficient method for a haplotype-based simulation of case-parent trios when the disease risk is thought to depend on possibly higher-order epistatic interactions or gene-environment interactions with binary exposures. Copyright (C) 2013 S. Karger AG, Basel C1 [Li, Qing] NHGRI, Stat Genet Sect, NIH, Baltimore, MD USA. [Schwender, Holger] Univ Dusseldorf, Inst Math, Dusseldorf, Germany. [Louis, Thomas A.; Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Fallin, M. Daniele] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. RP Ruczinski, I (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. EM ingo@jhu.edu FU Deutsche Forschungsgemeinschaft [SCHW 1508/3-1]; National Institutes of Health [R03 DE021437]; CTSA grant FX Support was provided by the Deutsche Forschungsgemeinschaft (SCHW 1508/3-1 to H.S.), the National Institutes of Health (R03 DE021437 to I.R.), and a CTSA grant to the Johns Hopkins Medical Institutions. NR 73 TC 1 Z9 1 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2013 VL 75 IS 1 BP 12 EP 22 DI 10.1159/000348789 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 140XD UT WOS:000318688900003 PM 23548797 ER PT J AU Gorden, A Yang, RZ Yerges-Armstrong, LM Ryan, KA Speliotes, E Borecki, IB Harris, TB Chu, X Wood, GC Still, CD Shuldiner, AR Gerhard, GS AF Gorden, Alexis Yang, Rongze Yerges-Armstrong, Laura M. Ryan, Kathleen A. Speliotes, Elizabeth Borecki, Ingrid B. Harris, Tamara B. Chu, Xin Wood, G. Craig Still, Christopher D. Shuldiner, Alan R. Gerhard, Glenn S. CA GOLD Consortium TI Genetic Variation at NCAN Locus Is Associated with Inflammation and Fibrosis in Non-Alcoholic Fatty Liver Disease in Morbid Obesity SO HUMAN HEREDITY LA English DT Article DE Obesity; Dyslipidemia; Steatohepatitis; Cirrhosis; Steatosis ID CHONDROITIN SULFATE PROTEOGLYCAN; VLDL-TRIGLYCERIDE SECRETION; HEPATIC STEATOSIS; CELL-ADHESION; BARIATRIC SURGERY; LIPID-METABOLISM; GASTRIC BYPASS; NERVOUS-SYSTEM; RISK-FACTORS; LOW-DENSITY AB Objective: Obesity-associated non-alcoholic fatty liver disease (NAFLD) may cause liver dysfunction and failure. In a previously reported genome-wide association meta-analysis, single nucleotide polymorphisms (SNPs) near PNPLA3, NCAN, GCKR, LYPLAL1 and PPP1R3B were associated with NAFLD and with distinctive serum lipid profiles. The present study examined the relevance of these variants to NAFLD in extreme obesity. Methods: In 1,092 bariatric surgery patients, the candidate SNPs were genotyped and association analyses with liver histology and serum lipids were performed. Results: We replicated the association of hepatosteatosis with PNPLA3 rs738409[G] and with NCAN rs2228603[T]. We also replicated the association of rs2228603[T] with hepatic inflammation and fibrosis. rs2228603[T] was associated with lower serum low-density lipoprotein, total cholesterol and triglycerides. After stratification by the presence or absence of NAFLD, these associations were present predominantly in the subgroup with NAFLD. Conclusion: NCAN rs2228603[T] is a risk factor for liver inflammation and fibrosis, suggesting that this locus is responsible for progression from steatosis to steatohepatitis. In this bariatric cohort, rs2228603[T] was associated with low serum lipids only in patients with NAFLD. This supports a NAFLD model in which the liver may sequester triglycerides as a result of either increased triglyceride uptake and/or decreased lipolysis. Copyright (C) 2013 S. Karger AG, Basel C1 [Gorden, Alexis] Univ Maryland, Sch Med, Div Gastroenterol, Baltimore, MD 21201 USA. [Yang, Rongze; Yerges-Armstrong, Laura M.; Ryan, Kathleen A.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Yang, Rongze; Yerges-Armstrong, Laura M.; Ryan, Kathleen A.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Speliotes, Elizabeth] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Chu, Xin; Wood, G. Craig; Still, Christopher D.; Gerhard, Glenn S.] Weis Ctr Res, Geisinger Clin, Obes Inst, Danville, PA 17822 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. RP Gerhard, GS (reprint author), Penn State Univ, Coll Med, Inst Personalized Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. EM ggerhard@hmc.psu.edu RI Hernaez, Ruben/C-4039-2014; Gudnason, Vilmundur/K-6885-2015; Feitosa, Mary/K-8044-2012; Smith, Albert Vernon/K-5150-2015 OI Hernaez, Ruben/0000-0002-1518-4020; Gudnason, Vilmundur/0000-0001-5696-0084; Feitosa, Mary/0000-0002-0933-2410; Smith, Albert Vernon/0000-0003-1942-5845 FU NIH [R01 DK088231, DK091601, T32 DK067872, F32 DK093267, F32 AR59469, K23 DK080145]; Obesity Research Institute of Geisinger Medical Center; Mid-Atlantic Nutrition and Obesity Research Center [NIH P30 DK072488]; Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC); Biological Scholars Program; University of Michigan; Ethicon-Endosurgery FX This work was supported by NIH R01 DK088231 and DK091601, the Obesity Research Institute of Geisinger Medical Center, the Mid-Atlantic Nutrition and Obesity Research Center (NIH P30 DK072488), and the Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC). Dr. A. Gorden was supported by NIH T32 DK067872 and is currently supported by NIH F32 DK093267. Dr. L.M. Yerges-Armstrong is supported by NIH F32 AR59469. Dr. E. Speliotes is supported by NIH K23 DK080145, the Biological Scholars Program and other funds from the University of Michigan.; Dr. C. D. Still receives grant and consulting support from Ethicon-Endosurgery. NR 43 TC 39 Z9 40 U1 2 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2013 VL 75 IS 1 BP 34 EP 43 DI 10.1159/000346195 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 140XD UT WOS:000318688900005 PM 23594525 ER PT J AU Kim, J Chang, PH Park, HS AF Kim, Jonghyun Chang, Pyung Hun Park, Hyung-Soon TI Two-Channel Transparency-Optimized Control Architectures in Bilateral Teleoperation With Time Delay SO IEEE TRANSACTIONS ON CONTROL SYSTEMS TECHNOLOGY LA English DT Article DE Bilateral control; switched delay system; teleoperation; telerobotics; time delay; transparency-optimized control architecture (TOCA); two-channel architecture ID STABILITY ROBUSTNESS; TELEPRESENCE SYSTEMS; TELEMANIPULATION; ENVIRONMENTS; IMPEDANCE; FEEDBACK; DESIGN; ARM AB This paper introduces transparency-optimized control architectures (TOCAs) using two communication channels. Two classes of two-channel TOCAs are found, thereby showing that two channels are sufficient to achieve transparency. These TOCAs achieve a greater level of transparency but poorer stability than three-channel TOCAs and four-channel TOCAs. Stability of the two-channel TOCAs has been enhanced while minimizing transparency degradation by adding a filter; and a combined use of the two classes of two-channel TOCAs is proposed for both free space and constrained motion, which involve switching between two TOCAs for transition between free space and constrained motions. The stability condition of the switched teleoperation system is derived for practical applications. Through the one degree-of-freedom (DOF) experiment, the proposed two-channel TOCAs were shown to operate stably, while achieving better transparency under time delay than the other TOCAs. C1 [Kim, Jonghyun; Park, Hyung-Soon] NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. [Chang, Pyung Hun] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. RP Kim, J (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20892 USA. EM parkhs@cc.nih.gov RI Park, Hyung-Soon/B-3334-2010 OI Park, Hyung-Soon/0000-0003-4274-7420 FU Intramural Research Program of the National Institutes of Health (NIH); Clinical Research Center; DGIST R&D Program of the Ministry of Education, Science, and Technology of Korea [11-BD-0402] FX Manuscript received July 08, 2011; accepted October 01, 2011. Manuscript received in final form October 14, 2011. Date of publication November 11, 2011; date of current version December 14, 2012. Recommended by Associate Editor M. Zefran. This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), by the Clinical Research Center, and by the DGIST R&D Program of the Ministry of Education, Science, and Technology of Korea (11-BD-0402). NR 29 TC 19 Z9 20 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1063-6536 EI 1558-0865 J9 IEEE T CONTR SYST T JI IEEE Trans. Control Syst. Technol. PD JAN PY 2013 VL 21 IS 1 BP 40 EP 51 DI 10.1109/TCST.2011.2172945 PG 12 WC Automation & Control Systems; Engineering, Electrical & Electronic SC Automation & Control Systems; Engineering GA 139IP UT WOS:000318576100004 PM 23833548 ER PT J AU Howden, R Gougian, E Lawrence, M Cividanes, S Gladwell, W Miller-DeGraff, L Myers, PH Rouse, DC Devlin, RB Cho, HY Kleeberger, SR AF Howden, Reuben Gougian, Eva Lawrence, Marcus Cividanes, Samantha Gladwell, Wesley Miller-DeGraff, Laura Myers, Page H. Rouse, D. Clay Devlin, Robert B. Cho, Hye-Youn Kleeberger, Steven R. TI The Influence of Nrf2 on Cardiac Responses to Environmental Stressors SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Article ID PARTICULATE AIR-POLLUTION; HEART-RATE-VARIABILITY; DIESEL EXHAUST PARTICLES; ACUTE LUNG INJURY; OXIDATIVE STRESS; ULTRAFINE PARTICLES; CARDIOVASCULAR-DISEASE; EXTRACELLULAR-MATRIX; ANTIOXIDANT DEFENSE; PULMONARY RESPONSE AB Nrf2 protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role of Nrf2 on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption of Nrf2 would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures. Nrf2(-/-) and Nrf2(+/+) mice were instrumented for continuous ECG recording to calculate HR and HRV (low frequency (LF), high frequency (HF), and total power (TP)). Mice were then either exposed to hyperoxia for up to 72 hrs or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P < 0.001) and HF HRV (P < 0.001) in Nrf2(-/-) mice compared to Nrf2(+/+) mice Nrf2(-/-) mice tolerated hyperoxia significantly less than Nrf2(+/+) mice (similar to 22 hrs; P < 0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater in Nrf2(-/-) compared to Nrf2(+/+) mice (P < 0.01). Results demonstrate that Nrf2 deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations. C1 [Howden, Reuben; Lawrence, Marcus; Cividanes, Samantha] Univ N Carolina, Dept Kinesiol, Lab Syst Physiol, Charlotte, NC 28223 USA. [Gougian, Eva; Gladwell, Wesley; Miller-DeGraff, Laura; Cho, Hye-Youn; Kleeberger, Steven R.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. [Myers, Page H.] Natl Inst Hlth, Natl Inst Environm Hlth Sci, Comparat Med Branch, Res Triangle Pk, NC USA. [Rouse, D. Clay] Duke Univ, Med Ctr, Div Lab Anim Resources, Durham, NC USA. [Devlin, Robert B.] US EPA, Res Triangle Pk, NC 27711 USA. RP Howden, R (reprint author), Univ N Carolina, Dept Kinesiol, Lab Syst Physiol, Charlotte, NC 28223 USA. EM rhowden@uncc.edu FU Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services FX This research was supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services. The contents of this publication do not necessarily reflect the views and policies of the US Environmental Protection Agency. NR 71 TC 1 Z9 1 U1 1 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR 901239 DI 10.1155/2013/901239 PG 10 WC Cell Biology SC Cell Biology GA 141MH UT WOS:000318728800001 ER PT J AU Ling, X Li, FZ AF Ling, Xiang Li, Fengzhi TI An intravenous (i.v.) route-compatible formulation of FL118, a survivin, Mcl-1, XIAP, and cIAP2 selective inhibitor, improves FL118 antitumor efficacy and therapeutic index (TI) SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Article DE FL118; maximum tolerated doses (MTD); antitumor activity; human tumor animal model; intravenous (i.v.); intraperitoneal (i.p.) ID X-LINKED INHIBITOR; CELL LUNG-CANCER; APOPTOSIS-INDUCING LIGAND; NF-KAPPA-B; ACUTE LYMPHOBLASTIC-LEUKEMIA; DOWN-REGULATION; UP-REGULATION; PROSTATE-CANCER; MEDIATED APOPTOSIS; CONFERS RESISTANCE AB We recently reported a novel anticancer small molecule, designated FL118, which was discovered via high throughput screening (HTS), and followed by hit-lead in vitro and in vivo analysis. FL118 selectively inhibits the expression of four major cancer survival-associated gene products (survivin, Mcl-1, XIAP, and cIAP2) and shows promising antitumor activity in animal models of human cancers when administered using a weekly x 4 schedule (Ling et al., PLOS ONE. 2012, 7: e45571). Here, we compared the antitumor efficacy and therapeutic index (TI) of FL118 in a newly developed Tween 80-free formulation that can be delivered intravenously (i.v.) and intraperitoneally (i.p.) against the previous Tween 80-containing formulation that can only be delivered via an i.p. route. We found that the maximum tolerated dose (MTD) for FL118 in the i.v. formulation increases 3-7 fold in comparison with the MTD of FL118 in the i.p. formulation. FL118 in the i.v. recipe was able to eliminate human tumor xenografts in all three major schedules tested (daily x 5, q2 x 5 and weekly x 5). In contrast, FL118 was able to eliminate human tumor xenografts in the i.p. formulation only with the weekly x 4 schedule previously reported. The TI of FL118 in the i.v. formulation reached 5-6 in the most effective schedule, while the TI of FL118 in the i.p. formulation was only 1.3 -2. These findings overcome several clinical challenges including FL118 formulation to realize clinically compatible drug administration routes, and expanding effective treatment schedules. The striking improvement of the TI makes FL118 a much safer drug for further development toward clinical trials. C1 [Ling, Xiang; Li, Fengzhi] Roswell Pk Canc Inst, Dept Pharmacol, Buffalo, NY 14263 USA. [Ling, Xiang; Li, Fengzhi] Roswell Pk Canc Inst, Dept Therapeut, Buffalo, NY 14263 USA. [Li, Fengzhi] Roswell Pk Canc Inst, NCI CCSG Supported Expt Therapeut ET Program, Buffalo, NY 14263 USA. RP Li, FZ (reprint author), Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Elm & Carlton St,CGP L4-301, Buffalo, NY 14263 USA. EM fengzhi.li@roswellpark.org FU US Army Department of Defense (DOD) [PC110408]; Mesothelioma Applied Research Foundation (Alexandria, VA); Roswell Park Alliance Foundation; NCI Cancer Center Support Grant [CA016056] FX This work was sponsored in part by grants from the US Army Department of Defense (DOD, PC110408), Mesothelioma Applied Research Foundation (Alexandria, VA), and the Roswell Park Alliance Foundation to FL, and by shared resources supported by NCI Cancer Center Support Grant to Roswell Park Cancer Institute (CA016056). Of note, SC was partially paid by grants from FL during this work. We thank Dr. Shousong Cao (SC) for his help in some of animal experiments in this work. The authors would like to thank the Faculty Writing Group from the Pharmacology & Therapeutics Department of Roswell Park Cancer Institute for critically reading and commenting on this manuscript. These authors would also like to thank Dr. Suzanne M. Hess (Research Support Services, Roswell Park Cancer Institute, Buffalo NY) for critically reading and revising this manuscript. Finally, we would like to thank the Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program (DTP), Division of Cancer Treatment and Diagnosis, National Cancer Institute (NCI) for providing chemical libraries and relevant hit analogs in the public domain they collected and/or synthesized as major compound sources during the process of drug screening and characterization. NR 87 TC 8 Z9 9 U1 1 U2 8 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2013 VL 5 IS 2 BP 139 EP 154 PG 16 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA 135IH UT WOS:000318281300004 PM 23573360 ER PT J AU Abu-Asab, MS Abu-Asab, N Loffredo, CA Clarke, R Amri, H AF Abu-Asab, M. S. Abu-Asab, N. Loffredo, C. A. Clarke, R. Amri, H. TI Identifying Early Events of Gene Expression in Breast Cancer with Systems Biology Phylogenetics SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article DE Cancer; Early events; Heterogeneity; Parsimony; Phylogenetics; Synapomorphies; Systems biology ID EPIGENETIC HETEROGENEITY; MEDICINE; ACCUMULATION; EPITHELIUM; MUTATIONS; THERAPY; GENOME AB Advanced omics technologies such as deep sequencing and spectral karyotyping are revealing more of cancer heterogeneity at the genetic, genomic, gene expression, epigenetic, proteomic, and metabolomic levels. With this increasing body of emerging data, the task of data analysis becomes critical for mining and modeling to better understand the relevant underlying biological processes. However, the multiple levels of heterogeneity evident within and among populations, healthy and diseased, complicate the mining and interpretation of biological data, especially when dealing with hundreds to tens of thousands of variables. Heterogeneity occurs in many diseases, such as cancers, autism, macular degeneration, and others. In cancer, heterogeneity has hampered the search for validated biomarkers for early detection, and it has complicated the task of finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We show that subtyping of cancer (classification of specimens) should be an a priori step to the identification of early events of cancers. Studying early events in oncogenesis can be done on histologically normal tissues from diseased individuals (HNTDI), since they most likely have been exposed to the same mutagenic insults that caused the cancer in their neighboring tissues. Polarity assessment of HNTDI data variables by using healthy specimens as outgroup(s), followed by the application of parsimony phylogenetic analysis, produces a hierarchical classification of specimens that reveals the early events of the disease ontogeny within its subtypes as shared derived changes (abnormal changes) or synapomorphies in phylogenetic terminology. Copyright (C) 2013 S. Karger AG, Basel C1 [Abu-Asab, M. S.] NEI, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. [Loffredo, C. A.] Georgetown Univ, Sch Med, Dept Biostat Bioinformat & Biomath, Washington, DC USA. [Loffredo, C. A.; Clarke, R.] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20005 USA. [Amri, H.] Georgetown Univ, Sch Med, Dept Biochem Cellular & Mol Biol, Washington, DC 20057 USA. [Abu-Asab, N.] Univ New England, Armidale Rural Referral Hosp, Armidale, NSW, Australia. [Abu-Asab, N.] Univ Newcastle, Armidale, NSW, Australia. RP Amri, H (reprint author), Georgetown Univ, Sch Med, Dept Biochem Cellular & Mol Biol, 217 Basic Sci Bldg,3900 Reservoir Rd, Washington, DC 20057 USA. EM amrih@georgetown.edu RI Clarke, Robert/A-6485-2008; OI Clarke, Robert/0000-0002-9278-0854; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 EY999999]; NCI NIH HHS [U54 CA149147] NR 31 TC 5 Z9 6 U1 0 U2 9 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2013 VL 139 IS 3 BP 206 EP 214 DI 10.1159/000348433 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 137YS UT WOS:000318475100009 PM 23548567 ER PT J AU Farmer, C Thurm, A Grant, P AF Farmer, Cristan Thurm, Audrey Grant, Paul TI Pharmacotherapy for the Core Symptoms in Autistic Disorder: Current Status of the Research SO DRUGS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; OPEN-LABEL TRIAL; CONTROLLED CROSSOVER TRIAL; CONTROLLED PILOT TRIAL; BEHAVIOR RATING FORM; SPECTRUM DISORDERS; DOUBLE-BLIND; REPETITIVE BEHAVIORS; PSYCHIATRIC-DISORDERS AB The current review covers extant literature on pharmacotherapy for core symptoms of autism. The core symptoms of autism include impairments in social interaction and communication, as well as the presence of restricted and repetitive behaviors. There are no known efficacious treatments for the core social symptoms, although effects on repetitive behaviors are indicated with some data. While studies of fenfluramine, secretin, opiates, and mood stabilizers generally find no effect, mixed results suggest more research is needed on antidepressants and atypical antipsychotics. Newer lines of research, including cholinergic and glutamatergic agents and oxytocin, will be of considerable interest in the future. However, research on the treatment of core symptoms is plagued by limitations in study design, statistical power, and other issues inherent to the study of treatments for autism (e.g., heterogeneity of the disorder) that continue to prevent the elucidation of efficacious treatments. C1 [Farmer, Cristan; Thurm, Audrey; Grant, Paul] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA. RP Farmer, C (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr MSC 1255,Bldg 10,Room 1C250, Bethesda, MD 20892 USA. EM farmerca@mail.nih.gov FU National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH) FX This work was supported by the Intramural Program of the National Institute of Mental Health (NIMH) of the National Institutes of Health (NIH). The views expressed in this article do not necessarily represent the views of the NIMH, NIH, the Department of Health and Human Services, or the United States Government. The authors have no conflicts of interest to report. NR 92 TC 18 Z9 19 U1 4 U2 26 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 2013 VL 73 IS 4 BP 303 EP 314 DI 10.1007/s40265-013-0021-7 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 138UP UT WOS:000318535800002 PM 23504356 ER PT S AU Agarwal, SK AF Agarwal, Sunita K. BE Stratakis, CA TI Multiple Endocrine Neoplasia Type 1 SO ENDOCRINE TUMOR SYNDROMES AND THEIR GENETICS SE Frontiers of Hormone Research LA English DT Review; Book Chapter ID HISTONE METHYLTRANSFERASE COMPLEX; TUMOR-SUPPRESSOR MENIN; MISSENSE MUTANTS; FACTOR JUND; GENE; EXPRESSION; MLL; TRANSCRIPTION; BINDING; PROTEIN AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant tumor syndrome characterized by the occurrence of tumors in multiple endocrine tissues and nonendocrine tissues. The three main endocrine tissues most frequently affected by tumors are parathyroid (95%), enteropancreatic neuroendocrine (50%) and anterior pituitary (40%). Tumors are caused by a heterozygous germline-inactivating mutation in the MEN1 gene (1st hit) followed by somatic inactivating mutation or loss of the normal copy of the gene (2nd hit), leading to complete loss of function of the encoded protein menin. Most of the disease features and tumors are recapitulated in mouse models with heterozygous germline loss of the Men1 gene. Also, tissue-specific tumors are observed in mouse models with homozygous somatic loss of the Men1 gene specifically in MEN1-associated endocrine tissues. Hence, mouse models could serve as possible surrogates for studying MEN1 and related states. To gain insights into MEN1 pathophysiology, menin-interacting partners and pathways have been identified to investigate its tumor suppressor and other functions. Also, the 3D crystal structure of menin has been deciphered which could be useful to reveal the relevance of MEN1 gene mutations and menin's interactions. This chapter covers clinical, genetic and basic findings about the MEN1 syndrome, MEN1 gene and its product protein menin. Copyright (C) 2013 S. Karger AG, Basel C1 NIDDK, NIH, Metab Dis Branch, Bethesda, MD 20892 USA. RP Agarwal, SK (reprint author), NIDDK, NIH, Metab Dis Branch, Bldg 10,Room 8C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SunitaA@mail.nih.gov RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 FU Intramural NIH HHS; PHS HHS [1ZIADK075035-03] NR 39 TC 20 Z9 21 U1 0 U2 6 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 978-3-318-02330-5 J9 FRONT HORM RES JI Front.Horm.Res. PY 2013 VL 41 BP 1 EP 15 DI 10.1159/000345666 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BEY64 UT WOS:000318737500003 PM 23652667 ER PT S AU Lodish, M AF Lodish, Maya BE Stratakis, CA TI Multiple Endocrine Neoplasia Type 2 SO ENDOCRINE TUMOR SYNDROMES AND THEIR GENETICS SE Frontiers of Hormone Research LA English DT Review; Book Chapter ID MEDULLARY-THYROID CARCINOMA; RET PROTOONCOGENE; PRIMARY HYPERPARATHYROIDISM; PROGNOSTIC-FACTORS; MEN 2A; TRANSFORMING GENE; SPARING SURGERY; PHEOCHROMOCYTOMA; CANCER; 2B AB Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter. Copyright (C) 2013 S. Karger AG, Basel C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Lodish, M (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bldg 10-CRC,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov NR 51 TC 5 Z9 5 U1 0 U2 3 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-3073 BN 978-3-318-02330-5 J9 FRONT HORM RES JI Front.Horm.Res. PY 2013 VL 41 BP 16 EP 29 DI 10.1159/000345667 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BEY64 UT WOS:000318737500004 PM 23652668 ER PT J AU Nishijima, T Takano, M Ishisaka, M Komatsu, H Gatanaga, H Kikuchi, Y Endo, T Horiba, M Kaneda, S Uchiumi, H Koibuchi, T Naito, T Yoshida, M Tachikawa, N Ueda, M Yokomaku, Y Fujii, T Higasa, S Takada, K Yamamoto, M Matsushita, S Tateyama, M Tanabe, Y Mitsuya, H Oka, S AF Nishijima, Takeshi Takano, Misao Ishisaka, Michiyo Komatsu, Hirokazu Gatanaga, Hiroyuki Kikuchi, Yoshimi Endo, Tomoyuki Horiba, Masahide Kaneda, Satoru Uchiumi, Hideki Koibuchi, Tomohiko Naito, Toshio Yoshida, Masaki Tachikawa, Natsuo Ueda, Mikio Yokomaku, Yoshiyuki Fujii, Teruhisa Higasa, Satoshi Takada, Kiyonori Yamamoto, Masahiro Matsushita, Shuzo Tateyama, Masao Tanabe, Yoshinari Mitsuya, Hiroaki Oka, Shinichi CA Epzicom-Truvada Study Team TI Abacavir/Lamivudine versus Tenofovir/Emtricitabine with Atazanavir/Ritonavir for Treatment-naive Japanese Patients with HIV-1 Infection: A Randomized Multicenter Trial SO INTERNAL MEDICINE LA English DT Article DE HIV-1 infection; tenofovir/emtricitabine; abacavir/lamivudine; ritonavir-boosted atazanavir; treatment-naive Asian patients; HLA-B*5701-negative ID TENOFOVIR DISOPROXIL FUMARATE; ANTIRETROVIRAL-NAIVE; ABACAVIR HYPERSENSITIVITY; MYOCARDIAL-INFARCTION; TUBULAR DYSFUNCTION; RENAL SAFETY; THERAPY; HLA-B-ASTERISK-5701; EMTRICITABINE; METAANALYSIS AB Objective To compare the efficacy and safety of fixed-dose abacavir/lamivudine (ABC/3TC) and tenofovir/ emtricitabine (TDF/FTC) with ritonavir-boosted atazanavir (ATV/r) in treatment-nave Japanese patients with HIV-1 infection. Methods A 96-week multicenter, randomized, open-label, parallel group pilot study was conducted. The endpoints were times to virologic failure, safety event and regimen modification. Results 109 patients were enrolled and randomly allocated (54 patients received ABC/3TC and 55 patients received TDF/FTC). All randomized subjects were analyzed. The time to virologic failure was not significantly different between the two arms by 96 weeks (HR, 2.09; 95% CI, 0.72-6.13; p=0.178). Both regimens showed favorable viral efficacy, as in the intention-to-treat population, 72.2% (ABC/3TC) and 78.2% (TDF/FTC) of the patients had an HIV-1 viral load <50 copies/mL at 96 weeks. The time to the first grade 3 or 4 adverse event and the time to the first regimen modification were not significantly different between the two arms (adverse event: HR 0.66; 95% CI, 0.25-1.75, p=0.407) (regimen modification: HR 1.03; 95% CI, 0.33-3.19, p=0.964). Both regimens were also well-tolerated, as only 11.1% (ABC/3TC) and 10.9% (TDF/FTC) of the patients discontinued the allocated regimen by 96 weeks. Clinically suspected abacavir-associated hyper-sensitivity reactions occurred in only one (1.9%) patient in the ABC/3TC arm. Conclusion Although insufficiently powered to show non-inferiority of viral efficacy of ABC/3TC relative to TDF/FTC, this pilot trial suggested that ABC/3TC with ATV/r is a safe and efficacious initial regimen for HLA-B*5701-negative patients, such as the Japanese population. C1 [Nishijima, Takeshi; Gatanaga, Hiroyuki; Matsushita, Shuzo; Oka, Shinichi] Kumamoto Univ, Grad Sch Med Sci, Ctr AIDS Res, Kumamoto 860, Japan. [Komatsu, Hirokazu] Saku Cent Hosp, Dept Community Care, Saku, Japan. [Endo, Tomoyuki] Hokkaido Univ Hosp, Dept Hematol, Sapporo, Hokkaido, Japan. [Horiba, Masahide] Higashisaitama Natl Hosp, Div Resp Med, Saitama, Japan. [Kaneda, Satoru] Natl Hosp Org Chiba Med Ctr, Dept Gastroenterol, Chiba, Japan. [Uchiumi, Hideki] Gunma Univ, Grad Sch Med, Dept Med & Clin Sci, Gunma, Japan. [Koibuchi, Tomohiko] Univ Tokyo, Inst Med Sci, Res Hosp, Dept Infect Dis & Appl Immunol, Tokyo 1138654, Japan. [Naito, Toshio] Juntendo Univ, Sch Med, Dept Gen Med, Tokyo, Japan. [Yoshida, Masaki] Jikei Univ, Sch Med, Dept Infect Dis & Infect Control, Tokyo, Japan. [Tachikawa, Natsuo] Yokohama Municipal Citizens Hosp, Dept Infect Dis, Yokohama, Kanagawa, Japan. [Ueda, Mikio] Ishikawa Prefectural Cent Hosp, Ishikawa, Japan. [Yokomaku, Yoshiyuki] Natl Hosp Org Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan. [Fujii, Teruhisa] Hiroshima Univ Hosp, Div Blood Transfus, Hiroshima, Japan. [Higasa, Satoshi] Hyogo Coll Med, Dept Internal Med, Div Hematol, Kobe, Hyogo, Japan. [Takada, Kiyonori] Ehime Univ Hosp, Postgrad Clin Training Ctr, Matsuyama, Ehime, Japan. [Tateyama, Masao] Univ Ryukyus, Fac Med, Dept Infect Resp & Digest Med Control & Prevent I, Nishihara, Okinawa 90301, Japan. [Tanabe, Yoshinari] Niigata Univ, Med & Dent Hosp, Div Infect Control & Prevent, Niigata 95021, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto 860, Japan. [Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto 860, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. EM oka@acc.ncgm.go.jp RI Kumamoto University, CAIDS/G-8446-2013; Matsushita, Shuzo/F-5782-2013 NR 31 TC 9 Z9 10 U1 0 U2 9 PU JAPAN SOC INTERNAL MEDICINE PI TOKYO PA 34-3 3-CHOME HONGO BUNKYO-KU, TOKYO, 113, JAPAN SN 0918-2918 J9 INTERNAL MED JI Intern. Med. PY 2013 VL 52 IS 7 BP 735 EP 744 DI 10.2169/internalmedicine.52.9155 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 134WJ UT WOS:000318246200005 PM 23545667 ER PT J AU Fan, MY Pfeffer, SR Lynch, HT Cassidy, P Leachman, S Pfeffer, LM Kopelovich, L AF Fan, Meiyun Pfeffer, Susan R. Lynch, Henry T. Cassidy, Pamela Leachman, Sancy Pfeffer, Lawrence M. Kopelovich, Levy TI Altered transcriptome signature of phenotypically normal skin fibroblasts heterozygous for CDKN2A in familial melanoma: relevance to early intervention SO ONCOTARGET LA English DT Article DE Familial Melanoma; gene expression; CDKN2A; p16; Mutations; Melanoma ID PANCREATIC-CANCER; GENE-EXPRESSION; KAPPA-B; MUTATIONS; P16; INTERFERON; CELLS AB Familial melanoma (FM) is a dominantly heritable cancer that is associated with mutations in the tumor suppressor CDKN2A/p16. In FM, a single inherited "hit" occurs in every somatic cell, enabling interrogation of cultured normal skin fibroblasts (SFs) from FM gene carriers as surrogates for the cell of tumor origin, namely the melanocyte. We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma. We show an altered transcriptome signature in normal SFs bearing a single-hit inherited mutation in the CDKN2A/p16 gene, wherein some of these abnormal alterations recapitulate changes observed in the corresponding cancer. Significantly, the extent of the alterations is mutation-site specific with the R87P-p16 mutation being more disruptive than the V126D-p16 mutation. We also examined changes in gene expression after exposure to ultraviolet (UV) radiation to define potential early biomarkers triggered by sun exposure. UV treatment of SFs from FM families induces distinct alterations in genes related to cell cycle regulation and DNA damage responses that are also reported to be dysregulated in melanoma. Importantly, these changes were diametrically opposed to UV-induced changes in SF from normal controls. We posit that changes identified in the transcriptome of SF from FM mutation carriers represent early events critical for melanoma development. As such, they may serve as specific biomarkers of increased risk as well as molecular targets for personalized prevention strategies in high-risk populations. C1 [Fan, Meiyun; Pfeffer, Susan R.; Pfeffer, Lawrence M.] Univ Tennessee, Ctr Hlth Sci, Dept Pathol & Lab Med, Memphis, TN 38163 USA. [Fan, Meiyun; Pfeffer, Susan R.; Pfeffer, Lawrence M.] Univ Tennessee, Ctr Hlth Sci, Ctr Canc Res, Memphis, TN 38163 USA. [Lynch, Henry T.] Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. [Cassidy, Pamela; Leachman, Sancy] Univ Utah, Melanoma & Cutaneous Oncol Program, Huntsman Canc Inst, Salt Lake City, UT USA. [Cassidy, Pamela; Leachman, Sancy] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Kopelovich, L (reprint author), NCI, Canc Prevent Div, Bethesda, MD 20892 USA. EM lpfeffer@uthsc.edu; kopelovich@nih.gov FU National Cancer Institute [HHSN261200433000C]; Muirhead Chair Endowment at the University of Tennessee Health Science Center FX This work was supported by National Cancer Institute HHSN261200433000C and by funds from the Muirhead Chair Endowment at the University of Tennessee Health Science Center. We thank Judy Fay for editorial assistance. NR 31 TC 4 Z9 4 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2013 VL 4 IS 1 BP 128 EP 141 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 138IB UT WOS:000318501100015 PM 23371019 ER PT J AU Bourboulia, D Han, HY Jensen-Taubman, S Gavil, N Isaac, B Wei, BY Neckers, L Stetler-Stevenson, WG AF Bourboulia, Dimitra Han, HuiYing Jensen-Taubman, Sandra Gavil, Noah Isaac, Biju Wei, Beiyang Neckers, Len Stetler-Stevenson, William G. TI TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells SO ONCOTARGET LA English DT Article DE TIMP-2; microarray analysis; E-cadherin; cell adhesion; tumor growth inhibition ID TISSUE INHIBITOR; METALLOPROTEINASE-2 TIMP-2; MATRIX METALLOPROTEINASES; TUMOR MICROENVIRONMENT; ANGIOGENESIS INHIBITOR; DOWN-REGULATION; BETA-CATENIN; GROWTH; INVASION; MECHANISM AB Tissue Inhibitor of Metalloproteinase 2 (TIMP-2) plays an essential role in regulating matrix remodeling, cell growth, differentiation, angiogenesis and apoptosis in vitro and in vivo. We have recently shown that TIMP-2-mediated inhibition of tumor growth is independent of matrix metalloproteinase-mediated mechanisms, and is a consequence of modulating both the tumor cells and the tumor microenvironment. In the current study we aim to identify the molecular pathways associated with these effects. We analyzed the transcriptional profile of the human lung cancer cell line A549 upon overexpression of TIMP-2 and Ala+TIMP-2 (mutant that does not inhibit MMP activity), and we found changes in gene expression predominantly related to decreased tumor development and metastasis. Increased E-cadherin expression in response to both TIMP-2 and Ala+TIMP-2 expression was confirmed by real time quantitative RT-PCR and immunoblotting. A549 cells treated with epidermal growth factor (EGF) displayed loss of cobblestone morphology and cell-cell contact, while cells overexpressing TIMP-2 or Ala+TIMP-2 were resistant to EGF-induced morphological changes. Moreover, exogenous treatment with recombinant Ala+TIMP-2 blocked EGF induced down-regulation of E-cadherin. In vivo, immunohistochemistry of A549 xenografts expressing either TIMP-2 or Ala+TIMP-2 demonstrated increased E-cadherin protein levels. More importantly, transcriptional profile analysis of tumor tissue revealed critical pathways associated with effects on tumor-host interaction and inhibition of tumor growth. In conclusion, we show that TIMP-2 promotes an anti-tumoral transcriptional profile in vitro and in vivo, including upregulation of E-cadherin, in A549 lung cancer cells. C1 [Bourboulia, Dimitra; Han, HuiYing; Jensen-Taubman, Sandra; Gavil, Noah; Isaac, Biju; Wei, Beiyang; Stetler-Stevenson, William G.] NCI, Radiat Oncol Branch, Ctr Canc Res, Adv Technol Ctr, Bethesda, MD 20892 USA. [Gavil, Noah] Bowdoin Coll, Brunswick, ME 04011 USA. [Isaac, Biju] Univ Miami, Ctr Computat Sci, Miami, FL USA. [Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM neckers@nih.gov; sstevenw@mail.nih.gov RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Gavil, Noah/0000-0003-4686-4181 FU NCI Center for Cancer Research Intramural Research Program [ZIA SC009179-22] FX This work was funded by the NCI Center for Cancer Research Intramural Research Program Grant # ZIA SC009179-22. NR 55 TC 15 Z9 17 U1 1 U2 3 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD JAN PY 2013 VL 4 IS 1 BP 166 EP 176 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 138IB UT WOS:000318501100018 PM 23371049 ER PT J AU Styn, MA Nukui, T Romkes, M Perkins, KA Land, SR Weissfeld, JL AF Styn, Mindi A. Nukui, Tomoko Romkes, Marjorie Perkins, Kenneth A. Land, Stephanie R. Weissfeld, Joel L. TI CYP2A6 Genotype and Smoking Behavior in Current Smokers Screened for Lung Cancer SO SUBSTANCE USE & MISUSE LA English DT Article DE smoking cessation; smoking initiation; cigarette smoking; genetics; cytochrome P450; nicotine metabolism ID GENETIC-VARIATION; NICOTINE; METABOLISM; PREDICTS; RATIO AB Functional CYP2A6 genetic variation partially determines nicotine metabolism. In 2005, we examined functional CYP2A6 variants associated with reduced metabolism (CYP2A6*2, CYP2A6*9, CYP2A6*4), smoking history, and change in smoking in 878 adult smokers undergoing lung cancer screening in an urban setting. At one year, 216 quit smoking for more than 30 days while 662 continued smoking. Compared to subjects who smoked 30 cigarettes per day at baseline, the odds of a reduced metabolism genotype was 52% higher in subjects smoking 20-29 cigarettes per day and 86% higher in subjects smoking less than 20 cigarettes per day (p-trend = 0.016). Reduced metabolism genotypes appeared unrelated to quitting. Though related to smoking dose, CYP2A6 may not influence cessation. C1 [Styn, Mindi A.] Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, Pittsburgh, PA 15261 USA. [Styn, Mindi A.; Weissfeld, Joel L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Nukui, Tomoko; Romkes, Marjorie] Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Pittsburgh, PA 15261 USA. [Romkes, Marjorie; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15261 USA. [Perkins, Kenneth A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Land, Stephanie R.] NCI, Tobacco Control Branch, Behav Res Program, Washington, DC USA. RP Styn, MA (reprint author), Univ Pittsburgh, Sch Nursing, Dept Hlth & Community Syst, 415 Victoria Bldg,3500 Victoria St, Pittsburgh, PA 15261 USA. EM mimst31@pitt.edu FU University of Pittsburgh Cancer Institute Specialized Program of Research Excellence in Lung Cancer [NCI P50 CA90440] FX This study received financial support from the University of Pittsburgh Cancer Institute Specialized Program of Research Excellence in Lung Cancer grant NCI P50 CA90440. NR 12 TC 2 Z9 2 U1 0 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2013 VL 48 IS 7 BP 490 EP 494 DI 10.3109/10826084.2013.778280 PG 5 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 137JX UT WOS:000318433000003 PM 23528144 ER PT J AU Eiden, RD Homish, GG Colder, CR Schuetze, P Gray, TR Huestis, MA AF Eiden, Rina D. Homish, Gregory G. Colder, Craig R. Schuetze, Pamela Gray, Teresa R. Huestis, Marilyn A. TI Changes in Smoking Patterns During Pregnancy SO SUBSTANCE USE & MISUSE LA English DT Article DE nicotine; pregnant smokers; expectancies; smoking trajectories; depression; stress ID MATERNAL SMOKING; DEPRESSIVE SYMPTOMS; DEVELOPMENTAL TRAJECTORIES; OUTCOME EXPECTANCIES; CIGARETTE-SMOKING; PRENATAL EXPOSURE; ALCOHOL RESEARCH; NEONATAL GROWTH; DRUG-USE; HOSTILITY AB This study examined trajectories of smoking during pregnancy among low-income smokers and differences on demographics, psychopathology, and smoking outcome expectancies among women with different smoking trajectories. The sample consisted of 215 urban pregnant smokers living in the United States. Results indicated four trajectories of smoking and significant changes over time within each trajectory. Persistent smokers had the highest demographic and mental health risks, reported higher craving compared to light smokers, and were more likely to endorse smoking to reduce negative affect, for state enhancement motives. Implications for intervention are discussed. The study was funded by the National Institute on Drug Abuse. C1 [Eiden, Rina D.] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14203 USA. [Homish, Gregory G.] SUNY Buffalo, Dept Hlth Behav, Buffalo, NY 14203 USA. [Colder, Craig R.] SUNY Buffalo, Buffalo, NY 14203 USA. [Schuetze, Pamela] SUNY Coll Buffalo, Buffalo, NY 14222 USA. [Gray, Teresa R.] NIDA, Baltimore, MD USA. [Huestis, Marilyn A.] NIDA, IRP, Baltimore, MD USA. RP Eiden, RD (reprint author), SUNY Buffalo, Res Inst Addict, 1021 Main St, Buffalo, NY 14203 USA. EM eiden@ria.buffalo.edu FU National Institute on Drug Abuse, National Institutes on Health [R01DA019632]; National Institute on Drug Abuse FX The study was funded by the National Institute on Drug Abuse.; We thank the families who participated in the study and research staff who were responsible for data collection. Special thanks to Dr. Amol Lele for collaboration on data collection and Dr. Gerard Connors for collaboration on the larger study. The study was made possible by a grant from the National Institute on Drug Abuse, National Institutes on Health (R01DA019632). NR 50 TC 8 Z9 8 U1 5 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2013 VL 48 IS 7 BP 513 EP 522 DI 10.3109/10826084.2013.787091 PG 10 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 137JX UT WOS:000318433000006 PM 23581507 ER PT J AU Huertas, A Das, SR Emin, M Sun, L Rifkind, JM Bhattacharya, J Bhattacharya, S AF Huertas, Alice Das, Shonit R. Emin, Memet Sun, Li Rifkind, Joseph M. Bhattacharya, Jahar Bhattacharya, Sunita TI Erythrocytes Induce Proinflammatory Endothelial Activation in Hypoxia SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE hypoxia; erythrocytes; endothelium; lung; inflammation ID NF-KAPPA-B; ALTITUDE PULMONARY-EDEMA; RED-BLOOD-CELLS; NITRIC-OXIDE; LUNG INFLAMMATION; OXIDATIVE STRESS; CYTOPLASMIC DOMAIN; HEME DEGRADATION; HEMOGLOBIN; MEMBRANE AB Although exposure to ambient hypoxia is known to cause proinflammatory vascular responses, the mechanisms initiating these responses are not understood. We tested the hypothesis that in systemic hypoxia, erythrocyte-derived H2O2 induces proinflammatory gene transcription in vascular endothelium. We exposed mice or isolated, perfused murine lungs to 4 hours of hypoxia (8% O-2). Leukocyte counts increased in the bronchoalveolar lavage. The expression of leukocyte adhesion receptors, reactive oxygen species, and protein tyrosine phosphorylation increased in freshly recovered lung endothelial cells (FLECs). These effects were inhibited by extracellular catalase and by the removal of erythrocytes, indicating that the responses were attributable to erythrocyte- derived H2O2. Concomitant nuclear translocation of the p65 subunit of NF-kappa B and hypoxia-inducible factor-1 alpha stabilization in FLECs occurred only in the presence of erythrocytes. Hemoglobin binding to the erythrocyte membrane protein, band 3, induced the release of H2O2 from erythrocytes and the p65 translocation in FLECs. These data indicate for the first time, to our knowledge, that erythrocytes are responsible for endothelial transcriptional responses in hypoxia. C1 [Huertas, Alice; Das, Shonit R.; Emin, Memet; Sun, Li; Bhattacharya, Jahar; Bhattacharya, Sunita] Columbia Univ, Lung Biol Lab, Div Pulm, Dept Med,Med Ctr, New York, NY 10032 USA. [Bhattacharya, Sunita] Columbia Univ, Med Ctr, Dept Pediat, New York, NY 10032 USA. [Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Bhattacharya, J (reprint author), Columbia Univ, Lung Biol Lab, Div Pulm, Dept Med,Med Ctr, 630 West 168th St,BB 17-1705, New York, NY 10032 USA. EM jb39@columbia.edu RI Huertas, Alice/E-8244-2017 OI Huertas, Alice/0000-0001-8545-747X FU National Heart, Lung, and Blood Institute through the National Institutes of Health [HL57556, HL36024, HL64896] FX This work was supported by National Heart, Lung, and Blood Institute grants HL57556, HL36024, and HL64896 (J.B.) through the National Institutes of Health. NR 50 TC 7 Z9 8 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2013 VL 48 IS 1 BP 78 EP 86 DI 10.1165/rcmb.2011-0402OC PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 135DX UT WOS:000318268200010 PM 23043086 ER PT J AU Park, S Gildersleeve, JC Blixt, O Shin, I AF Park, Sungjin Gildersleeve, Jeffrey C. Blixt, Ola Shin, Injae TI Carbohydrate microarrays SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID GLYCAN-BINDING-PROTEINS; COATED GLASS SLIDES; RESISTANT PROSTATE-CANCER; SELF-ASSEMBLED MONOLAYERS; BLOOD-GROUP ANTIGENS; LABEL-FREE ANALYSIS; C-TYPE LECTIN; MASS-SPECTROMETRY; OLIGOSACCHARIDE MICROARRAYS; MONOCLONAL-ANTIBODIES AB In the last decade, carbohydrate microarrays have been core technologies for analyzing carbohydrate-mediated recognition events in a high-throughput fashion. A number of methods have been exploited for immobilizing glycans on the solid surface in a microarray format. This microarray-based technology has been widely employed for rapid analysis of the glycan binding properties of lectins and antibodies, the quantitative measurements of glycan-protein interactions, detection of cells and pathogens, identification of disease-related anti-glycan antibodies for diagnosis, and fast assessment of substrate specificities of glycosyltransferases. This review covers the construction of carbohydrate microarrays, detection methods of carbohydrate microarrays and their applications in biological and biomedical research. C1 [Park, Sungjin; Shin, Injae] Yonsei Univ, Dept Chem, Natl Creat Res Initiat Ctr Biofunct Mol, Seoul 120749, South Korea. [Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Blixt, Ola] Univ Copenhagen, Panum Inst, Inst Cellular & Mol Med, Copenhagen Ctr Glyc, DK-2200 Copenhagen, Denmark. RP Gildersleeve, JC (reprint author), NCI, Biol Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM gildersj@mail.nih.gov; olablixt@sund.ku.dk; injae@yonsei.ac.kr RI Gildersleeve, Jeffrey/N-3392-2014 FU National Creative Research Initiative; WCU; NIH; NCI; Benzon Foundation; Danish Agency for Science; EU [215536]; EU FP7-GlycoBioM; Danish National Research Foundation; University of Copenhagen Programme of Excellence FX This work was supported by grants from the National Creative Research Initiative (IS), WCU (IS), the intramural research program of the NIH (JG), NCI (JG), Benzon Foundation (OB), Danish Agency for Science (OB), EU FP7/2007-2013-EuroGlycoArrays 215536 (OB), EU FP7-GlycoBioM (OB), Danish National Research Foundation (OB) and University of Copenhagen Programme of Excellence (OB). Maya Bonde Haaland is acknowledged for linguistic help. NR 236 TC 97 Z9 99 U1 15 U2 171 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2013 VL 42 IS 10 BP 4310 EP 4326 DI 10.1039/c2cs35401b PG 17 WC Chemistry, Multidisciplinary SC Chemistry GA 135NG UT WOS:000318294300005 PM 23192235 ER PT J AU Chen, GB Shannon, MF AF Chen, Guobing Shannon, M. Frances TI Transcription Factors and Th17 Cell Development in Experimental Autoimmune Encephalomyelitis SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article DE Th17 cell; EAE; transcription factor; signaling pathway; gene expression regulation; plasticity ID ROR-GAMMA-T; ARYL-HYDROCARBON RECEPTOR; NF-KAPPA-B; BINDING INHIBITOR ID3; GROWTH-FACTOR-BETA; FACTOR C-REL; TGF-BETA; T(H)17 CELLS; HELPER-CELLS; T-H-17 CELLS AB Experimental autoimmune encephalomyelitis (EAE), a widely studied animal model of human central nervous system demyelinating diseases such as multiple sclerosis, is a T-cell-mediated autoimmune disease involving effector T helper (Th) subsets such as Th1 and Th17. Recently, Th17 cells have been shown to play a major role in many autoimmune and other inflammatory diseases. The development of Th subsets is controlled by a complex network of cytoldnes and signaling and transcription molecules that act to augment the development of one cell type while restricting the development of other lineages. Here, we review the transcription factors (TFs) that are required for Th17 cell development in EAE and classify them into three types: major or essential such as ROR gamma t and STAT3, an array of helper factors that work in combination with or regulate the expression of the major factors, and regulatory TFs that attenuate the expression of Th17 genes. The plasticity of the Th17 cell lineage is also discussed in relation to the interaction of TFs that play a major role in the development of other Th or regulatory T cell (Treg) lineages such as T-bet and Foxp3 with the Th17 TFs. C1 [Chen, Guobing; Shannon, M. Frances] Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Biol, Gene Express & Epigen Lab, Canberra, ACT 2600, Australia. [Shannon, M. Frances] Univ Canberra, Canberra, ACT 2601, Australia. RP Chen, GB (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM guobing.chen@nih.gov RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 NR 96 TC 8 Z9 10 U1 0 U2 10 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2013 VL 33 IS 2 BP 165 EP 182 PG 18 WC Immunology SC Immunology GA 135AP UT WOS:000318258700004 PM 23582061 ER PT J AU Man, YG Stojadinovic, A Mason, J Avital, I Bilchik, A Bruecher, B Protic, M Nissan, A Izadjoo, M Zhang, XC Jewett, A AF Man, Yan-gao Stojadinovic, Alexander Mason, Jeffrey Avital, Itzhak Bilchik, Anton Bruecher, Bjoern Protic, Mladjan Nissan, Aviram Izadjoo, Mina Zhang, Xichen Jewett, Anahid TI Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories SO JOURNAL OF CANCER LA English DT Review DE immune cell; tumor progression; invasion; metastasis ID NATURAL-KILLER-CELLS; PROSTATIC INTRAEPITHELIAL NEOPLASIA; RESULTANT AUTO-IMMUNOREACTIONS; ENDOTHELIAL GROWTH-FACTOR; MAMMARY EPITHELIAL-CELLS; FAS LIGAND EXPRESSION; CANCER DNA PHENOTYPE; MARROW-DERIVED CELLS; REGULATORY T-CELLS; HUMAN COLON-CANCER AB It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness. C1 [Man, Yan-gao; Izadjoo, Mina] Henry Jackson Fdn, Diagnost & Translat Res Ctr, Gaithersburg, MD USA. [Man, Yan-gao; Zhang, Xichen] Jilin Univ, Coll Anim Sci & Vet Med, Changchun 130023, Jilin, Peoples R China. [Stojadinovic, Alexander] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Stojadinovic, Alexander] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Mason, Jeffrey] Vet Affair Med Ctr, Washington, DC USA. [Avital, Itzhak] Bon Secours Natl Canc Inst BSNCI, Richmond, VA USA. [Bilchik, Anton] Univ Calif Los Angeles, Calif Oncol Res Inst, John Wayne Canc Inst, Los Angeles, CA USA. [Bilchik, Anton] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bruecher, Bjoern] Theodor Billroth Acad, Munich, Germany. [Protic, Mladjan] Univ Novi Sad, Fac Med, Clin Ctr Vojvodina, Clin Abdominal Endocrine & Transplantat Surg, Novi Sad 21000, Serbia. [Nissan, Aviram] Hadassah Hebrew Univ, Med Ctr, Dept Surg, Surg Oncol Lab, Jerusalem, Israel. [Jewett, Anahid] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90024 USA. RP Man, YG (reprint author), Henry Jackson Fdn, Diagnost & Translat Res Ctr, Gaithersburg, MD USA. EM ymann@dtrc-hjfresearch.org; ajewett@dentistry.ucla.edu OI Brucher, Bjorn/0000-0002-3930-6416 NR 163 TC 25 Z9 26 U1 0 U2 9 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2013 VL 4 IS 1 BP 84 EP 95 DI 10.7150/jca.5482 PG 12 WC Oncology SC Oncology GA 135PZ UT WOS:000318302300009 PM 23386907 ER PT J AU Zimerman, M Heise, KF Gerloff, C Cohen, LG Hummel, FC AF Zimerman, M. Heise, K. -F Gerloff, C. Cohen, L. G. Hummel, F. C. TI Disrupting the Ipsilateral Motor Cortex Interferes With Training of a Complex Motor Task in Older Adults SO JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 [Zimerman, M.; Heise, K. -F; Gerloff, C.; Hummel, F. C.] Univ Klinikum Hamburg Eppendorf, Brain Imaging & Neurostimulat BINS Lab, Hamburg, Germany. [Cohen, L. G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0269-8803 J9 J PSYCHOPHYSIOL JI J. Psychophysiol. PY 2013 VL 27 SU 1 BP 47 EP 47 PG 1 WC Psychology, Biological; Neurosciences SC Psychology; Neurosciences & Neurology GA 130ZI UT WOS:000317959400101 ER PT J AU Long, RE Smith, A Machotka, SV Chlipala, E Cann, J Knight, B Kawano, Y Ellin, J Lowe, A AF Long, Richard E. Smith, Adam Machotka, Sam V. Chlipala, Elizabeth Cann, Jennifer Knight, Brian Kawano, Yoshihiro Ellin, Jesus Lowe, Amanda TI Scientific and Regulatory Policy Committee (SRPC) Paper: Validation of Digital Pathology Systems in the Regulated Nonclinical Environment SO TOXICOLOGIC PATHOLOGY LA English DT Article DE validation; digital pathology systems; whole slide scanner; nonclinical; computerized systems AB Digital Pathology Systems (DPS) are dynamic, image-based computer systems that enable the acquisition, management, and interpretation of pathology information generated from digitized glass slides. This article provides a roadmap for (1) qualification of a whole slide scanner (WSS) during a validation project, (2) validation of software required to generate the whole slide image (WSI), and (3) an introduction to visual digital image evaluation and image analysis. It describes a validation approach that can be utilized when validating a DPS. It is not the intent of this article to provide guidance on when validation of DPS is required. Rather, the article focuses on technical aspects of validation of the WSS system (WSS, IT infrastructure, and associated software) portion of a DPS and covers the processes of setting up the WSS for scanning a glass slide through saving a WSI on a server. Validation of a computerized system, such as a DPS, for use in a regulated nonclinical environment is governed by Code of Federal Regulations (CFR) Title 21 part 11: Electronic Records; Electronic Signature and predicate rules associated with Good Laboratory Practices documents including 21 CFR part 58. Similar regulation and predicate rules apply in the European Union and Japan. C1 [Long, Richard E.] Charles River Labs, Lees Summit, MO 64082 USA. [Smith, Adam; Machotka, Sam V.] Merck Res Labs, West Point, PA USA. [Chlipala, Elizabeth] Premier Lab, Boulder, CO USA. [Cann, Jennifer] NIH, Frederick, MD USA. [Knight, Brian] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Kawano, Yoshihiro] Olympus, Center Valley, PA USA. [Ellin, Jesus] Yuma Reg Med Ctr, Yuma, AZ USA. [Lowe, Amanda] Digital Pathol Consultants LLC, Broomfield, CO USA. RP Long, RE (reprint author), Charles River Labs, 3912 Windjammer Court, Lees Summit, MO 64082 USA. EM richard.long@crl.com OI Kawano, Yoshihiro/0000-0001-6442-8733 NR 15 TC 9 Z9 9 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2013 VL 41 IS 1 BP 115 EP 124 DI 10.1177/0192623312451162 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 129CD UT WOS:000317815100013 PM 22723045 ER PT J AU Bucher, JR AF Bucher, John R. TI Regulatory Forum Opinion Piece*: Tox21 and Toxicologic Pathology SO TOXICOLOGIC PATHOLOGY LA English DT Article DE alternative models in toxicology; animal models; toxicogenomics; in vitro toxicology; mechanisms of toxicity; risk identification; safety assessment ID PROTECTION AB Tox21 is a transformative effort on the part of several U.S. Federal agencies (the National Toxicology Program/National Institute of Environmental Health Sciences [NTP], the National Institutes of Health (NIH) Chemical Genomics Center/National Human Genome Research Institute [NCGC; now called the NIH Center for Translational Therapeutics, National Center for Advancing Translational Sciences] the Environmental Protection Agency's (EPA) National Center for Computational Toxicology, and recently the Food and Drug Administration) that are partnering to fundamentally change the science of safety toxicology. These agencies bring a comprehensive suite of capabilities and are working diligently together to develop, evaluate, and ultimately implement a new safety assessment paradigm. Toxicologic pathology has an important ongoing role in establishing the validity of this transformation, and may ultimately benefit as a discipline through an enhanced understanding of chemically induced disease mechanisms. C1 NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov NR 5 TC 8 Z9 8 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2013 VL 41 IS 1 BP 125 EP 127 DI 10.1177/0192623312450632 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 129CD UT WOS:000317815100014 PM 22692375 ER PT J AU Du, XJ Lipman, DJ Cherry, JL AF Du, Xiangjun Lipman, David J. Cherry, Joshua L. TI Why Does a Protein's Evolutionary Rate Vary over Time? SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE protein evolution; evolutionary rate; overdispersion; molecular clock ID MOLECULAR CLOCK; SUBSTITUTION RATES; DROSOPHILA; DATABASE; GENES; YEAST; OVERDISPERSION; GENOMES; MODELS AB The sequences of different proteins evolve at different rates. The relative evolutionary rate (ER) of a single protein also changes over evolutionary time. The cause of this ER fluctuation remains uncertain, and study of this phenomenon may shed light on protein evolution more broadly. We have characterized ER fluctuation in mammals and Drosophila. We found little correlation between the amount of rate variation observed for a protein and such factors as its expression level or phylogenetic distribution. Perhaps more surprisingly, we found little correlation between our measure of rate variation and ER itself. We also investigated the extent to which the ERs of different domains of a protein vary independently. We found that rates of different domains do tend to vary together. In fact, rates at positions in different domains are coupled just as strongly as rates at equally distant positions in the same domain. These findings provide clues to the protein evolutionary process. C1 [Du, Xiangjun; Lipman, David J.; Cherry, Joshua L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Cherry, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM jcherry@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX The authors thank Richa Agarwala for assembling the D. simulans RNA-Seq data and Alexandre Souvorov for producing gene predictions for the Chinese rhesus macaque. They also thank Trevor Bedford and Yuri Wolf for sharing data. This work was supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 31 TC 5 Z9 5 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 3 BP 494 EP 503 DI 10.1093/gbe/evt024 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 126NS UT WOS:000317625200003 PM 23436005 ER PT J AU Sherman, E Barr, V Samelson, LE AF Sherman, Eilon Barr, Valarie Samelson, Lawrence E. TI Super-resolution characterization of TCR-dependent signaling clusters SO IMMUNOLOGICAL REVIEWS LA English DT Review DE T-cell activation; microclusters; super-resolution microscopy; nanostructure; single molecule microscopy ID T-CELL-RECEPTOR; FC-EPSILON-RI; ANTIGEN RECEPTOR; IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; FLUORESCENCE MICROSCOPY; PHOSPHOLIPASE C-GAMMA-1; PROTEIN HETEROGENEITY; DIFFRACTION-LIMIT; ADAPTER PROTEINS AB Multi-molecular signaling complexes drive the earliest events of immune cell activation via immunoreceptors with unexplained specificity and speed. Fluorescence microscopy has shown that these complexes form microclusters at the plasma membrane of activated T cells upon engagement of their antigen receptors (TCRs). Although crucial for cell function, much remains to be learned about the molecular content, fine structure, formation mechanisms, and function of these microclusters. Recent advancements in super-resolution microscopy have enabled the study of signaling microclusters at the single molecule level with resolution down to approximately 20 nm. These techniques have now helped to characterize the size distributions of signaling clusters at the plasma membrane of intact cells and to shed light on the formation mechanisms that govern their assembly. Surprisingly, dynamic and functional nanostructures have been identified within the signaling clusters. We expect that these novel methodologies, combined with older techniques, will shed new light on the nature of signaling clusters and their critical role in T-cell activation. C1 [Sherman, Eilon; Barr, Valarie; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, CCR, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM samelsonl@helix.nih.gov RI Sherman, Eilon /B-3688-2014 OI Sherman, Eilon /0000-0002-7403-6036 FU National Cancer Institute (The Center for Cancer Research) FX The authors thank Lakshmi Balagopalan and Connie Sommers for their comments on the manuscript. This work was supported by the Intramural Research Programs of the National Cancer Institute (The Center for Cancer Research). NR 73 TC 20 Z9 21 U1 5 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2013 VL 251 SI SI BP 21 EP 35 DI 10.1111/imr.12010 PG 15 WC Immunology SC Immunology GA 119DK UT WOS:000317077400003 PM 23278738 ER PT J AU Pitcher, D AF Pitcher, David TI TMS EVIDENCE FOR CATEGORY-SELECTIVE CORTICAL REGIONS IN HUMAN EXTRASTRIATE CORTEX SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Pitcher, David] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 20 EP 20 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030500016 ER PT J AU Coderre, E Smith, J van Heuven, W Horwitz, B AF Coderre, Emily Smith, Jason van Heuven, Walter Horwitz, Barry TI THE NEURAL LOCUS OF THE BILINGUAL ADVANTAGE SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Coderre, Emily; van Heuven, Walter] Univ Nottingham, Nottingham NG7 2RD, England. [Coderre, Emily; Smith, Jason; Horwitz, Barry] NIDCD, NIH, Bethesda, MD USA. RI van Heuven, Walter/K-9034-2013 OI van Heuven, Walter/0000-0003-3183-4449 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 77 EP 77 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030500259 ER PT J AU Keisler, A Frank, S Wassermann, E AF Keisler, Aysha Frank, Samantha Wassermann, Eric TI MOTOR COSTS MODULATE PRIMARY MOTOR CORTEX EXCITABILITY SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Keisler, Aysha; Frank, Samantha; Wassermann, Eric] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 118 EP 118 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030500456 ER PT J AU Satyshur, M Japee, S Mukai, I Ungerleider, L AF Satyshur, Maureen Japee, Shruti Mukai, Ikuko Ungerleider, Leslie TI A ROLE OF THE RIGHT MIDDLE FRONTAL GYRUS (RMFG) IN ENDOGENOUS AND EXOGENOUS VISUAL ATTENTION: A CASE STUDY SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Satyshur, Maureen; Japee, Shruti; Ungerleider, Leslie] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 122 EP 122 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030500472 ER PT J AU Mills, K Goddings, AL Clasen, LS Blakemore, SJ Giedd, JN AF Mills, Kathryn Goddings, Anne-Lise Clasen, Liv S. Blakemore, Sarah-Jayne Giedd, Jay N. TI THE DEVELOPMENTAL MISMATCH IN STRUCTURAL BRAIN MATURATION DURING ADOLESCENCE SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Mills, Kathryn; Goddings, Anne-Lise; Blakemore, Sarah-Jayne] UCL, Inst Cognit Neurosci, London, England. [Mills, Kathryn; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Goddings, Anne-Lise] UCL, Inst Child Hlth, London, England. RI Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 1 U2 8 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 153 EP 153 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030500617 ER PT J AU Krimsky, M Charney, D Vytal, K Ernst, M Cornwell, B Grillon, C AF Krimsky, Marissa Charney, Danielle Vytal, Katherine Ernst, Monique Cornwell, Brian Grillon, Christian TI OXYTOCIN INCREASES ANXIETY TO UNPREDICTABLE THREAT SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Krimsky, Marissa; Charney, Danielle; Vytal, Katherine; Ernst, Monique; Cornwell, Brian; Grillon, Christian] NIMH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 185 EP 186 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501060 ER PT J AU Shibata, M Terasawa, Y Umeda, S AF Shibata, Midori Terasawa, Yuri Umeda, Satoshi TI NEURAL CORRELATES OF HUMOR COMPREHENSION AND APPRECIATION: A FUNCTIONAL MRI STUDY SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Shibata, Midori] Hokkaido Univ, Sapporo, Hokkaido 060, Japan. [Shibata, Midori; Terasawa, Yuri; Umeda, Satoshi] Keio Univ, Tokyo 108, Japan. [Terasawa, Yuri] NIMH, Natl Ctr Neurol & Psychiat, Bethesda, MD USA. [Terasawa, Yuri] Japan Soc Promot Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 214 EP 214 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501192 ER PT J AU Williams, V Salmeron, BJ Ross, TJ Black, M Riggins, T AF Williams, Vanessa Salmeron, Betty Jo Ross, Thomas J. Black, Maureen Riggins, Tracy TI A FUNCTIONAL MAGNETIC RESONANCE IMAGING INVESTIGATION OF THE EFFECTS OF PRENATAL DRUG EXPOSURE ON EMOTIONAL PROCESSING AND MEMORY PERFORMANCE SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Williams, Vanessa; Riggins, Tracy] Univ Maryland, College Pk, MD 20742 USA. [Salmeron, Betty Jo; Ross, Thomas J.] NIDA, Intramural Res Program, Baltimore, MD USA. [Black, Maureen] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 257 EP 257 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501399 ER PT J AU Sottile, M Kippenhan, JS Roe, K Mervis, CB Eisenberg, D Masdeu, J Bloch, J Turner, N Kohn, P Jabbi, M Wei, SM Berman, KF AF Sottile, Melanie Kippenhan, J. Shane Roe, Katherine Mervis, Carolyn B. Eisenberg, Daniel Masdeu, Joseph Bloch, Jeffrey Turner, Nicholas Kohn, Philip Jabbi, Mbemba Wei, Shau-Ming Berman, Karen Faith TI INTRAPARIETAL SULCAL DEPTH REDUCTIONS IN CHILDREN WITH WILLIAMS SYNDROME SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Sottile, Melanie; Kippenhan, J. Shane; Roe, Katherine; Eisenberg, Daniel; Masdeu, Joseph; Bloch, Jeffrey; Turner, Nicholas; Kohn, Philip; Jabbi, Mbemba; Wei, Shau-Ming; Berman, Karen Faith] NIMH, Sect Integrat Neuroimaging, IRP, NIH, Bethesda, MD USA. [Mervis, Carolyn B.] U Lousiville, Dept Psych & Brain Sci, Neurodev Sci Lab, Louisville, KY USA. [Berman, Karen Faith] NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD USA. RI Eisenberg, Daniel/C-7432-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 259 EP 260 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501411 ER PT J AU Wilkinson, L Steel, A Knutson, K Wassermann, E AF Wilkinson, Leonora Steel, Adam Knutson, Kris Wassermann, Eric TI INHIBITORY TMS OVER THE PRIMARY MOTOR CORTEX IMPAIRS IMPLICIT MOTOR SEQUENCE LEARNING AND ITS NEURAL CORRELATES. A COMBINED FMRI TMS STUDY SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Wilkinson, Leonora; Steel, Adam; Knutson, Kris; Wassermann, Eric] NINDS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 259 EP 259 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501410 ER PT J AU Stevens, WD Tessler, MH Kravitz, DJ Martin, A AF Stevens, W. Dale Tessler, M. Henry Kravitz, Dwight J. Martin, Alex TI FUNCTIONAL SPECIFICITY AND CONNECTIVITY OF THE VISUAL WORD FORM AREA SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract CT 20th Annual Meeting of the Cognitive-Neuroscience-Society CY APR 13-16, 2013 CL San Francisco, CA SP Cognit Neuroscience Soc C1 [Stevens, W. Dale; Tessler, M. Henry; Kravitz, Dwight J.; Martin, Alex] NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 5 U2 6 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PY 2013 SU S BP 263 EP 263 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 118MV UT WOS:000317030501427 ER PT J AU Jackson, JC Albert, PS Zhang, ZW Simons-Morton, B AF Jackson, John C. Albert, Paul S. Zhang, Zhiwei Simons-Morton, Bruce TI Ordinal latent variable models and their application in the study of newly licensed teenage drivers SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Driving study; Latent class modelling; Monte Carlo expectationmaximization ID LONGITUDINAL BINARY DATA; EM ALGORITHM; MAXIMUM-LIKELIHOOD; BEHAVIOR; TIME AB . In a unique longitudinal study of teen driving, risky driving behaviour and the occurrence of crashes or near crashes are measured prospectively over the first 18 months of licensure. Of scientific interest is relating the two processes and developing a predictor of crashes from previous risky driving behaviour. In this work, we propose two latent class models for relating risky driving behaviour to the occurrence of a crash or near-crash event. The first approach models the binary longitudinal crash or near-crash outcome by using a binary latent variable which depends on risky driving covariates and previous outcomes. A random-effects model introduces heterogeneity among subjects in modelling the mean value of the latent state. The second approach extends the first model to the ordinal case where the latent state is composed of K ordinal classes. Additionally, we discuss an alternative hidden Markov model formulation. Estimation is performed by using the expectationmaximization algorithm and Monte Carlo expectationmaximization. We illustrate the importance of using these latent class modelling approaches through the analysis of the teen driving behaviour. C1 [Jackson, John C.] US Mil Acad, West Point, NY 10996 USA. [Albert, Paul S.; Zhang, Zhiwei; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Jackson, JC (reprint author), US Mil Acad, Dept Math Sci, Thayer Rd, West Point, NY 10996 USA. EM John.Jackson@usma.edu OI Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX We thank the Center for Information Technology, National Institutes of Health, for providing access to the high performance computational capabilities of the Biowulf cluster computing system. The research of Paul S. Albert, Zhiwei Zhang and Bruce Simons-Morton was supported by the intramural research programme of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. We also thank the referees for their thoughtful comments and suggestions which improved our manuscript. NR 19 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2013 VL 62 IS 3 BP 435 EP 450 DI 10.1111/j.1467-9876.2012.01065.x PG 16 WC Statistics & Probability SC Mathematics GA 123RW UT WOS:000317409400005 PM 25284899 ER PT J AU Diniz, BS Machado-Vieira, R Forlenza, OV AF Diniz, Breno Satler Machado-Vieira, Rodrigo Forlenza, Orestes Vicente TI Lithium and neuroprotection: translational evidence and implications for the treatment of neuropsychiatric disorders SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE lithium; Alzheimer's disease; prevention; GSK-3 beta; neuroprotection ID GLYCOGEN-SYNTHASE KINASE-3; AMYLOID-INDUCED NEURODEGENERATION; OXIDATIVE STRESS PARAMETERS; MILD COGNITIVE IMPAIRMENT; CULTURED CORTICAL-NEURONS; EUTHYMIC BIPOLAR PATIENTS; EARLY ALZHEIMERS-DISEASE; N-ACETYL-ASPARTATE; NEUROTROPHIC FACTOR; PRECURSOR PROTEIN AB In the last two decades, a growing body of evidence has shown that lithium has several neuroprotective effects. Several neurobiological mechanisms have been proposed to underlie these clinical effects. Evidence from preclinical studies suggests that neuroprotection induced by lithium is mainly related to its potent inhibition of the enzyme glycogen synthase kinase-3 beta (GSK-3 beta) and its downstream effects, ie, reduction of both tau protein phosphorylation and amyloid-beta(42) production. Additional neuroprotective effects include increased neurotrophic support, reduced proinflammatory status, and decreased oxidative stress. More recently, neuroimaging studies in humans have demonstrated that chronic use is associated with cortical thickening, higher volume of the hippocampus and amygdala, and neuronal viability in bipolar patients on lithium treatment. In line with this evidence, observational and case registry studies have shown that chronic lithium intake is associated with a reduced risk of Alzheimer's disease in subjects with bipolar disorder. Evidence from recent clinical trials in patients with mild cognitive impairment suggests that chronic lithium treatment at subtherapeutic doses can reduce cerebral spinal fluid phosphorylated tau protein. Overall, convergent lines of evidence point to the potential of lithium as an agent with disease modifying properties in Alzheimer's disease. However, additional long-term studies are necessary to confirm its efficacy and safety for these patients, particularly as chronic intake is necessary to achieve the best therapeutic results. C1 [Diniz, Breno Satler] Univ Fed Minas Gerais, Dept Mental Hlth, Natl Inst Sci & Technol Mol Med, Belo Horizonte, MG, Brazil. [Machado-Vieira, Rodrigo; Forlenza, Orestes Vicente] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] NIMH, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA. RP Diniz, BS (reprint author), Dept Mental Hlth, Av Alfredo Balena 190,Off 235, BR-30130100 Belo Horizonte, MG, Brazil. EM brenosatler@gmail.com RI Forlenza, Orestes/B-8848-2013; MACHADO-VIEIRA, RODRIGO/D-8293-2012; OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Diniz, Breno/0000-0003-0653-1905 NR 86 TC 39 Z9 40 U1 1 U2 25 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2013 VL 9 BP 493 EP 500 DI 10.2147/NDT.S33086 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 125UD UT WOS:000317566000001 PM 23596350 ER PT J AU Song, BJ Abdelmegeed, MA Henderson, LE Yoo, SH Wan, J Purohit, V Hardwick, JP Moon, KH AF Song, Byoung-Joon Abdelmegeed, Mohamed A. Henderson, Lauren E. Yoo, Seong-Ho Wan, Jie Purohit, Vishnudutt Hardwick, James P. Moon, Kwan-Hoon TI Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease SO OXIDATIVE MEDICINE AND CELLULAR LONGEVITY LA English DT Review ID ASCORBATE-DEPENDENT ARTIFACT; MEDIATED OXIDATIVE STRESS; CYTOCHROME-C-OXIDASE; BIOTIN-SWITCH ASSAY; ALDEHYDE-DEHYDROGENASE; NITRIC-OXIDE; RAT-LIVER; LIPID-PEROXIDATION; S-NITROSYLATION; HEPATOMA-CELLS AB Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/ nitration) under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s) of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM) as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research. C1 [Song, Byoung-Joon; Abdelmegeed, Mohamed A.; Henderson, Lauren E.; Yoo, Seong-Ho; Wan, Jie; Moon, Kwan-Hoon] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Yoo, Seong-Ho] Seoul Natl Univ, Coll Med, Dept Forens Med, Seoul 110, South Korea. [Purohit, Vishnudutt] Natl Inst Drug Abuse, Bethesda, MD 20892 USA. [Hardwick, James P.] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Dept Integrat Med Sci, Rootstown, OH 44272 USA. [Moon, Kwan-Hoon] Loyola Univ, Med Ctr, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. RP Song, BJ (reprint author), NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bj.song@nih.gov FU Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism; Grant for the Chronic Liver Disease Project from the Center for Biological Modulators in the Republic of Korea FX This research was supported by the Intramural Program Fund at the National Institute on Alcohol Abuse and Alcoholism. Part of this research was also supported by a Grant for the Chronic Liver Disease Project (to B. J. Song) from the Center for Biological Modulators in the Republic of Korea. The authors thank Dr. Klaus Gawrisch for his support. They are also grateful to Drs. Timothy D. Veenstra, Brian L. Hood, Thomas P. Conrads, Li-Rong Yu, and Xiaoying Ye at the Laboratory of Proteomics and Analytical Technologies, Advanced Technology Program, SAIC-Frederick, Inc., for determining the protein sequences of oxidatively modified mitochondrial proteins in our studies. The authors do not have any conflict of interest. NR 146 TC 10 Z9 11 U1 2 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1942-0900 J9 OXID MED CELL LONGEV JI Oxidative Med. Cell. Longev. PY 2013 AR 781050 DI 10.1155/2013/781050 PG 14 WC Cell Biology SC Cell Biology GA 125AO UT WOS:000317510700001 ER PT J AU Prislovsky, A Zeng, XY Sokolic, RA Garabedian, EN Anur, P Candotti, F Strom, TS AF Prislovsky, Amanda Zeng, Xueying Sokolic, Robert A. Garabedian, Elizabeth N. Anur, Praveen Candotti, Fabio Strom, Ted S. TI Platelets from WAS patients show an increased susceptibility to ex vivo phagocytosis SO PLATELETS LA English DT Article DE Wiskott-Aldrich syndrome; phagocytosis; numerical analysis; thrombocytopenia ID WISKOTT-ALDRICH-SYNDROME; THROMBOCYTOPENIA; DEFECTS AB The thrombocytopenia of Wiskott-Aldrich syndrome (WAS) is thought to be due to both reduced platelet production and accelerated platelet consumption. We have previously demonstrated that platelets from WASP-deficient mice are consumed more rapidly in vivo than are WT platelets, and that opsonization accelerates their uptake by bone marrow-derived macrophages more than it does that of WT platelets. Here we asked whether platelets from WAS patients show similar features. We show that ex vivo phagocytosis by activated THP-1 cells of DIO-labeled platelets from a series of WAS or XLT patients is increased in comparison to that of normal control platelets. Using a numerical analysis method, we distinguish this effect from a concurrent effect on the amount of detectable fluorescent signal transferred to the macrophage per phagocytosed platelet. We show that the latter quantity is reduced by platelet WASP deficiency, as might be expected if the fluorescence transferred from these smaller platelets is more rapidly quenched. We are unable to detect a differential effect of opsonization with anti-CD61 antibody on the uptake of WASP(-) vs. WT platelets. However, the high probability of phagocytosis per adsorbed WASP(-) platelet could limit the sensitivity of the assay in this case. We also see no effect of sera from WAS patients on the uptake of normal control platelets, suggesting that in vivo opsonization is not the cause of increased uptake of WASP(-) platelets. Finally, we show little, if any, increase in the reticulated platelet fraction in WAS patients, suggesting that impaired production of reticulated platelets contributes to the thrombocytopenia. Our findings suggest that rapid in vivo platelet consumption contributes significantly to the thrombocytopenia of WAS. They also demonstrate the feasibility of routinely performing functional assays of phagocytosis of small numbers of platelets obtained at remote locations, a method which should be applicable to the study of other types of thrombocytopenia such as ITP. C1 [Prislovsky, Amanda; Strom, Ted S.] Memphis VA Med Ctr, Dept Pathol & Lab Med, Memphis, TN 38104 USA. [Zeng, Xueying; Strom, Ted S.] Univ Tennessee, Ctr Hlth Sci, Dept Pathol & Lab Med, Memphis, TN 38163 USA. [Sokolic, Robert A.; Garabedian, Elizabeth N.; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. [Anur, Praveen] Oregon Hlth & Sci Univ, Portland, OR USA. RP Strom, TS (reprint author), Memphis VA Med Ctr, Dept Pathol & Lab Med, 1030 Jefferson Ave, Memphis, TN 38104 USA. EM tstrom@uthsc.edu FU National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) [1R21AI079757]; Department of Veterans Affairs; National Human Genome Research Institute, National Institutes of Health FX This work was supported by National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) award 1R21AI079757 (TS, PI) and by the Department of Veterans Affairs. This research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 22 TC 3 Z9 3 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2013 VL 24 IS 4 BP 288 EP 296 DI 10.3109/09537104.2012.693991 PG 9 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 124XL UT WOS:000317501800007 PM 22812495 ER PT J AU Clay, JR AF Clay, John R. TI A comparative analysis of models of Na+ channel gating for mammalian and invertebrate nonmyelinated axons: Relationship to energy efficient action potentials SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE Nerve excitability; Sodium ion channel; Channel gating; Ionic models ID SQUID GIANT-AXON; SODIUM-CHANNELS; SINGLE-CHANNEL; KINETIC-MODEL; INACTIVATION; CURRENTS; EXCITABILITY; NERVE; MEMBRANE; FIBERS AB The rapidly activating, voltage gated Na+ current, I-Na, has recently been measured in mammalian nonmyelinated axons. Those results have been incorporated in simulations of the action potential, results that demonstrate a significant separation in time during the spike between I-Na and the repolarizing K+ current, I-K. The original Hodgkin and Huxley (1952) model of Na+ channel gating, m(3)h, where m and h are channel activation and inactivation, respectively, has been used in this analysis. This model was originally developed for invertebrate nonmyelinated axons, squid giant axons in particular. The model has not survived challenges based on results from invertebrate preparations using a double-step voltage clamp protocol and measurements of gating currents, results that demonstrate a kinetic link between activation and inactivation leading to a delayed onset of inactivation following a voltage step. These processes are independent of each other in the Hodgkin and Huxley (1952) model. Application of the double-step protocol to the m(3)h model for mammalian I-Na results reveals a surprising prediction, an apparent delay in onset of inactivation even though activation and inactivation are uncoupled in the model. Other results, most notably gating currents, will be required to demonstrate such a link, if indeed it exists for mammalian Na+ channels. The information obtained will be significant in determining the way in which the Na+ channel is sequestered away from its open state during repolarization, thereby allowing for a separation in time between I-Na and I-K during a spike, an energetically efficient mechanism of neuronal signaling in the mammalian brain. Published by Elsevier Ltd. C1 NINDS, Ion Channel Biophys Grp, NIH, Rockville, MD 20852 USA. RP Clay, JR (reprint author), NINDS, Ion Channel Biophys Grp, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA. EM jrclay@ninds.nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. The author gratefully acknowledges Dr. David Paydarfar for helpful comments on the manuscript. NR 33 TC 3 Z9 3 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JAN PY 2013 VL 111 IS 1 BP 1 EP 7 DI 10.1016/j.pbiomolbio.2012.08.005 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 120LM UT WOS:000317171800001 PM 22922062 ER PT S AU Kim, HJ Park, Y King, GC Choi, SH AF Kim, Hyun Jung Park, Yeonjoon King, Glen C. Choi, Sang H. BE Vincenzini, P Ferrari, M Righini, G TI Development of Field-controlled Smart Optic Materials (ScN, AlN) with Rare Earth Dopants SO SMART & ADAPTIVE OPTICS SE Advances in Science and Technology LA English DT Proceedings Paper CT Symposium F on Smart and Adaptive Optics / 4th International Conference on Smart Materials, Structures and Systems CY JUN 10-14, 2012 CL Montecatini Terme, ITALY DE Smart optics; ScN; AlN; Rare earth elements; Zeeman/Stark effect; Bandgap engineering; Kramers-Kronig relation (KKR); Index of refraction ID ELECTROABSORPTION; SEMICONDUCTORS AB Development of the fundamental materials for field-controlled spectrally active optics is essential for new concept of optics, such as: membrane optics, filters for LIDARs, windows for sensors and probes, telescopes, spectroscopes, cameras, light valves, light switches, flat-panel displays, etc. The dopants of rare earth elements create a number of absorption and emission band structures and can easily be incorporated into many high quality crystalline and amorphous hosts. In wide band-gap semiconductors, like ScN and AlN with rare earth dopants, the existing deep levels can capture or emit the mobile charges, and can be ionized with the loss or capture of the carriers. This is a fundamental basis for smart optic materials. ScN and AlN doped with rare earth elements (Er, Ho) were tested under an applied electric field to characterize spectral and refractive index shifts by the Stark Effect. Decrease in refractive index under an applied electric field was observed as a shift in absorption coefficient using a variable angle spectroscopic ellipsometer. Under an electric field, mobile carriers are redistributed within the space charge region (SCR) to reveal this electro-refractive effect. The main research goal is to facilitate concept demonstration and testing of field-controlled spectrally smart active optics for optical multi-functional capabilities in a selected spectral range. C1 [Kim, Hyun Jung; Park, Yeonjoon] NIA, 100 Explorat Way, Hampton, VA 23666 USA. [King, Glen C.] NASA Langley Res Ctr, Hampton, VA 23681 USA. RP Kim, HJ (reprint author), NIA, 100 Explorat Way, Hampton, VA 23666 USA. EM Hyunjung.Kim@NASA.Gov; Yeonjoon.Park-1@NASA.Gov; Glen.C.King@NASA.Gov; Sang.H.Choi@NASA.Goy NR 11 TC 1 Z9 1 U1 1 U2 13 PU TRANS TECH PUBLICATIONS LTD PI DURNTEN-ZURICH PA KREUZSTRASSE 10, 8635 DURNTEN-ZURICH, SWITZERLAND SN 1662-0356 BN 978-3-908158-68-4 J9 ADV SCI TECH PY 2013 VL 82 BP 38 EP + DI 10.4028/www.scientific.net/AST.82.38 PG 2 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA BEO33 UT WOS:000317550500006 ER PT J AU Lakomek, NA Kaufman, JD Stahl, SJ Louis, JM Grishaev, A Wingfield, PT Bax, A AF Lakomek, Nils-Alexander Kaufman, Joshua D. Stahl, Stephen J. Louis, John M. Grishaev, Alexander Wingfield, Paul T. Bax, Ad TI Internal Dynamics of the Homotrimeric HIV-1 Viral Coat Protein gp41 on Multiple Time Scales SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE glycoproteins; membrane proteins; NMR spectroscopy; protein dynamics; viruses ID MODEL-FREE APPROACH; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; MEDIATED FUSION; VIRUS; RELAXATION; DOMAIN; ENTRY; N-15; ECTODOMAIN C1 [Lakomek, Nils-Alexander; Louis, John M.; Grishaev, Alexander; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bax@nih.gov RI Lakomek, Nils/K-6568-2016 OI Lakomek, Nils/0000-0002-4285-6339 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH); Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH; US Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38] FX We thank Yang Shen for expert advice and Jinfa Ying and James Baber for experimental assistance. This research was funded by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH) and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH. We acknowledge use of the shared scattering beamline resource allocated under the PUP-77 agreement between the National Cancer Institute and the Argonne National Laboratory and thank Dr. Soenke Seifert (Argonne National Laboratory) for his support of the SAXS experiments. Use of the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science under Contract W-31-109-ENG-38. HIV=human immunodeficiency virus. NR 31 TC 25 Z9 25 U1 1 U2 42 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2013 VL 52 IS 14 BP 3911 EP 3915 DI 10.1002/anie.201207266 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 116XB UT WOS:000316915500016 PM 23450638 ER PT S AU Kaplan, RM Stone, AA AF Kaplan, Robert M. Stone, Arthur A. BE Fiske, ST TI Bringing the Laboratory and Clinic to the Community: Mobile Technologies for Health Promotion and Disease Prevention SO ANNUAL REVIEW OF PSYCHOLOGY, VOL 64 SE Annual Review of Psychology LA English DT Review; Book Chapter DE mHealth; ambulatory assessment; short message service (SMS); ecological momentary assessment (EMA); representative design ID RANDOMIZED-CONTROLLED-TRIAL; AMBULATORY BLOOD-PRESSURE; SHORT-MESSAGE SERVICE; ALL-CAUSE MORTALITY; OF-THE-LITERATURE; USE SELF HOME; WEIGHT-LOSS; BEHAVIOR-CHANGE; MASKED HYPERTENSION; PHYSICAL-ACTIVITY AB Health-related information collected in psychological laboratories may not be representative of people's everyday health. For at least 70 years, there has been a call for methods that sample experiences from everyday environments and circumstances. New technologies, including cell phones, sensors, and monitors, now make it possible to collect information outside of the laboratory in environments representative of everyday life. We review the role of mobile technologies in the assessment of health-related behaviors, physiological responses, and self-reports. Ecological momentary assessment offers a wide range of new opportunities for ambulatory assessment and evaluation. The value of mobile technologies for interventions to improve health is less well established. Among 21 randomized clinical trials evaluating interventions that used mobile technologies, more than half failed to document significant improvements on health outcomes or health risk factors. Theoretical and practical issues for future research are discussed. C1 [Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Stone, Arthur A.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. RP Kaplan, RM (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA. EM robert.kaplan@nih.gov RI Emchi, Karma/Q-1952-2016 NR 120 TC 46 Z9 47 U1 5 U2 55 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4308 BN 978-0-8243-0264-1 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol PY 2013 VL 64 BP 471 EP 498 DI 10.1146/annurev-psych-113011-143736 PG 28 WC Psychology; Psychology, Multidisciplinary SC Psychology GA BEF29 UT WOS:000316383600019 PM 22994919 ER PT S AU Soubias, O Gawrisch, K AF Soubias, Olivier Gawrisch, Klaus BE Conn, PM TI Rhodopsin-Lipid Interactions Studied by NMR SO G PROTEIN COUPLED RECEPTORS: MODELING, ACTIVATION, INTERACTIONS AND VIRTUAL SCREENING SE Methods in Enzymology LA English DT Review; Book Chapter ID TRANSFER DIFFERENCE NMR; MEMBRANE-PROTEIN FUNCTION; ORDER PARAMETERS; DISK MEMBRANES; BILAYERS; SPECTROSCOPY; RECEPTOR; DISTRIBUTIONS; CURVATURE; SPECTRA AB The biophysical properties of the lipid matrix are known to influence function of integral membrane proteins. We report on a sample preparation method for reconstitution of membrane proteins which uses porous anodic aluminum oxide (AAO) filters with 200-nm-wide pores of high density. The substrate permits formation of tubular, single membranes that line the inner surface of pores. One square centimeter of filter with a thickness of 60 mu m yields on the order of 500 cm(2) of solid-supported single bilayer surface, sufficient for NMR studies. The tubular bilayers are free of detergent, fully hydrated, and accessible for ligands from one side of the membrane. The use of AAO filters greatly improves reproducibility of the reconstitution process such that the influence of protein on lipid order parameters can be studied with high resolution. As an example, results for the G protein-coupled receptor of class A, bovine rhodopsin, are shown. By H-2 NMR order parameter measurements, it is detected that rhodopsin insertion elastically deforms membranes near the protein. Furthermore, by H-1 saturation-transfer NMR under conditions of magic angle spinning, we demonstrate detection of preferences in interactions of rhodopsin with particular lipid species. It is assumed that function of integral membrane proteins depends on both protein-induced elastic deformations of the lipid matrix and preferences for interaction of the protein with particular lipid species in the first layer of lipids surrounding the protein. C1 [Soubias, Olivier; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. EM gawrisch@helix.nih.gov FU Intramural NIH HHS [Z01 AA000003-15] NR 34 TC 12 Z9 12 U1 1 U2 25 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-407865-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 522 BP 209 EP 227 DI 10.1016/B978-0-12-407865-9.00012-1 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEL04 UT WOS:000317147300012 PM 23374188 ER PT S AU Vilar, S Costanzi, S AF Vilar, Santiago Costanzi, Stefano BE Conn, PM TI Application of Monte Carlo-Based Receptor Ensemble Docking to Virtual Screening for GPCR Ligands SO G PROTEIN COUPLED RECEPTORS: MODELING, ACTIVATION, INTERACTIONS AND VIRTUAL SCREENING SE Methods in Enzymology LA English DT Review; Book Chapter ID PROTEIN-COUPLED RECEPTOR; STRUCTURE-BASED DISCOVERY; BETA(2)-ADRENERGIC RECEPTOR; CONFORMATIONAL SEARCH; DRUG DISCOVERY; CRYSTAL-STRUCTURE; IN-SILICO; FLEXIBILITY; ANTAGONISTS; IDENTIFICATION AB Receptor ensemble docking (RED) is an effective strategy to account for receptor flexibility in the course of a docking-based virtual screening campaign. Such an approach can be applied when multiple crystal structures of a receptor have been solved, but it can also be applied when only a single crystal structure is available. In this case, alternative structures can be generated from the latter by computational means and subsequently applied to RED. Here, we illustrate how such conformers can be generated by subjecting a crystal structure to Monte Carlo conformational searches. Through a controlled virtual screening experiment, we then show the applicability of such a strategy to the identification of ligands of the beta(2) adrenergic receptor, a G protein-coupled receptor activated by epinephrine. Requiring the availability of one crystal structure only, this strategy is applicable to all systems for which multiple experimentally elucidated structures are not available. C1 [Vilar, Santiago] Univ Santiago de Compostela, Fac Pharm, Dept Organ Chem, Santiago The Compostela, Spain. [Costanzi, Stefano] NIDDKD, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA. RP Costanzi, S (reprint author), NIDDKD, Lab Biol Modeling, NIH, DHHS, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Vilar Varela, Santiago/0000-0003-2663-4370; Costanzi, Stefano/0000-0003-3183-7332 NR 37 TC 4 Z9 4 U1 0 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-407865-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 522 BP 263 EP 278 DI 10.1016/B978-0-12-407865-9.00014-5 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEL04 UT WOS:000317147300014 PM 23374190 ER PT J AU Schlom, J Jochems, C Gulley, JL Huang, JP AF Schlom, Jeffrey Jochems, Caroline Gulley, James L. Huang, Jianping TI The role of soluble CD40L in immunosuppression SO ONCOIMMUNOLOGY LA English DT Editorial Material DE immunosuppression; myeloid derived suppressor cells (MDSC); regulatory T cells (Tregs); sCD40L; vaccine therapy ID RESISTANT PROSTATE-CANCER; VACCINE; LIGAND; TRIAL AB We have recently performed the first comprehensive study of the potential immunosuppressive role of soluble CD40L (sCD40L). In addition, we demonstrated that serum sCD40L can potentially be used as an indicator of response to anticancer therapy, and/or to better identify those patients who would have best chances to benefit from tumor-targeting vaccines or other therapeutic modalities. C1 [Schlom, Jeffrey; Jochems, Caroline; Gulley, James L.; Huang, Jianping] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 10 TC 5 Z9 6 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2162-4011 J9 ONCOIMMUNOLOGY JI OncoImmunology PD JAN PY 2013 VL 2 IS 1 AR e22546 DI 10.4161/onco.22546 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA 121RT UT WOS:000317262600033 ER PT B AU Jakubovics, NS Palmer, RJ AF Jakubovics, Nick S. Palmer, Robert J., Jr. BE Jakubovics, NS Palmer, RJ TI Oral Microbial Ecology Current Research and New Perspectives Preface SO ORAL MICROBIAL ECOLOGY: CURRENT RESEARCH AND NEW PERSPECTIVES LA English DT Editorial Material; Book Chapter C1 [Jakubovics, Nick S.] Newcastle Univ, Sch Dent Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Palmer, Robert J., Jr.] Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Jakubovics, NS (reprint author), Newcastle Univ, Sch Dent Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. EM nick.jakubovics@nd.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-17-1 PY 2013 BP IX EP X PG 2 WC Microbiology SC Microbiology GA BEI46 UT WOS:000316708000001 ER PT S AU Kassis, JA Brown, JL AF Kassis, Judith A. Brown, J. Lesley BE Friedmann, T Dunlap, JC Goodwin, SF TI Polycomb Group Response Elements in Drosophila and Vertebrates SO ADVANCES IN GENETICS, VOL 81 SE Advances in Genetics LA English DT Review; Book Chapter ID TRANSCRIPTION FACTOR YY1; ENHANCER-PROMOTER COMMUNICATION; TRITHORAX GROUP PROTEINS; CONVEYS EPIGENETIC INHERITANCE; DNA-BINDING PROTEINS; BITHORAX COMPLEX; HOMEOTIC GENE; GAGA FACTOR; REGULATORY ELEMENTS; ENGRAILED GENE AB Polycomb group genes (PcG) encode a group of about 16 proteins that were first identified in Drosophila as repressors of homeotic genes. PcG proteins are present in all metazoans and are best characterized as transcriptional repressors. In Drosophila, these proteins are known as epigenetic regulators because they remember, but do not establish, the patterned expression state of homeotic genes throughout development. PcG proteins, in general, are not DNA binding proteins, but act in protein complexes to repress transcription at specific target genes. How are PcG proteins recruited to the DNA? In Drosophila, there are specific regulatory DNA elements called Polycomb group response elements (PREs) that bring PcG protein complexes to the DNA. Drosophila PREs are made up of binding sites for a complex array of DNA binding proteins. Functional PRE assays in transgenes have shown that PREs act in the context of other regulatory DNA and PRE activity is highly dependent on genomic context. Drosophila PREs tend to regulate genes with a complex array of regulatory DNA in a cell or tissue-specific fashion and it is the interplay between regulatory DNA that dictates PRE function. In mammals, PcG proteins are more diverse and there are multiple ways to recruit PcG complexes, including RNA-mediated recruitment. In this review, we discuss evidence for PREs in vertebrates and explore similarities and differences between Drosophila and vertebrate PREs. C1 [Kassis, Judith A.; Brown, J. Lesley] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Kassis, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. EM jkassis@mail.nih.gov OI Kassis, Judith/0000-0001-9268-3213 FU Intramural NIH HHS [ZIA HD005003-13] NR 153 TC 53 Z9 53 U1 1 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2660 BN 978-0-12-407677-8 J9 ADV GENET JI Adv. Genet. PY 2013 VL 81 BP 83 EP 118 DI 10.1016/B978-0-12-407677-8.00003-8 PG 36 WC Genetics & Heredity SC Genetics & Heredity GA BEI43 UT WOS:000316707100003 PM 23419717 ER PT S AU Otto, M AF Otto, Michael BE Caskey, CT TI Staphylococcal Infections: Mechanisms of Biofilm Maturation and Detachment as Critical Determinants of Pathogenicity SO ANNUAL REVIEW OF MEDICINE, VOL 64 SE Annual Review of Medicine LA English DT Review; Book Chapter DE Staphylococcus aureus; Staphylococcus epidermidis; biofilm; phenol-soluble modulins ID POLYSACCHARIDE INTERCELLULAR ADHESIN; ACCUMULATION-ASSOCIATED PROTEIN; PHENOL-SOLUBLE MODULINS; QUORUM-SENSING SYSTEM; PSEUDOMONAS-AERUGINOSA; VIRULENCE DETERMINANTS; BACTERIAL BIOFILMS; BACILLUS-SUBTILIS; GENE-EXPRESSION; CYSTIC-FIBROSIS AB Biofilm-associated infections are a significant cause of morbidity and death. Staphylococci, above all Staphylococcus aureus and S. epidermidis, are the most frequent causes of biofilm-associated infections on indwelling medical devices. Although the mechanistic basis for the agglomeration of staphylococcal cells in biofilms has been investigated in great detail, we lack understanding of the forces and molecular determinants behind the structuring of biofilms and the detachment of cellular clusters from biofilms. These processes are of key importance for the formation of vital biofilms in vivo with the capacity of bacterial dissemination to secondary sites of infection. Recent studies showed that the phenol-soluble modulins, surfactant peptides secreted by staphylococci in a quorum-sensing controlled fashion, structure biofilms in vitro and in vivo and lead to biofilm detachment with the in vivo consequence of bacterial dissemination. These findings substantiate that quorum sensing and surfactants have widespread importance for biofilm maturation processes in bacteria and establish a novel theory of the molecular determinants driving dissemination of biofilm-associated infection. C1 NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU Intramural NIH HHS NR 71 TC 121 Z9 124 U1 20 U2 110 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0564-2 J9 ANNU REV MED JI Annu. Rev. Med. PY 2013 VL 64 BP 175 EP 188 DI 10.1146/annurev-med-042711-140023 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BEF31 UT WOS:000316384400013 PM 22906361 ER PT S AU Shea, PR Shianna, KV Carrington, M Goldstein, DB AF Shea, Patrick R. Shianna, Kevin V. Carrington, Mary Goldstein, David B. BE Caskey, CT TI Host Genetics of HIV Acquisition and Viral Control SO ANNUAL REVIEW OF MEDICINE, VOL 64 SE Annual Review of Medicine LA English DT Review; Book Chapter DE AIDS; progression; setpoint; GWAS; genome sequencing ID MAJOR HISTOCOMPATIBILITY COMPLEX; CHEMOKINE-RECEPTOR GENE; IMMUNODEFICIENCY-VIRUS TYPE-1; DEFICIENCY SYNDROME AIDS; HLA-C EXPRESSION; CD8(+) T-CELLS; CLASS-I; DISEASE PROGRESSION; PROMOTER POLYMORPHISM; RESTRICTION FACTORS AB Since the discovery of HIV as the cause of AIDS, numerous insights have been gained from studies of its natural history and epidemiology. It has become clear that there are substantial interindividual differences in the risk of HIV acquisition and course of disease. Meanwhile, the field of human genetics has undergone a series of rapid transitions that have fundamentally altered the approach to studying HIV host genetics. We aim to describe the field as it has transitioned from the era of candidate-gene studies and the era of genome-wide association studies (GWAS) to its current state in the infancy of comprehensive sequencing. In some ways the field has come full circle, having evolved from being driven almost exclusively by our knowledge of immunology, to a bias-free GWAS approach, to a point where our ability to catalogue human variation far outstrips our ability to biologically interpret it. C1 [Shea, Patrick R.; Shianna, Kevin V.; Goldstein, David B.] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA. [Carrington, Mary] SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. RP Shea, PR (reprint author), Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC 27708 USA. EM patrick.shea@dm.duke.edu; k.shianna@dm.duke.edu; carringm@mail.nih.gov; d.goldstein@dm.duke.edu OI Shea, Patrick/0000-0001-6804-5131 FU Intramural NIH HHS; PHS HHS [HHSN261200800001E] NR 78 TC 14 Z9 14 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0564-2 J9 ANNU REV MED JI Annu. Rev. Med. PY 2013 VL 64 BP 203 EP 217 DI 10.1146/annurev-med-052511-135400 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BEF31 UT WOS:000316384400015 PM 23020875 ER PT S AU Kumar, J Mayer, ML AF Kumar, Janesh Mayer, Mark L. BE Julius, D TI Functional Insights from Glutamate Receptor Ion Channel Structures SO ANNUAL REVIEW OF PHYSIOLOGY, VOL 75 SE Annual Review of Physiology LA English DT Review; Book Chapter DE synaptic transmission; AMPA receptors; kainate receptors; NMDA receptors; crystallography ID LIGAND-BINDING DOMAIN; N-TERMINAL DOMAIN; POSITIVE ALLOSTERIC MODULATORS; D-ASPARTATE RECEPTOR; HETEROMERIC KAINATE RECEPTORS; NR1/NR2C NMDA RECEPTORS; PARTIAL AGONIST ACTION; MOSSY FIBER SYNAPSES; AMPA RECEPTOR; CRYSTAL-STRUCTURES AB X-ray crystal structures for the soluble amino-terminal and ligand-binding domains of glutamate receptor ion channels, combined with a 3.6-angstrom-resolution structure of the full-length AMPA receptor GluA2 homotetramer, provide unique insights into the mechanisms of the assembly and function of glutamate receptor ion channels. Increasingly sophisticated biochemical, computational, and electrophysiological experiments are beginning to reveal the mechanism of action of partial agonists and suggest new models for the mechanism of action of allosteric modulators. Newly identified NMDA receptor ligands acting at novel sites offer hope for the development of subtype-selective modulators. The many unresolved issues include the role of the amino-terminal domain in AMPA receptor signaling and the mechanisms by which auxiliary proteins regulate receptor activity. The structural basis for ion permeation and ion channel block also remain areas of uncertainty, and despite substantial progress, molecular dynamics simulations have yet to reveal how glutamate binding opens the ion channel pore. C1 [Kumar, Janesh; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Kumar, J (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. EM mayerm@mail.nih.gov RI Mayer, Mark/H-5500-2013 FU Intramural NIH HHS [ZIA HD000707-29] NR 147 TC 48 Z9 48 U1 1 U2 46 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4278 BN 978-0-8243-0375-4 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2013 VL 75 BP 313 EP 337 DI 10.1146/annurev-physiol-030212-183711 PG 25 WC Physiology SC Physiology GA BEF28 UT WOS:000316381400015 PM 22974439 ER PT J AU Vyas, NS Patel, NH Herscovitch, P Puri, BK Lanzenberger, R AF Vyas, Nora S. Patel, Neva H. Herscovitch, Peter Puri, Basant K. Lanzenberger, Rupert TI Recent Developments in Neurochemical Imaging in Schizophrenia: An Update SO CURRENT MEDICINAL CHEMISTRY LA English DT Article DE dopamine; glutamate; serotonin; occupancy; schizophrenia; PET ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-AFFINITY STATE; SEROTONIN TRANSPORTER AVAILABILITY; MAGNETIC-RESONANCE-SPECTROSCOPY; EARLY-ONSET SCHIZOPHRENIA; HUMAN BRAIN; GLUTAMATE HYPOTHESIS; COGNITIVE DEFICITS; MAJOR DEPRESSION; RECEPTOR-BINDING AB The advent of neurochemical brain imaging methods has provided an opportunity to study the neurochemistry of the human brain in normal and abnormal development. The aim of this article is to provide an update on recent major developments in neurochemical imaging in schizophrenia research. In this concise review, we discuss the major findings on three neurotransmitters, namely dopamine, serotonin and glutamate. The most promising radioligand for D-2/D-3 neuroreceptor imaging is the agonist [C-11] PHNO, with higher in vivo affinity for D-3 than D-2 receptors, which can be used to measure amphetamine-induced release of dopamine, and therefore a potential model of dopaminergic alterations in schizophrenia. Recent development of selective radiotracers allow imaging of the serotonin transporter (SERT) using positron emission tomography (PET) with selective tracers such as [C-11] DASB. Additionally, the glutamatergic hypothesis has evolved from theory to phase III clinical trials of newer agents with novel mechanisms. With the development of newer radioligands and the in vivo application of magnetic resonance spectroscopy (MRS) at relatively high magnetic field strengths, there is ample scope for further neuroimaging advances. C1 [Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Vyas, Nora S.] Univ Kingston, Dept Psychol, Kingston Upon Thames KT1 2EE, Surrey, England. [Patel, Neva H.] Imperial Coll Healthcare NHS Trust, Hammersmith Hosp, Radiol Sci Unit, London, England. [Patel, Neva H.] Imperial Coll Healthcare NHS Trust, Charing Cross Hosp, Dept Nucl Med, London, England. [Herscovitch, Peter] NIH, PET Dept, Bethesda, MD 20892 USA. [Puri, Basant K.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Directorate Imaging, London, England. [Lanzenberger, Rupert] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria. RP Vyas, NS (reprint author), NIH, Child Psychiat Branch, Bldg 10,Rm3N202,Ctr Dr, Bethesda, MD 20892 USA. EM nora.vyas@nih.gov FU Fulbright Distinguished Scholar Award by the UK-US Fulbright Commission; Lindemann Trust Fellowship of the English Speaking Union FX We thank Dr. techn. Markus Savli, MSc, for generating the figures (http://www.meduniwien.ac.at/neuroimaging/). Nora S Vyas, PhD, is supported by the Fulbright Distinguished Scholar Award by the UK-US Fulbright Commission, and the Lindemann Trust Fellowship of the English Speaking Union. NR 65 TC 3 Z9 3 U1 4 U2 31 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD JAN PY 2013 VL 20 IS 3 BP 351 EP 356 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 112QU UT WOS:000316608400005 PM 23157626 ER PT J AU Wu, SH Shu, XO Chow, WH Xiang, YB Zhang, XL Cai, QY Li, HL Milne, G Wen, WQ Ji, BT Rothman, N Gao, YT Zheng, W Yang, G AF Wu, Sheng-Hui Shu, Xiao-Ou Chow, Wong-Ho Xiang, Yong-Bing Zhang, Xianglan Cai, Qiuyin Li, Hong-Lan Milne, Ginger Wen, Wanqing Ji, Bu-Tian Rothman, Nathaniel Gao, Yu-Tang Zheng, Wei Yang, Gong TI Adiposity and fat distribution in relation to inflammation and oxidative stress in a relatively lean population of Chinese women SO DISEASE MARKERS LA English DT Article DE Adiposity; inflammation; oxidative stress; biomarker ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; HEALTHY-YOUNG ADULTS; INSULIN-RESISTANCE; VISCERAL ADIPOSITY; METABOLIC SYNDROME; OBESITY; MARKERS; SHANGHAI; RISK AB OBJECTIVES: This study evaluated associations of various anthropometric measures of adiposity with a panel of inflammatory and oxidative stress markers in a relatively lean population of Chinese women. METHODS: This analysis included 1,005 Chinese women aged 40-70 years. Plasma concentrations of inflammatory and oxidative stress markers were measured. Anthropometric measurements were taken by trained interviewers. RESULTS: Body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were all positively and linearly associated with the inflammatory markers, CRP, TNF-alpha, soluble TNF-receptor 1 (sTNF-R1), and IL-6. A significant positive association of these measures of adiposity with the oxidative stress marker F-2-IsoP-M, a metabolite of F-2-IsoPs, but with not F-2-IsoPs was found. Differences in biomarkers between extreme quartiles of anthropometric measurements varied widely, ranging from 9.7% for sTNF-R1 to 162.0% for CRP. For each specific biomarker, various anthropometric measurements exhibited similar ability to explain variations in the biomarker, with the biggest partial r(2)(11%) observed for CRP. CONCLUSIONS: This study suggests that both general adiposity (measured by BMI) and central adiposity (measured by WC and WHtR) are positively and similarly associated with various markers of inflammation and oxidative stress in relatively lean Chinese women. The metabolite F-2-IsoP-M of F-2-IsoPs may be a better marker of in vivo oxidative stress than its parent compounds. C1 [Wu, Sheng-Hui; Shu, Xiao-Ou; Zhang, Xianglan; Cai, Qiuyin; Wen, Wanqing; Zheng, Wei; Yang, Gong] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN 37203 USA. [Chow, Wong-Ho; Ji, Bu-Tian; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Xiang, Yong-Bing; Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. [Milne, Ginger] Vanderbilt Univ, Med Ctr, Dept Med, Div Clin Pharmacol, Nashville, TN 37203 USA. RP Yang, G (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 2525 West End Ave,Suite 600 IMPH, Nashville, TN 37203 USA. EM Gong.Yang@Vanderbilt.edu OI Milne, Ginger/0000-0003-3890-151X FU US National Institute of Health [R01CA122364, R37CA070867, R01HL095931, N02 CP1101066]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This study was supported by US National Institute of Health (grants R01CA122364 to G. Yang, R37CA070867 to W. Zheng, R01HL095931 to X. Zhang, and N02 CP1101066 to X.O. Shu). The plasma and urine sample preparation was performed at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 42 TC 3 Z9 3 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2013 VL 34 IS 4 BP 279 EP 293 DI 10.3233/DMA-130969 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 116AG UT WOS:000316853500007 PM 23396296 ER PT J AU Lu, H Fang, ZZ Cao, YF Hu, CM Hong, M Sun, XY Li, H Liu, Y Fu, XG Sun, HZ AF Lu, Hang Fang, Zhong-Ze Cao, Yun-Feng Hu, Cui-Min Hong, Mo Sun, Xiao-Yu Li, Hua Liu, Yan Fu, Xiaoguang Sun, Hongzhi TI Isoliquiritigenin showed strong inhibitory effects towards multiple UDP-glucuronosyltransferase (UGT) isoform-catalyzed 4-methylumbelliferone (4-MU) glucuronidation SO FITOTERAPIA LA English DT Article DE Isoliquiritigenin; UDP-glucuronosyltransferase (UGT); Enzyme inhibition ID DALBERGIA-ODORIFERA; DRUG-INTERACTIONS; GILBERT-SYNDROME; CANCER; IDENTIFICATION; METABOLISM; CELLS; POLYMORPHISM; EXPRESSION; INDUCTION AB Isoliquiritigenin, a herbal ingredient with chalcone structure, has been speculated to be able to inhibit one of the most drug-metabolizing enzymes (DMEs) UDP-glucuronosyltransferase (UGT). Therefore, the aim of the present study was to investigate the inhibition of isoliquiritigenin towards important UGT isoforms in the liver and intestine, including UGT1A1, 1A3, 1A6, 1A7, 1A8, 1A9 and 1A10. The recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as probe reactions. The results showed that 100 mu M of isoliquiritigenin inhibited the activity of UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, and UGT1A10 by 95.2%, 76.1%, 78.9%, 87.2%, 67.2%, 94.8%, and 91.7%, respectively. The data fitting using Dixon plot and Lineweaver-Burk plot showed that the inhibition of UGT1A1, UGT1A9 and UGT1A10 by isoliquiritigenin was all best fit to the competitive inhibition, and the second plot using the slopes from the Lineweaver-Burk plot versus isoliquiritigenin concentrations was used to calculate the inhibition kinetic parameter (K-i) to be 0.7 mu M, 0.3 mu M, and 18.3 mu M for UGT1A1, UGT1A9, and UGT1A10, respectively. All these results indicated the risk of clinical application of isoliquiritigenin on the drug-drug interaction and other possible diseases induced by the inhibition of isoliquiritigenin towards these UGT isoforms. (c) 2012 Published by Elsevier B.V. C1 [Lu, Hang; Li, Hua; Liu, Yan; Fu, Xiaoguang; Sun, Hongzhi] Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China. [Fang, Zhong-Ze; Cao, Yun-Feng; Hong, Mo; Sun, Xiao-Yu] Chinese Acad Sci, Dalian Inst Chem Phys, Joint Ctr Translat Med, Dalian 116023, Peoples R China. [Fang, Zhong-Ze; Cao, Yun-Feng; Hong, Mo; Sun, Xiao-Yu] Liaoning Med Univ, Affiliated Hosp 1, Dalian 116023, Peoples R China. [Cao, Yun-Feng] Shanghai Inst Planned Parenthood Res, Shanghai Engineer & Technol Res Ctr Reprod Hlth D, Key Lab Contracept & Devices Res NPFPC, Shanghai 200032, Peoples R China. [Fang, Zhong-Ze; Hu, Cui-Min] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Sun, HZ (reprint author), Liaoning Med Univ, Affiliated Hosp 1, Jinzhou 121001, Peoples R China. EM cmushz@163.com FU National Natural Science Foundation of China [81202586] FX This work was supported by the National Natural Science Foundation of China (no. 81202586). NR 28 TC 14 Z9 14 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JAN PY 2013 VL 84 BP 208 EP 212 DI 10.1016/j.fitote.2012.12.002 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 111OU UT WOS:000316531400029 PM 23237733 ER PT S AU Jacobson, KA Costanzi, S Deflorian, F AF Jacobson, Kenneth A. Costanzi, Stefano Deflorian, Francesca BE Conn, PM TI Probing GPCR Structure: Adenosine and P2Y Nucleotide Receptors SO G PROTEIN COUPLED RECEPTORS: STRUCTURE SE Methods in Enzymology LA English DT Review; Book Chapter ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; A(2A) RECEPTOR; BINDING-SITE; CRYSTAL-STRUCTURE; AGONIST BINDING; RECOGNITION; NUCLEOSIDES; ANTAGONIST; ACTIVATION AB The adenosine receptors (ARs) provide an example of how to accurately predict ligand recognition, even prior to the availability of a crystallographic structure. Homology modeling has been used to gain structural insight, in conjunction with site-directed mutagenesis, and structure activity relationships of small molecular ligands. Recent X-ray structures greatly improved the accuracy of knowledge of AR ligand recognition and furthermore characterized conformational changes induced by receptor activation. Now, homology modeling extends these structural insights to related GPCRs and suggests new ligand structures. This strategy is also being applied to the eight subtypes of P2Y receptors for extracellular nucleotides, which lack X-ray structures and are best modeled by homology to the CXCR4 (peptide) receptor. Neoceptors, as studied for three of the four AR subtypes, create a molecular complementarity between a mutant receptor and a chemically tailored agonist ligand to selectively enhance affinity, implying direct physical contact and thus validating docking hypotheses. C1 [Jacobson, Kenneth A.; Deflorian, Francesca] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Costanzi, Stefano/G-8990-2013; Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z99 DK999999, ZIA DK031116-24, ZIA DK031117-24, ZIA DK031126-05] NR 43 TC 2 Z9 2 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-391861-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 520 BP 199 EP 217 DI 10.1016/B978-0-12-391861-1.00009-5 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDZ26 UT WOS:000315698600009 PM 23332701 ER PT J AU Ji, JF Yu, L Yu, ZP Forgues, M Uenishi, T Kubo, S Wakasa, K Zhou, J Fan, J Tang, ZY Fu, SJ Zhu, HG Jin, JG Sun, HC Wang, XW AF Ji, Junfang Yu, Lei Yu, Zhipeng Forgues, Marshonna Uenishi, Takahiro Kubo, Shoji Wakasa, Kenichi Zhou, Jian Fan, Jia Tang, Zhao-You Fu, Shijun Zhu, Hongguang Jin, Jason Gang Sun, Hui-Chuan Wang, Xin Wei TI Development of a miR-26 Companion Diagnostic Test for Adjuvant Interferon-alpha Therapy in Hepatocellular Carcinoma SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE miR-26; hepatocellular carcinoma; interferon-alpha; adjuvant therapy; companion diagnostics ID BREAST-CANCER; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; RECURRENCE; SURVIVAL; IDENTIFICATION; RESECTION; CELLS; CHEMOTHERAPY; TRIALS AB Background & Aims: Adjuvant therapies for hepatocellular carcinoma (HCC) such as interferon-alpha are effective only in a subset of patients. Previously we found that HCC patients with low level of miR-26 have survival benefits from interferon-alpha. The purpose of this study is to develop a standardized miR-26 diagnostic test (referred as MIR26-DX) to assist identification of candidate HCC patients for adjuvant interferon-alpha therapy. Methods: We developed a multiplex reverse-transcription quantitative polymerase-chain-reaction assay to determine the levels of two HCC-related miR-26 transcripts along with six small RNA reference transcripts. We evaluated archived paraffin-embedded tissues from three cohorts of HCC patients (n=248) who underwent radical resection at three different clinical centers. Fifty-two percent of them underwent adjuvant interferon-alpha therapy. We used Cox-Mantel log-rank test to evaluate patient survival. Results: We found that the multiplexing assay was stable and reproducible regardless of differences in sample preparations and operators. We developed a matrix template and a scoring algorithm based on a training cohort (n=129) to assign HCC patients, and then applied the template in two test cohorts (n=119). The proportions of HCC patients assigned as low miR-26 by this algorithm were 68, 4, and 63 percent in the training cohort and two test cohorts, respectively. Consistently, HCC with low miR-26 had a favorable response to interferon-alpha with improved median overall survival (>= 3year). Conclusions: MIR26-DX is a simple and reliable companion diagnostic test to select HCC patients for adjuvant interferon-alpha therapy. C1 [Ji, Junfang; Yu, Lei; Yu, Zhipeng; Forgues, Marshonna; Wang, Xin Wei] NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Yu, Lei; Zhou, Jian; Fan, Jia; Tang, Zhao-You; Sun, Hui-Chuan] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [Yu, Lei; Zhou, Jian; Fan, Jia; Tang, Zhao-You; Sun, Hui-Chuan] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Uenishi, Takahiro; Kubo, Shoji] Osaka City Univ, Grad Sch Med, Dept Hepatobiliary Pancreat Surg, Osaka 558, Japan. [Wakasa, Kenichi] Osaka City Univ, Grad Sch Med, Dept Diagnost Pathol, Osaka 558, Japan. [Fu, Shijun; Zhu, Hongguang; Jin, Jason Gang] ShanghaiBio Corp, Shanghai, Peoples R China. [Fu, Shijun; Zhu, Hongguang; Jin, Jason Gang] ShanghaiBio Corp, N Brunswick, NJ USA. RP Ji, JF (reprint author), NCI, 37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. EM jijun@mail.nih.gov; xw3u@nih.gov RI Wang, Xin/B-6162-2009; Fan, Jia/C-6689-2017 FU Intramural Research Program of the Center for Cancer Research, the National Cancer Institute [Z01 BC 010876, Z01-BC 010313]; Ministry of Science of China [2013ZX10002007-004]; Bureau of Science and Technology of Shanghai [12DZ1941300] FX We thank Karen Yarrick for bibliographic assistance and the NIH Fellows Editorial Board for editing the manuscript. This work was supported in part by research grants from the Intramural Research Program of the Center for Cancer Research, the National Cancer Institute (Z01 BC 010876 and Z01-BC 010313). JZ, JF, ZYT, SF, HZ, JGJ and HCS were supported by research grants from the Ministry of Science of China (#2013ZX10002007-004) and Bureau of Science and Technology of Shanghai (#12DZ1941300) for supporting clinical development of MIR26-DX. NR 26 TC 8 Z9 12 U1 1 U2 6 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2013 VL 9 IS 3 BP 303 EP 312 DI 10.7150/ijbs.6214 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 118BG UT WOS:000316996800009 PM 23569435 ER PT J AU Saidha, S Sotirchos, ES Oh, J Syc, SB Seigo, MA Shiee, N Eckstein, C Durbin, MK Oakley, JD Meyer, SA Frohman, TC Newsome, S Ratchford, JN Balcer, LJ Pham, DL Crainiceanu, CM Frohman, EM Reich, DS Calabresi, PA AF Saidha, Shiv Sotirchos, Elias S. Oh, Jiwon Syc, Stephanie B. Seigo, Michaela A. Shiee, Navid Eckstein, Chistopher Durbin, Mary K. Oakley, Jonathan D. Meyer, Scott A. Frohman, Teresa C. Newsome, Scott Ratchford, John N. Balcer, Laura J. Pham, Dzung L. Crainiceanu, Ciprian M. Frohman, Elliot M. Reich, Daniel S. Calabresi, Peter A. TI Relationships Between Retinal Axonal and Neuronal Measures and Global Central Nervous System Pathology in Multiple Sclerosis SO JAMA NEUROLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; FIBER LAYER THICKNESS; PATTERN ELECTRORETINOGRAM; NEURITIS; ATROPHY; ABNORMALITIES; RESPONSES; DISEASE; OUTCOMES; LESIONS AB Objective: To determine the relationships between conventional and segmentation-derived optical coherence tomography (OCT) retinal layer thickness measures with intracranial volume (a surrogate of head size) and brain substructure volumes in multiple sclerosis (MS). Design: Cross-sectional study. Setting: Johns Hopkins University, Baltimore, Maryland. Participants: A total of 84 patients with MS and 24 healthy control subjects. Main Outcome Measures: High-definition spectral-domain OCT conventional and automated segmentation-derived discrete retinal layer thicknesses and 3-T magnetic resonance imaging brain substructure volumes. Results: Peripapillary retinal nerve fiber layer as well as composite ganglion cell layer + inner plexiform layer thicknesses in the eyes of patients with MS without a history of optic neuritis were associated with cortical gray matter (P=.01 and P=.04, respectively) and caudate (P=.04 and P=.03, respectively) volumes. Inner nuclear layer thickness, also in eyes without a history of optic neuritis, was associated with fluid-attenuated inversion recovery lesion volume (P=.007) and inversely associated with normal-appearing white matter volume (P=.005) in relapsing-remitting MS. As intracranial volume was found to be related with several of the OCT measures in patients with MS and healthy control subjects and is already known to be associated with brain substructure volumes, all OCT-brain substructure relationships were adjusted for intracranial volume. Conclusions: Retinal measures reflect global central nervous system pathology in multiple sclerosis, with thicknesses of discrete retinal layers each appearing to be associated with distinct central nervous system processes. Moreover, OCT measures appear to correlate with intracranial volume in patients with MS and healthy control subjects, an important unexpected factor unaccounted for in prior studies examining the relationships between peripapillary retinal nerve fiber layer thickness and brain substructure volumes. JAMA Neurol. 2013;70(1):34-43. Published online October 1, 2012. doi:10.1001/jamaneurol.2013.573 C1 [Saidha, Shiv; Sotirchos, Elias S.; Oh, Jiwon; Syc, Stephanie B.; Seigo, Michaela A.; Eckstein, Chistopher; Newsome, Scott; Ratchford, John N.; Reich, Daniel S.; Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Shiee, Navid; Pham, Dzung L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Shiee, Navid; Pham, Dzung L.; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Neuroradiol Div, Baltimore, MD USA. [Crainiceanu, Ciprian M.; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Crainiceanu, Ciprian M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Shiee, Navid] NINDS, NIH, Bethesda, MD USA. [Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. [Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Durbin, Mary K.; Oakley, Jonathan D.; Meyer, Scott A.] Carl Zeiss Meditec Inc, Dublin, CA USA. [Frohman, Teresa C.; Frohman, Elliot M.] Univ Texas Southwestern, Dept Neurol & Ophthalmol, Dallas, TX USA. [Balcer, Laura J.] Univ Penn, Dept Neurol & Ophthalmol, Philadelphia, PA 19104 USA. RP Saidha, S (reprint author), 600 N Wolfe St, Baltimore, MD 21287 USA. EM shivsaidha@physicians.ie RI Reich, Daniel/E-5701-2010; OI Reich, Daniel/0000-0002-2628-4334; Sotirchos, Elias/0000-0002-8812-1637 FU MedicalLogix; Teva Neurosciences; Biogen Idec; Novartis; Merck; On-X; Teva; Athena; Abbott Laboratories; Intramural Research Program of the National Institute of Neurological Disorders and Stroke; EMD-Serono; Biogen-Idec; Genentech; Bayer; Vertex; National Multiple Sclerosis Society [TR 3760-A-3, RG 4212-A-4]; National Eye Institute [R01 EY 014993, R01 EY 019473]; Braxton Debbie Angela Dillon and Skip Donor Advisor Fund FX Dr Saidha has received consulting fees from MedicalLogix for the development of continuing medical education programs in neurology, and educational grant support from Teva Neurosciences. Dr Oh has received educational grant support from Teva Neurosciences. Drs Durbin, Oakley, and Meyer are employed by Carl Zeiss Meditec Inc. Dr Newsome has received speaker honoraria and consulting fees from Biogen Idec. Dr Ratchford has consulted for Bristol-Myers Squibb and received a speaking honorarium from Teva. He receives research funding for clinical trials from Biogen-Idec and Novartis. Dr Balcer has received consulting honoraria for advising boards and development of visual outcomes for multiple sclerosis trials from Biogen-Idec, Novartis, Acorda Therapeutics, and Vaccinex. Dr Crainiceanu has received consulting fees from Merck and On-X. Dr E. M. Frohman has received speaker honoraria and consulting fees from Biogen Idec, Teva, and Athena. He has also received consulting fees from Abbott Laboratories. Dr Reich receives research support from the Intramural Research Program of the National Institute of Neurological Disorders and Stroke. Dr Calabresi has provided consultation services to Novartis, EMD-Serono, Teva, Biogen-Idec, Vertex, Vaccinex, Genzyme, and Genentech. He has received grant support from EMD-Serono, Teva, Biogen-Idec, Genentech, Bayer, Abbott Laboratories, and Vertex.; This study was funded by grants TR 3760-A-3 to Dr Calabresi and RG 4212-A-4 to Dr Balcer, subcontracted to Dr Calabresi, from the National Multiple Sclerosis Society; grants R01 EY 014993 and R01 EY 019473 to Dr Balcer, subcontracted to Dr Calabresi, from the National Eye Institute; and funding to Drs Balcer, E. M. Frohman, and Calabresi from the Braxton Debbie Angela Dillon and Skip Donor Advisor Fund. The study was partially supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke to Dr Reich. NR 43 TC 52 Z9 53 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2013 VL 70 IS 1 BP 34 EP 43 DI 10.1001/jamaneurol.2013.573 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 115GJ UT WOS:000316800300005 PM 23318513 ER PT J AU Quinn, CT McKinstry, RC Dowling, MM Ball, WS Kraut, MA Casella, JF Dlamini, N Ichord, RN Jordan, LC Kirkham, FJ Noetzel, MJ Roach, ES Strouse, JJ Kwiatkowski, JL Hirtz, D DeBaun, MR AF Quinn, Charles T. McKinstry, Robert C. Dowling, Michael M. Ball, William S. Kraut, Michael A. Casella, James F. Dlamini, Nomazulu Ichord, Rebecca N. Jordan, Lori C. Kirkham, Fenella J. Noetzel, Michael J. Roach, E. Steve Strouse, John J. Kwiatkowski, Janet L. Hirtz, Deborah DeBaun, Michael R. TI Acute Silent Cerebral Ischemic Events in Children With Sickle Cell Anemia SO JAMA NEUROLOGY LA English DT Article ID BLOOD-TRANSFUSION THERAPY; ACUTE STROKE; REPERFUSION INJURY; IMAGING FINDINGS; SIT TRIAL; DISEASE; BRAIN; PATHOPHYSIOLOGY; INFARCTS; RISK AB Background: Irregular, sporadic episodes of ischemic brain injury are known to occur in sickle cell anemia (SCA), resulting in overt stroke and silent cerebral infarction. Ongoing ischemia in other organs is common in SCA but has never been documented in the brain. Objective: To test the hypothesis that acute silent cerebral ischemic events (ASCIEs) are frequent and potentially transient. Design: Cross-sectional and cohort study of children with SCA screened by magnetic resonance imaging (MRI) of the brain for a randomized clinical trial. Setting: Clinical trial setting in tertiary care centers. Patients: Asymptomatic children with SCA without known stroke, neurologic injury, or epilepsy not receiving treatment with transfusions or hydroxyurea. Main Outcome Measure: Incidence of ASCIEs calculated using single diffusion-weighted MRI scans (acute ischemic events that occurred within 10 days of the MRI). Results: Acute silent cerebral ischemic events were detected on 1.3% of MRIs (10 of 771) in 652 children (mean age, 10.0 years), with an incidence of 47.3 events per 100 patient-years (95% CI, 22.7-87.2). Two of 10 children with ASCIEs had follow-up MRIs of the brain; only 1 had silent cerebral infarction in the same location as the previously detected ASCIE. Conclusions: Children with SCA experience ongoing (chronic, intermittent) cerebral ischemia, sometimes reversible, far more frequently than previously recognized. The brain in SCA is at constant threat of ischemia. JAMA Neurol. 2013;70(1):58-65. Published online October 29, 2012. doi:10.1001/jamaneurol.2013.576 C1 [Quinn, Charles T.] Cincinnati Childrens Hosp Med Ctr, Dept Hematol, Cincinnati, OH USA. [Quinn, Charles T.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH USA. [Roach, E. Steve] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA. [Roach, E. Steve] Nationwide Childrens Hosp, Dept Neurol, Columbus, OH USA. [McKinstry, Robert C.] Washington Univ, Sch Med, Dept Radiol & Pediat, St Louis, MO USA. [Noetzel, Michael J.] Washington Univ, Sch Med, Dept Neurol & Pediat, St Louis, MO USA. [Dowling, Michael M.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA. [Dowling, Michael M.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Casella, James F.; Strouse, John J.] Johns Hopkins Univ, Sch Med, Div Pediat Hematol, Baltimore, MD USA. [Hirtz, Deborah] NINDS, Div Extramural Res, NIH, Bethesda, MD 20892 USA. NINDS, Div Extramural Res, NIH, Bethesda, MD 20892 USA. [Kirkham, Fenella J.] UCL, Inst Child Hlth, Dept Pediat Neurol, Guys & St Thomas Hosp,Evelina Childrens Hosp, London, England. Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Kwiatkowski, Janet L.] Childrens Hosp Philadelphia, Dept Hematol, Philadelphia, PA 19104 USA. [Kwiatkowski, Janet L.] Univ Penn, Philadelphia, PA 19104 USA. [Jordan, Lori C.] Vanderbilt Univ, Sch Med, Div Pediat Neurol, Dept Neurol, Nashville, TN USA. [DeBaun, Michael R.] Vanderbilt Childrens Hosp, Nashville, TN USA. RP DeBaun, MR (reprint author), Vanderbilt Meharry Ctr Sickle Cell Dis Excellence, 220 Childrens Way,Rm 11206 DOT, Nashville, TN 37232 USA. EM m.debaun@vanderbilt.edu RI Kirkham, Fenella/C-2442-2009; Quinn, Charles/J-6842-2012 OI Kirkham, Fenella/0000-0002-2443-7958; Quinn, Charles/0000-0002-2372-2175 FU National Institutes of Health [U01-NS42804] FX This study was supported by grant U01-NS42804 from the National Institutes of Health. NR 25 TC 19 Z9 19 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2013 VL 70 IS 1 BP 58 EP 65 DI 10.1001/jamaneurol.2013.576 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 115GJ UT WOS:000316800300008 PM 23108767 ER PT J AU Guerreiro, RJ Lohmann, E Bras, JM Gibbs, JR Rohrer, JD Gurunlian, N Dursun, B Bilgic, B Hanagasi, H Gurvit, H Emre, M Singleton, A Hardy, J AF Guerreiro, Rita Joao Lohmann, Ebba Bras, Jose Miguel Gibbs, Jesse Raphael Rohrer, Jonathan D. Gurunlian, Nicole Dursun, Burcu Bilgic, Basar Hanagasi, Hasmet Gurvit, Hakan Emre, Murat Singleton, Andrew Hardy, John TI Using Exome Sequencing to Reveal Mutations in TREM2 Presenting as a Frontotemporal Dementia-like Syndrome Without Bone Involvement SO JAMA NEUROLOGY LA English DT Article ID NASU-HAKOLA-DISEASE; HEXANUCLEOTIDE REPEAT; DIAGNOSTIC-CRITERIA; PARKINSON DISEASE; COMPLEX; C9ORF72; VPS35; CYSTS; TAU; ALS AB Objective: To identify new genes and risk factors associated with frontotemporal dementia (FTD). Several genes and loci have been associated with different forms of FTD, but a large number of families with dementia do not harbor mutations in these genes. Design: Whole-exome sequencing and whole-genome genotyping were performed in all patients. Genetic variants obtained from whole-exome sequencing were integrated with the data obtained from whole-genome genotyping. Setting: Database of the Behavioral Neurology Outpatient-Clinic of the Department of Neurology, Istanbul Faculty of Medicine, Istanbul, Turkey. Patients: Forty-four Turkish patients with an FTD-like clinical diagnosis were included in the study. Relatives were screened when appropriate. Main Outcome Measure: Mutations in the triggering receptor expressed on myeloid cells 2 gene (TREM2). Results: In 3 probands with FTD-like disease, we identified different homozygous mutations in TREM2 that had previously been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). None of these 3 patients had a typical clinical presentation of PLOSL: they presented with behavioral change and subsequent cognitive impairment and motor features but without any bone cysts or bone-associated phenotypes. Imaging showed white matter abnormalities as well as frontal atrophy in all 3 patients. Conclusions: Our results show that TREM2 is responsible for an unexpectedly high number of dementia cases in our cohort, suggesting that this gene should be taken into account when mutations in other dementia genes are excluded. Even for complex syndromes such as dementia, exome sequencing has proven to be a rapid and cost-effective tool to identify genetic mutations, allowing for the association of clinical phenotypes with unexpected molecular underpinnings. JAMA Neurol. 2013;70(1):78-84. Published online October 8, 2012. doi:10.1001/jamaneurol.2013.579 C1 [Guerreiro, Rita Joao; Bras, Jose Miguel; Gibbs, Jesse Raphael; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Guerreiro, Rita Joao; Bras, Jose Miguel] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Guerreiro, Rita Joao; Bras, Jose Miguel; Gibbs, Jesse Raphael; Gurunlian, Nicole; Hardy, John] Inst Neurol, Reta Lilla Weston Labs, London WC1N 3BG, England. [Guerreiro, Rita Joao; Bras, Jose Miguel; Gibbs, Jesse Raphael; Gurunlian, Nicole; Hardy, John] Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. [Rohrer, Jonathan D.] UCL, UCL Inst Neurol, Dementia Res Ctr, Dept Neurodegenerat Dis, London, England. [Lohmann, Ebba; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat] Istanbul Univ, Behav Neurol & Movement Disorders Unit, Istanbul Fac Med, Dept Neurol, Istanbul, Turkey. [Dursun, Burcu] Istanbul Univ, Inst Expt Med, Istanbul, Turkey. RP Guerreiro, RJ (reprint author), UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. EM r.guerreiro@ucl.ac.uk RI Bras, Jose/A-1428-2011; Hardy, John/C-2451-2009; Singleton, Andrew/C-3010-2009; bilgic, basar/E-4821-2012; Guerreiro, Rita/A-1327-2011; OI Rohrer, Jonathan/0000-0002-6155-8417; Bras, Jose/0000-0001-8186-0333 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000950-06]; Alzheimer's Research UK, an Istanbul Neuropsychiatric Hospital (NPIstanbul) research grant; Motor Neurone Disease Association FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project Z01 AG000950-06, Alzheimer's Research UK, an Istanbul Neuropsychiatric Hospital (NPIstanbul) research grant, the Motor Neurone Disease Association, and an anonymous donor. NR 26 TC 98 Z9 98 U1 1 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6149 J9 JAMA NEUROL JI JAMA Neurol. PD JAN PY 2013 VL 70 IS 1 BP 78 EP 84 DI 10.1001/jamaneurol.2013.579 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 115GJ UT WOS:000316800300011 PM 23318515 ER PT J AU Feuer, WJ Yehoshua, Z Gregori, G Penha, FM Chew, EY Ferris, FL Clemons, TE Lindblad, AS Rosenfeld, PJ AF Feuer, William J. Yehoshua, Zohar Gregori, Giovanni Penha, Fernando M. Chew, Emily Y. Ferris, Frederick L. Clemons, Traci E. Lindblad, Anne S. Rosenfeld, Philip J. TI Square Root Transformation of Geographic Atrophy Area Measurements to Eliminate Dependence of Growth Rates on Baseline Lesion Measurements: A Reanalysis of Age-Related Eye Disease Study Report No. 26 SO JAMA OPHTHALMOLOGY LA English DT Letter ID OPTICAL COHERENCE TOMOGRAPHY C1 [Feuer, William J.; Yehoshua, Zohar; Gregori, Giovanni; Penha, Fernando M.; Rosenfeld, Philip J.] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL 33136 USA. [Chew, Emily Y.; Ferris, Frederick L.] NEI, Bethesda, MD 20892 USA. [Clemons, Traci E.; Lindblad, Anne S.] EMMES Corp, Rockville, MD USA. RP Rosenfeld, PJ (reprint author), Bascom Palmer Eye Inst, Dept Ophthalmol, 900 17th St NW, Miami, FL 33136 USA. EM prosenfeld@med.miami.edu FU NEI NIH HHS [P30 EY014801] NR 5 TC 22 Z9 22 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD JAN PY 2013 VL 131 IS 1 BP 110 EP 111 PG 2 WC Ophthalmology SC Ophthalmology GA 113QP UT WOS:000316683000026 PM 23307222 ER PT J AU Arnold, MFF Haag, AF Capewell, S Boshoff, HI James, EK McDonald, R Mair, I Mitchell, AM Kerscher, B Mitchell, TJ Mergaert, P Barry, CE Scocchi, M Zanda, M Campopiano, DJ Ferguson, GP AF Arnold, M. F. F. Haag, A. F. Capewell, S. Boshoff, H. I. James, E. K. McDonald, R. Mair, I. Mitchell, A. M. Kerscher, B. Mitchell, T. J. Mergaert, P. Barry, C. E., III Scocchi, M. Zanda, M. Campopiano, D. J. Ferguson, G. P. TI Partial Complementation of Sinorhizobium meliloti bacA Mutant Phenotypes by the Mycobacterium tuberculosis BacA Protein SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BACTEROID DEVELOPMENT; ESCHERICHIA-COLI; ANTIMICROBIAL ACTIVITY; LEGUME SYMBIOSIS; EPITHELIAL-CELLS; ATP-BINDING; LIPID-A; PEPTIDE; TRANSPORTERS; EVOLUTION AB The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human beta-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac7(1-16). This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections. C1 [Arnold, M. F. F.; Haag, A. F.; McDonald, R.; Kerscher, B.; Ferguson, G. P.] Univ Aberdeen, Inst Med Sci, Sch Med & Dent, Aberdeen, Scotland. [Capewell, S.; Mair, I.; Campopiano, D. J.] Univ Edinburgh, EastChem Sch Chem, Edinburgh, Midlothian, Scotland. [Boshoff, H. I.; Barry, C. E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA. [James, E. K.] James Hutton Inst, Dundee, Scotland. [Mitchell, A. M.; Mitchell, T. J.] Univ Birmingham, Coll Med & Dent Sci, Sch Immun & Infect, Birmingham, W Midlands, England. [Mergaert, P.] CNRS, Inst Sci Vegetales, F-91198 Gif Sur Yvette, France. [Scocchi, M.] Univ Trieste, Dept Life Sci, Trieste, Italy. [Zanda, M.] Univ Aberdeen, Inst Med Sci, Sch Med Sci, Aberdeen, Scotland. [Zanda, M.] CNR, Ist Chim Riconoscimento Mol, I-20133 Milan, Italy. RP Arnold, MFF (reprint author), Univ Aberdeen, Inst Med Sci, Sch Med & Dent, Aberdeen, Scotland. EM m-arnold@gmx.de RI Barry, III, Clifton/H-3839-2012; James, Euan/K-1135-2012; Kerscher, Bernhard/B-1907-2015; OI James, Euan/0000-0001-7969-6570; Kerscher, Bernhard/0000-0001-9300-7401; Mergaert, Peter/0000-0002-5919-7317; Mitchell, Timothy/0000-0002-8309-5556; Haag, Andreas/0000-0002-6783-0231 FU MRC [G0501107]; Scottish Universities Life Science Allianc; Institute of Medical Sciences Ph.D. studentship; EPSRC/BBSRC Life Science Interface Doctoral Training Centre (DTC) in Cell & Proteomic Technologies; Intramural Research Program of the NIH, NIAID; Agence Nationale de la Recherche [ANR-09-BLAN-0396-01] FX An MRC New Investigator (G0501107) grant awarded to G. P. F. supported this work. M. F. F. A. is a Scottish Universities Life Science Alliance-funded Ph.D. student, and A. F. H. was supported by an Institute of Medical Sciences Ph.D. studentship. S. C. is funded through a studentship from the EPSRC/BBSRC Life Science Interface Doctoral Training Centre (DTC) in Cell & Proteomic Technologies. This research was supported in part by the Intramural Research Program of the NIH, NIAID. P. M. is indebted to the Agence Nationale de la Recherche for grant ANR-09-BLAN-0396-01. NR 39 TC 9 Z9 9 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2013 VL 195 IS 2 BP 389 EP 398 DI 10.1128/JB.01445-12 PG 10 WC Microbiology SC Microbiology GA 117NG UT WOS:000316959600023 PM 23161027 ER PT J AU Raja, MR Waterman, SR Qiu, J Bleher, R Williamson, PR O'Halloran, TV AF Raja, Meera R. Waterman, Scott R. Qiu, Jin Bleher, Reiner Williamson, Peter R. O'Halloran, Thomas V. TI A copper hyperaccumulation phenotype correlates with pathogenesis in Cryptococcus neoformans SO METALLOMICS LA English DT Article ID SUPEROXIDE-DISMUTASE; IRON; VIRULENCE; YEAST; MACROPHAGES; ACQUISITION; HOMEOSTASIS; CHAPERONE; PROTEINS; BALANCE AB Cryptococcus neoformans is a major human pathogen and a cause of meningoencephalitis in immunocompromised patients. Many factors contribute to the extraordinary survivability and pathogenicity of this fungus in humans, including copper homeostasis pathways. Previous work has shown that deletion of the copper-dependent regulator Cuf1 results in decreased virulence and dissemination in brain infection, suggesting that copper acquisition is important to the persistence of this pathogen. Here, we show that the minimal copper quota of C. neoformans is maintained at a high level even when grown under conditions of stringent copper limitation. Intriguingly, when this fungal pathogen is grown in standard and copper-enriched media, it sequesters even higher levels of this essential metal, achieving levels that are far higher than non-pathogenic S. cerevisiae. The hypothesis that copper acquisition plays an essential role in virulence is further corroborated by the findings that a hypovirulent CUF1-deletant strain of C. neoformans retrieved from infected mice contains almost a 6-fold lower concentration of intracellular copper than the pathogenic wild-type strain. The concentration difference arises in part from larger-sized cuf1 Delta cell. Under in vitro growth conditions, the size of the cuf1 Delta cells is normal and the hypertrophy phenotype is readily induced in vitro under conditions of copper starvation. Taken together, these data suggest that acquisition of extraordinary levels of copper is an important factor in the survivability of the pathogen in the copper-deplete environment of infection, and effective copper concentration may play an important role in the pathogenesis of C. neoformans. C1 [Raja, Meera R.; Bleher, Reiner; O'Halloran, Thomas V.] Northwestern Univ, Dept Chem, Chem Life Proc Inst, Evanston, IL 60208 USA. [Waterman, Scott R.; Qiu, Jin; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Williamson, Peter R.] Univ Illinois, Infect Dis Sect, Dept Med, Chicago, IL USA. RP O'Halloran, TV (reprint author), Northwestern Univ, Dept Chem, Chem Life Proc Inst, 2145 Sheridan Rd, Evanston, IL 60208 USA. EM t-ohalloran@northwestern.edu FU United States Public Health Service Grant [NIH-AI45995, AI49371]; NIH, NIAID; NASA Ames Research Center [NNA04CC36G]; NSF-NSEC; NSF-MRSEC; Keck Foundation; State of Illinois at Northwestern University; Northwestern University Quantitative Bioelemental Imaging Center; Chicago Biomedical Consortium [C2006-00997]; NU [CNVR48279]; [GM038784]; [GM038784-2251]; [GM54111] FX This research was funded, in part, by the following grants: GM038784, GM038784-2251, and GM54111. This study was also partly supported by United States Public Health Service Grant NIH-AI45995, AI49371 and by the Intramural Research Program of the NIH, NIAID. ICP-MS metal analysis was performed at the Northwestern University Quantitative Bioelemental Imaging Center generously supported by NASA Ames Research Center NNA04CC36G. Electron microscopy work was performed in the Electron Probe Instrumentation Center (EPIC) facility of NUANCE Center (supported by NSF-NSEC, NSF-MRSEC, Keck Foundation, and the State of Illinois) at Northwestern University. Also, we gratefully acknowledge support by the Northwestern University Quantitative Bioelemental Imaging Center, generously funded by the Keck Foundation and the Chicago Biomedical Consortium sponsor #C2006-00997, NU #CNVR48279. NR 41 TC 7 Z9 7 U1 0 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1756-5901 EI 1756-591X J9 METALLOMICS JI Metallomics PY 2013 VL 5 IS 4 BP 363 EP 371 DI 10.1039/c3mt20220h PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117MB UT WOS:000316956400010 PM 23511945 ER PT S AU Finkielstain, GP Lui, JC Baron, J AF Finkielstain, G. P. Lui, J. C. Baron, J. BE Shamir, R Turck, D Phillip, M TI Catch-Up Growth: Cellular and Molecular Mechanisms SO NUTRITION AND GROWTH SE World Review of Nutrition and Dietetics LA English DT Article; Proceedings Paper CT 1st International Conference on Nutrition and Growth CY MAR 01-03, 2012 CL Paris, FRANCE ID PLATE SENESCENCE; RAT TIBIA; DIFFERENTIATION; KINETICS; TRANSPLANTATION; HYPOTHYROIDISM; CARTILAGE; ANIMALS; GENES; SIZE AB In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple nonskeletal tissues. Copyright (C) 2013 S. Karger AG, Basel C1 [Finkielstain, G. P.] Hosp Ninos Dr Ricardo Gutierrez, Div Endocrinol, Ctr Invest Endocrinol CEDIE CONICET, RA-1360 Buenos Aires, DF, Argentina. [Lui, J. C.; Baron, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Baron, J (reprint author), NIH, Sect Growth & Dev, CRC, Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov FU Intramural NIH HHS [ZIA HD000640-16]; NICHD NIH HHS [HD000640-16, Z01 HD000640] NR 25 TC 4 Z9 4 U1 2 U2 6 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0084-2230 BN 978-3-318-02265-0 J9 WORLD REV NUTR DIET JI World Rev.Nutr.Diet. PY 2013 VL 106 BP 100 EP 104 DI 10.1159/000342535 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BEH97 UT WOS:000316645700015 PM 23428687 ER PT J AU dos Santos, ED Prado, PC de Carvalho, WR de Lima, RV Beatriz, A de Lima, DP Hamel, E Dyba, MA Albuquerque, S AF dos Santos, Edson dos A. Prado, Paulo C. de Carvalho, Wanderley R. de Lima, Ricardo V. Beatriz, Adilson de Lima, Denis P. Hamel, Ernest Dyba, Marzena A. Albuquerque, Sergio TI SYNTHESIS AND BIOLOGICAL ACTIVITY OF SULFUR COMPOUNDS SHOWING STRUCTURAL ANALOGY WITH COMBRETASTATIN A-4 SO QUIMICA NOVA LA English DT Article DE combretastatin A-4; antitubulin activity; leishmanicidal activity ID VASCULAR DISRUPTING AGENTS; ANTIMITOTIC AGENTS; TUBULIN; POLYMERIZATION; SULFENYLATION; SULFOXIDE; SULFIDE; SULFONE AB We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl) thio] benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio) benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl] benzene (15). C1 [dos Santos, Edson dos A.; Prado, Paulo C.; de Carvalho, Wanderley R.; de Lima, Ricardo V.; Beatriz, Adilson; de Lima, Denis P.] Univ Fed Mato Grosso do Sul, Dept Quim, BR-79074460 Campo Grande, MS, Brazil. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Dyba, Marzena A.] NCI, Basic Sci Program, SAIC Frederick Inc, Struct Biophys Lab, Frederick, MD 21702 USA. [Albuquerque, Sergio] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP, Brazil. RP dos Santos, ED (reprint author), Univ Fed Mato Grosso do Sul, Dept Quim, Av Senador Filinto Muller 1555, BR-79074460 Campo Grande, MS, Brazil. EM denis.lima@ufms.br RI Beatriz, Adilson/H-9394-2012; dos Santos, Edson/I-6324-2016; de Lima, Denis/I-4607-2013 OI Beatriz, Adilson/0000-0001-6864-6092; de Lima, Denis/0000-0002-6023-4867 FU FUNDECT-MS; CAPES; PROPP-UFMS; National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX The authors are grateful to FUNDECT-MS, CAPES and PROPP-UFMS for financial support and scholarships. We are also indebted to all UFMS technicians involved in this work. This work has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 24 TC 1 Z9 1 U1 1 U2 7 PU SOC BRASILEIRA QUIMICA PI SAO PAULO PA CAIXA POSTAL 26037, 05599-970 SAO PAULO, BRAZIL SN 0100-4042 J9 QUIM NOVA JI Quim. Nova PY 2013 VL 36 IS 2 BP 279 EP U104 PG 25 WC Chemistry, Multidisciplinary SC Chemistry GA 114TV UT WOS:000316766400014 PM 23766547 ER PT J AU Niu, G Zhu, L Ho, DN Zhang, F Gao, HK Quan, QM Hida, N Ozawa, T Liu, G Chen, XY AF Niu, Gang Zhu, Lei Ho, Don N. Zhang, Fan Gao, Haokao Quan, Qimeng Hida, Naoki Ozawa, Takeaki Liu, Gang Chen, Xiaoyuan TI Longitudinal Bioluminescence Imaging of the Dynamics of Doxorubicin Induced Apoptosis SO THERANOSTICS LA English DT Article DE apoptosis; cyclic firefly luciferase; bioluminescence imaging; doxorubicin; caspase-3 ID CELL-DEATH; ANNEXIN-V; CYCLIC LUCIFERASE; DRUG DISCOVERY; LIVING MAMMALS; TUMOR RESPONSE; CANCER; CASPASE-3; NANOPARTICLES; CHEMOTHERAPY AB Objectives: Most chemotherapy agents cause tumor cell death primarily by the induction of apoptosis. The ability to noninvasively image apoptosis in vivo could dramatically benefit pre-clinical and clinical evaluation of chemotherapeutics targeting the apoptotic pathway. This study aims to visualize the dynamics of apoptotic process with temporal bioluminescence imaging (BLI) using an apoptosis specific bioluminescence reporter gene. Methods: Both UM-SCC-22B human head and neck squamous carcinoma cells and 4T I murine breast cancer cells were genetically modified with a caspase-3 specific cyclic firefly luciferase reporter gene (pcFluc-DEVD). Apoptosis induced by different concentrations of doxorubicin in the transfected cells was evaluated by both annexin V staining and BLI. Longitudinal BLI was performed in xenografted tumor models at different time points after doxorubicin or Doxil treatment, to evaluate apoptosis. After imaging, DNA fragmentation in apoptotic cells was assessed in frozen tumor sections using TUNEL staining. Results: Dose- and time-dependent apoptosis induced by doxorubicin in pcFluc-DEVD transfected UM-SCC-22B and 4T I cells was visualized and quantified by BLI. Caspase-3 activation was confirmed by both caspase activity assay and Glo (TM) luciferase assay. One dose of doxorubicin treatment induced a dramatic increase in BLI intensity as early as 24 h after treatment in 22B-pcFluc-DEVD xenografted tumors. Sustained signal increase was observed for the first 3 days and the fluorescent signal from ex vivo TUNEL staining was consistent with BLI imaging results. Long-term imaging revealed that BLI signal consistently increased and reached a maximum at around day 12 after the treatment with one dose of Doxil. Conclusions: BLI of apoptosis with pcFluc-DEVD as a reporter gene facilitates the determination of kinetics of the apoptotic process in a real-time manner, which provides a unique tool for drug development and therapy response monitoring. C1 [Niu, Gang; Zhu, Lei; Ho, Don N.; Zhang, Fan; Gao, Haokao; Quan, Qimeng; Hida, Naoki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhu, Lei; Zhang, Fan; Liu, Gang] Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361002, Fujian, Peoples R China. [Ozawa, Takeaki] Univ Tokyo, Dept Chem, Sch Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Liu, G (reprint author), Xiamen Univ, Ctr Mol Imaging & Translat Med, Sch Publ Hlth, Xiamen 361002, Fujian, Peoples R China. EM gangliu.cmitm@xmu.edu.cn RI Zhu, Lei/P-9786-2016 OI Zhu, Lei/0000-0002-1820-4795 FU Major State Basic Research Development Program of China (973 Program) [2013CB733800, 2013CB733802]; National Science Foundation of China (NSFC) [8101101, 81201086, 81201129, 51273165]; Chinese Academy of Sciences professorship for Senior International Scientists [2011T2J06]; Key Project of Chinese Ministry of Education [212149]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) FX This work was supported by the Major State Basic Research Development Program of China (973 Program) (No. 2013CB733800 and 2013CB733802), National Science Foundation of China (NSFC) (8101101, 81201086, 81201129, 51273165), Chinese Academy of Sciences professorship for Senior International Scientists (2011T2J06), Key Project of Chinese Ministry of Education (212149), and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). NR 48 TC 19 Z9 20 U1 3 U2 22 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2013 VL 3 IS 3 BP 190 EP 200 DI 10.7150/thno.5825 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 118BC UT WOS:000316996400006 PM 23471295 ER PT J AU Fricker, Z Levy, E Kleiner, D Taylor, JG Koh, C Holland, SM Heller, T AF Fricker, Zachary Levy, Elliot Kleiner, David Taylor, James G. Koh, Christopher Holland, Steven M. Heller, Theo TI Case Series: Biliary Leak After Transjugular Liver Biopsy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID COMPLICATIONS; NEEDLE C1 [Fricker, Zachary] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Levy, Elliot] NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA. [Kleiner, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Taylor, James G.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Koh, Christopher; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. [Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Fricker, Z (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM zfricker@gmail.com; theoh@intra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS NR 12 TC 2 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2013 VL 108 IS 1 BP 145 EP 147 DI 10.1038/ajg.2012.352 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 107AI UT WOS:000316186600024 PM 23287950 ER PT J AU Stokes, RA Cheng, K Deters, N Lau, SM Hawthorne, WJ O'Connell, PJ Stolp, J Grey, S Loudovaris, T Kay, TW Thomas, HE Gonzalez, FJ Gunton, JE AF Stokes, Rebecca A. Cheng, Kim Deters, Natasha Lau, Sue Mei Hawthorne, Wayne J. O'Connell, Philip J. Stolp, Jessica Grey, Shane Loudovaris, Thomas Kay, Thomas W. Thomas, Helen E. Gonzalez, Frank J. Gunton, Jenny E. TI Hypoxia-Inducible Factor-la (HIF-l alpha) Potentiates beta-Cell Survival After Islet Transplantation of Human and Mouse Islets SO CELL TRANSPLANTATION LA English DT Article DE Hypoxia-inducible factor-1 alpha (HIP-l alpha); beta-Cell function; Islet transplantation; Deferoxamine (DFO); Diabetes; Hypoxia ID HUMAN PANCREATIC-ISLETS; TYPE-1 DIABETES-MELLITUS; GROWTH-FACTOR GENE; INSULIN-SECRETION; ISOLATED RAT; HIF-1-ALPHA; LANGERHANS; EXPRESSION; HYPOXIA-INDUCIBLE-FACTOR-1-ALPHA; DYSFUNCTION AB A high proportion of beta-cells die within days of islet transplantation. Reports suggest that induction of hypoxia-inducible factor-l alpha (HIF-1 alpha) predicts adverse transplant outcomes. We hypothesized that this was a compensatory response and that HIF-l alpha protects beta-cells during transplantation. Transplants were performed using human islets or murine beta-cell-specific HIP-la-null (beta-HIP-1 alpha-null) islets with or without treatment with deferoxamine (DFO) to increase HIF-l alpha. beta-HIF-1 alpha-null transplants had poor outcomes, demonstrating that lack of HIP-l alpha impaired transplant efficiency. Increasing HIP-la improved outcomes for mouse and human islets. No effect was seen in beta-HIF-l alpha-null islets. The mechanism was decreased apoptosis, resulting in increased beta-cell mass posttransplantation. These findings show that HIP-1 alpha is a protective factor and is required for successful islet transplant outcomes. Iron chelation with DFO markedly improved transplant success in a HIPl alpha-dependent manner, thus demonstrating the mechanism of action. DFO, approved for human use, may have a therapeutic role in the setting of human islet transplantation. C1 [Stokes, Rebecca A.; Cheng, Kim; Deters, Natasha; Lau, Sue Mei; Gunton, Jenny E.] Garvan Inst Med Res, Diabet & Transcript Factors Grp, Sydney, NSW 2010, Australia. [Hawthorne, Wayne J.; O'Connell, Philip J.] Westmead Hosp, National Pancreas Transplant Unit, Sydney, NSW, Australia. [Stolp, Jessica] Garvan Inst Med Res, Sydney, NSW 2010, Australia. [Grey, Shane] Garvan Inst Med Res, Gene Therapy & Autoimmun Grp, Sydney, NSW 2010, Australia. [Loudovaris, Thomas; Kay, Thomas W.; Thomas, Helen E.] St Vincents Inst, Tom Mandel Islet Transplant Program, Melbourne, Vic, Australia. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MA USA. [Gunton, Jenny E.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW, Australia. [Gunton, Jenny E.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Gunton, Jenny E.] Westmead Hosp, Dept Diabet & Endocrinol, Sydney, NSW, Australia. RP Gunton, JE (reprint author), Garvan Inst Med Res, Diabet & Transcript Factors Grp, 384 Victoria St, Sydney, NSW 2010, Australia. EM j.gunton@garvan.org.au RI Grey, Shane/B-3020-2008 OI Grey, Shane/0000-0003-2160-1625 FU Juvenile Diabetes Research Foundation (JDRF); National Health and Medical Research Council (NHMRC) of Australia; Diabetes Australia Research Trust (DART); L'Oreal Australian Women in Science Fellowship FX This work was funded by the Juvenile Diabetes Research Foundation (JDRF), National Health and Medical Research Council (NHMRC) of Australia, and Diabetes Australia Research Trust (DART), and J.E.G was additionally funded by the L'Oreal Australian Women in Science Fellowship. We would like to thank Alice Boulghourjian from the histology core at Garvan, Biological Testing Facility (BTF) at the Garvan and the Animal Bioresources Centre (ABR) at Moss Vale for breeding and maintenance of our mice; Anita Patel and Lindy Williams from NPTU and Lina Mariana from St. Vincent's Melbourne for preparation of islets. We would also like to thank Dr. Andrew Dwyer (Concord Hospital, Sydney) and Professors Donald Chisholm, Anthony Basten, and Robert Brink (all Garvan Institute) for helpful comments on the manuscript. R.A.S., K.C., N.D., S.M.L., W.J.H., P.J.O., T.L, T.W.K., F.J.G., and J.E.G. researched, discussed, wrote, and reviewed the paper S.G. discussed the paper H.T. and J.S. researched the paper The authors declare no conflict of interest. NR 55 TC 21 Z9 21 U1 0 U2 13 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2013 VL 22 IS 2 BP 253 EP 266 DI 10.3727/096368912X647180 PG 14 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 106PV UT WOS:000316158100005 PM 22710383 ER PT J AU Miyata, Y Nakamoto, H Neckers, L AF Miyata, Yoshihiko Nakamoto, Hitoshi Neckers, Len TI The Therapeutic Target Hsp90 and Cancer Hallmarks SO CURRENT PHARMACEUTICAL DESIGN LA English DT Article DE Hsp90; co-chaperone; cancer; geldanamycin; Cdc37; protein kinase; CK2 ID HEAT-SHOCK-PROTEIN; MOLECULAR CHAPERONE HSP90; CASEIN KINASE-II; CELL-CYCLE CONTROL; POLO-LIKE KINASES; WILD-TYPE P53; TUMOR-SUPPRESSOR PROTEIN; METASTATIC BREAST-CANCER; ESCHERICHIA-COLI HSP90; NITRIC-OXIDE SYNTHASE AB Hsp90 is a major molecular chaperone that is expressed abundantly and plays a pivotal role in assisting correct folding and functionality of its client proteins in cells. The Hsp90 client proteins include a wide variety of signal transducing molecules such as protein kinases and steroid hormone receptors. Cancer is a complex disease, but most types of human cancer share common hallmarks, including self-sufficiency in growth signals, insensitivity to growth-inhibitory mechanism, evasion of programmed cell death, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. A surprisingly large number of Hsp90-client proteins play crucial roles in establishing cancer cell hallmarks. We start the review by describing the structure and function of Hsp90 since conformational changes during the ATPase cycle of Hsp90 are closely related to its function. Many co-chaperones, including Hop, p23, Cdc37, Aha1, and PP5, work together with Hsp90 by modulating the chaperone machinery. Post-translational modifications of Hsp90 and its co-chaperones are vital for their function. Many tumor-related Hsp90-client proteins, including signaling kinases, steroid hormone receptors, p53, and telomerase, are described. Hsp90 and its co-chaperones are required for the function of these tumor-promoting client proteins; therefore, inhibition of Hsp90 by specific inhibitors such as geldanamycin and its derivatives attenuates the tumor progression. Hsp90 inhibitors can be potential and effective cancer chemotherapeutic drugs with a unique profile and have been examined in clinical trials. We describe possible mechanisms why Hsp90 inhibitors show selectivity to cancer cells even though Hsp90 is essential also for normal cells. Finally, we discuss the "Hsp90-addiction" of cancer cells, and suggest a role for Hsp90 in tumor evolution. C1 [Miyata, Yoshihiko] Kyoto Univ, Grad Sch Biostudies, Dept Cell & Dev Biol, Sakyo Ku, Kyoto 6068502, Japan. [Nakamoto, Hitoshi] Saitama Univ, Grad Sch Sci & Engn, Mol Biol Course, Saitama 3388570, Japan. [Nakamoto, Hitoshi] Saitama Univ, Inst Environm Sci & Technol, Saitama 3388570, Japan. [Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Miyata, Y (reprint author), Kyoto Univ, Grad Sch Biostudies, Dept Cell & Dev Biol, Sakyo Ku, Kitashirakawa Oiwake Cho, Kyoto 6068502, Japan. EM ymiyata@lif.kyoto-u.ac.jp; nakamoto@mail.saitama-u.ac.jp; neckersl@mail.nih.gov RI Nakamoto, Hitoshi/H-5315-2012 NR 271 TC 68 Z9 69 U1 7 U2 44 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD JAN PY 2013 VL 19 IS 3 BP 347 EP 365 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110MJ UT WOS:000316446800003 PM 22920906 ER PT J AU Csermely, P Nussinov, R Szilagyi, A AF Csermely, Peter Nussinov, Ruth Szilagyi, Andras TI From Allosteric Drugs to Allo-Network Drugs: State of the Art and Trends of Design, Synthesis, and Computational Methods SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material DE Allo-network drugs; allosteric drugs; glutamatergic transmission; GPCR receptors; networks; quaternary structure; SAR landscapes; schizophrenia ID PROTEIN-COUPLED RECEPTORS; SCHIZOPHRENIA; MODULATORS AB Allosteric drugs bind to sites which are usually less conserved evolutionarily as compared to orthosteric sites. As such, they can discriminate between closely related proteins, have fewer side effects, and a consequent lower concentration can convey a lesser likelihood of receptor desensitization. However, an allosteric mode of action may also make the results of preclinical and animal experiments less predictive. The sensitivity of the allosteric consequences to the environment further increases the importance of accounting for patient population diversity. Even subtle differences in protein sequence, in cellular metabolic states or in target tissues, can result in different outcomes. This mini-hot-topic issue of CTMC showcases some successes and challenges of allosteric drug development through the examples of seven-transmembrane (GPCR), AMPA, NMDA and metabotropic glutamate receptors, as well as the morpheein model of allosterism involved in inherent metabolic errors. Finally, the development of allo-network drugs, which are allosteric drugs acting indirectly on the neighborhood of the pharmacological target in protein-protein interaction or signaling networks, is described. C1 [Csermely, Peter; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. [Csermely, Peter; Szilagyi, Andras] Semmelweis Univ, Dept Med Chem, H-1444 Budapest 8, Hungary. [Szilagyi, Andras] Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, H-1113 Budapest, Hungary. RP Csermely, P (reprint author), NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick Natl Lab Canc Res, POB B Bldg 469,Rm 149, Frederick, MD 21702 USA. EM nussinor@helix.nih.gov RI Szilagyi, Andras/A-3561-2008 OI Szilagyi, Andras/0000-0002-1773-6861 FU Intramural NIH HHS; PHS HHS [HHSN261200800001E] NR 26 TC 11 Z9 11 U1 0 U2 15 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD JAN PY 2013 VL 13 IS 1 BP 2 EP 4 PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 110LY UT WOS:000316445300002 PM 23409761 ER PT J AU Szilagyi, A Nussinov, R Csermely, P AF Szilagyi, Andras Nussinov, Ruth Csermely, Peter TI Allo-Network Drugs: Extension of the Allosteric Drug Concept to Protein-Protein Interaction and Signaling Networks SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Allo-network drugs; allosteric drugs; interactome; protein-protein interaction networks; protein structure networks; signaling networks ID TRANSFER-RNA SYNTHETASE; AMINO-ACID; MOLECULAR-DYNAMICS; COMPLEX NETWORKS; DIHYDROFOLATE-REDUCTASE; FUNCTIONAL RESIDUES; SEQUENCE VARIATIONS; CHAPERONIN GROEL; MEDIATOR COMPLEX; CONTACT NETWORKS AB Allosteric drugs are usually more specific and have fewer side effects than orthosteric drugs targeting the same protein. Here, we overview the current knowledge on allosteric signal transmission from the network point of view, and show that most intra-protein conformational changes may be dynamically transmitted across protein-protein interaction and signaling networks of the cell. Allo-network drugs influence the pharmacological target protein indirectly using specific inter-protein network pathways. We show that allo-network drugs may have a higher efficiency to change the networks of human cells than those of other organisms, and can be designed to have specific effects on cells in a diseased state. Finally, we summarize possible methods to identify allo-network drug targets and sites, which may develop to a promising new area of systems-based drug design. C1 [Szilagyi, Andras; Csermely, Peter] Semmelweis Univ, Dept Med Chem, H-1444 Budapest 8, Hungary. [Szilagyi, Andras] Res Ctr Nat Sci, Inst Enzymol, H-1113 Budapest, Hungary. [Nussinov, Ruth] NCI, Ctr Canc Res, SAIC Frederick Inc, Frederick Natl Lab Canc Res,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Szilagyi, A (reprint author), Hungarian Acad Sci, Res Ctr Nat Sci, Inst Enzymol, Karolina Ut 29, H-1113 Budapest, Hungary. EM szia@enzim.hu RI Szilagyi, Andras/A-3561-2008 OI Szilagyi, Andras/0000-0002-1773-6861 FU Hungarian National Science Foundation [OTKA K83314, K105415]; EU [TAMOP-4.2.2/B-10/1-2010-0013]; NCI, NIH [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX Work in the authors' laboratory was supported by research grants from the Hungarian National Science Foundation (OTKA K83314, K105415), by the EU (TAMOP-4.2.2/B-10/1-2010-0013). This project has been funded, in part, with federal funds from the NCI, NIH, under contract HHSN261200800001E. This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. 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 217 TC 33 Z9 33 U1 2 U2 55 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD JAN PY 2013 VL 13 IS 1 BP 64 EP 77 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 110LY UT WOS:000316445300007 PM 23409766 ER PT J AU Dias, TGC Wilson, VB Bathula, DR Iyer, SP Mills, KL Thurlow, BL Stevens, CA Musser, ED Carpenter, SD Grayson, DS Mitchell, SH Nigg, JT Fair, DA AF Dias, Taciana G. Costa Wilson, Vanessa B. Bathula, Deepti R. Iyer, Swathi P. Mills, Kathryn L. Thurlow, Bria L. Stevens, Corinne A. Musser, Erica D. Carpenter, Samuel D. Grayson, David S. Mitchell, Suzanne H. Nigg, Joel T. Fair, Damien A. TI Reward circuit connectivity relates to delay discounting in children with attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE Attention deficit hyperactivity disorder; Reward; Nucleus accumbens; fMRI; Delay discounting; Functional connectivity ID FUNCTIONAL CONNECTIVITY; DEFAULT NETWORK; ADHD; FMRI; HYPORESPONSIVENESS; HETEROGENEITY; IMPULSIVITY; IMMEDIATE; DEFICITS; SUBTYPES AB Attention-deficit/hyperactivity disorder (ADHD) is a prevalent psychiatric disorder that has poor long-term outcomes and remains a major public health concern. Recent theories have proposed that ADHD arises from alterations in multiple neural pathways. Alterations in reward circuits are hypothesized as one core dysfunction, leading to altered processing of anticipated rewards. The nucleus accumbens (NAcc) is particularly important for reward processes; task-based fMRI studies have found atypical activation of this region while the participants performed a reward task. Understanding how reward circuits are involved with ADHD may be further enhanced by considering how the NAcc interacts with other brain regions. Here we used the technique of resting-state functional connectivity MRI (rs-fcMRI) to examine the alterations in the NAcc interactions and how they relate to impulsive decision making in ADHD. Using rs-fcMRI, this study: examined differences in functional connectivity of the NAcc between children with ADHD and control children; correlated the functional connectivity of NAcc with impulsivity, as measured by a delay discounting task; and combined these two initial segments to identify the atypical NAcc connections that were associated with impulsive decision making in ADHD. We found that functional connectivity of NAcc was atypical in children with ADHD and the ADHD-related increased connectivity between NAcc and the prefrontal cortex was associated with greater impulsivity (steeper delayed-reward discounting). These findings are consistent with the hypothesis that atypical signaling of the NAcc to the prefrontal cortex in ADHD may lead to excessive approach and failure in estimating future consequences; thus, leading to impulsive behavior. (C) 2012 Elsevier B.V. and ECNP. All rights reserved. C1 [Dias, Taciana G. Costa; Wilson, Vanessa B.; Iyer, Swathi P.; Thurlow, Bria L.; Stevens, Corinne A.; Carpenter, Samuel D.; Grayson, David S.; Mitchell, Suzanne H.; Nigg, Joel T.; Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. [Dias, Taciana G. Costa; Thurlow, Bria L.; Stevens, Corinne A.; Musser, Erica D.; Carpenter, Samuel D.; Grayson, David S.; Mitchell, Suzanne H.; Nigg, Joel T.; Fair, Damien A.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Bathula, Deepti R.] Indian Inst Technol, Ropar, India. [Mills, Kathryn L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Mills, Kathryn L.] UCL, Inst Cognit Neurosci, London, England. [Fair, Damien A.] Oregon Hlth & Sci Univ, Adv Imaging Res Ctr, Portland, OR 97239 USA. RP Dias, TGC (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci & Psychiat, Mail Code HRC5D30,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM tacigcdias@yahoo.com.br; faird@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 NR 51 TC 35 Z9 35 U1 2 U2 37 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 2013 VL 23 IS 1 SI SI BP 33 EP 45 DI 10.1016/j.euroneuro.2012.10.015 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 105SC UT WOS:000316091800005 ER PT J AU Verma, A McNichol, B Dominguez-Castillo, RI Amador-Molina, JC Arciniega, JL Reiter, K Meade, BD Ngundi, MM Stibitz, S Burns, DL AF Verma, Anita McNichol, Beth Dominguez-Castillo, Rocio I. Amador-Molina, Juan C. Arciniega, Juan L. Reiter, Karine Meade, Bruce D. Ngundi, Miriam M. Stibitz, Scott Burns, Drusilla L. TI Use of Site-Directed Mutagenesis To Model the Effects of Spontaneous Deamidation on the Immunogenicity of Bacillus anthracis Protective Antigen SO INFECTION AND IMMUNITY LA English DT Article ID ASPARAGINE DEAMIDATION; ISOASPARTATE FORMATION; MOLECULAR CLOCKS; GUINEA-PIGS; PROTEINS; TOXIN; DETERMINANTS; CHALLENGE; RESIDUES; EFFICACY AB Long-term stability is a desired characteristic of vaccines, especially anthrax vaccines, which must be stockpiled for large-scale use in an emergency situation; however, spontaneous deamidation of purified vaccine antigens has the potential to adversely affect vaccine immunogenicity over time. In order to explore whether spontaneous deamidation of recombinant protective antigen (rPA)-the major component of new-generation anthrax vaccines-affects vaccine immunogenicity, we created a "genetically deamidated" form of rPA using site-directed mutagenesis to replace six deamidation-prone asparagine residues, at positions 408, 466, 537, 601, 713, and 719, with either aspartate, glutamine, or alanine residues. We found that the structure of the six-Asp mutant rPA was not significantly altered relative to that of the wild-type protein as assessed by circular dichroism (CD) spectroscopy and biological activity. In contrast, immunogenicity of aluminum-adjuvanted six-Asp mutant rPA, as measured by induction of toxin-neutralizing antibodies, was significantly lower than that of the corresponding wild-type rPA vaccine formulation. The six-Gln and six-Ala mutants also exhibited lower immunogenicity than the wild type. While the wild-type rPA vaccine formulation exhibited a high level of immunogenicity initially, its immunogenicity declined significantly upon storage at 25 degrees C for 4 weeks. In contrast, the immunogenicity of the six-Asp mutant rPA vaccine formulation was low initially but did not change significantly upon storage. Taken together, results from this study suggest that spontaneous deamidation of asparagine residues predicted to occur during storage of rPA vaccines would adversely affect vaccine immunogenicity and therefore the storage life of vaccines. C1 [Verma, Anita; McNichol, Beth; Dominguez-Castillo, Rocio I.; Amador-Molina, Juan C.; Arciniega, Juan L.; Ngundi, Miriam M.; Stibitz, Scott; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Reiter, Karine] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD USA. [Meade, Bruce D.] Meade Biol, Hillsborough, NC USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM drusilla.burns@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the Intramural Research Programs of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Center for Biologics Evaluation and Research, Food and Drug Administration, as well as an interagency agreement between the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and the Food and Drug Administration. NR 29 TC 9 Z9 9 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2013 VL 81 IS 1 BP 278 EP 284 DI 10.1128/IAI.00863-12 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108MQ UT WOS:000316298000028 PM 23115046 ER PT J AU Hyams, C Trzcinski, K Camberlein, E Weinberger, DM Chimalapati, S Noursadeghi, M Lipsitch, M Brown, JS AF Hyams, Catherine Trzcinski, Krzysztof Camberlein, Emilie Weinberger, Daniel M. Chimalapati, Suneeta Noursadeghi, Mahdad Lipsitch, Marc Brown, Jeremy S. TI Streptococcus pneumoniae Capsular Serotype Invasiveness Correlates with the Degree of Factor H Binding and Opsonization with C3b/iC3b SO INFECTION AND IMMUNITY LA English DT Article ID CLASSICAL COMPLEMENT PATHWAY; PNEUMOCOCCAL SURFACE; DEPOSITION; PHAGOCYTOSIS; ACTIVATION; DISEASE; C3B; ANTIBODIES; RESISTANCE; IMMUNITY AB Different capsular serotypes of Streptococcus pneumoniae vary markedly in their ability to cause invasive infection, but the reasons why are not known. As immunity to S. pneumoniae infection is highly complement dependent, variations in sensitivity to complement between S. pneumoniae capsular serotypes could affect invasiveness. We have used 20 capsule-switched variants of strain TIGR4 to investigate whether differences in the binding of the alternative pathway inhibitor factor H (FH) could be one mechanism causing variations in complement resistance and invasive potential between capsular serotypes. Flow cytometry assays were used to assess complement factor binding and complement-dependent neutrophil association for the TIGR4 capsule-switched strains. FH binding varied with the serotype and inversely correlated with the results of factor B binding, C3b/iC3b deposition, and neutrophil association. Differences between strains in FH binding were lost when assays were repeated with pspC mutant strains, and loss of PspC also reduced differences in C3b/iC3b deposition between strains. Median FH binding was high in capsule-switched mutant strains expressing more invasive serotypes, and a principal component analysis demonstrated a strong correlation between serotype invasiveness, high FH binding, and resistance to complement and neutrophil association. Further data obtained with 33 clinical strains also demonstrated that FH binding negatively correlated with C3b/iC3b deposition and that median FH binding was high in strains expressing more invasive serotypes. These data suggest that variations in complement resistance between S. pneumoniae strains and the association of a serotype with invasiveness could be related to capsular serotype effects on FH binding. C1 [Hyams, Catherine; Camberlein, Emilie; Chimalapati, Suneeta; Brown, Jeremy S.] UCL, Sch Med, Rayne Inst, Ctr Inflammat & Tissue Repair,Div Med, London W1N 8AA, England. [Trzcinski, Krzysztof] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Pediat Immunol & Infect Dis, Utrecht, Netherlands. [Weinberger, Daniel M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Noursadeghi, Mahdad] UCL, Div Infect & Immun, London, England. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Brown, JS (reprint author), UCL, Sch Med, Rayne Inst, Ctr Inflammat & Tissue Repair,Div Med, Mortimer St, London W1N 8AA, England. EM jeremy.brown@ucl.ac.uk OI Trzcinski, Krzysztof/0000-0002-5433-8846; Lipsitch, Marc/0000-0003-1504-9213; Weinberger, Daniel/0000-0003-1178-8086 FU Astor Foundation; Glaxo Smith Kline through the University College London M.B. Ph.D. program; Medical Research Council, United Kingdom; NIH [R01 AI048935] FX This work was undertaken at UCLH/UCL, who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centre's funding scheme. C.H. was supported by the Astor Foundation and Glaxo Smith Kline through the University College London M.B. Ph.D. program. E.C. was supported by the Medical Research Council, United Kingdom. M.L. was supported by NIH research grant R01 AI048935. The funders had no role in the study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. NR 34 TC 25 Z9 26 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2013 VL 81 IS 1 BP 354 EP 363 DI 10.1128/IAI.00862-12 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108MQ UT WOS:000316298000036 PM 23147038 ER PT J AU Mannisto, T AF Maennistoe, Tuija TI Is There Enough Evidence of Poor Fetal Growth to Merit Narrowing Free T-4 Reference Ranges during Pregnancy? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID POSTPARTUM; MANAGEMENT C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Biostat & Prevent Res, NIH, Rockville, MD 20852 USA. RP Mannisto, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Biostat & Prevent Res, NIH, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA. EM mannistoTI@mail.nih.gov OI Mannisto, Tuija/0000-0002-6382-9153 FU Intramural NIH HHS NR 9 TC 2 Z9 2 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP 43 EP 44 DI 10.1210/jc.2012-4010 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300033 PM 23293336 ER PT J AU Liu-Chittenden, Y Kebebew, E AF Liu-Chittenden, Yi Kebebew, Electron TI CpG Island Methylator Phenotype in Adrenocortical Carcinoma: Fact or Fiction? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID HUMAN GENOME; CANCER; TUMORS; MARKERS C1 [Liu-Chittenden, Yi; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, 10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov OI Liu-Chittenden, Yi/0000-0001-6357-5360 FU Intramural NIH HHS NR 17 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP 48 EP 50 DI 10.1210/jc.2012-4063 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300035 PM 23293338 ER PT J AU Major, JM Graubard, BI Dodd, KW Iwan, A Alexander, BH Linet, MS Freedman, DM AF Major, Jacqueline M. Graubard, Barry I. Dodd, Kevin W. Iwan, Allison Alexander, Bruce H. Linet, Martha S. Freedman, D. Michal TI Variability and Reproducibility of Circulating Vitamin D in a Nationwide U.S. Population SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM 25-HYDROXYVITAMIN D; D DEFICIENCY; POSTMENOPAUSAL WOMEN; MEASUREMENT ERROR; ASSAYS; RISK; PLASMA; HEALTH; CANCER; ADULTS AB Context: Most studies examining associations between circulating vitamin D and disease are based on a single measure of vitamin D, which may not reflect levels over time, particularly because vitamin D concentrations vary by season. Few studies evaluated how well multiple 25-hydroxyvitamin D [25(OH)D] measures track within the same individual over time. Objective: This study examined variability and reproducibility of vitamin D by evaluating repeat measurements of plasma 25(OH)D concentrations while accounting for determinants of circulating concentrations including dietary supplement use and latitude of residence from a population of U. S. radiologic technologists. Design and Participants: We analyzed circulating 25(OH)D in blood samples taken from 538 men and women from a prospective, nationwide study at two time points within a 1-yr period, most measured in different seasons. Inter- and intra-individual variability, reliability coefficients, and measurement error were examined. Results: The spearman rank correlation between two measurements of 25(OH)D concentrations was moderate (r = 0.75, P < 0.001) and did not vary significantly by participant characteristics including age, race, or latitude. The intraclass correlation coefficient was 0.72 (95% confidence interval = 0.68-0.76). The deattenuation factor of plasma 25(OH)D levels was 1.39, suggesting that a single measure of vitamin D on a continuous scale in regression analyses may result in attenuated relationships of about 40%. Conclusion: Our results suggest that a single blood sample obtained in spring or fall provides a reasonable average for 25(OH)D over a 1-yr period, but additional studies are needed to estimate variability and agreement in plasma 25(OH)D measurements over longer intervals and younger populations. (J Clin Endocrinol Metab 98: 97-104, 2013) C1 [Major, Jacqueline M.; Graubard, Barry I.; Linet, Martha S.; Freedman, D. Michal] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20852 USA. [Dodd, Kevin W.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20852 USA. [Iwan, Allison; Alexander, Bruce H.] Univ Minnesota, Div Environm Hlth Sci, Sch Publ Hlth, Minneapolis, MN 55455 USA. RP Major, JM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM majorjm@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; U.S. Public Health Service of the Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the U.S. Public Health Service of the Department of Health and Human Services. NR 42 TC 20 Z9 21 U1 1 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP 97 EP 104 DI 10.1210/jc.2012-2643 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300041 PM 23144464 ER PT J AU Trikudanathan, S Pedley, A Massaro, JM Hoffmann, U Seely, EW Murabito, JM Fox, CS AF Trikudanathan, Subbulaxmi Pedley, Alison Massaro, Joseph M. Hoffmann, Udo Seely, Ellen W. Murabito, Joanne M. Fox, Caroline S. TI Association of Female Reproductive Factors with Body Composition: The Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GESTATIONAL DIABETES-MELLITUS; ADIPOSE-TISSUE VOLUMES; METABOLIC RISK-FACTORS; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; FAT DISTRIBUTION; MENOPAUSAL TRANSITION; WAIST CIRCUMFERENCE; PHYSICAL-ACTIVITY; RELATIVE WEIGHT AB Background: Identifying reproductive risk factors in women offers a life course approach to obesity and cardiovascular disease prevention. The association of female reproductive factors with measures of regional body fat distribution has not been comprehensively studied. Methods: We examined the association of female reproductive factors (age at menarche, parity, age at natural menopause, menopausal status) in association with body composition data from women who participated in the Offspring and the Third Generation Framingham Heart Study cohorts. Visceral adipose tissue (VAT) and sc adipose tissue (SAT) were measured volumetrically by multidetector computerized tomography. We modeled the relationship between each fat depot and female reproductive factors after adjusting for various factors such as age, smoking status, alcohol intake, physical activity index, hormone replacement therapy, and menopausal status. Results: Earlier age at menarche was associated with increased body mass index (BMI), waist circumference (WC), VAT, and SAT (P < 0.0001). This association of earlier menarche with adiposity measures was attenuated after adjusting for BMI (all P > 0.70). We observed no association between parity and all parameters of adiposity measurements (all P > 0.24). Similarly, age at natural menopause was not associated with measures of body composition. Despite higher mean BMI among the post-(BMI 27.3 kg/m(2)) compared with the premenopausal women(BMI 25.9 kg/m(2)) in an age-matched analysis, mean VAT was not different between the two groups (P = 0.30). Conclusions: Earlier menarche is associated with overall obesity but not with VAT or SAT after accounting for measures of generalized adiposity. Parity and menopausal age were not associated with adiposity measures. Although postmenopausal women had increased BMI, VAT, and SAT, the association was predominantly due to age. (J Clin Endocrinol Metab 98: 236-244, 2013) C1 [Trikudanathan, Subbulaxmi; Seely, Ellen W.; Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Metab & Diabet,Dept Med, Boston, MA 02115 USA. [Hoffmann, Udo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Pedley, Alison] NIH, Bethesda, MD 20892 USA. [Massaro, Joseph M.; Murabito, Joanne M.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Fox, Caroline S.] NHLBI, Ctr Populat Studies, Bethesda, MD 20824 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, T32 HL 007609-26] FX This work was partially supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (Contract N01-HC-25195) and Grant T32 HL 007609-26. This research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute of the National Institutes of Health and Boston University School of Medicine. NR 43 TC 17 Z9 18 U1 4 U2 14 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP 236 EP 244 DI 10.1210/jc.2012-1785 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300057 PM 23093491 ER PT J AU Kizer, JR Benkeser, D Arnold, AM Djousse, L Zieman, SJ Mukamal, KJ Tracy, RP Mantzoros, CS Siscovick, DS Gottdiener, JS Ix, JH AF Kizer, Jorge R. Benkeser, David Arnold, Alice M. Djousse, Luc Zieman, Susan J. Mukamal, Kenneth J. Tracy, Russell P. Mantzoros, Christos S. Siscovick, David S. Gottdiener, John S. Ix, Joachim H. TI Total and High-Molecular-Weight Adiponectin and Risk of Coronary Heart Disease and Ischemic Stroke in Older Adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FASTING PLASMA-GLUCOSE; CARDIOVASCULAR HEALTH; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; WOMEN; MEN; PARTICIPANTS; INFLAMMATION; MORTALITY; FAILURE AB Context: Adiponectin is atheroprotective in the laboratory, but prospective studies have shown opposite associations with cardiovascular disease (CVD) in healthy middle-aged populations (protective) and older cohorts (adverse). Whether this relates to different proportions of high-molecular-weight (HMW) adiponectin is unknown. Objective: The aim of the study was to test the hypothesis that total adiponectin is directly associated, but HMW adiponectin is inversely related, with CVD in older adults. Design, Setting, and Participants: We evaluated 3290 participants free of prevalent CVD in a longitudinal cohort study of U. S. adults aged 65 yr and older. Main Outcome Measures: We measured incident CVD (n = 1291), comprising coronary heart disease and ischemic stroke. Results: Total and HMW adiponectin were tightly correlated (r = 0.94). Cubic splines adjusted for potential confounders revealed that the associations of total and HMW adiponectin with CVD were U-shaped, with inflection points of 20 and 10 mg/liter, respectively. After controlling for potential confounding, levels of total and HMW adiponectin below these cutpoints tended to be inversely associated with incident CVD, driven by their significant or near-significant relations with coronary heart disease [hazard ratio (HR), 0.85 per SD increase; 95% confidence interval (CI), 0.75-96; and HR, 0.87; 95% CI, 0.75-1.01, respectively]. These associations were abrogated by additional inclusion of putative metabolic intermediates. Above these cutpoints, however, both total and HMW adiponectin were significantly directly associated with CVD after adjustment for confounders and, particularly, mediators (HR, 1.20 per SD increase; 95% CI, 1.06-1.35; and HR, 1.12; 95% CI, 1.02-1.24, respectively). Conclusion: In community-living elders, total and HMW adiponectin showed similar U-shaped relationships with CVD. The inverse relation in the lower range, but not the direct association at the higher end, disappeared after inclusion of putative intermediates, suggesting that high levels may reflect adverse processes separate from adiponectin's beneficial glycometabolic properties. (J Clin Endocrinol Metab 98: 255-263, 2013) C1 [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Kizer, Jorge R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10065 USA. [Benkeser, David; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02130 USA. [Djousse, Luc; Mantzoros, Christos S.] Harvard Univ, Sch Med, Boston, MA 02130 USA. [Djousse, Luc] Boston Vet Affairs Med Ctr, Boston, MA 02130 USA. [Zieman, Susan J.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20814 USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Mukamal, Kenneth J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Tracy, Russell P.] Univ Vermont, Dept Pathol, Colchester, VT 05401 USA. [Tracy, Russell P.] Univ Vermont, Dept Biochem, Colchester, VT 05401 USA. [Mantzoros, Christos S.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02130 USA. [Mantzoros, Christos S.] Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA 02130 USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Gottdiener, John S.] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA. [Ix, Joachim H.] Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, Dept Med, San Diego, CA 92093 USA. [Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92093 USA. RP Kizer, JR (reprint author), Albert Einstein Coll Med, Cardiovasc Clin Res Unit, Mazer Bldg,Room 114,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jorge.kizer@einstein.yu.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU National Heart, Lung and Blood Institute (NHLBI) [R01 HL-094555, HHSN268201200036C, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, HL080295]; National Institute on Aging [AG-023629, AG-15928, AG-20098, AG-027058] FX This work was supported by Grant R01 HL-094555 from the National Heart, Lung and Blood Institute (NHLBI). The Cardiovascular Health Study was supported by NHLBI contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086; N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, and NHLBI Grant HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided through Grants AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging. See also http://www.chs-nhlbi.org/pi.htm. NR 40 TC 18 Z9 19 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP 255 EP 263 DI 10.1210/jc.2012-2103 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300059 PM 23162097 ER PT J AU Boyce, AM Glover, M Kelly, MH Brillante, BA Butman, JA Fitzgibbon, EJ Brewer, CC Zalewski, CK Peck, CMC Kim, HJ Collins, MT AF Boyce, Alison M. Glover, McKinley Kelly, Marilyn H. Brillante, Beth A. Butman, John A. Fitzgibbon, Edmond J. Brewer, Carmen C. Zalewski, Christopher K. Peck, Carolee M. Cutler Kim, H. Jeffrey Collins, Michael T. TI Optic Neuropathy in McCune-Albright Syndrome: Effects of Early Diagnosis and Treatment of Growth Hormone Excess SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; FIBROUS DYSPLASIA; SOMATOSTATIN ANALOG; PEGVISOMANT; THERAPY; GH; HYPERSECRETION; DYSFUNCTION; MUTATION; STATURE AB Context: GH excess is a serious complication of McCune-Albright syndrome (MAS) and has been associated with craniofacial morbidity. Objective: The aim of the study was to determine whether early diagnosis and treatment of MAS-associated GH excess prevents optic neuropathy and hearing impairment, the major morbidities associated with GH excess. Design and Setting: A retrospective cross-sectional analysis was conducted at a clinical research center. Patients: Twenty-two subjects with MAS-associated GH excess and 21 control MAS subjects without GH excess were included in the study. Intervention: Biochemical testing included random GH, nadir GH after glucose load, nadir GH on frequent sampling, and IGF-I Z-score. Subjects underwent imaging, ophthalmological, audiological, and otolaryngological assessment. Treatment included octreotide, pegvisomant, transphenoidal surgery, and/or radiotherapy as indicated. Main Outcome Measure: Association of optic neuropathy and hearing impairment to age at GH excess diagnosis/treatment was measured. Results: Of 129 MAS subjects, 26 (20%) were diagnosed with GH excess based on elevation of two measures of GH function. Of these, 22 subjects were candidates for pharmacological intervention. Optic neuropathy was significantly correlated with intervention status, with no cases in the early intervention group (diagnosed/treated before age 18) or the control group, and four of seven (57%) in the late intervention group (diagnosed/treated after age 18) (Fisher's exact test; odds ratio, 0.027; P = 0.0058). Early diagnosis/intervention was not associated with reduction in hearing deficits (odds ratio, 1.25; P = 1.00). Mean head circumference SD score was significantly higher in the late (6.08; range, 2.70 to 22.56) than the early intervention (2.67; range, -0.65 to 6.72) or control groups (2.13; range, -2.06 to 7.79) (P = 0.003). Conclusions: Early diagnosis/treatment of GH excess in MAS is important to prevent optic neuropathy and craniofacial expansion. The relationship between hearing deficits and GH excess remains less clear and requires further study. (J Clin Endocrinol Metab 98: E126-E134, 2013) C1 [Boyce, Alison M.; Glover, McKinley; Kelly, Marilyn H.; Brillante, Beth A.; Peck, Carolee M. Cutler; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Boyce, Alison M.] NICHHD, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Boyce, Alison M.] Childrens Natl Med Ctr, Bone Hlth Program, Div Orthopaed & Sports Med, Washington, DC 20010 USA. [Glover, McKinley] Duke Univ, Sch Med, Durham, NC 27710 USA. [Glover, McKinley] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Fitzgibbon, Edmond J.] NEI, NIH, Bethesda, MD 20892 USA. [Brewer, Carmen C.; Zalewski, Christopher K.] Natl Inst Deafness & Other Commun Disorders, Audiol Unit, Otolaryngol Branch, NIH, Bethesda, MD 20892 USA. [Peck, Carolee M. Cutler] Univ Tennessee, Hlth Sci Ctr, Hamilton Eye Inst, Memphis, TN 38163 USA. [Kim, H. Jeffrey] Natl Inst Deafness & Other Commun Disorders, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Kim, H. Jeffrey] Georgetown Univ Hosp, Dept Otolaryngol, Washington, DC 20007 USA. RP Boyce, AM (reprint author), Childrens Natl Med Ctr, Bone Hlth Program, Div Orthopaed & Sports Med, 111 Michigan Ave NW, Washington, DC 20010 USA. EM aboyce@childrensnational.org; mcollins@mail.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; National Institute of Child Health and Human Development; National Institute on Deafness and Other Communication Disorders; National Eye Institute, National Institutes of Health, Department of Health and Human Services; Clinical Research Training Program; NIH; Pfizer Pharmaceutical Group FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institute of Child Health and Human Development, National Institute on Deafness and Other Communication Disorders, and the National Eye Institute, National Institutes of Health, Department of Health and Human Services, and in part by the Clinical Research Training Program, a public-private partnership supported by the NIH, and a grant to the Foundation for the NIH from Pfizer Pharmaceutical Group (to M.G.). NR 33 TC 17 Z9 19 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP E126 EP E134 DI 10.1210/jc.2012-2111 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300020 PM 23093488 ER PT J AU Lee, P Brychta, RJ Linderman, J Smith, S Chen, KY Celi, FS AF Lee, Paul Brychta, Robert J. Linderman, Joyce Smith, Sheila Chen, Kong Y. Celi, Francesco S. TI Mild Cold Exposure Modulates Fibroblast Growth Factor 21 (FGF21) Diurnal Rhythm in Humans: Relationship between FGF21 Levels, Lipolysis, and Cold-Induced Thermogenesis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BROWN ADIPOSE-TISSUE; HEALTHY-ADULTS; PPAR-ALPHA; ADIPOCYTES; FAT; FIBROBLAST-GROWTH-FACTOR-21; METABOLISM; INDUCTION; CELL AB Context: Cold exposure stimulates fibroblast growth factor 21 (FGF21) secretion in animals, enhancing the cold-induced thermogenesis (CIT) response through browning of white adipose tissue. In humans, the effects of cold exposure on circulating FGF21 levels are unknown. Objective: Our objective was to evaluate the effects of mild cold exposure on circulating FGF21 and its relationship with CIT and lipolysis in humans. Design and Setting: We conducted a randomized, single-blind, crossover intervention study at the National Institutes of Health Clinical Center. Participants: Participants were healthy adults. Intervention: Subjects were exposed to a 12-h exposure to 24 or 19 C in a whole-room indirect calorimeter. Outcome Measures: Energy expenditure, plasma FGF 21, nonesterified fatty acid, and adipose tissue microdialysis glycerol concentrations were evaluated. Results: At 24 C, plasma FGF21 exhibited a diurnal rhythm, peaking at 0800 h [110 (59-178) pg/ml], and progressively dropped to a nadir at 1700 h [41 (21-71) pg/ml, P < 0.0001] before rising at 1900 h [60 (11-81) pg/ml, P < 0.0001]. Exposure at 19 C lessened the diurnal reduction of FGF21 observed at 24 C from 0800-1700 h and augmented overall FGF21 levels by 37 +/- 45% (P = 0.01). The change in area under the curve plasma FGF21 between 19 and 24 C correlated positively with the change in area under the curve adipose microdialysate glycerol (R-2 = 0.35, P = 0.04) but not with nonesterified fatty acid. Cold-induced increase in FGF21 predicted greater rise in energy expenditure during cold exposure (beta = 0.66, P = 0.027), independent of age, gender, fat mass, and lean mass. Conclusions: Mild cold exposure increased circulating FGF21 levels, predicting greater lipolysis and CIT. A small reduction in environmental temperature is sufficient to modulate FGF21 diurnal rhythm in humans, which may mediate cold-induced metabolic changes similar to those in animals. (J Clin Endocrinol Metab 98: E98-E102, 2013) C1 [Lee, Paul; Brychta, Robert J.; Linderman, Joyce; Smith, Sheila; Chen, Kong Y.; Celi, Francesco S.] NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Lee, P (reprint author), NIDDKD, Diabet Endocrinol & Obes Branch, NIH, Clin Res Ctr, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM pcylee@gmail.com OI Chen, Kong/0000-0002-0306-1904 FU National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Intramural Research Program [Z01-DK047057-01, Z01-DK047057-02]; Australian National Health Medical Research Council Early Career Fellowship; Diabetes Australia Fellowship; Bushell Traveling Fellowship, Foundation; Royal Australasian College of Physicians FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Intramural Research Program Z01-DK047057-01 and Z01-DK047057-02; P.L. was supported by an Australian National Health Medical Research Council Early Career Fellowship, the Diabetes Australia Fellowship and Bushell Traveling Fellowship, Foundation, Royal Australasian College of Physicians. NR 19 TC 39 Z9 39 U1 3 U2 13 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP E98 EP E102 DI 10.1210/jc.2012-3107 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300015 PM 23150685 ER PT J AU Weisbrod, AB Nilubol, N Weinstein, LS Simonds, WF Libutti, SK Jensen, RT Marx, SJ Kebebew, E AF Weisbrod, Allison B. Nilubol, Naris Weinstein, Lee S. Simonds, William F. Libutti, Steven K. Jensen, Robert T. Marx, Stephen J. Kebebew, Electron TI Association of Type-O Blood with Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PANCREATIC-CANCER; GROUP ANTIGENS; GROUP ALLELES; LEWIS-B; EXPRESSION; RISK; ABH; CARCINOMA; TISSUE; COHORT AB Context: The ABO blood type system describes the expression of human blood group antigens found on both erythrocytes and normal tissue throughout the body. We recently reported an association between O blood type and the manifestation of pancreatic neuroendocrine tumors in a cohort of patients with Von Hippel-Lindau syndrome. Objective: The aim of the study was to determine whether there is an association of ABO blood type with the development of neuroendocrine tumors in patients with multiple endocrine neoplasia, type 1 (MEN-1). Design: Aretrospective analysis of 105 patients with MEN-1 was performed. Demographic, clinical, and biochemical data were analyzed by ABO blood type. Fisher's exact test was used to determine association between ABO blood type and manifestation of neuroendocrine tumor. Results: Demographic and clinical characteristics were similar amongst blood type cohorts. We found an association between O blood type and the manifestation of a primary neuroendocrine tumor of the gastrointestinal tract, lung, pancreas, and thymus in patients with MEN-1 (P = 0.01). Sixteen of 17 (94%) metastatic tumors had type-O blood, compared to 32 of 43 (74%) with a benign tumor who had non-O blood type. Conclusions: Our findings suggest an association between O blood type and the manifestation of a primary neuroendocrine tumor in patients with MEN-1. Prospective clinical studies are warranted to see whether patient blood type status may be a useful addition to current screening and surveillance practices. (J Clin Endocrinol Metab 98: E109-E114, 2013) C1 [Weisbrod, Allison B.; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA. [Weinstein, Lee S.; Simonds, William F.; Marx, Stephen J.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Libutti, Steven K.] Montefiore Med Ctr, Dept Surg, Bronx, NY 10461 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. [Jensen, Robert T.] NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weisbrod, AB (reprint author), NIH, Hatfield Clin Res Ctr, Room 4-5952,10 Ctr Dr, Bethesda, MD 20892 USA. EM abweisbrod@gmail.com FU Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 20 TC 6 Z9 7 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 2013 VL 98 IS 1 BP E109 EP E114 DI 10.1210/jc.2012-2781 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 107IT UT WOS:000316210300017 PM 23093487 ER PT J AU Kobayashi, SD DeLeo, FR AF Kobayashi, Scott D. DeLeo, Frank R. TI Systems Biology and Innate Immunity SO JOURNAL OF INNATE IMMUNITY LA English DT Editorial Material ID CIRCADIAN CLOCK; INFLAMMATORY RESPONSES; METABOLISM; INFECTION; APOPTOSIS; CYTOKINES; RHYTHMS; C5A C1 [Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, South 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nth.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS [ZIA AI000900-11] NR 26 TC 2 Z9 2 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2013 VL 5 IS 2 BP 97 EP 99 DI 10.1159/000347135 PG 3 WC Immunology SC Immunology GA 106PX UT WOS:000316158300001 PM 23428597 ER PT J AU Schwartz, JT Bandyopadhyay, S Kobayashi, SD McCracken, J Whitney, AR Deleo, FR Allen, LAH AF Schwartz, Justin T. Bandyopadhyay, Sarmistha Kobayashi, Scott D. McCracken, Jenna Whitney, Adeline R. DeLeo, Frank R. Allen, Lee-Ann H. TI Francisella tularensis Alters Human Neutrophil Gene Expression: Insights into the Molecular Basis of Delayed Neutrophil Apoptosis SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Neutrophil; Polymorphonuclear leukocyte; Apoptosis; Gene expression; Microarray; Tularemia; XIAP; BAX ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; NF-KAPPA-B; DIFFERENTIATION PROGRAM; INFLAMMASOME ACTIVATION; CONSTITUTIVE APOPTOSIS; BACTERIAL PATHOGENS; NLRP3 INFLAMMASOME; INHIBITION AB We demonstrated recently that Francisella tularensis profoundly impairs human neutrophil apoptosis, but how this is achieved is largely unknown. Herein we used human oligonucleotide microarrays to test the hypothesis that changes in neutrophil gene expression contribute to this phenotype, and now demonstrate that F. tularensis live vaccine strain (LVS) caused significant changes in neutrophil gene expression over a 24-hour time period relative to the uninfected controls. Of approximately 47,000 genes analyzed, 3,435 were significantly up- or downregulated by LVS, including 365 unique genes associated with apoptosis and cell survival. Specific targets in this category included genes associated with the intrinsic and extrinsic apoptotic pathways (CFLAR, TNFAIP3, TNFRSF10D, SOD2, BCL2A1, BIRC4, PIM2, TNFSF10, TNFRSF10C, CASP2 and CASP8) and genes that act via the NF kappa B pathway and other mechanisms to prolong cell viability (NFKB1, NFKB2 and RELA, IL1B, CAST, CDK2, GADD45B, BCL3, BIRC3,CDK2, IL1A, PBEF1, IL6,CXCL1, CCL4 and VEGF). The microarray data were confirmed by qPCR and pathway analysis. Moreover, we demonstrate that the X-linked inhibitor of apoptosis protein remained abundant in polymorphonuclear leukocytes over 48 h of LVS infection, whereas BAX mRNA and protein were progressively downregulated. These data strongly suggest that antiapoptotic and prosurvival mechanisms collaborate to sustain the viability of F. tularensis-infected neutrophils. Copyright (C) 2012 S. Karger AG, Basel C1 [Schwartz, Justin T.; Bandyopadhyay, Sarmistha; McCracken, Jenna; Allen, Lee-Ann H.] Univ Iowa, Inflammat Program, Iowa City, IA USA. [Schwartz, Justin T.; McCracken, Jenna; Allen, Lee-Ann H.] Univ Iowa, Dept Microbiol, Iowa City, IA 52242 USA. [Bandyopadhyay, Sarmistha; Allen, Lee-Ann H.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Vet Adm Med Ctr, Iowa City, IA USA. [Kobayashi, Scott D.; Whitney, Adeline R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Allen, LAH (reprint author), Univ Iowa, Inflammat Program, 2501 Crosspk Rd,MTF D-154, Coralville, IA 52241 USA. EM lee-ann-allen@uiowa.edu OI DeLeo, Frank/0000-0003-3150-2516; Allen, Lee-Ann/0000-0001-8929-6968 FU Public Health Service: NIH NIAID [R01AI073835-05, T32-AI007511]; NIAID, NIH FX This work was supported in part by funds from the Public Health Service: NIH NIAID R01AI073835-05 to L.-A.H.A.; a T32-AI007511 predoctoral fellowship to J.T.S., and the Intramural Research Program of the NIAID, NIH. We thank Swarup Bhattacharya of the University of Iowa Hospitals and Clinics (Iowa City, Iowa, USA) for his help with data analysis. NR 42 TC 13 Z9 14 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2013 VL 5 IS 2 BP 124 EP 136 DI 10.1159/000342430 PG 13 WC Immunology SC Immunology GA 106PX UT WOS:000316158300004 PM 22986450 ER PT J AU Johnston, CO Sutton, K Prabhu, D Bose, D AF Johnston, Christopher O. Sutton, Kenneth Prabhu, Dinesh Bose, Deepak TI Radiative Heating Uncertainty for Hyperbolic Earth Entry, Part 2: Comparisons with 1960s-Era Shock-Tube Measurements SO JOURNAL OF SPACECRAFT AND ROCKETS LA English DT Article ID TOTAL EMISSION COEFFICIENT; LINE RADIATION; AIR; CONDUCTIVITY; NITROGEN; PLASMA AB The computational technique and uncertainty analysis presented in Part 1 (Johnston et al., "Assessment of Radiative Heating Uncertainty for Hyperbolic Earth Entry Part 1: Flight Simulation Modeling and Uncertainty," Journal of Spacecraft and Rockets, Vol. 50, No. 1, 2013, pp. 19-38.) for Mars-return radiative heating simulations are applied to 1960s era shock-tube and constricted-arc experimental cases. It is shown that these experiments contain shock-layer temperatures and radiative flux values relevant to the Mars-return cases of present interest. Comparisons between the predictions and measurements, accounting for the uncertainty in both, are made for a range of experiments. A measure of comparison quality is defined, which consists of the percent overlap of the predicted uncertainty bar with the corresponding measurement uncertainty bar. For nearly all cases, this percent overlap is greater than zero, and for most of the higher temperature cases (T > 13,000 K), it is greater than 50%. These favorable comparisons provide evidence that the baseline computational technique and uncertainty analysis presented in Part 1 are adequate for Mars-return simulations. C1 [Johnston, Christopher O.] NASA, Langley Res Ctr, Hampton, VA 23669 USA. [Sutton, Kenneth] NIA, Hampton, VA 23669 USA. [Prabhu, Dinesh] ERG Corp, Mountain View, CA 94035 USA. [Bose, Deepak] NASA, Ames Res Ctr, Mountain View, CA 94035 USA. RP Johnston, CO (reprint author), NASA, Langley Res Ctr, Hampton, VA 23669 USA. FU NASA's Fundamental Aeronautics Program; NASA [NNA10DE12C] FX The authors would like to thank NASA's Fundamental Aeronautics Program for funding this work. Dinesh Prabhu was supported by NASA contract NNA10DE12C to ERC Corporation. The authors thank James L. Brown (NASA Ames), Scott Berry (NASA Langley), Brain Hollis (NASA Langley), and Joseph G. Marvin (ERC Corporation) for their comments and recommendations as members of the Uncertainty Quantification Team. NR 22 TC 3 Z9 3 U1 1 U2 6 PU AMER INST AERONAUT ASTRONAUT PI RESTON PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA SN 0022-4650 J9 J SPACECRAFT ROCKETS JI J. Spacecr. Rockets PD JAN-FEB PY 2013 VL 50 IS 1 BP 39 EP 47 DI 10.2514/1.A32483 PG 9 WC Engineering, Aerospace SC Engineering GA 102HN UT WOS:000315835800004 ER PT J AU Shulman, ST Long, SS AF Shulman, Stanford T. Long, Sarah S. TI A Conversation with Sarah S. Long, MD SO PEDIATRIC ANNALS LA English DT Editorial Material C1 [Long, Sarah S.] NIH, Res Advisory Comm, Bethesda, MD USA. [Long, Sarah S.] Ctr Dis Control & Prevent, Res Advisory Comm, Atlanta, GA USA. NR 0 TC 0 Z9 0 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 JAN PY 2013 VL 42 IS 1 BP 40 EP 40 DI 10.3928/00904481-20121221-18 PG 1 WC Pediatrics SC Pediatrics GA 107VC UT WOS:000316247900022 ER PT J AU Bektas, A Zhang, YQ Wood, WH Becker, KG Madara, K Ferrucci, L Sen, R AF Bektas, Arsun Zhang, Yongqing Wood, William H. Becker, Kevin G. Madara, Karen Ferrucci, Luigi Sen, Ranjan TI Age-associated alterations in inducible gene transcription in human CD4(+) T lymphocytes SO AGING-US LA English DT Article DE human; CD4(+) T cell; NF-kappa B; aging; aene expression ID FACTOR-KAPPA-B; IG-LIKE RECEPTORS; NAIVE CD4(+); UP-REGULATION; CELL SUBSETS; EXPRESSION; ACTIVATION; PROFILES; MEMORY; SENESCENCE AB Age associated immune dysregulation results in a pro-inflammatory state and increased susceptibility to infections and autoimmune diseases. Studies show that signaling initiated at the T cell antigen receptor (TCR) is impaired in CD4(+) T cells from old compared to young mice. Here we examined TCR-inducible gene expression changes in CD4(+) T cells during human aging. We reveal a dichotomy in gene expression mediated by the inducible transcription factor NF-kappa B. Most NF-kappa B target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-kappa B target genes including genes associated with chronic pro-inflammatory state in the elderly, such as interleukin 1 and 6, continue to be up-regulated even in the absence of NF-kappa B induction. In addition, we identify other widespread changes in gene expression between cells derived from older and younger individuals. Surprisingly, many of the most noteworthy age-associated changes in human CD4(+) T cells differ from those seen in murine models. Our studies provide the first view of age-associated alteration of TCR-inducible gene expression in human CD4(+) T cells. C1 [Sen, Ranjan] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Bektas, Arsun; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing; Wood, William H.; Becker, Kevin G.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. [Madara, Karen] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Sen, R (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM senra@mail.nih.gov OI Becker, Kevin/0000-0002-6794-6656 FU Intramural Research Program of the National Institute on Aging (Baltimore, MD) FX We thank Drs. Nan-Ping Weng and Shepherd Schurman for critically reading this manuscript and offering suggestions throughout the course of this work, and Ms. Susanne Feehley for editorial assistance. This work was supported by the Intramural Research Program of the National Institute on Aging (Baltimore, MD). NR 42 TC 7 Z9 7 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2013 VL 5 IS 1 BP 18 EP 36 PG 19 WC Cell Biology SC Cell Biology GA 104HH UT WOS:000315982300003 PM 23385138 ER PT J AU Howcroft, TK Campisi, J Louis, GB Smith, MT Wise, B Wyss-Coray, T Augustine, AD McElhaney, JE Kohanski, R Sierra, F AF Howcroft, T. Kevin Campisi, Judith Louis, Germaine Buck Smith, Martyn T. Wise, Bradley Wyss-Coray, Tony Augustine, Alison Deckhut McElhaney, Janet E. Kohanski, Ron Sierra, Felipe TI The role of inflammation in age-related disease SO AGING-US LA English DT Article AB The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified. C1 [Howcroft, T. Kevin] NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. [Campisi, Judith] Buck Inst Res Aging, Novato, CA 94945 USA. [Campisi, Judith] Lawrence Berkeley Natl Lab, Berkeley, CA 94702 USA. [Louis, Germaine Buck] NICHD, Off Director, NIH, Bethesda, MD 20892 USA. [Smith, Martyn T.] Univ Calif Berkeley, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Wise, Bradley] NIA, Div Neurosci, NIH, Bethesda, MD 20892 USA. [Wyss-Coray, Tony] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Stanford, CA 94305 USA. [Augustine, Alison Deckhut] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [McElhaney, Janet E.] Adv Med Res Inst Canada, Sudbury, ON P3E 5J1, Canada. [Kohanski, Ron; Sierra, Felipe] NIA, Div Aging Biol, NIH, Bethesda, MD 20892 USA. RP Howcroft, TK (reprint author), NCI, Div Canc Biol, NIH, Bethesda, MD 20892 USA. EM Howcrofk@mail.nih.gov; Kohanskir@mail.nih.gov; sierraf@mail.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU NIEHS NIH HHS [P42 ES004705] NR 0 TC 50 Z9 53 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2013 VL 5 IS 1 BP 84 EP 93 PG 10 WC Cell Biology SC Cell Biology GA 104HH UT WOS:000315982300007 PM 23474627 ER PT J AU Grady, C AF Grady, Christine TI Reflections on Two Decades of Bioethics: Where We Have Been and Where We Are Going SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Grady, Christine] NIH, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10-1C118, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 2 TC 3 Z9 3 U1 0 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JAN 1 PY 2013 VL 13 IS 1 BP 8 EP 10 DI 10.1080/15265161.2013.747310 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 104HO UT WOS:000315983000004 PM 23311831 ER PT J AU Master, Z Resnik, DB AF Master, Zubin Resnik, David B. TI Promoting Public Trust: ESCROs Won't Fix the Problem of Stem Cell Tourism SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 [Master, Zubin] Albany Med Coll, Albany, NY 12208 USA. [Resnik, David B.] NIEHS, Res Triangle Pk, NC USA. RP Master, Z (reprint author), Albany Med Coll, Alden March Bioeth Inst, 47 New Scotland Ave,MC 153, Albany, NY 12208 USA. EM zubin@zubsplace.com FU Cancer Stem Cell Consortium; Canadian Stem Cell Network FX We thank Professor Timothy Caulfield for helpful suggestions. This work was partially supported by the Cancer Stem Cell Consortium and the Canadian Stem Cell Network. Zubin Master is also affiliated with the Health Law and Science Policy Group at the University of Alberta. This article is the work product of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). However, the statements, opinions, or conclusions contained herein do not necessarily represent the statements, opinions, or conclusions of NIEHS, NIH, or the U.S. government. NR 11 TC 1 Z9 1 U1 1 U2 9 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JAN 1 PY 2013 VL 13 IS 1 BP 53 EP 55 DI 10.1080/15265161.2012.747028 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 104HO UT WOS:000315983000019 PM 23311846 ER PT J AU Novak, MA Hamel, AF Kelly, BJ Dettmer, AM Meyer, JS AF Novak, Melinda A. Hamel, Amanda F. Kelly, Brian J. Dettmer, Amanda M. Meyer, Jerrold S. TI Stress, the HPA axis, and nonhuman primate well-being: A review SO APPLIED ANIMAL BEHAVIOUR SCIENCE LA English DT Review DE Stress; HPA axis; Nursery rearing; Social housing; Environmental enrichment; Cortisol ID SELF-INJURIOUS-BEHAVIOR; MONKEYS MACACA-MULATTA; CHIMPANZEES PAN-TROGLODYTES; URINARY CORTISOL RESPONSES; REARED RHESUS-MONKEYS; BRIEF PAIN STRESSOR; SQUIRREL-MONKEY; PLASMA-CORTISOL; HAIR CORTISOL; ENVIRONMENTAL ENRICHMENT AB Numerous stressors are routinely encountered by wild-living primates (e.g., food scarcity, predation, aggressive interactions, and parasitism). Although many of these stressors are eliminated in laboratory environments, other stressors may be present in that access to space and social partners is often restricted. Stress affects many physiological systems including the hypothalamic pituitary adrenocortical (HPA) axis, which is the focus of this review. The glucocorticoid, cortisol, is the ultimate output of this system in nonhuman primates, and levels of this hormone are used as an index of stress. Researchers can measure cortisol from several sampling matrices that include blood, saliva, urine, faeces, and hair. A comparison of the advantages and disadvantages of each sampling matrix is provided to aid researchers in selecting an optimal strategy for their research. Stress and its relationship to welfare have been examined in nonhuman primates using two complimentary approaches: comparing baseline cortisol levels under different conditions, or determining the reactivity of the system through exposure to a stressor. Much of this work is focused on colony management practices and developmental models of abnormal behaviour. Certain colony practices are known to increase stress at least temporarily. Both blood sampling and relocation are examples of this effect, and efforts have been made to reduce some of the more stressful aspects of these procedures. In contrast, other colony management practices such as social housing and environmental enrichment are hypothesized to reduce stress. Testing this hypothesis by comparing baseline cortisol levels has not proved useful, probably due to "floor" effects; however, social buffering studies have shown the powerful role of social housing in mitigating reactions of nonhuman primates to stressful events. Models of abnormal behaviour come from two sources: experimentally induced alterations in early experience (e.g., nursery rearing), and the spontaneous development of behavioural pathology (e.g., self-injurious behaviour). Investigators have often assumed that abnormal behaviour is a marker for stress and thus such monkeys are predicted to have higher cortisol levels than controls. However, an emerging finding is that monkeys with abnormal behaviour are more likely to show a pattern of lowered cortisol concentrations which may reflect either an altered set point or a blunting of the stress response system. These findings parallel human clinical studies demonstrating that neuropsychiatric disorders may be associated with either increased or decreased activity of the HPA system, depending on the aetiology and manifestation of the disorder and their potential influence in provoking allostatic shifts in system functioning. (C) 2012 Elsevier B.V. All rights reserved. C1 [Novak, Melinda A.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01002 USA. [Hamel, Amanda F.] Univ Massachusetts, Neurosci & Behav Grad Program, Amherst, MA 01002 USA. [Kelly, Brian J.] Fitchburg State Univ, Dept Behav Sci, Fitchburg, MA 01420 USA. [Dettmer, Amanda M.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Dettmer, Amanda M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, DHHS, Poolesville, MD 20837 USA. RP Novak, MA (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall,135 Hicks Way, Amherst, MA 01002 USA. EM mnovak@psych.umass.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU National Institutes of Health, USA [8R24OD011180-15, RR000168] FX The preparation of this review was supported by federal grants from the National Institutes of Health, USA (8R24OD011180-15 to MAN and RR000168 to the New England Primate Research Center). NR 135 TC 20 Z9 21 U1 12 U2 106 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1591 J9 APPL ANIM BEHAV SCI JI Appl. Anim. Behav. Sci. PD JAN PY 2013 VL 143 IS 2-4 SI SI BP 135 EP 149 DI 10.1016/j.applanim.2012.10.012 PG 15 WC Agriculture, Dairy & Animal Science; Behavioral Sciences; Veterinary Sciences SC Agriculture; Behavioral Sciences; Veterinary Sciences GA 106OJ UT WOS:000316154100008 PM 23459687 ER PT J AU Wu, I Shin, SC Cao, Y Bender, IK Jafari, N Feng, G Lin, S Cidlowski, JA Schleimer, RP Lu, NZ AF Wu, I. Shin, S. C. Cao, Y. Bender, I. K. Jafari, N. Feng, G. Lin, S. Cidlowski, J. A. Schleimer, R. P. Lu, N. Z. TI Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes SO CELL DEATH & DISEASE LA English DT Article DE glucocorticoid; glucocorticoid receptor; apoptosis; T cell; alternative translation ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC; ANTIINFLAMMATORY ACTION; ILLUMINA MICROARRAY; DIRECT REPRESSION; CELL APOPTOSIS; PROTEIN BIM; EXPRESSION; GENES; BCL-2 AB Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. Cell Death and Disease (2013) 4, e453; doi:10.1038/cddis.2012.193; published online 10 January 2013 C1 [Wu, I.; Shin, S. C.; Cao, Y.; Bender, I. K.; Schleimer, R. P.; Lu, N. Z.] Northwestern Univ, Feinberg Sch Med, Div Allergy Immunol, Dept Med, Chicago, IL 60611 USA. [Jafari, N.] Genom Core Facil, Chicago, IL USA. [Feng, G.; Lin, S.] Northwestern Univ, Feinberg Sch Med, Biomed Informat Ctr, Chicago, IL 60611 USA. [Cidlowski, J. A.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Lu, NZ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Allergy Immunol, Dept Med, Room M301,240 East Huron, Chicago, IL 60611 USA. EM nickzlu@northwestern.edu FU NIH [NIH 1R01HL094558-01A1, NIH 3R01HL094558-01A1S1, NIH 2R37HL068546-26] FX We thank Dr. Navdeep Chandel for a critical review of the manuscript. This work was supported by the NIH Grants, NIH 1R01HL094558-01A1 (NZL), NIH 3R01HL094558-01A1S1 (NZL), and NIH 2R37HL068546-26 (RPS). NR 52 TC 20 Z9 20 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD JAN PY 2013 VL 4 AR e453 DI 10.1038/cddis.2012.193 PG 12 WC Cell Biology SC Cell Biology GA 101IE UT WOS:000315767600003 PM 23303127 ER PT J AU Vaish, A Silin, V Walker, ML Steffens, KL Krueger, S Yeliseev, AA Gawrisch, K Vanderah, DJ AF Vaish, Amit Silin, Vitalii Walker, Marlon L. Steffens, Kristen L. Krueger, Susan Yeliseev, Alexei A. Gawrisch, Klaus Vanderah, David J. TI A generalized strategy for immobilizing uniformly oriented membrane proteins at solid interfaces SO CHEMICAL COMMUNICATIONS LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; SURFACE-PLASMON RESONANCE; BILAYER-LIPID MEMBRANES; CANNABINOID RECEPTOR; COUPLED RECEPTORS; GOLD; RECONSTITUTION; SPECTROSCOPY; DENSITY; SOLVENT AB We have developed a method based on self-assembly of thiols on Au substrates to immobilize membrane proteins at interfaces. Using water soluble nitrilotriacetic acid (NTA)-terminated oligo(ethylene glycol) thiols, a histidine-tagged G protein-coupled membrane receptor (GPCR) was captured in a defined orientation with little nonspecific binding. C1 [Vaish, Amit; Silin, Vitalii; Krueger, Susan] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. [Vaish, Amit; Silin, Vitalii] Univ Maryland, Dept Mat Sci & Engn, College Pk, MD 20742 USA. [Walker, Marlon L.; Steffens, Kristen L.] NIST, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Yeliseev, Alexei A.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Vanderah, David J.] NIST, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. RP Vaish, A (reprint author), NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. EM amit.vaish@nist.gov; vanderah@ibbr.umd.edu FU National Institute of Standards and Technology-American Recovery and Reinvestment Act (NIST-ARRA); Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX A.V. and V. S. acknowledge the National Institute of Standards and Technology-American Recovery and Reinvestment Act (NIST-ARRA) fellowship for supporting this work. K. G. and A.Y. acknowledge support from the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. The authors acknowledge Dr Lee Richter and Hirsh Nanda of National Institute of Standards and Technology for useful discussions. NR 21 TC 7 Z9 7 U1 0 U2 35 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2013 VL 49 IS 26 BP 2685 EP 2687 DI 10.1039/c3cc00077j PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 099UP UT WOS:000315648400028 PM 23435270 ER PT J AU Lim, KH Staudt, LM AF Lim, Kian-Huat Staudt, Louis M. TI Toll-Like Receptor Signaling SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Editorial Material ID IMMUNITY C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov OI Lim, Kian-Huat/0000-0002-2766-200X NR 14 TC 29 Z9 30 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JAN PY 2013 VL 5 IS 1 AR a011247 DI 10.1101/cshperspect.a011247 PG 3 WC Cell Biology SC Cell Biology GA 104HT UT WOS:000315983600015 PM 23284045 ER PT J AU Zielke, N Edgar, BA DePamphilis, ML AF Zielke, Norman Edgar, Bruce A. DePamphilis, Melvin L. TI Endoreplication SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID DROSOPHILA FOLLICLE CELLS; F-BOX PROTEIN; ORIGIN RECOGNITION COMPLEX; TROPHOBLAST GIANT-CELLS; KINASE INHIBITOR DACAPO; CYCLIN-E LEVELS; S-PHASE; DNA-REPLICATION; DOWN-REGULATION; CDK INHIBITORS AB Developmentally programmed polyploidy occurs by at least four different mechanisms, two of which (endoreduplication and endomitosis) involve switching from mitotic cell cycles to endocycles by the selective loss of mitotic cyclin-dependent kinase (CDK) activity and bypassing many of the processes of mitosis. Here we review the mechanisms of endoreplication, focusing on recent results from Drosophila and mice. C1 [Zielke, Norman; Edgar, Bruce A.] Univ Heidelberg ZMBH Allianz, Zentrum Mol Biol, Deutsch Krebsforschungszentrum DKFZ, D-69120 Heidelberg, Germany. [DePamphilis, Melvin L.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Edgar, BA (reprint author), Univ Heidelberg ZMBH Allianz, Zentrum Mol Biol, Deutsch Krebsforschungszentrum DKFZ, Neuenheimer Feld 282, D-69120 Heidelberg, Germany. EM n.zielke@DKFZ-heidelberg.de; b.edgar@Dkfz-Heidelberg.de FU DKFZ; National Institutes of Health [GM51186]; NICHD/NIH intramural program FX We thank Terry Orr-Weaver and Michel Gho for helpful comments. Furthermore, we apologize to the authors whose work could not be included due to space restrictions. The research in the Edgar Laboratory is supported by the DKFZ and the National Institutes of Health (grant GM51186). M. DePamphilis thanks the NICHD/NIH intramural program for funding. NR 97 TC 33 Z9 33 U1 1 U2 25 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD JAN PY 2013 VL 5 IS 1 AR a012948 DI 10.1101/cshperspect.a012948 PG 15 WC Cell Biology SC Cell Biology GA 104HT UT WOS:000315983600002 PM 23284048 ER PT J AU Behrens, G Matthews, CE Moore, SC Freedman, ND McGlynn, KA Everhart, JE Hollenbeck, AR Leitzmann, MF AF Behrens, Gundula Matthews, Charles E. Moore, Steven C. Freedman, Neal D. McGlynn, Katherine A. Everhart, James E. Hollenbeck, Albert R. Leitzmann, Michael F. TI The association between frequency of vigorous physical activity and hepatobiliary cancers in the NIH-AARP Diet and Health Study SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Physical activity; Liver cancer; Biliary cancer; Gallbladder cancer; Cohort study ID HEPATOCELLULAR-CARCINOMA; LIVER-CANCER; REPRODUCTIVE FACTORS; OXIDATIVE STRESS; PROSPECTIVE COHORT; OBESE INDIVIDUALS; RISK; EXERCISE; ANTIOXIDANT; INCREASES AB Despite a potential preventive effect of physical activity on hepatobiliary cancer, little information is available on the relation between the two. We studied the association between frequency of vigorous physical activity and hepatobiliary cancer among 507,897 participants of the NIH-AARP Diet and Health Study, aged 50-71 years at baseline in 1995/1996. During 10 years of follow-up, 628 incident cases of liver cancer and 317 cases of extrahepatic biliary tract cancer were registered. Physical activity levels were assigned according to the frequency of engagement in 20 min or more of vigorous physical activity per week: never/rarely (lowest level), less than once per week, 1-2 times per week, 3-4 times per week, 5 or more times per week (highest level). Using Cox regression, multivariate-adjusted relative risks (RR) comparing the highest with the lowest level of physical activity revealed a statistically significant decreased risk for liver cancer (RR = 0.64, 95 % confidence interval (CI) = 0.49-0.84, p-trend < 0.001), particularly hepatocellular carcinoma (RR = 0.56, 95 % CI = 0.41-0.78, p-trend < 0.001), independent of body mass index. By comparison, multivariate analyses indicated that physical activity was not statistically significantly associated with extrahepatic bile duct cancer (RR = 0.86, 95 % CI = 0.45-1.65), ampulla of Vater cancer (RR = 0.66, 95 % CI = 0.29-1.48), or gallbladder cancer (RR = 0.63, 95 % CI = 0.33-1.21). These results suggest a potential preventive effect of physical activity on liver cancer but not extrahepatic biliary tract cancer, independent of body mass index. C1 [Behrens, Gundula; Leitzmann, Michael F.] Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, D-93053 Regensburg, Germany. [Matthews, Charles E.; Moore, Steven C.; Freedman, Neal D.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Behrens, G (reprint author), Univ Regensburg, Dept Epidemiol & Prevent Med, Med Ctr, Franz Josef Strauss Allee 11, D-93053 Regensburg, Germany. EM gundula.behrens@klinik.uni-regensburg.de RI matthews, Charles/E-8073-2015; Freedman, Neal/B-9741-2015; Moore, Steven/D-8760-2016; OI matthews, Charles/0000-0001-8037-3103; Freedman, Neal/0000-0003-0074-1098; Moore, Steven/0000-0002-8169-1661; Behrens, Gundula/0000-0002-9355-6491 FU Intramural NIH HHS [ZIA CP010197-06] NR 52 TC 11 Z9 11 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 EI 1573-7284 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD JAN PY 2013 VL 28 IS 1 BP 55 EP 66 DI 10.1007/s10654-013-9767-1 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 104OF UT WOS:000316003200006 PM 23354983 ER PT J AU Merril, CR AF Merril, Carl R. TI Is Sporadic Alzheimer's Disease Associated with Diphtheria Toxin? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; booster vaccine; diphtheria toxin; DPT vaccine; elongation factor 2; EF2; immune system; vaccination ID CENTRAL-NERVOUS-SYSTEM; AGING IMMUNE-SYSTEM; RISK-FACTORS; DELIVERY; AGE; REDUCTION; DEMENTIA; PRIONS; BRAIN; PHAGE AB The two major aspects of Alzheimer's disease (AD) that must be considered in a search for causative agents are its association with aging and its widespread epidemiology. While a number of agents have been identified, additional factors may play a role. An association with diphtheria toxin was suggested by observations that vaccinations may provide protective effects, and the observation that decreased proteins synthesis in cortical regions from AD patients is associated with modification of elongation factor 2, the target of diphtheria toxin. While protection against diphtheria toxin is provided by vaccination, the known decline in the immune system associated with aging would result in a renewed sensitivity to the toxin. An association with diphtheria toxin would be consistent with the observations that the bacteria associated with the toxin, Corynebacterium diphtheria, is often found in the nasopharynx and an early symptom of AD is the loss of smell with a disease progression from the entorhinal cortex to the hippocampus and the neocortical areas. If diphtheria toxin is involved in sporadic AD, booster vaccinations given to elderly individuals might result in a decreased incidence of this disease. As booster DPT vaccinations are already recommended for individuals over 65, cognitive testing at the time of the booster and 5 years later, along with similar cognitive testing in age-matched individuals who decline vaccination, might provide an inexpensive method to investigate whether diphtheria toxin plays a role in AD and the efficacy of DPT booster vaccines for AD. C1 [Merril, Carl R.] NIH, Bethesda, MD 20892 USA. EM merrilcarl@msn.com NR 35 TC 3 Z9 3 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2013 VL 34 IS 3 BP 595 EP 600 DI 10.3233/JAD-121948 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 104KK UT WOS:000315991500003 PM 23271314 ER PT J AU Nacif, MS Liu, YX Yao, JH Liu, ST Sibley, CT Summers, RM Bluemke, DA AF Nacif, Marcelo Souto Liu, Yixun Yao, Jianhua Liu, Songtao Sibley, Christopher T. Summers, Ronald M. Bluemke, David A. TI 3D left ventricular extracellular volume fraction by low-radiation dose cardiac CT: Assessment of interstitial myocardial fibrosis SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Cardiac computed tomography; Diffuse myocardial fibrosis; 3D extracellular volume ID MULTIDETECTOR COMPUTED-TOMOGRAPHY; CARDIOVASCULAR MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; DIPYRIDAMOLE STRESS; INFARCTION; PERFUSION; IMAGES; ENHANCEMENT; CALCIUM; MRI AB Background: Myocardial fibrosis leads to impaired cardiac function and events. Extracellular volume fraction (ECV) assessed with an iodinated contrast agent and measured by cardiac CT may be a useful noninvasive marker of fibrosis. Objective: The purpose of this study was to develop and evaluate a 3-dimensional (3D) ECV calculation tookit (ECVTK) for ECV determination by cardiac CT. Methods: Twenty-four subjects (10 systolic heart failure age, 60 +/- 17 years; 5 diastolic failure, age 56 +/- 20 years; 9 matched healthy subjects, age 59 +/- 7 years) were evaluated. Cardiac CT examinations were done on a 320-multidetector CT scanner before and after 130 mL of iopamidol (Isovue- 370; Bracco Diagnositcs, Plainsboro, NJ USA) was administered. A calcium score type sequence was performed before and 7 minutes after contrast with single gantry rotation during 1 breath hold and single cardiac phase acquisition. ECV was calculated as (Delta HUmyocardium/Delta HUblood) x (1 - Hct) where Hct is the hematocrit, and Delta Hu is the change is Hounsfield unit = attenuation = HUafter (iodine) - HUbefore iodone. Cardiac magnetic resonance imaging was performed to assess myocardial structure and function. Results: Mean 3D ECV values were significantly higher in the subjects with systolic hear failure than in healthy subjects and subjects with diastolic heart failure (mean, 41% +/- 6%, 33 +/- 2%, and 35% +/- 5, respectively; P = 0.02). Interobserver and intraobserver agreements were excellent for myocardial, blood pool, and ECV (intraclass correlation coefficient, >0.90 for all). Higher 3D ECV by cardiac CT was associated with reduced systolic circumferential strain, greater end-diastolic and -systolic volumes, and lower ejection fraction (r = 0.70, r = 0.60, r = 0.73, and r = -0.68, respectively, all P < 0.001). Conclusion: 3D ECV by cardiac CT can be performed with ECVTK. we demonstrated increased ECV in subjects with systolic heart failure compared with healthy subjects. Cardiac CT results also showed good correlation with important functional heart biomarkers, suggesting the potential for myocardial tissue characterization with the use of 3D ECV by cardiac CT. This trial is registered at www.ClinicalTrials.gov as NCT01160471. (C) 2013 Published by Elsevier Inc. on behalf of Society of Cardiovascular Computed Tomography. C1 [Nacif, Marcelo Souto; Liu, Yixun; Yao, Jianhua; Liu, Songtao; Sibley, Christopher T.; Summers, Ronald M.; Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Nacif, Marcelo Souto] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. [Nacif, Marcelo Souto] Univ Fed Fluminense, Dept Radiol, Niteroi, RJ, Brazil. [Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. RP Bluemke, DA (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health (NIH) FX Funded by the National Institutes of Health (NIH) Intramural program. NR 29 TC 6 Z9 6 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD JAN-FEB PY 2013 VL 7 IS 1 BP 51 EP 57 DI 10.1016/j.jcct.2012.10.010 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 105BW UT WOS:000316041600009 PM 23333188 ER PT J AU King, EM Filep, S Smith, B Platts-Mills, T Hamilton, RG Schmechel, D Sordillo, JE Milton, D van Ree, R Krop, EJM Heederik, DJJ Metwali, N Thorne, PS Zeldin, DC Sever, ML Calatroni, A Arbes, SJ Mitchell, HE Chapman, MD AF King, Eva M. Filep, Stephanie Smith, Bryan Platts-Mills, Thomas Hamilton, Robert G. Schmechel, Detlef Sordillo, Joanne E. Milton, Donald van Ree, Ronald Krop, Esmeralda J. M. Heederik, Dick J. J. Metwali, Nervana Thorne, Peter S. Zeldin, Darryl C. Sever, Michelle L. Calatroni, Agustin Arbes, Samuel J., Jr. Mitchell, Herman E. Chapman, Martin D. TI A multi-center ring trial of allergen analysis using fluorescent multiplex array technology SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Allergen measurement; Asthma; Indoor air quality; Immunoassay; Multiplex array; Occupational health ID INNER-CITY CHILDREN; 1ST NATIONAL-SURVEY; DUST MITE ALLERGEN; MOUSE ALLERGEN; BIRTH COHORT; CAT ALLERGEN; ASTHMA; EXPOSURE; SENSITIZATION; LEAD AB Background: Consistent Consistent performance of allergen assays is essential to ensure reproducibility of exposure assessments for investigations of asthma and occupational allergic disease. This study evaluated intra- and inter-laboratory reproducibility of a fluorescent multiplex array, which simultaneously measures eight indoor allergens in a single reaction well. Methods: A multi-center study was performed in nine laboratories in the US and Europe to determine the inter-laboratory variability of an 8-plex array for dust mite, cat, dog, rat, mouse and cockroach allergens. Aliquots of 151 dust extract samples were sent to participating centers and analyzed by each laboratory on three separate occasions. Agreement within and between laboratories was calculated by the concordance correlation coefficient (CCC). Results: Results were obtained for over 32,000 individual allergen measurements. Levels covered a wide range for all allergens from below the lower limit of detection (LLOD.=0.1-9.8 ng/ml) to higher than 6800 ng/ml for all allergens except Mus m 1, which was up to 1700 ng/ml. Results were reproducible within as well as between laboratories. Within laboratories, 94% of CCC were >= 0.90, and 80% of intra-laboratory results fell within a 10% coefficient of variance (CV%). Results between laboratories also showed highly significant positive correlations for all allergens (similar to 0.95, p<0.001). Overall means of results were comparable, and inter-laboratory CV% for all allergens except Rat n 1 ranged between 17.6% and 26.6%. C1 [King, Eva M.; Filep, Stephanie; Smith, Bryan; Chapman, Martin D.] INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA. [Platts-Mills, Thomas] Univ Virginia, Div Allergy, Charlottesville, VA USA. [Hamilton, Robert G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Schmechel, Detlef] CDC, NIOSH, Morgantown, WV USA. [Sordillo, Joanne E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. [van Ree, Ronald] Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol & Otorhinolaryngol, NL-1105 AZ Amsterdam, Netherlands. [Krop, Esmeralda J. M.; Heederik, Dick J. J.] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3508 TC Utrecht, Netherlands. [Metwali, Nervana; Thorne, Peter S.] Univ Iowa, Dept Occupat & Environm Hlth, Iowa City, IA USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Sever, Michelle L.; Calatroni, Agustin; Arbes, Samuel J., Jr.; Mitchell, Herman E.] Rho Inc, Chapel Hill, NC USA. [Milton, Donald] Univ Maryland, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. RP King, EM (reprint author), INDOOR Biotechnol Inc, 1216 Harris St, Charlottesville, VA 22903 USA. EM eking@inbio.com RI Milton, Donald/G-3286-2010; OI Milton, Donald/0000-0002-0550-7834; Sever, Michelle/0000-0002-2435-1214 FU U.S. National Institutes of Health Small Business Innovation and Research (SBIR) Phase II Award from the National Institute of Environmental Health Sciences [ES55545C]; Intramural Research Program of the NIH, National Institute of Environmental Health Sciences FX This study was supported in part by U.S. National Institutes of Health Small Business Innovation and Research (SBIR) Phase II Award ES55545C from the National Institute of Environmental Health Sciences, by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, and by internal funds of all participating centers. Indoor Biotechnologies provided all reagents for use in the study and also provided travel and accommodation support for technician training. NR 36 TC 16 Z9 16 U1 0 U2 24 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 JAN PY 2013 VL 387 IS 1-2 BP 89 EP 95 DI 10.1016/j.jim.2012.09.015 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 101AB UT WOS:000315746200010 PM 23085532 ER PT J AU Zhu, DM Qian, F Wu, YM Jones, DS Rowe, C Narum, DL Duffy, P Miller, LH Saul, A AF Zhu, Daming Qian, Feng Wu, Yimin Jones, David S. Rowe, Christopher Narum, David L. Duffy, Patrick Miller, Louis H. Saul, Allan TI Determination of protein concentration for protein-protein conjugates using ultraviolet absorption SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Concentration of protein-protein conjugate; Molar ratio; Microsoft Excel solver; Amino acid analysis; Least squares analysis ID AMINO-ACID-ANALYSIS; VACCINE; IMMUNOGENICITY; HAPTEN; RATIO AB The present study reports a method to determine the total protein concentration or concentration of a protein of interest in a protein-protein conjugate using ultraviolet absorption, after determining the molar ratio of proteins in the conjugates, from which an extinction coefficient can be calculated. A Microsoft Excel solver-based template using amino acid analysis data was developed for determining the molar ratio. The percent mass of each protein in the conjugate is calculated from the amino add composition data using the least squares method in the Microsoft Excel solver function, and the percent mass is converted to molar portion of each protein using corresponding molecular weight. A molar ratio is obtained by dividing the molar portion of protein 1 by the molar portion of protein 2. A weighted extinction coefficient is calculated using the molar ratio, and the total protein concentration is determined using ultraviolet absorption at 280 nm. The accuracy of the method was verified using mixtures of known proteins. The present study provides a rapid, simple and accurate method for determining protein concentration in protein-protein conjugates. Published by Elsevier B.V. C1 [Zhu, Daming; Qian, Feng; Wu, Yimin; Jones, David S.; Rowe, Christopher; Narum, David L.; Duffy, Patrick; Miller, Louis H.; Saul, Allan] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. RP Zhu, DM (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA. EM dzhu@niaid.nih.gov; allan.saul@novartis.com RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Division of Intramural Research, NIAID, NIH FX We thank Dr. Myron Crawford, Keck Biotechnology Resource Laboratory, Yale School of Medicine for the amino acid analysis. This work was supported in part by the Division of Intramural Research, NIAID, NIH. NR 12 TC 1 Z9 2 U1 0 U2 20 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 JAN PY 2013 VL 387 IS 1-2 BP 317 EP 321 DI 10.1016/j.jim.2012.10.011 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 101AB UT WOS:000315746200038 PM 23098838 ER PT J AU Romero, R Yeo, L Miranda, J Hassan, SS Conde-Agudelo, A Chaiworapongsa, T AF Romero, Roberto Yeo, Lami Miranda, Jezid Hassan, Sonia S. Conde-Agudelo, Agustin Chaiworapongsa, Tinnakorn TI A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Cervical cerclage; cost-effective analysis; infant mortality; pessary; pregnancy; prematurity; respiratory distress syndrome; 17-alpha-hydroxyprogesterone caproate (17OHP-C or 17P) ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; MATERNAL ANTIFETAL REJECTION; SONOGRAPHIC SHORT CERVIX; POSITIVE AMNISURE TEST; UTERINE CERVIX; PREMATURE RUPTURE; DOUBLE-BLIND; CHRONIC CHORIOAMNIONITIS; CLINICAL-SIGNIFICANCE AB Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two thirds of preterm births occur after the spontaneous onset of labor, and the remaining one third after "indicated" preterm birth; however, the causes of spontaneous preterm labor and "indicated" preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identified in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at <33 weeks of gestation by 44%, along with the rate of admission to the neonatal intensive care unit, respiratory distress syndrome, requirement for mechanical ventilation, and composite neonatal morbidity/mortality score. There is no evidence that 17-alpha-hydroxyprogesterone caproate can reduce the rate of preterm delivery in women with a short cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and the implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (<25 mm). C1 [Romero, Roberto; Yeo, Lami; Miranda, Jezid; Hassan, Sonia S.; Conde-Agudelo, Agustin; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto; Yeo, Lami; Miranda, Jezid; Hassan, Sonia S.; Conde-Agudelo, Agustin; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. [Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS,Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM romeror@mail.nih.gov FU Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS FX This work was supported, in part, by the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH/DHHS. NR 178 TC 38 Z9 42 U1 3 U2 13 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PY 2013 VL 41 IS 1 SI SI BP 27 EP 44 DI 10.1515/jpm-2012-0272 PG 18 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 095ZJ UT WOS:000315373200006 PM 23314512 ER PT B AU Pattaradilokrat, S Mu, JB Awadalla, P Su, XZ AF Pattaradilokrat, Sittiporn Mu, Jianbing Awadalla, Philip Su, Xin-zhuan BE Carlton, JM Perkins, SL Deitsch, KW TI Genome Diversity and Applications in Genetic Studies of the Human Malaria Parasites Plasmodium falciparum and Plasmodium vivax SO MALARIA PARASITES: COMPARATIVE GENOMICS , EVOLUTION AND MOLECULAR BIOLOGY LA English DT Article; Book Chapter ID SINGLE-NUCLEOTIDE POLYMORPHISMS; APICAL MEMBRANE ANTIGEN-1; ANTIMALARIAL-DRUG RESISTANCE; VACCINE-CANDIDATE ANTIGENS; RECENT POSITIVE SELECTION; SURFACE PROTEIN-1 MSP-1; HIGH-THROUGHPUT SCREEN; ANOPHELES-GAMBIAE; POPULATION-STRUCTURE; CHLOROQUINE-RESISTANCE AB The publication of the genomes of the human malaria parasites Plasmodium falciparum and Plasmodium vivax has provided the foundation for developing high-throughput methods for systematic investigation into genomic variability in parasite populations. Various tools for discovering genome-wide polymorphisms and genotyping, including DNA microarrays and high-throughput sequencing, are readily available for the malaria research community. Elucidating the genetic diversity within and between populations forms the basis of population genetic analysis that not only will aid in deciphering the evolution and adaptation of the parasites but also has important implications for the development and implementation of therapeutic interventions. Here we summarize the recent advances in the studies of genome variation, population genetics, and the development of high-throughput genetic tools for investigating gene function in P. falciparum and P. vivax. C1 [Pattaradilokrat, Sittiporn] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Mu, Jianbing; Su, Xin-zhuan] NIAID, NIH, Bethesda, MD 20892 USA. [Awadalla, Philip] Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. RP Pattaradilokrat, S (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pattaradilokrats@gmail.com; jmu@niaid.nih.gov; philip.awadalla@umontreal.ca; xsu@niaid.nih.gov NR 276 TC 4 Z9 4 U1 1 U2 8 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-07-2 PY 2013 BP 59 EP 90 PG 32 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA BDY05 UT WOS:000315604200004 ER PT B AU Ranford-Cartwright, LC Hayton, KL Ferdig, MT AF Ranford-Cartwright, Lisa C. Hayton, Karen L. Ferdig, Michael T. BE Carlton, JM Perkins, SL Deitsch, KW TI Plasmodium Experimental Genetic Crosses SO MALARIA PARASITES: COMPARATIVE GENOMICS , EVOLUTION AND MOLECULAR BIOLOGY LA English DT Article; Book Chapter ID DOUBLE-STRAND BREAKS; FRAGMENT-LENGTH-POLYMORPHISMS; FALCIPARUM MALARIA PARASITES; CHLOROQUINE-RESISTANCE LOCUS; RECOMBINATION HOT-SPOTS; QUANTITATIVE TRAIT LOCI; LINKAGE GROUP SELECTION; DIHYDROFOLATE-REDUCTASE; DRUG-RESISTANCE; IN-VITRO AB Experimental genetic crosses mimic the sexual reproduction process, and accompanying genetic recombination, that occurs between individuals of the same species during natural transmission. Experimental crosses performed using rodent and human species of Plasmodium have been used to link phenotype and genotype for a variety of traits, and have been particularly useful for understanding phenotypes for which no obvious candidate genes are known. In addition, analysis of experimental crosses has provided insights into the frequency and types of recombination that occur. Some biological traits are explained by inheritance of single genes, whereas several loci, known as quantitative trait loci (qtl), contribute to a 'complex trait'. Linkage analyses of experimental genetic crosses of Plasmodium falciparum have identified parasite loci contributing to resistance to a number of antimalarial drugs such as chloroquine and quinine, as well as loci controlling the ability of parasites to invade erythrocytes of different primate species, the ability to infect mosquitoes, and intraerythrocytic growth rates. Genetic mapping can also identify genomic regions associated with the control of gene expression (expression qtl or eQTL). Genetic crosses and genetic mapping continue to play a significant role in our understanding of malaria parasite biology, transmission, and drug resistance. C1 [Ranford-Cartwright, Lisa C.] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. [Hayton, Karen L.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Ferdig, Michael T.] Univ Notre Dame, Eck Inst Global Hlth, Dept Biol, Notre Dame, IN 46556 USA. RP Ranford-Cartwright, LC (reprint author), Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland. EM lisa.ranford-cartwright@glasgow.ac.uk; khayton1@gmail.com; ferdig.1@nd.edu RI Ranford-Cartwright, Lisa/H-4701-2013 OI Ranford-Cartwright, Lisa/0000-0003-1992-3940 NR 135 TC 1 Z9 1 U1 0 U2 3 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-07-2 PY 2013 BP 127 EP 144 PG 18 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA BDY05 UT WOS:000315604200006 ER PT B AU Parish, LA Garver, LS Colquhoun, DR Mohien, CU Weissbrod, E Dinglasan, RR AF Parish, Lindsay A. Garver, Lindsey S. Colquhoun, David R. Mohien, Ceereena Ubaida Weissbrod, Elizabeth Dinglasan, Rhoel R. BE Carlton, JM Perkins, SL Deitsch, KW TI Dissecting Mosquito-Parasite Interactions through Molecular Biology and Biochemistry: Genomic, Proteomic and Glycomic Analyses SO MALARIA PARASITES: COMPARATIVE GENOMICS , EVOLUTION AND MOLECULAR BIOLOGY LA English DT Article; Book Chapter ID VECTOR ANOPHELES-GAMBIAE; PERITROPHIC MATRIX PROTEIN; COMPLEMENT-LIKE PROTEIN; DIFFERENCE GEL-ELECTROPHORESIS; TANDEM MASS-SPECTROMETRY; BORDER MEMBRANE-VESICLES; INNATE IMMUNE-SYSTEM; PLASMODIUM-FALCIPARUM; MALARIA PARASITES; SALIVARY-GLANDS AB Our understanding of the malaria parasite-mosquito vector host interactions has grown significantly in the post-genomic era. The sequencing of the Anopheles gambiae genome and functional genomics has revolutionized our approaches at examining the role of the mosquito vector host in malaria transmission. It is hoped that 13 other anopheline species (including the major vectors for Plasmodium vivax) will be completely sequenced within the next decade. Now, more than ever, there is a heightened research focus on Vector Biology and the transmission stages of the malaria parasite through the mosquito, from gametocytes to sporozoites, with the underlying aim of developing novel transmission-blocking vaccines/interventions. This chapter provides an overview of what is currently known at the genomic, proteomic and glycomic levels, about the role of different molecules, tissue compartments and molecular pathways in the mosquito vector and the ensuing strategies that have evolved, which can potentially impact malaria parasite transmission. C1 [Parish, Lindsay A.; Dinglasan, Rhoel R.] Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Garver, Lindsey S.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Colquhoun, David R.; Mohien, Ceereena Ubaida] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA. [Weissbrod, Elizabeth] Johns Hopkins Univ, Sch Med, Dept Art Appl Med, Baltimore, MD USA. RP Parish, LA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Johns Hopkins Malaria Res Inst, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. EM lindsayannparish@gmail.com; garverls@niaid.nih.gov; dcolquh1@jhmi.edu; ceereena@jhmi.edu; leftfieldart@gmail.com; rdinglas@jhsph.edu NR 201 TC 0 Z9 0 U1 0 U2 12 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-07-2 PY 2013 BP 221 EP 248 PG 28 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA BDY05 UT WOS:000315604200010 ER PT J AU de Jong, MF Starr, T Winter, MG den Hartigh, AB Child, R Knodler, LA van Dijl, JM Celli, J Tsolis, RM AF de Jong, Maarten F. Starr, Tregei Winter, Maria G. den Hartigh, Andreas B. Child, Robert Knodler, Leigh A. van Dijl, Jan Maarten Celli, Jean Tsolis, Renee M. TI Sensing of Bacterial Type IV Secretion via the Unfolded Protein Response SO MBIO LA English DT Article ID NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; BRUCELLA-ABORTUS INFECTION; CHAIN BINDING-PROTEIN; INNATE IMMUNE-SYSTEM; TRANSCRIPTION FACTOR; INTRACELLULAR REPLICATION; MESSENGER-RNA; VIRB MUTANT; ER STRESS AB Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory responses. Ectopically expressed VceC interacted with the endoplasmic reticulum (ER) chaperone BiP/Grp78 and localized to the ER of HeLa cells. ER localization of VceC required a transmembrane domain in its N terminus. Notably, the expression of VceC resulted in reorganization of ER structures. In macrophages, VceC was required for B. abortus-induced inflammation by induction of the unfolded protein response by a process requiring inositol-requiring transmembrane kinase/endonuclease 1. Altogether, these findings suggest that translocation of the T4SS effector VceC induces ER stress, which results in the induction of proinflammatory host cell responses during B. abortus infection. IMPORTANCE Brucella species are pathogens that require a type IV secretion system (T4SS) to survive in host cells and to maintain chronic infection. By as-yet-unknown pathways, the T4SS also elicits inflammatory responses in infected cells. Here we show that inflammation caused by the T4SS results in part from the sensing of a T4SS substrate, VceC, that localizes to the endoplasmic reticulum (ER), an intracellular site of Brucella replication. Possibly via binding of the ER chaperone BiP, VceC causes ER stress with concomitant expression of proinflammatory cytokines. Thus, induction of the unfolded protein response may represent a novel pathway by which host cells can detect pathogens deploying a T4SS. C1 [de Jong, Maarten F.; Winter, Maria G.; den Hartigh, Andreas B.; Tsolis, Renee M.] Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. [Starr, Tregei; Child, Robert; Knodler, Leigh A.; Celli, Jean] NIAID, Rocky Mt Labs, Intracellular Parasites Lab, Hamilton, MT 59840 USA. [de Jong, Maarten F.; van Dijl, Jan Maarten] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol, Groningen, Netherlands. RP Tsolis, RM (reprint author), Univ Calif Davis, Dept Med Microbiol & Immunol, Davis, CA 95616 USA. EM rmtsolis@ucdavis.edu RI van Dijl, Jan Maarten/G-1205-2013; OI Tsolis, Renee/0000-0001-9131-6657 FU PHS [AI050553, AI097107, AI090387]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by PHS grants AI050553, AI097107, and AI090387 to R.M.T. and in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 53 TC 21 Z9 21 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2013 VL 4 IS 1 AR e00418-12 DI 10.1128/mBio.00418-12 PG 10 WC Microbiology SC Microbiology GA 102AA UT WOS:000315814300013 PM 23422410 ER PT J AU Liang, Y Quenelle, D Vogel, JL Mascaro, C Ortega, A Kristie, TM AF Liang, Yu Quenelle, Debra Vogel, Jodi L. Mascaro, Cristina Ortega, Alberto Kristie, Thomas M. TI A Novel Selective LSD1/KDM1A Inhibitor Epigenetically Blocks Herpes Simplex Virus Lytic Replication and Reactivation from Latency SO MBIO LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HISTONE DEMETHYLASE LSD1; GENE-EXPRESSION; CHROMATIN-STRUCTURE; DNA METHYLATION; DRUG DISCOVERY; EARLY TIMES; INFECTION; PROMOTERS; EFFICACY AB Cellular processes requiring access to the DNA genome are regulated by an overlay of epigenetic modifications, including histone modification and chromatin remodeling. Similar to the cellular host, many nuclear DNA viruses that depend upon the host cell's transcriptional machinery are also subject to the regulatory impact of chromatin assembly and modification. Infection of cells with alphaherpesviruses (herpes simplex virus [HSV] and varicella-zoster virus [VZV]) results in the deposition of nucleosomes bearing repressive histone H3K9 methylation on the viral genome. This repressive state is modulated by the recruitment of a cellular coactivator complex containing the histone H3K9 demethylase LSD1 to the viral immediate-early (IE) gene promoters. Inhibition of the activity of this enzyme results in increased repressive chromatin assembly and suppression of viral gene expression during lytic infection as well as reactivation from latency in a mouse ganglion explant model. However, available small-molecule LSD1 inhibitors are not originally designed to inhibit LSD1, but rather monoamine oxidases (MAO) in general. Thus, their specificity for and potency to LSD1 is low. In this study, a novel specific LSD1 inhibitor was identified that potently repressed HSV IE gene expression, genome replication, and reactivation from latency. Importantly, the inhibitor also suppressed primary infection of HSV in vivo in a mouse model. Based on common control of a number of DNA viruses by epigenetic modulation, it was also demonstrated that this LSD1 inhibitor blocks initial gene expression of the human cytomegalovirus and adenovirus type 5. IMPORTANCE Epigenetic mechanisms, including histone modification and chromatin remodeling, play important regulatory roles in all cellular processes requiring access to the genome. These mechanisms are often altered in disease conditions, including various cancers, and thus represent novel targets for drugs. Similarly, many viral pathogens are regulated by an epigenetic overlay that determines the outcome of infection. Therefore, these epigenetic targets also represent novel antiviral targets. Here, a novel inhibitor was identified with high specificity and potency for the histone demethylase LSD1, a critical component of the herpes simplex virus (HSV) gene expression paradigm. This inhibitor was demonstrated to have potent antiviral potential in both cultured cells and animal models. Thus, in addition to clearly demonstrating the critical role of LSD1 in regulation of HSV infection, as well as other DNA viruses, the data extends the therapeutic potential of chromatin modulation inhibitors from the focused field of oncology to the arena of antiviral agents. C1 [Liang, Yu; Vogel, Jodi L.; Kristie, Thomas M.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Quenelle, Debra] Univ Alabama Birmingham, Dept Pediat, Div Infect Dis, Birmingham, AL USA. [Mascaro, Cristina; Ortega, Alberto] Oryzon Genom SA, Barcelona, Spain. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM Thomas_kristie@nih.gov FU Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health; Spanish Ministry of Economy and Competitiveness and Oryzon Genomics SA [CENIT-2008-1013]; [HHSN272201000027I] FX These studies were supported by the Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health (T.M.K.) and contract HHSN272201000027I (D.Q.). The development of compounds was co-funded by CENIT-2008-1013 grant from the Spanish Ministry of Economy and Competitiveness and Oryzon Genomics SA. NR 57 TC 26 Z9 26 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2013 VL 4 IS 1 AR e00558-12 DI 10.1128/mBio.00558-12 PG 9 WC Microbiology SC Microbiology GA 102AA UT WOS:000315814300035 PM 23386436 ER PT J AU Zhang, Q Chen, CY Yedavalli, VSRK Jeang, KT AF Zhang, Quan Chen, Chia-Yen Yedavalli, Venkat S. R. K. Jeang, Kuan-Teh TI NEAT1 Long Noncoding RNA and Paraspeckle Bodies Modulate HIV-1 Posttranscriptional Expression SO MBIO LA English DT Article ID HEPATITIS-C VIRUS; CELLULAR MICRORNA; MESSENGER-RNA; REV PROTEIN; RESTRICTION FACTORS; HUMAN RETROVIRUSES; NUCLEAR RETENTION; GENE-EXPRESSION; FUNCTIONAL-ROLE; HUMAN GENOME AB Most of the human genome is transcribed into protein-noncoding RNAs (ncRNAs), including small ncRNAs and long ncRNAs (lncRNAs). Over the past decade, rapidly emerging evidence has increasingly supported the view that lncRNAs serve key regulatory and functional roles in mammal cells. HIV-1 replication relies on various cell functions. To date, while the involvement of host protein factors and microRNAs (miRNAs) in the HIV-1 life cycle has been extensively studied, the relationship between lncRNAs and HIV-1 remains uncharacterized. Here, we have profiled 83 disease-related lncRNAs in HIV-1-infected T cells. We found NEAT1 to be one of several lncRNAs whose expression is changed by HIV-1 infection, and we have characterized its role in HIV-1 replication. We report here that the knockdown of NEAT1 enhances virus production through increased nucleus-to-cytoplasm export of Rev-dependent instability element (INS)-containing HIV-1 mRNAs. IMPORTANCE Long protein-noncoding RNAs (lncRNAs) play roles in regulating gene expression and modulating protein activities. There is emerging evidence that lncRNAs are involved in the replication of viruses. To our knowledge, this report is the first to characterize a role contributed by an lncRNA, NEAT1, to HIV-1 replication. NEAT1 is essential for the integrity of the nuclear paraspeckle substructure. Based on our findings from NEAT1 knockdown, we have identified the nuclear paraspeckle body as another important subcellular organelle for HIV-1 replication. C1 [Zhang, Quan; Chen, Chia-Yen; Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov FU NIAID; NIH; IATAP program from the Office of the Director, NIH FX Work in K.-T.J.'s laboratory was supported by intramural funding from NIAID, NIH, and the IATAP program from the Office of the Director, NIH. NR 77 TC 50 Z9 55 U1 6 U2 27 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD JAN-FEB PY 2013 VL 4 IS 1 AR e00596-12 DI 10.1128/mBio.00596-12 PG 9 WC Microbiology SC Microbiology GA 102AA UT WOS:000315814300040 PM 23362321 ER PT J AU Zhou, L Zhang, AB Wang, R Marcotte, EM Vogel, C AF Zhou, Li Zhang, Ang B. Wang, Rong Marcotte, Edward M. Vogel, Christine TI The proteomic response to mutants of the Escherichia coli RNA degradosome SO MOLECULAR BIOSYSTEMS LA English DT Article ID TANDEM MASS-SPECTROMETRY; MESSENGER-RNA; IN-VIVO; POLY(A) POLYMERASE; STATISTICAL-MODEL; PROTEIN ABUNDANCE; DNA MICROARRAYS; GLOBAL ANALYSIS; HELICASE; DECAY AB The Escherichia coli RNA degradosome recognizes and degrades RNA through the coordination of four main protein components, the endonuclease RNase E, the exonuclease PNPase, the RhlB helicase and the metabolic enzyme enolase. To help our understanding of the functions of the RNA degradosome, we quantified expression changes of >2300 proteins using mass spectrometry based shotgun proteomics in E. coli strains deficient in rhlB, eno, pnp (which displays temperature sensitive growth), or rne(1-602) which encodes a C-terminal truncation mutant of RNase E and is deficient in degradosome assembly. Global protein expression changes are most similar between the pnp and rhlB mutants, confirming the functional relationship between the genes. We observe down-regulation of protein chaperones including GroEL and DnaK (which associate with the degradosome), a decrease in translation related proteins in Delta pnp, Delta rhlB and rne(1-602) cells, and a significant increase in the abundance of aminoacyl-tRNA synthetases. Analysis of the observed proteomic changes points to a shared motif, CGCTGG, that may be associated with RNA degradosome targets. Further, our data provide information on the expression modulation of known degradosome-associated proteins, such as DeaD and RNase G, as well as other RNA helicases and RNases - suggesting or confirming functional complementarity in some cases. Taken together, our results emphasize the role of the RNA degradosome in the modulation of the bacterial proteome and provide the first large-scale proteomic description of the response to perturbation of this major pathway of RNA degradation. C1 [Zhou, Li; Wang, Rong; Marcotte, Edward M.; Vogel, Christine] Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. [Zhou, Li] Scripps Res Inst, Dept Chem, Dept Mol Biol, La Jolla, CA 92037 USA. [Zhou, Li] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Zhang, Ang B.; Vogel, Christine] NYU, Dept Biol, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Wang, Rong] NHLBI, NIH, Bethesda, MD 20892 USA. RP Vogel, C (reprint author), Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Austin, TX 78712 USA. EM cvogel@nyu.edu RI zhou, li/G-3756-2013 OI zhou, li/0000-0001-9032-0910 FU N.I.H.; U.S. Army Research [58343-MA]; Office of Naval Research [BAA 11-26]; Welch Foundation [F1515] FX We thank Dr Stanley Cohen from Stanford University for providing E. coli strains. We thank George Georgiou and Manuel Santos for helpful discussions. EMM acknowledges funding from the N.I.H., U.S. Army Research (58343-MA), Office of Naval Research (BAA 11-26), and Welch Foundation (F1515). NR 43 TC 4 Z9 4 U1 0 U2 7 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2013 VL 9 IS 4 BP 750 EP 757 DI 10.1039/c3mb25513a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 103IG UT WOS:000315908800024 PM 23403814 ER PT J AU Lau, WL Linnes, M Chu, EY Foster, BL Bartley, BA Somerman, MJ Giachelli, CM AF Lau, Wei Ling Linnes, Michael Chu, Emily Y. Foster, Brian L. Bartley, Bryan A. Somerman, Martha J. Giachelli, Cecilia M. TI High phosphate feeding promotes mineral and bone abnormalities in mice with chronic kidney disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE chronic kidney disease-mineral bone disorder; high-turnover renal osteodystrophy; phosphate; vascular calcification ID CHRONIC-RENAL-FAILURE; DYSTROPHIC CARDIAC CALCINOSIS; ARTERIAL MEDIAL CALCIFICATION; MYOCARDIAL-CELL NECROSIS; GROWTH-FACTOR 23; VASCULAR CALCIFICATION; HEMODIALYSIS-PATIENTS; PARATHYROID-HORMONE; MOUSE MODEL; SERUM PHOSPHORUS AB Background. Chronic kidney disease-mineral bone disorder (CKD-MBD) is a systemic syndrome characterized by imbalances in mineral homeostasis, renal osteodystrophy (ROD) and ectopic calcification. The mechanisms underlying this syndrome in individuals with chronic kidney disease (CKD) are not yet clear. Methods. We examined the effect of normal phosphate (NP) or high phosphate (HP) feeding in the setting of CKD on bone pathology, serum biochemistry and vascular calcification in calcification-prone dilute brown non-agouti (DBA/2) mice. Results. In both NP and HP-fed CKD mice, elevated serum parathyroid hormone and alkaline phosphatase (ALP) levels were observed, but serum phosphorus levels were equivalent compared with sham controls. CKD mice on NP diet showed trabecular alterations in the long bone consistent with high turnover ROD, including increased trabecular number with abundant osteoblasts and osteoclasts. Despite trabecular bone and serum biochemical changes, CKD/NP mice did not develop vascular calcification. In contrast, CKD/HP mice developed arterial medial calcification (AMC), more severe trabecular bone alterations and cortical bone abnormalities that included decreased cortical thickness and density, and increased cortical porosity. Cortical bone porosity and trabecular number strongly correlated with the degree of aortic calcification. Conclusions. BP feeding was required to induce the full spectrum of CKD-MBD symptoms in CKD mice. C1 [Lau, Wei Ling] Univ Washington, Dept Nephrol, Seattle, WA 98195 USA. [Linnes, Michael] Mayo Clin, Dept Hypertens & Nephrol, Rochester, MN USA. [Chu, Emily Y.; Giachelli, Cecilia M.] Univ Washington, Sch Dent, Dept Oral Hlth Sci, Seattle, WA 98195 USA. [Foster, Brian L.; Somerman, Martha J.] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA. [Bartley, Bryan A.; Giachelli, Cecilia M.] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. RP Giachelli, CM (reprint author), Univ Washington, Sch Dent, Dept Oral Hlth Sci, Seattle, WA 98195 USA. EM ceci@u.washington.edu RI Foster, Brian/H-8375-2015; OI Foster, Brian/0000-0003-3444-0576; Linnes, Michael/0000-0003-0504-7177 FU NIH [HL62329, HL081785, DE15109]; [T32 HL007828]; [T32 DK007467] FX This research was supported by NIH grants HL62329 and HL081785 to C.M.G. and NIH grant DE15109 to M.J.S.. W.L.L. received funding from T32 HL007828 and T32 DK007467. Studies were performed while B.L.F. and M.J.S. were affiliated with the University of Washington School of Dentistry, Department of Periodontics (Seattle, WA). NR 52 TC 6 Z9 6 U1 0 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JAN PY 2013 VL 28 IS 1 BP 62 EP 69 DI 10.1093/ndt/gfs333 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 098HN UT WOS:000315540100015 PM 23045434 ER PT J AU Bui, M Walkiewicz, MP Dimitriadis, EK Dalal, Y AF Bui, Minh Walkiewicz, Marcin P. Dimitriadis, Emilios K. Dalal, Yamini TI The CENP-A nucleosome A battle between Dr Jekyll and Mr Hyde SO NUCLEUS-AUSTIN LA English DT Article DE CENP-A; nucleosome; structure; oscillation; octamer; tetramer; hemisome; cell-cycle; AFM; acetylation ID CELL-CYCLE; CENTROMERIC NUCLEOSOMES; BUDDING YEAST; HISTONE H3; CHROMATIN; COMPLEX; HJURP; DEPOSITION; REQUIRES; ATRX AB The structure of the centromere-specific histone centromeric protein A (CENP-A) nucleosome has been a hot topic of debate for the past five years. Structures proposed include octamers, hexamers, homotypic and heterotypic tetramers. This controversy has led to the proposal that CENP-A nucleosomes undergo cell-cycle dependent transitions between the multiple states previously documented to exist in vivo and in vitro. In recent work from our laboratory, we sought to test this hypothesis. We discovered that CENP-A nucleosomes undergo unique oscillations in human cells, a finding mirrored in a parallel study performed in budding yeast. This review provides additional insights into the potential mechanisms for the interconversion of CENP-A nucleosomal species, and speculates on a biological role for oscillations in vivo. C1 [Bui, Minh; Walkiewicz, Marcin P.; Dalal, Yamini] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Dimitriadis, Emilios K.] Natl Inst Biomed Imaging & Bioengn, Lab Biomed Engn & Phys Sci, NIH, Bethesda, MD USA. RP Dalal, Y (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. EM dalaly@mail.nih.gov OI Dalal, Yamini/0000-0002-7655-6182 FU CCR/NCI Intramural Research Program; NIBIB Intramural Research Program FX M.B., M. P. W. and Y.D. are supported by the CCR/NCI Intramural Research Program, E. K. D. is supported by the NIBIB Intramural Research Program. We thank Delphine Quenet for comments on the manuscript. NR 45 TC 10 Z9 10 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1949-1034 J9 NUCLEUS-AUSTIN JI Nucleus-Austin PD JAN-FEB PY 2013 VL 4 IS 1 BP 37 EP 42 DI 10.4161/nucl.23588 PG 6 WC Cell Biology SC Cell Biology GA 103SL UT WOS:000315939100007 PM 23324462 ER PT J AU Kaila, VRI Send, R Sundholm, D AF Kaila, Ville R. I. Send, Robert Sundholm, Dage TI Electrostatic spectral tuning mechanism of the green fluorescent protein SO PHYSICAL CHEMISTRY CHEMICAL PHYSICS LA English DT Article ID EXCITED-STATES; BASIS-SETS; AEQUOREA; DENSITY; CHROMOPHORE; ENERGY; ENVIRONMENT; ABSORPTION; DYNAMICS; SYSTEM AB Understanding the mechanism of spectral tuning of biological chromophores is a major challenge in photobiology. We show here using large-scale full quantum chemical calculations of the green fluorescent protein that state-of-the-art coupled-cluster calculations provide accurate excitation energies and detailed insight about specific environmental effects. We obtain vertical excitation energies of 3.13 eV (396 nm) and 2.68 eV (463 nm), which are in quantitative agreement with the experimental absorption energies of 3.12 eV (397 nm) and 2.61 eV (475 nm) for the A-and B-forms of the protein. We find that the protein environment redshifts the absorption spectra by similar to 0.56 eV and similar to 0.22 eV for the two states, which can be attributed to similar to 80% electrostatic effects and similar to% steric effects. C1 [Kaila, Ville R. I.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Send, Robert] BASF SE, Quantum Chem Grp, D-67056 Ludwigshafen, Germany. [Sundholm, Dage] Univ Helsinki, Dept Chem, FIN-00014 Helsinki, Finland. RP Kaila, VRI (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM ville.kaila@nih.gov; robert.send@basf.com; dage.sundholm@helsinki.fi OI Sundholm, Dage Matts Borje/0000-0002-2367-9277 FU European Molecular Biology Organization (EMBO); National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Academy of Finland; Center for Functional Nanostructures (CFN) of the Deutsche Forschungsgemeinschaft (DFG) [C3.9]; HPC-EUROPA2 project [228398]; European Commission-Capacities Area-Research Infrastructures FX V.R.I.K. acknowledges the European Molecular Biology Organization (EMBO) for a Long-Term Fellowship, and the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases for support. This research has been supported by the Academy of Finland through its Computational Science Research Programme (LASTU), by the Center for Functional Nanostructures (CFN) of the Deutsche Forschungsgemeinschaft (DFG) within project C3.9, and by the HPC-EUROPA2 project (project number: 228398) with the support of the European Commission-Capacities Area-Research Infrastructures. CSC - the Finnish IT Center for Science and the Biowulf cluster (http://biowulf.nih.gov) at NIH are acknowledged for computer time. CSC is also acknowledged for hosting the HPC-EUROPA2 project. NR 38 TC 16 Z9 16 U1 0 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9076 J9 PHYS CHEM CHEM PHYS JI Phys. Chem. Chem. Phys. PY 2013 VL 15 IS 13 BP 4491 EP 4495 DI 10.1039/c3cp00058c PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 099VA UT WOS:000315649500003 PM 23420178 ER PT J AU Nayak, B Nayak, S Paldurai, A Kumar, S De Nardi, R Terregino, C Collins, PL Samal, SK AF Nayak, Baibaswata Nayak, Shreeraj Paldurai, Anandan Kumar, Sachin De Nardi, Roberta Terregino, Calogero Collins, Peter L. Samal, Siba K. TI Evaluation of the genetic diversity of avian paramyxovirus type 4 SO VIRUS RESEARCH LA English DT Article DE Avulavirus; Avian paramyxovirus type 4; Phylogenetic analysis ID COMPLETE GENOME SEQUENCE; NEWCASTLE-DISEASE-VIRUS; DUCKS ANAS-PLATYRHYNCHOS; NUCLEOTIDE-SEQUENCE; INFLUENZA-VIRUSES; FERAL DUCKS; SEROTYPE; PROTEIN; TURKEYS; YUCAIPA AB Avian paramyxoviruses (APMVs) belong to the genus Avulavirus in the family Paramyxoviridae and include at least nine serotypes, APMV-1 to -9, as well as two additional provisional serotypes. Newcastle disease virus (NDV), which comprises APMV-1, is the most extensively studied APMV because it is an important poultry pathogen. A moderate level of antigenic and genetic diversity is recognized for APMV-1 isolates, but our knowledge of the antigenic and genetic diversity of the other APMV serotypes is limited. APMV-4 is frequently isolated from waterfowl around the world. To date complete genome sequences of APMV-4 are available for only strains, which were isolated from ducks in Hong Kong, Korea and Belgium over a period of 37 years. We have carried out genome sequencing from the nucleocapsid (N) gene-end signal to the polymerase (L) gene-start signal of five APMV-4 strains recently isolated from Italy. Each of the eight APMV-4 strains has the same F protein cleavage site, DIQPR down arrow F. They also share a high level of nucleotide and amino acid sequence identity: for example, the F and HN glycoproteins have greater than 97% sequence identity between the various strains. Thus, comparison of these eight strains of APMV-4 did not provide evidence of substantial diversity, in contrast to similar studies with APMV-2, -3, and -6, in which the F and HN glycoproteins exhibited up to 20-30% amino acid sequence variation within a subgroup. Reciprocal cross-HI assay using post infection chicken sera also failed to detect significant antigenic variation among the available APMV-4 strains. Published by Elsevier B.V. C1 [Nayak, Baibaswata; Nayak, Shreeraj; Paldurai, Anandan; Kumar, Sachin; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [De Nardi, Roberta; Terregino, Calogero] Ist Zooprofilatt Sperimentale Venezie, OIE FAO, Legnaro, PD, Italy. [De Nardi, Roberta; Terregino, Calogero] Ist Zooprofilatt Sperimentale Venezie, Natl Reference Lab Newcastle Dis & Avian Influenz, Legnaro, PD, Italy. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. EM ssamal@umd.edu RI Nayak, Baibaswata/L-6156-2016 FU NIAID [N01A060009]; NIAID-NIH FX We thank Drs. Ilaria Capua and Isabella Monne at IZSV, Italy for helpful support and advice. We thank Daniel Rockemann for his excellent technical assistance and Peggy Barrot for proofreading the manuscript. "This research was supported by funding from NIAID contract no. N01A060009 (85% support) and NIAID-NIH Intramural Research Program (15% support). The views expressed herein do not necessarily reflect the official policies of the Department of Health and Human Services; nor does the mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government." NR 51 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD JAN PY 2013 VL 171 IS 1 BP 103 EP 110 DI 10.1016/j.virusres.2012.10.031 PG 8 WC Virology SC Virology GA 099FQ UT WOS:000315607300013 PM 23178589 ER PT J AU Wind, JJ Ohaegbulam, C Iwamoto, FM Black, PM Park, JK AF Wind, Joshua J. Ohaegbulam, Chima Iwamoto, Fabio M. Black, Peter M. Park, John K. TI Immediate Titanium Mesh Cranioplasty for Treatment of Postcraniotomy Infections SO WORLD NEUROSURGERY LA English DT Article DE Cranioplasty; Postcraniotomy infection; Titanium mesh ID VERTEBRAL OSTEOMYELITIS; HYDROXYAPATITE CEMENT; BONE FLAPS; CAGES; CRANIOTOMY; DEFECTS; SURGERY; RECONSTRUCTION; PRESERVATION; SKULL AB OBJECTIVE: Postcraniotomy infections have generally been treated by debridement of infected tissues, disposal of the bone flap, and delayed cranioplasty several months later to repair the resulting skull defect. Debridement followed by retention of the bone flap has also been advocated. Here we propose an alternative operative strategy for the treatment of postcraniotomy infections. METHODS: Two patients presenting with clinical and radiographic signs and symptoms of postcraniotomy infections were treated by debridement, bone flap disposal, and immediate titanium mesh cranioplasty. The patients were subsequently administered antibiotics, and their clinical courses were followed. RESULTS: The patients treated in this fashion did not have recurrence of their infections during 3-year follow-up periods. CONCLUSIONS: Surgical debridement, bone flap disposal, and immediate titanium mesh cranioplasty may be a suitable option for the treatment of postcraniotomy infections. This treatment strategy facilitates the eradication of infectious sources and obviates the risks and costs associated with a second surgical procedure. C1 [Wind, Joshua J.; Park, John K.] NINDS, Surg & Mol Neurooncol Unit, NIH, Bethesda, MD 20892 USA. [Wind, Joshua J.] George Washington Univ, Dept Neurol Surg, Washington, DC USA. [Ohaegbulam, Chima] New England Baptist Hosp, Boston, MA USA. [Iwamoto, Fabio M.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Black, Peter M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Park, JK (reprint author), NINDS, Surg & Mol Neurooncol Unit, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM parkjk@ninds.nih.gov RI Wind, Joshua/D-5480-2013 OI Wind, Joshua/0000-0003-3443-8476 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. NR 25 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1878-8750 J9 WORLD NEUROSURG JI World Neurosurg. PD JAN PY 2013 VL 79 IS 1 AR 207.e11 DI 10.1016/j.wneu.2011.02.013 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 100RB UT WOS:000315717800047 PM 22120410 ER PT J AU Maggio, M Snyder, PJ Ceda, GP Milaneschi, Y Luci, M Cattabiani, C Masoni, S Vignali, A Volpi, R Lauretani, F Peachey, H Valenti, G Cappola, AR Longo, D Ferrucci, L AF Maggio, M. Snyder, P. J. Ceda, G. P. Milaneschi, Y. Luci, M. Cattabiani, C. Masoni, S. Vignali, A. Volpi, R. Lauretani, F. Peachey, H. Valenti, G. Cappola, A. R. Longo, D. Ferrucci, L. TI Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men SO ANDROLOGY LA English DT Article DE erythropoietin; haemoglobin; older men; testosterone ID STAGE RENAL-DISEASE; ADULT MEN; THERAPY; ANEMIA; ANDROGENS; METAANALYSIS; POLYCYTHEMIA; DEFICIENCY; MECHANISM AB The stimulatory effects of testosterone on erythropoiesis are very well known, but the mechanisms underlying the erythropoietic action of testosterone are still poorly understood, although erythropoietin has long been considered a potential mediator. A total of 108 healthy men >65 years old with serum testosterone concentration <475 ng/dL were recruited by direct mailings to alumni of the University of Pennsylvania and Temple University, and randomized to receive a 60-cm(2) testosterone or placebo patch for 36 months. Ninety-six subjects completed the trial. We used information and stored serum specimens from this trial to test the hypothesis that increasing testosterone increases haemoglobin by stimulating erythropoietin production. We used information of 67 men, 43 in the testosterone group and 24 in the placebo group who had banked specimens available for assays of testosterone, haemoglobin and erythropoietin at baseline and after 36 months. The original randomized clinical study was primarily designed to verify the effects of testosterone on bone mineral density. The primary outcome of this report was to investigate whether or not transdermal testosterone increases haemoglobin by increasing erythropoietin levels. The mean age +/- SD of the 67 subjects at baseline was 71.8 +/- 4.9 years. Testosterone replacement therapy for 36 months, as compared with placebo, induced a significant increase in haemoglobin (0.86 +/- 0.31 g/dL, p = 0.01), but no change in erythropoietin levels (-0.24 +/- 2.16 mIU/mL, p = 0.91). Included time-varying measure of erythropoietin did not significantly account for the effect of testosterone on haemoglobin (Treatment-by-time: beta = 0.93, SE = 0.33, p = 0.01). No serious adverse effect was observed. Transdermal testosterone treatment of older men for 36 months significantly increased haemoglobin, but not erythropoietin levels. The haematopoietic effect of testosterone does not appear to be mediated by stimulation of erythropoietin production. C1 [Maggio, M.; Ceda, G. P.; Luci, M.; Cattabiani, C.; Masoni, S.; Vignali, A.; Volpi, R.; Valenti, G.] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. [Maggio, M.; Ceda, G. P.; Lauretani, F.] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy. [Snyder, P. J.; Peachey, H.; Cappola, A. R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Milaneschi, Y.; Longo, D.] NIA, NIH, Baltimore, MD 21224 USA. [Milaneschi, Y.; Ferrucci, L.] Vrije Univ Amsterdam, Med Ctr, GGZ InGeest, Dept Psychiat, Amsterdam, Netherlands. RP Maggio, M (reprint author), Univ Parma, Dept Clin & Expt Med, Sect Geriatr, Via Gramsci 14, I-43100 Parma, Italy. EM marcellomaggio2001@yahoo.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU US National Institute on Aging FX The Study was supported as a 'targeted project' by the US National Institute on Aging and by the Intramural Research Program of the US National Institute on Aging. None of the sponsoring institutions interfered with the collection, analysis, presentation, or interpretation of the data reported here. None of the authors have declared a conflict of interest. We thank all participants in the Study. NR 29 TC 23 Z9 23 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-2919 J9 ANDROLOGY-US JI Andrology PD JAN PY 2013 VL 1 IS 1 BP 24 EP 28 DI 10.1111/j.2047-2927.2012.00009.x PG 5 WC Andrology SC Endocrinology & Metabolism GA 097GJ UT WOS:000315461700004 PM 23258626 ER PT J AU Yi, DG AF Yi, Doogab TI Biology is Technology: The Promise, Peril, and New Business of Engineering Life SO ANNALS OF SCIENCE LA English DT Book Review C1 [Yi, Doogab] NIH, Off Hist, Bethesda, MD 20892 USA. RP Yi, DG (reprint author), NIH, Off Hist, 45 Ctr Dr,MSC 6330, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0003-3790 J9 ANN SCI JI Ann. Sci. PD JAN 1 PY 2013 VL 70 IS 1 BP 109 EP 111 DI 10.1080/00033790.2010.510941 PG 3 WC History & Philosophy Of Science SC History & Philosophy of Science GA 096AZ UT WOS:000315377400007 ER PT J AU Lee, BC Sung, B Eom, KH Park, ES Kim, MS Kim, SH Ogay, V Kim, KW Ryu, Y Yoon, YS Soh, KS AF Lee, Byung-Cheon Sung, Baeckkyoung Eom, Ki-Hoon Park, Eun-Sung Kim, Min Su Kim, Se Hoon Ogay, Vyacheslav Kim, Ki Woo Ryu, Yeonhee Yoon, Yeo-Sung Soh, Kwang-Sup TI Novel Threadlike Structures on the Surfaces of Mammalian Abdominal Organs are Loose Bundles of Fibrous Stroma with Microchannels Embedded with Fibroblasts and Inflammatory Cells SO CONNECTIVE TISSUE RESEARCH LA English DT Article DE abdominal organ surface; novel threadlike structure; loose connective tissue; fibrous bundle; interstitial microchannel; fibroblast; inflammatory cell ID INTERSTITIAL-TISSUE; LYMPHATIC VESSELS; COLLAGEN-FIBERS; PATHWAYS; FLUID; ACUPUNCTURE; CORPUSCLES; PERITONEAL; MESHWORK; CHANNELS AB Novel threadlike structures (NTSs) on the surfaces of mammalian abdominal organs have recently attracted interests regarding their ability to transport fluid, enable cell migration, and possibly facilitate cancer metastasis. Nevertheless, histological studies of NTSs have been sporadic and often have inconsistent interpretations of the NTS internal structure. In this article, we provide a synthetic and consistent view of the NTS internal structure: the NTS is a loose bundle of fibrous stroma that forms interstitial channels and microsinusoids infiltrated with inflammatory cells. The fibroblasts are embedded in the stroma and mostly aligned along the major axis of the NTS. The sinusoids, which are in inconsecutive cross sections, have boundaries more or less delineated by extracellular fibers, partly surrounded by endothelial-like cells, or both. We compare these morphological features to other well-known connective tissues (i.e., trabecular meshwork and lymphatic capillary) and discuss the biomechanical and biological functions of NTSs based on their structural characteristics. C1 [Lee, Byung-Cheon] Pharmacopuncture Med Res Inst, Seoul, South Korea. [Lee, Byung-Cheon] Korea Adv Inst Sci & Technol, Div Elect Engn, KAIST Inst Informat Technol Convergence, Taejon 305701, South Korea. [Sung, Baeckkyoung; Eom, Ki-Hoon; Soh, Kwang-Sup] Seoul Natl Univ, Dept Phys & Astron, Biomed Phys Lab, Seoul, South Korea. [Park, Eun-Sung; Yoon, Yeo-Sung] Seoul Natl Univ, Coll Vet Med, Dept Anat & Cell Biol, Seoul, South Korea. [Park, Eun-Sung] KOATECH Inc, Pyeongtaek, South Korea. [Kim, Min Su] Chonbuk Natl Univ, Coll Vet Med, Dept Surg, Jeonju, South Korea. [Kim, Se Hoon] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea. [Ogay, Vyacheslav] Natl Biotechnol Ctr, Stem Cell Lab, Astana, Kazakhstan. [Kim, Ki Woo] Kyungpook Natl Univ, Sch Ecol & Environm Syst, Sangju, South Korea. [Ryu, Yeonhee] Korea Inst Oriental Med, Dept Acupuncture, Taejon, South Korea. [Soh, Kwang-Sup] Seoul Natl Univ, Adv Inst Convergence Technol, Nano Primo Res Ctr, Suwon, South Korea. RP Kim, SH (reprint author), Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea. EM paxco@yuhs.ac OI Soh, Kwang-Sup/0000-0001-8776-7877; Kim, Se Hoon/0000-0001-7516-7372 FU National Research Foundation of Korea (NRF); Korea Government's Ministry of Education, Science and Technology (MEST) [2010-0025289]; Korean Pharmacopuncture Foundation; Korean Pharmacopuncture Institute [KPI-2010-003]; Traditional Korean Medicine R&D Project, Ministry for Health & Welfare, Republic of Korea FX This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea Government's Ministry of Education, Science and Technology (MEST) in 2010 (No. 2010-0025289), by a Korean Pharmacopuncture Foundation grant funded by the Korean Pharmacopuncture Institute (KPI-2010-003), and by the grant of the Traditional Korean Medicine R&D Project, Ministry for Health & Welfare, Republic of Korea. NR 57 TC 1 Z9 1 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0300-8207 J9 CONNECT TISSUE RES JI Connect. Tissue Res. PY 2013 VL 54 IS 2 BP 94 EP 100 DI 10.3109/03008207.2012.748757 PG 7 WC Cell Biology; Orthopedics SC Cell Biology; Orthopedics GA 099QD UT WOS:000315635400002 PM 23186263 ER PT J AU Whitehead, TP Ward, MH Colt, JS Nishioka, MG Buffler, PA Rappaport, SM Metayer, C AF Whitehead, Todd P. Ward, Mary H. Colt, Joanne S. Nishioka, Marcia G. Buffler, Patricia A. Rappaport, Stephen M. Metayer, Catherine TI Determinants of polychlorinated biphenyls in dust from homes in California, USA SO ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS LA English DT Article ID IN-HOUSE DUST; PERSISTENT ORGANIC POLLUTANTS; LAWN APPLICATIONS; TEMPORAL TRENDS; CARPET DUST; EXPOSURE; CHILDREN; AIR; PESTICIDE; BLOOD AB Polychlorinated biphenyl (PCB) production ceased in the U.S. over 30 years ago, but these persistent chemicals remain ubiquitous contaminants. Here, we evaluate potential determinants of PCB levels in dust from California homes including characteristics of the residence as well as the residents' habits and occupations. Dust was collected from 415 households as part of a large case-control study (the Northern California Childhood Leukaemia Study), using a high-volume small surface sampler. Dust concentrations of 6 PCBs (PCB-105, PCB-118, PCB-138, PCB-153, PCB-170, and PCB-180) were measured using gas chromatography-mass spectrometry. Individual PCB detection rates ranged from 9% to 54% with PCB concentrations ranging from below detection (1 or 2 ng g(-1)) to 270 ng g(-1) and PCB loadings ranging from below detection to 960 ng m(-2). Multivariable linear and logistic regression models were used to identify potential determinants of residential PCB contamination based on in-home interviews and residential geographic locations. We observed that residences built prior to 1980 had higher odds of PCB detection and higher PCB loadings than more recently constructed homes. Households where residents typically did not remove their shoes had higher PCB dust loadings than households where residents did. PCBs were less likely to be detected in carpet dust from households that had frequently vacuumed or replaced carpets compared to other households. Since we used a cross-sectional dust sampling protocol and report significant, but modest, effects of these determinants on levels of PCBs in residential dust, our results should be interpreted with caution. Longitudinal studies to determine optimal strategies for reducing PCBs in homes are warranted. C1 [Whitehead, Todd P.; Buffler, Patricia A.; Rappaport, Stephen M.; Metayer, Catherine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Ward, Mary H.; Colt, Joanne S.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH 43201 USA. RP Whitehead, TP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. EM toddpwhitehead@berkeley.edu FU Intramural NIH HHS [Z01 CP010125-12] NR 45 TC 4 Z9 4 U1 1 U2 39 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-7887 J9 ENVIRON SCI-PROC IMP JI Environ. Sci.-Process Impacts PY 2013 VL 15 IS 2 BP 339 EP 346 DI 10.1039/c2em30721a PG 8 WC Chemistry, Analytical; Environmental Sciences SC Chemistry; Environmental Sciences & Ecology GA 096IP UT WOS:000315397700003 PM 25208698 ER PT J AU Kim, M Chen, Z Shim, MS Lee, MS Kim, JE Kwon, YE Yoo, TJ Kim, JY Bang, JY Carlson, BA Seol, JH Hatfield, DL Lee, BJ AF Kim, Mijin Chen, Zifan Shim, Myoung Sup Lee, Myoung Sook Kim, Ji Eon Kwon, Young Eun Yoo, Tack Jin Kim, Jin Young Bang, Je Young Carlson, Bradley A. Seol, Jae Hong Hatfield, Dolph L. Lee, Byeong Jae TI SUMO Modification of NZFP Mediates Transcriptional Repression through TBP Binding SO MOLECULES AND CELLS LA English DT Article DE development; NZFP; SUMO; TATA binding protein; Xenopus ID GLUCOCORTICOID RECEPTOR; COVALENT MODIFICATION; MODIFIER-1 SUMO-1; XENOPUS-LAEVIS; PROTEIN; SUMOYLATION; CONJUGATION; DOMAIN; LOCALIZATION; DISEASE AB The negatively regulating zinc finger protein (NZFP) is an essential transcription repressor required for early development during gastrulation in Xenopus laevis. In this study, we found that NZFP interacts with the small ubiquitin-like modifier (SUMO) conjugation E2 enzyme, Ubc9, and contains three putative SUMO conjugation sites. Studies with NZFP mutants containing mutations at the putative SUMO conjugation sites showed that these sites were able to be modified independently with SUMO. NZFP was found to be localized in the same nuclear bodies with SUMO-1. However, sumoylation of NZFP did not play a role either in the translocation of NZFP into the nucleus or on nuclear body formation. While wild type NZFP showed significant transcriptional repression, SUMO-conjugation site mutants manifested a decrease in transcriptional repression activity which is reversely proportional to the amount of sumoylation. The sumoylation defective mutant lost its TBP binding activity, while wild type NZFP interacted with TBP and inhibited transcription complex formation. These results strongly suggest that the sumoylation of NZFP facilitates NZFP to bind to TBP and the NZFP/TBP complex then represses the transcription of the target gene by inhibiting basal transcription complex formation. C1 [Kim, Mijin; Chen, Zifan; Shim, Myoung Sup; Lee, Myoung Sook; Kim, Ji Eon; Kwon, Young Eun; Yoo, Tack Jin; Kim, Jin Young; Seol, Jae Hong; Lee, Byeong Jae] Seoul Natl Univ, Sch Biol Sci, Inst Mol Biol & Genet, Seoul 151742, South Korea. [Bang, Je Young; Lee, Byeong Jae] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151742, South Korea. [Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Lee, BJ (reprint author), Seoul Natl Univ, Sch Biol Sci, Inst Mol Biol & Genet, Seoul 151742, South Korea. EM imbglmg@snu.ac.kr FU National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2010-0029694, 2011-0012947]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; Korea Ministry of Education and Human Resources Development FX We thank Drs. Chin Ha Chung and Yongsok Kim for kindly providing vectors. This work was supported by the Priority Research Centers Program and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (Grant Nos 2010-0029694 and 2011-0012947 to BJL) and in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research to DLH. MK, ZC, MSS, MSL, JEK, JYK, and JB were supported by Brain Korea 21 Research Fellowship from the Korea Ministry of Education and Human Resources Development. NR 31 TC 3 Z9 3 U1 1 U2 1 PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY PI SEOUL PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD JAN PY 2013 VL 35 IS 1 BP 70 EP 78 DI 10.1007/s10059-013-2281-1 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 098XE UT WOS:000315581600010 PM 23269432 ER PT J AU Zhang, XL Lenburg, ME Spira, A AF Zhang, Xiaoling Lenburg, Marc E. Spira, Avrum TI Comparison of Nasal Epithelial Smoking-Induced Gene Expression on Affymetrix Exon 1.0 and Gene 1.0 ST Arrays SO SCIENTIFIC WORLD JOURNAL LA English DT Article ID LUNG-CANCER AB We have previously defined the impact of tobacco smoking on nasal epithelium gene expression using Affymetrix Exon 1.0 ST arrays. In this paper, we compared the performance of the Affymetrix GeneChip Human Gene 1.0 ST array with the Human Exon 1.0 ST array for detecting nasal smoking-related gene expression changes. RNA collected from the nasal epithelium of five current smokers and five never smokers was hybridized to both arrays. While the intersample correlation within each array platform was relatively higher in the Gene array than that in the Exon array, the majority of the genes most changed by smoking were tightly correlated between platforms. Although neither array dataset was powered to detect differentially expressed genes (DEGs) at a false discovery rate (FDR) < 0.05, we identified more DEGs than expected by chance using the Gene ST array. These findings suggest that while both platforms show a high degree of correlation for detecting smoking-induced differential gene expression changes, the Gene ST array may be a more cost-effective platform in a clinical setting for gene-level genomewide expression profiling and an effective tool for exploring the host response to cigarette smoking and other inhaled toxins. C1 [Zhang, Xiaoling; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Sch Med, Div Computat Biomed, Boston, MA 02118 USA. [Zhang, Xiaoling] NHLBI, Div Intramural Res, NHLBIs Framingham Heart Study, Framingham, MA 01702 USA. [Spira, Avrum] Boston Univ, Med Ctr, Ctr Pulm, Boston, MA 02118 USA. RP Zhang, XL (reprint author), Boston Univ, Sch Med, Div Computat Biomed, 72 East Concord St,E631, Boston, MA 02118 USA. EM shirley0818@gmail.com RI Lenburg, Marc/B-8027-2008 OI Lenburg, Marc/0000-0002-5760-4708 FU NIH/NIEHS [UO1ES016035] FX This work was supported by NIH/NIEHS UO1ES016035 (Genes, Environment and Health Initiative). NR 11 TC 0 Z9 0 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2013 AR 951416 DI 10.1155/2013/951416 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 097WT UT WOS:000315504900001 ER PT J AU Primack, BA Land, SR Fan, JY Kim, KH Rosen, D AF Primack, Brian A. Land, Stephanie R. Fan, Jieyu Kim, Kevin H. Rosen, Daniel TI Associations of Mental Health Problems With Waterpipe Tobacco and Cigarette Smoking Among College Students SO SUBSTANCE USE & MISUSE LA English DT Article DE cigarette smoking; college students; tobacco use; waterpipe smoking ID UNIVERSITY-STUDENTS; MAJOR DEPRESSION; UNITED-STATES; PREVALENCE; BEHAVIORS; CESSATION; AEROSOL; YOUTH; PIPE; WEB AB Associations between the emerging trend of waterpipe tobacco smoking and mental health among college students have not been sufficiently explored. This study analyzed data collected from 152 academic institutions that participated in the National College Health Assessment during the 2008-2009 academic year to examine associations between mental health and waterpipe tobacco smoking among college students (N = 100,891). For comparison, cigarette smoking was also examined. Associations with mental health variables were very strong for cigarette smoking but only moderate for waterpipe smoking. Study implications and limitations are noted. C1 [Primack, Brian A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. [Land, Stephanie R.] NCI, Behav Res Program, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Fan, Jieyu] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15213 USA. [Kim, Kevin H.] Univ Pittsburgh, Sch Educ, Res Methodol Program, Pittsburgh, PA 15213 USA. [Kim, Kevin H.] Univ Pittsburgh, Joseph M Katz Grad Sch Business, Pittsburgh, PA 15213 USA. [Rosen, Daniel] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15213 USA. RP Primack, BA (reprint author), Univ Pittsburgh, Sch Med, 230 McKee Pl 600, Pittsburgh, PA 15213 USA. EM bprimack@pitt.edu FU NIH [R01-CA140150] FX Funding was provided by NIH Grant R01-CA140150. NR 39 TC 10 Z9 10 U1 1 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2013 VL 48 IS 3 BP 211 EP 219 DI 10.3109/10826084.2012.750363 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 096MY UT WOS:000315409600003 PM 23302059 ER PT J AU Lee, H Williams, RA AF Lee, Hyunhwa Williams, Reg A. TI Effects of Parental Alcoholism, Sense of Belonging, and Resilience on Depressive Symptoms: A Path Model SO SUBSTANCE USE & MISUSE LA English DT Article DE adult children of alcoholics; sense of belonging; resilience; depressive symptoms; Koreans ID CONNOR-DAVIDSON RESILIENCE; SCALE CD-RISC; SOCIAL SUPPORT; ADULT CHILDREN; OLDER-ADULTS; STRESS; SYMPTOMATOLOGY; SAMPLE; BDI AB This paper explored the relationships between parental alcoholism, sense of belonging, resilience, and depressive symptoms among Koreans in the U. S. Data from 206 Koreans (Mean age = 28.4 years; 59.8% females) living in a Midwestern state were collected in 2009, using a web-based survey, which included Children of Alcoholic Screening Test, Sense of Belonging Instrument, Connor-Davidson Resilience Scale, and Beck Depression Inventory-II. Path analysis results revealed sense of belonging as the most powerful, and resilience as the second important factor, resisting depressive symptoms associated with parental alcoholism. Implications for practice and research and study limitations are discussed. The study's limitations are noted. C1 [Lee, Hyunhwa] NINR, Intramural Res Program, NIH, Bethesda, MD 20895 USA. [Williams, Reg A.] Univ Michigan, Sch Med, Sch Nursing & Psychiat, Ann Arbor, MI USA. RP Lee, H (reprint author), NINR, Intramural Res Program, NIH, 9 Mem Rd, Bethesda, MD 20895 USA. EM leeh9@mail.nih.gov FU Rackham Graduate School; School of Nursing, University of Michigan FX This project was supported in part by grants from Rackham Graduate School (One-term Dissertation Fellowship) and School of Nursing (Awards for New Investigators), University of Michigan. NR 49 TC 2 Z9 2 U1 2 U2 25 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2013 VL 48 IS 3 BP 265 EP 273 DI 10.3109/10826084.2012.754899 PG 9 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 096MY UT WOS:000315409600009 PM 23302055 ER PT J AU Liu, SH Zhang, Y Hoover, B Leppla, SH AF Liu, Shihui Zhang, Yi Hoover, Benjamin Leppla, Stephen H. TI The Receptors that Mediate the Direct Lethality of Anthrax Toxin SO TOXINS LA English DT Article DE anthrax; CMG2; FP59; integrin beta 1; Tem8 ID CAPILLARY MORPHOGENESIS PROTEIN-2; KINASE-KINASE; MICE; INTERNALIZATION; ENDOCYTOSIS; DIPHTHAMIDE; POTENCY; CELLS AB Tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) are the two well-characterized anthrax toxin receptors, each containing a von Willebrand factor A (vWA) domain responsible for anthrax protective antigen (PA) binding. Recently, a cell-based analysis was used to implicate another vWA domain-containing protein, integrin beta 1 as a third anthrax toxin receptor. To explore whether proteins other than TEM8 and CMG2 function as anthrax toxin receptors in vivo, we challenged mice lacking TEM8 and/or CMG2. Specifically, we used as an effector protein the fusion protein FP59, a fusion between the PA-binding domain of anthrax lethal factor (LF) and the catalytic domain of Pseudomonas aeruginosa exotoxin A. FP59 is at least 50-fold more potent than LF in the presence of PA, with 2 mu g PA + 2 mu g FP59 being sufficient to kill a mouse. While TEM8(-/-) and wild type control mice succumbed to a 5 mu g PA + 5 mu g FP59 challenge, CMG2(-/-) mice were completely resistant to this dose, confirming that CMG2 is the major anthrax toxin receptor in vivo. To detect whether any toxic effects are mediated by TEM8 or other putative receptors such as integrin beta 1, CMG2(-/-)/TEM8(-/-) mice were challenged with as many as five doses of 50 mu g PA + 50 mu g FP59. Strikingly, the CMG2(-/-)/TEM8(-/-) mice were completely resistant to the 5-dose challenge. These results strongly suggest that TEM8 is the only minor anthrax toxin receptor mediating direct lethality in vivo and that other proteins implicated as receptors do not play this role. C1 [Liu, Shihui; Zhang, Yi; Hoover, Benjamin; Leppla, Stephen H.] NIAID, Parasit Dis Lab, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Liu, SH (reprint author), NIAID, Parasit Dis Lab, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. EM shliu@niaid.nih.gov; zhangy23@niaid.nih.gov; hooverbj@niaid.nih.gov; sleppla@niaid.nih.gov FU intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank Rasem Fattah for protein purification. NR 27 TC 13 Z9 14 U1 0 U2 9 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD JAN PY 2013 VL 5 IS 1 BP 1 EP 8 DI 10.3390/toxins5010001 PG 8 WC Toxicology SC Toxicology GA 096MC UT WOS:000315407200001 ER PT J AU Gupta, GN Boris, R Chung, P Linehan, WM Pinto, PA Bratslavsky, G AF Gupta, Gopal N. Boris, Ronald Chung, Paul Linehan, W. Marston Pinto, Peter A. Bratslavsky, Gennady TI Robot-assisted laparoscopic partial nephrectomy for tumors greater than 4 cm and high nephrometry score: Feasibility, renal functional, and oncological outcomes with minimum 1 year follow-up SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Partial nephrectomy; Robotic surgery; Clinical stage T1B; Renal function; Kidney cancer; Nephrometry score ID SPARING SURGERY; CELL CARCINOMA; RADICAL NEPHRECTOMY; WARM ISCHEMIA; SERUM CREATININE; IMPACT; EXPERIENCE; LARGER; TIME AB Objectives: Minimally invasive robotic assistance is being increasingly utilized to treat larger complex renal masses. We report on the technical feasibility and renal functional and oncologic outcomes with minimum 1 year follow-up of robot-assisted laparoscopic partial nephrectomy (RALPN) for tumors greater than 4 cm. Materials and methods: The urologic oncology database was queried to identify patients treated with RALPN for tumors greater than 4 cm and a minimum follow-up of 12 months. We identified 19 RALPN on 17 patients treated between June 2007 and July 2009. Two patients underwent staged bilateral RALPN. Demographic, operative, and pathologic data were collected. Renal function was assessed by serum creatinine levels, estimated glomerular filtration rate, and nuclear renal scans assessed at baseline, 3, and 12 months postoperatively. All tumors were assigned R.E.N.A.L. nephrometry scores (http://www.nephrometry.com). Results: The median nephrometry score for the largest tumor from each kidney was 9 (range 6-11) while the median size was 5 cm (range 4.1-15). Three of 19 cases (16%) required intraoperative conversion to open partial nephrectomy. No renal units were lost. There were no statistically significant differences between preoperative and postoperative creatinine and eGFR. A statistically significant decline of ipsilateral renal scan function (49% vs. 46.5%, P = 0.006) was observed at 3 months and at 12 mo postoperatively (49% vs. 45.5%, P = 0.014). None of the patients had evidence of recurrence or metastatic disease at a median follow-up of 22 months (range 12-36). Conclusions: RALPN is feasible for renal tumors greater than 4 cm with moderate or high nephrometry scores. Although there was a modest decline in renal function of the operated unit, RALPN may afford the ability resect challenging tumors requiring complex renal reconstruction. The renal functional and oncologic outcomes are promising at a median follow-up of 22 months, but longer follow-up is required. Published by Elsevier Inc. C1 [Gupta, Gopal N.; Boris, Ronald; Chung, Paul; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU Intramural NIH HHS [Z01 BC011023-01]; NCI NIH HHS [Z01 BC011038-01, Z01 BC011043-01, Z01 BC011028-01, Z01 BC011023-01] NR 25 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2013 VL 31 IS 1 BP 51 EP 56 DI 10.1016/j.urolonc.2010.10.008 PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 097KL UT WOS:000315472900009 PM 21292511 ER PT J AU Wilson, M Mattson, MP Zou, SG AF Wilson, Mark Mattson, Mark P. Zou, Sige TI Invertebrates as workhorses for aging and intervention studies Preface SO AGEING RESEARCH REVIEWS LA English DT Editorial Material C1 [Wilson, Mark; Mattson, Mark P.; Zou, Sige] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA. RP Zou, SG (reprint author), NIA, Translat Gerontol Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM zous@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD JAN PY 2013 VL 12 IS 1 BP 402 EP 403 DI 10.1016/j.arr.2012.12.003 PN 2013 PG 2 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 092MD UT WOS:000315125800037 PM 23332640 ER PT J AU Carter, TC Kay, DM Browne, ML Liu, AY Romitti, PA Kuehn, D Conley, MR Caggana, M Druschel, CM Brody, LC Mills, JL AF Carter, Tonia C. Kay, Denise M. Browne, Marilyn L. Liu, Aiyi Romitti, Paul A. Kuehn, Devon Conley, Mary R. Caggana, Michele Druschel, Charlotte M. Brody, Lawrence C. Mills, James L. TI Anorectal atresia and Variants at Predicted Regulatory Sites in Candidate Genes SO ANNALS OF HUMAN GENETICS LA English DT Article DE Anorectal malformations; imperforate anus; hindgut; congenital abnormalities ID MCKUSICK-KAUFMAN-SYNDROME; STRUCTURAL BIRTH-DEFECTS; SONIC HEDGEHOG; HIRSCHSPRUNG DISEASE; RISK-FACTORS; CLEFT-LIP; MALFORMATIONS; ANOMALIES; OBESITY; COMMON AB Anorectal atresia is a serious birth defect of largely unknown etiology but candidate genes have been identified in animal studies and human syndromes. Because alterations in the activity of these genes might lead to anorectal atresia, we selected 71 common variants predicted to be in transcription factor binding sites, CpG windows, splice sites, and miRNA target sites of 25 candidate genes, and tested for their association with anorectal atresia. The study population comprised 150 anorectal atresia cases and 623 control infants without major malformations. Variants predicted to affect transcription factor binding, splicing, and DNA methylation in WNT3A, PCSK5, TCF4, MKKS, GLI2, HOXD12, and BMP4 were associated with anorectal atresia based on a nominal P value < 0.05. The GLI2 and BMP4 variants are reported to be moderately associated with gene expression changes (Spearman's rank correlation coefficients between -0.260 and 0.226). We did not find evidence for interaction between maternal pre-pregnancy obesity and variants in MKKS, a gene previously associated with obesity, on the risk of anorectal atresia. Our results for MKKS support previously suggested associations with anorectal malformations. Our findings suggest that more research is needed to determine whether altered GLI2 and BMP4 expression is important in anorectal atresia in humans. C1 [Carter, Tonia C.; Liu, Aiyi; Kuehn, Devon; Conley, Mary R.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD USA. [Kay, Denise M.; Caggana, Michele] New York State Dept Hlth, Wadsworth Ctr, Div Genet, Albany, NY USA. [Browne, Marilyn L.; Druschel, Charlotte M.] New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. [Browne, Marilyn L.; Druschel, Charlotte M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA. [Romitti, Paul A.] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHD, DESPR, NIH, 6100 Bldg,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov OI Kay, Denise/0000-0002-9928-2698; Liu, Aiyi/0000-0002-6618-5082 FU Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703431C, N01-DK-7-3431] FX We thank April J. Atkins, Emily C. McGrath, and Robert J. Sicko for laboratory and technical assistance. We are also grateful for the data management skills of Sandra D. Richardson. This work was supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (Contract # HHSN267200703431C; NICHD # N01-DK-7-3431). NR 45 TC 7 Z9 8 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2013 VL 77 BP 31 EP 46 DI 10.1111/j.1469-1809.2012.00734.x PN 1 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 093MU UT WOS:000315196800004 PM 23127126 ER PT J AU Kodaman, N Aldrich, MC Smith, JR Signorello, LB Bradley, K Breyer, J Cohen, SS Long, JR Cai, QY Giles, J Bush, WS Blot, WJ Matthews, CE Williams, SM AF Kodaman, Nuri Aldrich, Melinda C. Smith, Jeffrey R. Signorello, Lisa B. Bradley, Kevin Breyer, Joan Cohen, Sarah S. Long, Jirong Cai, Qiuyin Giles, Justin Bush, William S. Blot, William J. Matthews, Charles E. Williams, Scott M. TI A Small Number of Candidate Gene SNPs Reveal Continental Ancestry in African Americans SO ANNALS OF HUMAN GENETICS LA English DT Article DE Ancestry Informative Markers; AIMs; African Americans; candidate genes; genetic ancestry; STRUCTURE; admixture; population stratification ID GENOME-WIDE ASSOCIATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; SOUTHERN COMMUNITY COHORT; POPULATION-STRUCTURE; INFORMATIVE MARKERS; HEALTH DISPARITIES; EUROPEAN AMERICANS; ADMIXTURE; STRATIFICATION; ORIGIN AB Using genetic data from an obesity candidate gene study of self-reported African Americans and European Americans, we investigated the number of Ancestry Informative Markers (AIMs) and candidate gene SNPs necessary to infer continental ancestry. Proportions of African and European ancestry were assessed with STRUCTURE (K = 2), using 276 AIMs. These reference values were compared to estimates derived using 120, 60, 30, and 15 SNP subsets randomly chosen from the 276 AIMs and from 1144 SNPs in 44 candidate genes. All subsets generated estimates of ancestry consistent with the reference estimates, with mean correlations greater than 0.99 for all subsets of AIMs, and mean correlations of 0.99 +/- 0.003; 0.98 +/- 0.01; 0.93 +/- 0.03; and 0.81 +/- 0.11 for subsets of 120, 60, 30, and 15 candidate gene SNPs, respectively. Among African Americans, the median absolute difference from reference African ancestry values ranged from 0.01 to 0.03 for the four AIMs subsets and from 0.03 to 0.09 for the four candidate gene SNP subsets. Furthermore, YRI/CEU Fst values provided a metric to predict the performance of candidate gene SNPs. Our results demonstrate that a small number of SNPs randomly selected from candidate genes can be used to estimate admixture proportions in African Americans reliably. C1 [Kodaman, Nuri; Giles, Justin; Bush, William S.; Williams, Scott M.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Ctr Human Genet Res, Nashville, TN 37232 USA. [Aldrich, Melinda C.] Vanderbilt Univ, Dept Thorac Surg, Div Epidemiol, Nashville, TN USA. [Aldrich, Melinda C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Smith, Jeffrey R.; Signorello, Lisa B.; Bradley, Kevin; Breyer, Joan; Long, Jirong; Cai, Qiuyin; Blot, William J.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Signorello, Lisa B.; Cohen, Sarah S.; Blot, William J.] Int Epidemiol Inst, Rockville, MD USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Williams, SM (reprint author), Dartmouth Coll, Geisel Sch Med, Dept Genet, 78 Coll St,HB 6044, Hanover, NH 03755 USA. EM scott.williams@dartmouth.edu RI Williams, Scott/B-9491-2012; Smith, Jeff/C-3484-2012; matthews, Charles/E-8073-2015; OI matthews, Charles/0000-0001-8037-3103; Bush, William/0000-0002-9729-6519 FU Komen for the Cure grant [OP05-0927-DR1]; NIH [R01CA092447, 3T32GM080178-03S1]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX This project was supported in part by the Komen for the Cure grant OP05-0927-DR1 and by NIH grants R01CA092447 and 3T32GM080178-03S1. DNA sample preparation was conducted at the Survey and Biospecimen Shared Resource that is supported in part by the Vanderbilt-Ingram Cancer Center (P30 CA68485). Analysis was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville TN. We wish to thank Emily Phillips for help with graphics and Regina Courtney for DNA sample preparation. NR 33 TC 3 Z9 3 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2013 VL 77 BP 56 EP 66 DI 10.1111/j.1469-1809.2012.00738.x PN 1 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 093MU UT WOS:000315196800006 PM 23278390 ER PT J AU Zheng, G Xu, JF Yuan, A Wu, CO AF Zheng, Gang Xu, Jinfeng Yuan, Ao Wu, Colin O. TI Impact on Modes of Inheritance and Relative Risks of Using Extreme Sampling When Designing Genetic Association Studies SO ANNALS OF HUMAN GENETICS LA English DT Article DE Association studies; extreme sampling; genetic models; genotype relative risks; replication ID QUANTITATIVE-TRAIT LOCI; LINKAGE DISEQUILIBRIUM; TREND TESTS; SIB-PAIRS; POWER; ROBUSTNESS AB Using extreme phenotypes for association studies can improve statistical power. We study the impact of using samples with extremely high or low traits on the alternative model space, the genotype relative risks, and the genetic models in association studies. We prove the following results: when the risk allele causes high-trait values, the more extreme the high traits, the larger the genotype relative risks, which is not always true for using extreme low traits; we also prove that a genetic model theoretically changes with more extreme trait except for the recessive or dominant models. Practically, however, the impact of deviations from the true genetic model at a functional locus due to selective sampling is virtually negligible. The implications of our findings are discussed. Numerical values are reported for illustrations. C1 [Zheng, Gang; Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Xu, Jinfeng] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore. [Yuan, Ao] Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov OI Xu, Jinfeng/0000-0002-3165-2015 FU National University of Singapore [R-155-000-112-112]; National Center for Research Resources at NIH [2G12RR003048] FX The work of J Xu was partially supported by Research Grant No. R-155-000-112-112 of National University of Singapore. The work of A Yuan was supported in part by the National Center for Research Resources at NIH grant 2G12RR003048. The authors do not have conflict of interest. NR 17 TC 1 Z9 1 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2013 VL 77 BP 80 EP 84 DI 10.1111/j.1469-1809.2012.00733.x PN 1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 093MU UT WOS:000315196800008 PM 23163532 ER PT S AU Bodhak, S Kikuchi, M Oyane, A Sogo, Y Tsurushima, H Ito, A AF Bodhak, Subhadip Kikuchi, Masanori Oyane, Ayako Sogo, Yu Tsurushima, Hideo Ito, Atsuo BE Ishikawa, K Iwamoto, Y TI Calcium Phosphate Coated Hydroxyapatite/Collagen Nanocomposite Membrane for Surface-Mediated Gene Transfer SO BIOCERAMICS 24 SE Key Engineering Materials LA English DT Proceedings Paper CT 24th Symposium and Annual Meeting of International Society for Ceramics in Medicine (ISCM 2012) CY OCT 21-24, 2012 CL Fukuoka, JAPAN DE Hydroxyapatite/collagen nanocomposite membrane; Biomimetic process; Supersaturated solution; Calcium phosphate coating; Gene transfer ID SELF-ORGANIZATION MECHANISM; APATITE COMPOSITE LAYER; HIGHLY EFFICIENT AB Calcium phosphate (CaP) coating is an effective technique for surface functionalization of biomaterials. The objective of our research is to prepare calcium phosphate (CaP) coatings on a hydroxyapatite/collagen (HAp/Col) nanocomposite and subsequently provide it with gene delivery function through the immobilization of DNA in the coating. We have specifically selected the HAp/Col nanocomposite since it has the high potential as bone substitutes due to its similar composition, nanostructure, and biological properties to those of human bone. CaP coatings consisting of different sized particles were prepared on the HAp/Col nanocomposite membrane by immersing it in supersaturaterd CaP solutions (so-called RKM solutions) with the varied Ca and P concentration levels. We immobilized DNA in the CaP coatings together with lipid and fibronectin by supplementing DNA, lipid, and fibronectin to the RKM solutions (DLF-RKM solutions). Gene transfer capability of the resulting HAp/Col nanocomposite membrane was improved with decreasing concentration level of the DLF-RKM solution. It was confirmed that the present CaP coating technique was effective in providing the HAp/Col nanocomposite membrane with gene transfer capability and that the Ca and P concentration level of the DLF-RKM solution was a controlling factor affecting the gene transfer efficiency. C1 [Bodhak, Subhadip] NIST, NIH, Gaithersburg, MD USA. [Bodhak, Subhadip; Kikuchi, Masanori] Natl Inst Mat Sci NIMS, Int Ctr Mat Nanoarchitecton MANA, Biomat Unit, NanoBio Field, Tsukuba, Ibaraki, Japan. [Bodhak, Subhadip; Oyane, Ayako] Natl Inst Adv Ind Sci & Technol, Nanosystenn Res Inst, Tsukuba, Ibaraki, Japan. [Sogo, Yu; Ito, Atsuo] Natl Inst Adv Ind Sci & Technol, Human Technol Res Inst, Tsukuba, Ibaraki, Japan. [Tsurushima, Hideo] Univ Tsukuba, Dept Neurosurgery, Med Clin, Tsukuba, Ibaraki, Japan. RP Bodhak, S (reprint author), NIST, NIH, Gaithersburg, MD USA. EM subhadip.bodhak@nist.gov; KIKUCHI.Masanori@nims.go.jp; a-oyane@aist.go.jp RI Bodhak, Subhadip/N-9882-2014 FU Japan Society for the Promotion of Science (JSPS) FX Authors would like to acknowledge the financial support from Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. NR 13 TC 0 Z9 0 U1 1 U2 9 PU TRANS TECH PUBLICATIONS LTD PI DURNTEN-ZURICH PA KREUZSTRASSE 10, 8635 DURNTEN-ZURICH, SWITZERLAND SN 1013-9826 J9 KEY ENG MATER PY 2013 VL 529-530 BP 490 EP + DI 10.4028/www.scientific.net/KEM.529-530.490 PG 2 WC Materials Science, Ceramics; Materials Science, Biomaterials SC Materials Science GA BDT66 UT WOS:000314795800101 ER PT J AU Gao, R Reece, KM Sissung, T Fu, SH Venzon, DJ Reed, E Spencer, SD Price, DK Figg, WD AF Gao, Rui Reece, Kelie M. Sissung, Tristan Fu, Samuel H. Venzon, David J. Reed, Eddie Spencer, Shawn D. Price, Douglas K. Figg, William D. TI Are race-specific ERCC1 haplotypes in melanoma cases versus controls related to the predictive and prognostic value of ERCC1 N118N? SO BMJ OPEN LA English DT Article ID REPAIR GENE POLYMORPHISMS; CELL LUNG-CANCER; PROSTATE-CANCER; CUTANEOUS MELANOMA; ETHNIC DISPARITIES; AFRICAN DESCENT; BREAST-CANCER; RISK; SUSCEPTIBILITY; CHEMOTHERAPY AB Objectives: Although it does not alter the ERCC1 phenotype, the ERCC1 500C>T (rs11615) polymorphism has undergone a myriad of investigations into its role as a marker for nucleotide excision repair (NER) function in different races, diseases and treatment outcomes. The goal of our study was to test the hypothesis that 500C>T is in linkage disequilibrium (LD) with causative alleles, and that these haplotypes are more frequent in Caucasians with melanoma than in healthy Caucasians or African Americans. Design: In this case-control study, we selected race-specific ERCC1 single-nucleotide polymorphism (SNPs), conducted LD analysis with ERCC1 500C>T and compared the frequency of ERCC1 diplotypes in Caucasians with melanoma (n=165), healthy Caucasians (n=150) and healthy African Americans (n=159). The haplotype was further studied using a fusion gene containing multiple ERCC1 SNPs. Setting: Large cancer institute in the USA. Participants: A total of 165 Caucasian melanoma patients, 159 healthy Caucasian controls and 159 African American healthy controls. Men and women were enrolled in the clinical trial; however, since the screening trial included prostate cancer screening in addition to screening for other cancers, only male controls were available. Outcome measures: The outcome measures were melanoma risk in Caucasians, and LD between ERCC1 SNP, N118N and other race-specific allelic variants. Results: When compared to ERCC1 500C>T alone, a race-specific three-SNP variant haplotype in ERCC1 (comprised of rs11615, rs3212950 and rs3212948) was even more frequent in Caucasians with melanoma than in healthy Caucasians (p=0.0034) or African Americans (p<0.0001). A plasmid containing the variant haplotype was not differentially expressed. Conclusions: We demonstrate that ERCC1 500C>T participates in a previously characterised cancer-risk haplotype found more frequently in Caucasians, while LD is weak in African Americans; this haplotype appears to also be related to melanoma. It is therefore likely that ERCC1 500C>T is only a valid NER, disease or treatment outcome marker in Caucasians. C1 [Gao, Rui; Reece, Kelie M.; Price, Douglas K.; Figg, William D.] NCI, Frederick Canc Res & Dev Ctr, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. [Sissung, Tristan; Fu, Samuel H.; Figg, William D.] Ctr Canc Res, Med Oncol Branch, Bethesda, MD USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Reed, Eddie] Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. [Spencer, Shawn D.; Price, Douglas K.] NCI Frederick, Clin Pharmacol Program, SAIC Frederick, Frederick, MD USA. RP Figg, WD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Pharmacol Sect, Med Oncol Branch, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA; National Institutes of Health, National Cancer Institute, Bethesda, MD, USA FX The authors would like to thank Dr Steven Rosenberg (NCI) for providing us with the samples of patients with melanoma. This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, Maryland, USA.; This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD, USA. NR 32 TC 2 Z9 2 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2013 VL 3 IS 1 AR e002030 DI 10.1136/bmjopen-2012-002030 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 091XF UT WOS:000315082400040 ER PT B AU Bell, KR Shenouda, CN AF Bell, Kathleen R. Shenouda, Christian N. BE Zasler, ND Katz, DI Zafonte, RD TI Complications Associated With Immobility SO BRAIN INJURY MEDICINE: PRINCIPLES AND PRACTICE, SECOND EDITION LA English DT Article; Book Chapter ID TRAUMATIC BRAIN-INJURY; HUMAN SKELETAL-MUSCLE; BED-REST; VENOUS THROMBOEMBOLISM; SIMULATED MICROGRAVITY; HOSPITALIZED-PATIENTS; POSTMENOPAUSAL OSTEOPOROSIS; HETEROTOPIC OSSIFICATION; CARDIOVASCULAR-RESPONSES; MYOTENDINOUS JUNCTION C1 [Bell, Kathleen R.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Shenouda, Christian N.] NIH, CNRM, Bethesda, MD 20892 USA. RP Bell, KR (reprint author), Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. NR 137 TC 0 Z9 0 U1 1 U2 3 PU DEMOS MEDICAL PUBLICATIONS PI NEW YORK PA 11 WEST 42ND STREET, 15TH FLOOR, NEW YORK, NY 10036 USA BN 978-1-936287-27-7 PY 2013 BP 810 EP 820 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA BDJ25 UT WOS:000313536100049 ER PT S AU Puverel, S Tessarollo, L AF Puverel, Sandrine Tessarollo, Lino BE Wassarman, PM TI RanBPM, a Scaffolding Protein for Gametogenesis SO GAMETOGENESIS SE Current Topics in Developmental Biology LA English DT Review; Book Chapter ID PRIMORDIAL GERM-CELLS; MICROTUBULE-ORGANIZING CENTER; SPERMATOGONIAL STEM-CELLS; MALE-MOUSE MEIOSIS; SYNAPTONEMAL COMPLEX; CHROMOSOME SYNAPSIS; MICE LACKING; ANDROGEN RECEPTOR; MEIOTIC PROPHASE; BINDING-PROTEIN AB RanBPM is a multimodular scaffold protein that interacts with a great variety of molecules including nuclear, cytoplasmic, and membrane proteins. By building multiprotein complexes, RanBPM is thought to regulate various signaling pathways, especially in the immune and nervous system. However, the diversity of these interactions does not facilitate the identification of its precise mechanism of action, and therefore the physiological role of RanBPM still remains unclear. Recently, RanBPM has been shown to be critical for the fertility of both genders in mouse. Although mechanistically it is still unclear how RanBPM affects gametogenesis, the data collected so far suggest that it is a key player in this process. Here, we examine the RanBPM sterility phenotype in the context of other genetic mutations affecting mouse gametogenesis to investigate whether this scaffold protein affects the function of other known proteins whose deficiency results in similar sterility phenotypes. C1 [Puverel, Sandrine; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Puverel, S (reprint author), NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. EM puverels@gmail.com; tessarol@mail.nih.gov NR 127 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 BN 978-0-12-416024-8 J9 CURR TOP DEV BIOL JI Curr. Top. Dev. Biol. PY 2013 VL 102 BP 357 EP 384 DI 10.1016/B978-0-12-416024-8.00013-1 PG 28 WC Developmental Biology; Genetics & Heredity; Reproductive Biology SC Developmental Biology; Genetics & Heredity; Reproductive Biology GA BDO73 UT WOS:000314252800013 PM 23287040 ER PT J AU Capo-Chichi, JM Bharti, SK Sommers, JA Yammine, T Chouery, E Patry, L Rouleau, GA Samuels, ME Hamdan, FF Michaud, JL Brosh, RM Megarbane, A Kibar, Z AF Capo-Chichi, Jose-Mario Bharti, Sanjay Kumar Sommers, Joshua A. Yammine, Tony Chouery, Eliane Patry, Lysanne Rouleau, Guy A. Samuels, Mark E. Hamdan, Fadi F. Michaud, Jacques L. Brosh, Robert M., Jr. Megarbane, Andre Kibar, Zoha TI Identification and Biochemical Characterization of a Novel Mutation in DDX11 Causing Warsaw Breakage Syndrome SO HUMAN MUTATION LA English DT Article DE DDX11; Warsaw breakage syndrome; WABS; helicase ID SISTER-CHROMATID COHESION; HELICASE-LIKE PROTEIN; DNA HELICASE; XERODERMA-PIGMENTOSUM; XPD; TRICHOTHIODYSTROPHY; TRANSLOCATION; GENE AB Mutations in the gene encoding the iron-sulfur-containing DNA helicase DDX11 (ChlR1) were recently identified as a cause of a new recessive co-hesinopathy, Warsaw breakage syndrome (WABS), in a single patient with severe microcephaly, pre- and postnatal growth retardation, and abnormal skin pigmentation. Here, using homozygosity mapping in a Lebanese consanguineous family followed by exome sequencing, we identified a novel homozygous mutation (c.788G>A [p.R263Q]) in DDX11 in three affected siblings with severe intellectual disability and many of the congenital abnormalities reported in the WABS original case. Cultured lymphocytes from the patients showed increased mitomycin C-induced chromosomal breakage, as found in WABS. Biochemical studies of purified recombinant DDX11 indicated that the p.R263Q mutation impaired DDX11 helicase activity by perturbing its DNA binding and DNA-dependent ATP hydrolysis. Our findings thus confirm the involvement of DDX11 in WABS, describe its phenotypical spectrum, and provide novel insight into the structural requirement for DDX11 activity. Hum Mutat 34:103-107, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Capo-Chichi, Jose-Mario; Patry, Lysanne; Samuels, Mark E.; Hamdan, Fadi F.; Michaud, Jacques L.; Kibar, Zoha] Univ Montreal, Ctr Rech, CHU St Justine, Ctr Excellence Neurosci, Montreal, PQ, Canada. [Bharti, Sanjay Kumar; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. [Yammine, Tony; Chouery, Eliane; Megarbane, Andre] Univ St Joseph, UMR S910, Unite Genet Med & Lab, INSERM, Beirut, Lebanon. [Rouleau, Guy A.] Univ Montreal, CHUM Notre Dame Hosp Res Ctr, Montreal, PQ, Canada. [Rouleau, Guy A.] Univ Montreal, Dept Med, Ctr Excellence Neurosci, Montreal, PQ H3C 3J7, Canada. [Samuels, Mark E.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Megarbane, Andre] Inst Jerome Lejeune, Paris, France. [Kibar, Zoha] Univ Montreal, Dept Obstet & Gynecol, Montreal, PQ, Canada. RP Kibar, Z (reprint author), CHU St Justine Res Ctr, 3175 Cote Ste Catherine,Room A711, Montreal, PQ H3T 1C5, Canada. EM broshr@mail.nih.gov; zoha.kibar@recherche-ste-justine.qc.ca FU March of Dimes [12-FY10-236]; Lebanese CNRS; NIH, National Institute on Aging; Reseau de Medecine Genetique Appliquee du Quebec (RMGA) FX Contract grant sponsors: March of Dimes (grant no. 12-FY10-236 to Z.K., M. S., and J.L.M.); Lebanese CNRS (A. M.); Intramural Research program of the NIH, National Institute on Aging (to R.B. Jr).; J.L.M. is a National Scientist of the Fonds de Recherche en Sante du Quebec. J.M.C. holds a salary award from the Reseau de Medecine Genetique Appliquee du Quebec (RMGA). We thank the patients and their family for participating in this study. We also thank the members of the RMGA bioinformatic team (Alexandre Dionne-Laporte, Dan Spiegelman, Edouard Henrion, and Ousmane Diallo) for the primary analysis of the exome sequencing data. NR 17 TC 24 Z9 26 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2013 VL 34 IS 1 BP 103 EP 107 DI 10.1002/humu.22226 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 083PI UT WOS:000314476900016 PM 23033317 ER PT J AU Luksch, H Romanowski, MJ Chara, O Tungler, V Caffarena, ER Heymann, MC Lohse, P Aksentijevich, I Remmers, EF Flecks, S Quoos, N Gramatte, J Petzold, C Hofmann, SR Winkler, S Pessler, F Kallinich, T Ganser, G Nimtz-Talaska, A Baumann, U Runde, V Grimbacher, B Birmelin, J Gahr, M Roesler, J Rosen-Wolff, A AF Luksch, Hella Romanowski, Michael J. Chara, Osvaldo Tuengler, Victoria Caffarena, Ernesto R. Heymann, Michael C. Lohse, Peter Aksentijevich, Ivona Remmers, Elaine F. Flecks, Silvana Quoos, Nadine Gramatte, Johannes Petzold, Cathleen Hofmann, Sigrun R. Winkler, Stefan Pessler, Frank Kallinich, Tilmann Ganser, Gerd Nimtz-Talaska, Antje Baumann, Ulrich Runde, Volker Grimbacher, Bodo Birmelin, Jennifer Gahr, Manfred Roesler, Joachim Roesen-Wolff, Angela TI Naturally Occurring Genetic Variants of Human Caspase-1 Differ Considerably in Structure and the Ability to Activate Interleukin-1 beta SO HUMAN MUTATION LA English DT Article DE autoinflammatory; rheumatic; procaspase; heterozygous; cytokine; homozygous ID MACROMOLECULAR STRUCTURES; INFLAMMATORY CASPASES; STRUCTURE REFINEMENT; NALP3 INFLAMMASOME; PROTEIN STRUCTURES; INNATE; CRYOPYRIN/NALP3; ANTAGONIST; INHIBITORS; IL-1-BETA AB Caspase-1 (Interleukin-1 Converting Enzyme, ICE) is a proinflammatory enzyme that plays pivotal roles in innate immunity and many inflammatory conditions such as periodic fever syndromes and gout. Inflammation is often mediated by enzymatic activation of interleukin (IL)-1 beta and IL-18. We detected seven naturally occurring human CASP1 variants with different effects on protein structure, expression, and enzymatic activity. Most mutations destabilized the caspase-1 dimer interface as revealed by crystal structure analysis and homology modeling followed by molecular dynamics simulations. All variants demonstrated decreased or absent enzymatic and IL-1 beta releasing activity in vitro, in a cell transfection model, and as low as 25% of normal ex vivo in a whole blood assay of samples taken from subjects with variant CASP1, a subset of whom suffered from unclassified autoinflammation. We conclude that decreased enzymatic activity of caspase-1 is compatible with normal life and does not prevent moderate and severe autoinflammation. Hum Mutat 34:122-131, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Luksch, Hella; Tuengler, Victoria; Heymann, Michael C.; Flecks, Silvana; Quoos, Nadine; Gramatte, Johannes; Petzold, Cathleen; Hofmann, Sigrun R.; Winkler, Stefan; Pessler, Frank; Gahr, Manfred; Roesler, Joachim; Roesen-Wolff, Angela] Univ Hosp Carl Gustav Carus, Dept Pediat, Dresden, Germany. [Romanowski, Michael J.] Sunesis Pharmaceut Inc, Dept Struct Biol, San Francisco, CA USA. [Chara, Osvaldo] Univ La Plata UNLP, CONICET, Inst Fis Fluidos & Sistemas Biol IFLYSIB, La Plata, Buenos Aires, Argentina. [Chara, Osvaldo] Tech Univ Dresden, Ctr Informat Serv & High Performance Comp, D-01062 Dresden, Germany. [Caffarena, Ernesto R.] Fiocruz MS, Fundacao Oswaldo Cruz, Programa Comp Cient, Manguinho, Brazil. [Lohse, Peter] Univ Munich, Dept Clin Chem, Munich, Germany. [Aksentijevich, Ivona; Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. [Pessler, Frank] Helmholtz Ctr Infect Res, Braunschweig, Germany. [Kallinich, Tilmann] Charite, Dept Pediat Pneumol & Immunol, D-13353 Berlin, Germany. [Ganser, Gerd] St Josef Stift, Sendenhorst, Germany. [Nimtz-Talaska, Antje] Arztehaus, Frankfurt, Germany. [Baumann, Ulrich] Hannover Med Sch, Hannover, Germany. [Runde, Volker] Wilhelm Anton Hosp, Goch, Germany. [Grimbacher, Bodo; Birmelin, Jennifer] Univ Hosp Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. RP Roesler, J (reprint author), Univ Med Ctr Carl Gustav Carus, Dept Pediat, Fetscherstr 74, D-01307 Dresden, Germany. EM Roeslerj@rcs.urz.tu-dresden.de RI Caffarena, Ernesto/G-4467-2011; OI Caffarena, Ernesto/0000-0002-8353-3034; Chara, Osvaldo/0000-0002-0868-2507 FU German Research Foundation (DFG) [KFO249, TP1, RO/471-11, TP2, HO 4510/1-1]; Federal Ministry of Education and Research (PID-NET) [A4]; Medical faculty of the University of Technology Dresden, MeDDrive33, Germany [(08/09): 60.153]; Marie Curie International Reintegration Grant, European Union [224894] FX Contract grant sponsors: German Research Foundation (DFG, KFO249, TP1, RO/471-11 and TP2, HO 4510/1-1); Federal Ministry of Education and Research (PID-NET, Project A4); Medical faculty of the University of Technology Dresden, MeDDrive33 (08/09): 60.153 to S. W., Germany; Marie Curie International Reintegration Grant, # 224894 to F. P., European Union. NR 44 TC 14 Z9 15 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2013 VL 34 IS 1 BP 122 EP 131 DI 10.1002/humu.22169 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 083PI UT WOS:000314476900019 PM 22833538 ER PT J AU FitzGerald, LM Zhang, XT Kolb, S Kwon, EM Liew, YC Hurtado-Coll, A Knudsen, BS Ostrander, EA Stanford, JL AF FitzGerald, Liesel M. Zhang, Xiaotun Kolb, Suzanne Kwon, Erika M. Liew, Ying Ching Hurtado-Coll, Antonio Knudsen, Beatrice S. Ostrander, Elaine A. Stanford, Janet L. TI Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression SO HUMAN MUTATION LA English DT Article DE prostate cancer; MSMB; PSP94; NCOA4 ID 94 AMINO-ACIDS; GENOME-WIDE ASSOCIATION; SECRETORY PROTEIN; SUSCEPTIBILITY LOCI; FUNCTIONAL-ANALYSIS; ANDROGEN; RISK; PROGRESSION; ANTIGEN; LINES AB Two genome-wide association studies (GWAS) identified the beta-microseminoprotein (MSMB) promoter SNP, rs10993994: C>T, as significantly associated with prostate cancer (PC) risk. Follow-up studies demonstrate that the variant allele directly affects expression of the MSMB-encoded protein, PSP94, and also suggest that it affects mRNA expression levels of an adjacent gene, NCOA4, which is involved in androgen receptor transactivation. In a population-based study of 1,323 cases and 1,268 age-matched controls, we found the NCOA4 SNP, rs7350420:T>C, was associated with a 15% reduction in PC risk, but the association was not significant after adjustment for the rs10993994:C>T genotype. Tumor tissue microarrays of 519 radical prostatectomy patients were used to measure PSP94 and NCOA4 protein expression. Taken together, these data confirm that the rs10993994:C>T variant allele is associated with decreased PSP94 expression, and the association is stronger in tumor compared to normal prostate tissue. No association was observed between rs10993994:C>T and NCOA4 expression, and only moderate associations were seen between two NCOA4 SNPs, rs10761618:T>C and rs7085433:G>A, and NCOA4 protein expression. These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here. Hum Mutat 34:149-156, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [FitzGerald, Liesel M.; Kolb, Suzanne; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Zhang, Xiaotun] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Kwon, Erika M.] Johns Hopkins Univ, Sch Med, Program Human Genet & Mol Biol, Baltimore, MD USA. [Liew, Ying Ching; Hurtado-Coll, Antonio] Univ British Columbia, Vancouver Prostate Ctr, Vancouver, BC V5Z 1M9, Canada. [Knudsen, Beatrice S.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Knudsen, Beatrice S.] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute, National Institutes of Health [RO1 CA056678, R01 CA092579, R03 CA121871, R03 CA137799, P50 CA097186]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX Contract grant sponsors: National Cancer Institute, National Institutes of Health (RO1 CA056678, R01 CA092579, R03 CA121871, R03 CA137799 [to J.L.S.], P50 CA097186 [to J.L.S. and L. M. F.]); Fred Hutchinson Cancer Research Center; Intramural Program of the National Human Genome Research Institute. NR 25 TC 11 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2013 VL 34 IS 1 BP 149 EP 156 DI 10.1002/humu.22176 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 083PI UT WOS:000314476900022 PM 22887727 ER PT J AU Lokanga, RA Entezam, A Kumari, D Yudkin, D Qin, M Smith, CB Usdin, K AF Lokanga, Rachel Adihe Entezam, Ali Kumari, Daman Yudkin, Dmitry Qin, Mei Smith, Carolyn Beebe Usdin, Karen TI Somatic Expansion in Mouse and Human Carriers of Fragile X Premutation Alleles SO HUMAN MUTATION LA English DT Article DE fragile X-related disorders; FMR1; somatic expansion; MutS beta ID PREMATURE OVARIAN FAILURE; TRIPLET REPEAT INSTABILITY; DISEASE TRANSGENIC MICE; CAG-REPEAT; CGG-REPEAT; HUMAN-CELLS; MESSENGER-RNA; DNA-DAMAGE; STEM-CELLS; TRANSCRIPTION AB Repeat expansion diseases result from expansion of a specific tandem repeat. The three fragile X-related disorders (FXDs) arise from germline expansions of a CGG center dot CCG repeat tract in the 5' UTR (untranslated region) of the fragile X mental retardation 1 (FMR1) gene. We show here that in addition to germline expansion, expansion also occurs in the somatic cells of both mice and humans carriers of premutation alleles. Expansion in mice primarily affects brain, testis, and liver with very little expansion in heart or blood. Our data would be consistent with a simple two-factor model for the organ specificity. Somatic expansion in humans may contribute to the mosaicism often seen in individuals with one of the FXDs. Because expansion risk and disease severity are related to repeat number, somatic expansion may exacerbate disease severity and contribute to the age-related increased risk of expansion seen on paternal transmission in humans. As little somatic expansion occurs in murine lymphocytes, our data also raise the possibility that there may be discordance in humans between repeat numbers measured in blood and that present in brain. This could explain, at least in part, the variable penetrance seen in some of these disorders. Hum Mutat 34:157-166, 2013. Published 2012 Wiley Periodicals, Inc.* C1 [Lokanga, Rachel Adihe; Entezam, Ali; Kumari, Daman; Yudkin, Dmitry; Usdin, Karen] NIDDKD, Sect Gene Struct & Dis, NIH, Bethesda, MD 20892 USA. [Qin, Mei; Smith, Carolyn Beebe] NIMH, Sect Neuroadaptat & Prot Metab, NIH, Bethesda, MD 20892 USA. RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr DR MSC 0830, Bethesda, MD 20892 USA. EM ku@helix.nih.gov RI Yudkin, Dmitry/N-6135-2015 OI Yudkin, Dmitry/0000-0002-8940-9173 FU NIDDK, NIH [DK057808] FX Contract grant sponsors: Intramural program of the NIDDK, NIH (DK057808 to K.U.). NR 60 TC 31 Z9 31 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2013 VL 34 IS 1 BP 157 EP 166 DI 10.1002/humu.22177 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 083PI UT WOS:000314476900023 PM 22887750 ER PT J AU Vester, A Velez-Ruiz, G McLaughlin, HM Lupski, JR Talbot, K Vance, JM Zuchner, S Roda, RH Fischbeck, KH Biesecker, LG Nicholson, G Beg, AA Antonellis, A AF Vester, Aimee Velez-Ruiz, Gisselle McLaughlin, Heather M. Lupski, James R. Talbot, Kevin Vance, Jeffery M. Zuechner, Stephan Roda, Ricardo H. Fischbeck, Kenneth H. Biesecker, Leslie G. Nicholson, Garth Beg, Asim A. Antonellis, Anthony CA NISC Comparative Sequencing Progra TI A Loss-of-Function Variant in the Human Histidyl-tRNA Synthetase (HARS) Gene is Neurotoxic In Vivo SO HUMAN MUTATION LA English DT Article DE aminoacyl-tRNA synthetases; peripheral neuropathy; HARS; neurotoxicity ID MARIE-TOOTH-DISEASE; SPINAL MUSCULAR-ATROPHY; CAENORHABDITIS-ELEGANS; PERIPHERAL NEUROPATHY; BRAIN-STEM; C-ELEGANS; MUTATIONS; LEUKOENCEPHALOPATHY; INVOLVEMENT; SELECTION AB Aminoacyl-tRNA synthetases (ARSs) are ubiquitously expressed enzymes responsible for ligating amino acids to cognate tRNA molecules. Mutations in four genes encoding an ARS have been implicated in inherited peripheral neuropathy with an axonal pathology, suggesting that all ARS genes are relevant candidates for disease in patients with related phenotypes. Here, we present results from a mutation screen of the histidyl-tRNA synthetase (HARS) gene in a large cohort of patients with peripheral neuropathy. These efforts revealed a rare missense variant (c.410G>A/p.Arg137Gln) that resides at a highly conserved amino acid, represents a loss-of-function allele when evaluated in yeast complementation assays, and is toxic to neurons when expressed in a worm model. In addition to the patient with peripheral neuropathy, p.Arg137Gln HARS was detected in three individuals by genome-wide exome sequencing. These findings suggest that HARS is the fifth ARS locus associated with axonal peripheral neuropathy. Implications for identifying ARS alleles in human populations and assessing them for a role in neurodegenerative phenotypes are discussed. Hum Mutat 34: 191-199, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Vester, Aimee; McLaughlin, Heather M.; Antonellis, Anthony] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA. [Velez-Ruiz, Gisselle; Beg, Asim A.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [NISC Comparative Sequencing Progra] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. [Talbot, Kevin] Univ Oxford, Dept Clin Neurol, Oxford, England. [Vance, Jeffery M.; Zuechner, Stephan] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA. [Roda, Ricardo H.; Fischbeck, Kenneth H.] Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA. [Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Nicholson, Garth] Concord Hosp, Northcott Neurosci Lab, ANZAC Res Inst, Concord, NSW, Australia. [Nicholson, Garth] Concord Hosp, Mol Med Lab, Concord, NSW, Australia. [Nicholson, Garth] Univ Sydney, Fac Med, Camperdown, NSW, Australia. [Antonellis, Anthony] Univ Michigan, Sch Med, Dept Neurol, Ann Arbor, MI 48109 USA. RP Antonellis, A (reprint author), Univ Michigan, Sch Med, 3710A Med Sci 2,1241 E Catherine St,SPC 5618, Ann Arbor, MI 48109 USA. EM asimbeg@umich.edu; antonell@umich.edu FU National Institute of Neurological Diseases and Stroke [NS060983, R01NS052767, U54NS065712]; National Human Genome Research Institute (National Institutes of Health); National Institute of Neurological Diseases and Stroke (National Institutes of Health) FX Contract Grant Sponsor: National Institute of Neurological Diseases and Stroke (grants NS060983 to A.A., R01NS052767 to S.Z., and U54NS065712 to S.Z.); Intramural Research Programs of the National Human Genome Research Institute and National Institute of Neurological Diseases and Stroke (National Institutes of Health). NR 40 TC 26 Z9 28 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2013 VL 34 IS 1 BP 191 EP 199 DI 10.1002/humu.22210 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 083PI UT WOS:000314476900027 PM 22930593 ER PT J AU Kato, H Jochim, RC Gomez, EA Uezato, H Mimori, T Korenaga, M Sakurai, T Katakura, K Valenzuela, JG Hashiguchi, Y AF Kato, Hirotomo Jochim, Ryan C. Gomez, Eduardo A. Uezato, Hiroshi Mimori, Tatsuyuki Korenaga, Masataka Sakurai, Tatsuya Katakura, Ken Valenzuela, Jesus G. Hashiguchi, Yoshihisa TI Analysis of salivary gland transcripts of the sand fly Lutzomyia ayacuchensis, a vector of Andean-type cutaneous leishmaniasis SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Lutzomyia ayacuchensis; Salivary gland; Transcript; Bioinformatics; cDNA library ID BLOODSUCKING BUG; IMMUNE-RESPONSE; VISCERAL LEISHMANIASIS; VASODILATORY PEPTIDE; TRIATOMA-INFESTANS; FEMALE MOSQUITO; CHAGAS-DISEASE; PROTEIN; LONGIPALPIS; SIALOME AB The saliva of blood sucking insects contains potent pharmacologically active components that assist them in counteracting the host hemostatic and inflammatory systems during blood feeding. In addition, sand fly salivary proteins affect host immunity and have the potential to be a vaccine against Leishmania infection. In the present study, the salivary gland transcripts of Lutzomyia ayacuchensis, a vector of cutaneous leishmaniasis in Ecuadorian and Peruvian Andes, were analyzed by sequencing randomly selected clones of the salivary gland cDNA library of this sand fly. This resulted in the identification of the most abundant transcripts coding for secreted proteins. These proteins were homologous to the salivary molecules present in other sand flies including the RGD-containing peptide, PpSP15/SL1 family protein, yellow-related protein, putative apyrase, antigen 5-related protein, D7 family protein, and 27 kDa salivary protein. Of note, homologues of maxadilan, an active vasodilator abundantly present in saliva of Lutzomyia longipalpis, were not identified. This analysis is the first description of salivary proteins from a sand fly of the subgenus Helcocyrtomyia and from vector of cutaneous leishmaniasis in the New World. The present analysis will provide further insights into the evolution of salivary components in blood sucking arthropods. (C) 2012 Elsevier B.V. All rights reserved. C1 [Kato, Hirotomo; Sakurai, Tatsuya; Katakura, Ken] Hokkaido Univ, Grad Sch Vet Med, Parasitol Lab, Dept Dis Control, Sapporo, Hokkaido 0600818, Japan. [Jochim, Ryan C.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD USA. [Uezato, Hiroshi] Univ Ryukyus, Fac Med, Dept Dermatol, Nishihara, Okinawa 90301, Japan. [Mimori, Tatsuyuki] Kumamoto Univ, Sch Hlth Sci, Dept Microbiol, Kumamoto, Japan. [Korenaga, Masataka; Hashiguchi, Yoshihisa] Kochi Univ, Kochi Med Sch, Dept Parasitol, Kochi 780, Japan. [Hashiguchi, Yoshihisa] Univ Cent Ecuador, Ctr Biomed, Quito, Ecuador. RP Kato, H (reprint author), Hokkaido Univ, Grad Sch Vet Med, Parasitol Lab, Dept Dis Control,Kita Ku, North 18,West 9, Sapporo, Hokkaido 0600818, Japan. EM hkato@vetmed.hokudai.ac.jp RI Jochim, Ryan/C-6756-2013; Kato, Hirotomo/A-4820-2012 OI Kato, Hirotomo/0000-0001-5429-9536 FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [18256004, 10037385, 23580424] FX We are grateful to Dr. Jose M. C. Ribeiro (Vector Biology Section, Laboratory of Malaria and Vector Research, NIAID, NIH, USA) for the development and training of all custom bioinformatics programs used in this research. This Study was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (Grant Nos. 18256004, 10037385 and 23580424). NR 68 TC 11 Z9 11 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2013 VL 13 BP 56 EP 66 DI 10.1016/j.meegid.2012.08.024 PG 11 WC Infectious Diseases SC Infectious Diseases GA 089HQ UT WOS:000314902000008 PM 23000112 ER PT J AU Chen, WC Wu, PH Phillip, JM Khatau, SB Choi, JM Dallas, MR Konstantopoulos, K Sun, SX Lee, JSH Hodzic, D Wirtz, D AF Chen, Wei-Chiang Wu, Pei-Hsun Phillip, Jude M. Khatau, Shyam B. Choi, Jae Min Dallas, Matthew R. Konstantopoulos, Konstantinos Sun, Sean X. Lee, Jerry S. H. Hodzic, Didier Wirtz, Denis TI Functional interplay between the cell cycle and cell phenotypes SO INTEGRATIVE BIOLOGY LA English DT Article ID DISTINCT ROLES; FIBROBLASTS; CONNECTIONS; PROGRESSION; CANCER; ACTIN; SYNCHRONIZATION; RESOLUTION; INHIBITOR; NUCLEUS AB Cell cycle distribution of adherent cells is typically assessed using flow cytometry, which precludes the measurements of many cell properties and their cycle phase in the same environment. Here we develop and validate a microscopy system to quantitatively analyze the cell-cycle phase of thousands of adherent cells and their associated cell properties simultaneously. This assay demonstrates that population-averaged cell phenotypes can be written as a linear combination of cell-cycle fractions and phase-dependent phenotypes. By perturbing the cell cycle through inhibition of cell-cycle regulators or changing nuclear morphology by depletion of structural proteins, our results reveal that cell cycle regulators and structural proteins can significantly interfere with each other's prima facie functions. This study introduces a high-throughput method to simultaneously measure the cell cycle and phenotypes at single-cell resolution, which reveals a complex functional interplay between the cell cycle and cell phenotypes. C1 [Chen, Wei-Chiang; Wu, Pei-Hsun; Phillip, Jude M.; Khatau, Shyam B.; Dallas, Matthew R.; Konstantopoulos, Konstantinos; Sun, Sean X.; Wirtz, Denis] Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA. [Chen, Wei-Chiang; Wu, Pei-Hsun; Phillip, Jude M.; Khatau, Shyam B.; Choi, Jae Min; Dallas, Matthew R.; Konstantopoulos, Konstantinos; Lee, Jerry S. H.; Wirtz, Denis] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Sun, Sean X.] Johns Hopkins Univ, Dept Mech Engn, Baltimore, MD 21218 USA. [Lee, Jerry S. H.] NCI, Ctr Strateg Sci Initiat, Off Director, NIH, Bethesda, MD 20892 USA. [Hodzic, Didier] Washington Univ, Sch Med, Dept Ophthalmol, St Louis, MO 63110 USA. RP Chen, WC (reprint author), Johns Hopkins Univ, Johns Hopkins Phys Sci Oncol Ctr, Baltimore, MD 21218 USA. EM wirtz@jhu.edu RI Sun, Sean/C-6755-2009; Lee, Jerry/A-3189-2008; Konstantopoulos, Konstantinos/A-7045-2011; Lee, Jerry/K-4553-2014 OI Sun, Sean/0000-0002-9077-7088; Lee, Jerry/0000-0003-1515-0952; FU NCI NIH HHS [R01 CA174388, R25 CA153952]; NEI NIH HHS [R01 EY022632]; NIGMS NIH HHS [R01 GM075305, R01 GM084204] NR 33 TC 15 Z9 15 U1 1 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2013 VL 5 IS 3 BP 523 EP 534 DI 10.1039/c2ib20246h PG 12 WC Cell Biology SC Cell Biology GA 095SL UT WOS:000315354900007 PM 23319145 ER PT J AU Sultan, E Najafizadeh, L Gandjbakhche, AH Pourrezaei, K Daryoush, A AF Sultan, Ebraheem Najafizadeh, Laleh Gandjbakhche, Amir H. Pourrezaei, Kambiz Daryoush, Afshin TI Accurate optical parameter extraction procedure for broadband near-infrared spectroscopy of brain matter SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE functional near-infrared; traumatic brain injury; finite element method; diffusion equation; COMSOL; optical transmitter; optical receiver; tri-wavelength; continuous wave; time domain; frequency domain; photon density wave; vertical cavity surface emitting laser; insertion loss; insertion phase ID NONINVASIVE DETERMINATION; PHOTON MIGRATION; FREQUENCY-DOMAIN; TURBID MEDIA; MONTE-CARLO; DIFFUSE-REFLECTANCE; SCATTERING MEDIA; MODEL; PROPAGATION; LIGHT AB Modeling behavior of broadband (30 to 1000 MHz) frequency modulated near-infrared (NIR) photons through a phantom is the basis for accurate extraction of optical absorption and scattering parameters of biological turbid media. Photon dynamics in a phantom are predicted using both analytical and numerical simulation and are related to the measured insertion loss (IL) and insertion phase (IP) for a given geometry based on phantom optical parameters. Accuracy of the extracted optical parameters using finite element method (FEM) simulation is compared to baseline analytical calculations from the diffusion equation (DE) for homogenous brain phantoms. NIR spectroscopy is performed using custom-designed, broadband, free-space optical transmitter (Tx) and receiver (Rx) modules that are developed for photon migration at wavelengths of 680, 780, and 820 nm. Differential detection between two optical Rx locations separated by 0.3 cm is employed to eliminate systemic artifacts associated with interfaces of the optical Tx and Rx with the phantoms. Optical parameter extraction is achieved for four solid phantom samples using the least-square-error method in MATLAB (for DE) and COMSOL (for FEM) simulation by fitting data to measured results over broadband and narrowband frequency modulation. Confidence in numerical modeling of the photonic behavior using FEM has been established here by comparing the transmission mode's experimental results with the predictions made by DE and FEM for known commercial solid brain phantoms. (c) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. [DOI: 10.1117/1.JBO.18.1.017008] C1 [Sultan, Ebraheem; Daryoush, Afshin] Drexel Univ, Dept ECE, Philadelphia, PA 19104 USA. [Pourrezaei, Kambiz] Drexel Univ, Sch Biomed Engn & Hlth Syst, Philadelphia, PA 19104 USA. [Najafizadeh, Laleh; Gandjbakhche, Amir H.] NIH, Bethesda, MD 20892 USA. RP Sultan, E (reprint author), Drexel Univ, Dept ECE, Philadelphia, PA 19104 USA. EM medxe@medxe.com FU Center for Neuroscience and Regenerative Medicine (CNRM); Intramural Research Program (IRP) of Eunice Shriver National Institute of Child Health and Human Development (NICHD) of the National Institute of Health FX This research is partly supported by the Center for Neuroscience and Regenerative Medicine (CNRM), and the Intramural Research Program (IRP) of Eunice Shriver National Institute of Child Health and Human Development (NICHD) of the National Institute of Health. We are grateful to Professor Jessica Rammella-Roman, at the Catholic University of America, for her support in providing the phantoms. NR 29 TC 1 Z9 1 U1 0 U2 13 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JAN PY 2013 VL 18 IS 1 AR 017008 DI 10.1117/1.JBO.18.1.017008 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 092XT UT WOS:000315157000029 PM 23322361 ER PT J AU Cortese, I Cornblath, DR AF Cortese, Irene Cornblath, David R. TI Therapeutic plasma exchange in neurology: 2012 SO JOURNAL OF CLINICAL APHERESIS LA English DT Article DE apheresis; neurologic indications; plasmapheresis; therapeutic plasma exchange; Guillain-Barre syndrome; CIDP; myasthenia gravis ID PERIPHERAL-NERVE SOCIETY; GUILLAIN-BARRE-SYNDROME; JOINT TASK-FORCE; MYASTHENIA-GRAVIS; EUROPEAN FEDERATION; MEDICAL PROGRESS; 1ST REVISION; PLASMAPHERESIS; GUIDELINE; ANTIBODIES AB In treating neuroimmunological diseases, neurologists have a number of different drugs to choose from ranging from corticosteroids to IVIg to more specific cell based therapies, the latter most frequently from the world of oncology. In some diseases, therapeutic plasma exchange, a procedure rather than a drug, is used. The most obvious advantage of therapeutic plasma exchange is the usually rapid onset of action presumably due to removal of pathogenic auto-antibodies. In some diseases, a single course of therapeutic plasma exchange is used while in others prolonged treatment with therapeutic plasma exchange is used. This article will review the use of therapeutic plasma exchange in neurology and will draw heavily upon recent consensus statements from the American Society for Apheresis and the American Academy of Neurology and by Cochrane reviews. J. Clin. Apheresis 28:1619, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Cortese, Irene] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Cornblath, David R.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RP Cornblath, DR (reprint author), Meyer Bldg,Room 6-181A,600 N Wolfe St, Baltimore, MD 21287 USA. EM dcornbl@jhmi.edu FU Abbott Laboratories; Acorda Therapeutics, Inc.; Alexion Pharmaceuticals Inc.; Ardea Biosciences, Inc.; Astellas Pharma US, Inc.; Avigen, Inc.; AxelaCare Health Solutions, LLC; Baxter International, Inc.; Biogen Idec Inc.; Bionevia Pharmaceuticals, Inc.; Bristol-Myers Squibb Company; CaridianBCT, Inc.; Cebix, Inc.; CSL Behring GmbH; DP Clinical, Inc.; Eisai Co., Ltd.; Eli Lilly, Co.; Exelixis, Inc.; FoldRx Pharmaceuticals, Inc.; Genzyme Corporation; Geron Corporation; Gerson Lehrman Group; GlaxoSmithKline plc.; H.I.G. Capital Management, Inc.; Impeto Medical SAS; Isis Pharmaceuticals Inc.; Johnson Johnson; Merck Co., Inc.; Mitsubishi Tanabe Pharma Corporation; Neryx Biopharmaceuticals, Inc.; NeurogesX, Inc.; Octapharma AG; Pfizer Inc.; Sangamo BioSciences, Inc.; Sanofi-Aventis; Schwarz Pharma, Inc.; Seattle Genetics, Inc.; Sigma-Tau Pharmaceuticals, Inc.; SK Life Science, Inc.; Solvay Pharmaceuticals, Inc.; Talecris Biotherapeutics, Inc.; Warburg Pincus LLC; YM Biosciences Australia PTY Ltd.; NINDS FX Dr. Cortese has nothing to disclose. Dr. Cornblath discloses that he has received consulting fees for activities with Abbott Laboratories, Acorda Therapeutics, Inc., Alexion Pharmaceuticals Inc., Ardea Biosciences, Inc., Astellas Pharma US, Inc., Avigen, Inc., AxelaCare Health Solutions, LLC, Baxter International, Inc., Biogen Idec Inc., Bionevia Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CaridianBCT, Inc., Cebix, Inc., CSL Behring GmbH, DP Clinical, Inc., Eisai Co., Ltd., Eli Lilly, Co., Exelixis, Inc., FoldRx Pharmaceuticals, Inc., Genzyme Corporation, Geron Corporation, Gerson Lehrman Group, GlaxoSmithKline plc., H.I.G. Capital Management, Inc., Impeto Medical SAS, Isis Pharmaceuticals Inc., Johnson & Johnson, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Neryx Biopharmaceuticals, Inc., NeurogesX, Inc., Octapharma AG, Pfizer Inc., Sangamo BioSciences, Inc., Sanofi-Aventis, Schwarz Pharma, Inc., Seattle Genetics, Inc., Sigma-Tau Pharmaceuticals, Inc., SK Life Science, Inc., Solvay Pharmaceuticals, Inc., Talecris Biotherapeutics, Inc., Warburg Pincus LLC and YM Biosciences Australia PTY Ltd. He has received royalty payments from Abbott Laboratories, Johnson & Johnson, and Sanofi-Aventis. David R. Cornblath, MD is on the Board of Directors of the GBS-CIDP Foundation International and the Foundation for Peripheral Neuropathy.; The contents of this review were presented by David R. Cornblath, MD, at the September 2012 Therapeutic Apheresis Academy, University of Virginia, Charlottesville, VA. The Intramural Research Program of NINDS partially supported this research. NR 25 TC 3 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0733-2459 J9 J CLIN APHERESIS JI J. Clin. Apheresis PY 2013 VL 28 IS 1 SI SI BP 16 EP 19 DI 10.1002/jca.21266 PG 4 WC Hematology SC Hematology GA 093UN UT WOS:000315218300004 PM 23420591 ER PT J AU Hunt, S Cimino, JJ Koziol, DE AF Hunt, Sevgin Cimino, James J. Koziol, Deloris E. TI A comparison of clinicians' access to online knowledge resources using two types of information retrieval applications in an academic hospital setting SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID PRIMARY-CARE; SEEKING; NURSES AB Objective: The research studied whether a clinician's preference for online health knowledge resources varied with the use of two applications that were designed for information retrieval in an academic hospital setting. Methods: The researchers analyzed a year's worth of computer log files to study differences in the ways that four clinician groups (attending physicians, housestaff physicians, nurse practitioners, and nurses) sought information using two types of information retrieval applications (health resource links or Infobutton icons) across nine resources while they reviewed patients' laboratory results. Results: From a set of 14,979 observations, the authors found statistically significant differences among the 4 clinician groups for accessing resources using the health resources application (P<0.001) but not for the Infobuttons application (P=0.31). For the health resources application, the preferences of the 4 clinical groups varied according to the specific resources examined (all P <= 0.02). Conclusion: The information-seeking behavior of clinicians may vary in relation to their role and the way in which the information is presented. Studying these behaviors can provide valuable insights to those tasked with maintaining information retrieval systems' links to appropriate online knowledge resources. C1 [Cimino, James J.] NIH, CRC Hatfield Clin Res Ctr 10, Bethesda, MD 20892 USA. [Koziol, Deloris E.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Hunt, S (reprint author), 7495 Merrymaker Way, Elkridge, MD 21075 USA. EM shunt1@umm.edu; ciminoj@cc.nih.gov; DKoziol@cc.nih.gov OI Cimino, James/0000-0003-4101-1622 FU Intramural NIH HHS NR 13 TC 2 Z9 3 U1 0 U2 14 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2013 VL 101 IS 1 BP 26 EP 31 DI 10.3163/1536-5050.101.1.005 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA 092LW UT WOS:000315124900005 PM 23405044 ER PT J AU Rethlefsen, ML Livinski, AA AF Rethlefsen, Melissa L. Livinski, Alicia A. TI Infectious diseases citation patterns: mapping the literature 2008-2010 SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID BIBLIOMETRIC EVALUATION; HEALTH-EDUCATION; PUBLICATIONS; JOURNALS; SCIENCES; SERIALS AB Objectives: The research identified the publication types and ages most frequently cited in the infectious diseases literature and the most commonly cited journals. Methods: From 2008-2010, 5,056 articles in 5 infectious diseases journals cited 166,650 items. Two random samples were drawn: one (n=1,060) from the total set of citations and one (n=1,060) from the citations to journal articles. For each sample citation, publication type and date, age of cited item, and inclusion of uniform resource locator (URL) were collected. For each item in the cited journal articles sample, journal title, publication date, and age of the cited article were collected. Bradford zones were used for further analysis. Results: Journal articles (91%, n=963) made up the bulk of cited items, followed by miscellaneous items (4.6%, n=49). Dates of publication for cited items ranged from 1933-2010 (mean=2001, mode=2007). Over half (50.2%, n=483) of cited journal articles were published within the previous 5 years. The journal article citations included 358 unique journal titles. Discussion: The citations to current and older publications in a range of disciplines, heavy citation of journals, and citation of miscellaneous and government documents revealed the depth and breadth of resources needed for the study of infectious diseases. C1 [Rethlefsen, Melissa L.] Mayo Clin, Mayo Clin Lib, Rochester, MN 55905 USA. [Livinski, Alicia A.] NIH, NIH Lib, Bethesda, MD 20892 USA. RP Rethlefsen, ML (reprint author), Mayo Clin, Mayo Clin Lib, 200 1st St SW, Rochester, MN 55905 USA. EM mlrethlefsen@gmail.com; Alicia.Livinski@nih.gov OI Rethlefsen, Melissa/0000-0001-5322-9368 NR 40 TC 3 Z9 3 U1 0 U2 14 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JAN PY 2013 VL 101 IS 1 BP 55 EP 62 DI 10.3163/1536-5050.101.1.009 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA 092LW UT WOS:000315124900009 PM 23405047 ER PT J AU Williams, L Bosselut, R AF Williams, Linus Bosselut, Remy TI Interleukin 22 may represent a new therapeutic tool towards thymic regeneration in vivo SO M S-MEDECINE SCIENCES LA French DT News Item ID CELLS; MAINTENANCE; IMMUNITY; MICE C1 [Williams, Linus; Bosselut, Remy] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Williams, L (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM remy@helix.nih.gov NR 14 TC 1 Z9 1 U1 1 U2 4 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD JAN PY 2013 VL 29 IS 1 BP 11 EP 14 DI 10.1051/medsci/2013291003 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 093FK UT WOS:000315176900003 PM 23351684 ER PT J AU Rao, SS Mohan, KVK Gao, YM Atreya, CD AF Rao, Shilpakala Sainath Mohan, Ketha V. Krishna Gao, Yamei Atreya, Chintamani D. TI Identification and evaluation of a novel peptide binding to the cell surface of Staphylococcus aureus SO MICROBIOLOGICAL RESEARCH LA English DT Article DE Microbial detection; Peptides; Phage-display; Quantum dots; S. aureus ID PHAGE-DISPLAY; SALMONELLA-TYPHIMURIUM; PLATELET TRANSFUSION; BACILLUS-ANTHRACIS; LIGANDS; SPORES; STRAIN; PROBE AB Identification of short peptides that serve as specific ligands to biological materials such as microbial cell surfaces has major implications in better understanding the molecular recognition of cell surfaces. In this study we screened a commercially available random phage-display library against Staphylococcus aureus cells and identified peptides specifically binding to the bacteria. A synthetic peptide (SA5-1) representing the consensus sequence (VPHNPGLISLQG) of the bacteria-binding peptide was evaluated for its binding potential against S. aureus. Dot-blot, immunoblot assay and ELISA results revealed the SA5-1 peptide to be highly specific to S. aureus. The SA5-1 peptide binding was optimal between pH 6.0 and 8.0. Nanogold Transmission Electron Microscopy demonstrated that the SA5-1 binds to the outer membrane surface of S. aureus. Diagnostic potential of the SA5-1 peptide was evaluated in human platelet samples spiked with S. aureus and specific detection of the bacteria by biotinylated-SA5-1 and streptavidin-conjugated fluorescent quantum dots. Fluorometry results indicated that the peptide was able to detect similar to 100 organisms per ml in a spiked biological sample providing a proof-of-concept towards potential of this peptide as a S. aureus diagnostic tool that can be of use in different detection platforms. Published by Elsevier GmbH. C1 [Rao, Shilpakala Sainath; Mohan, Ketha V. Krishna; Atreya, Chintamani D.] US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Gao, Yamei] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM chintamani.atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) FX SSR is a recipient of a postdoctoral fellowship at the Center for Biologics Evaluation and Research (CBER) administered by the Oak Ridge Institute for Science and Education (ORISE) through an intra agency agreement between the U. S. Department of Energy and the U.S. Food and Drug Administration. Review of the manuscript by Drs. Salim Haddad and Xuan Chi, CBER is highly appreciated. NR 30 TC 7 Z9 9 U1 4 U2 38 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-5013 J9 MICROBIOL RES JI Microbiol. Res. PY 2013 VL 168 IS 2 BP 106 EP 112 DI 10.1016/j.micres.2012.07.004 PG 7 WC Microbiology SC Microbiology GA 093GJ UT WOS:000315179400007 PM 23017232 ER PT J AU Lountos, GT Tropea, JE Waugh, DS AF Lountos, George T. Tropea, Joseph E. Waugh, David S. TI Structure of the Trypanosoma cruzi protein tyrosine phosphatase TcPTP1, a potential therapeutic target for Chagas' disease SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Trypanosoma cruzi; Chagas' disease; Phosphatase; Drug design; Crystal structure; Inhibitors ID CRYSTAL-STRUCTURE; PARASITIC INFECTIONS; SIGNAL-TRANSDUCTION; DRUG DISCOVERY; INHIBITORS; DESIGN; IDENTIFICATION; MECHANISM; INTERMEDIATE; CHEMOTHERAPY AB Chagas' disease, a neglected tropical affliction transmitted by the flagellated protozoan Trypanosoma cruzi, is prevalent in Latin America and affects nearly 18 million people worldwide, yet few approved drugs are available to treat the disease. Moreover, the currently available drugs exhibit severe toxicity or are poorly effective in the chronic phase of the disease. This limitation, along with the large population at risk, underscores the urgent need to discover new molecular targets and novel therapeutic agents. Recently, the T. cruzi protein tyrosine phosphatase TcPTP1 has been implicated in the cellular differentiation and infectivity of the parasite and is therefore a promising target for the design of novel anti-parasitic drugs. Here, we report the X-ray crystal structure of TcPTP1 refined to a resolution of 2.18 angstrom, which provides structural insights into the active site environment that can be used to initiate structure-based drug design efforts to develop specific TcPTP1 inhibitors. Potential strategies to develop such inhibitors are also discussed. Published by Elsevier B.V. C1 [Lountos, George T.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Lountos, George T.; Tropea, Joseph E.; Waugh, David S.] Ctr Canc Res, Macromol Crystallog Lab, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. RP Lountos, GT (reprint author), Frederick Natl Lab Canc Res, Macromol Crystallog Lab, POB B, Frederick, MD 21702 USA. EM lountosg@mail.nih.gov; waughd@mail.nih.gov RI Lountos, George/B-3983-2015 FU Frederick National Laboratory for Cancer Research; National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX We thank Scott Cherry for technical assistance. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under Contract HHSN261200800001E and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. 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 tradenames, commercial products or organizations imply endorsement by the US Government. We thank the Biophysics Resource in the Structural Biophysics Laboratory, Frederick National Lab, for use of the LC/ESMS instrument. X-ray diffraction data were collected at the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22-BM of the Advanced Photon Source, Argonne National Laboratory. Supporting institutions may be found at http://www.ser-cat.org/members.html. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. NR 83 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JAN PY 2013 VL 187 IS 1 BP 1 EP 8 DI 10.1016/j.molbiopara.2012.10.006 PG 8 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 094CG UT WOS:000315240000001 PM 23137716 ER PT J CA NIH TI Research resources for tuberculosis at the National Institute of Allergy and Infectious Diseases SO TUBERCULOSIS LA English DT Review DE Mycobacteria; Tuberculosis; Funding opportunities; NIAID; Research resources; Mycobacterial animal models; Tuberculosis therapeutics; Tuberculosis vaccines; Tuberculosis diagnostics; Clinical trials; Mycobacterial reagents; Bioinformatics; Databases; Genomics sequencing ID MYCOBACTERIUM-TUBERCULOSIS; EFFICACY; DRUGS AB Global control of tuberculosis (TB) requires the participation of multiple stakeholders that cross the spectrum of biomedical research, product development, and implementation and operational research. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), plays a critical role in TB biomedical research and product development by directly supporting and leveraging other funding support strategies and providing research resources to facilitate the translation of knowledge about TB into strategies and tools to more effectively combat disease. The primary mission of NIAID is to support high quality, peer reviewed, investigator initiated research that contributes to innovation in infectious disease research. It is also within the mission of NIAID to assure that research findings are translated into vaccines, diagnostics, and drugs to better prevent, diagnose, and treat this devastating disease. (C) 2012 Published by Elsevier Ltd. C1 NIAID, NIH, DMID, TB & Other Mycobacterial Dis Sect,Resp Dis Branch, Bethesda, MD 20892 USA. RP NIAID, NIH, DMID, TB & Other Mycobacterial Dis Sect,Resp Dis Branch, 6610 Rockledge Dr, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 1 U2 6 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 JAN PY 2013 VL 93 IS 1 BP 6 EP 11 DI 10.1016/j.tube.2012.11.009 PG 6 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 094UC UT WOS:000315288300002 ER PT J AU Slayden, RA Jackson, M Zucker, J Ramirez, MV Dawson, CC Crew, R Sampson, NS Thomas, ST Jamshidi, N Sisk, P Caspi, R Crick, DC McNeil, MR Pavelka, MS Niederweis, M Siroy, A Dona, V McFadden, J Boshoff, H Lew, JM AF Slayden, Richard A. Jackson, Mary Zucker, Jeremy Ramirez, Melissa V. Dawson, Clinton C. Crew, Rebecca Sampson, Nicole S. Thomas, Suzanne T. Jamshidi, Neema Sisk, Peter Caspi, Ron Crick, Dean C. McNeil, Michael R. Pavelka, Martin S. Niederweis, Michael Siroy, Axel Dona, Valentina McFadden, Johnjoe Boshoff, Helena Lew, Jocelyne M. TI Updating and curating metabolic pathways of TB SO TUBERCULOSIS LA English DT Review DE Metabolic pathways; Cell envelope; Outer membrane proteins; Cholesterol; Cell division; Regulation; Toxin antitoxin; Reannotation; Curate; Bioinformatics; Mycobacterium tuberculosis ID MYCOBACTERIUM-TUBERCULOSIS H37RV; CHROMOSOMAL TOXIN-ANTITOXIN; OUTER-MEMBRANE PROTEINS; CHOLESTEROL SIDE-CHAIN; 3-KETOSTEROID 9-ALPHA-HYDROXYLASE; BIOCHEMICAL-CHARACTERIZATION; CARBON METABOLISM; GENOME SEQUENCE; BETA-BARREL; IDENTIFICATION AB The sequencing of complete genomes has accelerated biomedical research by providing information about the overall coding capacity of bacterial chromosomes. The original TB annotation resulted in putative functional assignment of similar to 60% of the genes to specific metabolic functions, however, the other 40% of the encoded ORFs where annotated as conserved hypothetical proteins, hypothetical proteins or encoding proteins of unknown function. The TB research community is now at the beginning of the next phases of post-genomics; namely reannotation and functional characterization by targeted experimentation. Arguably, this is the most significant time for basic microbiology in recent history. To foster basic TB research, the Tuberculosis Community Annotation Project (TBCAP) jamboree exercise began the reannotation effort by providing additional information for previous annotations, and refining and substantiating the functional assignment of ORFs and genes within metabolic pathways. The overall goal of the TBCAP 2012 exercise was to gather and compile various data types and use this information with oversight from the scientific community to provide additional information to support the functional annotations of encoding genes. Another objective of this effort was to standardize the publicly accessible Mycobacterium tuberculosis reference sequence and its annotation. The greatest benefit of functional annotation information of genome sequence is that it fuels TB research for drug discovery, diagnostics, vaccine development and epidemiology. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Slayden, Richard A.; Jackson, Mary; Ramirez, Melissa V.; Dawson, Clinton C.; Crew, Rebecca; Crick, Dean C.; McNeil, Michael R.] Colorado State Univ, Ft Collins, CO 80523 USA. [Zucker, Jeremy; Sisk, Peter] Broad Inst MIT & Harvard, Cambridge, MA USA. [Sampson, Nicole S.; Thomas, Suzanne T.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Jamshidi, Neema] Univ Calif San Diego, San Diego, CA 92103 USA. [Caspi, Ron] SRI Int, Menlo Pk, CA 94025 USA. [Pavelka, Martin S.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Niederweis, Michael; Siroy, Axel] Univ Alabama Birmingham, Birmingham, AL USA. [Dona, Valentina; Boshoff, Helena] NIAID, NIH, Bethesda, MD 20892 USA. [McFadden, Johnjoe] Univ Surrey, Guildford GU2 5XH, Surrey, England. [Lew, Jocelyne M.] Ecole Polytech Fed Lausanne, Global Hlth Inst, CH-1015 Lausanne, Switzerland. RP Slayden, RA (reprint author), Colorado State Univ, Ft Collins, CO 80523 USA. EM Richard.slayden@colostate.edu RI Sampson, Nicole/C-4598-2014; Zucker, Jeremy/M-3643-2016; Slayden, Richard/O-8626-2016; Jackson, Mary/D-5345-2017; OI Sampson, Nicole/0000-0002-2835-7760; Zucker, Jeremy/0000-0002-7276-9009; Slayden, Richard/0000-0001-6857-7277; Niederweis, Michael/0000-0003-4068-8092 FU Intramural Research Program of NIAID, NIH FX This work was funded in part by the Intramural Research Program of NIAID, NIH. Most of the top annotators were from OSDD [A], MTB regulatory network [B], iNJ661 MTB metabolic model [C], and GSMN-TB metabolic model [D]. NR 100 TC 12 Z9 12 U1 0 U2 25 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 JAN PY 2013 VL 93 IS 1 BP 47 EP 59 DI 10.1016/j.tube.2012.11.001 PG 13 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 094UC UT WOS:000315288300008 PM 23375378 ER PT J AU Sizemore, CF AF Sizemore, Christine F. TI NIAID TB research program - Priorities, funding and collaborations in global TB research SO TUBERCULOSIS LA English DT Meeting Abstract C1 [Sizemore, Christine F.] NIAID, TB Leprosy & Other Mycobacterial Dis Sect, US Dept HHS, NIH,DMID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2013 VL 93 IS 1 BP 108 EP 108 PG 1 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 094UC UT WOS:000315288300017 ER PT J AU Judson, R Kavlock, R Martin, M Reif, D Houck, K Knudsen, T Richard, A Tice, RR Whelan, M Xia, MH Huang, RL Austin, C Daston, G Hartung, T Fowle, JR Wooge, W Tong, WD Dix, D AF Judson, Richard Kavlock, Robert Martin, Matthew Reif, David Houck, Keith Knudsen, Thomas Richard, Ann Tice, Raymond R. Whelan, Maurice Xia, Menghang Huang, Ruili Austin, Christopher Daston, George Hartung, Thomas Fowle, John R., III Wooge, William Tong, Weida Dix, David TI Perspectives on Validation of High-Throughput Assays Supporting 21st Century Toxicity Testing SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article; Proceedings Paper CT Workshop on Evidence-Based Toxicology for the 21st Century - Opportunities and Challenges CY JAN 24-25, 2012 CL Environm Protect Agcy Campus, NC HO Environm Protect Agcy Campus DE validation; in vitro; high-throughput screening ID APPLICABILITY DOMAIN; TOXICOLOGY; FRAMEWORK; CHEMICALS; THOUGHT; FOOD; RECOMMENDATIONS; TOXICOGENOMICS; PRINCIPLES; RELEVANCE AB In vitro high-throughput screening (HTS) assays are seeing increasing use in toxicity testing. HTS assays can simultaneously test many chemicals but have seen limited use in the regulatory arena, in part because of the need to undergo rigorous, time-consuming formal validation. Here we discuss streamlining the validation process, specifically for prioritization applications. By prioritization, we mean a process in which less complex, less expensive, and faster assays are used to prioritize which chemicals are subjected first to more complex, expensive, and slower guideline assays. Data from the HTS prioritization assays is intended to provide a priori evidence that certain chemicals have the potential to lead to the types of adverse effects that the guideline tests are assessing. The need for such prioritization approaches is driven by the fact that there are tens of thousands of chemicals to which people are exposed, but the yearly throughput of most guideline assays is small in comparison. The streamlined validation process would continue to ensure the reliability and relevance of assays for this application. We discuss the following practical guidelines: (1) follow current validation practice to the extent possible and practical; (2) make increased use of reference compounds to better demonstrate assay reliability and relevance; (3) de-emphasize the need for cross-laboratory testing; and (4) implement a web-based, transparent, and expedited peer review process. C1 [Judson, Richard; Kavlock, Robert; Martin, Matthew; Reif, David; Houck, Keith; Knudsen, Thomas; Richard, Ann; Dix, David] US EPA, Res Triangle Pk, NC 27711 USA. [Tice, Raymond R.] NIEHS, Res Triangle Pk, NC 27709 USA. [Whelan, Maurice] Commiss European Communities, Joint Res Ctr, EURL ECVAM, I-21020 Ispra, Italy. [Xia, Menghang; Huang, Ruili; Austin, Christopher] Natl Ctr Adv Translat Sci, Rockville, MD USA. [Daston, George] Procter & Gamble Co, Cincinnati, OH USA. [Hartung, Thomas] Johns Hopkins Univ, Baltimore, MD USA. [Wooge, William] US EPA, Washington, DC 20460 USA. [Tong, Weida] US FDA, Jefferson, AR USA. RP Judson, R (reprint author), US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, 109 TW Alexander Dr,B205-01, Res Triangle Pk, NC 27711 USA. EM judson.richard@epa.gov OI Judson, Richard/0000-0002-2348-9633; Reif, David/0000-0001-7815-6767 FU Intramural NIH HHS [Z99 ES999999] NR 67 TC 52 Z9 53 U1 4 U2 23 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 1 BP 51 EP 66 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090XH UT WOS:000315012800005 PM 23338806 ER PT J AU Sprankle, C AF Sprankle, Catherine TI INT: Report on applicability of alternatives in regulatory frameworks SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT News Item C1 NIEHS, NTP Interagcy Ctr Evaluat Alternat Toxicol Method, Res Triangle Pk, NC 27709 USA. EM niceatm@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 1 BP 112 EP 112 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090XH UT WOS:000315012800015 ER PT J AU Sprankle, C AF Sprankle, Catherine TI USA: New US Consumer Product Safety Commission policy on animal testing SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT News Item C1 [Sprankle, Catherine] NIEHS, NTP Interagcy Ctr Evaluat Alternat Toxicol Method, Res Triangle Pk, NC USA. EM spranklec@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 4 PU SPEKTRUM AKADEMISCHER VERLAG-SPRINGER-VERLAG GMBH PI HEILDEBERG PA TIERGARTENSTRASSE 17, HEILDEBERG, 69121, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2013 VL 30 IS 1 BP 115 EP 116 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 090XH UT WOS:000315012800023 ER PT J AU Gilbert, SA Grobman, WA Landon, MB Spong, CY Rouse, DJ Leveno, KJ Varner, MW Wapner, RJ Sorokin, Y O'Sullivan, MJ Sibai, BM Thorp, JM Ramin, SM Mercer, BM AF Gilbert, Sharon A. Grobman, William A. Landon, Mark B. Spong, Catherine Y. Rouse, Dwight J. Leveno, Kenneth J. Varner, Michael W. Wapner, Ronald J. Sorokin, Yoram O'Sullivan, Mary J. Sibai, Baha M. Thorp, John M. Ramin, Susan M. Mercer, Brian M. CA Eunice Kennedy Shriver Natl Inst C TI Cost-Effectiveness of Trial of Labor after Previous Cesarean in a Minimally Biased Cohort SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE cost-effectiveness; elective repeat cesarean; trial of labor; propensity scores ID CEREBRAL-PALSY; DELIVERY; MULTICENTER; OUTCOMES; UTILITY; RISK; TERM AB Objective To estimate the cost-effectiveness of a trial of labor after one previous cesarean delivery (TOLAC). Study Design A model comparing TOLAC with elective repeat cesarean delivery (ERCD) was developed for a hypothetical cohort with no contraindication to a TOLAC. Probabilistic estimates were obtained from women matched on their baseline characteristics using propensity scores. Cost data, quality-adjusted life-years (QALYs), and data on cerebral palsy were incorporated from the literature. Results The TOLAC strategy dominated the ERCD strategy at baseline, with $138.6 million saved and 1703 QALYs gained per 100,000 women. The model was sensitive to five variables: the probability of uterine rupture, the probability of successful TOLAC, the QALY of failed TOLAC, the cost of ERCD, and the cost of successful TOLAC without complications. When the probability of TOLAC success was at the base value, 68.5%, TOLAC was preferred if the probability of uterine rupture was 4.2% or less. When the probability of uterine rupture was at the base value, 0.8%, the TOLAC strategy was preferred as long as the probability of success was 42.6% or more. Conclusion A TOLAC is less expensive and more effective than an ERCD in a group of women with balanced baseline characteristics. C1 [Gilbert, Sharon A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Grobman, William A.] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Landon, Mark B.] Ohio State Univ, Columbus, OH 43210 USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Rouse, Dwight J.] Univ Alabama Birmingham, Birmingham, AL USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Wapner, Ronald J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [O'Sullivan, Mary J.] Univ Miami, Miami, FL USA. [Sibai, Baha M.] Univ Tennessee, Memphis, TN USA. [Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Mercer, Brian M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. RP Gilbert, SA (reprint author), George Washington Univ, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM sgilbert@bsc.gwu.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801] FX The project described was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) [HD21410, HD21414, HD27860, HD27861, HD27869, HD27905, HD27915, HD27917, HD34116, HD34122, HD34136, HD34208, HD34210, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, and HD36801] and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NICHD or the NIH. NR 26 TC 5 Z9 5 U1 0 U2 8 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD JAN PY 2013 VL 30 IS 1 BP 11 EP 20 DI 10.1055/s-0032-1333206 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 088AF UT WOS:000314805500003 PM 23292916 ER PT J AU Hussain, S Vanoirbeek, JAJ Haenen, S Haufroid, V Boland, S Marano, F Nemery, B Hoet, PHM AF Hussain, Salik Vanoirbeek, Jeroen A. J. Haenen, Steven Haufroid, Vincent Boland, Sonja Marano, Francelyne Nemery, Benoit Hoet, Peter H. M. TI Prior Lung Inflammation Impacts on Body Distribution of Gold Nanoparticles SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID PARTICLES; DELIVERY; EXPOSURE; RATS; MICE; LIPOPOLYSACCHARIDE; CYTOTOXICITY; CIRCULATION; CLEARANCE; INJURY AB Introduction. Gold- (Au-) based nanomaterials have shown promising potential in nanomedicine. The individual health status is an important determinant of the response to injury/exposure. It is, therefore, critical to evaluate exposure to Au-nanomaterials with varied preexisting health status. Objective. The goal of this research was to determine the extent of extrapulmonary translocation from healthy and inflamed lungs after pulmonary exposure to AuNPs. Male BALB/c mice received a single dose of 0.8 mg . kg(-1) AuNPs (40 nm) by oropharyngeal aspiration 24 hours after priming with LPS (0.4 mg.kg(-1)) through the same route. Metal contents were analyzed in different organs by inductively coupled plasma-mass spectrometry (ICP-MS). Results. Oropharyngeal aspiration resulted in high metal concentrations in lungs (P < 0.001); however, these were much lower after pretreatment with LPS (P < 0.05). Significantly higher concentrations of Au were detected in heart and thymus of healthy animals, whereas higher concentrations of Au NPs were observed in spleen in LPS-primed animals. Conclusions. The distribution of AuNPs from lungs to secondary target organs depends upon the health status, indicating that targeting of distinct secondary organs in nanomedicine needs to be considered carefully under health and inflammatory conditions. C1 [Hussain, Salik; Boland, Sonja; Marano, Francelyne] Univ Paris Diderot, Unit Funct & Adapt Biol BFA, CNRS, Lab Mol & Cellular Responses Xenobiot,EAC 7059, F-75013 Paris, France. [Hussain, Salik; Vanoirbeek, Jeroen A. J.; Haenen, Steven; Nemery, Benoit; Hoet, Peter H. M.] Katholieke Univ Leuven, Lung Toxicol Res Unit, B-3000 Louvain, Belgium. [Hussain, Salik] NIEHS, Clin Res Unit, Res Triangle Pk, NC 27709 USA. [Haufroid, Vincent] Catholic Univ Louvain, Louvain Ctr Toxicol & Appl Pharmacol, B-1200 Brussels, Belgium. RP Hoet, PHM (reprint author), Katholieke Univ Leuven, Lung Toxicol Res Unit, B-3000 Louvain, Belgium. EM peter.hoet@med.kuleuven.be RI Nemery, Benoit/D-1224-2013; Vanoirbeek, Jeroen/D-5183-2016; Hussain, Salik/O-1687-2016; Hoet, Peter/H-9987-2013 OI Vanoirbeek, Jeroen/0000-0001-5508-3518; Hoet, Peter/0000-0002-0292-6603 FU Research Foundation Flanders [FWO G.0707.09] FX Jean-Pierre Abid is acknowledged for preparing the particles and Gladys Deumer for her technical assistance for Au determination. This work was supported by the Research Foundation Flanders (FWO G.0707.09). NR 29 TC 7 Z9 7 U1 0 U2 9 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 923475 DI 10.1155/2013/923475 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 090DE UT WOS:000314958600001 ER PT J AU Totonchy, MB Tamura, D Pantell, MS Zalewski, C Bradford, PT Merchant, SN Nadol, J Khan, SG Schiffmann, R Pierson, TM Wiggs, E Griffith, AJ DiGiovanna, JJ Kraemer, KH Brewer, CC AF Totonchy, Mariam B. Tamura, Deborah Pantell, Matthew S. Zalewski, Christopher Bradford, Porcia T. Merchant, Saumil N. Nadol, Joseph Khan, Sikandar G. Schiffmann, Raphael Pierson, Tyler Mark Wiggs, Edythe Griffith, Andrew J. DiGiovanna, John J. Kraemer, Kenneth H. Brewer, Carmen C. TI Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration SO BRAIN LA English DT Article DE xeroderma pigmentosum; sensorineural hearing loss; neurodegeneration; photosensitivity; DNA repair ID COCKAYNE-SYNDROME; TRICHOTHIODYSTROPHY; DISEASE; MANIFESTATIONS; ABNORMALITIES; PHENOTYPE; SYMPTOMS; MUTATION; DEAFNESS; DAMAGE AB To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (> 20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average epsilon 10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system. C1 [Totonchy, Mariam B.; Tamura, Deborah; Khan, Sikandar G.; DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Totonchy, Mariam B.; Pantell, Matthew S.] NIH, Clin Res Training Programme, Bethesda, MD 20892 USA. [Pantell, Matthew S.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Zalewski, Christopher; Griffith, Andrew J.; Brewer, Carmen C.] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Bethesda, MD 20892 USA. [Bradford, Porcia T.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Merchant, Saumil N.; Nadol, Joseph] Harvard Univ, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Schiffmann, Raphael; Pierson, Tyler Mark; Wiggs, Edythe] NINDS, Bethesda, MD 20892 USA. RP Kraemer, KH (reprint author), NCI, Dermatol Branch, Bldg 37,Room 4002, Bethesda, MD 20892 USA. EM Kraemerk@nih.gov FU Center for Cancer Research, National Cancer Institute; Division of Cancer Epidemiology and Genetics, National Cancer Institute; National Institute on Deafness and Other Communication Disorders (NIDCD); National Institute of Aging; National Institutes of Health; NIDCD [1U24DC011943-01]; Pfizer Inc FX Intramural Research Programs of the Center for Cancer Research, National Cancer Institute (M.B.T., D.T., S.G.K., J.J.D. and K.H.K.), of the Division of Cancer Epidemiology and Genetics, National Cancer Institute (P.T.B.), of the National Institute on Deafness and Other Communication Disorders (NIDCD) (C.Z., A.J.G. and C.C.B.) and of the National Institute of Aging (M. S. P.) of the National Institutes of Health and from NIDCD (1U24DC011943-01 to S.M. and J.N.). Clinical Research Training Program (to M.B.T. and M.S.P.), a public-private partnership supported jointly by the National Institutes of Health and Pfizer Inc (via a grant to the Foundation for National Institutes of Health from Pfizer Inc). NR 45 TC 14 Z9 14 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2013 VL 136 BP 194 EP 208 DI 10.1093/brain/aws317 PN 1 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 089KR UT WOS:000314909900016 PM 23365097 ER PT J AU Metz, G Coppard, N Cooper, JM Delatycki, MB Durr, A Di Prospero, NA Giunti, P Lynch, DR Schulz, JB Rummey, C Meier, T AF Metz, Guenther Coppard, Nicholas Cooper, Jonathon M. Delatycki, Martin B. Duerr, Alexandra Di Prospero, Nicholas A. Giunti, Paola Lynch, David R. Schulz, J. B. Rummey, Christian Meier, Thomas TI Rating disease progression of Friedreich's ataxia by the International Cooperative Ataxia Rating Scale: analysis of a 603-patient database SO BRAIN LA English DT Article DE Friedreich's ataxia; ratings scale; ICARS; disease progression; natural history ID PLACEBO-CONTROLLED TRIAL; IDEBENONE; RELIABILITY; SEVERITY AB The aim of this cross-sectional study was to analyse disease progression in Friedreich's ataxia as measured by the International Cooperative Ataxia Rating Scale. Single ratings from 603 patients with Friedreich's ataxia were analysed as a function of disease duration, age of onset and GAA repeat lengths. The relative contribution of items and subscales to the total score was studied as a function of disease progression. In addition, the scaling properties were assessed using standard statistical measures. Average total scale progression per year depends on the age of disease onset, the time since diagnosis and the GAA repeat length. The age of onset inversely correlates with increased GAA repeat length. For patients with an age of onset 14 years associated with a longer repeat length, the average yearly rate of decline was 2.5 +/- 0.18 points in the total International Cooperative Ataxia Rating Scale for the first 20 years of disease duration, whereas patients with a later onset progress more slowly (1.8 +/- 0.27 points/year). Ceiling effects in posture, gait and lower limb scale items lead to a reduced sensitivity of the scale in the severely affected population with a total score of > 60 points. Psychometric scaling analysis shows generally favourable properties for the total scale, but the subscale grouping could be improved. This cross-sectional study provides a detailed characterization of the International Cooperative Ataxia Rating Scale. The analysis further provides rates of change separated for patients with early and late disease onset, which is driven by the GAA repeat length. Differences in the subscale dynamics merit consideration in the design of future clinical trials applying this scale as a neurological assessment instrument in Friedreich's ataxia. C1 [Metz, Guenther; Coppard, Nicholas; Meier, Thomas] Santhera Pharmaceut, CH-4410 Liestal, Switzerland. [Cooper, Jonathon M.] UCL Inst Neurol, Dept Clin Neurosci, London, England. [Delatycki, Martin B.] Murdoch Childrens Res Inst, Bruce Lefroy Ctr Genet Hlth Res, Parkville, Vic, Australia. [Duerr, Alexandra] Hop La Pitie Salpetriere, Dept Genet & Cytogenet, Paris, France. [Duerr, Alexandra] Inst Cerveau & Moelle Epiniere, INSERM, U975, Ctr Rech, Paris, France. [Di Prospero, Nicholas A.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Giunti, Paola] UCL Inst Neurol, Dept Mol Neurosci, London, England. [Lynch, David R.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Schulz, J. B.] Rhein Westfal TH Aachen, Dept Neurol, Univ Hosp, Aachen, Germany. [Schulz, J. B.] JARA Brain, Aachen, Germany. [Rummey, Christian] 4Pharma, Liestal, Switzerland. RP Metz, G (reprint author), Santhera Pharmaceut, Hammerstr 49, CH-4410 Liestal, Switzerland. EM guenther.metz@santhera.com RI Schulz, Jorg/D-9786-2012; Cooper, J Mark/D-5826-2013; Giunti, Paola /E-5526-2012; OI Schulz, Jorg/0000-0002-8903-0593; Cooper, J Mark/0000-0002-3007-3054; Giunti, Paola /0000-0003-3508-4788; Rummey, Christian/0000-0003-4911-911X FU National Institutes of Health; Muscular Dystrophy Association; Friedreich's Ataxia Research Alliance (FARA); Ataxia UK; National Health and Medical Research Council; Friedreich's Ataxia Research Association (Australasia); NINDS; Santhera Pharmaceuticals FX D.R.L. was supported by a grant for other projects from the National Institutes of Health, the Muscular Dystrophy Association and the Friedreich's Ataxia Research Alliance (FARA). J.M.C. received funding from Ataxia UK. M.B.D. received funding from the National Health and Medical Research Council, the Friedreich's Ataxia Research Alliance (FARA) and the Friedreich's Ataxia Research Association (Australasia). N.A.D. was supported in part by intramural research funds from NINDS.; G.M., N.C. and T.M. are regular employees of Santhera Pharmaceuticals, the sponsor of the IONIA and MICONOS studies. C.R. has been a regular employee of Santhera Pharmaceuticals, the sponsor of the IONIA and MICONOS studies. All other authors declare no conflict of interest. NR 20 TC 17 Z9 17 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2013 VL 136 BP 259 EP 268 DI 10.1093/brain/aws309 PN 1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 089KR UT WOS:000314909900020 PM 23365101 ER PT J AU Bradberry, TJ Metman, LV Contreras-Vidal, JL Schulz, GM Braun, AR AF Bradberry, Trent J. Metman, Leonard Verhagen Contreras-Vidal, Jose L. Schulz, Geralyn M. Braun, Allen R. TI Reply to Letter to the Editor "(H2O)-O-15 PET responses to deep brain stimulation" SO BRAIN STIMULATION LA English DT Letter ID SUBTHALAMIC NUCLEUS STIMULATION; PARKINSONS-DISEASE C1 [Bradberry, Trent J.; Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD USA. [Bradberry, Trent J.; Contreras-Vidal, Jose L.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA. [Metman, Leonard Verhagen] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA. [Contreras-Vidal, Jose L.] Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. [Contreras-Vidal, Jose L.] Univ Maryland, Grad Program Neurosci & Cognit Sci, College Pk, MD 20742 USA. [Schulz, Geralyn M.] George Washington Univ, Dept Speech & Hearing Sci, Washington, DC USA. RP Braun, AR (reprint author), Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bldg 10,Room 8S235A, Bethesda, MD USA. EM brauna@nidcd.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD JAN PY 2013 VL 6 IS 1 BP 94 EP 95 DI 10.1016/j.brs.2012.01.005 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 092PW UT WOS:000315135500015 PM 22410479 ER PT J AU Muallem, S Machaca, K AF Muallem, Shmuel Machaca, Khaled TI Ca+ signaling and ionic homeostasis in Gamete Maturation and Function Preface SO CELL CALCIUM LA English DT Editorial Material C1 [Muallem, Shmuel] NIDCR, NIH, Bethesda, MD USA. [Machaca, Khaled] Qatar Fdn, Dept Physiol & Biophys, Weill Cornell Med Coll Qatar, Doha, Qatar. RP Machaca, K (reprint author), Qatar Fdn, Dept Physiol & Biophys, Weill Cornell Med Coll Qatar, Doha, Qatar. EM khm2002@qatar-med.cornell.edu NR 0 TC 0 Z9 0 U1 0 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 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD JAN PY 2013 VL 53 IS 1 SI SI BP 1 EP 1 DI 10.1016/j.ceca.2012.12.002 PG 1 WC Cell Biology SC Cell Biology GA 092QF UT WOS:000315136400001 PM 23306093 ER PT J AU Chun, JH Morse, CL Chinz, FT Pike, VW AF Chun, Joong-Hyun Morse, Cheryl L. Chinz, Frederick T. Pike, Victor W. TI No-carrier-added [F-18]fluoroarenes from the radiofluorination of diaryl sulfoxides SO CHEMICAL COMMUNICATIONS LA English DT Article ID BENZODIAZEPINE BINDING-SITES; DIARYLIODONIUM-SALTS; GRIGNARD-REAGENTS; LIGAND; ROUTE; ION AB No-carrier-added [F-18]fluoroarenes were synthesized through the radiofluorination of diaryl sulfoxides with [F-18]fluoride ion. Diaryl sulfoxides bearing a para electron-withdrawing substituent readily gave the corresponding 4-[F-18]fluoroarenes in high RCYs. This process broadens the scope for preparing novel F-18-labeling synthons and PET radiotracers. C1 [Chun, Joong-Hyun; Morse, Cheryl L.; Chinz, Frederick T.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346A,10 Ctr Dr, Bethesda, MD 20892 USA. EM pikev@mail.nih.gov FU Intramural Research Program of the National Institutes of Health (NIMH) FX This work was funded by the Intramural Research Program of the National Institutes of Health (NIMH). We are grateful to the NIH clinical PET center for supplying fluorine-18. NR 29 TC 11 Z9 11 U1 0 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2013 VL 49 IS 21 BP 2151 EP 2153 DI 10.1039/c3cc37795d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 089ER UT WOS:000314893200018 PM 23388835 ER PT J AU Nikolic, D Van Breemen, RB AF Nikolic, Dejan Van Breemen, Richard B. TI Analytical Methods for Quantitation of Prenylated Flavonoids from Hops SO CURRENT ANALYTICAL CHEMISTRY LA English DT Article DE Hops; Mass spectrometry; 8-prenylanaringenin; Prenylated flavonoids; Quantitation; Xanthohumol ID HUMULUS-LUPULUS L.; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; ALLEVIATE MENOPAUSAL DISCOMFORTS; HUMAN LIVER-MICROSOMES; ELECTROSPRAY-IONIZATION; POTENT PHYTOESTROGEN; IN-VITRO; EFFICIENT SYNTHESIS; TRIFOLIUM-PRATENSE AB The female flowers of hops (Humulus lupulus L.) are used as a flavoring agent in the brewing industry. There is growing interest in possible health benefits of hops, particularly as estrogenic and chemopreventive agents. Among the possible active constituents, most of the attention has focused on prenylated flavonoids, which can chemically be classified as prenylated chalcones and prenylated flavanones. Among chalcones, xanthohumol (XN) and desmethylxanthohumol (DMX) have been the most studied, while among flavanones, 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN) have received the most attention. Because of the interest in medicinal properties of prenylated flavonoids, there is demand for accurate, reproducible and sensitive analytical methods to quantify these compounds in various matrices. Such methods are needed, for example, for quality control and standardization of hop extracts, measurement of the content of prenylated flavonoids in beer, and to determine pharmacokinetic properties of prenylated flavonoids in animals and humans. This review summarizes currently available analytical methods for quantitative analysis of the major prenylated flavonoids, with an emphasis on the LC-MS and LC-MS-MS methods and their recent applications to biomedical research on hops. This review covers all methods in which prenylated flavonoids have been measured, either as the primary analytes or as a part of a larger group of analytes. The review also discusses methodological issues relating to the quantitative analysis of these compounds regardless of the chosen analytical approach. C1 [Nikolic, Dejan; Van Breemen, Richard B.] Univ Illinois, Dept Med Chem & Pharmacognosy, NIH, Ctr Bot Dietary Supplements Res,Coll Pharm, Chicago, IL 60612 USA. RP Nikolic, D (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA. EM dnikol1@uic.edu FU Office of Dietary Supplements [P50AT00155]; National Institute of General Medical Sciences; Office for Research on Women's Health; National Center for Complementary and Alternative Medicine FX The work in the authors' laboratory is supported by grant P50AT00155 from the Office of Dietary Supplements, the National Institute of General Medical Sciences, the Office for Research on Women's Health and the National Center for Complementary and Alternative Medicine. NR 77 TC 9 Z9 9 U1 3 U2 52 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4110 J9 CURR ANAL CHEM JI Curr. Anal. Chem. PD JAN PY 2013 VL 9 IS 1 BP 71 EP 85 PG 15 WC Chemistry, Analytical SC Chemistry GA 089AA UT WOS:000314878800010 PM 24077106 ER PT J AU Bi, HC Li, F Krausz, KW Qu, AJ Johnson, CH Gonzalez, FJ AF Bi, Huichang Li, Fei Krausz, Kristopher W. Qu, Aijuan Johnson, Caroline H. Gonzalez, Frank J. TI Targeted Metabolomics of Serum Acylcarnitines Evaluates Hepatoprotective Effect of Wuzhi Tablet (Schisandra sphenanthera Extract) against Acute Acetaminophen Toxicity SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID HEPATIC MITOCHONDRIAL GLUTATHIONE; TETRACHLORIDE-INTOXICATED MICE; OXIDATIVE STRESS; LIVER-INJURY; HEPATOTOXICITY; RATS; PARACETAMOL; CLOFIBRATE; METABOLISM; ALPHA AB Possible prevention and therapeutic intervention strategies to counteract acetaminophen (APAP) hepatotoxicity would be of great value. Wuzhi tablet (WZ, extract of Schisandrae sphenanthera) possesses hepatoprotective effects against hepatitis and the hepatic dysfunction induced by various chemical hepatotoxins. In this study, the protective effect of WZ on APAP-induced hepatic injury was evaluated and targeted metabolomics by LC-MS-based metabolomics was used to examine whether WZ influences hepatic metabolism. The results demonstrated significant hepatoprotection of WZ against APAP-induced liver injury; pretreatment with WZ prior to APAP administration blocks the increase in serum palmitoylcarnitine and oleoylcarnitine and thus restores the APAP-impaired fatty acid beta-oxidation to normal levels. These studies further revealed a significant and prolonged upregulation of the PPAR alpha target genes Cpt1 and Acot1 by WZ mainly contributing to the maintenance of normal fatty acid metabolism and thus potentially contributing to the hepatic protection of WZ against APAP-induced hepatic toxicity. Taken together, the current study provides new insights into understanding the hepatoprotective effect of WZ against APAP-induced liver toxicity. C1 [Bi, Huichang] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China. [Bi, Huichang; Li, Fei; Krausz, Kristopher W.; Qu, Aijuan; Johnson, Caroline H.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Johnson, Caroline H.] Scripps Res Inst, Ctr Metabol & Mass Spectrometry, La Jolla, CA 92037 USA. RP Bi, HC (reprint author), Sun Yat Sen Univ, Sch Pharmaceut Sci, 132 Waihuandong Rd, Guangzhou 510006, Guangdong, Peoples R China. EM bihchang@mail.sysu.edu.cn RI Li, Fei/F-6849-2013 FU NCI Intramural Research Program of the NIH; Natural Science Foundation of China [81001685] FX This study was supported by the NCI Intramural Research Program of the NIH. The authors thank the Natural Science Foundation of China for collaborative research for a grant to Dr. H. Bi. (Grant no. 81001685). NR 33 TC 18 Z9 18 U1 3 U2 28 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 985257 DI 10.1155/2013/985257 PG 13 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 090EO UT WOS:000314962200001 ER PT J AU Lobkovsky, AE Wolf, YI Koonin, EV AF Lobkovsky, Alexander E. Wolf, Yuri I. Koonin, Eugene V. TI Gene Frequency Distributions Reject a Neutral Model of Genome Evolution SO GENOME BIOLOGY AND EVOLUTION LA English DT Article DE gene frequency distribution; steady genome model; goodness of fit; evolution mechanisms ID ESCHERICHIA-COLI O157-H7; UNIVERSAL COMMON ANCESTOR; BACTERIAL PAN-GENOME; STRAINS; MICROBIOLOGY; PROKARYOTES; PANGENOME; DIVERSITY; NETWORKS; SEARCH AB Evolution of prokaryotes involves extensive loss and gain of genes, which lead to substantial differences in the gene repertoires even among closely related organisms. Through a wide range of phylogenetic depths, gene frequency distributions in prokaryotic pangenomes bear a characteristic, asymmetrical U-shape, with a core of (nearly) universal genes, a "shell" of moderately common genes, and a "cloud" of rare genes. We employ mathematical modeling to investigate evolutionary processes that might underlie this universal pattern. Gene frequency distributions for almost 400 groups of 10 bacterial or archaeal species each over a broad range of evolutionary distances were fit to steady-state, infinite allele models based on the distribution of gene replacement rates and the phylogenetic tree relating the species in each group. The fits of the theoretical frequency distributions to the empirical ones yield model parameters and estimates of the goodness of fit. Using the Akaike Information Criterion, we show that the neutral model of genome evolution, with the same replacement rate for all genes, can be confidently rejected. Of the three tested models with purifying selection, the one in which the distribution of replacement rates is derived from a stochastic population model with additive per-gene fitness yields the best fits to the data. The selection strength estimated from the fits declines with evolutionary divergence while staying well outside the neutral regime. These findings indicate that, unlike some other universal distributions of genomic variables, for example, the distribution of paralogous gene family membership, the gene frequency distribution is substantially affected by selection. C1 [Lobkovsky, Alexander E.; Wolf, Yuri I.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 47 TC 16 Z9 16 U1 1 U2 32 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1759-6653 J9 GENOME BIOL EVOL JI Genome Biol. Evol. PY 2013 VL 5 IS 1 BP 233 EP 242 DI 10.1093/gbe/evt002 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 087RA UT WOS:000314778600019 PM 23315380 ER PT J AU Schwarz, J Astermark, J Menius, ED Carrington, M Donfield, SM Gomperts, ED Nelson, GW Oldenburg, J Pavlova, A Shapiro, AD Winkler, CA Berntorp, E AF Schwarz, J. Astermark, J. Menius, E. D. Carrington, M. Donfield, S. M. Gomperts, E. D. Nelson, G. W. Oldenburg, J. Pavlova, A. Shapiro, A. D. Winkler, C. A. Berntorp, E. CA Hemophilia Inhibitor Genetics TI F8 haplotype and inhibitor risk: results from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort SO HAEMOPHILIA LA English DT Article DE F8 haplotype; FVIII inhibitors; haplotype mismatch ID PREVIOUSLY UNTREATED PATIENTS; PREVIOUSLY TREATED PATIENTS; FACTOR-VIII; POLYMORPHISMS; RECOMBINANT; EFFICACY; SAFETY; MULTICENTER; GENES AB Ancestral background, specifically African descent, confers higher risk for development of inhibitory antibodies to factor VIII (FVIII) in haemophilia A. It has been suggested that differences in the distribution of FVIII gene (F8) haplotypes, and mismatch between endogenous F8 haplotypes and those comprising products used for treatment could contribute to risk. Data from the Hemophilia Inhibitor Genetics Study (HIGS) Combined Cohort were used to determine the association between F8 haplotype 3 (H3) vs. haplotypes 1 and 2 (H1 + H2) and inhibitor risk among individuals of genetically determined African descent. Other variables known to affect inhibitor risk including type of F8 mutation and human leucocyte antigen (HLA) were included in the analysis. A second research question regarding risk related to mismatch in endogenous F8 haplotype and recombinant FVIII products used for treatment was addressed. Haplotype 3 was associated with higher inhibitor risk among those genetically identified (N = 49) as of African ancestry, but the association did not remain significant after adjustment for F8 mutation type and the HLA variables. Among subjects of all racial ancestries enrolled in HIGS who reported early use of recombinant products (N = 223), mismatch in endogenous haplotype and the FVIII proteins constituting the products used did not confer greater risk for inhibitor development. Haplotype 3 was not an independent predictor of inhibitor risk. Furthermore, our findings did not support a higher risk of inhibitors in the presence of a haplotype mismatch between the FVIII molecule infused and that of the individual. C1 [Schwarz, J.; Menius, E. D.; Donfield, S. M.] Rho Inc, Dept Biostat, Chapel Hill, NC USA. [Astermark, J.; Berntorp, E.] Lund Univ, Ctr Thrombosis & Haemostasis, Skane Univ Hosp, SE-20502 Malmo, Sweden. [Carrington, M.] SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD USA. [Carrington, M.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Gomperts, E. D.] Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA. [Nelson, G. W.] SAIC Frederick Inc, Ctr Canc Res Genet Core, Frederick Natl Lab Canc Res, Frederick, MD USA. [Oldenburg, J.; Pavlova, A.] Univ Clin, Inst Expt Haematol & Transfus Med, Bonn, Germany. [Shapiro, A. D.] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA. [Winkler, C. A.] SAIC Frederick Inc, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD USA. RP Berntorp, E (reprint author), Lund Univ, Ctr Thrombosis & Haemostasis, Skane Univ Hosp, SE-20502 Malmo, Sweden. EM erik.berntorp@med.lu.se FU Baxter BioScience; Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH) [HHSN261200800001E]; Wyeth; Research Fund at Malmo University Hospital; NIH, National Institute of Child Health and Human Development [R01-HD-41224]; Bayer; Inspiration Biopharmaceuticals, Inc.; Grifols, Inc.; Baxter; Biogen Idec; Biotest; CSL Behring; Grifols; Inspiration Biopharmaceuticals; NovoNordisk; Octapharma; Swedish Orphan Biovitrum; Wyeth/Pfizer FX This work is supported by an investigator-initiated grant from Baxter BioScience, and in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health (NIH), under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US government. The Malmo International Brother Study is funded through grants from Wyeth and the Research Fund at Malmo University Hospital. The Hemophilia Growth and Development Study is funded by the NIH, National Institute of Child Health and Human Development, R01-HD-41224. We are grateful to the participants and parents who volunteered to participate in these studies. We wish to thank Donna M. DiMichele, MD, Deputy Director, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute, National Institutes of Health, for her contributions as a Scientific Advisor to HIGS; Elizabeth Binns-Roemer (NCI Frederick) for management of study samples and genotyping and Yuko Yuki (NCI Frederick) for completion of HLA class II typing.; J. Astermark has received research grants from Baxter BioScience and Bayer. He is a consultant and participant in Advisory Boards for Baxter, Bayer, NovoNordisk, CSL Behring and Pfizer. E. Berntorp, S. Donfield, E. Menius and J. Schwarz have received funding for research carried out in this work from Baxter BioScience. E. Gomperts is a paid consultant to Inspiration Biopharmaceuticals, Inc. and Grifols, Inc., neither of which contributed support for this research. J. Oldenburg receives reimbursement for attending symposia/congresses and/or honoraria for speaking, consulting or for conducting research from Baxter, Bayer, Biogen Idec, Biotest, CSL Behring, Grifols, Inspiration Biopharmaceuticals, NovoNordisk, Octapharma, Swedish Orphan Biovitrum and Wyeth/Pfizer. M. Carrington, G. Nelson, A. Pavlova, A. Shapiro and C. Winkler have no competing interests to declare. NR 23 TC 25 Z9 26 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JAN PY 2013 VL 19 IS 1 BP 113 EP 118 DI 10.1111/hae.12004 PG 6 WC Hematology SC Hematology GA 088IJ UT WOS:000314827200025 PM 22958194 ER PT J AU Cote, LR Yuen, CX AF Cote, Linda R. Yuen, Cynthia X. TI Children Abroad: Immigrant Children's Development in Worldwide Perspective Essay Review of The Immigrant Paradox in Children and Adolescents: Is Becoming an American a Developmental Risk? by Cynthia Garcia Coll and Amy Kerivan Marks, and The Impact of Immigration on Children's Development by Cynthia Garcia Coll SO HUMAN DEVELOPMENT LA English DT Review ID ACCULTURATION C1 [Cote, Linda R.] Marymount Univ, Arlington, VA 22207 USA. [Yuen, Cynthia X.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Cote, LR (reprint author), Marymount Univ, Dept Psychol, Arlington, VA 22207 USA. EM lcote@marymount.edu NR 24 TC 0 Z9 0 U1 3 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0018-716X J9 HUM DEV JI Hum. Dev. PY 2013 VL 56 IS 1 BP 76 EP 81 DI 10.1159/000342934 PG 6 WC Psychology, Developmental SC Psychology GA 087IO UT WOS:000314755100007 ER PT J AU Elena, JW Travis, LB Simonds, NI Ambrosone, CB Ballard-Barbash, R Bhatia, S Cerhan, JR Hartge, P Heist, RS Kushi, LH Lash, TL Morton, LM Onel, K Pierce, JP Robison, LL Rowland, JH Schrag, D Sellers, TA Seminara, D Shu, XO Thomas, NE Ulrich, CM Freedman, AN AF Elena, Joanne W. Travis, Lois B. Simonds, Naoko I. Ambrosone, Christine B. Ballard-Barbash, Rachel Bhatia, Smita Cerhan, James R. Hartge, Patricia Heist, Rebecca S. Kushi, Lawrence H. Lash, Timothy L. Morton, Lindsay M. Onel, Kenan Pierce, John P. Robison, Leslie L. Rowland, Julia H. Schrag, Deborah Sellers, Thomas A. Seminara, Daniela Shu, Xiao Ou Thomas, Nancy E. Ulrich, Cornelia M. Freedman, Andrew N. TI Leveraging Epidemiology and Clinical Studies of Cancer Outcomes: Recommendations and Opportunities for Translational Research SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LONG-TERM SURVIVORS; 2ND MALIGNANT NEOPLASMS; DISEASE-FREE SURVIVAL; ACUTE LYMPHOBLASTIC-LEUKEMIA; TREATMENT-RELATED TOXICITY; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; BREAST-CANCER; COLORECTAL-CANCER; TESTICULAR-CANCER AB As the number of cancer survivors continues to grow, research investigating the factors that affect cancer outcomes, such as disease recurrence, risk of second malignant neoplasms, and the late effects of cancer treatments, becomes ever more important. Numerous epidemiologic studies have investigated factors that affect cancer risk, but far fewer have addressed the extent to which demographic, lifestyle, genomic, clinical, and psychosocial factors influence cancer outcomes. To identify research priorities as well as resources and infrastructure needed to advance the field of cancer outcomes and survivorship research, the National Cancer Institute sponsored a workshop titled "Utilizing Data from Cancer Survivor Cohorts: Understanding the Current State of Knowledge and Developing Future Research Priorities" on November 3, 2011, in Washington, DC. This commentary highlights recent findings presented at the workshop, opportunities to leverage existing data, and recommendations for future research, data, and infrastructure needed to address high priority clinical and research questions. Multidisciplinary teams that include epidemiologists, clinicians, biostatisticians, and bioinformaticists will be essential to facilitate future cancer outcome studies focused on improving clinical care of cancer patients, identifying those at high risk of poor outcomes, and implementing effective interventions to ultimately improve the quality and duration of survival. J Natl Cancer Inst ;2013;105:85-94 C1 [Elena, Joanne W.; Simonds, Naoko I.; Ballard-Barbash, Rachel; Seminara, Daniela; Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hartge, Patricia; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, Rubin Ctr Canc Survivorship, Rochester, NY 14642 USA. [Travis, Lois B.] Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Bhatia, Smita] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA. [Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Heist, Rebecca S.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Kushi, Lawrence H.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Lash, Timothy L.] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark. [Lash, Timothy L.] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Onel, Kenan] Univ Chicago, Dept Pediat, Sect Hematol Oncol, Chicago, IL 60637 USA. [Pierce, John P.] Univ Calif San Diego, Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Schrag, Deborah] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. [Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Shu, Xiao Ou] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, Nashville, TN USA. [Shu, Xiao Ou] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Thomas, Nancy E.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Ulrich, Cornelia M.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. [Ulrich, Cornelia M.] German Canc Res Ctr, Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Heidelberg, Germany. RP Elena, JW (reprint author), Clin & Translat Epidemiol Branch, DCCPS 6130 Execut Blvd,Rm 5136, Bethesda, MD 20892 USA. EM elenajw@mail.nih.gov RI Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X; Kushi, Lawrence/0000-0001-9136-1175 NR 74 TC 25 Z9 25 U1 1 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JAN PY 2013 VL 105 IS 2 BP 85 EP 94 DI 10.1093/jnci/djs473 PG 10 WC Oncology SC Oncology GA 088VK UT WOS:000314865100006 PM 23197494 ER PT J AU Sinder, BP Eddy, MM Ominsky, MS Caird, MS Marini, JC Kozloff, KM AF Sinder, Benjamin P. Eddy, Mary M. Ominsky, Michael S. Caird, Michelle S. Marini, Joan C. Kozloff, Kenneth M. TI Sclerostin Antibody Improves Skeletal Parameters in a Brtl/+ Mouse Model of Osteogenesis Imperfecta SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOGENESIS IMPERFECTA; SCLEROSTIN ANTIBODY; COLLAGEN; BONE MASS; ANABOLIC THERAPY ID SUPPRESSED BONE TURNOVER; MICRODAMAGE ACCUMULATION; BIOMECHANICAL PROPERTIES; DOG RIB; STRENGTH; CHILDREN; MICE; BISPHOSPHONATES; GROWTH; GENE AB Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by osteopenia and easy susceptibility to fracture. Symptoms are most prominent during childhood. Although antiresorptive bisphosphonates have been widely used to treat pediatric OI, controlled trials show improved vertebral parameters but equivocal effects on long-bone fracture rates. New treatments for OI are needed to increase bone mass throughout the skeleton. Sclerostin antibody (Scl-Ab) therapy is potently anabolic in the skeleton by stimulating osteoblasts via the canonical wnt signaling pathway, and may be beneficial for treating OI. In this study, Scl-Ab therapy was investigated in mice heterozygous for a typical OI-causing Gly -> Cys substitution in col1a1. Two weeks of Scl-Ab successfully stimulated osteoblast bone formation in a knock-in model for moderately severe OI (Brtl/+) and in WT mice, leading to improved bone mass and reduced long-bone fragility. Image-guided nanoindentation revealed no alteration in local tissue mineralization dynamics with Scl-Ab. These results contrast with previous findings of antiresorptive efficacy in OI both in mechanism and potency of effects on fragility. In conclusion, short-term Scl-Ab was successfully anabolic in osteoblasts harboring a typical OI-causing collagen mutation and represents a potential new therapy to improve bone mass and reduce fractures in pediatric OI. (C) 2013 American Society for Bone and Mineral Research. C1 [Sinder, Benjamin P.; Eddy, Mary M.; Caird, Michelle S.; Kozloff, Kenneth M.] Univ Michigan, Orthopaed Res Labs, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA. [Sinder, Benjamin P.; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. [Ominsky, Michael S.] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA. [Marini, Joan C.] NICHHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD 20892 USA. RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM kenkoz@umich.edu FU Intramural NIH HHS [ZIA HD008830-04]; NIAMS NIH HHS [R01 AR062522] NR 37 TC 47 Z9 48 U1 2 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2013 VL 28 IS 1 BP 73 EP 80 DI 10.1002/jbmr.1717 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 092EY UT WOS:000315103200008 PM 22836659 ER PT J AU Zanuy, D Sayago, FJ Revilla-Lopez, G Ballano, G Agemy, L Kotamraju, VR Jimenez, AI Cativiela, C Nussinov, R Sawvel, AM Stucky, G Ruoslahti, E Aleman, C AF Zanuy, David Sayago, Francisco J. Revilla-Lopez, Guillem Ballano, Gema Agemy, Lilach Kotamraju, Venkata Ramana Jimenez, Ana I. Cativiela, Carlos Nussinov, Ruth Sawvel, April M. Stucky, Galen Ruoslahti, Erkki Aleman, Carlos TI Engineering strategy to improve peptide analogs: from structure-based computational design to tumor homing SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE Computational design; Bioactive conformation dynamics; Tumor-homing peptide; Peptide synthesis; Tumor growth inhibitors ID ALPHA-AMINO-ACIDS; SOLID-PHASE SYNTHESIS; STEREOSELECTIVE-SYNTHESIS; RECEPTOR ANTAGONISTS; MOLECULAR-DYNAMICS; HIGHLY POTENT; INHIBITORS; PENTAPEPTIDE; CONFORMATION; SIMULATION AB We present a chemical strategy to engineer analogs of the tumor-homing peptide CREKA (Cys-Arg-Glu-Lys-Ala), which binds to fibrin and fibrin-associated clotted plasma proteins in tumor vessels (Simberg et al. in Proc Natl Acad Sci USA 104:932-936, 2007) with improved ability to inhibit tumor growth. Computer modeling using a combination of simulated annealing and molecular dynamics were carried out to design targeted replacements aimed at enhancing the stability of the bioactive conformation of CREKA. Because this conformation presents a pocket-like shape with the charged groups of Arg, Glu and Lys pointing outward, non-proteinogenic amino acids alpha-methyl and N-methyl derivatives of Arg, Glu and Lys were selected, rationally designed and incorporated into CREKA analogs. The stabilization of the bioactive conformation predicted by the modeling for the different CREKA analogs matched the tumor fluorescence results, with tumor accumulation increasing with stabilization. Here we report the modeling, synthetic procedures, and new biological assays used to test the efficacy and utility of the analogs. Combined, our results show how studies based on multi-disciplinary collaboration can converge and lead to useful biomedical advances. C1 [Zanuy, David; Revilla-Lopez, Guillem; Aleman, Carlos] Univ Politecn Cataluna, ETSEIB, Dept Chem Engn, E-08028 Barcelona, Spain. [Sayago, Francisco J.; Ballano, Gema; Jimenez, Ana I.; Cativiela, Carlos] Univ Zaragoza, Dept Organ Chem, ISQCH, CSIC, E-50009 Zaragoza, Spain. [Agemy, Lilach; Kotamraju, Venkata Ramana; Ruoslahti, Erkki] Univ Calif Santa Barbara, Burnham Inst Med Res, Sanford Burnham Med Res Inst, Ctr Nanomed, Santa Barbara, CA 93106 USA. [Nussinov, Ruth] NCI, SAIC Frederick Inc, Ctr Canc Res, Basic Sci Program,Nanobiol Program, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. [Sawvel, April M.; Stucky, Galen] Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. [Ruoslahti, Erkki] Sanford Burnham Med Res Inst, Ctr Canc, La Jolla, CA 92037 USA. [Aleman, Carlos] Univ Politecn Cataluna, Ctr Res Nanoengn, E-08028 Barcelona, Spain. RP Zanuy, D (reprint author), Univ Politecn Cataluna, ETSEIB, Dept Chem Engn, Diagonal 647, E-08028 Barcelona, Spain. EM david.zanuy@upc.edu; carlos.aleman@upc.edu RI Zanuy, David/G-3930-2014 OI Zanuy, David/0000-0001-7704-2178 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research; MICINN; FEDER [MAT2009-09138, CTQ2010-17436]; Generalitat de Catalunya [2009 SGR 925, XRQTC]; Gobierno de Aragon-FSE [E-40]; Generalitat de Catalunya; NIH/NCI [5 P30 CA30199-28]; DOD/CDMRP [W81XWH-10-1-0199] FX Computer resources were generously provided by the Centre de Supercomputacio de Catalunya (CESCA), the Barcelona Supercomputing Center-Centro Nacional de Supecomputacion (BSC-CNS), the National Cancer Institute for partial allocation of computing time and staff support at the Advanced Biomedical Computing Center of the Frederick Cancer Research and Development Center and the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD(http://biowulf.nih.gov). This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the view of the policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government. This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The work developed by the Spanish groups has been supported by MICINN and FEDER (MAT2009-09138 and CTQ2010-17436), by the Generalitat de Catalunya (research group 2009 SGR 925 and XRQTC), and Gobierno de Aragon-FSE (research group E-40). Support for the research of C. A. was received through the prize "ICREA Academia" for excellence in research funded by the Generalitat de Catalunya. Research in the Ruoslahti laboratory is supported by grants from the NIH/NCI 5 P30 CA30199-28, awarded to the Sanford-Burnham Medical Research Institute, Cancer Center, and a DOD/CDMRP grant W81XWH-10-1-0199. NR 48 TC 5 Z9 5 U1 1 U2 27 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD JAN PY 2013 VL 27 IS 1 BP 31 EP 43 DI 10.1007/s10822-012-9623-5 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 091JK UT WOS:000315045400003 PM 23239171 ER PT J AU Kantovitz, KR Pascon, FM Nociti, FH Tabchoury, CPM Puppin-Rontani, RM AF Kantovitz, Kamila Rosamilia Pascon, Fernanda Miori Nociti, Francisco Humberto, Jr. Machado Tabchoury, Cinthia P. Puppin-Rontani, Regina Maria TI Inhibition of enamel mineral loss by fissure sealant: An in situ study SO JOURNAL OF DENTISTRY LA English DT Article DE Dental enamel; Dental caries; In situ model; Occlusal surface; Sealants; Tooth remineralization; White spots ID SCHREGER BAND PATTERNS; LESIONS; CARIES; DEMINERALIZATION; FLUORIDE; RESTORATIONS; DENTISTRY; COMPOSITE; SUCROSE; MICRORADIOGRAPHY AB Objectives: This study evaluated the effect of fluoride and non-fluoride sealants on hardness decrease (HD) and marginal adaptation (MA) on enamel substrates after cariogenic challenge. Methods: Occlusal enamel blocks, from human third molars, were randomly divided into six groups (n = 12), according to occlusal fissures condition (S - sound; C - caries-like lesion; CF - caries-like lesion + topical fluoride) and sealants (F - FluroShield; H - Helioseal Clear Chroma). Lesion depths were 79.3 +/- 33.9 and 61.3 +/- 23.9 for C and CF groups, respectively. Sealants were placed on occlusal surface and stored at 100% humidity (37 degrees C; 24 h/d). HD was measured by cross-sectional microhardness analysis at the sealant margin distances: -1 (under sealant), 0 (sealant margin), 1, 2 (outer sealant). Sealant MA was observed by polarized light microscopy and scored according to: 0 - failure (no sealant MA or total sealant loss); 1 - success (sealant MA present). MA and HD were analysed by ANOVA-R and mixed model analysis, respectively. Results: For HD (Delta S), F values (6900.5 +/- 3686.6) were significantly lower than H values (8534.6 +/- 5375.3) regardless of enamel substrates and sealant margin distances. Significant differences were observed among sealant margin distances: -1 (5934.0 +/- 3282.6) < 0 (8701.5 +/- 6175.7) = 1 (8473.2 +/- 4299.4) = 2 (7761.5 +/- 4035.1), regardless of sealant and substrate. MA was similar for all groups (p >= 0.05). Conclusion: MA was not affected by sealant type or substrate condition, whereas enamel HD was favourably impacted by fluoride in the sealant. In addition, sealants were more effective as a physical barrier than as its chemical potency in reducing enamel HD. Clinical significance: Sealing with a fluoride material is a recommended procedure to prevent caries of occlusal permanent molars in high-caries-risk patients, even though those exhibiting white spot lesions, since the enamel hardness decrease when fluoride sealant was used in vitro. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kantovitz, Kamila Rosamilia; Nociti, Francisco Humberto, Jr.] NIAMS, NIH Natl Inst Hlth, Natl Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD USA. [Pascon, Fernanda Miori; Puppin-Rontani, Regina Maria] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Pediat Dent, BR-13414900 Piracicaba, SP, Brazil. [Nociti, Francisco Humberto, Jr.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Prosthodont & Periodont, BR-13414900 Piracicaba, SP, Brazil. [Machado Tabchoury, Cinthia P.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Physiol Sci, BR-13414900 Piracicaba, SP, Brazil. RP Puppin-Rontani, RM (reprint author), Univ Estadual Campinas, Piracicaba Dent Sch, Dept Pediat Dent, Av Limeira 901, BR-13414900 Piracicaba, SP, Brazil. EM rmpuppin@fop.unicamp.br RI Kantovitz, Kamila/J-4567-2013; Nociti, Francisco/G-4907-2015 OI Kantovitz, Kamila/0000-0003-2045-7924; FU FAPESP - Sao Paulo Research Support Foundation [05/60595-1] FX The authors are grateful to the Department of Pediatric Dentistry and Physiologic Sciences - Cariology Division, State University of Campinas, Piracicaba Dental School. Specifically our thanks extend to Mr. Marcelo Correa Maistro, Mr. Waldomiro Vieira, Ms. ElieneOrsini Romani, Dr. Renata Andrea Salvitti de Sa Rocha, and Norman Schiff for their cooperation and assistance. This research was supported by FAPESP - Sao Paulo Research Support Foundation (grant # 05/60595-1). NR 41 TC 6 Z9 7 U1 1 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0300-5712 J9 J DENT JI J. Dent. PD JAN PY 2013 VL 41 IS 1 BP 42 EP 50 DI 10.1016/j.jdent.2012.09.015 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 088YO UT WOS:000314874000007 PM 23044387 ER PT J AU Wu, WM Chen, ZC Cheng, NQ Watts, NR Stahl, SJ Farci, P Purcell, RH Wingfield, PT Steven, AC AF Wu, Weimin Chen, Zhaochun Cheng, Naiqian Watts, Norman R. Stahl, Stephen J. Farci, Patrizia Purcell, Robert H. Wingfield, Paul T. Steven, Alasdair C. TI Specificity of an anti-capsid antibody associated with Hepatitis B Virus-related acute liver failure SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Cryo-electron microscopy; Three-dimensional image reconstruction; Monoclonal antibody; Conformational epitope; Fulminant hepatitis ID CORE ANTIGEN; FULMINANT-HEPATITIS; ELECTRON-MICROSCOPY; CRYO-EM; RESOLUTION; PROTEIN; BINDING; EPITOPE; DIVERSITY; SYSTEM AB Previously, the livers of patients suffering from acute liver failure (ALF), a potentially fatal syndrome arising from infection by Hepatitis B Virus (HBV), were found to contain massive amounts of an antibody specific for the core antigen (HBcAg) capsid. We have used cryo-electron microscopy and molecular modeling to define its epitope. HBV capsids are icosahedral shells with 25 angstrom-long dimeric spikes, each a 4-helix bundle, protruding from the contiguous "floor". Of the anti-HBcAg antibodies previously characterized, most bind around the spike tip while one binds to the floor. The ALF-associated antibody binds tangentially to a novel site on the side of the spike. This epitope is conformational. The Fab binds with high affinity to its principal determinants but has lower affinities for quasi-equivalent variants. The highest occupancy site is on one side of a spike, with no detectable binding to the corresponding site on the other side. Binding of one Fab per dimer was also observed by analytical ultracentrifugation. The Fab did not bind to the e-antigen dimer, a non-assembling variant of capsid protein. These findings support the propositions that antibodies with particular specificities may correlate with different clinical expressions of HBV infection and that antibodies directed to particular HBcAg epitopes may be involved in ALF pathogenesis. Published by Elsevier Inc. C1 [Wu, Weimin; Cheng, Naiqian; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. [Chen, Zhaochun; Farci, Patrizia; Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Watts, Norman R.; Stahl, Stephen J.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, 50 South Dr,Rm 1517, Bethesda, MD 20892 USA. EM stevena@mail.nih.gov FU intramural research program of NIAMS; intramural research program of NIAID FX We thank Dr. Giovanni Cardone for guidance on labeling simulations, Ms. Liane Agulto for preparing the E1 Fabs, and Dr. Clinton Leysath for determining their KD. This research was supported by the intramural research programs of NIAMS and NIAID. NR 32 TC 11 Z9 12 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2013 VL 181 IS 1 BP 53 EP 60 DI 10.1016/j.jsb.2012.10.004 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 073XH UT WOS:000313775900006 PM 23079477 ER PT J AU Singleton, AB Farrer, MJ Bonifati, V AF Singleton, Andrew B. Farrer, Matthew J. Bonifati, Vincenzo TI The Genetics of Parkinson's Disease: Progress and Therapeutic Implications SO MOVEMENT DISORDERS LA English DT Review DE genetics; Parkinson's disease; therapeutics ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; HEXANUCLEOTIDE REPEAT; RISK-FACTORS; MUTATIONS; LRRK2; MITOPHAGY; PATHOLOGY; VARIANTS; GENOTYPE AB The past 15 years has witnessed tremendous progress in our understanding of the genetic basis for Parkinson's disease (PD). Notably, whereas most mutations, such as those in SNCA, PINK1, PARK2, PARK7, PLA2G6, FBXO7, and ATP13A2, are a rare cause of disease, one particular mutation in LRRK2 has been found to be common in certain populations. There has been considerable progress in finding risk loci. To date, approximately 16 such loci exist; notably, some of these overlap with the genes known to contain disease-causing mutations. The identification of risk alleles has relied mostly on the application of revolutionary technologies; likewise, second-generation sequencing methods have facilitated the identification of new mutations in PD. These methods will continue to provide novel insights into PD. The utility of genetics in therapeutics relies primarily on leveraging findings to understand the pathogenesis of PD. Much of the investigation into the biology underlying PD has used these findings to define a pathway, or pathways, to pathogenesis by trying to fit disparate genetic defects onto the same network. This work has had some success, particularly in the context of monogenic disease, and is beginning to provide clues about potential therapeutic targets. Approaches toward therapies are also being provided more directly by genetics, notably by the reduction and clearance of alpha-synuclein and inhibition of Lrrk2 kinase activity. We believe this has been an exciting, productive time for PD genetics and, furthermore, that genetics will continue to drive the etiologic understanding and etiology-based therapeutic approaches in this disease. (C) 2012 Movement Disorder Society C1 [Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Farrer, Matthew J.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Bonifati, Vincenzo] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. RP Singleton, AB (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A1014,35 Convent Dr, Bethesda, MD 20892 USA. EM singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000949-06]; "Internationaal Parkinson Fonds," The Netherlands; Netherlands Organization for Scientific Research (NWO) FX This work was supported, in part, by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services (project no.: Z01 AG000949-06). This study was supported by grants from the "Internationaal Parkinson Fonds," The Netherlands, and the Netherlands Organization for Scientific Research (NWO, VIDI grant; to V.B.). NR 81 TC 129 Z9 135 U1 5 U2 67 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN PY 2013 VL 28 IS 1 SI SI BP 14 EP 23 DI 10.1002/mds.25249 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 090QY UT WOS:000314995300004 PM 23389780 ER PT J AU Yauk, CL Argueso, JL Auerbach, SS Awadalla, P Davis, SR DeMarini, DM Douglas, GR Dubrova, YE Elespuru, RK Glover, TW Hales, BF Hurles, ME Klein, CB Lupski, JR Manchester, DK Marchetti, F Montpetit, A Mulvihill, JJ Robaire, B Robbins, WA Rouleau, GA Shaughnessy, DT Somers, CM Taylor, JG Trasler, J Waters, MD Wilson, TE Witt, KL Bishop, JB AF Yauk, Carole Lyn Argueso, J. Lucas Auerbach, Scott S. Awadalla, Philip Davis, Sean R. DeMarini, David M. Douglas, George R. Dubrova, Yuri E. Elespuru, Rosalie K. Glover, Thomas W. Hales, Barbara F. Hurles, Matthew E. Klein, Catherine B. Lupski, James R. Manchester, David K. Marchetti, Francesco Montpetit, Alexandre Mulvihill, John J. Robaire, Bernard Robbins, Wendie A. Rouleau, Guy A. Shaughnessy, Daniel T. Somers, Christopher M. Taylor, James G. Trasler, Jacquetta Waters, Michael D. Wilson, Thomas E. Witt, Kristine L. Bishop, Jack B. TI Harnessing genomics to identify environmental determinants of heritable disease SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Editorial Material DE Germ cell; Heritable mutation; Next generation sequencing; Copy number variants ID GERM-CELL MUTAGENS; ANTICANCER DRUGS; MUTATION-RATES; AIR-POLLUTION; VARIANTS; EXPOSURE; SPECTRUM; TOBACCO; HUMANS; SMOKE AB Next-generation sequencing technologies can now be used to directly measure heritable de novo DNA sequence mutations in humans. However, these techniques have not been used to examine environmental factors that induce such mutations and their associated diseases. To address this issue, a working group on environmentally induced germline mutation analysis (ENIGMA) met in October 2011 to propose the necessary foundational studies, which include sequencing of parent-offspring trios from highly exposed human populations, and controlled dose-response experiments in animals. These studies will establish background levels of variability in germline mutation rates and identify environmental agents that influence these rates and heritable disease. Guidance for the types of exposures to examine come from rodent studies that have identified agents such as cancer chemotherapeutic drugs, ionizing radiation, cigarette smoke, and air pollution as germ-cell mutagens. Research is urgently needed to establish the health consequences of parental exposures on subsequent generations. Published by Elsevier B.V. C1 [Yauk, Carole Lyn; Douglas, George R.; Marchetti, Francesco] Hlth Canada, Toronto, ON, Canada. [Argueso, J. Lucas] Colorado State Univ, Ft Collins, CO 80523 USA. [Awadalla, Philip; Rouleau, Guy A.] Univ Montreal, Montreal, PQ H3C 3J7, Canada. [Davis, Sean R.] NIH, Bethesda, MD 20892 USA. [Dubrova, Yuri E.] Univ Leicester, Leicester LE1 7RH, Leics, England. [Elespuru, Rosalie K.] US FDA, Rockville, MD 20857 USA. [Glover, Thomas W.; Wilson, Thomas E.] Univ Michigan, Ann Arbor, MI 48109 USA. [Hales, Barbara F.; Montpetit, Alexandre; Robaire, Bernard; Trasler, Jacquetta] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Hurles, Matthew E.] Wellcome Trust Sanger Inst, Hinxton, England. [Klein, Catherine B.] NYU, Sch Med, New York, NY 10003 USA. [Lupski, James R.] Baylor Coll Med, Houston, TX 77030 USA. [Manchester, David K.] Childrens Hosp Colorado, Aurora, CO USA. [Mulvihill, John J.] Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. [Robbins, Wendie A.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Somers, Christopher M.] Univ Regina, Regina, SK S4S 0A2, Canada. [Taylor, James G.] NHLBI, Bethesda, MD 20892 USA. RP Yauk, CL (reprint author), Hlth Canada, Toronto, ON, Canada. EM carole.yauk@hc-sc.gc.ca OI Argueso, Juan Lucas/0000-0002-7157-1519; Dubrova, Yuri/0000-0001-5281-7539; Marchetti, Francesco/0000-0002-9435-4867; Yauk, Carole/0000-0003-4919-876X; Davis, Sean/0000-0002-8991-6458; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL006160-01] NR 30 TC 8 Z9 8 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD JAN-MAR PY 2013 VL 752 IS 1 BP 6 EP 9 DI 10.1016/j.mrrev.2012.08.002 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 091TN UT WOS:000315072800002 PM 22935230 ER PT J AU Wen, H Wolfe, DE Gomella, AA Miao, HX Xiao, XH Liu, CA Lynch, SK Morgan, N AF Wen, Han Wolfe, Douglas E. Gomella, Andrew A. Miao, Houxun Xiao, Xianghui Liu, Chian Lynch, Susanna K. Morgan, Nicole TI Interferometric hard x-ray phase contrast imaging at 204 nm grating period SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID FABRICATION AB We report on hard x-ray phase contrast imaging experiments using a grating interferometer of approximately 1/10th the grating period achieved in previous studies. We designed the gratings as a staircase array of multilayer stacks which are fabricated in a single thin film deposition process. We performed the experiments at 19 keV x-ray energy and 0.8 mu m pixel resolution. The small grating period resulted in clear separation of different diffraction orders and multiple images on the detector. A slitted beam was used to remove overlap of the images from the different diffraction orders. The phase contrast images showed detailed features as small as 10 mu m, and demonstrated the feasibility of high resolution x-ray phase contrast imaging with nanometer scale gratings. (C) 2013 American Institute of Physics. [http://dx.doi.org/10.1063/1.4788910] C1 [Wen, Han; Gomella, Andrew A.; Miao, Houxun; Lynch, Susanna K.] NHLBI, Imaging Phys Lab, Biophys & Biochem Ctr, NIH, Bethesda, MD 20892 USA. [Wolfe, Douglas E.] Penn State Univ, Appl Res Lab, State Coll, PA 16804 USA. [Xiao, Xianghui; Liu, Chian] Argonne Natl Lab, Adv Photon Source, Xray Sci Div, Argonne, IL 60439 USA. [Morgan, Nicole] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, Imaging Phys Lab, Biophys & Biochem Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Miao, Houxun/N-8233-2013; Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 FU Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health [HL006143-01]; US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-06CH11357] FX We thank Eric Bennett and Dr. Dumitru Mazilu of the National Institutes of Health (NIH) for their assistance with grating fabrication and imager assembly. We thank Cliff Sonnenbrot and Dr. Alan Michelson of NIH for assistance with fruit flies. The grating substrates were made at the Nanofab Facility of the National Institute of Standards and Technology. The work was funded by the Division of Intramural Research, National Heart, Lung and Blood Institute, National Institutes of Health, under Project No. HL006143-01. Use of the Advanced Photon Source at Argonne National Laboratory was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. NR 22 TC 5 Z9 5 U1 0 U2 19 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD JAN PY 2013 VL 84 IS 1 AR 013706 DI 10.1063/1.4788910 PG 5 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 086ZH UT WOS:000314729100029 PM 23387658 ER PT J AU Sano, K Nakajima, T Choyke, PL Kobayashi, H AF Sano, Kohei Nakajima, Takahito Choyke, Peter L. Kobayashi, Hisataka TI Markedly Enhanced Permeability and Retention Effects Induced by Photo-immunotherapy of Tumors SO ACS NANO LA English DT Article DE drug delivery; super-enhanced permeability and retention effect; photoimmunotherapy; nanomaterials; cancer imaging; cancer therapy ID CONTRAST AGENTS; SOLID TUMORS; CANCER; CARCINOMA; THERAPY; THERAPEUTICS; CHEMOTHERAPY; DELIVERY AB A major barrier to cancer treatment is the inability to deliver sufficient concentrations of drug to the tumor without incurring systemic toxicities. Nanomaterials are appealing because they can carry a large drug payload; however, tumor delivery is limited by modest leakage and retention in most tumors. We observed that after photoimmunotherapy (PIT), which is a light-mediated treatment based on an antibody photosensitizer conjugate, there was surprisingly high leakage of nanosized (10-200 nm) agents into the tumor bed. PIT rapidly Induced death in perivascular cancer cells, leading to immediate and dramatic increases in vascular permeability, resulting in up to 24-fold greater accumulation of nanomaterials within the PIT-treated tumor compared with controls, an effect termed "super-enhanced permeability and retention". In a treatment study, PIT followed by liposome-containing daunorubicin, DaunoXome (diameter 50 nm), resulted in greater survival In tumor-bearing mice than either PIT or DaunoXome alone. Thus, PIT greatly enhances delivery of nanosized reagents and thus holds promise to improve therapeutic responses. C1 [Sano, Kohei; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 26 TC 60 Z9 60 U1 8 U2 63 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD JAN PY 2013 VL 7 IS 1 BP 717 EP 724 DI 10.1021/nn305011p PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 078FB UT WOS:000314082800076 PM 23214407 ER PT J AU Chan, YM Bailey, R O'Connor, DL AF Chan, Yen-Ming Bailey, Regan O'Connor, Deborah L. TI Folate SO ADVANCES IN NUTRITION LA English DT Editorial Material ID FOLIC-ACID INTAKE; SUPPLEMENTS; RISK; FORTIFICATION; PREVALENCE; PREGNANCY; CANCER; SERUM C1 [Chan, Yen-Ming; O'Connor, Deborah L.] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Chan, Yen-Ming; O'Connor, Deborah L.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. [Bailey, Regan] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP O'Connor, DL (reprint author), Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. EM deborah_l.oconnor@sickkids.ca NR 15 TC 4 Z9 4 U1 0 U2 9 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 J9 ADV NUTR JI Adv. Nutr. PD JAN PY 2013 VL 4 IS 1 BP 123 EP 125 DI 10.3945/an.112003392 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 082FG UT WOS:000314377100014 PM 23319130 ER PT J AU Zimerman, M Nitsch, M Giraux, P Gerloff, C Cohen, LG Hummel, FC AF Zimerman, Maximo Nitsch, Marie Giraux, Pascal Gerloff, Christian Cohen, Leonardo G. Hummel, Friedhelm C. TI Neuroenhancement of the Aging Brain: Restoring Skill Acquisition in Old Subjects SO ANNALS OF NEUROLOGY LA English DT Article ID DIRECT-CURRENT STIMULATION; NONINVASIVE CORTICAL STIMULATION; PRIMARY MOTOR CORTEX; PLASTICITY; CONSOLIDATION; EXCITABILITY; MODULATION; MEMORY AB Objective: Decline in cognitive functions, including impaired acquisition of novel skills, is a feature of older age that impacts activities of daily living, independence, and integration in modern societies. Methods: We tested whether the acquisition of a complex motor skill can be enhanced in old subjects by the application of transcranial direct current stimulation (tDCS) to the motor cortex. Results: The main finding was that old participants experienced substantial improvements when training was applied concurrent with tDCS, with effects lasting for at least 24 hours. Interpretation: These results suggest noninvasive brain stimulation as a promising and safe tool to potentially assist functional independence of aged individuals in daily life. ANN NEUROL 2013;73:10-15 C1 [Zimerman, Maximo; Nitsch, Marie; Gerloff, Christian; Hummel, Friedhelm C.] Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat Lab, D-20246 Hamburg, Germany. [Giraux, Pascal] Univ Hosp Ctr St Etienne, Bellevue Hosp, Dept Phys Med & Rehabil, St Etienne, France. [Giraux, Pascal] Univ Hosp Ctr St Etienne, Bellevue Hosp, Exercise Physiol Lab, St Etienne, France. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. RP Hummel, FC (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Brain Imaging & Neurostimulat BINS Lab, D-20246 Hamburg, Germany. EM f.hummel@uke.uni-hamburg.de FU German Academic Exchange Service [A/07/95990]; Alexander von Humboldt Foundation (Feodor-Lynen); Medical Research Fund of the University of Hamburg [NWF-04/07, NWF-11/09]; German Research Foundation [SFB 936-C4]; NIH; Foundation for Medical Research; Pfizer; Boehringer Ingelheim; Sanofi Aventis; Bayer Vital FX This research was supported by grants from the German Academic Exchange Service (A/07/95990, M.Z.), Alexander von Humboldt Foundation (Feodor-Lynen; F. C. H), Medical Research Fund of the University of Hamburg (NWF-04/07, F. C. H.; NWF-11/09, M.Z.), German Research Foundation (SFB 936-C4, F. C. H.), NIH clinical fellowship (P.G.), and Foundation for Medical Research (P.G.).; P.G.: paid educational presentations, Pfizer; travel expenses, Merz Pharmaceuticals. C. G.: consultancy, Boehringer Ingelheim, Lundbeck, Glaxo Smith Kline, Bayer Vital, UCB, EBS Technologies, Silk Road Medical, Sanofi Aventis; speaking fees, Boehringer Ingelheim, Sanofi Aventis, Bayer Vital, Pfizer. F. C. H.: consultancy, UCB, Lundbeck. NR 23 TC 60 Z9 60 U1 1 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2013 VL 73 IS 1 BP 10 EP 15 DI 10.1002/ana.23761 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 086CN UT WOS:000314660800006 PM 23225625 ER PT J AU Sepanlou, SG Etemadi, A Kamangar, F Sepehr, A Pourshams, A Poustchi, H Islami, F Sadjadi, A Nasrollahzadeh, D Semnani, S Saidi, F Abnet, CC Ponder, B Pharoah, PD Day, NE Brennan, P Boffetta, P Dawsey, SM Malekzadeh, R AF Sepanlou, Sadaf G. Etemadi, Arash Kamangar, Farin Sepehr, Alireza Pourshams, Akram Poustchi, Hossein Islami, Farhad Sadjadi, Alireza Nasrollahzadeh, Dariush Semnani, Shahryar Saidi, Farrokh Abnet, Christian C. Ponder, Bruce Pharoah, Paul D. Day, Nicholas E. Brennan, Paul Boffetta, Paolo Dawsey, Sanford M. Malekzadeh, Reza TI The Gastro-Esophageal Malignancies in Northern Iran Research Project: Impact on the Health Research and Health Care Systems in Iran SO ARCHIVES OF IRANIAN MEDICINE LA English DT Review DE Chronic disease; esophageal cancer; gastric cancer; gastroenterology; Iran; research design ID SQUAMOUS-CELL CARCINOMA; HIGH-RISK AREA; POLYCYCLIC AROMATIC-HYDROCARBONS; UPPER GASTROINTESTINAL CANCERS; RANDOMIZED CONTROLLED-TRIALS; ESOPHAGEAL CANCER; GOLESTAN COHORT; NORTHEASTERN IRAN; GASTRIC-CANCER; CHRONIC DISEASES AB Background: The Gastro-Esophageal Malignancies in Northern Iran (GEMINI) research project is an example of recent progress in health research in Iran. The original aim of this project was to identify etiologic factors and prevention measures for upper gastrointestinal cancers in Northern provinces of Iran, but its achievements have gone much beyond this initial goal. Methods: GEMINI consists of several projects including cancer registries, pilot studies, case-control studies, and the Gojestan Cohort Study. GEMINI has been conducted through extensive collaborations between the Digestive Disease Research Center of Tehran University of Medical Sciences with other domestic and international health organizations. The achievements of GEMINI include producing new knowledge, introducing new research methods, developing and expanding health research and health care infrastructures, investing in human resources, and increasing the awareness and knowledge of policy makers and officials at all levels about the importance of chronic diseases in Iran's health priorities. Conclusions: The success of GEMINI reveals the feasibility of large-scale health research studies in developing countries and serves as a successful model not only for health research in Iran, but also for similar research studies in other developing nations. C1 [Sepanlou, Sadaf G.; Etemadi, Arash; Kamangar, Farin; Pourshams, Akram; Poustchi, Hossein; Islami, Farhad; Sadjadi, Alireza; Nasrollahzadeh, Dariush; Saidi, Farrokh; Malekzadeh, Reza] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran. [Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA. [Sepehr, Alireza] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Islami, Farhad; Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. [Islami, Farhad; Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Nasrollahzadeh, Dariush] Karolinska Inst, Stockholm, Sweden. [Semnani, Shahryar] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran. [Ponder, Bruce; Pharoah, Paul D.; Day, Nicholas E.] Univ Cambridge, Cambridge, England. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, POB 1411713135, Tehran, Iran. EM dr.reza.malekzadeh@gmail.com RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; Sepanlou, Sadaf/H-9343-2016; Semnani, Shahryar/N-2270-2016; OI Abnet, Christian/0000-0002-3008-7843; Etemadi, Arash/0000-0002-3458-1072; Sepanlou, Sadaf/0000-0002-3669-5129; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 FU Intramural NIH HHS [ZIA CP000185-08] NR 82 TC 5 Z9 5 U1 0 U2 4 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 J9 ARCH IRAN MED JI Arch. Iran. Med. PD JAN PY 2013 VL 16 IS 1 BP 46 EP 53 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 083UF UT WOS:000314490000012 PM 23273237 ER PT J AU Bornstein, MH Hahn, CS Wolke, D AF Bornstein, Marc H. Hahn, Chun-Shin Wolke, Dieter TI Systems and Cascades in Cognitive Development and Academic Achievement SO CHILD DEVELOPMENT LA English DT Article ID DIFFICULTIES QUESTIONNAIRE; VISUAL HABITUATION; INTELLIGENCE; INFANT; PERFORMANCE; IQ; STRENGTHS; CHILDREN; DISHABITUATION; METAANALYSIS AB A large-scale (N = 552) controlled multivariate prospective 14-year longitudinal study of a developmental cascade embedded in a developmental system showed that information-processing efficiency in infancy (4 months), general mental development in toddlerhood (18 months), behavior difficulties in early childhood (36 months), psychometric intelligence in middle childhood (8 years), and maternal education either directly or indirectly (or both) contribute to academic achievement in adolescence (14 years). C1 [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Wolke, Dieter] Univ Warwick, Coventry CV4 7AL, W Midlands, England. RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockledge 1,Suite 8030,6705 Rockledge Dr,MSC 7971, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov RI Wolke, Dieter/C-5372-2008 OI Wolke, Dieter/0000-0003-0304-268X FU Intramural NIH HHS [Z01 HD001119-20]; Medical Research Council [, G9815508]; Wellcome Trust [092731] NR 52 TC 17 Z9 17 U1 3 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2013 VL 84 IS 1 BP 154 EP 162 DI 10.1111/j.1467-8624.2012.01849.x PG 9 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 078PQ UT WOS:000314112000012 PM 22974268 ER PT J AU DiGiovanna, JJ Mauro, T Milstone, LM Schmuth, M Toro, JR AF DiGiovanna, John J. Mauro, Theodora Milstone, Leonard M. Schmuth, Matthias Toro, Jorge R. TI Systemic retinoids in the management of ichthyoses and related skin types SO DERMATOLOGIC THERAPY LA English DT Review DE acitretin; ectropion; ichthyosis; isotretinoin; retinoid ID PITYRIASIS-RUBRA-PILARIS; HAILEY-HAILEY-DISEASE; RECESSIVE CONGENITAL ICHTHYOSIS; VITAMIN-A-DEFICIENCY; DARIERS-DISEASE; ERYTHROKERATODERMIA VARIABILIS; DOUBLE-BLIND; KID SYNDROME; EPIDERMOLYTIC HYPERKERATOSIS; GENETIC-HETEROGENEITY AB The term retinoid includes both natural and synthetic derivatives of vitamin A. Retinoid-containing treatments have been used since approximate to 1550BC by the early Egyptians. Treatment of ichthyosiform disorders with retinoids dates back at least to the 1930s. Early use of high-dose vitamin A demonstrated efficacy, but because vitamin A is stored in the liver, toxicity limited usefulness. Interest turned to synthetic retinoids in an effort to enhance efficacy and limit toxicity. Acetretin, isotretinoin and, in the past etretinate, have provided the most effective therapy for ichthyosiform conditions. They have been used for a variety of ages, including in newborns with severe ichthyosis and for decades in some patients. Careful surveillance and management of mucous membrane, laboratory, skeletal, and teratogenic side effects has made systemic retinoids the mainstay of therapy for ichthyosis and related skin types. C1 [DiGiovanna, John J.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Toro, Jorge R.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Mauro, Theodora] Univ Calif San Francisco, Dept Dermatol, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. [Mauro, Theodora] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Milstone, Leonard M.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Schmuth, Matthias] Med Univ Innsbruck, Dept Dermatol & Venereol, A-6020 Innsbruck, Austria. [Toro, Jorge R.] Washington DC Vet Adm Med Ctr, Dept Dermatol, Washington, DC USA. RP DiGiovanna, JJ (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM jdigiova@mail.nih.gov OI Schmuth, Matthias/0000-0002-4064-1334 FU Intramural Research Program of the NCI, NIH, Medical Research Fund Tirol [MFF71, MFF153]; Austrian Science Fund [FWF J1901-MED, J2112-MED, P16990-B05]; European Cooperation in Science and Technology [COST Action BM0903] FX This research was supported in part by the Intramural Research Program of the NCI, NIH, Medical Research Fund Tirol (MFF71, MFF153), the Austrian Science Fund (FWF J1901-MED, J2112-MED, P16990-B05), the European Cooperation in Science and Technology (COST Action BM0903)" NR 101 TC 15 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD JAN-FEB PY 2013 VL 26 IS 1 BP 26 EP 38 DI 10.1111/j.1529-8019.2012.01527.x PG 13 WC Dermatology SC Dermatology GA 086CX UT WOS:000314661900003 PM 23384018 ER PT J AU Pihoker, C Badaru, A Anderson, A Morgan, T Dolan, L Dabelea, D Imperatore, G Linder, B Marcovina, S Mayer-Davis, E Reynolds, K Klingensmith, GJ AF Pihoker, Catherine Badaru, Angela Anderson, Andrea Morgan, Timothy Dolan, Lawrence Dabelea, Dana Imperatore, Giuseppina Linder, Barbara Marcovina, Santica Mayer-Davis, Elizabeth Reynolds, Kristi Klingensmith, Georgeanna J. CA SEARCH Diabet Youth Study Grp TI Insulin Regimens and Clinical Outcomes in a Type 1 Diabetes Cohort The SEARCH for Diabetes in Youth study SO DIABETES CARE LA English DT Article ID CHILDREN; COMPLICATIONS; ADOLESCENTS; FREQUENCY; CARE AB OBJECTIVE-To examine the patterns and associations of insulin regimens and change in regimens with clinical outcomes in a diverse population of children with recently diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS-The study sample consisted of youth with type 1 diabetes who completed a baseline SEARCH for Diabetes in Youth study visit after being newly diagnosed and at least one follow-up visit. Demographic, diabetes self-management, physical, and laboratory measures were collected at study visits. Insulin regimens and change in regimen compared with the initial visit were categorized as more intensive (MI), no change (NC), or less intensive (LI). We examined relationships between insulin regimens, change in regimen, and outcomes including A1C and fasting C-peptide. RESULTS-Of the 1,606 participants with a mean follow-up of 36 months, 51.7% changed to an MI regimen, 44.7% had NC, and 3.6% changed to an LI regimen. Participants who were younger, non-Hispanic white, and from families of higher income and parental education and who had private health insurance were more likely to be in MI or NC groups. Those in MI and NC groups had lower baseline A1C (P = 0.028) and smaller increase in A1C over time than LI (P < 0.01). Younger age, continuous subcutaneous insulin pump therapy, and change to MI were associated with higher probability of achieving target A1C levels. CONCLUSIONS-Insulin regimens were intensified over time in over half of participants but varied by sociodemographic domains. As more intensive regimens were associated with better outcomes, early intensification of management may improve outcomes in all children with diabetes. Although intensification of insulin regimen is preferred, choice of insulin regimen must be individualized based on the child and family's ability to comply with the prescribed plan. Diabetes Care 36: 27-33, 2013 C1 [Pihoker, Catherine; Badaru, Angela] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Anderson, Andrea; Morgan, Timothy] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat, Winston Salem, NC USA. [Dolan, Lawrence] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp, Cincinnati, OH USA. [Dabelea, Dana] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Imperatore, Giuseppina] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA. [Marcovina, Santica] Univ Washington, Dept Med, Seattle, WA USA. [Mayer-Davis, Elizabeth] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Mayer-Davis, Elizabeth] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Reynolds, Kristi] Kaiser Permanente So Calif, Dept Res & Evaluat, Pasadena, CA USA. [Klingensmith, Georgeanna J.] Univ Colorado Denver, Sch Med, Barbara Davis Ctr, Aurora, CO USA. [Klingensmith, Georgeanna J.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. RP Pihoker, C (reprint author), Univ Washington, Dept Pediat, Seattle, WA 98195 USA. EM catherine.pihoker@seattlechildrens.org FU Centers for Disease Control and Prevention [00097, DP-05-069, DP-10-001]; National Institute of Diabetes and Digestive and Kidney Diseases; Kaiser Permanente Southern California [U48/CCU919219, U01 DP000246, U18DP002714]; University of Colorado Denver [U48/CCU819241-3, U01 DP000247, U18DP000247-06A1]; Kuakini Medical Center [U58CCU919256, U01 DP000245]; Children's Hospital Medical Center (Cincinnati) [U48/CCU519239, U01 DP000248, 1U18DP002709]; University of North Carolina at Chapel Hill [U48/CCU419249, U01 DP000254, U18DP002708-01]; University of Washington School of Medicine [U58/CCU019235-4, U01 DP000244, U18DP002710-01]; Wake Forest University School of Medicine [U48/CCU919219, U01 DP000250, 200-2010-35171]; National Institutes of Health/National Center for Research Resources [UL1RR029882]; Children's Hospital and Regional Medical Center [M01RR00037]; Colorado Pediatric General Clinical Research Center [M01 RR00069]; Barbara Davis Center at the University of Colorado at Denver [DERC NIH P30 DK57516]; Institutional Clinical and Translational Science Award, National Institutes of Health/National Center for Research Resources, at the University of Cincinnati [1UL1RR026314-01] FX SEARCH for Diabetes in Youth is funded by the Centers for Disease Control and Prevention (PA nos. 00097, DP-05-069, and DP-10-001) and supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Site contract nos. are as follows: Kaiser Permanente Southern California (U48/CCU919219, U01 DP000246, and U18DP002714), University of Colorado Denver (U48/CCU819241-3, U01 DP000247, and U18DP000247-06A1), Kuakini Medical Center (U58CCU919256 and U01 DP000245), Children's Hospital Medical Center (Cincinnati) (U48/CCU519239, U01 DP000248, and 1U18DP002709), University of North Carolina at Chapel Hill (U48/CCU419249, U01 DP000254, and U18DP002708-01), University of Washington School of Medicine (U58/CCU019235-4, U01 DP000244, and U18DP002710-01), and Wake Forest University School of Medicine (U48/CCU919219, U01 DP000250, and 200-2010-35171). The authors acknowledge the involvement of general clinical research centers at the South Carolina Clinical & Translational Research Institute, Medical University of South Carolina (National Institutes of Health/National Center for Research Resources Grant UL1RR029882); Children's Hospital and Regional Medical Center (Grant M01RR00037); Colorado Pediatric General Clinical Research Center (Grant M01 RR00069) and the Barbara Davis Center at the University of Colorado at Denver (DERC NIH P30 DK57516); and the Institutional Clinical and Translational Science Award, National Institutes of Health/National Center for Research Resources, at the University of Cincinnati (grant 1UL1RR026314-01). NR 15 TC 18 Z9 19 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 IS 1 BP 27 EP 33 DI 10.2337/dc12-0720 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LP UT WOS:000314465700027 PM 22961571 ER PT J AU Espeland, MA Bryan, RN Goveas, JS Robinson, JG Siddiqui, MS Liu, SM Hogan, PE Casanova, R Coker, LH Yaffe, K Masaki, K Rossom, R Resnick, SM AF Espeland, Mark A. Bryan, R. Nick Goveas, Joseph S. Robinson, Jennifer G. Siddiqui, Mustafa S. Liu, Simin Hogan, Patricia E. Casanova, Ramon Coker, Laura H. Yaffe, Kristine Masaki, Kamal Rossom, Rebecca Resnick, Susan M. CA WHIMS-MRI Study Grp TI Influence of Type 2 Diabetes on Brain Volumes and Changes in Brain Volumes Results from the Women's Health Initiative Magnetic Resonance Imaging Studies SO DIABETES CARE LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER LESIONS; WHIMS-MRI; ALZHEIMER-DISEASE; ACCORD-MIND; MELLITUS; ATROPHY; MEMORY; PROGRESSION AB OBJECTIVE-To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function. RESEARCH DESIGN AND METHODS-Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 7289 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Crosssectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined. RESULTS-The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in graymatter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits. CONCLUSIONS-Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetesrelated deficits in cognitive function. Diabetes Care 36: 9097, 2013 C1 [Espeland, Mark A.; Hogan, Patricia E.; Casanova, Ramon] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Bryan, R. Nick] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. [Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol, Div Cardiol, Iowa City, IA USA. [Robinson, Jennifer G.] Univ Iowa, Dept Med, Div Cardiol, Iowa City, IA 52242 USA. [Siddiqui, Mustafa S.] Wake Forest Sch Med, Dept Neurol, Winston Salem, NC USA. [Liu, Simin] Univ Calif Los Angeles, Ctr Metab Dis Prevent, Los Angeles, CA USA. [Coker, Laura H.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Masaki, Kamal] Univ Hawaii Manoa, Dept Geriatr Med, Honolulu, HI 96822 USA. [Rossom, Rebecca] Hlth Partners Res Fdn, Bloomington, MN USA. [Resnick, Susan M.] NIA, Lab Behav Neurosci, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Espeland, MA (reprint author), Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. EM mespelan@wakehealth.edu RI Liu, Simin/I-3689-2014; Siddiqui, Mustafa/L-5495-2013 OI Liu, Simin/0000-0003-2098-3844; Siddiqui, Mustafa/0000-0003-4794-5119 FU National Heart, Lung, and Blood Institute of the National Institutes of Health, U.S. Department of Health and Human Services; Intramural Research Program, National Institute on Aging, National Institutes of Health; Wyeth Pharmaceuticals, Inc, St. Davids, PA; [HHSN-268200464221C]; [N01-WH-4-4221] FX The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health, U.S. Department of Health and Human Services. Contracts HHSN-268200464221C and N01-WH-4-4221 provided additional support. S. M. R. is supported by the Intramural Research Program, National Institute on Aging, National Institutes of Health. The Women's Health Initiative Memory Study was funded in part by Wyeth Pharmaceuticals, Inc, St. Davids, PA. No other potential conflicts of interest relevant to this article were reported. NR 40 TC 39 Z9 41 U1 1 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 IS 1 BP 90 EP 97 DI 10.2337/dc12-0555 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LP UT WOS:000314465700036 PM 22933440 ER PT J AU Peake, MJ Bruns, DE Sacks, DB Horvath, AR AF Peake, Michael J. Bruns, David E. Sacks, David B. Horvath, Andrea R. TI It's Time for a Better Blood Collection Tube to Improve the Reliability of Glucose Results SO DIABETES CARE LA English DT Letter ID GLYCOLYSIS; STABILIZATION; FLUORIDE; SAMPLES C1 [Peake, Michael J.] Flinders Med Ctr, Dept Biochem, Bedford Pk, SA, Australia. [Bruns, David E.] Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. [Sacks, David B.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. [Horvath, Andrea R.] Univ Sydney, Sch Publ Hlth, Screening & Test Evaluat Program, Sydney, NSW 2006, Australia. [Horvath, Andrea R.] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Horvath, Andrea R.] Prince Wales Hosp, SEALS Dept Clin Chem, Sydney, NSW, Australia. RP Horvath, AR (reprint author), Univ Sydney, Sch Publ Hlth, Screening & Test Evaluat Program, Sydney, NSW 2006, Australia. EM rita.horvath@sesiahs.health.nsw.gov.au OI Sacks, David/0000-0003-3100-0735 NR 5 TC 14 Z9 14 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 IS 1 BP E2 EP E2 DI 10.2337/dc12-1312 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LP UT WOS:000314465700002 PM 23264303 ER PT J AU Preis, SR Pencina, MJ D'Agostino, RB Meigs, JB Vasan, RS Fox, CS AF Preis, Sarah Rosner Pencina, Michael J. D'Agostino, Ralph B., Sr. Meigs, James B. Vasan, Ramachandran S. Fox, Caroline S. TI Neck Circumference and the Development of Cardiovascular Disease Risk Factors in the Framingham Heart Study SO DIABETES CARE LA English DT Letter ID RECLASSIFICATION; PREDICTION C1 [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Preis, Sarah Rosner; D'Agostino, Ralph B., Sr.; Vasan, Ramachandran S.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Preis, Sarah Rosner; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Preis, Sarah Rosner; Pencina, Michael J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA. RP Preis, SR (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. EM srpreis@bu.edu OI Preis, Sarah/0000-0002-9360-4166; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIDDK NIH HHS [R01DK080739, K24 DK080140, R01 DK080739] NR 6 TC 18 Z9 19 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2013 VL 36 IS 1 BP E3 EP E3 DI 10.2337/dc12-0738 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083LP UT WOS:000314465700003 PM 23264305 ER PT J AU Elliott, CA Tanofsky-Kraff, M Mirza, NM AF Elliott, Camden A. Tanofsky-Kraff, Marian Mirza, Nazrat M. TI Parent report of binge eating in Hispanic, African American and Caucasian youth SO EATING BEHAVIORS LA English DT Article DE Binge eating; Youth; Ethnicity; Race; Obesity ID WEIGHT PATTERNS; OVERWEIGHT CHILDREN; ADOLESCENT GIRLS; COMMUNITY SAMPLE; CONTROLLED-TRIAL; OBESE CHILDREN; PREVALENCE; DISORDER; BEHAVIOR; QUESTIONNAIRE AB Binge eating is prevalent among weight loss treatment-seeking youth. However, there are limited data on the relationship between binge eating and weight in racial or ethnically diverse youth. We therefore examined 409 obese (BMI >= 95th percentile for age and sex) treatment-seeking Hispanic (29.1%), Caucasian (31.7%), and African American (39.2%), boys and girls (6-18 years). Weight, height, waist circumference, and body fat were measured to assess body composition. Depressive symptoms were measured with the Children's Depression Inventory and disordered eating cognitions were measured with the Children's Eating Attitudes Test. Accounting for age, sex, body fat mass, and height, the odds of parents reporting that their child engaged in binge eating were significantly higher among Caucasian compared to African American youth, with Hispanic youth falling non-significantly between these two groups. Youth with binge eating had greater body adiposity (p=.02), waist circumference (p=.02), depressive symptoms (p=.01), and disordered eating attitudes (p=.04), with no difference between racial or ethnic group. We conclude that, regardless of race or ethnicity, binge eating is prevalent among weight loss treatment-seeking youth and is associated with adiposity and psychological distress. Further research is required to elucidate the extent to which binge eating among racially and ethnically diverse youth differentially impacts weight loss outcome. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Elliott, Camden A.; Tanofsky-Kraff, Marian; Mirza, Nazrat M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Elliott, Camden A.; Tanofsky-Kraff, Marian] USUHS, Bethesda, MD 20814 USA. [Mirza, Nazrat M.] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Elliott, CA (reprint author), USUHS, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM camden.elliott@usuhs.mil FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999, ZIA HD000641-17]; NCRR NIH HHS [K23 RR022227, K23-RR022227, M01 RR020359, M01-RR-020359]; NICHD NIH HHS [ZIA HD000641]; PHS HHS [1ZIAHD000641] NR 38 TC 7 Z9 7 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1471-0153 J9 EAT BEHAV JI Eat. Behav. PD JAN PY 2013 VL 14 IS 1 BP 1 EP 6 DI 10.1016/j.eatbeh.2012.10.007 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 086FT UT WOS:000314670200001 PM 23265393 ER PT J AU Cann, JA Jahrling, PB Hensley, LE Wahl-Jensen, V AF Cann, J. A. Jahrling, P. B. Hensley, L. E. Wahl-Jensen, V. TI Comparative Pathology of Smallpox and Monkeypox in Man and Macaques SO JOURNAL OF COMPARATIVE PATHOLOGY LA English DT Article DE macaque; monkeypox; smallpox; variola ID LETHAL MONKEYPOX; MACACA-IRUS; HAEMORRHAGIC SMALLPOX; CYNOMOLGUS MONKEYS; NONHUMAN-PRIMATES; VIRUS-INFECTION; VACCINIA VIRUS; VARIOLA; POXVIRUSES; CHALLENGE AB In the three decades since the eradication of smallpox and cessation of routine vaccination, the collective memory of the devastating epidemics caused by this orthopoxvirus has waned, and the human population has become increasingly susceptible to a disease that remains high on the list of possible bioterrorism agents. Research using surrogate orthopoxviruses in their natural hosts, as well as limited variola virus research in animal models, continues worldwide; however, interpretation of findings is often limited by our relative lack of knowledge about the naturally occurring disease. For modern comparative pathologists, many of whom have no first-hand knowledge of naturally occurring smallpox, this work provides a contemporary review of this historical disease, as well as discussion of how it compares with human monkeypox and the corresponding diseases in macaques. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Cann, J. A.; Jahrling, P. B.; Wahl-Jensen, V.] NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, Frederick, MD USA. [Hensley, L. E.] USA, Med Res Inst Infect Dis, Frederick, MD USA. RP Cann, JA (reprint author), NIAID, Integrated Res Facil Ft Detrick, Div Clin Res, NIH, 8200 Res Plaza, Frederick, MD USA. EM cannja@niaid.nih.gov FU Battelle Memorial Institute [HHSN2722007000161]; NIAID FX The authors wish to thank J. Kuhn, D. Perry, D. Ragland and A. Johnson for thoughtful discussions and critique, and L. Bollinger for technical assistance. JAC performed this work as an employee of Charles River Laboratories and VWJ as an employee of Tunnell Consulting, Inc., both subcontractors to Battelle Memorial Institute under its prime contract HHSN2722007000161 with NIAID. NR 65 TC 9 Z9 10 U1 1 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9975 J9 J COMP PATHOL JI J. Comp. Pathol. PD JAN PY 2013 VL 148 IS 1 BP 6 EP 21 DI 10.1016/j.jcpa.2012.06.007 PG 16 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 086HE UT WOS:000314673900003 PM 22884034 ER PT J AU Pothayee, N Balasubramaniam, S Pothayee, N Jain, N Hu, N Lin, YNA Davis, RM Sriranganathan, N Koretsky, AP Riffle, JS AF Pothayee, Nipon Balasubramaniam, Sharavanan Pothayee, Nikorn Jain, Neeta Hu, Nan Lin, Yinnian Davis, Richey M. Sriranganathan, Nammalwar Koretsky, Alan P. Riffle, J. S. TI Magnetic nanoclusters with hydrophilic spacing for dual drug delivery and sensitive magnetic resonance imaging SO JOURNAL OF MATERIALS CHEMISTRY B LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; MRI CONTRAST AGENTS; EMBRYONIC STEM-CELLS; IN-VIVO DETECTION; POLYMERIC MICELLES; T-2 RELAXATION; SINGLE CELLS; 1.5 T; NANOPARTICLES; PARTICLES AB Magnetic Block Ionomer Clusters (MBIClusters) with hydrophilic ionic cores and nonionic coronas have been prepared that have ultrahigh transverse NMR relaxivities together with capacities for incorporating high concentrations of polar antibiotic payloads. Magnetite-polymer nanoparticles were assembled by adsorbing the polyacrylate block of an aminofunctional poly(ethylene oxide-b-acrylate) (H2N-PEO-b-PAA) copolymer onto magnetite nanoparticles. The PEO blocks extended into aqueous media to keep the nanoparticles dispersed. Amines at the tips of the H2N-PEO corona were then linked through reaction with a PEO diacrylate oligomer to yield MBIClusters where the metal oxide in the precursor nanoparticles were distinctly separated by the hydrophilic polymer. The intensity average spacing between the magnetite nanoparticles within the clusters was estimated to be similar to 50 nm. These MBIClusters with hydrophilic intra-cluster space had transverse relaxivities (r(2)'s) that increased from 190 to 604 s(-1) mM Fe-1 measured at 1.4 T and 37 degrees C as their average sizes increased. The clusters were loaded with up to similar to 38 wt% of the multi-cationic drug gentamicin. MRI scans focused on the livers of mice demonstrated that these MBIClusters are sensitive contrast agents. C1 [Pothayee, Nipon; Balasubramaniam, Sharavanan; Hu, Nan; Lin, Yinnian; Davis, Richey M.; Riffle, J. S.] Virginia Tech, Macromol & Interfaces Inst, Blacksburg, VA 24061 USA. [Jain, Neeta; Sriranganathan, Nammalwar] Virginia Tech, VA MD Sch Vet Med, Blacksburg, VA 24061 USA. [Pothayee, Nikorn; Koretsky, Alan P.] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Pothayee, N (reprint author), Virginia Tech, Macromol & Interfaces Inst, 145 ICTAS 1, Blacksburg, VA 24061 USA. EM judyriffle@aol.com RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NSF [DMR-0805179]; Institute for Critical Technologies and Applied Sciences at Virginia Tech; Intramural Research Program (IRP) at NINDS/NIH FX The authors are grateful for the financial support from NSF under Contract DMR-0805179 and from the Institute for Critical Technologies and Applied Sciences at Virginia Tech. This work was also partially supported by the Intramural Research Program (IRP) at NINDS/NIH. NR 43 TC 23 Z9 23 U1 4 U2 49 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2050-750X J9 J MATER CHEM B JI J. Mat. Chem. B PY 2013 VL 1 IS 8 BP 1142 EP 1149 DI 10.1039/c2tb00275b PG 8 WC Materials Science, Biomaterials SC Materials Science GA 087YR UT WOS:000314801100009 PM 25328679 ER PT J AU Chen, SX Qin, J Tang, CY AF Chen, Song Xi Qin, Jing Tang, Cheng Yong TI Mann-Whitney test with adjustments to pretreatment variables for missing values and observational study SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Dimension reduction; Kernel smoothing; Mann-Whitney statistic; Missing outcomes; Observational studies; Selection bias ID PROPENSITY SCORE; NONPARAMETRIC-ESTIMATION; DIMENSION REDUCTION; TRAINING-PROGRAMS; REGRESSION; EFFICIENT; INFERENCE; RESPONSES AB The conventional Wilcoxon or Mann-Whitney test can be invalid for comparing treatment effects in the presence of missing values or in observational studies. This is because the missingness of the outcomes or the participation in the treatments may depend on certain pretreatment variables. We propose an approach to adjust the Mann-Whitney test by correcting the potential bias via consistently estimating the conditional distributions of the outcomes given the pretreatment variables. We also propose semiparametric extensions of the adjusted Mann-Whitney test which lead to dimension reduction for high dimensional covariates. A novel boot-strap procedure is devised to approximate the null distribution of the test statistics for practical implementations. Results from simulation studies and an economics observational study data analysis are presented to demonstrate the performance of the approach proposed. C1 [Chen, Song Xi] Peking Univ, Beijing 100871, Peoples R China. [Chen, Song Xi] Iowa State Univ, Ames, IA USA. [Qin, Jing] NIAID, Bethesda, MD 20892 USA. [Tang, Cheng Yong] Natl Univ Singapore, Singapore 117548, Singapore. [Tang, Cheng Yong] Univ Colorado, Denver, CO 80202 USA. RP Chen, SX (reprint author), Peking Univ, Guanghua Sch Management, Beijing 100871, Peoples R China. EM csx@gsm.pku.edu.cn OI Chen, Song Xi/0000-0002-2338-0873 FU Center for Statistical Science at Peking University; National Science Foundation of China [11131002]; National University of Singapore FX We are very grateful to the Joint Editor, Associate Editor and two referees for their insightful comments and constructive suggestions that have greatly improved this paper. Chen acknowledges support from the Center for Statistical Science at Peking University and National Science Foundation of China key grant 11131002, and Tang acknowledges research support from National University of Singapore academic research grants. NR 32 TC 4 Z9 4 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-7412 J9 J R STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2013 VL 75 IS 1 BP 81 EP 102 DI 10.1111/j.1467-9868.2012.01036.x PG 22 WC Statistics & Probability SC Mathematics GA 086BW UT WOS:000314659000005 ER PT J AU Wei, JW Carroll, RJ Muller, UU Van Keilegom, I Chatterjee, N AF Wei, Jiawei Carroll, Raymond J. Mueller, Ursula U. Van Keilegom, Ingrid Chatterjee, Nilanjan TI Robust estimation for homoscedastic regression in the secondary analysis of case-control data SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Biased samples; Homoscedastic regression; Secondary data; Secondary phenotypes; Semiparametric inference; Two-stage samples ID ENVIRONMENT INTERACTIONS; INFERENCE; ASSOCIATION; BOOTSTRAP; MODELS; PHENOTYPE AB Primary analysis of case-control studies focuses on the relationship between disease D and a set of covariates of interest (Y, X). A secondary application of the case-control study, which is often invoked in modern genetic epidemiologic association studies, is to investigate the interrelationship between the covariates themselves. The task is complicated owing to the case-control sampling, where the regression of Y on X is different from what it is in the population. Previous work has assumed a parametric distribution for Y given X and derived semiparametric efficient estimation and inference without any distributional assumptions about X. We take up the issue of estimation of a regression function when Y given X follows a homoscedastic regression model, but otherwise the distribution of Y is unspecified. The semiparametric efficient approaches can be used to construct semiparametric efficient estimates, but they suffer from a lack of robustness to the assumed model for Y given X. We take an entirely different approach. We show how to estimate the regression parameters consistently even if the assumed model for Y given X is incorrect, and thus the estimates are model robust. For this we make the assumption that the disease rate is known or well estimated. The assumption can be dropped when the disease is rare, which is typically so for most case-control studies, and the estimation algorithm simplifies. Simulations and empirical examples are used to illustrate the approach. C1 [Wei, Jiawei; Carroll, Raymond J.; Mueller, Ursula U.] Texas A&M Univ, College Stn, TX 77843 USA. [Van Keilegom, Ingrid] Catholic Univ Louvain, B-1348 Louvain, Belgium. [Van Keilegom, Ingrid] Tilburg Univ, Tilburg, Netherlands. [Chatterjee, Nilanjan] NCI, Rockville, MD USA. RP Carroll, RJ (reprint author), Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. EM carroll@stat.tamu.edu FU National Cancer Institute [R37-CA057030]; King Abdullah University of Science and Technology [KUS-CI-016-04]; National Heart, Lung and Blood Institute [RO1-HL091172-01]; Intramural Research Program of the National Cancer Institute; National Science Foundation [DMS-0907014]; Interuniversity Attraction Pole research network of the Belgian Government (Belgian science policy) [P6/03]; European Research Council under the European Community [203650] FX This paper represents part of the first author's doctoral dissertation at Texas A&M University. Wei and Carroll's research was supported by a grant from the National Cancer Institute (R37-CA057030). Carroll was also supported by award KUS-CI-016-04, made by King Abdullah University of Science and Technology. Chatterjee's research was supported by a gene-environment initiative grant from the National Heart, Lung and Blood Institute (RO1-HL091172-01) and by the Intramural Research Program of the National Cancer Institute. Muller was supported by a National Science Foundation grant (DMS-0907014). Van Keilegom gratefully acknowledges financial support from Interuniversity Attraction Pole research network P6/03 of the Belgian Government (Belgian science policy), and from the European Research Council under the European Community's seventh framework programme (FP7/2007-2013), European Research Council grant agreement 203650. NR 26 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-7412 EI 1467-9868 J9 J R STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 2013 VL 75 IS 1 BP 185 EP 206 DI 10.1111/j.1467-9868.2012.01052.x PG 22 WC Statistics & Probability SC Mathematics GA 086BW UT WOS:000314659000010 PM 23637568 ER PT J AU Kumazawa, A Mita, N Hirasawa, M Adachi, T Suzuki, H Shafeghat, N Kulkarni, AB Mikoshiba, K Inoue, T Ohshima, T AF Kumazawa, A. Mita, N. Hirasawa, M. Adachi, T. Suzuki, H. Shafeghat, N. Kulkarni, A. B. Mikoshiba, K. Inoue, T. Ohshima, T. TI Cyclin-dependent kinase 5 is required for normal cerebellar development SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Cdk5; Neuronal migration; Midbrain-hindbrain; Conditional KO; Dendrite ID NEURONAL MIGRATION; CEREBRAL-CORTEX; CRE RECOMBINASE; SONIC HEDGEHOG; NEUROTROPHIC FACTOR; P35/CDK5 KINASE; PURKINJE-CELLS; CDK5; BRAIN; PHOSPHORYLATION AB Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, and its kinase activity is dependent upon its association with either of the activating subunits p35 or p39, which are mainly expressed in neurons. We previously reported that Cdk5 knockout (KO) mice exhibit perinatal lethality, defective neuronal migration, and abnormal positioning of neurons in the facial motor nucleus and inferior olive in the hindbrain and Purkinje cells (PCs) in the cerebellum. In this study, we focused on the analysis of the role of Cdk5 in cerebellar development. For this purpose we generated midbrain-hindbrain-specific Cdk5 conditional knockout (MHB-Cdk5 KO) mice because the cerebellum develops postnatally, whereas Cdk5 KO mice die perinatally. Histological analysis of the MHB-Cdk5 KO mice revealed a significant size reduction of the cerebellum. In addition, profound disturbance of inward migration of granule cells (GC) was observed in the developing cerebellum. A normal dendritic development of the Purkinje cells (PCs) was disturbed in MHB-Cdk5 KO mice. Cultured Cdk5-null PCs showed similar dendritic abnormalities. These results indicate that Cdk5/p35 plays an important role in neuronal migration of PCs and GCs and dendrite formation of PCs in cerebellar development. (c) 2012 Elsevier Inc. All rights reserved. C1 [Kumazawa, A.; Mita, N.; Ohshima, T.] Waseda Univ, Dept Life Sci & Med Biosci Sci & Engn, Lab Mol Brain Sci, Tokyo 1628480, Japan. [Hirasawa, M.; Kulkarni, A. B.; Ohshima, T.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. [Adachi, T.; Suzuki, H.; Mikoshiba, K.] RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan. [Shafeghat, N.; Inoue, T.] Waseda Univ, Dept Life Sci & Med Biosci, Neurophysiol Lab, Tokyo 1628480, Japan. RP Ohshima, T (reprint author), Waseda Univ, Dept Life Sci & Med Biosci, Tokyo 1628480, Japan. EM ohshima@waseda.jp RI Mikoshiba, Katsuhiko/N-7943-2015; OI Inoue, Takafumi/0000-0002-2728-0060 FU Ministry of Education, Science, and Culture, Japan FX We thank Dr J. Miyazaki for the gift of the CAG-CAT-Z mice. We thank Dr D. Karagogeos for the in situ probe and J. Gleeson for the in situ probe as well as the anti-phospho-DCX antibody. We also thank Dr. M. Ogawa and E. Utreras for critical reading of the manuscript and Shelagh Johnson for editorial assistance. This work was partially supported by grants-in-aid from the Ministry of Education, Science, and Culture, Japan, to Toshio Ohshima. NR 41 TC 12 Z9 12 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN PY 2013 VL 52 BP 97 EP 105 DI 10.1016/j.mcn.2012.10.007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 085LB UT WOS:000314615200010 PM 23085039 ER PT J AU Wang, HF Livingston, KA Fox, CS Meigs, JB Jacques, PF AF Wang, Huifen Livingston, Kara A. Fox, Caroline S. Meigs, James B. Jacques, Paul F. TI Yogurt consumption is associated with better diet quality and metabolic profile in American men and women SO NUTRITION RESEARCH LA English DT Article DE Yogurt; Milk; Diet; Nutrition status; Metabolic profile; Human ID FOOD FREQUENCY QUESTIONNAIRE; DAIRY CONSUMPTION; INSULIN-RESISTANCE; CONTINUING SURVEY; MAGNESIUM INTAKE; MILK-PRODUCTS; UNITED-STATES; ADULTS; RISK; PLASMA AB The evidence-based Dietary Guidelines for Americans recommends increasing the intake of fat-free or low-fat milk and milk products. However, yogurt, a nutrient-dense milk product, has been understudied. This cross-sectional study examined whether yogurt consumption was associated with better diet quality and metabolic profile among adults (n = 6526) participating in the Framingham Heart Study Offspring (1998-2001) and Third Generation (2002-2005) cohorts. A validated food frequency questionnaire was used to assess dietary intake, and the Dietary Guidelines Adherence Index (DGAI) was used to measure overall diet quality. Standardized clinical examinations and laboratory tests were conducted. Generalized estimating equations examined the associations of yogurt consumption with diet quality and levels of metabolic factors. Approximately 64% of women (vs 41% of men) were yogurt consumers (ie, consumed >0 servings/week). Yogurt consumers had a higher DGAI score (ie, better diet quality) than nonconsumers. Adjusted for demographic and lifestyle factors and DGAI, yogurt consumers, compared with nonconsumers, had higher potassium intakes (difference, 0.12 g/d) and were 47%, 55%, 48%, 38%, and 34% less likely to have inadequate intakes (based on Dietary Reference Intake) of vitamins B2 and B12, calcium, magnesium, and zinc, respectively (all P <= .001). In addition, yogurt consumption was associated with lower levels of circulating triglycerides, glucose, and lower systolic blood pressure and insulin resistance (all P < .05). Yogurt is a good source of several micronutrients and may help to improve diet quality and maintain metabolic well-being as part of a healthy, energy-balanced dietary pattern. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wang, Huifen; Livingston, Kara A.; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. RP Jacques, PF (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Boston, MA 02111 USA. EM Paul.jacques@tufts.edu FU National Heart, Lung and Blood Institute of the National Institute of Health [NO1-HC-25195]; US Department of Agriculture [58-1950-7-707]; The Dannon Company, Inc. FX This work was supported by National Heart, Lung and Blood Institute of the National Institute of Health (contract number: NO1-HC-25195), US Department of Agriculture Agreement 58-1950-7-707, and a research grant from The Dannon Company, Inc. NR 40 TC 43 Z9 44 U1 7 U2 49 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2013 VL 33 IS 1 BP 18 EP 26 DI 10.1016/j.nutres.2012.11.009 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 084TE UT WOS:000314561200003 PM 23351406 ER PT J AU Range, RC Angerer, RC Angerer, LM AF Range, Ryan C. Angerer, Robert C. Angerer, Lynne M. TI Integration of Canonical and Noncanonical Wnt Signaling Pathways Patterns the Neuroectoderm Along the Anterior-Posterior Axis of Sea Urchin Embryos SO PLOS BIOLOGY LA English DT Article ID NUCLEAR BETA-CATENIN; ANIMAL-VEGETAL AXIS; VERTEBRATE FOREBRAIN DEVELOPMENT; GENE REGULATORY NETWORK; XENOPUS EMBRYOS; CELL FATES; SPEMANN ORGANIZER; WNT/BETA-CATENIN; PRECHORDAL PLATE; HEAD INDUCTION AB Patterning the neuroectoderm along the anterior-posterior (AP) axis is a critical event in the early development of deuterostome embryos. However, the mechanisms that regulate the specification and patterning of the neuroectoderm are incompletely understood. Remarkably, the anterior neuroectoderm (ANE) of the deuterostome sea urchin embryo expresses many of the same transcription factors and secreted modulators of Wnt signaling, as does the early vertebrate ANE (forebrain/eye field). Moreover, as is the case in vertebrate embryos, confining the ANE to the anterior end of the embryo requires a Wnt/beta-catenin-dependent signaling mechanism. Here we use morpholino-or dominant negative-mediated interference to demonstrate that the early sea urchin embryo integrates information not only from Wnt/beta-catenin but also from Wnt/Fzl5/8-JNK and Fzl1/2/7-PKC pathways to provide precise spatiotemporal control of neuroectoderm patterning along its AP axis. Together, through the Wnt1 and Wnt8 ligands, they orchestrate a progressive posterior-to-anterior wave of re-specification that restricts the initial, ubiquitous, maternally specified, ANE regulatory state to the most anterior blastomeres. There, the Wnt receptor antagonist, Dkk1, protects this state through a negative feedback mechanism. Because these different Wnt pathways converge on the same cell fate specification process, our data suggest they may function as integrated components of an interactive Wnt signaling network. Our findings provide strong support for the idea that the sea urchin ANE regulatory state and the mechanisms that position and define its borders represent an ancient regulatory patterning system that was present in the common echinoderm/vertebrate ancestor. C1 [Range, Ryan C.; Angerer, Robert C.; Angerer, Lynne M.] NIDCR, NIH, Bethesda, MD 20892 USA. RP Range, RC (reprint author), NIDCR, NIH, Bethesda, MD 20892 USA. EM langerer@mail.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health [ZO1 DE000712-08] FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, National Institutes of Health (ZO1 DE000712-08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 37 Z9 37 U1 2 U2 22 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 JAN PY 2013 VL 11 IS 1 AR e1001467 DI 10.1371/journal.pbio.1001467 PG 18 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 085XX UT WOS:000314648700007 PM 23335859 ER PT J AU Selimyan, R Gerstein, RM Ivanova, I Precht, P Subrahmanyam, R Perlot, T Alt, FW Sen, R AF Selimyan, Roza Gerstein, Rachel M. Ivanova, Irina Precht, Patricia Subrahmanyam, Ramesh Perlot, Thomas Alt, Frederick W. Sen, Ranjan TI Localized DNA Demethylation at Recombination Intermediates during Immunoglobulin Heavy Chain Gene Assembly SO PLOS BIOLOGY LA English DT Article ID V(D)J RECOMBINATION; INTRONIC ENHANCER; LYMPHOCYTE DEVELOPMENT; HISTONE MODIFICATIONS; TRANSGENIC SUBSTRATE; METHYLATION PATTERNS; IGH LOCUS; REARRANGEMENT; TRANSCRIPTION; MU AB Multiple epigenetic marks have been proposed to contribute to the regulation of antigen receptor gene assembly via V(D)J recombination. Here we provide a comprehensive view of DNA methylation at the immunoglobulin heavy chain (IgH) gene locus prior to and during V(D) J recombination. DNA methylation did not correlate with the histone modification state on unrearranged alleles, indicating that these epigenetic marks were regulated independently. Instead, pockets of tissue-specific demethylation were restricted to DNase I hypersensitive sites within this locus. Though unrearranged diversity (D-H) and joining (J(H)) gene segments were methylated, DJ(H) junctions created after the first recombination step were largely demethylated in pro-, pre-, and mature B cells. Junctional demethylation was highly localized, B-lineage-specific, and required an intact tissue-specific enhancer, E mu. We propose that demethylation occurs after the first recombination step and may mark the junction for secondary recombination. C1 [Selimyan, Roza; Ivanova, Irina; Precht, Patricia; Subrahmanyam, Ramesh; Sen, Ranjan] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. [Gerstein, Rachel M.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Perlot, Thomas] Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Boston, MA 02115 USA. [Perlot, Thomas; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Selimyan, R (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. EM senranja@grc.nia.nih.gov FU NIH [AI 2047, AI 43534]; Intramural Research Program of the National Institute on Aging (Baltimore, MD); NIH NIDDK Diabetes Endocrinology Research Center [5 P30DK32520] FX This work was supported by NIH grant AI 2047 (to F. W. A.) and AI 43534 (to R. M. G.), and by the Intramural Research Program of the National Institute on Aging (Baltimore, MD). The U-Mass Medical School Flow Cytometry Core is supported by NIH NIDDK Diabetes Endocrinology Research Center grant 5 P30DK32520. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 7 Z9 7 U1 0 U2 6 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 JAN PY 2013 VL 11 IS 1 AR e1001475 DI 10.1371/journal.pbio.1001475 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 085XX UT WOS:000314648700015 PM 23382652 ER PT J AU Buice, MA Chow, CC AF Buice, Michael A. Chow, Carson C. TI Dynamic Finite Size Effects in Spiking Neural Networks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID POPULATION-DENSITY APPROACH; MEAN-FIELD ANALYSIS; COUPLED OSCILLATORS; ASYNCHRONOUS STATES; MATHEMATICAL-THEORY; NEURONAL NETWORKS; PATTERN-FORMATION; KURAMOTO MODEL; FIRE NEURONS; LOCKED STATE AB We investigate the dynamics of a deterministic finite-sized network of synaptically coupled spiking neurons and present a formalism for computing the network statistics in a perturbative expansion. The small parameter for the expansion is the inverse number of neurons in the network. The network dynamics are fully characterized by a neuron population density that obeys a conservation law analogous to the Klimontovich equation in the kinetic theory of plasmas. The Klimontovich equation does not possess well-behaved solutions but can be recast in terms of a coupled system of well-behaved moment equations, known as a moment hierarchy. The moment hierarchy is impossible to solve but in the mean field limit of an infinite number of neurons, it reduces to a single well-behaved conservation law for the mean neuron density. For a large but finite system, the moment hierarchy can be truncated perturbatively with the inverse system size as a small parameter but the resulting set of reduced moment equations that are still very difficult to solve. However, the entire moment hierarchy can also be re-expressed in terms of a functional probability distribution of the neuron density. The moments can then be computed perturbatively using methods from statistical field theory. Here we derive the complete mean field theory and the lowest order second moment corrections for physiologically relevant quantities. Although we focus on finite-size corrections, our method can be used to compute perturbative expansions in any parameter. C1 [Buice, Michael A.; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Buice, MA (reprint author), NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM mabuice@mail.clm.utexas.edu; carsonc@mail.nih.gov FU Intramural Research Program of the NIH/NIDDK FX This work was funded 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 58 TC 14 Z9 14 U1 1 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2013 VL 9 IS 1 AR e1002872 DI 10.1371/journal.pcbi.1002872 PG 21 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 085ED UT WOS:000314595600029 PM 23359258 ER PT J AU Kim, Y Yewdell, JW Sette, A Peters, B AF Kim, Yohan Yewdell, Jonathan W. Sette, Alessandro Peters, Bjoern TI Positional Bias of MHC Class I Restricted T-Cell Epitopes in Viral Antigens Is Likely due to a Bias in Conservation SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DEFECTIVE RIBOSOMAL PRODUCTS; PEPTIDE BINDING; IMMUNE; MOLECULES; PREDICTION; PROTEINS; EVASION; DRIPS; HIV-1 AB The immune system rapidly responds to intracellular infections by detecting MHC class I restricted T-cell epitopes presented on infected cells. It was originally thought that viral peptides are liberated during constitutive protein turnover, but this conflicts with the observation that viral epitopes are detected within minutes of their synthesis even when their source proteins exhibit half-lives of days. The DRiPs hypothesis proposes that epitopes derive from Defective Ribosomal Products (DRiPs), rather than degradation of mature protein products. One potential source of DRiPs is premature translation termination. If this is a major source of DRiPs, this should be reflected in positional bias towards the N-terminus. By contrast, if downstream initiation is a major source of DRiPs, there should be positional bias towards the C-terminus. Here, we systematically assessed positional bias of epitopes in viral antigens, exploiting the large set of data available in the Immune Epitope Database and Analysis Resource. We show a statistically significant degree of positional skewing among epitopes; epitopes from both ends of antigens tend to be under-represented. Centric-skewing correlates with a bias towards class I binding peptides being over-represented in the middle, in parallel with a higher degree of evolutionary conservation. C1 [Kim, Yohan; Sette, Alessandro; Peters, Bjoern] La Jolla Inst Allergy & Immunol, La Jolla, CA USA. [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Kim, Y (reprint author), La Jolla Inst Allergy & Immunol, La Jolla, CA USA. EM bpeters@liai.org FU National Institutes of Health [HHSN272201200010C] FX The IEDB is funded by National Institutes of Health [contract number HHSN272201200010C]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 7 Z9 7 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2013 VL 9 IS 1 AR e1002884 DI 10.1371/journal.pcbi.1002884 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 085ED UT WOS:000314595600039 PM 23357871 ER PT J AU Wuchty, S Arjona, D Bauer, PO AF Wuchty, Stefan Arjona, Dolores Bauer, Peter O. TI Important miRs of Pathways in Different Tumor Types SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID MICRORNA EXPRESSION; CELL-PROLIFERATION; DOWN-REGULATION; GLIOMA-CELLS; CANCER CELLS; AKT PATHWAY; TARGETS; GROWTH; GENE; GLIOBLASTOMA AB We computationally determined miRs that are significantly connected to molecular pathways by utilizing gene expression profiles in different cancer types such as glioblastomas, ovarian and breast cancers. Specifically, we assumed that the knowledge of physical interactions between miRs and genes indicated subsets of important miRs (IM) that significantly contributed to the regression of pathway-specific enrichment scores. Despite the different nature of the considered cancer types, we found strongly overlapping sets of IMs. Furthermore, IMs that were important for many pathways were enriched with literature-curated cancer and differentially expressed miRs. Such sets of IMs also coincided well with clusters of miRs that were experimentally indicated in numerous other cancer types. In particular, we focused on an overlapping set of 99 overall important miRs (OIM) that were found in glioblastomas, ovarian and breast cancers simultaneously. Notably, we observed that interactions between OIMs and leading edge genes of differentially expressed pathways were characterized by considerable changes in their expression correlations. Such gains/losses of miR and gene expression correlation indicated miR/gene pairs that may play a causal role in the underlying cancers. C1 [Wuchty, Stefan] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Arjona, Dolores] GeneDx Inc, Gaithersburg, MD USA. [Bauer, Peter O.] NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. RP Wuchty, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM wuchtys@ncbi.nlm.nih.gov FU National Institutes of Health/Department of Health and Human Service (DHHS) (Intramural Research program of the National Library of Medicine) FX This work was supported by the National Institutes of Health/Department of Health and Human Service (DHHS) (Intramural Research program of the National Library of Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 73 TC 2 Z9 2 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2013 VL 9 IS 1 AR e1002883 DI 10.1371/journal.pcbi.1002883 PG 10 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 085ED UT WOS:000314595600038 PM 23358700 ER PT J AU Bateman, DA Wickner, RB AF Bateman, David A. Wickner, Reed B. TI The [PSI+] Prion Exists as a Dynamic Cloud of Variants SO PLOS GENETICS LA English DT Article ID BETA-SHEET STRUCTURE; YEAST SUP35 PROTEIN; TERMINATION FACTOR ERF3; MESSENGER-RNA DECAY; SACCHAROMYCES-CEREVISIAE; TRANSLATION TERMINATION; SPECIES BARRIER; RELEASE FACTOR; IN-VITRO; TRANSMISSION AB [PSI+] is an amyloid-based prion of Sup35p, a subunit of the translation termination factor. Prion "strains" or "variants" are amyloids with different conformations of a single protein sequence, conferring different phenotypes, but each relatively faithfully propagated. Wild Saccharomyces cerevisiae isolates have SUP35 alleles that fall into three groups, called reference, Delta 19, and E9, with limited transmissibility of [PSI+] between cells expressing these different polymorphs. Here we show that prion transmission pattern between different Sup35 polymorphs is prion variant-dependent. Passage of one prion variant from one Sup35 polymorph to another need not change the prion variant. Surprisingly, simple mitotic growth of a [PSI+] strain results in a spectrum of variant transmission properties among the progeny clones. Even cells that have grown for >150 generations continue to vary in transmission properties, suggesting that simple variant segregation is insufficient to explain the results. Rather, there appears to be continuous generation of a cloud of prion variants, with one or another becoming stochastically dominant, only to be succeeded by a different mixture. We find that among the rare wild isolates containing [PSI+], all indistinguishably "weak" [PSI+], are several different variants based on their transmission efficiencies to other Sup35 alleles. Most show some limitation of transmission, indicating that the evolved wild Sup35 alleles are effective in limiting the spread of [PSI+]. Notably, a "strong [PSI+]" can have any of several different transmission efficiency patterns, showing that "strong" versus "weak" is insufficient to indicate prion variant uniformity. C1 [Bateman, David A.; Wickner, Reed B.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. RP Bateman, DA (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. EM wickner@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 22 Z9 22 U1 0 U2 5 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 JAN PY 2013 VL 9 IS 1 AR e1003257 DI 10.1371/journal.pgen.1003257 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500082 PM 23382698 ER PT J AU Pendergrass, SA Brown-Gentry, K Dudek, S Frase, A Torstenson, ES Goodloe, R Ambite, JL Avery, CL Buyske, S Buzkova, P Deelman, E Fesinmeyer, MD Haiman, CA Heiss, G Hindorff, LA Hsu, CN Jackson, RD Kooperberg, C Le Marchand, L Lin, Y Matise, TC Monroe, KR Moreland, L Park, SL Reiner, A Wallace, R Wilkens, LR Crawford, DC Ritchie, MD AF Pendergrass, Sarah A. Brown-Gentry, Kristin Dudek, Scott Frase, Alex Torstenson, Eric S. Goodloe, Robert Ambite, Jose Luis Avery, Christy L. Buyske, Steve Buzkova, Petra Deelman, Ewa Fesinmeyer, Megan D. Haiman, Christopher A. Heiss, Gerardo Hindorff, Lucia A. Hsu, Chu-Nan Jackson, Rebecca D. Kooperberg, Charles Le Marchand, Loic Lin, Yi Matise, Tara C. Monroe, Kristine R. Moreland, Larry Park, Sungshim L. Reiner, Alex Wallace, Robert Wilkens, Lynn R. Crawford, Dana C. Ritchie, Marylyn D. TI Phenome-Wide Association Study (PheWAS) for Detection of Pleiotropy within the Population Architecture using Genomics and Epidemiology (PAGE) Network SO PLOS GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; METABOLIC SYNDROME; LOCI; RISK; DESIGN; REPLICATION; CHOLESTEROL; CONSORTIUM; TRAITS; COHORT AB Using a phenome-wide association study (PheWAS) approach, we comprehensively tested genetic variants for association with phenotypes available for 70,061 study participants in the Population Architecture using Genomics and Epidemiology (PAGE) network. Our aim was to better characterize the genetic architecture of complex traits and identify novel pleiotropic relationships. This PheWAS drew on five population-based studies representing four major racial/ethnic groups (European Americans (EA), African Americans (AA), Hispanics/Mexican-Americans, and Asian/Pacific Islanders) in PAGE, each site with measurements for multiple traits, associated laboratory measures, and intermediate biomarkers. A total of 83 single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) were genotyped across two or more PAGE study sites. Comprehensive tests of association, stratified by race/ethnicity, were performed, encompassing 4,706 phenotypes mapped to 105 phenotype-classes, and association results were compared across study sites. A total of 111 PheWAS results had significant associations for two or more PAGE study sites with consistent direction of effect with a significance threshold of p<0.01 for the same racial/ethnic group, SNP, and phenotype-class. Among results identified for SNPs previously associated with phenotypes such as lipid traits, type 2 diabetes, and body mass index, 52 replicated previously published genotype-phenotype associations, 26 represented phenotypes closely related to previously known genotype-phenotype associations, and 33 represented potentially novel genotype-phenotype associations with pleiotropic effects. The majority of the potentially novel results were for single PheWAS phenotype-classes, for example, for CDKN2A/B rs1333049 (previously associated with type 2 diabetes in EA) a PheWAS association was identified for hemoglobin levels in AA. Of note, however, GALNT2 rs2144300 (previously associated with high-density lipoprotein cholesterol levels in EA) had multiple potentially novel PheWAS associations, with hypertension related phenotypes in AA and with serum calcium levels and coronary artery disease phenotypes in EA. PheWAS identifies associations for hypothesis generation and exploration of the genetic architecture of complex traits. C1 [Pendergrass, Sarah A.; Frase, Alex; Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, Dept Biochem & Mol Biol, Eberly Coll Sci,Huck Inst Life Sci, University Pk, PA 16802 USA. [Brown-Gentry, Kristin; Dudek, Scott; Torstenson, Eric S.; Goodloe, Robert; Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Ambite, Jose Luis; Deelman, Ewa; Hsu, Chu-Nan] Univ So Calif, Inst Informat Sci, Marina Del Rey, CA 90292 USA. [Avery, Christy L.; Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Buyske, Steve; Matise, Tara C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Buyske, Steve] Rutgers State Univ, Dept Stat, Piscataway, NJ USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Fesinmeyer, Megan D.; Kooperberg, Charles; Lin, Yi; Reiner, Alex] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Seattle, WA 98104 USA. [Haiman, Christopher A.; Monroe, Kristine R.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hindorff, Lucia A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA. [Le Marchand, Loic; Park, Sungshim L.; Wilkens, Lynn R.] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA. [Moreland, Larry] Univ Pittsburgh, Pittsburgh, PA USA. [Reiner, Alex] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Wallace, Robert] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Wallace, Robert] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. [Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Pendergrass, SA (reprint author), Penn State Univ, Ctr Syst Genom, Dept Biochem & Mol Biol, Eberly Coll Sci,Huck Inst Life Sci, University Pk, PA 16802 USA. EM marylyn.ritchie@psu.edu RI Ritchie, Marylyn/C-1114-2012; OI Buyske, Steven/0000-0001-8539-5416 FU National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating Center [U01HG004801]; NHGRI PAGE program [U01HG004798-01]; Johns Hopkins University from NHLBI [N01-HV-48195]; University of Washington's Center for Ecogenetics and Environmental Health (CEEH) pilot study; National Institute of Environmental Health Sciences [5 P30 ES007033-12]; Centers for Disease Control and Prevention; NHGRI PAGE [U01HG004802]; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]; Women's Health Initiative through the NHGRI PAGE program [U01HG004790]; National Heart, Lung, and Blood Institute; NIH; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Genetic Epidemiology of Causal Variants Across the Life Course (CALiCo) through the NHGRI PAGE program [U01HG004803]; Atherosclerosis Risk in Communities (ARIC); National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; National Institutes of Health, 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]; National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201200036C, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295]; National Institute of Neurological Disorders and Stroke (NINDS); National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; NHLBI [U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, U01 HL65521.]; National Institutes of Mental Health also contributes FX The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center), and their respective NHGRI ARRA supplements. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The complete list of PAGE members can be found at http://www.pagestudy.org. The data and materials included in this report result from a collaboration between the following studies: The "Epidemiologic Architecture for Genes Linked to Environment (EAGLE)" is funded through the NHGRI PAGE program (U01HG004798-01 and its NHGRI ARRA supplement). Genotyping services for select NHANES III SNPs presented here were also provided by the Johns Hopkins University under federal contract number (N01-HV-48195) from NHLBI and from the University of Washington's Center for Ecogenetics and Environmental Health (CEEH) pilot study funded by the National Institute of Environmental Health Sciences grant 5 P30 ES007033-12. The study participants derive from the National Health and Nutrition Examination Surveys (NHANES), and these studies are supported by the Centers for Disease Control and Prevention. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. The Multiethnic Cohort study (MEC) characterization of epidemiological architecture is funded through the NHGRI PAGE program (U01HG004802 and its NHGRI ARRA supplement). The MEC study is funded through the National Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and U01CA98758). Funding support for the "Epidemiology of putative genetic variants: The Women's Health Initiative" study is provided through the NHGRI PAGE program (U01HG004790 and its NHGRI ARRA supplement). The WHI program is funded by the National Heart, Lung, and Blood Institute; NIH; and U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. Funding support for the Genetic Epidemiology of Causal Variants Across the Life Course (CALiCo) program was provided through the NHGRI PAGE program (U01HG004803 and its NHGRI ARRA supplement). The following studies contributed to this manuscript and are funded by the following agencies: The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The Coronary Artery Risk Development in Young Adults (CARDIA) study is supported by the following National Institutes of Health, National Heart, Lung, and Blood Institute contracts: N01-HC-95095, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-45134, N01-HC-05187, and N01-HC-45205.; The Cardiovascular Health Study (CHS) is supported by contracts HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). The Strong Heart Study (SHS) is supported by NHLBI grants U01 HL65520, U01 HL41642, U01 HL41652, U01 HL41654, and U01 HL65521. The opinions expressed in this paper are those of the author(s) and do not necessarily reflect the views of the Indian Health Service. Assistance with phenotype harmonization, SNP selection and annotation, data cleaning, data management, integration and dissemination, and general study coordination was provided by the PAGE Coordinating Center (U01HG004801-01 and its NHGRI ARRA supplement). The National Institutes of Mental Health also contributes to the support for the Coordinating Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 47 Z9 48 U1 1 U2 12 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 JAN PY 2013 VL 9 IS 1 AR e1003087 DI 10.1371/journal.pgen.1003087 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500001 PM 23382687 ER PT J AU Peters, U North, KE Sethupathy, P Buyske, S Haessler, J Jiao, S Fesinmeyer, MD Jackson, RD Kuller, LH Rajkovic, A Lim, U Cheng, I Schumacher, F Wilkens, L Li, RL Monda, K Ehret, G Nguyen, KDH Cooper, R Lewis, CE Leppert, M Irvin, MR Gu, CC Houston, D Buzkova, P Ritchie, M Matise, TC Le Marchand, L Hindorff, LA Crawford, DC Haiman, CA Kooperberg, C AF Peters, Ulrike North, Kari E. Sethupathy, Praveen Buyske, Steve Haessler, Jeff Jiao, Shuo Fesinmeyer, Megan D. Jackson, Rebecca D. Kuller, Lew H. Rajkovic, Aleksandar Lim, Unhee Cheng, Iona Schumacher, Fred Wilkens, Lynne Li, Rongling Monda, Keri Ehret, Georg Nguyen, Khanh-Dung H. Cooper, Richard Lewis, Cora E. Leppert, Mark Irvin, Marguerite R. Gu, C. Charles Houston, Denise Buzkova, Petra Ritchie, Marylyn Matise, Tara C. Le Marchand, Loic Hindorff, Lucia A. Crawford, Dana C. Haiman, Christopher A. Kooperberg, Charles TI A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study SO PLOS GENETICS LA English DT Article ID BODY-MASS INDEX; FTO GENE VARIANTS; WIDE ASSOCIATION; ADULT OBESITY; FAT MASS; GENOTYPE IMPUTATION; EXTREME OBESITY; EARLY-ONSET; RISK; POLYMORPHISMS AB Genetic variants in intron 1 of the fat mass-and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3x10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations. C1 [Peters, Ulrike; Haessler, Jeff; Jiao, Shuo; Fesinmeyer, Megan D.; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [North, Kari E.; Sethupathy, Praveen; Monda, Keri] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [North, Kari E.; Monda, Keri] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Sethupathy, Praveen] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. [Buyske, Steve; Matise, Tara C.] Rutgers State Univ, Dept Genet, Piscataway, NJ USA. [Buyske, Steve] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ USA. [Jackson, Rebecca D.] Ohio State Med Ctr, Dept Internal Med, Columbus, OH USA. [Kuller, Lew H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Rajkovic, Aleksandar; Cheng, Iona] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Lim, Unhee; Wilkens, Lynne; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA. [Schumacher, Fred; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Schumacher, Fred; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Li, Rongling; Hindorff, Lucia A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. [Ehret, Georg; Nguyen, Khanh-Dung H.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA. [Ehret, Georg] Univ Hosp Geneva, Div Cardiol, Geneva, Switzerland. [Cooper, Richard] Loyola Univ, Chicago, IL 60611 USA. [Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Leppert, Mark] Univ Utah, Dept Human Genet, Salt Lake City, UT USA. [Irvin, Marguerite R.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Gu, C. Charles] Washington Univ, Dept Biostat, St Louis, MO USA. [Houston, Denise] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Ritchie, Marylyn] Penn State Univ, State Coll, PA USA. [Crawford, Dana C.] Vanderbilt Univ, Med Ctr, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Crawford, Dana C.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA. RP Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM upeters@fhcrc.org RI Ritchie, Marylyn/C-1114-2012; Crawford, Dana/C-1054-2012; EHRET, Georg/A-9532-2009; Gu, Charles/A-7934-2010; OI EHRET, Georg/0000-0002-5730-0675; Gu, Charles/0000-0002-8527-8145; Buyske, Steven/0000-0001-8539-5416 FU NHGRI PAGE program [U01HG004802]; National Cancer Institute [R37CA54281, R01 CA63, P01CA33619, U01CA136792, U01CA98758]; NHGRI PAGE [U01HG004790]; National Heart, Lung, and Blood Institute; NIH; U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022]; NIDDK/NIH [1K99DK091318-01]; PAGE Coordinating Center [U01HG004801]; National Human Genome Research Institute (NHGRI); CALiCo [U01HG004803]; EAGLE [U01HG004798]; MEC [U01HG004802]; WHI [U01HG004790]; Coordinating Center [U01HG004801] FX The Multiethnic Cohort study (MEC) characterization of epidemiological architecture is funded through the NHGRI PAGE program (U01HG004802). The MEC study is funded through the National Cancer Institute (R37CA54281, R01 CA63, P01CA33619, U01CA136792, and U01CA98758). Funding support for the "Epidemiology of putative genetic variants: The Women's Health Initiative" study is provided through the NHGRI PAGE program (U01HG004790). The WHI program is funded by the National Heart, Lung, and Blood Institute; NIH; and U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A full listing of WHI investigators can be found at: http://www.whiscience.org/publications/WHI_investigators_shortlist.pdf. The Atherosclerosis Risk in Communities (ARIC) Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022. PS was supported in part by NIDDK/NIH K99 grant 1K99DK091318-01. Assistance with phenotype harmonization, SNP selection and annotation, data cleaning, data management, integration and dissemination, and general study coordination was provided by the PAGE Coordinating Center (U01HG004801). The National Institutes of Mental Health also contributes to the support for the Coordinating Center. The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by U01HG004803 (CALiCo), U01HG004798 (EAGLE), U01HG004802 (MEC), U01HG004790 (WHI), and U01HG004801 (Coordinating Center). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, except for RL and LAH, who as part of their role in the NHGRI PAGE program (U01HG004802, U01HG004790, U01HG004801) collaboratively worked on this manuscript. NR 61 TC 31 Z9 33 U1 1 U2 10 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 JAN PY 2013 VL 9 IS 1 AR e1003171 DI 10.1371/journal.pgen.1003171 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500023 PM 23341774 ER PT J AU Watkins-Chow, DE Cooke, J Pidsley, R Edwards, A Slotkin, R Leeds, KE Mullen, R Baxter, LL Campbell, TG Salzer, MC Biondini, L Gibney, G Tuy, FPD Chelly, J Morris, HD Riegler, J Lythgoe, MF Arkell, RM Loreni, F Flint, J Pavan, WJ Keays, DA AF Watkins-Chow, Dawn E. Cooke, Joanna Pidsley, Ruth Edwards, Andrew Slotkin, Rebecca Leeds, Karen E. Mullen, Raymond Baxter, Laura L. Campbell, Thomas G. Salzer, Marion C. Biondini, Laura Gibney, Gretchen Tuy, Francoise Phan Dinh Chelly, Jamel Morris, H. Douglas Riegler, Johannes Lythgoe, Mark F. Arkell, Ruth M. Loreni, Fabrizio Flint, Jonathan Pavan, William J. Keays, David A. TI Mutation of the Diamond-Blackfan Anemia Gene Rps7 in Mouse Results in Morphological and Neuroanatomical Phenotypes SO PLOS GENETICS LA English DT Article ID RIBOSOMAL-PROTEIN GENE; MESSENGER-RNA; P53-DEPENDENT CHECKPOINT; INITIATION-FACTOR; P53; ABNORMALITIES; EXPRESSION; ZEBRAFISH; CELLS; MICE AB The ribosome is an evolutionarily conserved organelle essential for cellular function. Ribosome construction requires assembly of approximately 80 different ribosomal proteins (RPs) and four different species of rRNA. As RPs co-assemble into one multi-subunit complex, mutation of the genes that encode RPs might be expected to give rise to phenocopies, in which the same phenotype is associated with loss-of-function of each individual gene. However, a more complex picture is emerging in which, in addition to a group of shared phenotypes, diverse RP gene-specific phenotypes are observed. Here we report the first two mouse mutations (Rps7(Mtu) and Rps7(Zma)) of ribosomal protein S7 (Rps7), a gene that has been implicated in Diamond-Blackfan anemia. Rps7 disruption results in decreased body size, abnormal skeletal morphology, mid-ventral white spotting, and eye malformations. These phenotypes are reported in other murine RP mutants and, as demonstrated for some other RP mutations, are ameliorated by Trp53 deficiency. Interestingly, Rps7 mutants have additional overt malformations of the developing central nervous system and deficits in working memory, phenotypes that are not reported in murine or human RP gene mutants. Conversely, Rps7 mouse mutants show no anemia or hyperpigmentation, phenotypes associated with mutation of human RPS7 and other murine RPs, respectively. We provide two novel RP mouse models and expand the repertoire of potential phenotypes that should be examined in RP mutants to further explore the concept of RP gene-specific phenotypes. C1 [Watkins-Chow, Dawn E.; Slotkin, Rebecca; Leeds, Karen E.; Mullen, Raymond; Baxter, Laura L.; Gibney, Gretchen; Pavan, William J.] NHGRI, NIH, Bethesda, MD 20892 USA. [Cooke, Joanna; Pidsley, Ruth; Edwards, Andrew; Campbell, Thomas G.; Flint, Jonathan] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Salzer, Marion C.; Keays, David A.] Inst Mol Pathol, A-1030 Vienna, Austria. [Biondini, Laura; Loreni, Fabrizio] Univ Roma Tor Vergata, Dept Biol, I-00173 Rome, Italy. [Tuy, Francoise Phan Dinh; Chelly, Jamel] Univ Paris 05, Inst Cochin, CNRS, UMR 8104, Paris, France. [Morris, H. Douglas] NINDS, NIH, Bethesda, MD 20892 USA. [Riegler, Johannes; Lythgoe, Mark F.] UCL, Dept Med, Ctr Adv Biomed Imaging, London, England. [Riegler, Johannes; Lythgoe, Mark F.] UCL, Inst Child Hlth, London, England. [Arkell, Ruth M.] Australian Natl Univ, Early Mammalian Dev Lab, Res Sch Biol, Coll Med Biol & Environm, Canberra, ACT, Australia. RP Watkins-Chow, DE (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM bpavan@nhgri.nih.gov RI Campbell, Thomas/A-6964-2014; Pidsley, Ruth/D-8127-2012; Chelly, Jamel/J-7528-2015; OI Campbell, Thomas/0000-0002-4508-0089; Chelly, Jamel/0000-0002-0939-8719; Morris, H. Douglas/0000-0002-7942-3748; Flint, Jonathan/0000-0002-9427-4429; Watkins-Chow, Dawn/0000-0002-4355-0868 FU NHGRI, NIH; Wellcome Trust; NHMRC Australia [366746] FX This research was supported in part by the Intramural Research Program of NHGRI, NIH, and the Wellcome Trust and by NHMRC Australia grant 366746. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 17 Z9 17 U1 1 U2 7 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 JAN PY 2013 VL 9 IS 1 AR e1003094 DI 10.1371/journal.pgen.1003094 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 085YZ UT WOS:000314651500002 PM 23382688 ER PT J AU Rapoport, SI AF Rapoport, Stanley I. TI Translational studies on regulation of brain docosahexaenoic acid (DHA) metabolism in vivo SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 10th Fatty Acids and Cell Signaling meeting (FACS) CY NOV 06-09, 2011 CL Louisiana State Univ Hlth Sci Ctr, New Orleans, LA SP Sch Med Neuroscience Ctr Excellence HO Louisiana State Univ Hlth Sci Ctr ID ALPHA-LINOLENIC ACID; POSITRON-EMISSION-TOMOGRAPHY; POLYUNSATURATED FATTY-ACIDS; CYTOSOLIC PHOSPHOLIPASE A(2); RAT-BRAIN; ARACHIDONIC-ACID; ALZHEIMERS-DISEASE; UNANESTHETIZED RATS; NUTRITIONAL DEPRIVATION; SIGNAL-TRANSDUCTION AB One goal in the field of brain polyunsaturated fatty acid (PUFA) metabolism is to translate the many studies that have been conducted in vitro and in animal models to the clinical setting. Doing so should elucidate the role of PUFAs in the human brain, and effects of diet, drugs, disease and genetics on this role. This review discusses new in vivo radiotracer kinetic and neuroimaging techniques that allow us to do this, with a focus on docosahexaenoic acid (DHA). We illustrate how brain PUFA metabolism is influenced by graded reductions in dietary n-3 PUFA content in unanesthetized rats. We also show how kinetic tracer techniques in rodents have helped to identify mechanisms of action of mood stabilizers used in bipolar disorder, how DHA participates in neurotransmission, and how brain DHA metabolism is regulated by calcium-independent iPLA(2)beta. In humans, regional rates of brain DHA metabolism can be quantitatively imaged with positron emission tomography following intravenous injection of [1-C-11]DHA. Published by Elsevier Ltd. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S128, Bethesda, MD 20892 USA. EM sir@helix.nih.gov FU Intramural Program of the National Institute on Aging FX This study was supported entirely by the Intramural Program of the National Institute on Aging. NR 81 TC 15 Z9 15 U1 2 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2013 VL 88 IS 1 SI SI BP 79 EP 85 DI 10.1016/j.plefa.2012.05.003 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 085LD UT WOS:000314615400013 PM 22766388 ER PT J AU Kim, HY Spector, AA AF Kim, Hee-Yong Spector, Arthur A. TI Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 10th Fatty Acids and Cell Signaling meeting (FACS) CY NOV 06-09, 2011 CL Louisiana State Univ Hlth Sci Ctr, New Orleans, LA SP Sch Med Neuroscience Ctr Excellence HO Louisiana State Univ Hlth Sci Ctr DE Synaptamide; Synaptogenesis; Neuritogenesis; N-docosahexaenoylethanolamine; Docosahexaenoic acid; Omega-3 fatty acid; Fatty acid amide hydrolase; Endocannabinoids; Anandamide ID CANCER CELL-LINES; N-ACYLETHANOLAMINES; RAT-BRAIN; ENDOGENOUS LIGAND; RECEPTOR; ANANDAMIDE; BIOSYNTHESIS; ETHANOLAMIDES; TRANSDUCTION; MEMBRANES AB Docosahexaenoylethanolamide, the structural analog of the endogenous cannabinoid receptor ligand anandamide, is synthesized from docosahexaenoic acid (DHA) in the brain. Although docosahexaenoylethanolamide binds weakly to cannabinoid receptors, it stimulates neurite growth, synaptogenesis and glutamatergic synaptic activity in developing hippocampal neurons at concentrations of 10-100 nM. We have previously proposed the term synaptamide for docosahexaenoylethanolamide to emphasize its potent synaptogenic activity and structural similarity to anandamide. Synaptamide is subjected to hydrolysis by fatty acid amide hydrolase, and can be oxygenated to bioactive metabolites. The brain synaptamide content is dependent on the dietary DHA intake, suggesting an endogenous mechanism whereby diets containing adequate amounts of omega-3 fatty acids improve synaptogenesis in addition to well-recognized anti-inflammatory effects. Published by Elsevier Ltd. C1 [Kim, Hee-Yong; Spector, Arthur A.] NIAAA, Lab Mol Signaling, DICBR, NIH, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, NIH, 5625 Fishers Lane,Rm 3N-07, Bethesda, MD 20892 USA. EM hykim@nih.gov FU intramural program of NIAAA, NIH FX This work was supported by the intramural program of NIAAA, NIH. NR 31 TC 22 Z9 22 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 EI 1532-2823 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD JAN PY 2013 VL 88 IS 1 SI SI BP 121 EP 125 DI 10.1016/j.plefa.2012.08.002 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 085LD UT WOS:000314615400019 PM 22959887 ER PT J AU Murphy, DL Maile, MS Vogt, NM AF Murphy, Dennis L. Maile, Michelle S. Vogt, Nicholas M. TI 5HTTLPR: White Knight or Dark Blight? SO ACS CHEMICAL NEUROSCIENCE LA English DT Editorial Material DE serotonin; 5HTTLPR; serotonin transporter gene; SLC6A4 ID SEROTONIN TRANSPORTER GENE; OBSESSIVE-COMPULSIVE DISORDER; SLC6A4; POLYMORPHISMS; ASSOCIATION; VARIANTS; ANXIETY; REGION AB In over 100 neuroscience genetics reports on SLC6A4 published in the first part of 2012, >40% reported data from genotyping only the serotonin transporter-linked promoter region [5HTTLPR] indel, omitting genotyping of two nearby SNPs that substantially alter 5HTTLPR allele frequencies and functionality. And 25% of these papers did not report ethnicity of the subjects genotyped, another factor that alters allele frequencies. This field thus seems stultified. Improved science for the present and future will be better served by attention to more complete methods for genotyping and subject sample reporting. C1 [Murphy, Dennis L.; Maile, Michelle S.; Vogt, Nicholas M.] NIMH, Clin Sci Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, Intramural Res Program, NIH, 10-3D41,10 Ctr Dr, Bethesda, MD 20892 USA. EM dennismurphy@mail.nih.gov FU Intramural NIH HHS NR 13 TC 11 Z9 11 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JAN PY 2013 VL 4 IS 1 BP 13 EP 15 DI 10.1021/cn3002224 PG 3 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 075XN UT WOS:000313920600004 PM 23336038 ER PT J AU Cunningham, KA Anastasio, NC Fox, RG Stutz, SJ Bubar, MJ Swinford, SE Watson, CS Gilbertson, SR Rice, KC Rosenzweig-Lipson, S Moeller, FG AF Cunningham, Kathryn A. Anastasio, Noelle C. Fox, Robert G. Stutz, Sonja J. Bubar, Marcy J. Swinford, Sarah E. Watson, Cheryl S. Gilbertson, Scott R. Rice, Kenner C. Rosenzweig-Lipson, Sharon Moeller, F. Gerard TI Synergism Between a Serotonin 5-HT2A Receptor (5-HT2AR) Antagonist and 5-HT2CR Agonist Suggests New Pharmacotherapeutics for Cocaine Addiction SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE 1-Choice serial reaction time task; 5-HT2A receptor; 5-HT2C receptor; cocaine; cue reactivity; impulsivity; self-administration; serotonin ID REACTION-TIME-TASK; SEEKING BEHAVIOR; INDUCED REINSTATEMENT; SELECTIVE AGONIST; DRUG-ABUSE; MDL 100907; PART 5; IMPULSIVITY; RATS; LORCASERIN AB Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote cocaine-seeking). These factors have been mechanistically linked to serotonin (5-hydroxytryptamine, 5-HT) signaling through the 5-HT2A receptor (5-HT2AR) and 5-HT2CR; either a selective 5-HT2AR antagonist or a 5-HT2CR agonist suppresses impulsivity and cocaine-seeking in preclinical models. We conducted proof-of-concept analyses to evaluate whether a combination of 5-HT2AR antagonist plus 5-HT2CR agonist would have synergistic effects over these liability factors for relapse as measured in a 1-choice serial reaction time task and cocaine self-administration/reinstatement assay. Combined administration of a dose of the selective 5-HT2AR antagonist M100907 plus the 5-HT2CR agonist WAY163909, each ineffective alone, synergistically suppressed cocaine-induced hyperactivity, inherent and cocaine-evoked impulsive action, as well as cue- and cocaine-primed reinstatement of cocaine-seeking behavior. The identification of synergism between a 5-HT2AR antagonist plus a 5-HT2CR agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules. C1 [Cunningham, Kathryn A.; Anastasio, Noelle C.; Fox, Robert G.; Stutz, Sonja J.; Bubar, Marcy J.; Swinford, Sarah E.; Watson, Cheryl S.; Gilbertson, Scott R.; Moeller, F. Gerard] Univ Texas Med Branch, Addict Res Ctr, Galveston, TX 77555 USA. [Cunningham, Kathryn A.; Anastasio, Noelle C.; Fox, Robert G.; Stutz, Sonja J.] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA. [Gilbertson, Scott R.] Univ Houston, Dept Chem, Houston, TX USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. [Rice, Kenner C.] NIAAA, Bethesda, MD USA. [Rosenzweig-Lipson, Sharon] IVS Pharma Consulting LLC, Princeton, NJ USA. [Moeller, F. Gerard] Univ Texas Hlth Sci Ctr Houston, Dept Psychiat & Behav Sci, Ctr Neurobehav Res Addict, Houston, TX USA. RP Cunningham, KA (reprint author), Univ Texas Med Branch, Addict Res Ctr, Galveston, TX 77555 USA. EM kcunning@utmb.edu RI Cunningham, Kathryn/O-2718-2013 FU NIDA [P20 DA024157, K05 DA020087, K02 DA000403]; Center for Addiction Research at the University of Texas Medical Branch; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by NIDA grants P20 DA024157, K05 DA020087 (K.A.C.), and K02 DA000403 (F.G.M.) and by the Center for Addiction Research at the University of Texas Medical Branch. A portion of this work was also supported by the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism (K.C.R.). NR 52 TC 25 Z9 25 U1 2 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JAN PY 2013 VL 4 IS 1 BP 110 EP 121 DI 10.1021/cn300072u PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 075XN UT WOS:000313920600017 PM 23336050 ER PT J AU Diskin, B Thomas, JL AF Diskin, Boris Thomas, James L. TI Comparison of Node-Centered and Cell-Centered Unstructured Finite-Volume Discretizations: Inviscid Fluxes (vol 49, pg 836, 2011) SO AIAA JOURNAL LA English DT Correction C1 [Diskin, Boris] Univ Virginia, NIA, Dept Mech & Aerosp Engn, Charlottesville, VA 22904 USA. [Thomas, James L.] NASA, Langley Res Ctr, Computat AeroSci Branch, Hampton, VA 23681 USA. RP Diskin, B (reprint author), Univ Virginia, NIA, Dept Mech & Aerosp Engn, 100 Explorat Way, Charlottesville, VA 22904 USA. EM bdiskin@nianet.org; james.l.thomas@nasa.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER INST AERONAUT ASTRONAUT PI RESTON PA 1801 ALEXANDER BELL DRIVE, STE 500, RESTON, VA 22091-4344 USA SN 0001-1452 J9 AIAA J JI AIAA J. PD JAN PY 2013 VL 51 IS 1 BP 277 EP 277 DI 10.2514/1.J051870 PG 1 WC Engineering, Aerospace SC Engineering GA 081JZ UT WOS:000314319400025 ER PT J AU Dawson, DA Goldstein, RB Grant, BF AF Dawson, Deborah A. Goldstein, Rise B. Grant, Bridget F. TI Differences in the Profiles of DSM-IV and DSM-5 Alcohol Use Disorders: Implications for Clinicians SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE DSM-5; AUD; Treatment; Severity; Clinical Profile ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; DRUG-USE DISORDERS; UNITED-STATES; DEPENDENCE SYMPTOMS; PROBLEM DRINKERS; AUDADIS-IV; ABUSE AB Background Existing information on consequences of the DSM-5 revision for the diagnosis of alcohol use disorders (AUD) has gaps, including missing information critical to understanding implications of the revision for clinical practice. Methods Data from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were used to compare AUD severity, alcohol consumption and treatment, sociodemographic and health characteristics, and psychiatric comorbidity among individuals with DSM-IV abuse versus DSM-5 moderate AUD and DSM-IV dependence versus DSM-5 severe AUD. For each pair of disorders, we additionally compared 3 mutually exclusive groups: individuals positive solely for the DSM-IV disorder, those positive solely for the DSM-5 disorder, and those positive for both. Results Whereas 80.5% of individuals positive for DSM-IV dependence were positive for DSM-5 severe AUD, only 58.0% of those positive for abuse were positive for moderate AUD. The profiles of individuals with DSM-IV dependence and DSM-5 severe AUD were almost identical. The only significant (p < 0.005) difference, more AUD criteria among the former, reflected the higher criterion threshold (>= 4 vs. >= 3) for severe AUD relative to dependence. In contrast, the profiles of individuals with DSM-5 moderate AUD and DSM-IV abuse differed substantially. The former endorsed more AUD criteria, had higher rates of physiological dependence, were less likely to be White individuals and men, had lower incomes, were less likely to have private and more likely to have public health insurance, and had higher levels of comorbid anxiety disorders than the latter. Conclusions Similarities between the profiles of DSM-IV and DSM-5 AUD far outweigh differences; however, clinicians may face some changes with respect to appropriate screening and referral for cases at the milder end of the AUD severity spectrum, and the mechanisms through which these will be reimbursed may shift slightly from the private to public sector. C1 [Dawson, Deborah A.] Kelly Govt Serv Contractor, Bethesda, MD USA. [Dawson, Deborah A.; Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, NIH, Bethesda, MD USA. RP Dawson, DA (reprint author), 5111 Duvall Dr, Bethesda, MD 20816 USA. EM deborah.anne.dawson@gmail.com OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism; National Institutes of Health; U.S. Department of Health and Human Services; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX This study is based on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, with supplemental support from the National Institute on Drug Abuse. This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. NR 40 TC 19 Z9 20 U1 3 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 SU 1 BP E305 EP E313 DI 10.1111/j.1530-0277.2012.01930.x PG 9 WC Substance Abuse SC Substance Abuse GA 073BT UT WOS:000313719000037 PM 22974144 ER PT J AU Kline-Simon, AH Falk, DE Litten, RZ Mertens, JR Fertig, J Ryan, M Weisner, CM AF Kline-Simon, Andrea H. Falk, Daniel E. Litten, Raye Z. Mertens, Jennifer R. Fertig, Joanne Ryan, Megan Weisner, Constance M. TI Posttreatment Low-Risk Drinking as a Predictor of Future Drinking and Problem Outcomes Among Individuals with Alcohol Use Disorders SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Low-Risk Drinking; Drinking Outcomes; Social Functioning; Alcohol ID RANDOMIZED CONTROLLED-TRIAL; ADDICTION SEVERITY INDEX; DRUG-TREATMENT OUTCOMES; SUBSTANCE USE OUTCOMES; GENDER-DIFFERENCES; OLDER-ADULTS; DEPENDENCE; CARE; HMO; MEMBERS AB Background Treatment for alcohol disorders has traditionally been abstinence-oriented, but evaluating the merits of a low-risk drinking outcome as part of a primary treatment endpoint is a timely issue given new pertinent regulatory guidelines. This study explores a posttreatment low-risk drinking outcome as a predictor of future drinking and problem severity outcomes among individuals with alcohol use disorders in a large private, not for profit, integrated care health plan. Methods Study participants include adults with alcohol use disorders at 6 months (N = 995) from 2 large randomized studies. Logistic regression models were used to explore the relationship between past 30-day drinker status at 6 months posttreatment (abstinent [66%], low-risk drinking [14%] defined as nonabstinence and no days of 5+ drinking, and heavy drinking [20%] defined as 1 or more days of 5+ drinking) and 12-month outcomes, including drinking status and Addiction Severity Index measures of medical, psychiatric, family/social, and employment severity, controlling for baseline covariates. Results Compared to heavy drinkers, abstinent individuals and low-risk drinkers at 6 months were more likely to be abstinent or low-risk drinkers at 12 months (adj. ORs = 16.7 and 3.4, respectively; p < 0.0001); though, the benefit of abstinence was much greater than that of low-risk drinking. Compared to heavy drinkers, abstinent and low-risk drinkers were similarly associated with lower 12-month psychiatric severity (adj. ORs = 1.8 and 2.2, respectively, p < 0.01) and family/social problem severity (adj. OR = 2.2; p < 0.01). While abstinent individuals had lower 12-month employment severity than heavy drinkers (adj. OR = 1.9; p < 0.01), low-risk drinkers did not differ from heavy drinkers. The drinking groups did not differ on 12-month medical problem severity. Conclusions Compared to heavy drinkers, low-risk drinkers did as well as abstinent individuals for many of the outcomes important to health and addiction policy. Thus, an endpoint that allows low-risk drinking may be tenable for individuals undergoing alcohol specialty treatment. C1 [Kline-Simon, Andrea H.; Mertens, Jennifer R.; Weisner, Constance M.] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Falk, Daniel E.; Litten, Raye Z.; Fertig, Joanne; Ryan, Megan] NIAAA, Bethesda, MD USA. [Weisner, Constance M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Kline-Simon, AH (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM andrea.h.kline-simon@kp.org FU National Institute on Alcoholism and Alcohol Abuse [R37 AA10359]; National Institute on Drug Abuse [R37 DA10572] FX This study was supported by grants from the National Institute on Alcoholism and Alcohol Abuse Grant (R37 AA10359) and the National Institute on Drug Abuse (R37 DA10572). We thank Agatha Hinman, BA, for editorial assistance. NR 24 TC 18 Z9 18 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 SU 1 BP E373 EP E380 DI 10.1111/j.1530-0277.2012.01908.x PG 8 WC Substance Abuse SC Substance Abuse GA 073BT UT WOS:000313719000045 PM 22827502 ER PT J AU Becker, RE Greig, NH AF Becker, Robert E. Greig, Nigel H. TI Fire in the ashes: Can failed Alzheimer's disease drugs succeed with second chances? SO ALZHEIMERS & DEMENTIA LA English DT Article DE AD drug development; (-)-Phenserine; Validity; Scientific practices ID PROTEIN MESSENGER-RNA; CLINICAL-TRIALS; AMYLOID-BETA; MACULAR DEGENERATION; TREATMENT EFFICACY; RATING-SCALE; INTERLEUKIN-1; TRANSLATION; DISORDERS; OUTCOMES AB Background: Since Cognex, more than 200 Alzheimer's disease (AD) drug candidates have failed. Investigations have identified vulnerabilities of these AD drug developments to methodological errors. (-)-Phenserine has been discussed as possibly failing due to flawed methods and practices in development. Methods: We analyzed documentation of (-)-phenserine's development for vulnerabilities to errors and designed interventions for a redevelopment that could provide fair or unbiased assessments of (-)-phenserine target engagement, target relevance for human diseases, and adequate presumptive evidence of efficacy as a therapeutic for one or more diagnoses to justify registration-required clinical trials. Results: Similar to studies of 40 other AD developments, with (-)-phenserine, we found little evidence of preemptive interventions against potentially invalidating errors, grounds to judge progress in development through stages as not scientifically justifiable, and variance excess and placebo group improvements as capable of accounting for outcomes from various studies in the development. We propose to compare a redevelopment resourced to counter these deficiencies with the original development as historical control to evaluate further our hypothesis that errors in development accounted for the (-)-phenserine failure, specifically, and other AD drug failures, potentially. Conclusions: We find support for our earlier proposal that (-)-phenserine did not fail, but the methods of development did fail, to provide conditions where efficacy could be tested. We propose that redevelopment under conditions aimed to correct methodological deficiencies common in AD drug developments will successfully test efficacy for (-)-phenserine and hopefully lead to a disease-modifying addition to the AD therapeutic armamentarium. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Becker, Robert E.] Aristea Translat Med Corp, Freeport, ME USA. [Greig, Nigel H.] NIH, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD USA. RP Becker, RE (reprint author), Aristea Translat Med Corp, Freeport, ME USA. EM rebecker2008@comcast.net FU Intramural Research Program, National Institute on Aging; NIH FX N.H.G. was supported by the Intramural Research Program, National Institute on Aging, and NIH. NR 55 TC 13 Z9 13 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2013 VL 9 IS 1 BP 50 EP 57 DI 10.1016/j.jalz.2012.01.007 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 078EO UT WOS:000314081400006 PM 22465172 ER PT J AU Prince, M Bryce, R Albanese, E Wimo, A Ribeiro, W Ferri, CP AF Prince, Martin Bryce, Renata Albanese, Emiliano Wimo, Anders Ribeiro, Wagner Ferri, Cleusa P. TI The global prevalence of dementia: A systematic review and metaanalysis SO ALZHEIMERS & DEMENTIA LA English DT Review DE Dementia; Prevalence; Epidemiology; Projection; WHO Global Burden of Disease regions; Worldwide; Systematic review; Metaanalysis ID DWELLING BRAZILIAN POPULATION; ALZHEIMERS-DISEASE; ELDERLY-PEOPLE; AFRICAN-AMERICANS; COGNITIVE IMPAIRMENT; DEVELOPING-COUNTRIES; MAJOR SUBTYPES; 2 COMMUNITIES; WEST-AFRICA; SAO-PAULO AB Background: The evidence base on the prevalence of dementia is expanding rapidly, particularly in countries with low and middle incomes. A reappraisal of global prevalence and numbers is due, given the significant implications for social and public policy and planning. Methods: In this study we provide a systematic review of the global literature on the prevalence of dementia (1980-2009) and metaanalysis to estimate the prevalence and numbers of those affected, aged >= 60 years in 21 Global Burden of Disease regions. Results: Age-standardized prevalence for those aged >= 60 years varied in a narrow band, 5%-7% in most world regions, with a higher prevalence in Latin America (8.5%), and a distinctively lower prevalence in the four sub-Saharan African regions (2%-4%). It was estimated that 35.6 million people lived with dementia worldwide in 2010, with numbers expected to almost double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. In 2010, 58% of all people with dementia lived in countries with low or middle incomes, with this proportion anticipated to rise to 63% in 2030 and 71% in 2050. Conclusion: The detailed estimates in this study constitute the best current basis for policy-making, planning, and allocation of health and welfare resources in dementia care. The age-specific prevalence of dementia varies little between world regions, and may converge further. Future projections of numbers of people with dementia may be modified substantially by preventive interventions (lowering incidence), improvements in treatment and care (prolonging survival), and disease-modifying interventions (preventing or slowing progression). All countries need to commission nationally representative surveys that are repeated regularly to monitor trends. (C) 2013 The Alzheimer's Association. All rights reserved. C1 [Prince, Martin; Bryce, Renata; Albanese, Emiliano; Ribeiro, Wagner; Ferri, Cleusa P.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Albanese, Emiliano] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Wimo, Anders] Karolinska Inst, KI Alzheimer Dis Res Ctr, Stockholm, Sweden. [Wimo, Anders] Karolinska Inst, Aging Res Ctr, Stockholm, Sweden. [Ribeiro, Wagner; Ferri, Cleusa P.] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. RP Prince, M (reprint author), Kings Coll London, Inst Psychiat, London WC2R 2LS, England. EM Martin.Prince@kcl.ac.uk RI Prince, Martin/A-9170-2010; Ferri, Cleusa/B-2922-2010; OI Prince, Martin/0000-0003-1379-7146; Ferri, Cleusa/0000-0002-1815-7685; Ribeiro, Wagner/0000-0001-6735-3861; Wimo, Anders/0000-0003-0963-5750 FU Alzheimer's Disease International (ADI) FX Disclosures: Anders Wimo has been acting as consultant to drug companies (e.g., Pfizer, Janssen-Cilag, Astra-Zeneca, Novartis, Merz, Lundbeck, Forest, GSK, Wyeth, Sanofi, Elan, Neurochem, Lilly, BMS) purchasing or developing drugs for treatment of Alzheimer's disease or other dementias, but this has not influenced work associated with this study nor has there been any financing from these companies of this work. This systematic review was supported by a small grant from Alzheimer's Disease International (ADI) to King's College London. ADI has acknowledged support for the production and dissemination of the World Alzheimer Report 2009 from the Vradenburg Foundation, Geoffrey Beene Foundation, Alzheimer's Association, Alzheimer's Australia, Alzheimer's Australia WA, Alzheimer Scotland, Alzheimer's Society, Association Alzheimer Suisse, Alzheimerforeningen i Sverige, Deutsche Alzheimer Gesellschaft, and Stichting Alzheimer Nederland. The sponsors had no role in study design, data collection, data analysis, data interpretation, or the writing of this review. NR 64 TC 725 Z9 756 U1 55 U2 276 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2013 VL 9 IS 1 BP 63 EP 75 DI 10.1016/j.jalz.2012.11.007 PG 13 WC Clinical Neurology SC Neurosciences & Neurology GA 078EO UT WOS:000314081400008 PM 23305823 ER PT J AU Micklitsch, CM Oquare, BY Zhao, C Appella, DH AF Micklitsch, Christopher M. Oquare, Bereket Yemane Zhao, Chao Appella, Daniel H. TI Cyclopentane-Peptide Nucleic Acids for Qualitative, Quantitative, and Repetitive Detection of Nucleic Acids SO ANALYTICAL CHEMISTRY LA English DT Article ID BINDING-AFFINITY; DNA; DIAGNOSTICS; RNA; IDENTIFICATION; STABILITY; BACKBONE; BIOLOGY; SYSTEM AB We report the development of chemically modified peptide nucleic acids (PNAs) as probes for qualitative and quantitative detection of DNA. The remarkable stability of PNAs toward enzymatic degradation makes this class of molecules ideal to develop as part of a diagnostic device that can be used outside of a laboratory setting. Using an enzyme-linked reporter assay, we demonstrate that excellent levels of detection and accuracy for anthrax DNA can be achieved using PNA probes with suitable chemical components designed into the probe. In addition, we report on DNA-templated cross-linking of PNA probes as a way to preserve genetic information for repetitive and subsequent analysis. This report is the first detailed examination of the qualitative and quantitative properties of chemically modified PNA for nucleic acid detection and provides a platform for studying and optimizing PNA probes prior to incorporation into new technological platforms. C1 [Micklitsch, Christopher M.; Oquare, Bereket Yemane; Zhao, Chao; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov FU NIDDK; NIAID NIH/FDA Intramural Biodefense Research Program FX We acknowledge support from the Intramural Research Program of NIDDK and the NIAID NIH/FDA Intramural Biodefense Research Program. NR 31 TC 9 Z9 9 U1 3 U2 51 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 1 PY 2013 VL 85 IS 1 BP 251 EP 257 DI 10.1021/ac3026459 PG 7 WC Chemistry, Analytical SC Chemistry GA 065NZ UT WOS:000313156500037 PM 23214925 ER PT J AU Wiley, TRA Lynne-Landsman, SD Maholmes, V AF Wiley, Tisha R. A. Lynne-Landsman, Sarah D. Maholmes, Valerie TI Advancing the Next Generation of Applied Developmental Science SO APPLIED DEVELOPMENTAL SCIENCE LA English DT Article C1 [Wiley, Tisha R. A.] NIDA, Kensington, NSW, Australia. [Lynne-Landsman, Sarah D.] Univ Florida, Gainesville, FL 32611 USA. [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Maholmes, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 4B05A, Bethesda, MD 20892 USA. EM maholmev@mail.nih.gov OI Wiley, Tisha/0000-0001-6399-1647 NR 0 TC 0 Z9 0 U1 0 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1088-8691 J9 APPL DEV SCI JI Appl. Dev. Sci. PD JAN 1 PY 2013 VL 17 IS 1 SI SI BP 1 EP 3 DI 10.1080/10888691.2013.750189 PG 3 WC Psychology, Developmental SC Psychology GA 079JH UT WOS:000314165900001 ER PT J AU Cousens, LP Tassone, R Mazer, BD Ramachandiran, V Scott, DW De Groot, AS AF Cousens, Leslie P. Tassone, Ryan Mazer, Bruce D. Ramachandiran, Vasanthi Scott, David W. De Groot, Anne S. TI Tregitope update: Mechanism of action parallels IVIg SO AUTOIMMUNITY REVIEWS LA English DT Review DE Treg; Tregitope; IVIg; Autoimmunity; MHC; Tolerance ID REGULATORY T-CELLS; IMMUNE TOLERANCE INDUCTION; INTRAVENOUS IMMUNOGLOBULIN; B-CELLS; IGG FC; ANTIINFLAMMATORY ACTIVITY; AUTOIMMUNE-DISEASES; MONOCLONAL-ANTIBODY; TGF-BETA; PEPTIDE AB In the course of screening immunoglobulin G (IgG) sequences for T cell epitopes, we identified novel Treg epitope peptides, now called Tregitopes, contained in the highly conserved framework regions of Fab and Fc. Tregitopes may provide one explanation for the expansion and stimulation of Treg cells following intravenous immunoglobulin (IVIg) therapy. Their distinguishing characteristics include in silico signatures that suggest high-affinity binding to multiple human HLA class II DR and conservation across IgG isotypes and mammalian species with only minor amino acid modifications. Tregitopes induce expansion of CD4(+)/CD25(hi)/FoxP3(+) T cells and suppress immune responses to co-incubated antigens in vitro. By comparing the human IgG Tregitopes (hTregitopes 167 and 289, located in the IgG CH1 and CH2 domains) and Fab to murine sequences, we identified class II-restricted murine Tregitope homologs (mTregitopes). In vivo, mTregitopes suppress inflammation and reproducibly induce Tregs to expand. In vitro studies suggest that the Tregitope mechanism of action is to induce Tregs to respond, leading to production of regulatory signals, followed by modulation of dendritic cell phenotype. The identification of Treg epitopes in IgG suggests that additional Tregitopes may also be present in other autologous proteins; methods for identifying and validating such peptides are described here. The discovery of Tregitopes in IgG and other autologous proteins may lead to the development of new insights as to the role of Tregs in autoimmune diseases. (c) 2012 Elsevier B.V. All rights reserved. C1 [Cousens, Leslie P.; Tassone, Ryan; De Groot, Anne S.] EpiVax Inc, Providence, RI 02903 USA. [Mazer, Bruce D.] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Ramachandiran, Vasanthi] Emory Univ, NIH Tetramer Facil, Atlanta, GA 30322 USA. [Scott, David W.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [De Groot, Anne S.] Univ Rhode Isl, Kingston, RI 02881 USA. RP De Groot, AS (reprint author), EpiVax Inc, 146 Clifford St, Providence, RI 02903 USA. EM AnnieD@EpiVax.com RI De Groot, Anne/B-6221-2013 OI De Groot, Anne/0000-0001-5911-1459 FU NIH for the Emory Tetramer Facility, Emory University [N01-AI25456] FX The authors are grateful to the following individuals who made significant contributions to the research summarized in this paper: Elizabeth McClaine, Yan Su, Lauren Levitz, Lenny Moise, and Bill Martin (EpiVax). We are also grateful for the support of NIH for the Emory Tetramer Facility (N01-AI25456), Emory University. NR 61 TC 41 Z9 42 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9972 J9 AUTOIMMUN REV JI Autoimmun. Rev. PD JAN PY 2013 VL 12 IS 3 BP 436 EP 443 DI 10.1016/j.autrev.2012.08.017 PG 8 WC Immunology SC Immunology GA 083AN UT WOS:000314435200014 PM 22944299 ER PT J AU Mercer, N Ramakrishnan, B Boeggeman, E Verdi, L Qasba, PK AF Mercer, Natalia Ramakrishnan, Boopathy Boeggeman, Elizabeth Verdi, Luke Qasba, Pradman K. TI Use of Novel Mutant Galactosyltransferase for the Bioconjugation of Terminal N-Acetylglucosamine (GlcNAc) Residues on Live Cell Surface SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MODIFIED PROTEINS; CRYSTAL-STRUCTURE; CHEMICAL HANDLE; LIVING CELLS; GLYCANS; CANCER; BETA-1,4-GALACTOSYLTRANSFERASE; GLYCOSYLATION; GLYCOPROTEINS; SPECIFICITY AB On the basis of the crystal structure of bovine beta 4Gal-T1 enzyme, mutation of a single amino acid Y289 to L289 (Y289L) changed its donor specificity from Gal to N-acetyl-galactosamine (GalNAc). A chemoenzymatic method that uses GalNAc analogues like GalNAz or 2-keto-Gal as sugar donors with the enzyme Y289L-beta 4Gal-T1 has identified hundreds of cytosolic and nuclear proteins that have O-GlcNAc modifications. To avoid potential cytotoxicity at Mn2+ concentrations required to selectively modify GlcNAc residues on the surface of live cells, we have engineered a Mg2+-dependent enzyme. Previously, we found that the mutation of the metal-binding residue Met-344 to His-344 in bovine beta 4Gal-T1 enzyme altered its metal-ion specificity in such a way that the M344H-beta 4Gal-T1 enzyme exhibits better catalytic activity with Mg2+ than with Mn2+. Here, we find that, when these two mutations are combined, the double mutant, Y289L-M344H-beta 4Gal-T1, transfers GalNAc and its analogue sugars to the acceptor GlcNAc in the presence of Mg2+. Using this mutant enzyme, we have detected free GlcNAc residues on the surface glycans of live HeLa cells and platelets. The specific transfer of a synthetic sugar with a chemical handle to the terminal GlcNAc residues on the surface of live cells provides a novel tool for selective modification, detection, and isolation of GlcNAc-ending glycans present on the cellular surface. C1 [Mercer, Natalia; Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Verdi, Luke; Qasba, Pradman K.] SAIC Frederick Inc, Struct Glycobiol Sect, CCR Nanobiol Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Ramakrishnan, Boopathy; Boeggeman, Elizabeth] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), SAIC Frederick Inc, Struct Glycobiol Sect, CCR Nanobiol Program, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, Frederick National Laboratory for Cancer Research FX We thank Dr. Lockett and Ms. Kim Peifley for confocal microscopy assistance, Dr. Mc Vicar and Ms. Laura Quigley for platelet isolation, and Dr. Floris L. van Delft from Nijamen, The Netherlands, for BCN-biotin reagent. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the view 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 NIH, Frederick National Laboratory for Cancer Research. NR 38 TC 7 Z9 7 U1 5 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2013 VL 24 IS 1 BP 144 EP 152 DI 10.1021/bc300542z PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 076CI UT WOS:000313933700016 PM 23259695 ER PT J AU Abidi, MH Agarwal, R Tageja, N Ayash, L Deol, A Al-Kadhimi, Z Abrams, J Cronin, S Ventimiglia, M Lum, L Ratanatharathorn, V Zonder, J Uberti, J AF Abidi, Muneer H. Agarwal, Rishi Tageja, Nishant Ayash, Lois Deol, Abhinav Al-Kadhimi, Zaid Abrams, Judith Cronin, Simon Ventimiglia, Marie Lum, Lawrence Ratanatharathorn, Voravit Zonder, Jeffrey Uberti, Joseph TI A Phase I Dose-Escalation Trial of High-Dose Melphalan with Palifermin for Cytoprotection Followed by Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Normal Renal Function SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Palifermin; Oral mucositis; High-dose melphalan ID KERATINOCYTE GROWTH-FACTOR; BONE-MARROW-TRANSPLANTATION; RANDOMIZED-TRIAL; ORAL MUCOSITIS; INTRAVENOUS MELPHALAN; MUCOSAL DAMAGE; RISK-FACTORS; CHEMOTHERAPY; THERAPY; AMIFOSTINE AB Melphalan 200 mg/m(2) is the standard conditioning regimen for patients with multiple myeloma (MM) with normal renal function (NRF) undergoing autologous stem cell transplant (ASCT). In an effort to escalate the dose of melphalan and to improve the efficacy, we designed a dose-escalation study of melphalan in conjunction with palifermin in patients with NRF, with the hope that a higher dose of melphalan can be administered with an acceptable degree of oral mucositis (OM). We enrolled 19 patients (18 evaluable) with NRF. Dose-escalation of melphalan administered on day 2 began at 200 mg/m2 with palifermin administered at a fixed dose of 60 mcg/kg/day. Palifermin was given as an i.v. bolus on day 5, 4, and 3, and then on day +1, +2, and +3. Subsequent close escalations of melphalan were done at 20 mg/m2 increments up to a maximum dose of 280 mg/m2. Of 18 evaluable patients, there were no treatment-related deaths by day 100. The median age was 48.5 years (range, 33-65 years). The most common adverse events related to palifermin included rash (18 events, no >= grade 3 events), elevation of amylase (10 events, 4 were grade 3 but asymptomatic), and lipase (5 events, 2 were grade 3 but asymptomatic), edema (11 events, no >= grade 3). The overall incidence of OM grade 3 was 44% (8/18) with a median duration of severe mucositis of 5 days (range, 3-6 days). Eleven patients (61%) required opioid analgesics. None of the patients received total parenteral nutrition (TPN)/nasogastric feeding. Two of 6 patients who were given melphalan 280 mg/m2 did not develop OM. Cardiac dose-limiting toxicity (DLT) in the form of atrial fibrillation did occur in 1 of 6 patients treated with melphalan 280 mg/m2. Palifermin has permitted safe dose escalation of melphalan up to 280 mg/m2, thus reaching the cumulative dosage of melphalan administered in tandem ASCT. This higher dose of melphalan has the potential to improve the efficacy and, hopefully, outcomes of patients with MM with a single ASCT. A phase 2 trial is necessary to better delineate the antimyeloma efficacy of this regimen. (C) 2013 American Society for Blood and Marrow Transplantation. C1 [Abidi, Muneer H.] Karmanos Canc Inst, Dept Bone Marrow Transplantat, Detroit, MI 48201 USA. [Agarwal, Rishi] Synergy Med Educ Alliance, Saginaw, MI USA. [Abidi, Muneer H.; Ayash, Lois; Deol, Abhinav; Al-Kadhimi, Zaid; Abrams, Judith; Lum, Lawrence; Ratanatharathorn, Voravit; Uberti, Joseph] Wayne State Univ, Detroit, MI USA. [Tageja, Nishant] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Abidi, MH (reprint author), Karmanos Canc Inst, Dept Bone Marrow Transplantat, 4100 John R,4 HWCRC,Room 4257, Detroit, MI 48201 USA. EM abidim@karmanos.org OI Abidi, Muneer/0000-0002-9936-6031 FU Biovitrum pharmaceuticals FX Biovitrum pharmaceuticals provided palifermin and an unrestricted research grant for this study. NR 29 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 BP 56 EP 61 DI 10.1016/j.bbmt.2012.08.003 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZP UT WOS:000313998000009 PM 22892551 ER PT J AU Rezvani, K Brody, JD Kohrt, HE Logan, AC Advani, R Czerwinski, DK Weng, WK Negrin, RS Carlton, V Faham, M Levy, R Barrett, J AF Rezvani, Katayoun Brody, Joshua D. Kohrt, Holbrook E. Logan, Aaron C. Advani, Ranjana Czerwinski, Debra Katherine Weng, Wen-Kai Negrin, Robert S. Carlton, Victoria Faham, Malek Levy, Ronald Barrett, John TI Cancer Vaccines and T Cell Therapy SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID WT1 PEPTIDE VACCINATION; MINOR HISTOCOMPATIBILITY ANTIGENS; MYELOID MALIGNANCIES; GENETIC-MODIFICATION; COMPLETE REMISSION; LEUKEMIA; LYMPHOCYTES; TRANSPLANTATION; LYMPHOMA; REGRESSION C1 [Rezvani, Katayoun] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Brody, Joshua D.; Kohrt, Holbrook E.; Logan, Aaron C.; Advani, Ranjana; Czerwinski, Debra Katherine; Weng, Wen-Kai; Negrin, Robert S.; Levy, Ronald] Mt Sinai Sch Med, Lymphoma Immunotherapy Program, New York, NY USA. [Carlton, Victoria; Faham, Malek] Sequenta Inc, San Francisco, CA USA. [Barrett, John] NHLBI, Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM KRezvani@mdanderson.org OI Logan, Aaron/0000-0002-1179-5879 FU NCI NIH HHS [P30 CA016672] NR 27 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 SU 1 BP S97 EP S101 DI 10.1016/j.bbmt.2012.09.020 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100024 PM 23041602 ER PT J AU Tisdale, JF Eapen, M Saccardi, R AF Tisdale, John F. Eapen, Mary Saccardi, Riccardo TI HCT for Nonmalignant Disorders SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID SICKLE-CELL-DISEASE; BONE-MARROW-TRANSPLANTATION; ANEMIA; EXPERIENCE; CHIMERISM C1 [Tisdale, John F.] NHLBI, Mol & Clin Hematol Branch, NIDDKD, NIH, Bethesda, MD 20892 USA. [Eapen, Mary] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Saccardi, Riccardo] Careggi Univ Hosp, Dept Hematol, Florence, Italy. RP Saccardi, R (reprint author), Careggi Univ Hosp, Dept Hematol, Florence, Italy. EM riccardo.saccardi@aouc.unifi.it NR 12 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 SU 1 BP S6 EP S7 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100003 PM 23104188 ER PT J AU van Den Brinki, M Leen, AM Baird, K Merchant, M Mackall, C Bollard, CM AF van Den Brinki, Marcel Leen, Ann M. Baird, Kristin Merchant, Melinda Mackall, Crystal Bollard, Catherine M. TI Enhancing Immune Reconstitution: From Bench to Bedside SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; ADOPTIVE TRANSFER; CANCER; CYTOMEGALOVIRUS; TRANSPLANTATION; LYMPHOCYTES; IMMUNOTHERAPY; REGENERATION; EXPANSION C1 [van Den Brinki, Marcel] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Leen, Ann M.; Bollard, Catherine M.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Baird, Kristin; Merchant, Melinda; Mackall, Crystal] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Bollard, CM (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, 1102 Bates Ave,Suite 1770-01, Houston, TX 77030 USA. EM cmbollar@txccc.org FU NCI NIH HHS [P01 CA148600, P30 CA125123, R21 CA149967] NR 28 TC 3 Z9 3 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2013 VL 19 IS 1 SU 1 BP S79 EP S83 DI 10.1016/j.bbmt.2012.09.016 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 076ZQ UT WOS:000313998100020 PM 23041603 ER PT J AU Monti, M Zanoni, M Calligaro, A Ko, MSH Mauri, P Redi, CA AF Monti, Manuela Zanoni, Mario Calligaro, Alberto Ko, Minoru S. H. Mauri, Pierluigi Redi, Carlo Alberto TI Developmental Arrest and Mouse Antral Not-Surrounded Nucleolus Oocytes SO BIOLOGY OF REPRODUCTION LA English DT Article DE cytoplasmic lattices; Mater; oocyte maturation; oocyte to embryo transition; oogenesis; preimplantation embryo development ID GENE-EXPRESSION; PREIMPLANTATION DEVELOPMENT; PROTEIN; COMPETENCE; EMBRYOS; MATER; MICE; ORGANIZATION; MATURATION; CHROMATIN AB The antral compartment in the ovary consists of two populations of oocytes that differ by their ability to resume meiosis and to develop to the blastocyst stage. For reasons still not entirely clear, antral oocytes termed surrounded nucleolus (SN; 70% of the population of antral oocytes) develop to the blastocyst stage, whereas those called not-surrounded nucleolus (NSN) arrest at two cells. We profiled transcriptomic, proteomic, and morphological characteristics of antral oocytes and observed that NSN oocyte arrest is associated with lack of cytoplasmic lattices coincident with reduced expression of MATER and ribosomal proteins. Cytoplasmic lattices have been shown to store maternally derived mRNA and ribosomes in mammalian oocytes and embryos, and MATER has been shown to be required for cytoplasmic lattice formation. Thus, we isolated antral oocytes from a Mater(tm/tm) mouse and we observed that 84% of oocytes are of the NSN type. Our results provide the first molecular evidence to account for inability of NSN-derived embryos to progress beyond the two-cell stage; these results may be relevant to naturally occurring preimplantation embryo demise in mammals. C1 [Monti, Manuela; Redi, Carlo Alberto] Fdn IRCCS Policlin San Matteo, Res Ctr Regenerat Med, Dept Sci, I-27100 Pavia, Italy. [Zanoni, Mario; Redi, Carlo Alberto] Univ Pavia, Lab Dev Biol, I-27100 Pavia, Italy. [Calligaro, Alberto] Univ Pavia, Dept Expt Med, Histol & Embryol Unit, I-27100 Pavia, Italy. [Ko, Minoru S. H.] NIA, Lab Genet, NIH, Baltimore, MD 21224 USA. [Mauri, Pierluigi] Inst Biomed Technol ITB CNR, Prote & Metabol Unit, Segrate, Italy. RP Monti, M (reprint author), Fdn IRCCS Policlin San Matteo, Res Ctr Regenerat Med, Dept Sci, Viale Golgi 19, I-27100 Pavia, Italy. EM m.monti@smatteo.pv.it RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU National Institutes of Health, National Institute on Aging [1 ZIA AG000662]; Ministero della Salute, Ricerca Finalizzata/giovani ricercatori anno of the Fondazione IRCCS Ospedale San Matteo, Pavia (I). FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (grant 1 ZIA AG000662 to M. S. H. K.). M. M. and C. A. R. acknowledge the financial support of the Ministero della Salute, Ricerca Finalizzata/giovani ricercatori anno 2009 of the Fondazione IRCCS Ospedale San Matteo, Pavia (I). All DNA microarray data are available at the public depository (Gene Expression Omnibus [GEO], National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/geo/, GEO accession number GSE34671) and at the National Institute on Aging Array Analysis software (http://lgsun.grc.nia.nih.gov/ANOVA/). NR 33 TC 18 Z9 18 U1 0 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2013 VL 88 IS 1 AR 2 DI 10.1095/biolreprod.112.103887 PG 7 WC Reproductive Biology SC Reproductive Biology GA 081YD UT WOS:000314357700001 PM 23136301 ER PT J AU Flegel, WA AF Flegel, Willy A. TI ABO genotyping: the quest for clinical applications SO BLOOD TRANSFUSION LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; PARA-BOMBAY INDIVIDUALS; BLOOD-GROUP ANTIGENS; RED-CELL; GROUP GENES; LARGE-SCALE; H-ALLELE; EXPRESSION; PHENOTYPE C1 [Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Flegel, WA (reprint author), NIH, Ctr Clin, Dept Transfus Med, Bldg 10,Room 1C711,MSC-1184,10 Ctr Dr, Bethesda, MD 20892 USA. EM bill.flegel@nih.gov FU Intramural NIH HHS NR 36 TC 5 Z9 5 U1 0 U2 11 PU SIMITI SERVIZI SRL PI MILAN PA VIA DESIDERIO 21, MILAN, 20131, ITALY SN 1723-2007 J9 BLOOD TRANSFUS-ITALY JI Blood Transf. PD JAN PY 2013 VL 11 IS 1 BP 6 EP 9 DI 10.2450/2012.0250-12 PG 4 WC Hematology SC Hematology GA 082JZ UT WOS:000314389400003 PM 23245718 ER PT J AU Fojo, T Bates, S AF Fojo, Tito Bates, Susan TI Mechanisms of Resistance to PARP Inhibitors-Three and Counting SO CANCER DISCOVERY LA English DT Editorial Material ID HEREDITARY BREAST-CANCER; KINASE INHIBITORS; MAMMARY-TUMORS; MOUSE MODEL; 53BP1; COMBINATION AB Given the malleable nature of cancer cells, we should expect, and do see, the development of resistance to any new chemotherapeutic agent. Models that help us understand how this happens are a first step to better and more effective chemotherapeutics. Cancer Discov; 3(1); 20-3. (C) 2012 AACR. C1 [Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1906,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM fojot@mail.nih.gov NR 16 TC 17 Z9 17 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2013 VL 3 IS 1 BP 20 EP 23 DI 10.1158/2159-8290.CD-12-0514 PG 4 WC Oncology SC Oncology GA 072BI UT WOS:000313642900019 PM 23319766 ER PT J AU Jaspers, JE Kersbergen, A Boon, U Sol, W van Deemter, L Zander, SA Drost, R Wientjens, E Ji, J Aly, A Doroshow, JH Cranston, A Martin, NMB Lau, A O'Connor, MJ Ganesan, S Borst, P Jonkers, J Rottenberg, S AF Jaspers, Janneke E. Kersbergen, Ariena Boon, Ute Sol, Wendy van Deemter, Liesbeth Zander, Serge A. Drost, Rinske Wientjens, Ellen Ji, Jiuping Aly, Amal Doroshow, James H. Cranston, Aaron Martin, Niall M. B. Lau, Alan O'Connor, Mark J. Ganesan, Shridar Borst, Piet Jonkers, Jos Rottenberg, Sven TI Loss of 53BP1 Causes PARP Inhibitor Resistance in Brca1-Mutated Mouse Mammary Tumors SO CANCER DISCOVERY LA English DT Article ID STRAND-BREAK REPAIR; DNA-END RESECTION; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; CHEMOTHERAPY RESISTANCE; BRCA2-DEFICIENT TUMORS; OVARIAN CARCINOMAS; CELL-CYCLE; BRCA1; SENSITIVITY AB Inhibition of PARP is a promising therapeutic strategy for homologous recombination-deficient tumors, such as BRCA1-associated cancers. We previously reported that BRCA1-deficient mouse mammary tumors may acquire resistance to the clinical PARP inhibitor (PARPi) olaparib through activation of the P-glycoprotein drug efflux transporter. Here, we show that tumorspecific genetic inactivation of P-glycoprotein increases the long-term response of BRCA1-deficient mouse mammary tumors to olaparib, but these tumors eventually developed PARPi resistance. In a fraction of cases, this resistance is caused by partial restoration of homologous recombination due to somatic loss of 53BP1. Importantly, PARPi resistance was minimized by long-term treatment with the novel PARP inhibitor AZD2461, which is a poor P-glycoprotein substrate. Together, our data suggest that restoration of homologous recombination is an important mechanism for PARPi resistance in BRCA1-deficient mammary tumors and that the risk of relapse of BRCA1-deficient tumors can be effectively minimized by using optimized PARP inhibitors. C1 [Jaspers, Janneke E.; Kersbergen, Ariena; Sol, Wendy; van Deemter, Liesbeth; Zander, Serge A.; Borst, Piet; Rottenberg, Sven] Netherlands Canc Inst, Div Mol Oncol, NL-1066 CX Amsterdam, Netherlands. [Jaspers, Janneke E.; Boon, Ute; Drost, Rinske; Wientjens, Ellen; Jonkers, Jos] Netherlands Canc Inst, Div Mol Pathol, NL-1066 CX Amsterdam, Netherlands. [Ji, Jiuping] NCI, Natl Clin Target Validat Lab, Frederick, MD 21701 USA. [Doroshow, James H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Doroshow, James H.] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Aly, Amal; Ganesan, Shridar] Canc Inst New Jersey, New Brunswick, NJ USA. [Cranston, Aaron; Martin, Niall M. B.] KuDOS Pharmaceut, Cambridge, England. [Lau, Alan; O'Connor, Mark J.] AstraZeneca, Macclesfield, Cheshire, England. RP Jonkers, J (reprint author), Netherlands Canc Inst, Div Mol Pathol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands. EM s.rottenberg@nki.nl FU Netherlands Organization for Scientific Research [NWO-Toptalent 021.002.104, NWO-VIDI-91711302]; Dutch Cancer Society [NKI 2006-3566, NKI 2007-3772, NKI 2009-4303, NKI 2011-5220]; European Union (EU) [037665-CHEMORES, 260791-Eurocan-Platform]; CTMM Breast Care; NKI-AVL Cancer Systems Biology Centre FX This work was supported by grants from the Netherlands Organization for Scientific Research (NWO-Toptalent 021.002.104 to J.E. Jaspers and NWO-VIDI-91711302 to S. Rottenberg), the Dutch Cancer Society (projects NKI 2006-3566, NKI 2007-3772, NKI 2009-4303, and NKI 2011-5220), the European Union (EU) FP6 Integrated Project 037665-CHEMORES, the EU FP7 Project 260791-Eurocan-Platform, CTMM Breast Care, and the NKI-AVL Cancer Systems Biology Centre. NR 38 TC 109 Z9 109 U1 1 U2 32 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2159-8274 EI 2159-8290 J9 CANCER DISCOV JI Cancer Discov. PD JAN PY 2013 VL 3 IS 1 BP 68 EP 81 DI 10.1158/2159-8290.CD-12-0049 PG 14 WC Oncology SC Oncology GA 072BI UT WOS:000313642900025 PM 23103855 ER PT J AU Williams, RV Travison, T Kaltman, JR Cecchin, F Colan, SD Idriss, SF Lu, MM Margossian, R Reed, JH Silver, ES Stephenson, EA Vetter, VL AF Williams, Richard V. Travison, Thomas Kaltman, Jonathan R. Cecchin, Frank Colan, Steven D. Idriss, Salim F. Lu, Minmin Margossian, Renee Reed, John H. Silver, Eric S. Stephenson, Elizabeth A. Vetter, Victoria L. CA Pediatric Heart Network TI Comparison of Fontan Survivors with and without Pacemakers: A Report from the Pediatric Heart Network Fontan Cross-sectional Study SO CONGENITAL HEART DISEASE LA English DT Article DE Fontan Procedure; Pacemaker; Functional Status; Ventricular Function ID INTRAATRIAL LATERAL TUNNEL; OPERATION; IMPLANTATION; PALLIATION; MORBIDITY; CHILDREN AB Objective. Although many Fontan patients undergo pacemaker placement, there are few studies characterizing this population. Our purpose was to compare clinical characteristics, functional status and measures of ventricular performance in Fontan patients with and without a pacemaker. Patients and Design. The National Heart, Lung, and Blood Institute funded Pediatric Heart Network Fontan Cross-Sectional Study characterized 546 Fontan survivors. Clinical characteristics, medical history and study outcomes (Child Health Questionnaire [CHQ]), echocardiographic evaluation of ventricular function, and exercise testing) were compared between subjects with and without pacemakers. Results. Of 71 subjects with pacemakers (13%), 43/71 (61%) were in a paced rhythm at the time of study enrollment (age 11.9 +/- 3.4 years). Pacemaker subjects were older at study enrollment, more likely to have single left ventricles, and taking more medications. There were no differences in age at Fontan or Fontan type between the pacemaker and no pacemaker groups. There were no differences in exercise performance between groups. CHQ physical summary scores were lower in the pacemaker subjects (39.7 +/- 14.3 vs. 46.1 +/- 11.2, P =.001). Ventricular ejection fraction z-score was also lower (-1.4 +/- 1.9 vs. -0.8 +/- 2.0, P =.05) in pacemaker subjects. Conclusions. In our cohort of Fontan survivors, those with a pacemaker have poorer functional status and evidence of decreased ventricular systolic function compared to Fontan survivors without a pacemaker. C1 [Williams, Richard V.] Univ Utah, Salt Lake City, UT USA. [Travison, Thomas; Lu, Minmin] New England Res Inst, Waterton, MA USA. [Kaltman, Jonathan R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Cecchin, Frank; Colan, Steven D.; Margossian, Renee] Childrens Hosp, Boston, MA 02115 USA. [Idriss, Salim F.] Duke Univ, Durham, NC USA. [Reed, John H.] Med Univ S Carolina, Charleston, SC 29425 USA. [Silver, Eric S.] Columbia Univ, New York, NY USA. [Stephenson, Elizabeth A.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Vetter, Victoria L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Williams, RV (reprint author), 100 N Mario Capecchi Dr, Salt Lake City, UT 84113 USA. EM richard.williams@imail.org FU National Heart, Lung, and Blood Institute [HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288] FX Supported by grants from the National Heart, Lung, and Blood Institute (HL068269, HL068270, HL068279, HL068281, HL068285, HL068292, HL068290, HL068288). NR 22 TC 10 Z9 10 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1747-079X J9 CONGENIT HEART DIS JI Congenit. Heart Dis. PD JAN-FEB PY 2013 VL 8 IS 1 BP 32 EP 39 DI 10.1111/j.1747-0803.2012.00692.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 078VL UT WOS:000314127900011 PM 22762157 ER PT J AU Tomasi, D Volkow, ND AF Tomasi, Dardo Volkow, Nora D. TI Striatocortical pathway dysfunction in addiction and obesity: differences and similarities SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE Alcohol; cocaine; methamphetamine; marijuana; obesity; eating disorders; networks; receptors; dopamine; striatum ID METHAMPHETAMINE-DEPENDENT SUBJECTS; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; D-2/D-3 RECEPTOR AVAILABILITY; ADOLESCENT MARIJUANA USERS; ABSTINENT COCAINE ABUSERS; STRIATAL DOPAMINE RELEASE; MEDIAL PREFRONTAL CORTEX; BINGE-EATING DISORDER; WORKING-MEMORY TASK AB Neuroimaging techniques are starting to reveal significant overlap in the brain circuitry underlying addiction and disorders of dyscontrol over rewarding behaviors (such as binge eating disorder and obesity). Positron emission tomography (PET) has demonstrated impaired striatal dopamine (DA) signaling (decreased D2 receptors) in drug addiction and obesity that is associated with reduced baseline glucose metabolism in medial and ventral prefrontal brain regions. Functional magnetic resonance imaging (fMRI) has documented brain activation abnormalities that also implicate DA-modulated striato-cortical pathways. In this review we map findings from recent neuroimaging studies that differentiate brain activation in drug/food addiction from those in controls within brain networks functionally connected with ventral and dorsal striatum. We show that regions found to be abnormal in addiction and obesity frequently emerge at the overlap of the dorsal and the ventral striatal networks. Medial temporal and superior frontal regions functionally connected with dorsal striatum display greater vulnerability in obesity and eating disorders than in drug addictions, indicating more widespread abnormalities for obesity and eating disorders than for addictions. This corroborates involvement of both ventral striatal (predominantly associated with reward and motivation) and dorsal striatal networks (associated with habits or stimulus response learning) in addiction and obesity but also identify distinct patterns between these two disorders. C1 [Tomasi, Dardo; Volkow, Nora D.] NIAAA, Bethesda, MD USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. RP Tomasi, D (reprint author), Brookhaven Natl Lab, Dept Med, Lab Neuroimaging LNI NIAAA, Bldg 490,30 Bell Ave, Upton, NY 11973 USA. EM tomasi@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU National Institutes of Alcohol Abuse and Alcoholism [2RO1AA09481] FX This work was accomplished with support from the National Institutes of Alcohol Abuse and Alcoholism (2RO1AA09481). NR 177 TC 61 Z9 61 U1 6 U2 44 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-9238 EI 1549-7798 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD JAN-FEB PY 2013 VL 48 IS 1 BP 1 EP 19 DI 10.3109/10409238.2012.735642 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 078AO UT WOS:000314070700001 PM 23173916 ER PT J AU Enrico, P Sirca, D Mereu, M Peana, AT Mercante, B Diana, M AF Enrico, Paolo Sirca, Donatella Mereu, Maddalena Peana, Alessandra Tiziana Mercante, Beniamina Diana, Marco TI Acute restraint stress prevents nicotine-induced mesolimbic dopaminergic activation via a corticosterone-mediated mechanism: A microdialysis study in the rat SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Nicotine; Mesolimbic dopamine system; Immobilization stress; Corticosterone; Microdialysis; Nicotine ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; DRUG-ADDICTION; ACETYLCHOLINE-RECEPTOR; SYNAPTIC PLASTICITY; PREFRONTAL CORTEX; FOOTSHOCK STRESS; FRONTAL-CORTEX; PUTATIVE ROLE AB Background: Stress affects the responsiveness to nicotine (NIC), by increasing drug use, facilitating relapse and reinstating NIC self administration even after prolonged abstinence. In turn, high corticosterone (CURT) blood levels induced by stress may alter the neurobiological properties of NIC by acting on the dopamine (DA) mesolimbic system. Methods: In this study, we evaluated the effect of exposure to acute restraint stress on NIC-induced stimulation of the mesolimbic DA system of the rat, by studying extracellular DA levels in the nucleus accumbens shell (NAccs) with microdialysis. Results: NIC intravenous administration (130 mu g/kg) increased DA levels in the NAccs in control rats but not in subjects exposed to stress; this latter phenomenon was prevented by blockade of CURT effects with the inhibitor of corticosterone synthesis metirapone (100 mg/Kg) or the glucorticoid receptor antagonist mifepristone (150 mu mol/kg). Conclusions: These observations show that exposure to acute stress inhibits the stimulatory response of the mesolimbic DA system to NIC and suggest that this effect is mediated by circulating CURT acting on its receptors. These results may bear relevance in explaining the role played by stressful stimuli in NIC-seeking and taking behavior. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Enrico, Paolo; Sirca, Donatella; Mercante, Beniamina] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Enrico, Paolo; Peana, Alessandra Tiziana; Diana, Marco] Univ Sassari, Dept Drug Sci, G Minardi Lab Cognit Neurosci, I-07100 Sassari, Italy. [Mereu, Maddalena] NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Enrico, P (reprint author), Univ Sassari, Dept Biomed Sci, Vle S Pietro 43-B, I-07100 Sassari, Italy. EM enrico@uniss.it RI Diana, Marco/D-1475-2011; ENRICO, Paolo/B-4699-2009; OI Diana, Marco/0000-0002-6561-5642; ENRICO, Paolo/0000-0002-5662-4731; PEANA, Alessandra Tiziana/0000-0002-7369-9858 FU Fondazione Banco di Sardegna [1161/2009.0404, 979/2010.0386, 2009.0483, 2010.0407] FX Funding for this study was provided by Fondazione Banco di Sardegna (grant 1161/2009.0404 and 979/2010.0386). The Fondazione Banco di Sardegna had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.; This study was supported through grants from Fondazione Banco di Sardegna (2009.0483 and 2010.0407) to P.E. NR 88 TC 5 Z9 5 U1 2 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 EI 1879-0046 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JAN 1 PY 2013 VL 127 IS 1-3 BP 8 EP 14 DI 10.1016/j.drugalcdep.2012.06.006 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 079VK UT WOS:000314200100002 PM 22809896 ER PT J AU Jasinski, PE Molkov, YI Shevtsova, NA Smith, JC Rybak, IA AF Jasinski, Patrick E. Molkov, Yaroslav I. Shevtsova, Natalia A. Smith, Jeffrey C. Rybak, Ilya A. TI Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre-Botzinger complex: a computational modelling study SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE Ca2+-activated nonspecific cation current; Na; K plus pump; neural oscillations; persistent Na plus current; respiration ID METABOTROPIC GLUTAMATE RECEPTORS; DEPENDENT POTASSIUM CHANNELS; NONSPECIFIC CATION CURRENT; NEURONS IN-VITRO; RAT SPINAL-CORD; RESPIRATORY RHYTHM; PREBOTZINGER COMPLEX; PACEMAKER NEURONS; NEONATAL MICE; GENERATION AB The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre-Botzinger complex (pre-BotC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre-BotC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na+ current (INaP), and the other involving the voltage-gated Ca2+ current (ICa) and the Ca2+-activated nonspecific cation current (ICAN), activated by intracellular Ca2+ accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na+-dependent and Ca2+-dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons with INaP and ICa randomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca2+ release, and the Na+/K+ pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on INaP and/or ICAN, or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre-BotC and other brainstem/spinal cord circuits under different experimental conditions. C1 [Jasinski, Patrick E.; Molkov, Yaroslav I.; Shevtsova, Natalia A.; Rybak, Ilya A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. [Molkov, Yaroslav I.] Indiana Univ Purdue Univ, Dept Math Sci, Indianapolis, IN 46202 USA. [Smith, Jeffrey C.] Natl Inst Neurol Disorders & Stroke, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD USA. RP Rybak, IA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. EM rybak@drexel.edu OI Molkov, Yaroslav/0000-0002-0862-1974 FU National Institute of Neurological Disorders and Stroke (NINDS), NIH [R01 NS057815, R01 NS069220]; NIH, NINDS FX This study was supported by National Institute of Neurological Disorders and Stroke (NINDS), NIH grants R01 NS057815 and R01 NS069220, and in part by the Intramural Research Program of the NIH, NINDS (J. C. Smith). NR 56 TC 17 Z9 17 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2013 VL 37 IS 2 BP 212 EP 230 DI 10.1111/ejn.12042 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 074TD UT WOS:000313835700005 PM 23121313 ER PT J AU Grammatikakis, I Gorospe, M Abdelmohsen, K AF Grammatikakis, Ioannis Gorospe, Myriam Abdelmohsen, Kotb TI Modulation of Cancer Traits by Tumor Suppressor microRNAs SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE post-transcriptional gene regulation; oncomiR; tumor suppressor microRNA; senescence; carcinogenesis ID HUMAN GLIOBLASTOMA CELLS; BINDING PROTEIN HUR; GLIOMA STEM-CELLS; PROSTATE-CANCER; BREAST-CANCER; DOWN-REGULATION; GASTRIC-CANCER; POSTTRANSCRIPTIONAL REGULATION; PANCREATIC-CANCER; MESSENGER-RNA AB MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. In mammalian cells, miRNAs typically suppress mRNA stability and/or translation through partial complementarity with target mRNAs. Each miRNA can regulate a wide range of mRNAs, and a single mRNA can be regulated by multiple miRNAs. Through these complex regulatory interactions, miRNAs participate in many cellular processes, including carcinogenesis. By altering gene expression patterns, cancer cells can develop specific phenotypes that allow them to proliferate, survive, secure oxygen and nutrients, evade immune recognition, invade other tissues and metastasize. At the same time, cancer cells acquire miRNA signature patterns distinct from those of normal cells; the differentially expressed miRNAs contribute to enabling the cancer traits. Over the past decade, several miRNAs have been identified, which functioned as oncogenic miRNAs (oncomiRs) or tumor-suppressive miRNAs (TS-miRNAs). In this review, we focus specifically on TS-miRNAs and their effects on well-established cancer traits. We also discuss the rising interest in TS-miRNAs in cancer therapy. C1 [Grammatikakis, Ioannis; Gorospe, Myriam; Abdelmohsen, Kotb] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM yannis.grammatikakis@nih.gov; gorospem@mail.nih.gov; abdelmohsenk@mail.nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU NIA-IRP, NIH FX IG, KA and MG were supported by the NIA-IRP, NIH. Our apologies to those whose work could not be included due to space constraints. NR 139 TC 13 Z9 13 U1 0 U2 17 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JAN PY 2013 VL 14 IS 1 BP 1822 EP 1842 DI 10.3390/ijms14011822 PG 21 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 077SS UT WOS:000314048800104 PM 23325049 ER PT J AU Shreffler, CA AF Shreffler, Carol A. TI Introduction to the Research of the Outstanding New Environmental Health Scientists SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article C1 NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. RP Shreffler, CA (reprint author), NIEHS, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA. EM shreffl1@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PD JAN PY 2013 VL 27 IS 1 SI SI BP 1 EP 2 DI 10.1002/jbt.21445 PG 2 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 073XU UT WOS:000313777200001 PM 23335407 ER PT J AU Jang, H Connelly, L Arce, FT Ramachandran, S Kagan, BL Lal, R Nussinov, R AF Jang, Hyunbum Connelly, Laura Arce, Fernando Teran Ramachandran, Srinivasan Kagan, Bruce L. Lal, Ratnesh Nussinov, Ruth TI Mechanisms for the Insertion of Toxic, Fibril-like beta-Amyloid Oligomers into the Membrane SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; ATOMIC-FORCE MICROSCOPY; FORMS ION CHANNELS; ALL-D-ENANTIOMER; LIPID-BILAYERS; A-BETA; ALZHEIMERS-DISEASE; ANTIMICROBIAL PEPTIDE; CALCIUM-CHANNELS; PROTEIN AB Amyloid-beta (A beta) oligomers destabilize cellular ionic homeostasis, mediating Alzheimer's disease (AD). It is still unclear whether the mechanism (i) is mediated by cell surface receptors; (ii) is direct, with A beta oligomers interacting with membrane lipids; or (iii) both mechanisms take place. Recent studies indicate that A beta oligomers may act by either of the last two. Little is known about the oligomers' structures and how they spontaneously insert into the membrane. Using explicit solvent molecular dynamics (MD) simulations, we show that fibril-like A beta(17-42) (p3) oligomer is capable of penetrating the membrane. Insertion is similar to that observed for protegrin-1 (PG-1), a cytolytic beta-sheet-rich antimicrobial peptide (AMP). Both A beta and PG-1 favor the amphipathic interface of the lipid bilayer in the early stage of interaction with the membrane. U-shaped A beta oligomers are observed in solution and in the membrane, suggesting that the preformed seeds can be shared by amyloid fibrils in the growth phase and membrane toxicity. Here we provide sequential events in possible A beta oligomer membrane-insertion pathways. We speculate that for the U-shaped motif, a trimer is the minimal oligomer size to insert effectively. We propose that monomers and dimers may insert in (apparently on-pathway) aggregation-intermediate beta-hairpin state and may (or may not) convert to a U-shape in the bilayer. Together with earlier observations, our results point to a nonspecific, broadly heterogeneous landscape of membrane-inserting oligomer conformations, pathways, and membrane-mediated toxicity of beta-rich oligomers. C1 [Jang, Hyunbum] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA. [Connelly, Laura; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Calif San Diego, Mat Sci Program, La Jolla, CA 92093 USA. [Kagan, Bruce L.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Mol Genet & Biochem, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov RI Ramachandran, Srinivasan/G-5300-2010 OI Ramachandran, Srinivasan/0000-0002-4912-0279 FU Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research; National Institutes of Health (National Institute on Aging) [AG028709] FX This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. This research was supported [in part] by the Intramural Research Program of NIH, Frederick National Lab, Center for Cancer Research. This research was supported by the National Institutes of Health (National Institute on Aging AG028709 to R.L.). All simulations had been performed using the high-performance computational facilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 67 TC 41 Z9 43 U1 9 U2 102 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD JAN PY 2013 VL 9 IS 1 BP 822 EP 833 DI 10.1021/ct300916f PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 068PM UT WOS:000313378700082 PM 23316126 ER PT J AU Kanapuru, B Simonsick, EM Ershler, WB AF Kanapuru, Bindu Simonsick, Eleanor M. Ershler, William B. TI Is cancer incidence decreased in the frail elderly? Evidence from a prospective cohort study SO JOURNAL OF GERIATRIC ONCOLOGY LA English DT Article DE Frailty; Cancer; Incidence; Cellular senescence; Microenvironment; Elderly ID CELLULAR SENESCENCE; OLDER-ADULTS; STEM-CELLS; AGE; WOMEN; HEALTH; INTERLEUKIN-6; HETEROGENEITY; ANGIOGENESIS; DISABILITY AB Objectives: Lower rates of cancer in the oldest old and in nursing home populations may reflect the increasing prevalence of frailty and a diminished capacity to sustain cancer cell growth and proliferation. This study aimed to determine cancer incidence in the frail relative to non-frail community resident older adults. Materials and methods: Data from 3969 participants free of diagnosed cancer at the sixth follow-up from three sites of the Established Populations for Epidemiologic Studies of the Elderly (EPESE), a population-based cohort study. Frailty status was determined from physical performance testing and self reported dependency in activities of daily living. Cancer incidence over the four subsequent years was identified through linkage with Medicare claims data. Logistic regression was used to estimate the odds of cancer incidence with respect to frailty status in multiple models with progressive adjustment for covariates. Results: Of the 3969 participants, 1340 (33.8%) were identified as frail. Cancer incidence at 4 years was lower in frail participants overall (OR 0.64; 95% CI 0.46-0.89) and frail men in particular (OR 0.54; 95% CI 0.33-0.87). Incidence was lower in women (3.7%) than in men (8.8%), but was not lower in frail women compared with non-frail women (OR 0.77; 95% CI 0.48-1.23). Conclusion: Frailty status was associated with decreased cancer incidence, particularly in men, and suggests that mechanisms related to the pathogenesis of frailty may also play a role in inhibiting tumorigenesis. Why this would be more apparent in men than women remains to be clarified. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kanapuru, Bindu; Ershler, William B.] NIA, Hematol Immunol Unit, Translat Res Sect, Clin Res Branch,Intramural Res Program, Baltimore, MD 21225 USA. [Simonsick, Eleanor M.] NIA, Longitudinal Studies Sect, Clin Res Branch, Intramural Res Program, Baltimore, MD 21225 USA. RP Kanapuru, B (reprint author), Inst Adv Studies Aging, Hematol Oncol Div, 6400 Arlington Blvd,Ste 940, Falls Church, VA 22042 USA. EM bpalika@hotmail.com FU NIH, National Institute on Aging; Medstar Health Research Institute FX This work was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. A portion of this support was through a research and development contract with Medstar Health Research Institute. NR 39 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1879-4068 J9 J GERIATR ONCOL JI J. Geriatr. Oncol. PD JAN PY 2013 VL 4 IS 1 BP 19 EP 25 DI 10.1016/j.jgo.2012.08.005 PG 7 WC Oncology; Geriatrics & Gerontology SC Oncology; Geriatrics & Gerontology GA 082FB UT WOS:000314376600003 PM 24071488 ER PT J AU McAlearney, AS Reiter, KL Weiner, BJ Minasian, L Song, PH AF McAlearney, Ann Scheck Reiter, Kristin L. Weiner, Bryan J. Minasian, Lori Song, Paula H. TI Challenges and Facilitators of Community Clinical Oncology Program Participation: A Qualitative Study SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID OVERCOMING BARRIERS; RESEARCH ENTERPRISE; CANCER PREVENTION; RESEARCH NETWORKS; CARE PRACTICE; HEALTH-CARE; NIH ROADMAP; IMPLEMENTATION; SYSTEMS; TRIALS AB Successful participation in the National Cancer Institute's Community Clinical Oncology Program (CCOP) can expand access to clinical trials and promote cancer treatment innovations for patients and communities without access to major cancer centers. Yet CCOP participation involves administrative, financial, and organizational challenges that can affect hospital and provider participants. This study was designed to improve our understanding of challenges associated with CCOP participation from the perspectives of involved providers and to learn about opportunities to overcome these challenges. We conducted five case studies of hospitals and providers engaged with the CCOP. Across organizations, we interviewed 41 key administrative, physician, and nurse informants. We asked about CCOP participation, focusing on issues related to implementation, operations, and organizational support. Challenges associated with CCOP participation included lack of appreciation for the value of participation and poor understanding about CCOP operations, cost, and required workflow changes, among others. Informants also suggested opportunities to facilitate participation: (1) increase awareness of the CCOP, (2) enhance commitment to the CCOP, and (3) promote and support champions of the CCOP. Improving our understanding of the challenges and facilitators of CCOP participation may assist hospitals and providers in increasing and sustaining participation in the CCOP, thus helping to preserve access to innovative cancer treatment options for patients in need. C1 [McAlearney, Ann Scheck] Ohio State Univ, Dept Family Med, Coll Med, Columbus, OH 43210 USA. [Reiter, Kristin L.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA. [Weiner, Bryan J.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Song, Paula H.] Ohio State Univ, Div Hlth Serv Management & Policy, Coll Publ Hlth, Columbus, OH 43210 USA. RP McAlearney, AS (reprint author), Ohio State Univ, Dept Family Med, Coll Med, Columbus, OH 43210 USA. EM mcalearney.1@osu.edu RI McAlearney, Ann/J-3008-2013 OI McAlearney, Ann/0000-0001-9107-5419 FU NCI NIH HHS [R01 CA124402, R01CA124402] NR 34 TC 1 Z9 1 U1 2 U2 5 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD JAN-FEB PY 2013 VL 58 IS 1 BP 29 EP 44 PG 16 WC Health Policy & Services SC Health Care Sciences & Services GA 080RO UT WOS:000314261200007 PM 23424817 ER PT J AU Devkota, KP Wilson, J Henrich, CJ McMahon, JB Reilly, KM Beutler, JA AF Devkota, Krishna P. Wilson, Jennifer Henrich, Curtis J. McMahon, James B. Reilly, Karlyne M. Beutler, John A. TI Isobutylhydroxyamides from the Pericarp of Nepalese Zanthoxylum armatum Inhibit NF1-Defective Tumor Cell Line Growth SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ALIPHATIC ACID-AMIDES; CONSTITUENTS; PIPERITUM; BUNGEANUM; HUAJIAO; AGENTS; NF1 AB A neurofibromatosis type 1 (NF1)-based bioassay-guided phytochemical investigation on Zanthoxylum armatum collected in Nepal led to the isolation of new timuramides A-D (1-4) and six known sanshools (5-10). The structures of all compounds were established by using modern spectroscopic techniques, including 1D and 2D NMR analysis and comparison with previously reported data. Most of the compounds inhibited growth of an Nf1- and p53-deficient mouse glioma cell line at noncytotoxic concentrations. C1 [Devkota, Krishna P.; Wilson, Jennifer; Henrich, Curtis J.; McMahon, James B.; Beutler, John A.] Frederick Natl Lab Canc Res, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA. [Henrich, Curtis J.] Frederick Natl Lab Canc Res, SAIC Frederick, Frederick, MD 21702 USA. [Reilly, Karlyne M.] Frederick Natl Lab Canc Res, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Beutler, JA (reprint author), Frederick Natl Lab Canc Res, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA. EM beutlerj@mail.nih.gov RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH Office of Dietary Supplements [OD-Y2-OD-1557-01]; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, as well as by funds from the NIH Office of Dietary Supplements, Grant OD-Y2-OD-1557-01. This research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. 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. We gratefully acknowledge K. Woerpel and C. Rieder (NYU) for helpful suggestions on endoperoxide cleavage, and H. Bokesch (MTL), S. Tarasov, and M. Dyba (Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for acquiring high-resolution mass spectra. NR 23 TC 9 Z9 10 U1 1 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JAN PY 2013 VL 76 IS 1 BP 59 EP 63 DI 10.1021/np300696g PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 080SN UT WOS:000314263700010 PM 23268719 ER PT J AU Iannotti, RJ Chen, RS Kololo, H Petronyte, G Haug, E Roberts, C AF Iannotti, Ronald J. Chen, Rusan Kololo, Hania Petronyte, Gintare Haug, Ellen Roberts, Chris TI Motivations for Adolescent Participation in Leisure-Time Physical Activity: International Differences SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE health motivation; social motivation; personal motivation; gender and age differences; national samples ID SEDENTARY BEHAVIOR; HEALTH; COUNTRIES; YOUTH; INTENTIONS; AWARENESS; CHILDREN; EXERCISE; MOTIVES; OBESITY AB Background: Although there are substantial international differences in adolescent physical activity (PA), cross-country motivational differences have received limited attention, perhaps due to the lack of measures applicable internationally. Methods: Identical self-report measures assessing PA and motivations for PA were used to survey students ages 11,13, and 15 from 7 countries participating in the 2005-2006 Health Behavior in School-Aged Children (HBSC) study representing 3 regions: Eastern Europe, Western Europe and North America. Multigroup comparisons with Confirmatory Factor Analysis and Structural Equation Modeling examined the stability of factors across regions and regional differences in relations between PA and motives for PA. Results: Three PA motivation factors were identified as suitable for assessing international populations. There were significant regional, gender, and age differences in relations between PA and each of the 3 PA motives. Social and achievement motives were positively related to PA. However, the association of PA with health motivations varied significantly by region and gender. The patterns suggest the importance of social motives for PA and the possibility that health may not be a reliable motivator for adolescent PA. Conclusion: Programs to increase PA in adolescence need to determine which motives are effective for the particular population being targeted. C1 [Iannotti, Ronald J.] NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. [Chen, Rusan] Georgetown Univ, Res Curriculum & Dev Grp, Washington, DC USA. [Kololo, Hania] Mother & Child Res Inst, Dept Child & Adolescent Hlth, Warsaw, Poland. [Petronyte, Gintare] Mykolas Romeris Univ, Sch Polit & Management, Vilnius, Lithuania. [Haug, Ellen] Univ Bergen, Res Ctr Hlth Promot, N-5020 Bergen, Norway. RP Iannotti, RJ (reprint author), NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 35 TC 10 Z9 10 U1 7 U2 46 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD JAN PY 2013 VL 10 IS 1 BP 106 EP 112 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 078GP UT WOS:000314087000014 PM 23324482 ER PT J AU Vidal, JS Aspelund, T Jonsdottir, MK Jonsson, PV Harris, TB Lopez, OL Gudnason, V Launer, LJ AF Vidal, Jean-Sebastien Aspelund, Thor Jonsdottir, Maria K. Jonsson, Palmi V. Harris, Tamara B. Lopez, Oscar L. Gudnason, Vilmundur Launer, Lenore J. TI Pulmonary Function Impairment May Be an Early Risk Factor for Late-Life Cognitive Impairment SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognition; dementia; forced expiratory volume; longitudinal cohort studies ID APOLIPOPROTEIN-E GENOTYPE; LUNG-FUNCTION; BIRTH COHORT; FOLLOW-UP; PERFORMANCE; ASSOCIATION; MORTALITY; REYKJAVIK; AGE; PREDICTORS AB Objectives To determine the association between change in pulmonary function (PF) and mid- and late-life cognitive function. Design Prospective population-based cohort study that included measures of pulmonary function in midlife and brain magnetic resonance imaging data acquired in late life. Setting The Age, Gene/Environment SusceptibilityReykjavik Study. Participants Three thousand six hundred sixty-five subjects who had at least one measure of forced expiratory volume in 1 second (FEV1) and were cognitively tested on average 23 years later. A subset of 1,281 subjects had two or three measures of FEV1 acquired over a 7.8-year period. Measurements Pulmonary function was estimated as FEV1/height2. Rate of PF decline was estimated as the slope of decline over time. Cognitive status was measured with continuous scores of memory, speed of processing, and executive function and as the outcome of mild cognitive impairment (MCI) and dementia. Results Lower PF measured in midlife predicted poorer memory, slower speed of processing, poorer executive function, and greater likelihood of MCI and dementia 23 years later. Decrease in PF over a 7.8-year period in midlife was not associated with MCI or dementia. Conclusion Low PF measured in midlife may be an early marker of later cognitive problems. Additional studies characterizing early and late PF changes are needed. C1 [Vidal, Jean-Sebastien; Harris, Tamara B.; Launer, Lenore J.] NIA, NIH, LEDB, Bethesda, MD 20892 USA. [Vidal, Jean-Sebastien] Broca Hosp, AP HP, Dept Geriatr, Paris, France. [Aspelund, Thor; Jonsdottir, Maria K.; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Jonsdottir, Maria K.] Univ Iceland, Fac Psychol, Reykjavik, Iceland. [Jonsson, Palmi V.; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Jonsson, Palmi V.] Landspitali Univ Hosp, Geriatr Res Ctr, Reykjavik, Iceland. [Lopez, Oscar L.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Launer, LJ (reprint author), NIA, NIH, LEDB, 7201 Wisconsin Ave,Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. EM launerl@mail.nih.gov RI Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015; Vidal, Jean-Sebastien/D-1941-2016 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084; Vidal, Jean-Sebastien/0000-0001-6770-0720 FU National Institute on Aging [N01-AG-1-2100]; Intramural Research Program; Hjartavernd (Icelandic Heart Association); Althingi (Icelandic Parliament) FX This work was supported by the National Institute on Aging (N01-AG-1-2100), Intramural Research Program, the Hjartavernd (Icelandic Heart Association), and the Althingi (Icelandic Parliament). NR 33 TC 15 Z9 15 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 79 EP 83 DI 10.1111/jgs.12069 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600014 PM 23311554 ER PT J AU Gamaldo, AA Ferrucci, L Rifkind, J Longo, DL Zonderman, AB AF Gamaldo, Alyssa A. Ferrucci, Luigi Rifkind, Joseph Longo, Dan L. Zonderman, Alan B. TI Relationship Between Mean Corpuscular Volume and Cognitive Performance in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mean corpuscular volume; cognition; older adults ID MEMORY PERFORMANCE; OXIDATIVE STRESS; LIFE-SPAN; ANEMIA; PREVALENCE; DECLINE; YOUNG AB Objectives To examine the relationship between erythrocyte mean corpuscular volume (MCV) and cognitive performance over time. Design Longitudinal. Setting Sample from the Baltimore Longitudinal Study of Aging (BLSA). Participants Eight hundred twenty-seven participants from the BLSA (mean age 67, range 5096). Measurements Mean corpuscular volume and several other blood indices were measured, including hemoglobin, iron, ferritin, vitamin B12, folate, white blood cell count, albumin, and erythrocyte sedimentation rate. Cognitive performance was examined using neuropsychological measures of visual memory, verbal memory, language, attention, executive function, and global mental status. Results High MCV levels were significantly associated with lower global mental status even after adjusting for potential confounders. High MCV levels were also significantly associated with high rates of decline on tasks of global mental status, long delay memory, and attention, even after adjusting for potential confounders. Conclusion The findings confirm a previous observation that larger erythrocytes in older adults are associated with poorer cognitive function. Anemia and inflammation do not appear to explain the relationship between MCV and cognition. Further research is needed to clarify the mechanisms behind this association. J Am Geriatr Soc 61:84-89, 2013. C1 [Gamaldo, Alyssa A.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Rifkind, Joseph] NIA, Mol Dynam Sect, Baltimore, MD 21224 USA. [Longo, Dan L.] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA. RP Gamaldo, AA (reprint author), NIA, Lab Behav Neurosci, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM Alyssa.Gamaldo@nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX There were no relevant financial interests in our manuscript. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 34 TC 7 Z9 7 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 2013 VL 61 IS 1 BP 84 EP 89 DI 10.1111/jgs.12066 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 073AM UT WOS:000313715600015 PM 23301873 ER PT J AU Baker, SG Kramer, BS AF Baker, Stuart G. Kramer, Barnett S. TI The risky reliance on small surrogate end point studies when planning a large prevention trial SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES A-STATISTICS IN SOCIETY LA English DT Article DE Cancer prevention; Cardiovascular disease; Prentice criterion; Principal stratification; Sample size calculation; Surrogate end point ID BIOMARKERS; CRITERIA AB The definitive evaluation of treatment to prevent a chronic disease with low incidence in middle age, such as cancer or cardiovascular disease, requires a trial with a large sample size of perhaps 20000 or more. To help to decide whether to implement a large true end point trial, investigators first typically estimate the effect of treatment on a surrogate end point in a trial with a greatly reduced sample size of perhaps 200 subjects. If investigators reject the null hypothesis of no treatment effect in the surrogate end point trial they implicitly assume that they would probably correctly reject the null hypothesis of no treatment effect for the true end point. Surrogate end point trials are generally designed with adequate power to detect an effect of treatment on the surrogate end point. However, we show that a small surrogate end point trial is more likely than a large surrogate end point trial to give a misleading conclusion about the beneficial effect of treatment on the true end point, which can lead to a faulty (and costly) decision about implementing a large true end point prevention trial. If a small surrogate end point trial rejects the null hypothesis of no treatment effect, an intermediate-sized surrogate end point trial could be a useful next step in the decision-making process for launching a large true end point prevention trial. C1 [Baker, Stuart G.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Canc Prevent Div, EPN 3118,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov FU National Institutes of Health FX This research was supported by the National Institutes of Health. NR 13 TC 4 Z9 4 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0964-1998 EI 1467-985X J9 J R STAT SOC A STAT JI J. R. Stat. Soc. Ser. A-Stat. Soc. PY 2013 VL 176 IS 2 BP 603 EP 608 DI 10.1111/j.1467-985X.2012.01052.x PG 6 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 074LF UT WOS:000313813300016 PM 23565041 ER PT J AU Bubunenko, M Court, DL Al Refaii, A Saxena, S Korepanov, A Friedman, DI Gottesman, ME Alix, JH AF Bubunenko, Mikhail Court, Donald L. Al Refaii, Abdalla Saxena, Shivalika Korepanov, Alexey Friedman, David I. Gottesman, Max E. Alix, Jean-Herve TI Nus transcription elongation factors and RNase III modulate small ribosome subunit biogenesis in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID IN-VIVO; ANTITERMINATION COMPLEX; LEADER REGION; PHAGE-LAMBDA; DEFECTIVE ANTITERMINATION; TRANSLATION REPRESSION; RIBONUCLEASE-III; SECY24 MUTATION; LARGE RIBOZYME; PROTEIN S10 AB Escherichia coli NusA and NusB proteins bind specific sites, such as those in the leader and spacer sequences that flank the 16S region of the ribosomal RNA transcript, forming a complex with RNA polymerase that suppresses Rho-dependent transcription termination. Although antitermination has long been the accepted role for Nus factors in rRNA synthesis, we propose that another major role for the Nus-modified transcription complex in rrn operons is as an RNA chaperone insuring co-ordination of 16S rRNA folding and RNase III processing that results in production of proper 30S ribosome subunits. This contrarian proposal is based on our studies of nusA and nusB cold-sensitive mutations that have altered translation and at low temperature accumulate 30S subunit precursors. Both phenotypes are suppressed by deletion of RNase III. We argue that these results are consistent with the idea that the nus mutations cause altered rRNA folding that leads to abnormal 30S subunits and slow translation. According to this idea, functional Nus proteins stabilize an RNA loop between their binding sites in the 5' RNA leader and on the transcribing RNA polymerase, providing a topological constraint on the RNA that aids normal rRNA folding and processing. C1 [Bubunenko, Mikhail] SAIC Frederick Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Bubunenko, Mikhail; Court, Donald L.; Korepanov, Alexey] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Al Refaii, Abdalla; Alix, Jean-Herve] Univ Paris Diderot, Sorbonne Paris Cite Inst Biol Physicochim, CNRS UPR9073, F-75005 Paris, France. [Saxena, Shivalika; Gottesman, Max E.] Columbia Univ, Med Ctr, Dept Microbiol & Biochem, New York, NY 10032 USA. [Saxena, Shivalika; Gottesman, Max E.] Columbia Univ, Med Ctr, Dept Mol Biophys, New York, NY 10032 USA. [Friedman, David I.] Univ Michigan, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Court, DL (reprint author), NCI, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM courtd@mail.nih.gov; jean-herve.alix@ibpc.fr RI Korepanov, Alexey/I-9052-2012; Friedman, David/G-3198-2015 OI Friedman, David/0000-0002-2741-4671 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Trans National Institutes of Health/National Institutes of Allergy and Infectious Disease; Public Health Service Grant [AI11459- 10]; Syrian Government; Centre National de la Recherche Scientifique (CNRS) [UPR 9073]; Universite Paris 7-Diderot; NIH [GM37219] FX D. L. C. was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and in part by a Trans National Institutes of Health/Food and Drug Administration Intramural Biodefense Program Grant of National Institutes of Allergy and Infectious Disease. D. I. F. was supported by Public Health Service Grant AI11459- 10. A. Al Refaii was a recipient of a fellowship from the Syrian Government. J. - H. A. was supported by the UPR 9073 of the Centre National de la Recherche Scientifique (CNRS) and the Universite Paris 7-Diderot. M. E. G. was supported by NIH Grant GM37219. NR 72 TC 13 Z9 13 U1 2 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JAN PY 2013 VL 87 IS 2 BP 382 EP 393 DI 10.1111/mmi.12105 PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 078RX UT WOS:000314118300011 PM 23190053 ER PT J AU Ohayon, J Oh, U Richert, N Martin, J Vortmeyer, A McFarland, H Bielekova, B AF Ohayon, Joan Oh, Unsong Richert, Nancy Martin, Jayne Vortmeyer, Alexander McFarland, Henry Bielekova, Bibiana TI CNS vasculitis in a patient with MS on daclizumab monotherapy SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; T-CELLS; ANTIBODY; ACTIVATION; THERAPY AB Objective: To report the development of CNS vasculitis in a patient with multiple sclerosis (MS) treated with daclizumab. Methods: This report includes clinical, MRI, immunologic, and pathology data and CSF analysis. Results: After completing a phase II daclizumab monotherapy study with an optimal response as evidenced by significant decrease in MRI disease activity and stable clinical examinations, the patient elected to continue daclizumab therapy outside of NIH study. Daclizumab was discontinued after 21 doses due to the onset of new clinical symptoms and evidence of a vascular pattern of contrast enhancement on brain and spine MRI. Because of continued clinical deterioration, stereotactic brain biopsy was performed, showing small-vessel CNS vasculitis. Treatment was initiated with IV methylprednisolone followed by a regimen of cyclophosphamide. Immunologic studies suggest that unexpected lack of expansion of CD56(bright) NK cells and predictable decline in FoxP3+ T-regs combined with a transient interruption in daclizumab dosing may have contributed to this serious side effect. Conclusions: Only safety data from larger phase III studies and potentially postmarketing experience will define the exact risk of daclizumab-induced immunopathologies. Nevertheless, our case provides plausible hypothesis and potential biomarker that may be used to screen susceptible patients and implement preventive safety measures during potentially vulnerable periods. Neurology (R) 2013;80:453-457 C1 [Ohayon, Joan; McFarland, Henry; Bielekova, Bibiana] NINDS, Neuroimmunol Branch NIB, NIH, Bethesda, MD 20892 USA. [Oh, Unsong] Virginia Commonwealth Univ, Sch Med, Dept Neurol, Richmond, VA 23284 USA. [Richert, Nancy] Biogen Idec Inc, MS Clin Dev, Cambridge, MA USA. [Martin, Jayne] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY USA. [Vortmeyer, Alexander] Yale Univ, Dept Pathol, New Haven, CT USA. RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch NIB, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM Bibi.Bielekova@nih.gov FU National Institute of Neurological Disorders and Stroke, NIH; NIH FX Supported by the intramural research program of the National Institute of Neurological Disorders and Stroke, NIH. Study drug was provided to NIH for free by Roche, Inc. NIH CTSA (KL2TR000057 to U.O.).; J. Ohayon and U. Oh report no disclosures. N.D. Richert became an employee of Biogen Idec after study conclusion and after data analysis was finalized. J. Martin and A. Vortmeyer report no disclosures. H. McFarland is coinventor on several NIH patents related to daclizumab and as such has received patent royalty payments from NIH. B. Bielekova is coinventor on several NIH patents related to daclizumab and as such has received patent royalty payments from NIH. Go to Neurology.org for full disclosures. NR 10 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 5 BP 453 EP 457 DI 10.1212/WNL.0b013e31827f0f42 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 079GW UT WOS:000314159600013 PM 23303850 ER PT J AU Armstrong, MJ Litvan, I Lang, AE Bak, TH Bhatia, KP Borroni, B Boxer, AL Dickson, DW Grossman, M Hallett, M Josephs, KA Kertesz, A Lee, SE Miller, BL Reich, SG Riley, DE Tolosa, E Troster, AI Vidailhet, M Weiner, WJ AF Armstrong, Melissa J. Litvan, Irene Lang, Anthony E. Bak, Thomas H. Bhatia, Kailash P. Borroni, Barbara Boxer, Adam L. Dickson, Dennis W. Grossman, Murray Hallett, Mark Josephs, Keith A. Kertesz, Andrew Lee, Suzee E. Miller, Bruce L. Reich, Stephen G. Riley, David E. Tolosa, Eduardo Troester, Alexander I. Vidailhet, Marie Weiner, William J. TI Criteria for the diagnosis of corticobasal degeneration SO NEUROLOGY LA English DT Review ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTOTEMPORAL LOBAR DEGENERATION; BASAL GANGLIONIC DEGENERATION; CLINICAL-DIAGNOSIS; PARKINSONIAN-SYNDROMES; MOVEMENT-DISORDERS; ALZHEIMERS-DISEASE; PROGRANULIN GENE; DEMENTIA; ACCURACY AB Current criteria for the clinical diagnosis of pathologically confirmed corticobasal degeneration (CBD) no longer reflect the expanding understanding of this disease and its clinicopathologic correlations. An international consortium of behavioral neurology, neuropsychology, and movement disorders specialists developed new criteria based on consensus and a systematic literature review. Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed CBD cases from published reports and brain banks. Combined with consensus, 4 CBD phenotypes emerged: corticobasal syndrome (CBS), frontal behavioral-spatial syndrome (FBS), nonfluent/agrammatic variant of primary progressive aphasia (naPPA), and progressive supranuclear palsy syndrome (PSPS). Clinical features of CBD cases were extracted from descriptions of 209 brain bank and published patients, providing a comprehensive description of CBD and correcting common misconceptions. Clinical CBD phenotypes and features were combined to create 2 sets of criteria: more specific clinical research criteria for probable CBD and broader criteria for possible CBD that are more inclusive but have a higher chance to detect other tau-based pathologies. Probable CBD criteria require insidious onset and gradual progression for at least 1 year, age at onset >= 50 years, no similar family history or known tau mutations, and a clinical phenotype of probable CBS or either FBS or naPPA with at least 1 CBS feature. The possible CBD category uses similar criteria but has no restrictions on age or family history, allows tau mutations, permits less rigorous phenotype fulfillment, and includes a PSPS phenotype. Future validation and refinement of the proposed criteria are needed. Neurology (R) 2013;80:496-503 C1 [Armstrong, Melissa J.; Reich, Stephen G.; Weiner, William J.] Univ Maryland, Baltimore, MD 21201 USA. [Litvan, Irene] Univ Calif San Diego, San Diego, CA 92103 USA. [Lang, Anthony E.] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Ctr, Toronto, ON M5T 2S8, Canada. [Lang, Anthony E.] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada. [Bak, Thomas H.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Bhatia, Kailash P.] UCL, Inst Neurol, Sobell Dept Movement Neurosci, London, England. [Borroni, Barbara] Univ Brescia, Brescia, Italy. [Boxer, Adam L.; Lee, Suzee E.; Miller, Bruce L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dickson, Dennis W.] Mayo Clin, Jacksonville, FL 32224 USA. [Grossman, Murray] Univ Penn, Philadelphia, PA 19104 USA. [Hallett, Mark] NINDS, NIH, Bethesda, MD 20892 USA. [Josephs, Keith A.] Mayo Clin, Rochester, MN USA. [Kertesz, Andrew] Univ Western Ontario, London, ON, Canada. [Riley, David E.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Tolosa, Eduardo] Univ Barcelona, IDIBAPS, Hosp Clin,Neurol Serv, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08007 Barcelona, Spain. [Troester, Alexander I.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Vidailhet, Marie] Univ Paris 06, Hop La Pitie Salpetriere, Paris, France. CRICM UPMC INSERM UMR S975 CNRS UMR7225, Paris, France. RP Litvan, I (reprint author), Univ Calif San Diego, San Diego, CA 92103 USA. EM ilitvan@ucsd.edu OI Dickson, Dennis W/0000-0001-7189-7917; Bhatia, Kailash/0000-0001-8185-286X; Litvan, Irene/0000-0002-3485-3445 FU Litvan Neurological Research Foundation FX The 1st International CBD Investigators Meeting was funded by a donation from Irene Pollin and the late Abe Pollin and from the Litvan Neurological Research Foundation. Melissa J. Armstrong received support as an Edmond J. Safra fellow at Toronto Western Hospital while working on this project. NR 59 TC 178 Z9 181 U1 4 U2 33 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 5 BP 496 EP 503 DI 10.1212/WNL.0b013e31827f0fd1 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 079GW UT WOS:000314159600020 PM 23359374 ER PT J AU Bielekova, B AF Bielekova, Bibiana TI Daclizumab Therapy for Multiple Sclerosis SO NEUROTHERAPEUTICS LA English DT Article DE Multiple sclerosis; Autoimmunity; Biological therapy; IL-2; CD25 ID NATURAL-KILLER-CELLS; REGULATORY T-CELLS; EARLY-PREGNANCY DECIDUA; INNATE LYMPHOID-CELLS; HUMANIZED ANTI-TAC; INTERLEUKIN-2 RECEPTOR; IL-2 RECEPTOR; ALPHA-CHAIN; NK CELLS; MONOCLONAL-ANTIBODY AB Daclizumab is a humanized monoclonal antibody of IgG1 subtype that binds to the Tac epitope on the interleukin-2 (IL-2) receptor alpha-chain (CD25), thus, effectively blocking the formation of the high-affinity IL-2 receptor. Because the high-affinity IL-2 receptor signaling promotes expansion of activated T cells in vitro, daclizumab was designed as a therapy that selectively inhibits T-cell activation. Assuming the previous statement, daclizumab received regulatory approval as add-on therapy to standard immunosuppressive regimen for the prevention of acute allograft rejection in renal transplantation. Based on its putative mechanism of action (MOA), daclizumab represented an ideal therapy for T-cell-mediated autoimmune diseases and was subsequently tested in inflammatory uveitis and multiple sclerosis (MS). In both of these diseases, daclizumab therapy significantly inhibited target organ inflammation. Mechanistic studies in MS demonstrated that the MOA of daclizumab is surprisingly broad and that the drug exerts unexpected effects on multiple components of the innate immune system. Specifically, daclizumab dramatically expands and activates immunoregulatory CD56(bright) NK cells, which gain access to the intrathecal compartment in MS and can kill autologous activated T cells. Daclizumab also blocks trans-presentation of IL-2 by mature dendritic cells to primed T cells, resulting in profound inhibition of antigen-specific T cells. Finally, daclizumab modulates the development of innate lymphoid cells. In conclusion, daclizumab therapy, which is currently in phase III testing for inflammatory MS, has a unique MOA that does not limit migration of immune cells into the intrathecal compartment, but rather provides multifactorial immunomodulatory effects with resultant inhibition of MS-related inflammation. C1 [Bielekova, Bibiana] NINDS, NDU, Neuroimmunol Branch NIB, Bethesda, MD 20892 USA. [Bielekova, Bibiana] NIH, Bethesda, MD 20892 USA. RP Bielekova, B (reprint author), NINDS, NDU, Neuroimmunol Branch NIB, Bethesda, MD 20892 USA. EM Bibi.Bielekova@nih.gov FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS) FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS). B. B. is a co-inventor of the National Institutes of Health patents related to daclizumab therapy, and as such has received patent royalty payments. NR 96 TC 38 Z9 39 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2013 VL 10 IS 1 BP 55 EP 67 DI 10.1007/s13311-012-0147-4 PG 13 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 080WM UT WOS:000314274800007 PM 23055048 ER PT J AU Feng, G Leem, YE Levin, HL AF Feng, Gang Leem, Young-Eun Levin, Henry L. TI Transposon integration enhances expression of stress response genes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSFER-RNA GENES; POL-II PROMOTERS; SCHIZOSACCHAROMYCES-POMBE; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; INSERTIONAL MUTAGENESIS; RETROTRANSPOSON TY1; LTR-RETROTRANSPOSON; MAMMARY-CANCER; TRANSCRIPTION AB Transposable elements possess specific patterns of integration. The biological impact of these integration profiles is not well understood. Tf1, a long-terminal repeat retrotransposon in Schizosaccharomyces pombe, integrates into promoters with a preference for the promoters of stress response genes. To determine the biological significance of Tf1 integration, we took advantage of saturated maps of insertion activity and studied how integration at hot spots affected the expression of the adjacent genes. Our study revealed that Tf1 integration did not reduce gene expression. Importantly, the insertions activated the expression of 6 of 32 genes tested. We found that Tf1 increased gene expression by inserting enhancer activity. Interestingly, the enhancer activity of Tf1 could be limited by Abp1, a host surveillance factor that sequesters transposon sequences into structures containing histone deacetylases. We found the Tf1 promoter was activated by heat treatment and, remarkably, only genes that themselves were induced by heat could be activated by Tf1 integration, suggesting a synergy of Tf1 enhancer sequence with the stress response elements of target promoters. We propose that the integration preference of Tf1 for the promoters of stress response genes and the ability of Tf1 to enhance the expression of these genes co-evolved to promote the survival of cells under stress. C1 [Feng, Gang; Leem, Young-Eun; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. [Feng, Gang] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100191, Peoples R China. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU Intramural Research Program of the National Institutes of Health from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH intramural program; NICHD FX Intramural Research Program of the National Institutes of Health from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Funding for open access charge: NIH intramural program and NICHD. NR 58 TC 20 Z9 20 U1 2 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 2 BP 775 EP 789 DI 10.1093/nar/gks1185 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 078SZ UT WOS:000314121100017 PM 23193295 ER PT J AU Eun, B Sampley, ML Good, AL Gebert, CM Pfeifer, K AF Eun, Bokkee Sampley, Megan L. Good, Austin L. Gebert, Claudia M. Pfeifer, Karl TI Promoter cross-talk via a shared enhancer explains paternally biased expression of Nctc1 at the Igf2/H19/Nctc1 imprinted locus SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOUSE H19 GENE; RANGE CHROMATIN INTERACTIONS; CCCTC-BINDING-FACTOR; BETA-GLOBIN LOCUS; CONTROL REGION; IGF2 GENE; METHYLATED REGION; H19/IGF2 LOCUS; GERM-CELLS; TRANSCRIPTION AB Developmentally regulated transcription often depends on physical interactions between distal enhancers and their cognate promoters. Recent genomic analyses suggest that promoter-promoter interactions might play a similarly critical role in organizing the genome and establishing cell-type-specific gene expression. The Igf2/H19 locus has been a valuable model for clarifying the role of long-range interactions between cis-regulatory elements. Imprinted expression of the linked, reciprocally imprinted genes is explained by parent-of-origin-specific chromosomal loop structures between the paternal Igf2 or maternal H19 promoters and their shared tissue-specific enhancer elements. Here, we further analyze these loop structures for their composition and their impact on expression of the linked long non-coding RNA, Nctc1. We show that Nctc1 is co-regulated with Igf2 and H19 and physically interacts with the shared muscle enhancer. In fact, all three co-regulated genes have the potential to interact not only with the shared enhancer but also with each other via their enhancer interactions. Furthermore, developmental and genetic analyses indicate functional significance for these promoter-promoter interactions. Altogether, we present a novel mechanism to explain developmental specific imprinting of Nctc1 and provide new information about enhancer mechanisms and about the role of chromatin domains in establishing gene expression patterns. C1 [Eun, Bokkee; Sampley, Megan L.; Good, Austin L.; Gebert, Claudia M.; Pfeifer, Karl] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pfeiferk@mail.nih.gov OI Pfeifer, Karl/0000-0002-0254-682X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Research, National Institutes of Health [HD001804-17]; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Intramural Research, National Institutes of Health [HD001804-17 to K.P.]. Funding for open access charge: Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 63 TC 9 Z9 9 U1 0 U2 7 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 JAN PY 2013 VL 41 IS 2 BP 817 EP 826 DI 10.1093/nar/gks1182 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 078SZ UT WOS:000314121100020 PM 23221643 ER PT J AU Popuri, V Huang, J Ramamoorthy, M Tadokoro, T Croteau, DL Bohr, VA AF Popuri, Venkateswarlu Huang, Jing Ramamoorthy, Mahesh Tadokoro, Takashi Croteau, Deborah L. Bohr, Vilhelm A. TI RECQL5 plays co-operative and complementary roles with WRN syndrome helicase SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; WERNER-SYNDROME HELICASE; REPLICATION FORK PROGRESSION; BLOOMS-SYNDROME HELICASE; SYNDROME PROTEIN WRN; S-PHASE CHECKPOINT; RNA-POLYMERASE-II; DNA-DAMAGE; CELL-CYCLE; HOMOLOGOUS RECOMBINATION AB Humans have five RecQ helicases, whereas simpler organisms have only one. Little is known about whether and how these RecQ helicases co-operate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser-induced DNA double-strand breaks in the absence of Werner syndrome (WRN) protein, and that it interacts physically and functionally with WRN both in vivo and in vitro. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 and WRN re-localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase. Further, we show that RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 plays both co-operative and complementary roles with WRN. This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases. C1 [Popuri, Venkateswarlu; Huang, Jing; Ramamoorthy, Mahesh; Tadokoro, Takashi; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov OI Ramamoorthy, Mahesh/0000-0002-2359-5647 FU Intramural Research Program of the National Institute on Aging; National Institutes of Health [AG000726-20] FX Intramural Research Program of the National Institute on Aging. Funding for open access charge: National Institutes of Health [AG000726-20]. NR 74 TC 8 Z9 9 U1 1 U2 7 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 JAN PY 2013 VL 41 IS 2 BP 881 EP 899 DI 10.1093/nar/gks1134 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 078SZ UT WOS:000314121100025 PM 23180761 ER PT J AU Guo, S Zhuang, P Hallett, M Zheng, Z Zhang, YQ Li, JY Li, YJ AF Guo, Song Zhuang, Ping Hallett, Mark Zheng, Zhe Zhang, Yuqing Li, Jianyu Li, Yongjie TI Subthalamic deep brain stimulation for Parkinson's disease: Correlation between locations of oscillatory activity and optimal site of stimulation SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Subthalamic nucleus; Deep brain stimulation; Best contact; Oscillation; Microelectrode ID BASAL GANGLIA; NUCLEUS; BETA; SYNCHRONIZATION; IDENTIFICATION; ORGANIZATION; IMPROVEMENT; DOPAMINE; MOVEMENT; PALLIDUM AB Subthalamic nucleus deep brain stimulation (STN DBS) is an effective surgical treatment for Parkinson's disease (PD). Recent studies demonstrated that pathological oscillations are seen largely within the dorsolateral portion of the STN, which is the same location that predicts optimal therapeutic benefit with DBS; however, the precise nature of the relationship between these two phenomena remains unclear. The purpose of this study was to explore localization of oscillatory activity in relation to the optimal contacts of DBS which results in the best motor improvement. We studied 23 PD patients who underwent electrode implantation into the STN for motor symptoms. Microelectrode recordings were taken from the STN during surgery and neuronal activity was analyzed offline. Spectral characteristics were calculated. Clinical outcomes were evaluated pre- and post-STN DBS implantation using the Unified Parkinson's Disease Rating Scale (UPDRS III). The position of optimal electrode contacts was assessed by postoperative magnetic resonance imaging (MRI) and was compared to the location of oscillatory activity within the STN as well as its dorsal margin (where STN neuronal activity was first detected). Of the total 188 neurons obtained, 51(27.1%) neurons showed significant oscillatory activity. Of those, 47 (92.2%) were localized in the dorsal portion of the STN. Furthermore, there was no significant difference between the averaged coordinates of the position of 40 optimal contacts and the coordinates of the dorsal margin of the STN. The data indicate that the positions of the best contacts correlate with the locations of the oscillatory neurons supporting the prediction that stimulation of the dorsolateral oscillatory region leads to an effective clinical outcome for STN DBS surgery. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Guo, Song; Zhuang, Ping; Zheng, Zhe; Zhang, Yuqing; Li, Jianyu; Li, Yongjie] Capital Med Univ, Beijing Inst Funct Neurosurg, Key Lab Neurodegenerat Dis, Xuanwu Hosp,Minist Educ, Beijing 100053, Peoples R China. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, P (reprint author), Capital Med Univ, Beijing Inst Funct Neurosurg, Key Lab Neurodegenerat Dis, Xuanwu Hosp,Minist Educ, 45 Changchun St, Beijing 100053, Peoples R China. EM zhuangp@vip.sina.com FU National Natural Science Foundation of China [30370473, 30770746, 81171061]; National Institute of Neurological Disorders and Stroke, National Institutes of Health FX The study was supported by grants of National Natural Science Foundation of China (No. 30370473, 30770746, 81171061). Dr. Hallett is supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. We thank Devera Schoenberg, M.Sc., for skillful manuscript editing. NR 35 TC 9 Z9 11 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD JAN PY 2013 VL 19 IS 1 BP 109 EP 114 DI 10.1016/j.parkreldis.2012.08.005 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 082IM UT WOS:000314385500021 PM 22981262 ER PT J AU Schnermann, J Briggs, JP AF Schnermann, Jurgen Briggs, Josephine P. TI Tubular control of renin synthesis and secretion SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE Macula densa; Na-K-2Cl cotransporter; COX-2; Prostaglandins; Nitric oxide; Adenosine ID MACULA DENSA CELLS; NITRIC-OXIDE-SYNTHASE; THICK ASCENDING LIMB; CORTICAL CYCLOOXYGENASE-2 EXPRESSION; PERFUSED JUXTAGLOMERULAR APPARATUS; MEDULLARY COLLECTING DUCT; DISTAL CONVOLUTED TUBULE; VASCULAR SMOOTH-MUSCLE; DIETARY SALT INTAKE; GENE-KNOCKOUT MICE AB The intratubular composition of fluid at the tubulovascular contact site of the juxtaglomerular apparatus serves as regulatory input for secretion and synthesis of renin. Experimental evidence, mostly from in vitro perfused preparations, indicates an inverse relation between luminal NaCl concentration and renin secretion. The cellular transduction mechanism is initiated by concentration-dependent NaCl uptake through the Na-K-2Cl cotransporter (NKCC2) with activation of NKCC2 causing inhibition and deactivation of NKCC2 causing stimulation of renin release. Changes in NKCC2 activity are coupled to alterations in the generation of paracrine factors that interact with granular cells. Among these factors, generation of PGE2 in a COX-2-dependent fashion appears to play a dominant role in the stimulatory arm of tubular control of renin release. [NaCl] is a determinant of local PG release over an appropriate concentration range, and blockade of COX-2 activity interferes with the NaCl dependency of renin secretion. The complex array of local paracrine controls also includes nNOS-mediated synthesis of nitric oxide, with NO playing the role of a modifier of the intracellular signaling pathway. A role of adenosine may be particularly important when [NaCl] is increased, and at least some of the available evidence is consistent with an important suppressive effect of adenosine at higher salt concentrations. C1 [Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD 20892 USA. [Briggs, Josephine P.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Rm 4D50,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD FX Research from the laboratory of the authors was supported by intramural funds of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. NR 151 TC 9 Z9 9 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD JAN PY 2013 VL 465 IS 1 BP 39 EP 51 DI 10.1007/s00424-012-1115-x PG 13 WC Physiology SC Physiology GA 077TB UT WOS:000314049800005 PM 22665048 ER PT J AU DeBuysscher, BL de Wit, E Munster, VJ Scott, D Feldmann, H Prescott, J AF DeBuysscher, Blair L. de Wit, Emmie Munster, Vincent J. Scott, Dana Feldmann, Heinz Prescott, Joseph TI Comparison of the Pathogenicity of Nipah Virus Isolates from Bangladesh and Malaysia in the Syrian Hamster SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID TO-PERSON TRANSMISSION; NOSOCOMIAL TRANSMISSIBILITY; EMERGENT PARAMYXOVIRUS; SEVERE ENCEPHALITIS; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; PIG-FARMERS; OUTBREAK; INFECTION; PATHOLOGY AB Nipah virus is a zoonotic pathogen that causes severe disease in humans. The mechanisms of pathogenesis are not well described. The first Nipah virus outbreak occurred in Malaysia, where human disease had a strong neurological component. Subsequent outbreaks have occurred in Bangladesh and India and transmission and disease processes in these outbreaks appear to be different from those of the Malaysian outbreak. Until this point, virtually all Nipah virus studies in vitro and in vivo, including vaccine and pathogenesis studies, have utilized a virus isolate from the original Malaysian outbreak (NiV-M). To investigate potential differences between NiV-M and a Nipah virus isolate from Bangladesh (NiV-B), we compared NiV-M and NiV-B infection in vitro and in vivo. In hamster kidney cells, NiV-M-infection resulted in extensive syncytia formation and cytopathic effects, whereas NiV-B-infection resulted in little to no morphological changes. In vivo, NiV-M-infected Syrian hamsters had accelerated virus replication, pathology and death when compared to NiV-B-infected animals. NiV-M infection also resulted in the activation of host immune response genes at an earlier time point. Pathogenicity was not only a result of direct effects of virus replication, but likely also had an immunopathogenic component. The differences observed between NiV-M and NiV-B pathogeneis in hamsters may relate to differences observed in human cases. Characterization of the hamster model for NiV-B infection allows for further research of the strain of Nipah virus responsible for the more recent outbreaks in humans. This model can be used to study NiV-B pathogenesis, transmission, and countermeasures that could be used to control outbreaks. C1 [DeBuysscher, Blair L.; de Wit, Emmie; Munster, Vincent J.; Feldmann, Heinz; Prescott, Joseph] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. [DeBuysscher, Blair L.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. [Scott, Dana] NIAID, Rocky Mt Vet Branch, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. RP DeBuysscher, BL (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT 59840 USA. EM feldmannh@niaid.nih.gov; prescottjb@niaid.nih.gov OI de Wit, Emmie/0000-0002-9763-7758; Munster, Vincent/0000-0002-2288-3196 FU Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Disease, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 53 TC 19 Z9 19 U1 0 U2 19 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2013 VL 7 IS 1 AR e2024 DI 10.1371/journal.pntd.0002024 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 081ZB UT WOS:000314360200047 PM 23342177 ER PT J AU Facchinelli, L Valerio, L Ramsey, JM Gould, F Walsh, RK Bond, G Robert, MA Lloyd, AL James, AA Alphey, L Scott, TW AF Facchinelli, Luca Valerio, Laura Ramsey, Janine M. Gould, Fred Walsh, Rachael K. Bond, Guillermo Robert, Michael A. Lloyd, Alun L. James, Anthony A. Alphey, Luke Scott, Thomas W. TI Field Cage Studies and Progressive Evaluation of Genetically-Engineered Mosquitoes SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID VECTOR AEDES-AEGYPTI; DENGUE VECTOR; REPLACEMENT; STRATEGIES; SYSTEM; TRIALS AB Background: A genetically-engineered strain of the dengue mosquito vector Aedes aegypti, designated OX3604C, was evaluated in large outdoor cage trials for its potential to improve dengue prevention efforts by inducing population suppression. OX3604C is engineered with a repressible genetic construct that causes a female-specific flightless phenotype. Wild-type females that mate with homozygous OX3604C males will not produce reproductive female offspring. Weekly introductions of OX3604C males eliminated all three targeted Ae. aegypti populations after 10-20 weeks in a previous laboratory cage experiment. As part of the phased, progressive evaluation of this technology, we carried out an assessment in large outdoor field enclosures in dengue endemic southern Mexico. Methodology/Principal Findings: OX3604C males were introduced weekly into field cages containing stable target populations, initially at 10: 1 ratios. Statistically significant target population decreases were detected in 4 of 5 treatment cages after 17 weeks, but none of the treatment populations were eliminated. Mating competitiveness experiments, carried out to explore the discrepancy between lab and field cage results revealed a maximum mating disadvantage of up 59.1% for OX3604C males, which accounted for a significant part of the 97% fitness cost predicted by a mathematical model to be necessary to produce the field cage results. Conclusions/Significance: Our results indicate that OX3604C may not be effective in large-scale releases. A strain with the same transgene that is not encumbered by a large mating disadvantage, however, could have improved prospects for dengue prevention. Insights from large outdoor cage experiments may provide an important part of the progressive, stepwise evaluation of genetically-engineered mosquitoes. C1 [Facchinelli, Luca; Valerio, Laura; Walsh, Rachael K.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Valerio, Laura] Univ Roma La Sapienza, Ist Pasteur, Fdn Cenci Bolognetti, Rome, Italy. [Ramsey, Janine M.; Bond, Guillermo] Inst Nacl Salud Publ, Ctr Reg Invest Salud Publ, Tapachula, Chiapas, Mexico. [Gould, Fred; Walsh, Rachael K.] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA. [Gould, Fred; Lloyd, Alun L.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA. [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [James, Anthony A.] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. [James, Anthony A.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Alphey, Luke] Oxitec Ltd, Abingdon, Oxon, England. [Alphey, Luke] Univ Oxford, Dept Zool, Oxford OX1 3PS, England. RP Facchinelli, L (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM luca.facchinelli@uniroma1.it; twscott@ucdavis.edu RI Lloyd, Alun/H-4944-2012; OI Facchinelli, Luca/0000-0002-8987-1472 FU Regents of the University of California from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative, GC7 [316]; Istituto Pasteur-Fondazione Cenci Bolognetti; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Bill and Melinda Gates Foundation [OPP52250]; Oxitec Ltd FX This research was supported by funds from the Regents of the University of California from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative, GC7 #316 http://stopdengue.hs.uci.edu/; Istituto Pasteur-Fondazione Cenci Bolognetti; the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health; and the Bill and Melinda Gates Foundation (OPP52250). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Luke Alphey is an employee of Oxitec Ltd, which provided salary and other support for the research program. Also, such employee has shares or share options in Oxitec Ltd. Both Oxitec Ltd. and Oxford University have one or more patents or patent applications related to the subject of this paper. NR 31 TC 33 Z9 34 U1 3 U2 38 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2013 VL 7 IS 1 AR e2001 DI 10.1371/journal.pntd.0002001 PG 12 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 081ZB UT WOS:000314360200029 PM 23350003 ER PT J AU Rabaa, MA Klungthong, C Yoon, IK Holmes, EC Chinnawirotpisan, P Thaisomboonsuk, B Srikiatkhachorn, A Rothman, AL Tannitisupawong, D Aldstadt, J Nisalak, A Mammen, MP Gibbons, RV Endy, TP Fansiri, T Scott, TW Jarman, RG AF Rabaa, Maia A. Klungthong, Chonticha Yoon, In-Kyu Holmes, Edward C. Chinnawirotpisan, Piyawan Thaisomboonsuk, Butsaya Srikiatkhachorn, Anon Rothman, Alan L. Tannitisupawong, Darunee Aldstadt, Jared Nisalak, Ananda Mammen, Mammen P. Gibbons, Robert V. Endy, Timothy P. Fansiri, Thanyalak Scott, Thomas W. Jarman, Richard G. TI Frequent In-Migration and Highly Focal Transmission of Dengue Viruses among Children in Kamphaeng Phet, Thailand SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID PRIMARY-SCHOOL CHILDREN; POLYMERASE CHAIN-REACTION; HEMORRHAGIC-FEVER; INFECTIONS; EPIDEMIOLOGY; INAPPARENT; VILLAGES AB Revealing the patterns and determinants of the spread of dengue virus (DENV) at local scales is central to understanding the epidemiology and evolution of this major human pathogen. We performed a phylogenetic analysis of the envelope (E) genes of DENV-1, -2, -3, and -4 isolates (involving 97, 23, 5, and 74 newly collected sequences, respectively) sampled from school-based cohort and village-based cluster studies in Kamphaeng Phet, Thailand, between 2004 and 2007. With these data, we sought to describe the spatial and temporal patterns of DENV spread within a rural population where a future vaccine efficacy trial is planned. Our analysis revealed considerable genetic diversity within the study population, with multiple lineages within each serotype circulating for various lengths of time during the study period. These results suggest that DENV is frequently introduced into both semi-urban and rural areas in Kamphaeng Phet from other populations. In contrast, the persistence of viral lineages across sampling years was observed less frequently. Analysis of phylogenetic clustering indicated that DENV transmission was highly spatially and temporally focal, and that it occurred in homes rather than at school. Overall, the strength of temporal clustering suggests that seasonal bottlenecks in local DENV populations facilitate the invasion and establishment of viruses from outside of the study area, in turn reducing the extent of lineage persistence. C1 [Rabaa, Maia A.; Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Klungthong, Chonticha; Yoon, In-Kyu; Chinnawirotpisan, Piyawan; Thaisomboonsuk, Butsaya; Tannitisupawong, Darunee; Nisalak, Ananda; Mammen, Mammen P.; Gibbons, Robert V.; Jarman, Richard G.] Armed Forces Res Inst Med Sci, Dept Virol, Bangkok 10400, Thailand. [Holmes, Edward C.; Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Srikiatkhachorn, Anon] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA USA. [Rothman, Alan L.] Univ Rhode Isl, Inst Immunol & Informat, Providence, RI 02908 USA. [Aldstadt, Jared] SUNY Buffalo, Dept Geog, Buffalo, NY 14260 USA. [Endy, Timothy P.] SUNY Syracuse, Dept Infect Dis, Syracuse, NY USA. [Fansiri, Thanyalak] Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. RP Rabaa, MA (reprint author), Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. EM rick.jarman@us.army.mil RI Aldstadt, Jared/A-8508-2009; OI Aldstadt, Jared/0000-0001-9162-7439; Rabaa, Maia/0000-0003-0529-2228; Holmes, Edward/0000-0001-9596-3552 FU United States National Institutes of Health [P01 AI34533, R01 GM083224, R01 GM087405]; United States Military Infectious Diseases Research Program [S0016-04-AF]; Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health; Bill & Melinda Gates Foundation [OPP52250]; National Science Foundation Graduate Research Fellowship FX This work was supported by the United States National Institutes of Health [grant numbers P01 AI34533, R01 GM083224 and R01 GM087405]; United States Military Infectious Diseases Research Program [grant number S0016-04-AF]; the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health; and the Bill & Melinda Gates Foundation (OPP52250). Funding to MAR was provided by a National Science Foundation Graduate Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 13 Z9 13 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2013 VL 7 IS 1 AR e1990 DI 10.1371/journal.pntd.0001990 PG 14 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 081ZB UT WOS:000314360200020 PM 23350000 ER PT J AU Roy, M Bouma, MJ Ionides, EL Dhiman, RC Pascual, M AF Roy, Manojit Bouma, Menno J. Ionides, Edward L. Dhiman, Ramesh C. Pascual, Mercedes TI The Potential Elimination of Plasmodium vivax Malaria by Relapse Treatment: Insights from a Transmission Model and Surveillance Data from NW India SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID PRIMAQUINE THERAPY; HYPNOZOITES; INFECTIONS; INFERENCE; DYNAMICS; DISEASE AB Background: With over a hundred million annual infections and rising morbidity and mortality, Plasmodium vivax malaria remains largely a neglected disease. In particular, the dependence of this malaria species on relapses and the potential significance of the dormant stage as a therapeutic target, are poorly understood. Methodology/Principal Findings: To quantify relapse parameters and assess the population-wide consequences of anti-relapse treatment, we formulated a transmission model for P. vivax suitable for parameter inference with a recently developed statistical method based on routine surveillance data. A low-endemic region in NW India, whose strong seasonality demarcates the transmission season, provides an opportunity to apply this modeling approach. Our model gives maximum likelihood estimates of 7.1 months for the mean latency and 31% for the relapse rate, in close agreement with regression estimates and clinical evaluation studies in the area. With a baseline of prevailing treatment practices, the model predicts that an effective anti-relapse treatment of 65% of those infected would result in elimination within a decade, and that periodic mass treatment would dramatically reduce the burden of the disease in a few years. Conclusion/Significance: The striking dependence of P. vivax on relapses for survival reinforces the urgency to develop more effective anti-relapse treatments to replace Primaquine (PQ), the only available drug for the last fifty years. Our methods can provide alternative and simple means to estimate latency times and relapse frequency using routine epidemiological data, and to evaluate the population-wide impact of relapse treatment in areas similar to our study area. C1 [Roy, Manojit; Pascual, Mercedes] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Roy, Manojit; Pascual, Mercedes] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Bouma, Menno J.] Univ London, London Sch Hyg & Trop Med, Fac Publ Hlth & Policy, London, England. [Ionides, Edward L.] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. [Ionides, Edward L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Dhiman, Ramesh C.] Natl Inst Malaria Res, Delhi, India. RP Roy, M (reprint author), Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. EM pascual@umich.edu FU Graham Environmental Sustainability Institute (GESI) at the University of Michigan; National Science Foundation [DMS-0805533] FX This work was supported by a grant from the Graham Environmental Sustainability Institute (GESI) at the University of Michigan to MP, and the National Science Foundation grant (DMS-0805533) to ELI. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 18 Z9 18 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD JAN PY 2013 VL 7 IS 1 AR e1979 DI 10.1371/journal.pntd.0001979 PG 10 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 081ZB UT WOS:000314360200013 PM 23326611 ER PT J AU Arnold, MM Sen, A Greenberg, HB Patton, JT AF Arnold, Michelle M. Sen, Adrish Greenberg, Harry B. Patton, John T. TI The Battle between Rotavirus and Its Host for Control of the Interferon Signaling Pathway SO PLOS PATHOGENS LA English DT Review ID DOUBLE-STRANDED-RNA; INTESTINAL EPITHELIAL-CELLS; DEPRIVED NEWBORN CALVES; INNATE IMMUNE-RESPONSE; PROTEIN-KINASE R; INDUCIBLE GENE-I; TRANSLATION INITIATION; REGULATORY FACTOR-3; RIG-I; POLY(A)-BINDING PROTEIN AB Viral pathogens must overcome innate antiviral responses to replicate successfully in the host organism. Some of the mechanisms viruses use to interfere with antiviral responses in the infected cell include preventing detection of viral components, perturbing the function of transcription factors that initiate antiviral responses, and inhibiting downstream signal transduction. RNA viruses with small genomes and limited coding space often express multifunctional proteins that modulate several aspects of the normal host response to infection. One such virus, rotavirus, is an important pediatric pathogen that causes severe gastroenteritis, leading to similar to 450,000 deaths globally each year. In this review, we discuss the nature of the innate antiviral responses triggered by rotavirus infection and the viral mechanisms for inhibiting these responses. C1 [Arnold, Michelle M.; Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Sen, Adrish; Greenberg, Harry B.] Stanford Univ, Dept Med & Microbiol & Immunol, Stanford, CA 94305 USA. [Sen, Adrish; Greenberg, Harry B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Arnold, MM (reprint author), Louisiana State Univ, Dept Microbiol & Immunol, Hlth Sci Ctr Shreveport, Shreveport, LA 71105 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 FU VA Merit Award; NIH [R01 AI021362-26, P30DK56339]; Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (USA) [Z01 AI000754-16] FX AS and HGB were supported by a VA Merit Award (http://www.hsrd.research.va.gov/) and NIH grants R01 AI021362-26 and P30DK56339. MMA and JTP were supported by the Intramural Research Program (Z01 AI000754-16) of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (USA) (http://www.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 85 TC 29 Z9 32 U1 1 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003064 DI 10.1371/journal.ppat.1003064 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600004 PM 23359266 ER PT J AU Gilk, SD Cockrell, DC Luterbach, C Hansen, B Knodler, LA Ibarra, JA Steele-Mortimer, O Heinzen, RA AF Gilk, Stacey D. Cockrell, Diane C. Luterbach, Courtney Hansen, Bryan Knodler, Leigh A. Ibarra, J. Antonio Steele-Mortimer, Olivia Heinzen, Robert A. TI Bacterial Colonization of Host Cells in the Absence of Cholesterol SO PLOS PATHOGENS LA English DT Article ID PLASMA-MEMBRANE CHOLESTEROL; STRESS-INDUCED APOPTOSIS; PATHOGENICITY ISLAND 1; COXIELLA-BURNETII; CHLAMYDIA-TRACHOMATIS; LIPID RAFTS; OXIDATIVE STRESS; ANAPLASMA-PHAGOCYTOPHILUM; EPITHELIAL-CELLS; INTRACELLULAR CHOLESTEROL AB Reports implicating important roles for cholesterol and cholesterol-rich lipid rafts in host-pathogen interactions have largely employed sterol sequestering agents and biosynthesis inhibitors. Because the pleiotropic effects of these compounds can complicate experimental interpretation, we developed a new model system to investigate cholesterol requirements in pathogen infection utilizing DHCR24(-/-) mouse embryonic fibroblasts (MEFs). DHCR24(-/-) MEFs lack the Delta 24 sterol reductase required for the final enzymatic step in cholesterol biosynthesis, and consequently accumulate desmosterol into cellular membranes. Defective lipid raft function by DHCR24(-/-) MEFs adapted to growth in cholesterol-free medium was confirmed by showing deficient uptake of cholera-toxin B and impaired signaling by epidermal growth factor. Infection in the absence of cholesterol was then investigated for three intracellular bacterial pathogens: Coxiella burnetii, Salmonella enterica serovar Typhimurium, and Chlamydia trachomatis. Invasion by S. Typhimurium and C. trachomatis was unaltered in DHCR24(-/-) MEFs. In contrast, C. burnetii entry was significantly decreased in -cholesterol MEFs, and also in +cholesterol MEFs when lipid raft-associated alpha(V)beta(3) integrin was blocked, suggesting a role for lipid rafts in C. burnetii uptake. Once internalized, all three pathogens established their respective vacuolar niches and replicated normally. However, the C. burnetii-occupied vacuole within DHCR24(-/-) MEFs lacked the CD63-postive material and multilamellar membranes typical of vacuoles formed in wild type cells, indicating cholesterol functions in trafficking of multivesicular bodies to the pathogen vacuole. These data demonstrate that cholesterol is not essential for invasion and intracellular replication by S. Typhimurium and C. trachomatis, but plays a role in C. burnetii-host cell interactions. C1 [Gilk, Stacey D.; Cockrell, Diane C.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT USA. [Luterbach, Courtney; Knodler, Leigh A.; Ibarra, J. Antonio; Steele-Mortimer, Olivia] NIAID, Salmonella Host Cell Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT USA. [Hansen, Bryan] NIAID, Microscopy Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA. RP Gilk, SD (reprint author), NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT USA. EM rheinzen@niaid.nih.gov FU Division of Intramural Research, National Institutes of Allergy and Infectious Disease, National Institutes of Health FX This work was supported by the Division of Intramural Research, National Institutes of Allergy and Infectious Disease, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 83 TC 16 Z9 16 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003107 DI 10.1371/journal.ppat.1003107 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600019 PM 23358892 ER PT J AU Leibovitch, E Wohler, JE Macri, SMC Motanic, K Harberts, E Gaitan, MI Maggi, P Ellis, M Westmoreland, S Silva, A Reich, DS Jacobson, S AF Leibovitch, Emily Wohler, Jillian E. Macri, Sheila M. Cummings Motanic, Kelsey Harberts, Erin Gaitan, Maria I. Maggi, Pietro Ellis, Mary Westmoreland, Susan Silva, Afonso Reich, Daniel S. Jacobson, Steven TI Novel Marmoset (Callithrix jacchus) Model of Human Herpesvirus 6A and 6B Infections: Immunologic, Virologic and Radiologic Characterization SO PLOS PATHOGENS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CENTRAL-NERVOUS-SYSTEM; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; SERUM HHV-6 DNA; HUMAN-HERPESVIRUS-6 INFECTION; CEREBROSPINAL-FLUID; COMMON MARMOSETS; PRIMATE MODEL AB Human Herpesvirus 6 (HHV-6) is a ubiquitous virus with an estimated seroprevalence of 95% in the adult population. HHV-6 is associated with several neurologic disorders, including multiple sclerosis, an inflammatory demyelinating disease affecting the CNS. Animal models of HHV-6 infection would help clarify its role in human disease but have been slow to develop because rodents lack CD46, the receptor for cellular entry. Therefore, we investigated the effects of HHV-6 infections in a non-human primate, the common marmoset Callithrix jacchus. We inoculated a total of 12 marmosets with HHV-6A and HHV-6B intravenously and HHV-6A intranasally. Animals were monitored for 25 weeks post-inoculation clinically, immunologically and by MRI. Marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms and generated virus-specific antibody responses, while those inoculated intravenously with HHV-6B were asymptomatic and generated comparatively lower antibody responses. Viral DNA was detected at a low frequency in paraffin-embedded CNS tissue of a subset of marmosets inoculated with HHV-6A and HHV-6B intravenously. When different routes of HHV-6A inoculation were compared, intravenous inoculation resulted in virus-specific antibody responses and infrequent detection of viral DNA in the periphery, while intranasal inoculation resulted in negligible virus-specific antibody responses and frequent detection of viral DNA in the periphery. Moreover, marmosets inoculated with HHV-6A intravenously exhibited neurologic symptoms, while marmosets inoculated with HHV-6A intranasally were asymptomatic. We demonstrate that a marmoset model of HHV-6 infection can serve to further define the contribution of this ubiquitous virus to human neurologic disorders. C1 [Leibovitch, Emily; Wohler, Jillian E.; Motanic, Kelsey; Harberts, Erin; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Leibovitch, Emily] George Washington Univ, Inst Biomed Sci, Washington, DC USA. [Macri, Sheila M. Cummings; Ellis, Mary; Westmoreland, Susan] Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. [Gaitan, Maria I.; Maggi, Pietro; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Silva, Afonso] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Leibovitch, E (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) FX This work was supported through the intramural research program of the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 19 Z9 19 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003138 DI 10.1371/journal.ppat.1003138 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600043 PM 23382677 ER PT J AU Lionakis, MS Netea, MG AF Lionakis, Michail S. Netea, Mihai G. TI Candida and Host Determinants of Susceptibility to Invasive Candidiasis SO PLOS PATHOGENS LA English DT Article ID ALBICANS; RECOGNITION; POLYMORPHISMS; EXPRESSION; PROTECTION; INFECTION; IMMUNITY; THERAPY; FUNGI C1 [Lionakis, Michail S.] NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Med, Nijmegen Inst Infect Inflammat & Immun N4i, NL-6525 ED Nijmegen, Netherlands. RP Lionakis, MS (reprint author), NIAID, Fungal Pathogenesis Unit, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM lionakism@mail.nih.gov RI Netea, Mihai/N-5155-2014 FU Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA; ERC Consolidator Grant of the European Research Council FX This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA. M.G.N. was supported by an ERC Consolidator Grant of the European Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 44 Z9 44 U1 2 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003079 DI 10.1371/journal.ppat.1003079 PG 5 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600006 PM 23300452 ER PT J AU Nisii, C Castilletti, C Raoul, H Hewson, R Brown, D Gopal, R Eickmann, M Gunther, S Mirazimi, A Koivula, T Feldmann, H Di Caro, A Capobianchi, MR Ippolito, G AF Nisii, Carla Castilletti, Concetta Raoul, Herve Hewson, Roger Brown, David Gopal, Robin Eickmann, Markus Gunther, Stephan Mirazimi, Ali Koivula, Tuija Feldmann, Heinz Di Caro, Antonino Capobianchi, Maria R. Ippolito, Giuseppe TI Biosafety Level-4 Laboratories in Europe: Opportunities for Public Health, Diagnostics, and Research SO PLOS PATHOGENS LA English DT Editorial Material ID HIGHLY INFECTIOUS-DISEASES; HEMORRHAGIC-FEVER; OUTBREAK; ANGOLA C1 [Nisii, Carla; Castilletti, Concetta; Di Caro, Antonino; Capobianchi, Maria R.; Ippolito, Giuseppe] L Spallanzani Natl Inst Infect Dis, Rome, Italy. [Raoul, Herve] French Natl Inst Hlth & Med Res, Lyon, France. [Hewson, Roger] Hlth Protect Agcy, Salisbury, Wilts, England. [Brown, David; Gopal, Robin] Hlth Protect Agcy, London, England. [Eickmann, Markus] Univ Marburg, Marburg, Germany. [Gunther, Stephan] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany. [Mirazimi, Ali; Koivula, Tuija] Swedish Inst Communicable Dis Control, Solna, Sweden. [Feldmann, Heinz] NIAID, Div Intramural Res DIR, NIH, Rocky Mt Labs, Hamilton, MT USA. RP Nisii, C (reprint author), L Spallanzani Natl Inst Infect Dis, Rome, Italy. EM Giuseppe.ippolito@inmi.it RI raoul, herve/G-3403-2013; Di Caro, Antonino/K-6854-2016; Castilletti, Concetta/B-6545-2016; nisii, carla/B-8871-2017; OI Di Caro, Antonino/0000-0001-6027-3009; Castilletti, Concetta/0000-0001-9819-236X; nisii, carla/0000-0001-5369-0437; Ippolito, Giuseppe/0000-0002-1076-2979; Capobianchi, Maria Rosaria/0000-0003-3465-0071 NR 20 TC 5 Z9 5 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003105 DI 10.1371/journal.ppat.1003105 PG 4 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600017 PM 23349630 ER PT J AU Shabman, RS Hoenen, T Groseth, A Jabado, O Binning, JM Amarasinghe, GK Feldmann, H Basler, CF AF Shabman, Reed S. Hoenen, Thomas Groseth, Allison Jabado, Omar Binning, Jennifer M. Amarasinghe, Gaya K. Feldmann, Heinz Basler, Christopher F. TI An Upstream Open Reading Frame Modulates Ebola Virus Polymerase Translation and Virus Replication SO PLOS PATHOGENS LA English DT Article ID DOUBLE-STRANDED-RNA; MESSENGER-RNAS; VP35 PROTEIN; MARBURG-VIRUS; 5'-UNTRANSLATED REGIONS; PERSISTENT INFECTION; SECONDARY STRUCTURE; HEMORRHAGIC-FEVER; VIRAL TRANSLATION; REVERSE GENETICS AB Ebolaviruses, highly lethal zoonotic pathogens, possess longer genomes than most other non-segmented negative-strand RNA viruses due in part to long 5' and 3' untranslated regions (UTRs) present in the seven viral transcriptional units. To date, specific functions have not been assigned to these UTRs. With reporter assays, we demonstrated that the Zaire ebolavirus (EBOV) 5'-UTRs lack internal ribosomal entry site function. However, the 5'-UTRs do differentially regulate cap-dependent translation when placed upstream of a GFP reporter gene. Most dramatically, the 5'-UTR derived from the viral polymerase (L) mRNA strongly suppressed translation of GFP compared to a beta-actin 5'-UTR. The L 5'-UTR is one of four viral genes to possess upstream AUGs (uAUGs), and ablation of each uAUG enhanced translation of the primary ORF (pORF), most dramatically in the case of the L 5'-UTR. The L uAUG was sufficient to initiate translation, is surrounded by a "weak" Kozak sequence and suppressed pORF translation in a position-dependent manner. Under conditions where eIF2 alpha was phosphorylated, the presence of the uORF maintained translation of the L pORF, indicating that the uORF modulates L translation in response to cellular stress. To directly address the role of the L uAUG in virus replication, a recombinant EBOV was generated in which the L uAUG was mutated to UCG. Strikingly, mutating two nucleotides outside of previously-defined protein coding and cis-acting regulatory sequences attenuated virus growth to titers 10-100-fold lower than a wildtype virus in Vero and A549 cells. The mutant virus also exhibited decreased viral RNA synthesis as early as 6 hours post-infection and enhanced sensitivity to the stress inducer thapsigargin. Cumulatively, these data identify novel mechanisms by which EBOV regulates its polymerase expression, demonstrate their relevance to virus replication and identify a potential therapeutic target. C1 [Shabman, Reed S.; Basler, Christopher F.] Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. [Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USA. [Jabado, Omar] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Binning, Jennifer M.; Amarasinghe, Gaya K.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Binning, Jennifer M.] Iowa State Univ, Biochem Grad Program, Ames, IA USA. RP Shabman, RS (reprint author), Mt Sinai Sch Med, Dept Microbiol, New York, NY USA. EM chris.basler@mssm.edu OI Amarasinghe, Gaya/0000-0002-0418-9707; Hoenen, Thomas/0000-0002-5829-6305; Shabman, Reed/0000-0003-3272-3484 FU National Institutes of Health [AI059536, U54 AI 057158, 5F32AI084453, AI081914]; NIH, NIAID FX This work is supported by National Institutes of Health grants [AI059536, U54 AI 057158] (Northeast Biodefense Center-Lipkin) to CFB, [5F32AI084453] to RSS, and [AI081914] to GKA. This research was supported in part by the Intramural Research Program of the NIH, NIAID. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 25 Z9 25 U1 0 U2 28 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2013 VL 9 IS 1 AR e1003147 DI 10.1371/journal.ppat.1003147 PG 18 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 083LG UT WOS:000314464600049 PM 23382680 ER PT J AU Mallon, BS Chenoweth, JG Johnson, KR Hamilton, RS Tesar, PJ Yavatkar, AS Tyson, LJ Park, K Chen, KG Fann, YC McKay, RDG AF Mallon, Barbara S. Chenoweth, Josh G. Johnson, Kory R. Hamilton, Rebecca S. Tesar, Paul J. Yavatkar, Amarendra S. Tyson, Leonard J. Park, Kyeyoon Chen, Kevin G. Fann, Yang C. McKay, Ronald D. G. TI StemCellDB: The Human Pluripotent Stem Cell Database at the National Institutes of Health SO STEM CELL RESEARCH LA English DT Article ID HUMAN EMBRYONIC STEM; GENE-EXPRESSION SIGNATURES; HUMAN SOMATIC-CELLS; DEFINED FACTORS; LINES AB Much of the excitement generated by induced pluripotent stem cell technology is concerned with the possibility of disease modeling as well as the potential for personalized cell therapy. However, to pursue this it is important to understand the "normal" pluripotent state including its inherent variability. We have performed various molecular profiling assays for 21 hESC lines and 8 hiPSC lines to generate a comprehensive snapshot of the undifferentiated state of pluripotent stem cells. Analysis of the gene expression data revealed no iPSC-specific gene expression pattern in accordance with previous reports. We further compared cells, differentiated as embryoid bodies in 2 media proposed to initiate differentiation towards separate cell fates, as well as 20 adult tissues. From this analysis we have generated a gene list which defines pluripotency and establishes a baseline for the pluripotent state. Finally, we provide lists of genes enriched under both differentiation conditions which show the proposed bias toward independent cell fates. Published by Elsevier B.V. C1 [Mallon, Barbara S.; Hamilton, Rebecca S.; Park, Kyeyoon; Chen, Kevin G.; McKay, Ronald D. G.] NINDS, NIH, Stem Cell Unit, Div Intramural Res, Bethesda, MD 20892 USA. [Chenoweth, Josh G.; Tesar, Paul J.; McKay, Ronald D. G.] NINDS, Mol Biol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Johnson, Kory R.; Yavatkar, Amarendra S.; Tyson, Leonard J.; Fann, Yang C.] NINDS, Bioinformat Sect, Informat Technol & Bioinformat Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Mallon, BS (reprint author), 9000 Rockville Pike,Bldg 37,Rm 1000, Bethesda, MD 20892 USA. EM mallonb@mail.nih.gov RI Tesar, Paul/C-9848-2014; Chen, Kevin/D-6769-2011 OI Tesar, Paul/0000-0003-1532-3155; Chen, Kevin/0000-0003-2983-6330 FU NIH FX We would like to thank Dr. Pamela Gehron Robey for helpful discussions and Dr. Jeanette Beers for help with the fibroblast culture. This research was supported by the Intramural Research Program of the NIH. NR 16 TC 24 Z9 26 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1873-5061 J9 STEM CELL RES JI Stem Cell Res. PD JAN PY 2013 VL 10 IS 1 BP 57 EP 66 DI 10.1016/j.scr.2012.09.002 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 083RN UT WOS:000314483000006 PM 23117585 ER PT J AU Agier, L Broutin, H Bertherat, E Djingarey, MH Lingani, C Perea, W Hugonnet, S AF Agier, Lydiane Broutin, Helene Bertherat, Eric Djingarey, Mamoudou H. Lingani, Clement Perea, William Hugonnet, Stephane TI Timely detection of bacterial meningitis epidemics at district level: a study in three countries of the African Meningitis Belt SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE Bacterial meningitis; Africa; Epidemic timing; Spatiotemporal dynamics; Cluster analysis; Epidemic definition ID MENINGOCOCCAL MENINGITIS; SEROGROUP W135; BURKINA-FASO; WEST-AFRICA; DISEASE; VACCINE; NIGER; GHANA AB Background: Bacterial meningitis is a major public health problem in the African 'Meningitis Belt', where recurrent unpredictable epidemics occur. Despite the introduction in 2010 of the conjugate A vaccine, the reactive strategy remains important for responding to epidemics caused by other bacteria and in areas not yet vaccinated. Review of weekly numbers of suspected cases in Niger, Mali and Burkina Faso identified spatial disparities in the annual patterns of meningitis, which suggested a more local way of defining epidemics and initiating a timely vaccination campaign. Method: We defined an epidemic district-year as an excess of cases compared to the incidence previously experienced in the given district. Groups of similar districts in terms of seasonal patterns were identified by cluster analysis. We investigated a cluster-specific criterion of early epidemic onset to anticipate epidemic district-years. Results: These were encouraging, as epidemic district-years were fairly efficiently captured, with an average time gained of 2.5 weeks over the current strategy. Conclusion: This early-onset criterion could help ensure timely implementation of vaccination campaigns without the need to modify the implemented surveillance system. The next step is to extend this study to other countries of the Meningitis Belt, and to explain the differences in seasonal patterns in the different clusters. C1 [Agier, Lydiane; Bertherat, Eric; Perea, William; Hugonnet, Stephane] World Hlth Org, Epidem & Pandem Alert & Response, Geneva, Switzerland. [Agier, Lydiane] Univ Lancaster, Lancaster Med Sch, Lancaster LA1 4YD, England. [Broutin, Helene] Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, NIH, Bethesda, MD USA. [Broutin, Helene] Ctr IRD, CNRS 224, IRD UM1 UM2, MIVEGEC,UMR 5290, Montpellier, France. [Djingarey, Mamoudou H.; Lingani, Clement] WHO, Intercountry Support Team W Africa, Ouagadougou, Burkina Faso. RP Agier, L (reprint author), World Hlth Org, Epidem & Pandem Alert & Response, Geneva, Switzerland. EM Lagier@lancaster.ac.uk FU WHO, Geneva, Switzerland; Health and Climate Foundation, Washington DC, USA; Fogarty International Center, US National Institutes of Health, Bethesda, MD, USA FX LA was funded by WHO, Geneva, Switzerland and the Health and Climate Foundation, Washington DC, USA. HB was supported by the intramural research group of Fogarty International Center, US National Institutes of Health, Bethesda, MD, USA. No funding bodies had any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 7 Z9 7 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD JAN PY 2013 VL 107 IS 1 BP 30 EP 36 DI 10.1093/trstmh/trs010 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 079TI UT WOS:000314194700005 PM 23296695 ER PT J AU Kravitz, DJ Saleem, KS Baker, CI Ungerleider, LG Mishkin, M AF Kravitz, Dwight J. Saleem, Kadharbatcha S. Baker, Chris I. Ungerleider, Leslie G. Mishkin, Mortimer TI The ventral visual pathway: an expanded neural framework for the processing of object quality SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID MEDIAL TEMPORAL-LOBE; LATERAL PREFRONTAL CORTEX; PRIMATE ORBITOFRONTAL CORTEX; POSTERIOR INFEROTEMPORAL CORTEX; FEATURE-BASED ATTENTION; REWARD-GUIDED BEHAVIOR; FACE-SELECTIVE CORTEX; WORKING-MEMORY TASKS; MACAQUE MONKEY; CORTICAL CONNECTIONS AB Since the original characterization of the ventral visual pathway, our knowledge of its neuroanatomy, functional properties, and extrinsic targets has grown considerably. Here we synthesize this recent evidence and propose that the ventral pathway is best understood as a recurrent occipitotemporal network containing neural representations of object quality both utilized and constrained by at least six distinct cortical and subcortical systems. Each system serves its own specialized behavioral, cognitive, or affective function, collectively providing the raison d'etre for the ventral visual pathway. This expanded framework contrasts with the depiction of the ventral visual pathway as a largely serial staged hierarchy culminating in singular object representations and more parsimoniously incorporates attentional, contextual, and feedback effects. C1 [Kravitz, Dwight J.; Baker, Chris I.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Saleem, Kadharbatcha S.; Mishkin, Mortimer] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Kravitz, DJ (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM kravitzd@mail.nih.gov OI Saleem, Kadharbatcha S/0000-0002-4450-9234; Baker, Chris/0000-0001-6861-8964 FU Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Mental Health (NIMH) FX The authors thank B. Averbeck, M. Behrmann, M. Goodale, A. Harel, O. Hikosaka, D. Leopold, and A. Martin for their extremely helpful comments. This research was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Mental Health (NIMH). NR 313 TC 186 Z9 187 U1 12 U2 110 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JAN PY 2013 VL 17 IS 1 BP 26 EP 49 DI 10.1016/j.tics.2012.10.011 PG 24 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 077BZ UT WOS:000314004200009 PM 23265839 ER PT J AU Holmes, A Singewald, N AF Holmes, Andrew Singewald, Nicolas TI Individual differences in recovery from traumatic fear SO TRENDS IN NEUROSCIENCES LA English DT Review DE extinction; anxiety; amygdala; prefrontal cortex; PTSD; cross-species translation ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; HISTONE DEACETYLASE INHIBITORS; PLACEBO-CONTROLLED TRIAL; DEEP BRAIN-STIMULATION; GENETIC MOUSE MODEL; CONDITIONED FEAR; D-CYCLOSERINE; EXPOSURE THERAPY; BASOLATERAL AMYGDALA AB Although exposure to major psychological trauma is unfortunately common, risk for related neuropsychiatric conditions, such as post-traumatic stress disorder (PTSD), varies greatly among individuals. Fear extinction offers a tractable and translatable behavioral readout of individual differences in learned recovery from trauma. Studies in rodent substrains and subpopulations are providing new insights into neural system dysfunctions associated with impaired fear extinction. Rapid progress is also being made in identifying key molecular circuits, epigenetic mechanisms, and gene variants associated with differences in fear extinction. Here, we discuss how this research is informing understanding of the etiology and pathophysiology of individual differences in risk for trauma-related anxiety disorders, and how future work can help identify novel diagnostic biomarkers and pharmacotherapeutics for these disorders. C1 [Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA. [Singewald, Nicolas] Univ Innsbruck, Dept Pharmacol & Toxicol, Inst Pharm, A-6020 Innsbruck, Austria. [Singewald, Nicolas] Univ Innsbruck, Ctr Mol Biosci, A-6020 Innsbruck, Austria. RP Holmes, A (reprint author), NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD USA. EM Andrew.Holmes@nih.gov FU NIAAA Intramural Research Program; Austrian Science Fund FWF [SFB F4410-B19, W 1206-B18 SPIN] FX A.H. is supported by the NIAAA Intramural Research Program. N.S. is supported by the Austrian Science Fund FWF (SFB F4410-B19 and W 1206-B18 SPIN). NR 124 TC 45 Z9 45 U1 3 U2 53 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 2013 VL 36 IS 1 BP 23 EP 31 DI 10.1016/j.tins.2012.11.003 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 080QO UT WOS:000314258500004 PM 23260015 ER PT J AU Pommier, Y AF Pommier, Yves TI Drugging Topoisomerases: Lessons and Challenges SO ACS CHEMICAL BIOLOGY LA English DT Review ID TYROSYL-DNA PHOSPHODIESTERASE; BREAKAGE-REUNION REACTION; ADP-RIBOSE POLYMERASE; DOUBLE-STRAND BREAKS; QUANTIFIED IN-SITU; F-CAIN-MEMORIAL; ANTITUMOR DRUGS; II-BETA; COVALENT COMPLEXES; CRYSTAL-STRUCTURE AB Topoisomerases are ubiquitous enzymes that control DNA supercoiling and entanglements. They are essential during transcription and replication, and topoisomerase inhibitors are among the most effective and most commonly used anticancer and antibacterial drugs. This review consists of two parts. In the first part ("Lessons"), it gives background information on the catalytic mechanisms of the different enzyme families (6 different genes in humans and 4 in most bacteria), describes the "interfacial inhibition" by which topoisomerase-targeted drugs act as topoisomerase poisons, and describes clinically relevant topoisomerase inhibitors. It generalizes the interfacial inhibition principle, which was discovered from the mechanism of action of topoisornerase inhibitors, and discusses how topoisomerase inhibitors kill cells by trapping topoisomerases on DNA rather than by classical enzymatic inhibition. Trapping protein DNA complexes extends to a novel mechanism of action of PARP inhibitors and could be applied to the targeting of transcription factors. The second part of the review focuses on the challenges for discovery and precise use of topoisomerase inhibitors, including targeting topoisornerase inhibitors using chemical coupling and encapsulation for selective tumor delivery, use of pharmacodynarnic biomarkers to follow drug activity, complexity of the response determinants for anticancer activity and patient selection prospects of rational combinations with DNA repair inhibitors targeting tyrosyl-DNA-phosphodiesterases 1 and 2 (TDP1 and TDP2) and PARP, and the unmet need to develop inhibitors for type IA enzymes. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Center for Cancer Research [Z01 BC 0006161]; National Cancer Institute FX We wish to thank all of the members of the Laboratory of Molecular Pharmacology, past and present, for their contribution and constructive suggestions. A special thank to C. Marchand for Figure 2. Our studies are supported by the Center for Cancer Research (Z01 BC 0006161), National Cancer Institute. NR 154 TC 223 Z9 226 U1 13 U2 159 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2013 VL 8 IS 1 BP 82 EP 95 DI 10.1021/cb300648v PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077DL UT WOS:000314008000009 PM 23259582 ER PT J AU Hong, X Ma, MZ Gildersleeve, JC Chowdhury, S Barchi, JJ Mariuzza, RA Murphy, MB Mao, L Pancer, Z AF Hong, Xia Ma, Mark Z. Gildersleeve, Jeffrey C. Chowdhury, Sudipa Barchi, Joseph J., Jr. Mariuzza, Roy A. Murphy, Michael B. Mao, Li Pancer, Zeev TI Sugar-Binding Proteins from Fish: Selection of High Affinity "Lambodies" That Recognize Biomedically Relevant Glycans SO ACS CHEMICAL BIOLOGY LA English DT Article ID VARIABLE LYMPHOCYTE RECEPTORS; HISTO-BLOOD GROUP; ANTIGEN; ANTIBODIES; CANCER; SPECIFICITY; LECTINS; GLYCOSYLATION; DIVERSITY; LAMPREY AB Glycan-binding proteins are important for a wide variety of basic research and clinical applications, but proteins with high affinity and selectivity for carbohydrates are difficult to obtain. Here we describe a facile and cost-effective strategy to generate monoclonal lamprey antibodies, called lambodies, that target glycan determinants. We screened a library of yeast surface-displayed (YSD) lamprey variable lymphocyte receptors (VLR) for clones that can selectively bind various biomedically important glycotopes. These glycoconjugates included tumor-associated carbohydrate antigens (Tn and TF alpha), Lewis antigens (LeA and LeX), Nglycolylneuraminic acid, targets of broadly neutralizing HIV antibodies (poly-Man9 and the HIV gp120), and the glycoproteins asialo-ovine submwdllary mucin (a0SM) and asialohuman glycophorin A (aGPA). We isolated clones that bind each of these targets in a glycan-dependent manner and with very strong binding constants, for example, 6.2 nM for Man9 and 44.7 nM for gp120, determined by surface plasmon resonance (SPR). One particular lambody, VLRB.aGPA.23, was shown by glycan array analysis to be selective for the blood group I-I type 3 trisaccharide (BG-H3, Fucal-2Gal beta 1-3GalNAc alpha), aGPA, and TFa (Gal beta 1-3GalNAc alpha), with affinity constants of 0.2, 1, and 8 nM, respectively. In human tissue microarrays this lambody selectively detected cancer-associated carbohydrate antigens in 14 different types of cancers. It stained 27% of non-small cell lung cancer (NSCLC) samples in a pattern that correlated with poor patient survival. Lambodies with exquisite affinity and selectivity for glycans may find myriad uses in glycobiolog-y and biomedical research. C1 [Hong, Xia; Pancer, Zeev] Univ Maryland, Sch Med, Inst Marine & Environm Technol, Baltimore, MD 21202 USA. [Hong, Xia; Pancer, Zeev] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21202 USA. [Ma, Mark Z.; Mao, Li] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Gildersleeve, Jeffrey C.; Chowdhury, Sudipa; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Ctr Canc Res, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Mariuzza, Roy A.] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA. [Murphy, Michael B.] GE Healthcare Life Sci, Piscataway, NJ 08854 USA. RP Pancer, Z (reprint author), Univ Maryland, Sch Med, Inst Marine & Environm Technol, Columbus Ctr Suite 236,701 E Pratt St, Baltimore, MD 21202 USA. EM zpancer@som.umaryland.edu RI Mao, Li/C-7570-2011; Gildersleeve, Jeffrey/N-3392-2014; Barchi Jr., Joseph/N-3784-2014 OI Mao, Li/0000-0001-7263-3358; FU NIH [GM62116, GM098791, A1083892, CAl26818, CA136635]; NSF [MCB-0614672]; NCI FX We thank D. F. Smith and J. Heimburg-Molinaro for glycan profiling our lambody at the Consortium for Functional Glycomics (Emory University School of Medicine) supported by NIH Grants GM62116 and GM098791, and R. Lin for technical assistance (University of Maryland School of Dentistry). Supported by grants MCB-0614672 from NSF and A1083892 (Z.P.), CAl26818 and CA136635 (L.M.) from NIH. This work was supported in part by the intramural research program of the NIH, NCI. NR 33 TC 15 Z9 15 U1 5 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2013 VL 8 IS 1 BP 152 EP 160 DI 10.1021/cb300399s PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077DL UT WOS:000314008000018 PM 23030719 ER PT J AU Popp, O Veith, S Fahrer, J Bohr, VA Burkle, A Mangerich, A AF Popp, Oliver Veith, Sebastian Fahrer, Joerg Bohr, Vilhelm A. Buerkle, Alexander Mangerich, Aswin TI Site-Specific Noncovalent Interaction of the Biopolymer Poly(ADP-ribose) with the Werner Syndrome Protein Regulates Protein Functions SO ACS CHEMICAL BIOLOGY LA English DT Article ID DNA-DAMAGE; QUANTITATIVE-ANALYSIS; BINDING-PROTEINS; GENOTOXIC STRESS; WRN EXONUCLEASE; CHAIN-LENGTH; POLYMERASE-1; IDENTIFICATION; DOMAINS; APOPTOSIS AB Werner syndrome is a premature aging disorder that is caused by defects in the Werner protein (WRN). WRN is a member of the RecQ helicase family and possesses helicase and exonuclease activities. It is involved in various aspects of DNA metabolism such as DNA repair, telomere maintenance, and replication. Poly(ADP-ribose) polymerase 1 (PARP1) is also involved in these processes by catalyzing the formation of the nucleic-acid-like biopolymer poly(ADP-ribose) (PAR). It was previously shown that WRN interacts with PARP1 and that WRN activity is inhibited by PARP1. Using several bioanalytical approaches, here we demonstrate that the enzymatic product of PARP1, i.e., PAR, directly interacts with WRN physically and functionally. First, WRN binds HPLC-size-fractionated short and long PAR in a noncovalent manner. Second, we identified and characterized a PAR-binding motif (PBM) within the WRN sequence and showed that several basic and hydrophobic amino acids are of critical importance for mediating the PAR binding. Third, PAR-binding inhibits the DNA-binding, the helicase and the exonuclease activities of WRN in a concentration-dependent manner. On the basis of our results we propose that the transient nature of PAR produced by living cells would provide a versatile and swiftly reacting control system for WRN's function. More generally, our work underscores the important role of noncovalent PAR-protein interactions as a regulatory mechanism of protein function. C1 [Popp, Oliver; Veith, Sebastian; Fahrer, Joerg; Buerkle, Alexander; Mangerich, Aswin] Univ Konstanz, Dept Biol, Mol Toxicol Grp, D-78457 Constance, Germany. [Popp, Oliver] Univ Konstanz, Konstanz Res Sch Chem Biol, D-78457 Constance, Germany. [Veith, Sebastian] Univ Konstanz, Res Training Grp 1331, D-78457 Constance, Germany. [Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. RP Burkle, A (reprint author), Univ Konstanz, Dept Biol, Mol Toxicol Grp, D-78457 Constance, Germany. EM alexander.buerkle@uni-konstanz.de; aswin.mangerich@uni-konstanz.de FU Deutsche Forschungsgemeinschaft [FOR434]; Konstanz Research School Chemical Biology [KoRS-CB]; Research Training Group [RTG] 1331; Intramural Program of the National Institute on Aging; National Institutes of Health FX We thank M. Malanga for her initial help with in silico analysis. Furthermore we thank M. Miwa (Nagahama, Japan) and T. Sugimura (Tokyo, Japan) for the kind gift of 10H antibody and A. Marx (University of Konstanz) for sharing scientific equipment. This work was supported by the Deutsche Forschungsgemeinschaft (FOR434, Konstanz Research School Chemical Biology [KoRS-CB] and Research Training Group [RTG] 1331) and by the Intramural Program of the National Institute on Aging, National Institutes of Health. O.P. and S.V. were supported by fellowships of the KoRS-CB and the RTG 1331, respectively. NR 37 TC 16 Z9 16 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2013 VL 8 IS 1 BP 179 EP 188 DI 10.1021/cb300363g PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077DL UT WOS:000314008000021 PM 23082994 ER PT J AU Metifiot, M Maddali, K Johnson, BC Hare, S Smith, SJ Zhao, XZ Marchand, C Burke, TR Hughes, SH Cherepanov, P Pommier, Y AF Metifiot, Mathieu Maddali, Kasthuraiah Johnson, Barry C. Hare, Stephen Smith, Steven J. Zhao, Xue Zhi Marchand, Christophe Burke, Terrence R., Jr. Hughes, Stephen H. Cherepanov, Peter Pommier, Yves TI Activities, Crystal Structures, and Molecular Dynamics of Dihydro-1H-isoindole Derivatives, Inhibitors of HIV-1 lntegrase SO ACS CHEMICAL BIOLOGY LA English DT Article ID INTEGRASE INHIBITORS; STRAND TRANSFER; RALTEGRAVIR; RESISTANCE; ELVITEGRAVIR; INFECTION; INTASOME; MUTANTS; BINDING AB On the basis of a series of lactam and phthalimide derivatives that inhibit HIV-1 integrase, we developed a new molecule, XZ-259, with biochemical and antiviral activities comparable to raltegravir. We determined the crystal structures of XZ-259 and four other derivatives in complex with the prototype foamy virus intasome. The compounds bind at the integrase-Me2+-DNA interface of the integrase active site In biochemical and antiviral assays, XZ-259 inhibits raltegravir-resistant HIV-1 integrases harboring the Y143R mutation. Molecular modeling is also presented suggesting that XZ-259 can bind in the HIV-1 intasome with its dimethyl sulfonamide group adopting two opposite orientations. Molecular dynamics analyses of the HIV-1 intasome highlight the importance of the viral DNA in drug potency. C1 [Metifiot, Mathieu; Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hare, Stephen; Cherepanov, Peter] Univ London Imperial Coll Sci Technol & Med, Div Infect Dis, London, England. [Johnson, Barry C.; Smith, Steven J.; Hughes, Stephen H.] NIH, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NIH, Chem Biol Lab, Mol Discovery Program, Ctr Canc Res,Frederick Natl Lab, Frederick, MD 21702 USA. [Cherepanov, Peter] Canc Res UK London Res Inst, Clare Hall Labs, Potters Bar, Herts, England. RP Pommier, Y (reprint author), NCI, Lab Mol Pharmacol, Ctr Canc Res, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014; Cherepanov, Peter/F-6859-2010; OI Zhao, Xue Zhi/0000-0003-1006-6364; Cherepanov, Peter/0000-0002-0634-538X; Hare, Stephen/0000-0003-2951-1595 FU National Institutes of Health Intramural Program; Center for Cancer Research; National Cancer Institute; National Institutes of Health grants from the AIDS Intramural Targeted Program (IATAP) FX We thank the staff of the 102 and 103 beamlines from the Diamond Light Source (Oxfordshire, U.K.) and of the X06DA beamline from the Swiss Light Source (Villigen PSI, Switzerland) for assistance with X-ray data collection. Our studies were supported by the National Institutes of Health Intramural Program, Center for Cancer Research, National Cancer Institute and by National Institutes of Health grants from the AIDS Intramural Targeted Program (IATAP). NR 24 TC 23 Z9 23 U1 1 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD JAN PY 2013 VL 8 IS 1 BP 209 EP 217 DI 10.1021/cb300471n PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077DL UT WOS:000314008000024 PM 23075516 ER PT J AU Kahana, SY Rohan, J Allison, S Frazier, TW Drotar, D AF Kahana, Shoshana Y. Rohan, Jennifer Allison, Susannah Frazier, Thomas W. Drotar, Dennis TI A Meta-Analysis of Adherence to Antiretroviral Therapy and Virologic Responses in HIV-Infected Children, Adolescents, and Young Adults SO AIDS AND BEHAVIOR LA English DT Review DE Adherence; Pediatric; Youth; Young adult; Antiretroviral therapy; Highly active; HIV ID IMMUNODEFICIENCY-VIRUS-INFECTION; PATIENT-RELATED RISKS; OF-THE-LITERATURE; MEDICATION ADHERENCE; DRUG-RESISTANCE; UNITED-STATES; SOUTH-AFRICA; IMMUNOLOGICAL OUTCOMES; YOUTH; RECOMMENDATIONS AB The relationship between adherence to antiretroviral therapy (ART) and virologic outcomes in HIV+ children, adolescents, and young adults has been notably understudied, with much of the extant research focused on specific sub-literatures, such as resource-limited regions, specific clinical outcomes and time frames. The authors sought to better characterize the relationship between adherence to ART and virologic functioning along various sample and methodological factors. The authors conducted a meta-analysis of thirty-seven studies and utilized a random effects model to generate weighted mean effect sizes. In addition, the authors conducted meta-ANOVAs to examine potential factors influencing the relationship between adherence and three categories of clinical outcomes, specifically Viral Load (VL) < 100, VL < 400, and continuously measured VL. The analyses included 5,344 HIV+ children, adolescents, and young adults. The relationship between adherence behaviors and virologic outcomes varied across different methods of measurement and analysis. The relationship between adherence and continuously measured VL was significantly larger than for dichotomously-coded VL < 400 at Qb (20.69(1), p < .0005). Caregiver self-report indices elicited very small to small magnitude effects across both VL < 100 and VL < 400 outcomes and combined informant reporting (youth/adolescent and parent) produced significantly larger effects than caregiver report alone with adherence and VL < 400 outcomes at Qb (9.28(1), p < .005). More recently published trials reported smaller relationships between adherence and categorical clinical outcomes, such that year of publication significantly negatively correlated with VL < 100 (r = -.71(14), p < .005) and VL < 400 (r = -.43(26), p < .02). The data suggest that the magnitude of the relationship between ART adherence and virologic outcomes among heterogeneous samples of HIV+ children, adolescents and young adults varies across virologic outcomes and may be affected by moderating sample and methodological factors. Methodological and research recommendations for the interpretation of the current findings as well as for future HIV adherence related research are presented. C1 [Kahana, Shoshana Y.] NIDA, Serv Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. [Drotar, Dennis] Cincinnati Childrens Hosp Med Ctr, Div Behav Med & Clin Psychol, Cincinnati, OH USA. [Allison, Susannah] NIMH, Infants Children & Adolescents Program, Bethesda, MD 20892 USA. [Frazier, Thomas W.] Cleveland Clin, Ctr Autism, Cleveland, OH 44106 USA. [Frazier, Thomas W.] Cleveland Clin, ADHD Ctr, Cleveland, OH 44106 USA. RP Kahana, SY (reprint author), NIDA, Serv Res Branch, Div Epidemiol Serv & Prevent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM kahanas@mail.nih.gov NR 68 TC 28 Z9 30 U1 0 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD JAN PY 2013 VL 17 IS 1 BP 41 EP 60 DI 10.1007/s10461-012-0159-4 PG 20 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 073HL UT WOS:000313734000004 PM 22411426 ER PT J AU Miller, RL Sandoval, PC Pisitkun, T Knepper, MA Hoffert, JD AF Miller, R. Lance Sandoval, Pablo C. Pisitkun, Trairak Knepper, Mark A. Hoffert, Jason D. TI Vasopressin inhibits apoptosis in renal collecting duct cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE apoptosis; caspase; collecting duct; phosphorylation; vasopressin ID PROTEIN-KINASE-C; PHOSPHORYLATION; BAD; PATHWAYS; SURVIVAL; DEATH; AQUAPORIN-2; OCCURS; KIDNEY; AKT AB Miller RL, Sandoval PC, Pisitkun T, Knepper MA, Hoffert JD. Vasopressin inhibits apoptosis in renal collecting duct cells. Am J Physiol Renal Physiol 304: F177-F188, 2013. First published November 7, 2012; doi: 10.1152/ajprenal.00431.2012.-The peptide hormone arginine vasopressin (AVP) plays a critical role in regulating salt and water transport in the mammalian kidney. Recent studies have also demonstrated that AVP can promote cell survival in neuronal cells through V1 receptors. The current study addresses whether AVP can inhibit apoptosis in kidney collecting duct cells via V2 receptors and also explores the downstream signaling pathways regulating this phenomenon. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis and caspase cleavage assays demonstrated that 1-desamino-8-D-arginine vasopressin (dDAVP) inhibited apoptosis induced by various agents (staurosporine, actinomycin D, and cycloheximide) in cultured mouse cortical collecting duct cells (mpkCCD). Incubation with dDAVP also inhibited apoptosis induced by the phosphatidylinositol 3-kinase (PI3K) pathway inhibitor LY294002, suggesting that the antiapoptotic effects of dDAVP are largely independent of PI3K signaling. The V2 receptor antagonist SR121463 completely abolished the antiapoptotic effects of dDAVP. In addition, incubation with 8-cpt-cAMP, a cell-permeable analog of cAMP, reproduced the antiapoptotic effects of dDAVP. Both dDAVP and 8-cpt-cAMP increased phosphorylation of proapoptotic Bcl-2 family members Bad and Bok. Bad phosphorylation at Ser-112 and Ser-155 is known to inhibit its proapoptotic activity. Preincubation with H89 blocked dDAVP-induced phosphorylation of both Bad and Bok, suggesting dependence on protein kinase A (PKA). This study provides evidence that AVP can inhibit apoptosis through the V2 receptor and downstream cAMP-mediated pathways in mammalian kidney. The antiapoptotic action of AVP may be relevant to a number of physiological and pathophysiological conditions including osmotic tolerance in the inner medulla, escape from AVP-induced antidiuresis, and polycystic kidney disease. C1 [Miller, R. Lance; Sandoval, Pablo C.; Pisitkun, Trairak; Knepper, Mark A.; Hoffert, Jason D.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hoffert, JD (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr, Bethesda, MD 20892 USA. EM hoffertj@nhlbi.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU National Heart, Lung, and Blood Institute [ZO1-HL001285] FX This work was supported by the National Heart, Lung, and Blood Institute intramural budget (ZO1-HL001285). NR 46 TC 11 Z9 11 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2013 VL 304 IS 2 BP F177 EP F188 DI 10.1152/ajprenal.00431.2012 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 073JP UT WOS:000313739600005 PM 23136001 ER PT J AU Lavoue, J Friesen, MC Burstyn, I AF Lavoue, J. Friesen, M. C. Burstyn, I. TI Workplace Measurements by the US Occupational Safety and Health Administration since 1979: Descriptive Analysis and Potential Uses for Exposure Assessment SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE database; exposure reconstruction; IMIS; occupational hygiene ID CRYSTALLINE SILICA DUST; LONG-TERM TRENDS; UNITED-STATES; FORMALDEHYDE EXPOSURE; BERYLLIUM EXPOSURE; INFORMATION-SYSTEM; DATABASE; SURVEILLANCE; INDUSTRIES; DISEASE AB : Inspectors from the US Occupational Safety and Health Administration (OSHA) have been collecting industrial hygiene samples since 1972 to verify compliance with Permissible Exposure Limits. Starting in 1979, these measurements were computerized into the Integrated Management Information System (IMIS). In 2010, a dataset of over 1 million personal sample results analysed at OSHA's central laboratory in Salt Lake City [Chemical Exposure Health Data (CEHD)], only partially overlapping the IMIS database, was placed into public domain via the internet. We undertook this study to inform potential users about the relationship between this newly available OSHA data and IMIS and to offer insight about the opportunities and challenges associated with the use of OSHA measurement data for occupational exposure assessment. : We conducted a literature review of previous uses of IMIS in occupational health research and performed a descriptive analysis of the data recently made available and compared them to the IMIS database for lead, the most frequently sampled agent. : The literature review yielded 29 studies reporting use of IMIS data, but none using the CEHD data. Most studies focused on a single contaminant, with silica and lead being most frequently analysed. Sixteen studies addressed potential bias in IMIS, mostly by examining the association between exposure levels and ancillary information. Although no biases of appreciable magnitude were consistently reported across studies and agents, these assessments may have been obscured by selective under-reporting of non-detectable measurements. The CEHD data comprised 1 450 836 records from 1984 to 2009, not counting analytical blanks and erroneous records. Seventy eight agents with > 1000 personal samples yielded 1 037 367 records. Unlike IMIS, which contain administrative information (company size, job description), ancillary information in the CEHD data is mostly analytical. When the IMIS and CEHD measurements of lead were merged, 23 033 (39.2%) records were in common to both IMIS and CEHD datasets, 10 681 (18.2%) records were only in IMIS, and 25 012 (42.6%) records were only in the CEHD database. While IMIS-only records represent data analysed in other laboratories, CEHD-only records suggest partial reporting of sampling results by OSHA inspectors into IMIS. For lead, the percentage of non-detects in the CEHD-only data was 71% compared to 42% and 46% in the both-IMIS-CEHD and IMIS-only datasets, respectively, suggesting differential under-reporting of non-detects in IMIS. : IMIS and the CEHD datasets represent the biggest source of multi-industry exposure data in the USA and should be considered as a valuable source of information for occupational exposure assessment. The lack of empirical data on biases, adequate interpretation of non-detects in OSHA data, complicated by suspected differential under-reporting, remain the principal challenges to the valid estimation of average exposure conditions. We advocate additional comparisons between IMIS and CEHD data and discuss analytical strategies that may play a key role in meeting these challenges. C1 [Lavoue, J.] Univ Montreal, Hosp Res Ctr, Montreal, PQ, Canada. [Friesen, M. C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. [Burstyn, I.] Drexel Univ, Sch Publ Hlth, Dept Environm & Occupat Hlth, Philadelphia, PA 19104 USA. RP Lavoue, J (reprint author), Univ Montreal, Hosp Res Ctr, Montreal, PQ, Canada. EM jerome.lavoue@umontreal.ca RI Friesen, Melissa/A-5362-2009 FU Canadian Cancer Society Research Institutes; Fond de la Recherche en Sante du Quebec; Reseau de Recherche en Sante Environnementale; National Cancer Institute's Division of Cancer Epidemiology and Genetics FX We are thankful to Nardin Rezk and Jennifer Yu for background work on the CEHD data, to Warren Hendrick from the Salt Lake Technical Center for answering our questions about the CEHD data, to Sarah Locke for background work on the IMIS data, and to the OSHA Directorate of Information Technology for providing the IMIS data. JL was supported by the Canadian Cancer Society Research Institutes, the Fond de la Recherche en Sante du Quebec, and the Reseau de Recherche en Sante Environnementale. MF was supported by the Intramural Research Program of the National Cancer Institute's Division of Cancer Epidemiology and Genetics. NR 51 TC 11 Z9 11 U1 5 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD JAN PY 2013 VL 57 IS 1 BP 77 EP 97 DI 10.1093/annhyg/mes055 PG 21 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 073DX UT WOS:000313724800008 PM 22952385 ER PT J AU Jiang, H Xie, YQ Burnette, A Roach, J Giardina, SL Hecht, TT Creekmore, SP Mitra, G Zhu, JW AF Jiang, Hua Xie, Yueqing Burnette, Andrew Roach, John Giardina, Steven L. Hecht, Toby T. Creekmore, Stephen P. Mitra, Gautam Zhu, Jianwei TI Purification of clinical-grade disulfide stabilized antibody fragment variable-Pseudomonas exotoxin conjugate (dsFv-PE38) expressed in Escherichia coli SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Immunotoxin; Expression and purification; Refolding; cGMP production ID SINGLE-CHAIN IMMUNOTOXIN; FACTOR RECEPTOR GENE; PHASE-I TRIAL; RECOMBINANT IMMUNOTOXIN; HEMATOLOGIC MALIGNANCIES; GLIOMA XENOGRAFTS; COMPLETE REGRESSION; CYTOTOXIC ACTIVITY; ANTITUMOR-ACTIVITY; ANTIGEN-BINDING AB Immunotoxins are rationally designed cancer targeting and killing agents. Disulfide stabilized antibody Fv portion-toxin conjugates (dsFv-toxin) are third generation immunotoxins containing only the antibody fragment variable portions and a toxin fused to the V-H or V-L. Pseudomonas exotoxin fragment (PE-38) is a commonly used toxin in immunotoxin clinical trials. dsFv-toxin purification was previously published, but the recovery was not satisfactory. This report describes the development of a cGMP production process of the dsFv-toxin that incorporated a novel purification method. The method has been successfully applied to the clinical manufacturing of two dsFv-PE38 immunotoxins, MR1-1 targeting EGFRvIII and HA22 targeting CD22. The two subunits, V-L and V-H PE-38 were expressed separately in Escherichia coli using recombinant technology. Following cell lysis, inclusion bodies were isolated from the biomass harvested from fermentation in animal source component-free media. The dsFv-toxin was formed after denaturation and refolding, and subsequently purified to homogeneity through ammonium sulfate precipitation, hydrophobic interaction and ion-exchange chromatography steps. It was shown, in a direct comparison experiment using MR1-1 as model protein, that the recovery from the new purification method was improved three times over that from previously published method. The improved recovery was also demonstrated during the clinical production of two dsFv-PE38 immunotoxins-MR1-1 and HA22. C1 [Jiang, Hua; Xie, Yueqing; Burnette, Andrew; Roach, John; Giardina, Steven L.; Mitra, Gautam; Zhu, Jianwei] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Biopharmaceut Dev Program, Frederick, MD 21702 USA. [Hecht, Toby T.; Creekmore, Stephen P.] Frederick Natl Lab Canc Res, DCTD, DTP, Biol Resources Branch, Frederick, MD 21702 USA. RP Zhu, JW (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Biopharmaceut Dev Program, Frederick, MD 21702 USA. EM zhujianwei@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts 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 the mentioned of trade names, commercial products, or organizations imply endorsement by the US government. NR 48 TC 4 Z9 4 U1 0 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD JAN PY 2013 VL 97 IS 2 BP 621 EP 632 DI 10.1007/s00253-012-4319-2 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 072EJ UT WOS:000313651700013 PM 22890777 ER PT J AU Humeniuk, R Rosu-Myles, M Fares, J Koller, R Bies, J Wolff, L AF Humeniuk, R. Rosu-Myles, M. Fares, J. Koller, R. Bies, J. Wolff, L. TI The role of tumor suppressor p15Ink4b in the regulation of hematopoietic progenitor cell fate SO BLOOD CANCER JOURNAL LA English DT Article DE p15Ink4b; hematopoiesis; stem cell; cell fate; differentiation; erythropoiesis ID ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROME; ERYTHROPOIETIN RECEPTOR; DNA METHYLATION; STEM-CELLS; INACTIVATION; P15(INK4B); DIFFERENTIATION; TRANSFORMATION; P16(INK4A) AB Epigenetic silencing of the tumor suppressor gene p15Ink4b (CDKN2B) is a frequent event in blood disorders like acute myeloid leukemia and myelodysplastic syndromes. The molecular function of p15Ink4b in hematopoietic differentiation still remains to be elucidated. Our previous study demonstrated that loss of p15Ink4b in mice results in skewing of the differentiation pattern of the common myeloid progenitor towards the myeloid lineage. Here, we investigated a function of p15Ink4b tumor suppressor gene in driving erythroid lineage commitment in hematopoietic progenitors. It was found that p15Ink4b is expressed more highly in committed megakaryocyte-erythroid progenitors than granulocyte-macrophage progenitors. More importantly, mice lacking p15Ink4b have lower numbers of primitive red cell progenitors and a severely impaired response to 5-fluorouracil-and phenylhydrazine-induced hematopoietic stress. Introduction of p15Ink4b into multipotential progenitors produced changes at the molecular level, including activation of mitogen-activated protein kinase\extracellular signal-regulated kinase (MEK/ERK) signaling, increase GATA-1, erythropoietin receptor (EpoR) and decrease Pu1, GATA-2 expression. These changes rendered cells more permissive to erythroid commitment and less permissive to myeloid commitment, as demonstrated by an increase in early burst-forming unit-erythroid formation with concomitant decrease in myeloid colonies. Our results indicate that p15Ink4b functions in hematopoiesis, by maintaining proper lineage commitment of progenitors and assisting in rapid red blood cells replenishment following stress. Blood Cancer Journal (2013) 3, e99; doi: 10.1038/bcj.2012.44; published online 4 January 2013 C1 [Humeniuk, R.; Rosu-Myles, M.; Fares, J.; Koller, R.; Bies, J.; Wolff, L.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 4124,37 Convent Dr,MSC4263, Bethesda, MD 20892 USA. EM wolffl@mail.nih.gov FU National Cancer Institute, Center for Cancer Research FX We thank G Tosato, W Vass, X Qian and S Ruscetti for the reagents, and technical support. B Taylor, S Banerjee from NCI FACS Core Facility, M Albaugh from SAIC and Z Valivullah for technical support. This work was supported by intramural research program of The National Cancer Institute, Center for Cancer Research. NR 45 TC 2 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2044-5385 J9 BLOOD CANCER J JI Blood Cancer J. PD JAN PY 2013 VL 3 AR e99 DI 10.1038/bcj.2012.44 PG 11 WC Oncology SC Oncology GA 080AL UT WOS:000314213500001 PM 23359317 ER PT J AU Rees, MG Gloyn, AL AF Rees, Matthew G. Gloyn, Anna L. TI Small molecular glucokinase activators: has another new anti-diabetic therapeutic lost favour? SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE glucokinase; glucokinase regulatory protein; glucokinase activator; hepatic steatosis; type 2 diabetes; hepatopharmacology; triglycerides ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; TRIGLYCERIDE LEVELS; PLASMA-GLUCOSE; P446L VARIANT; LIVER; LOCI; OVEREXPRESSION; IMPACT AB Glucokinase activators (GKAs) represent one of the leading hopes for the next generation of type 2 diabetes (T2D) therapeutics, showing efficacy in reducing blood glucose and HbA1c levels in animal models of T2D and short-term human trials. While the hypoglycaemic risks of GCK activation in pancreatic beta-cells have long been appreciated, the hepatic effects of GKAs have generally been perceived to be without significant side effect. In this issue of the British Journal of Pharmacology, De Ceuninck et al. report that acute and chronic GKA treatment of normoglycaemic and hyperglycaemic rodent models results in significant accumulation of triglycerides in the liver. This suggests GKA-mediated activation of hepatic glucose uptake and suppression of endogenous glucose production may come at a significant cost; namely, the development of hepatic steatosis. This raises important questions regarding the safety of GKAs and emphasizes that both plasma and hepatic lipid profiles should be carefully monitored in on-going and future studies of these molecules. C1 [Rees, Matthew G.; Gloyn, Anna L.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Rees, Matthew G.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Gloyn, AL (reprint author), Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LE, England. EM Anna.Gloyn@drl.ox.ac.uk FU Wellcome Trust [095101/Z/10Z, 095101] NR 16 TC 18 Z9 18 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2013 VL 168 IS 2 BP 335 EP 338 DI 10.1111/j.1476-5381.2012.02201.x PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 073OB UT WOS:000313751200006 PM 22946641 ER PT J AU Madan, RA Gulley, JL Kantoff, PW AF Madan, Ravi A. Gulley, James L. Kantoff, Philip W. TI Demystifying Immunotherapy in Prostate Cancer Understanding Current and Future Treatment Strategies SO CANCER JOURNAL LA English DT Article DE Immunotherapy; prostate cancer; therapeutic cancer vaccines; immune-checkpoint inhibitors; combination immunotherapy ID RECOMBINANT VACCINIA VIRUS; RE INTERDISCIPLINARY CRITIQUE; ANDROGEN-DEPRIVATION THERAPY; DOSE-ESCALATION TRIAL; PHASE-I TRIAL; SIPULEUCEL-T; CELLULAR IMMUNOTHERAPY; METASTATIC MELANOMA; TUMOR-CELLS; ACID-PHOSPHATASE AB Immunotherapy has emerged as a viable therapeutic option for patients with prostate cancer. There are multiple potential strategies that use the immune system, including therapeutic cancer vaccines that are designed to stimulate immune cells to target antigens expressed by cancer cells. Sipuleucel-T is a vaccine currently approved for the treatment of minimally symptomatic metastatic prostate cancer, whereas the vaccine PSA-TRICOM and the immune-checkpoint inhibitor ipilimumab are in phase III testing. Although there are no short-term changes in disease progression or available biomarkers to assess response, these agents appear to improve survival. One hypothesis suggests that this apparent paradox can be explained by the growth-moderating effects of these treatments, which do not cause tumor size to diminish, but rather stall or slow their growth rate over time. For this reason, the use of immunotherapy earlier in the disease process is being investigated. Another approach is to block immune-regulatory mechanisms mediated by the molecules cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1. Additional future strategies will combine immunotherapy with other standard therapies, potentially enhancing the latter's clinical impact and thereby improving both time to progression and overall survival due to the combined effects of both treatments. Prospective trials are currently evaluating these hypotheses and will ultimately serve to optimize immunotherapy in the treatment of prostate cancer. C1 [Madan, Ravi A.; Gulley, James L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gulley, JL (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [ZIA BC010666-08] NR 84 TC 13 Z9 15 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2013 VL 19 IS 1 BP 50 EP 58 DI 10.1097/PPO.0b013e31828160a9 PG 9 WC Oncology SC Oncology GA 075SN UT WOS:000313906900008 PM 23337757 ER PT J AU Tokar, EJ Person, RJ Sun, Y Perantoni, AO Waalkes, MP AF Tokar, Erik J. Person, Rachel J. Sun, Yang Perantoni, Alan O. Waalkes, Michael P. TI Chronic Exposure of Renal Stem Cells to Inorganic Arsenic Induces a Cancer Phenotype SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID INDUCED MALIGNANT-TRANSFORMATION; DIMETHYLARSINIC ACID; METANEPHRIC MESENCHYME; WILMS-TUMOR; CD1 MICE; KIDNEY; CYCLOOXYGENASE-2; EXPRESSION; INDUCTION; PATHWAY AB Inorganic arsenic in the drinking water is a multisite human carcinogen that potentially targets the kidney. Recent evidence also indicates that developmental arsenic exposure impacts renal carcinogenesis in humans and mice. Emerging theory indicates that cancer may be a disease of stem cells (SCs) and that there are abundant active SCs during early life. Therefore, we hypothesized that inorganic arsenic targets SCs, or partially differentiated progenitor cells (PCs), for oncogenic transformation. Thus, a rat kidney SC/PC cell line, RIMM-18, was chronically exposed to low-level arsenite (500 nM) for up to 28 weeks. Multiple markers of acquired cancer phenotype were assessed biweekly during arsenic exposure, including secreted matrix metalloproteinase (MMP) activity, proliferation rate, colony formation in soft agar, and cellular invasiveness. Arsenic exposure by 10 weeks and after also induced marked and sustained increases in colony formation, indicative of the loss of contact inhibition, and increased invasiveness, both cancer cell characteristics. Compared to the passage-matched control, chronic arsenic exposure caused exposure-duration dependent increases in secreted MMP-2 and MMP-9 activity, Cox-2 expression, and more rapid proliferation (all >2-fold), characteristics typical of cancer cells. Dysregulation of SC maintenance genes and signaling pathways are common during oncogenesis. During arsenite exposure, expression of several genes associated with normal kidney development and SC regulation and differentiation (i.e., Wt-1, Wnt-4, Bmp-7, etc.) were aberrantly altered. Arsenic-exposed renal SCs produced more nonadherent spheroid bodies that grew much more aggressively in Matrigel, typical of cancer SCs (CSCs). The transformed cells also showed gene overexpression typical of renal SCs/CSCs (CD24, Osr1, Ncam) and arsenic adaptation such as overexpression of Mt-1, Mt2, Sod-1, and Abcc2. These data suggest that inorganic arsenic induced an acquired cancer phenotype in vitro in these rat kidney SCs potentially forming CSCs and, consistent with data in vivo, indicate that these multipotent SCs may be targets of arsenic during renal carcinogenesis. C1 [Tokar, Erik J.; Person, Rachel J.; Sun, Yang; Waalkes, Michael P.] NIEHS, Natl Toxicol Program Lab, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Perantoni, Alan O.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Waalkes, MP (reprint author), NIEHS, Natl Toxicol Program Lab, Div Natl Toxicol Program, POB 12233,MD E1-07, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999] NR 61 TC 11 Z9 12 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2013 VL 26 IS 1 BP 96 EP 105 DI 10.1021/tx3004054 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 077DD UT WOS:000314007200010 PM 23137061 ER PT J AU Schaaper, RM Mathews, CK AF Schaaper, Roel M. Mathews, Christopher K. TI Mutational consequences of dNTP pool imbalances in E-coli SO DNA REPAIR LA English DT Article DE DNA replication fidelity; dNTP pools; DNA polymerase; dCTP deaminase; Nucleoside diphosphate kinase ID NUCLEOSIDE DIPHOSPHATE KINASE; DNA PRECURSOR ASYMMETRIES; REPLICATION FIDELITY; MISMATCH-REPAIR; BASE SUBSTITUTIONS; ERROR CATASTROPHE; POLYMERASE-III; MUTAGENESIS; GENE; MUTANTS AB The accuracy of DNA synthesis depends on the accuracy of the polymerase as well as the quality and concentration(s) of the available 5'-deoxynucleoside-triphosphate DNA precursors (dNTPs). The relationships between dNTPs and error rates have been studied in vitro, but only limited insights exist into these correlations during in vivo replication. We have investigated this issue in the bacterium Escherichia coli by analyzing the mutational properties of dcd and ndk strains. These strains, defective in dCTP deaminase and nucleoside diphosphate kinase, respectively, are characterized by both disturbances of dNTP pools and a mutator phenotype. ndk strains have been studied before, but were included in this study, as controversies exist regarding the source of its mutator phenotype. We show that dcd strains suffer from increased intracellular levels of dCTP (4-fold) and reduced levels of dGTP (2-fold), while displaying, as measured using a set of lacZ reversion markers in a mismatch-repair defective (mutL) background, a strong mutator effect for G.C -> T.A and A-T -> T.A transversions (27- and 42-fold enhancement, respectively). In contrast, ndk strains possess a lowered dATP level (4-fold) and modestly enhanced dCTP level (2-fold), while its mutator effect is specific for just the A.T -> T.A transversions. The two strains also display differential mutability for rifampicin-resistant mutants. Overall, our analysis reveals for both strains a satisfactory correlation between dNTP pool alterations and the replication error rates, and also suggests that a minimal explanation for the ndk mutator does not require assumptions beyond the predicted effect of the dNTP pools. Published by Elsevier B.V. C1 [Schaaper, Roel M.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Mathews, Christopher K.] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov FU National Institute of Environmental Health Sciences (NIEHS) [Z01 ES065086]; NIH [R01 GM073744]; NIEHS Center [ES000210] FX The authors thank Linda Wheeler, Ronnie Dunn, and Pamela Allen for their excellent technical assistance in this project, and Damian Gawel and Scott Lujan of the NIEHS for their helpful comments on the manuscript for the paper. This work was supported by project Z01 ES065086 of the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS), and NIH Grant R01 GM073744 and NIEHS Center Grant ES000210. NR 48 TC 17 Z9 17 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 EI 1568-7856 J9 DNA REPAIR JI DNA Repair PD JAN 1 PY 2013 VL 12 IS 1 BP 73 EP 79 DI 10.1016/j.dnarep.2012.10.011 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 077ET UT WOS:000314011400009 PM 23218950 ER PT J AU Stagliano, KER Oppenheim, JJ AF Stagliano, Katherine E. R. Oppenheim, Joost J. TI DEXterity of tolerogenic APCs SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Editorial Material DE Macrophages; Self-; non-self-discrimination; Tolerance; Vaccination ID REGULATORY T-CELLS; DENDRITIC CELLS; IN-VIVO; GRAVES-DISEASE; MOUSE MODEL; IMMUNOTHERAPY; DEXAMETHASONE; MECHANISMS; SUBSETS AB A promising therapeutic approach for inducing tolerance in autoreactive T cells is the use of APCs such as DCs and macrophages. In this issue of the European Journal of Immunology, Zheng et al. [Eur. J. Immunol. 2013. 43: 219227] study the concept of tolerogenic adjuvants to induce tolerance via vaccination. These authors have previously identified dexamethasone (Dex) as an effective tolerogenic adjuvant and, in this study, they have identified a population of peripheral macrophages that is enriched by Dex treatment and that mediates Dex's tolerogenic effect. In addition to performing a phenotypic characterization of this population, the authors noted an increase in serum levels of IL-10 and Treg cells after Dex treatment of mice. As discussed in this Commentary, by employing Dex as a tolerogenic adjuvant in the presence of relevant peptides, we may have a means of restoring specific immune tolerance in cases of autoimmune disease and allergy. C1 [Stagliano, Katherine E. R.; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Frederick Natl Lab Canc Res, Ft Detrick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Frederick Natl Lab Canc Res, POB B,Bldg 560,Rm 21-89A, Ft Detrick, MD 21702 USA. EM Oppenhei@ncifcrf.gov NR 25 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2980 EI 1521-4141 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2013 VL 43 IS 1 BP 38 EP 41 DI 10.1002/eji.201243184 PG 4 WC Immunology SC Immunology GA 075KB UT WOS:000313883200009 PM 23322692 ER PT J AU Qi, YW Zhu, F Li, J Fu, Y Pattaradilokrat, S Hong, LX Liu, SF Huang, FS Xu, WY Su, XZ AF Qi, Yanwei Zhu, Feng Li, Jian Fu, Yong Pattaradilokrat, Sittiporn Hong, Linxian Liu, Shengfa Huang, Fusheng Xu, Wenyue Su, Xin-zhuan TI Optimized protocols for improving the likelihood of cloning recombinant progeny from Plasmodium yoelii genetic crosses SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Malaria; Genetic cross; Rodent; Parasite cloning; Microsatellite ID LINKAGE GROUP SELECTION; MALARIA PARASITE; CHLOROQUINE RESISTANCE; FALCIPARUM; CHABAUDI; TARGETS; BERGHEI; LOCI; POLYMORPHISMS; TRANSMISSION AB Genetic cross is a powerful tool for studying malaria genes contributing to drug resistance, parasite development, and pathogenesis. Cloning and identification of recombinant progeny (RP) is laborious and expensive, especially when a large proportion of progeny derived from self-fertilization are present in the uncloned progeny of a genetic cross. Since the frequency of cross-fertilization affects the number of recombinant progeny in a genetic cross, it is important to optimize the procedure of a genetic cross to maximize the cross-fertilization. Here we investigated the factors that might influence the chances of obtaining RP from a genetic cross and showed that different Plasmodium yoelii strains/subspecies/clones had unique abilities in producing oocysts in a mosquito midgut. When a genetic cross is performed between two parents producing different numbers of functional gametocytes, the ratio of parental parasites must be adjusted to improve the chance of obtaining RP. An optimized parental ratio could be established based on oocyst counts from single infection of each parent before crossing experiments, which may reflect the efficiency of gametocyte production and/or fertilization. The timing of progeny cloning is also important; cloning of genetic cross progeny from mice directly infected with sporozoites (vs. frozen blood after needle passage) at a time when parasitemia is low (usually <1%) could improve the chance of obtaining RP. This study provides an optimized protocol for efficiently cloning RPs from a genetic cross of malaria parasites. Published by Elsevier Inc. C1 [Qi, Yanwei; Zhu, Feng; Li, Jian; Hong, Linxian; Liu, Shengfa; Su, Xin-zhuan] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361005, Fujian, Peoples R China. [Fu, Yong; Huang, Fusheng; Xu, Wenyue] Third Mil Med Univ, Dept Pathogen Biol, Chongqing, Peoples R China. [Pattaradilokrat, Sittiporn; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Pattaradilokrat, Sittiporn] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok 10330, Thailand. RP Xu, WY (reprint author), Third Mil Med Univ, Dept Pathogen Biol, Chongqing, Peoples R China. EM xuwenyue@gmail.com; xsu@niaid.nih.gov OI Xu, Wenyue/0000-0003-3681-5052; Su, Xinzhuan/0000-0003-3246-3248 FU Fundamental Research Funds for the Central Universities [2011121031]; Project 111; State Bureau of Foreign Experts; Ministry of Education of China [B06016]; 973 National Basic Research Program of China [2007CB513103]; Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health FX This work was funded by the Fundamental Research Funds for the Central Universities (2011121031); by "Project 111" sponsored by the State Bureau of Foreign Experts and Ministry of Education of China (B06016); by a 973 National Basic Research Program of China #2007CB513103; and by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. We thank NIAID intramural editor Brenda Rae Marshall and Cindy Clark of NIH Library Writing Center for assistance in manuscript editing. NR 32 TC 2 Z9 2 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JAN PY 2013 VL 133 IS 1 BP 44 EP 50 DI 10.1016/j.exppara.2012.10.011 PG 7 WC Parasitology SC Parasitology GA 077AA UT WOS:000313999100007 PM 23116600 ER PT J AU Teague, WE Soubias, O Petrache, H Fuller, N Hines, KG Rand, RP Gawrisch, K AF Teague, Walter E., Jr. Soubias, Olivier Petrache, Horia Fuller, Nola Hines, Kirk G. Rand, R. Peter Gawrisch, Klaus TI Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function SO FARADAY DISCUSSIONS LA English DT Article ID PROTEIN-COUPLED RECEPTORS; HEXAGONAL-PHASE-TRANSITION; NUCLEAR-MAGNETIC-RESONANCE; DOCOSAHEXAENOIC ACID; MEMBRANE-PROTEINS; NERVOUS-SYSTEM; ACYL-CHAIN; MODEL; PHOSPHOLIPIDS; CURVATURE AB Membranes with a high content of polyunsaturated phosphatidylethanolamines (PE) facilitate formation of metarhodopsin-II (M-II), the photointermediate of bovine rhodopsin that activates the G protein transducin. We determined whether M-II-formation is quantitatively linked to the elastic properties of PEs. Curvature elasticity of monolayers of the polyunsaturated lipids 18 : 0-22 : 6(n - 3)PE, 18 : 0-22 : 5(n - 6)PE and the model lipid 18 : 1(n - 9)-18 : 1(n - 9)PE were investigated in the inverse hexagonal phase. All three lipids form lipid monolayers with rather low spontaneous radii of curvature of 26-28 angstrom. In membranes, all three PEs generate high negative curvature elastic stress that shifts the equilibrium of M-I/M-II photointermediates of rhodopsin towards M-II formation. C1 [Teague, Walter E., Jr.; Soubias, Olivier; Hines, Kirk G.; Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Petrache, Horia] Indiana Univ Perdue Univ, Dept Phys, Indianapolis, IN 46202 USA. [Fuller, Nola; Rand, R. Peter] Brock Univ, Dept Biol Sci, St Catharines, ON L2S 3A1, Canada. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM hpetrach@iupui.edu; rrand@brocku.ca; gawrisch@helix.nih.gov FU National Institute on Alcohol Abuse and Alcoholism, National Institute of Health FX This work was supported by the Intramural Research Program of the National Institute on Alcohol Abuse and Alcoholism, National Institute of Health. NR 40 TC 15 Z9 15 U1 1 U2 30 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-6640 J9 FARADAY DISCUSS JI Faraday Discuss. PY 2013 VL 161 BP 383 EP 395 DI 10.1039/c2fd20095c PG 13 WC Chemistry, Physical SC Chemistry GA 076PU UT WOS:000313970200020 PM 23805751 ER PT J AU Sun, JH Aponte, AM Kohr, MJ Tong, G Steenbergen, C Murphy, E AF Sun, Junhui Aponte, Angel M. Kohr, Mark J. Tong, Guang Steenbergen, Charles Murphy, Elizabeth TI Essential role of nitric oxide in acute ischemic preconditioning: S-Nitros(yl)ation versus sGC/cGMP/PKG signaling? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Nitric oxide; Protein S-nitros(yl)ation; sGC/cGMP/PKG; Ischemic preconditioning ID ISOLATED RAT-HEART; PROTEIN-KINASE-G; S-NITROSYLATION; GUANYLYL CYCLASE; INFARCT SIZE; CARDIOPROTECTION; NO; REPERFUSION; INJURY; CGMP AB Nitric oxide (NO) plays an important role in acute ischemic preconditioning (IPC). In addition to activating soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathways, NO-mediated protein S-nitros(yl)ation (SNO) has been recently shown to, play an essential role in cardioprotection against ischemia-reperfusion (I/R) injury. In our previous studies, we have shown that IPC-induced cardioprotection could be blocked by treatment with either N-nitro-L-arginine methyl ester (L-NAME, a constitutive NO synthase inhibitor) or ascorbate (a reducing agent to decompose SNO). To clarify NO-mediated sGC/cGMP/PKG-dependent or -independent (i.e., SNO) signaling involved in IPC-induced cardioprotection, mouse hearts were Langendorff-perfused in the dark to prevent SNO decomposition by light exposure. Treatment with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ a highly selective inhibitor of sGC) or KT5823 (a potent and selective inhibitor of PKG) did not abolish IPC-induced acute protection, suggesting that the sGC/cGMP/PKG signaling pathway does not play an important role in NO-mediated cardioprotective signaling during acute IPC. In addition, treatment with ODQ in IPC hearts provided an additional protective effect on functional recovery, in parallel with a higher SNO level in these ODQ+IPC hearts. In conclusion, these results suggest that the protective effect of NO is not related primarily to activation of the sGC/cGMP/PKG signaling pathway, but rather through SNO signaling in IPC-induced acute cardioprotection. Published by Elsevier Inc. C1 [Sun, Junhui] NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Aponte, Angel M.] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Kohr, Mark J.; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Tong, Guang] Fourth Mil Med Univ, Xijing Hosp, Dept Cardiovasc Surg, Xian 710032, Peoples R China. RP Sun, JH (reprint author), NHLBI, Cardiac Physiol Sect, Syst Biol Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N206, Bethesda, MD 20892 USA. EM sun1@mail.nih.gov OI Kohr, Mark/0000-0002-6034-5962 FU NIH [1F32HL096142, 5R01HL039752]; China Scholarship Council [2011659007] FX This work was supported by the NIH Intramural Program (J.S., A.A., and E.M.), NIH Grants 1F32HL096142 (M.K.) and 5R01HL039752 (C.S.), and the China Scholarship Council No. 2011659007 (G.T.). The authors declare that they have no conflict of interests. NR 53 TC 22 Z9 22 U1 2 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN PY 2013 VL 54 BP 105 EP 112 DI 10.1016/j.freeradbiomed.2012.09.005 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 078DA UT WOS:000314077200010 PM 22989471 ER PT J AU Ansenberger-Fricano, K Ganini, D Mao, M Chatterjee, S Dallas, S Mason, RP Stadler, K Santos, JH Bonini, MG AF Ansenberger-Fricano, Kristine Ganini, Douglas Mao, Mao Chatterjee, Saurabh Dallas, Shannon Mason, Ronald P. Stadler, Krisztian Santos, Janine H. Bonini, Marcelo G. TI The peroxidase activity of mitochondrial superoxide dismutase SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE MnSOD; SOD2; Peroxidase; Mitochondria; Overexpression; Free radicals ID MATRIX-METALLOPROTEINASE EXPRESSION; HT-1080 FIBROSARCOMA CELLS; BREAST-CANCER CELLS; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; MALIGNANT PHENOTYPE; OVEREXPRESSION; MNSOD; APOPTOSIS; GROWTH AB Manganese superoxide dismutase (MnSOD) is an integral mitochondrial protein known as a first-line antioxidant defense against superoxide radical anions produced as by-products of the electron transport chain. Recent studies have shaped the idea that by regulating the mitochondrial redox status and H2O2 outflow, MnSOD acts as a fundamental regulator of cellular proliferation, metabolism, and apoptosis, thereby assuming roles that extend far beyond its proposed antioxidant functions. Accordingly, allelic variations of MnSOD that have been shown to augment levels of MnSOD in mitochondria result in a 10-fold increase in prostate cancer risk. In addition, epidemiologic studies indicate that reduced glutathione peroxidase activity along with increases in H2O2 further increase cancer risk in the face of MnSOD overexpression. These facts led us to hypothesize that, like its Cu,ZnSOD counterpart, MnSOD may work as a peroxidase, utilizing H2O2 to promote mitochondrial damage, a known cancer risk factor. Here we report that MnSOD indeed possesses peroxidase activity that manifests in mitochondria when the enzyme is overexpressed. (C) 2012 Elsevier Inc. All rights reserved. C1 [Bonini, Marcelo G.] Univ Illinois, Sch Med, Cardiol Sect, Chicago, IL 60612 USA. [Ansenberger-Fricano, Kristine; Mao, Mao; Bonini, Marcelo G.] Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. [Ganini, Douglas; Chatterjee, Saurabh; Dallas, Shannon; Mason, Ronald P.; Bonini, Marcelo G.] NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. [Stadler, Krisztian] Pennington Biomed Res Ctr, Oxidat Stress & Dis Lab, Baton Rouge, LA 70808 USA. [Santos, Janine H.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pharmacol & Physiol, Newark, NJ 07103 USA. RP Bonini, MG (reprint author), Univ Illinois, Sch Med, Cardiol Sect, 909 S Wolcott Ave,COMRB 1131, Chicago, IL 60612 USA. EM mbonini@uic.edu RI Mao, Mao/E-3783-2013 OI Mao, Mao/0000-0003-1524-8853 FU National Institutes of Health (NIEHS); College of Medicine, University of Illinois at Chicago; American Heart Association [09SDG2250933]; NIH [HL072742-08] FX The authors acknowledge Dr. Ann Motten and Mrs. Mary J. Mason, for their valuable assistance in the preparation of the manuscript, and Dr. Larry Oberley (in memoriam) for the generous gift of neo and Mn11 cells. We are also indebted to Mrs. Debris Sutton (NIEHS/NIH) for the acquisition of the electron microscopy images. This work was supported in part by the Intramural Research Program of the National Institutes of Health (NIEHS), by funds from the College of Medicine, University of Illinois at Chicago, and American Heart Association Grant 09SDG2250933 to M.G.B. K.A. is supported by NIH T32 Training Grant HL072742-08. NR 59 TC 11 Z9 11 U1 0 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JAN PY 2013 VL 54 BP 116 EP 124 DI 10.1016/j.freeradbiomed.2012.08.573 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 078DA UT WOS:000314077200012 PM 22982047 ER PT J AU Grady, C Wendler, D AF Grady, Christine Wendler, David TI Making the Transition to a Learning Health Care System SO HASTINGS CENTER REPORT LA English DT Editorial Material AB The authors of the two main articles in this supplement recognize the enormous potential of learning health care systems. Their first article argues that the development of these systems calls into question existing guidelines and practices that treat clinical care and clinical research as distinct activities. Their second article proposes to replace this traditional approach with a new framework, one intended to promote two important goals: support the transformation to a learning health care system and help to ensure the ethical appropriateness of the activities carried out within such a system. To promote these goals, the authors propose a framework consisting of seven obligations. The authors are aware that their framework does not provide much guidance for promoting their second goal. At first glance, the seven obligations also might appear to offer little in the way of promoting the first goal. In what way, then, is the proposed framework novel and transformative, as the authors claim? The answer appears to lie largely in how the authors interpret the sixth obligation in the frameworkthe obligation to conduct learning activities. C1 [Wendler, David] NIA, Bethesda, MD 20892 USA. NR 6 TC 4 Z9 4 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD JAN-FEB PY 2013 VL 43 SU 1 BP S32 EP S33 DI 10.1002/hast.137 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 073AC UT WOS:000313714600006 ER PT J AU Kunii, N Zhao, YB Jiang, SG Liu, XJ Scholler, J Balagopalan, L Samelson, LE Milone, MC June, CH AF Kunii, Naoki Zhao, Yangbing Jiang, Shuguang Liu, Xiaojun Scholler, John Balagopalan, Lakshmi Samelson, Lawrence E. Milone, Michael C. June, Carl H. TI Enhanced Function of Redirected Human T Cells Expressing Linker for Activation of T Cells That Is Resistant to Ubiquitylation SO HUMAN GENE THERAPY LA English DT Article ID TRANSMEMBRANE ADAPTER PROTEINS; ANTIGEN RECEPTOR; GENE-THERAPY; LAT; LYMPHOCYTES; PROLIFERATION; SURVIVAL; DOMAINS; TUMORS; CD28 AB It is likely that the enhancement of signaling after antigenic stimulation, particularly in the tumor microenvironment, would improve the function of adoptively transferred T cells. Linker for activation of T cells (LAT) plays a central role in T cell activation. We hypothesized that the ubiquitylation-resistant form of LAT in cells would enhance T cell signaling and thus augment antitumor activity. To test this, human CD4(+) or CD8(+) T cells were electroporated with small interfering RNA (siRNA) to repress endogenous LAT and ubiquitylation-resistant LAT 2KR or wild-type LAT mRNA was introduced for reexpression. Significantly enhanced phosphorylation of LAT and phospholipase C-gamma (PLC gamma) was observed, and augmented calcium signaling after T cell receptor (TCR) triggering was observed in LAT 2KR-expressing T cells. TCR-induced calcium signaling was abrogated in LAT knockdown cells, but the baseline was higher than that of control siRNA-electroporated cells, suggesting a fundamental requirement of LAT to maintain calcium homeostasis. Redirected LAT 2KR T cells expressing a chimeric antigen receptor or an MHC class I-restricted TCR showed augmented function as assessed by enhanced cytokine secretion and cytotoxicity. These results indicate that interruption of LAT ubiquitylation is a promising strategy to augment effector T cell function for adoptive cell therapy. C1 [Kunii, Naoki; Zhao, Yangbing; Jiang, Shuguang; Liu, Xiaojun; Scholler, John; June, Carl H.] Univ Penn, Abramson Family Canc Res Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zhao, Yangbing; Milone, Michael C.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Balagopalan, Lakshmi; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP June, CH (reprint author), Univ Penn, Abramson Family Canc Res Inst, Perelman Sch Med, 3400 Civ Ctr Blvd,8th Floor,Room 08-123, Philadelphia, PA 19104 USA. EM cjune@exchange.upenn.edu FU National Institutes of Health (NIH) Common Fund Nanomedicine program [PN2 EY016586]; Intramural Research Program of the NIH, NCI, CCR FX The authors thank Carmine Carpenito, Michael Kalos, and Caleph Wilson (University of Pennsylvania) and Shinichiro Motohashi (Department of Immunology and Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan) for advice; and members of the Human Immunology Core (Abramson Cancer Center) for providing lymphocytes. This work was funded by the National Institutes of Health (NIH) Common Fund Nanomedicine program (PN2 EY016586), and this research was supported, in part, by the Intramural Research Program of the NIH, NCI, CCR (L.B. and L.E.S.). NR 41 TC 4 Z9 5 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2013 VL 24 IS 1 BP 27 EP 37 DI 10.1089/hum.2012.130 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 075QF UT WOS:000313900900005 PM 22998346 ER PT J AU Wu, CF Jares, A Winkler, T Xie, JJ Metais, JY Dunbar, CE AF Wu, Chuanfeng Jares, Alexander Winkler, Thomas Xie, Jianjun Metais, Jean-Yves Dunbar, Cynthia E. TI High Efficiency Restriction Enzyme-Free Linear Amplification-Mediated Polymerase Chain Reaction Approach for Tracking Lentiviral Integration Sites Does Not Abrogate Retrieval Bias SO HUMAN GENE THERAPY LA English DT Article ID CELL GENE-THERAPY; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE; HEMATOPOIETIC STEM-CELLS; RETROVIRAL INTEGRATION; CLONAL ANALYSIS; SEQUENCE; VECTORS; PCR; GENOTOXICITY AB Retroviral vectors are an efficient and widely employed means of introducing an exogenous expression cassette into target cells. These vectors have been shown to integrate semi-randomly into the cellular genome, and can be associated with genotoxicity due to impact on expression of proximate genes. Therefore, efficient and accurate integration site analysis, while quantifying contributions of individual vector-containing clones, is desirable. Linear amplification-mediated polymerase chain reaction (LAM-PCR) is a widely used technique for identifying integrated proviral and host genomic DNA junctions. However, LAM-PCR is subject to selection bias inherent in the reliance of the assay on the presence of a restriction enzyme-cutting site adjacent to a retrievable integration site, and it is further limited by an inability to discriminate prior to sequencing between the flanking genomic DNA of interest and uninformative internal vector DNA. We report a modified restriction enzyme-free LAM-PCR (Re-free LAM-PCR) approach that is less time and labor intensive compared to conventional LAM-PCR, but in contrast to some other nonrestrictive methods, compares in efficiency and sensitivity, excludes retrieval of uninformative internal vector sequences, and allows retrieval of integration sites unbiased by the presence of nearby restriction sites. However, we report that Re-free LAM-PCR remains inaccurate for quantitation of the relative contributions of individual integration site-containing clones in a polyclonal setting, suggesting that bias in LAM-PCR retrieval of integration sites is not wholly explained by restriction enzyme-related factors. C1 [Wu, Chuanfeng; Jares, Alexander; Winkler, Thomas; Xie, Jianjun; Metais, Jean-Yves; Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Rockville, MD 20852 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, CRC Bldg 10,Room 4E-5132,10 Ctr Dr, Rockville, MD 20852 USA. EM dunbarc@nhlbi.nih.gov RI Wu, Chuanfeng/A-1109-2016; OI Jares, Alexander/0000-0001-8387-2362 FU National Heart, Lung, and Blood Institute, National Institutes of Health; NIH Center for Regenerative Medicine (NIH CRM) FX This research was supported by the Intramural Research Programs of the National Heart, Lung, and Blood Institute, National Institutes of Health, and the NIH Center for Regenerative Medicine (NIH CRM) funding. We thank Leigh Samsel and the staff in the Flow Cytometry Core Facility at NHLBI for their assistance. NR 29 TC 16 Z9 16 U1 0 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2013 VL 24 IS 1 BP 38 EP 47 DI 10.1089/hum.2012.082 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 075QF UT WOS:000313900900006 PM 22992116 ER PT J AU Levinson, KL Abuelo, C Chyung, E Salmeron, J Belinson, SE Sologuren, CV Ortiz, CS Vallejos, MJ Belinson, JL AF Levinson, Kimberly L. Abuelo, Carolina Chyung, Eunice Salmeron, Jorge Belinson, Suzanne E. Vallejos Sologuren, Carlos Santos Ortiz, Carlos Jose Vallejos, Maria Belinson, Jerome L. TI The Peru Cervical Cancer Prevention Study (PERCAPS) Community-Based Participatory Research in Manchay, Peru SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE Cervical cancer; Prevention; Community-based participatory research ID HPV; PROGRAM; WOMEN AB Objective: Cervical cancer is a preventable disease which causes significant morbidity and mortality, particularly in developing countries. Although technology for early detection continues to improve, prevention programs suffer from significant barriers. Community-based participatory research is an approach to research which focuses on collaboration with the community to suonount these barriers. The objective of this study was to evaluate the utility of community-based participatory research techniques in a mother-child screen/treat and vaccinate program for cervical cancer prevention in Manchay, Peru. Materials and Methods: Human papillomavirus (HPV) self-sampling and cryotherapy were used for the screen/treat intervention, and the Gardasil vaccine was used for the vaccine intervention. Community health workers from Manchay participated in a 3-day educational course, designed by the research team. The community health workers then decided how to implement the interventions in their community. The success of the program was measured by (1) the ability of the community health workers to determine an implementation plan, (2) the successful use of research forms provided, (3) participation and retention rates, and (4) satisfaction of the participants. Results: (1) The community health workers used a door-to-door approach through which participants were successfully registered and both interventions were successfully carried out; (2) registration forms, consent forms, and result forms were used correctly with minimal error; (3) screen/treat intervention: 97% of registered participants gave an HPV sample, 94% of HPV-positive women were treated, and 90% returned for 6-month follow-up; vaccine intervention: 95% of registered girls received the first vaccine, 97% of those received the second vaccine, and 93% the third; (4) 96% of participants in the screen/treat intervention reported high satisfaction. Conclusions: Community-based participatory research techniques successfully helped to implement a screen/treat and vaccinate cervical cancer prevention program in Manchay, Peru. These techniques may help overcome barriers to large-scale preventive health-care interventions. C1 [Levinson, Kimberly L.] Cleveland Clin, Dept Obstet & Gynecol, Div Gynecol Oncol, Cleveland, OH 44106 USA. [Abuelo, Carolina] Johns Hopkins Univ Hosp, PRISMA, NIH, Baltimore, MD 21287 USA. [Chyung, Eunice] Case Western Reserve Sch Med, Cleveland, OH USA. [Salmeron, Jorge] Inst Mexicano Seguro Social, Cuernavaca, Morelos, Mexico. [Santos Ortiz, Carlos; Jose Vallejos, Maria] Div Invest Oncosalud, Lima, Peru. [Belinson, Jerome L.] Cleveland Clin, Lerner Coll Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Cleveland, OH 44106 USA. RP Levinson, KL (reprint author), 9500 Euclid Ave A81, Cleveland, OH 44195 USA. EM levinsk@ccf.org FU National Institutes of Health Office of the Director; Fogarty International Center; Office of AIDS Research; National Cancer Center; National Eye Institute; National Heart, Blood, and Lung Institute; National Institute of Dental and Craniofacial Research; National Institute on Drug Abuse; National Institute of Mental Health; National Institute of Allergy and Infectious Diseases; National Institutes of Health Office of Women's Health and Research through the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; American Relief and Recovery Act; Preventive Oncology International; Investigator-Initiated Studies Program of Merck Sharp Dohme Corp; Merck Co, Inc. FX Supported by the National Institutes of Health Office of the Director, Fogarty International Center, Office of AIDS Research, National Cancer Center, National Eye Institute, National Heart, Blood, and Lung Institute, National Institute of Dental and Craniofacial Research, National Institute on Drug Abuse, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, and National Institutes of Health Office of Women's Health and Research through the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University (R24 TW007988) and the American Relief and Recovery Act; Preventive Oncology International; and in part by a research grant from the Investigator-Initiated Studies Program of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. The opinions expressed in this paper are those of the authors and do not necessarily represent those of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc. NR 14 TC 6 Z9 7 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JAN PY 2013 VL 23 IS 1 BP 141 EP 147 DI 10.1097/IGC.0b013e318275b007 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 077CH UT WOS:000314005000020 PM 23165314 ER PT J AU Gorelick, DA Goodwin, RS Schwilke, E Schwope, DM Darwin, WD Kelly, DL McMahon, RP Liu, F Ortemann-Renon, C Bonnet, D Huestis, MA AF Gorelick, David A. Goodwin, Robert S. Schwilke, Eugene Schwope, David M. Darwin, William D. Kelly, Deanna L. McMahon, Robert P. Liu, Fang Ortemann-Renon, Catherine Bonnet, Denis Huestis, Marilyn A. TI Tolerance to Effects of High-Dose Oral 9-Tetrahydrocannabinol and Plasma Cannabinoid Concentrations in Male Daily Cannabis Smokers SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID MARIJUANA; USERS; DELTA-9-TETRAHYDROCANNABINOL; DEPENDENCE; INGESTION; HUMANS; PAIN AB Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic 9-tetrahydrocannabinol (THC) (20 mg every 3.56 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 24; 120 mg on Days 56. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects. C1 [Gorelick, David A.; Goodwin, Robert S.; Schwilke, Eugene; Schwope, David M.; Darwin, William D.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Kelly, Deanna L.; McMahon, Robert P.; Liu, Fang] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Ortemann-Renon, Catherine; Bonnet, Denis] Sanofi Aventis Rech, Montpellier, France. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Baltimore, MD USA. EM mhuestis@intra.nida.nih.gov RI McMahon, Robert/C-5462-2009 FU Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse (NIDA); NIDA Residential Research Support Services (PI: DK) [HHSN271200599091CADB] FX This work was funded by the Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse (NIDA); NIDA Residential Research Support Services Contract HHSN271200599091CADB (PI: DK) to the Maryland Psychiatric Research Center (MPRC); and a Cooperative Research and Development Agreement between Sanofi-aventis and the National Institutes of Health. DB and CO-R are employees of Sanofi-aventis. NR 27 TC 11 Z9 11 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JAN-FEB PY 2013 VL 37 IS 1 BP 11 EP 16 DI 10.1093/jat/bks081 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 074PB UT WOS:000313823600003 PM 23074216 ER PT J AU Panchal, RG Lane, D Boshoff, HI Butler, MM Moir, DT Bowlin, TL Bavari, S AF Panchal, Rekha G. Lane, Douglas Boshoff, Helena I. Butler, Michelle M. Moir, Donald T. Bowlin, Terry L. Bavari, Sina TI Bis-imidazolinylindoles are active against methicillin-resistant Staphylococcus aureus and multidrug-resistant Mycobacterium tuberculosis SO JOURNAL OF ANTIBIOTICS LA English DT Article DE antibacterials; antibiotic resistance; bis-imidazolinylindoles; broad-spectrum ID PUBLIC-HEALTH THREAT; EMERGENCE C1 [Panchal, Rekha G.; Bavari, Sina] USA, Target Discovery & Expt Microbiol Dept, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Lane, Douglas] NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21701 USA. [Boshoff, Helena I.] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. [Butler, Michelle M.; Moir, Donald T.; Bowlin, Terry L.] Microbiotix Inc, Worcester, MA USA. RP Panchal, RG (reprint author), USA, Target Discovery & Expt Microbiol Dept, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA. EM rekha.panchal@amedd.army.mil FU Defense Threat Reduction Agency (DTRA); National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH, NIAID; Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute; [HDTRA1-06-C-0042] FX This project has been funded in part by HDTRA1-06-C-0042 to Microbiotix Inc. and by Defense Threat Reduction Agency (DTRA) to RGP and SB, and with federal funds from the National Cancer Institute, National Institutes of Health (under contract N01-CO-12400) and in part by the Intramural Research Program of the NIH, NIAID. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the US Army. NR 8 TC 4 Z9 4 U1 1 U2 4 PU JAPAN ANTIBIOTICS RESEARCH ASSOC PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD JAN PY 2013 VL 66 IS 1 BP 47 EP 49 DI 10.1038/ja.2012.93 PG 3 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA 079JB UT WOS:000314165300008 PM 23149517 ER PT J AU Kotani, K AF Kotani, Kazuhiko TI Monitoring Blood Chemistry Data in the Japanese National Health and Nutrition Survey: A Method and Its Significance SO JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE biochemical data; total error; national survey C1 [Kotani, Kazuhiko] Jichi Med Univ, Dept Clin Lab Med, Shimotsuke, Tochigi 3290498, Japan. [Kotani, Kazuhiko] NHLBI, NIH, Bethesda, MD 20892 USA. RP Kotani, K (reprint author), Jichi Med Univ, Dept Clin Lab Med, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan. EM kazukotani@jichi.ac.jp NR 4 TC 0 Z9 0 U1 0 U2 2 PU JAPAN EPIDEMIOLOGICAL ASSOC PI TOKYO PA C/O UNIBO PRESS, HONGO MT BLDG 4F, 7-2-2 HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0917-5040 J9 J EPIDEMIOL JI J. Epidemiol. PD JAN PY 2013 VL 23 IS 1 BP 2 EP 3 DI 10.2188/jea.JE20120178 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 075XT UT WOS:000313921200002 PM 23258218 ER PT J AU Thurber, KR Potapov, A Yau, WM Tycko, R AF Thurber, Kent R. Potapov, Alexey Yau, Wai-Ming Tycko, Robert TI Solid state nuclear magnetic resonance with magic-angle spinning and dynamic nuclear polarization below 25 K SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE DNP; Hyperpolarization; C-13 NMR; Ultra-low-temperature NMR; Melittin ID ENHANCED NMR-SPECTROSCOPY; ROTATING SOLIDS; HIV-1 GP120; V3 LOOP; MELITTIN; SPECTROMETER; MEMBRANES; CONFORMATION; TRANSITION; RELAXATION AB We describe an apparatus for solid state nuclear magnetic resonance (NMR) with dynamic nuclear polarization (DNP) and magic-angle spinning (MAS) at 20-25 K and 9.4 Tesla. The MAS NMR probe uses helium to cool the sample space and nitrogen gas for MAS drive and bearings, as described earlier [1], but also includes a corrugated waveguide for transmission of microwaves from below the probe to the sample. With a 30 mW circularly polarized microwave source at 264 GHz, MAS at 6.8 kHz, and 21 K sample temperature, greater than 25-fold enhancements of cross-polarized C-13 NMR signals are observed in spectra of frozen glycerol/water solutions containing the triradical dopant DOTOPA-TEMPO when microwaves are applied. As demonstrations, we present DNP-enhanced one-dimensional and two-dimensional C-13 MAS NMR spectra of frozen solutions of uniformly C-13-labeled L-alanine and melittin, a 26-residue helical peptide that we have synthesized with four uniformly C-13-labeled amino acids. Published by Elsevier Inc. C1 [Thurber, Kent R.; Potapov, Alexey; Yau, Wai-Ming; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Thurber, KR (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 116, Bethesda, MD 20892 USA. EM thurberk@niddk.nih.gov OI Potapov, Alexey/0000-0002-9518-4679 FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, 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, National Institutes of Health. We thank Bernard Howder for fabricating numerous parts of our DNP MAS system. NR 49 TC 24 Z9 24 U1 4 U2 80 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2013 VL 226 BP 100 EP 106 DI 10.1016/j.jmr.2012.11.009 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 079RU UT WOS:000314190700013 PM 23238592 ER PT J AU Clark, AM AF Clark, Andrew M. TI Reward processing: a global brain phenomenon? SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE reward; punishment; reinforcement learning; fMRI ID NEURONAL-ACTIVITY; SIGNALS; CORTEX AB Clark AM. Reward processing: a global brain phenomenon? J Neurophysiol 109: 1-4, 2013. First published July 18, 2012; doi:10.1152/jn.00070.2012.-Rewards and punishments (reinforcement) powerfully shape behavior. Accordingly, their neuronal representation is of significant interest, both for understanding normal brain-behavior relationships and the pathophysiology of disorders such as depression and addiction. A recent article by Vickery and colleagues (Neuron 72: 166-177, 2011) provides evidence that the neural response to rewards and punishments is surprisingly widespread, suggesting the need for examination of the specific roles of areas not commonly included in the canonical reward circuitry in processing reinforcement. C1 [Clark, Andrew M.] NIMH, Neuropsychol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Clark, AM (reprint author), 49 S Convent Dr, Bethesda, MD 20892 USA. EM clarkand@mail.nih.gov FU National Institute of Mental Health FX This work was supported by the Intramural Research Programs of the National Institute of Mental Health. NR 15 TC 0 Z9 0 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 2013 VL 109 IS 1 BP 1 EP 4 DI 10.1152/jn.00070.2012 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 064EY UT WOS:000313056100001 PM 22815405 ER PT J AU Hines, CS Fujita, M Zoghbi, SS Kim, JS Quezado, Z Herscovitch, P Miao, N Araneta, MDF Morse, C Pike, VW Labovsky, J Innis, RB AF Hines, Christina S. Fujita, Masahiro Zoghbi, Sami S. Kim, Jin Su Quezado, Zenaide Herscovitch, Peter Miao, Ning Araneta, Maria D. Ferraris Morse, Cheryl Pike, Victor W. Labovsky, Julia Innis, Robert B. TI Propofol Decreases In Vivo Binding of C-11-PBR28 to Translocator Protein (18 kDa) in the Human Brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE anesthesia; cognitive impairment; neuroinflammation ID C-11-FLUMAZENIL BINDING; RADIOLIGAND BINDING; PET RADIOLIGAND; RECEPTOR; INFLAMMATION; MONKEY; TSPO; SEDATION/ANESTHESIA; ANESTHESIA; DISORDERS AB The PET radioligand C-11-PBR28 targets translocator protein (18 kDa) (TSPO) and is a potential marker of neuroimmune activation in vivo. Although several patient populations have been studied using C-11-PBR28, no investigators have studied cognitively impaired patients who would require anesthesia for the PET procedure, nor have any reports investigated the effects that anesthesia may have on radioligand uptake. The purpose of this study was to determine whether the anesthetic propofol alters brain uptake of C-11-PBR28 in healthy subjects. Methods: Ten healthy subjects (5 men; 5 women) each underwent 2 dynamic brain PET scans on the same day, first at baseline and then with intravenous propofol anesthesia. The subjects were injected with 680 +/- 14 MBq (mean +/- SD) of C-11-PBR28 for each PET scan. Brain uptake was measured as total distribution volume (V-T) using the Logan plot and metabolite-corrected arterial input function. Results: Propofol decreased V-T, which corrects for any alteration of metabolism of the radioligand, by about 26% (P = 0.011). In line with the decrease in V-T, brain time activity curves showed decreases of about 20% despite a 13% increase in plasma area under the curve with propofol. Reduction of V-T with propofol was observed across all brain regions, with no significant region X condition interaction (P = 0.40). Conclusion: Propofol anesthesia reduces the V-T of C-11-PBR28 by about 26% in the brains of healthy human subjects. Given this finding, future studies will measure neuroimmune activation in the brains of autistic volunteers and their age and sex-matched healthy controls using propofol anesthesia. We recommend that future PET studies using C-11-PBR28 and concomitant propofol anesthesia, as would be required in impaired populations, include a control arm to account for the effects of propofol on brain measurements of TSPO. C1 [Hines, Christina S.; Fujita, Masahiro; Zoghbi, Sami S.; Kim, Jin Su; Araneta, Maria D. Ferraris; Morse, Cheryl; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Kim, Jin Su] Korea Inst Radiol & Med Sci, Mol Imaging Res Ctr, Seoul, South Korea. [Quezado, Zenaide; Miao, Ning; Labovsky, Julia] NIH, Dept Perioperat Med, Ctr Clin, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, Dept Positron Emiss Tomog, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM masahiro.fujita@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [ZIA MH002852-08] NR 40 TC 11 Z9 11 U1 0 U2 6 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2013 VL 54 IS 1 BP 64 EP 69 DI 10.2967/jnumed.112.106872 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 071PN UT WOS:000313606800031 PM 23148296 ER PT J AU Loccisano, AE Longnecker, MP Campbell, JL Andersen, ME Clewell, HJ AF Loccisano, Anne E. Longnecker, Matthew P. Campbell, Jerry L., Jr. Andersen, Melvin E. Clewell, Harvey J., III TI Development of Pbpk Models for Pfoa and Pfos for Human Pregnancy and Lactation Life Stages SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID PERFLUOROOCTANE SULFONATE PFOS; FETAL-GROWTH RESTRICTION; PLASMA-PROTEIN BINDING; SPRAGUE-DAWLEY RATS; ANION TRANSPORTER 4; CORD BLOOD-SAMPLES; PERFLUORINATED COMPOUNDS; PERFLUOROALKYL ACIDS; POLYFLUOROALKYL CHEMICALS; PHARMACOKINETIC MODEL AB Perfluoroalkyl acid carboxylates and sulfonates (PFAA) have many consumer and industrial applications. Developmental toxicity studies in animals have raised concern about potential reproductive/developmental effects of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS); however, in humans conflicting results have been reported for associations between maternal PFAA levels and these outcomes. Risk assessments and interpretation of available human data during gestation and lactation are hindered due to lack of a framework for understanding and estimating maternal, fetal, and neonatal pharmacokinetics (PK). Physiologically based pharmacokinetic (PBPK) models were developed for PFOA and PFOS for the gestation and lactation life stages in humans to understand how the physiological changes associated with development affect pharmacokinetics of these compounds in the mother, fetus, and infant. These models were derived from PBPK models for PFOA/PFOS that were previously developed for adult humans and rats during gestation and lactation and from existing human pregnancy and lactation models developed for other chemicals. The models simulated PFOA and PFOS concentrations in fetal, infant, and maternal plasma and milk, were compared to available data in humans, and also were used to estimate maternal exposure. The models reported here identified several research needs, which include (1) the identification of transporters involved in renal resorption to explain the multiyear half-lives of these compounds in humans, (2) factors affecting clearance of PFOA/PFOS during gestation and lactation, and (3) data to estimate clearance of PFOA/PFOS in infants. These models may help address concerns regarding possible adverse health effects due to PFOA/PFOS exposure in the fetus and infant and may be useful in comparing pharmacokinetics across life stages. C1 [Loccisano, Anne E.; Campbell, Jerry L., Jr.; Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Ctr Human Hlth Assessment, Res Triangle Pk, NC USA. [Longnecker, Matthew P.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Loccisano, AE (reprint author), US EPA, 1200 Penn Ave NW,Mail Code 8601P, Washington, DC 20460 USA. EM Loccisano.Anne@epa.gov OI Andersen, Melvin/0000-0002-3894-4811; Longnecker, Matthew/0000-0001-6073-5322 FU 3M Company; DuPont Company; National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS) FX Financial support was provided by the 3M and DuPont Companies. This research was also supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences (NIEHS). The authors thank Dr. John Butenhoff at 3M Company for helpful discussions, comments, and revisions. They also thank Dr. Sofia Salas at Diego Portales University in Chile for generously sharing her data on maternal plasma volume expansion. NR 107 TC 31 Z9 31 U1 5 U2 42 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD JAN 1 PY 2013 VL 76 IS 1 BP 25 EP 57 DI 10.1080/15287394.2012.722523 PG 33 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 076GT UT WOS:000313945200003 PM 23151209 ER PT J AU Yap, TL Velayati, A Sidransky, E Lee, JC AF Yap, Thai Leong Velayati, Arash Sidransky, Ellen Lee, Jennifer C. TI Membrane-bound alpha-synuclein interacts with glucocerebrosidase and inhibits enzyme activity SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Gaucher disease; Parkinson disease; Fluorescence; Protein-lipid interactions ID PARKINSONS-DISEASE; LYSOSOMAL DEGRADATION; GAUCHER-DISEASE; UNILAMELLAR VESICLES; BETA-GLUCOSIDASE; LIPID-BINDING; BROKEN HELIX; LEWY BODIES; IN-VIVO; MUTATIONS AB Mutations in GBA, the gene encoding glucocerebrosidase, the lysosomal enzyme deficient in Gaucher disease increase the risk for developing Parkinson disease. Recent research suggests a relationship between glucocerebrosidase and the Parkinson disease-related amyloid-forming protein, alpha-synuclein; however, the specific molecular mechanisms responsible for association remain elusive. Previously, we showed that alpha-synuclein and glucocerebrosidase interact selectively under lysosomal conditions, and proposed that this newly identified interaction might influence cellular levels of alpha-synuclein by either promoting protein degradation and/or preventing aggregation. Here, we demonstrate that membrane-bound alpha-synuclein interacts with glucocerebrosidase, and that this complex formation inhibits enzyme function. Using site-specific fluorescence and Forster energy transfer probes, we mapped the protein-enzyme interacting regions on unilamellar vesicles. Our data suggest that on the membrane surface, the glucocerebrosidase-alpha-synuclein interaction involves a larger alpha-synuclein region compared to that found in solution. In addition, alpha-synuclein acts as a mixed inhibitor with an apparent IC50 in the submicromolar range. Importantly, the membrane-bound, alpha-helical form of alpha-synuclein is necessary for inhibition. This glucocerebrosidase interaction and inhibition likely contribute to the mechanism underlying GBA-associated parkinsonism. Published by Elsevier Inc. C1 [Yap, Thai Leong; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Velayati, Arash; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), 35 Convent Dr,Room 1A213, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov; leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute; National Human Genome Research Institute FX This work was supported by the Intramural Research Program at the National Institutes of Health, National Heart, Lung, and Blood Institute and the National Human Genome Research Institute. The recombinant glucocerebrosidase used was a gift from Protalix Biotherapeutics, Carmiel, Israel. We thank Duck-Yeon Lee (Biochemistry Core Facility, NHBLI) for technical assistance with mass spectrometry and Grzegorz Piszczek (Biophysics Core Facility, NHLBI) for the use of CD spectrometer and DLS instrument. We also are grateful to Ehud Goldin and Jim Gruschus for many helpful discussions. NR 61 TC 42 Z9 44 U1 0 U2 30 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 JAN PY 2013 VL 108 IS 1 BP 56 EP 64 DI 10.1016/j.ymgme.2012.11.010 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 075BW UT WOS:000313859800009 PM 23266198 ER PT J AU Pierson, TM Torres, PA Zeng, BJ Glanzman, AM Adams, D Finkel, RS Mahuran, DJ Pastores, GM Tennekoon, GI Kolodny, EH AF Pierson, Tyler Mark Torres, Paola A. Zeng, Bei-Jin Glanzman, Allan M. Adams, David Finkel, Richard S. Mahuran, Don J. Pastores, Gregory M. Tennekoon, Gihan I. Kolodny, Edwin H. TI Juvenile-onset motor neuron disease caused by novel mutations in beta-hexosaminidase SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Motor neuron disease; Sandhoff disease; beta-Hexosaminidase; Neurodegeneration; G(M2)-gangliosidosis; Lysosomal storage ID SANDHOFF-DISEASE; GM2 GANGLIOSIDOSIS; DEFICIENCY; VARIANT; FORMS; GENE; SITE AB A 12 year-old female presented with a seven-year history of progressive muscle weakness, atrophy, tremor and fasciculations. Cognition was normal. Rectal biopsy revealed intracellular storage material and biochemical testing indicated low hexosaminidase activity consistent with juvenile-onset G(M2)-gangliosidosis. Genetic evaluation revealed compound heterozygosity with two novel mutations in the hexosaminidase beta-subunit (c.512-3 C>A and c.1613+15_1613+18dup). Protein analysis was consistent with biochemical findings and indicated only a small portion of beta-subunits were properly processed. These results provide additional insight into juvenile-onset G(M2)-gangliosidoses and further expand the number of beta-hexosaminidase mutations associated with motor neuron disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Pierson, Tyler Mark; Finkel, Richard S.; Tennekoon, Gihan I.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Pierson, Tyler Mark] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. [Pierson, Tyler Mark] Cedars Sinai Med Ctr, Dept Neurol, Los Angeles, CA 90048 USA. [Torres, Paola A.; Zeng, Bei-Jin; Pastores, Gregory M.; Kolodny, Edwin H.] NYU, Dept Neurol, Div Neurogenet, Sch Med, New York, NY 10016 USA. [Glanzman, Allan M.] Childrens Hosp Philadelphia, Dept Phys Therapy, Philadelphia, PA 19104 USA. [Adams, David] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Mahuran, Don J.] Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. RP Pierson, TM (reprint author), Cedars Sinai Med Ctr, Dept Pediat, 8725 Alden Dr,SSB 3rd Floor 360, Los Angeles, CA 90048 USA. EM tyler.pierson@cshs.org FU Margaret Enoch Foundation; CIHR Team Grant [CTP-82944]; NIH [T32-HD043021-04]; Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular Diseases FX The NYU Neurogenetics Laboratory received funding for this work from the Margaret Enoch Foundation. Additional support was provided by a CIHR Team Grant, CTP-82944, to DM. TMP was funded by NIH grant T32-HD043021-04 and was also supported by the Diana and Steve Marienhoff Fashion Industries Guild Endowed Fellowship in Pediatric Neuromuscular Diseases. NR 22 TC 4 Z9 5 U1 0 U2 7 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 JAN PY 2013 VL 108 IS 1 BP 65 EP 69 DI 10.1016/j.ymgme.2012.10.023 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 075BW UT WOS:000313859800010 PM 23158871 ER PT J AU Rosenthal, M Wallace, GL Lawson, R Wills, MC Dixon, E Yerys, BE Kenworthy, L AF Rosenthal, Michael Wallace, Gregory L. Lawson, Rachel Wills, Meagan C. Dixon, Eunice Yerys, Benjamin E. Kenworthy, Lauren TI Impairments in Real-World Executive Function Increase From Childhood to Adolescence in Autism Spectrum Disorders SO NEUROPSYCHOLOGY LA English DT Article DE autism; executive function; BRIEF; development; age-related ID DIAGNOSTIC INTERVIEW; CHILDREN; DEFICITS; PERFORMANCE; SYMPTOMS; VERSION; SKILLS AB Objective: Although several studies have investigated developmental trajectories of executive functioning (EF) in individuals with autism spectrum disorders (ASD) using lab-based tasks, no study to date has directly measured how EF skills in everyday settings vary at different ages. The current study seeks to extend prior work by evaluating age-related differences in parent-reported EF problems during childhood and adolescence in a large cross-sectional cohort of children with ASD. Method: Children (N = 185) with an ASD without intellectual disability participated in the study. Participants were divided into four groups based on age (5-7, 8-10, 11-13, and 14-18-year-olds). The four age groups did not differ in IQ, sex ratio, or autism symptoms. Results: There were significant age effects (i.e., worsening scores with increasing age) in three of G. A. Gioia, P. K. Isquith, S. Guy, and L. Kenworthy's (2000) BRIEF: Behavior Rating Inventory of Executive Function, Odessa, FL, Psychological Assessment Resources scale scores: Initiate (p = .007), working memory (p = .003), and organization of materials (p = .023). In addition, analysis of the BRIEF scale profile revealed that, although multiple scales were elevated, the shift scale showed the greatest problems in both the youngest and oldest age cohorts. Conclusions: Older children with ASD show greater EF problems compared with the normative sample than younger children with ASD. Specifically, there is a widening divergence from the normative sample in metacognitive executive abilities in children with ASD as they age. This, in combination with significant, albeit more stable, impairments in flexibility, has implications for the challenges faced by high-functioning individuals with ASD as they attempt to enter mainstream work and social environments. C1 [Rosenthal, Michael; Wills, Meagan C.; Yerys, Benjamin E.; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA. [Wallace, Gregory L.; Dixon, Eunice] NIMH, Lab Brain & Cognit, US Dept HHS, NIH, Bethesda, MD USA. [Yerys, Benjamin E.] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. RP Rosenthal, M (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,Suite 350, Rockville, MD 20850 USA. EM MRosenthal01@gmail.com OI Wallace, Gregory/0000-0003-0329-5054 FU Intramural Research Program of the United States Department of Health and Human Services; National Institutes of Health, National Institute of Mental Health (NIMH); NIMH [5K23MH86111]; Isadore and Bertha Gudelsky Foundation FX We thank the families of the participants and the diagnostic team that characterized the participants for their efforts over the years. This research was supported by the Intramural Research Program of the United States Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIMH). B.E. Yerys was supported by the NIMH Grant 5K23MH86111. L. Kenworthy was supported by the Isadore and Bertha Gudelsky Foundation. NR 33 TC 44 Z9 46 U1 5 U2 55 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 2013 VL 27 IS 1 BP 13 EP 18 DI 10.1037/a0031299 PG 6 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 073QI UT WOS:000313757200002 PM 23356593 ER PT J AU Harford, TC Chen, CM Saha, TD Smith, SM Hasin, DS Grant, BF AF Harford, Thomas C. Chen, Chiung M. Saha, Tulshi D. Smith, Sharon M. Hasin, Deborah S. Grant, Bridget F. TI An Item Response Theory Analysis of DSM-IV Diagnostic Criteria for Personality Disorders: Findings From the National Epidemiologic Survey on Alcohol and Related Conditions SO PERSONALITY DISORDERS-THEORY RESEARCH AND TREATMENT LA English DT Article DE personality disorders; DSM-IV PD symptom criteria; DSM-IV distress/impairment requirement; epidemiology; item response theory ID GENERAL-POPULATION SAMPLE; UNITED-STATES; ANXIETY DISORDERS; AUDADIS-IV; PREVALENCE; COOCCURRENCE; COMORBIDITY; DISABILITY; RELIABILITY; MODULES AB The purpose of this study was to evaluate the psychometric properties of DSM-IV symptom criteria for assessing personality disorders (PDs) in a national population and to compare variations in proposed symptom coding for social and/or occupational dysfunction. Data were obtained from a total sample of 34,653 respondents from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). For each personality disorder, confirmatory factor analysis (CFA) established a 1-factor latent factor structure for the respective symptom criteria. A 2-parameter item response theory (IRT) model was applied to the symptom criteria for each PD to assess the probabilities of symptom item endorsements across different values of the underlying trait (latent factor). Findings were compared with a separate IRT model using an alternative coding of symptom criteria that requires distress/impairment to be related to each criterion. The CFAs yielded a good fit for a single underlying latent dimension for each PD. Findings from the IRT indicated that DSM-IV PD symptom criteria are clustered in the moderate to severe range of the underlying latent dimension for each PD and are peaked, indicating high measurement precision only within a narrow range of the underlying trait and lower measurement precision at lower and higher levels of severity. Compared with the NESARC symptom coding, the MT results for the alternative symptom coding are shifted toward the more severe range of the latent trait but generally have lower measurement precision for each PD. The IRT findings provide support for a reliable assessment of each PD for both NESARC and alternative coding for distress/impairment. The use of symptom dysfunction for each criterion, however, raises a number of issues and implications for the DSM-5 revision currently proposed for Axis II disorders (American Psychiatric Association, 2010). C1 [Harford, Thomas C.; Chen, Chiung M.] CSR Inc, Arlington, VA 22201 USA. [Saha, Tulshi D.; Smith, Sharon M.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Psychiat, Coll Phys & Surg, New York, NY 10027 USA. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. [Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Chen, CM (reprint author), CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA. EM cchen@csrincorporated.com FU Intramural NIH HHS; NIAAA NIH HHS [K05 AA014223, U01 AA018111, HHSN267200800023C] NR 28 TC 11 Z9 11 U1 0 U2 7 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1949-2715 J9 PERSONAL DISORD JI Personal. Disord. PD JAN PY 2013 VL 4 IS 1 BP 43 EP 54 DI 10.1037/a0027416 PG 12 WC Psychology, Clinical SC Psychology GA 076CW UT WOS:000313935100005 PM 22449066 ER PT J AU Chiu, CT Wang, ZF Hunsberger, JG Chuang, DM AF Chiu, Chi-Tso Wang, Zhifei Hunsberger, Joshua G. Chuang, De-Maw TI Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder SO PHARMACOLOGICAL REVIEWS LA English DT Review ID GLYCOGEN-SYNTHASE KINASE-3; AMYOTROPHIC-LATERAL-SCLEROSIS; FRAGILE-X-SYNDROME; TRAUMATIC BRAIN-INJURY; HISTONE DEACETYLASE INHIBITORS; FOCAL CEREBRAL-ISCHEMIA; SPINAL MUSCULAR-ATROPHY; ENDOTHELIAL GROWTH-FACTOR; OXIDATIVE STRESS PARAMETERS; RETINAL GANGLION-CELLS AB The mood stabilizers lithium and valproic acid (VPA) are traditionally used to treat bipolar disorder (BD), a severe mental illness arising from complex interactions between genes and environment that drive deficits in cellular plasticity and resiliency. The therapeutic potential of these drugs in other central nervous system diseases is also gaining support. This article reviews the various mechanisms of action of lithium and VPA gleaned from cellular and animal models of neurologic, neurodegenerative, and neuropsychiatric disorders. Clinical evidence is included when available to provide a comprehensive perspective of the field and to acknowledge some of the limitations of these treatments. First, the review describes how action at these drugs' primary targets-glycogen synthase kinase-3 for lithium and histone deacetylases for VPA-induces the transcription and expression of neurotrophic, angiogenic, and neuroprotective proteins. Cell survival signaling cascades, oxidative stress pathways, and protein quality control mechanisms may further underlie lithium and VPA's beneficial actions. The ability of cotreatment to augment neuroprotection and enhance stem cell homing and migration is also discussed, as are microRNAs as new therapeutic targets. Finally, preclinical findings have shown that the neuroprotective benefits of these agents facilitate anti-inflammation, angiogenesis, neurogenesis, blood-brain barrier integrity, and disease-specific neuroprotection. These mechanisms can be compared with dysregulated disease mechanisms to suggest core cellular and molecular disturbances identifiable by specific risk biomarkers. Future clinical endeavors are warranted to determine the therapeutic potential of lithium and VPA across the spectrum of central nervous system diseases, with particular emphasis on a personalized medicine approach toward treating these disorders. C1 [Chiu, Chi-Tso; Wang, Zhifei; Hunsberger, Joshua G.; Chuang, De-Maw] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, Bldg 10,Room 3D38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wang, Zhifei/I-2787-2013 FU Intramural Research Program of the National Institutes of Health National Institute of Mental Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX This work was supported by the Intramural Research Program of the National Institutes of Health National Institute of Mental Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). NR 555 TC 127 Z9 130 U1 5 U2 65 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD JAN PY 2013 VL 65 IS 1 BP 105 EP 142 DI 10.1124/pr.111.005512 PG 38 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071MB UT WOS:000313595800004 PM 23300133 ER PT J AU Benninghoff, J Grunze, H Schindler, C Genius, J Schloesser, RJ van der Ven, A Dehning, S Wiltfang, J Moller, HJ Rujescu, D AF Benninghoff, J. Grunze, H. Schindler, C. Genius, J. Schloesser, R. J. van der Ven, A. Dehning, S. Wiltfang, J. Moeller, H. -J. Rujescu, D. TI Ziprasidone - Not Haloperidol - Induces more de-novo Neurogenesis of Adult Neural Stem Cells Derived from Murine Hippocampus SO PHARMACOPSYCHIATRY LA English DT Article DE ziprasidone; haloperidol; beta-III-tubulin-positive neurons; adult neural stem cells; murine hippocampus; de-novo generation ID DENTATE GYRUS; ANTIPSYCHOTIC-DRUGS; 5-HT1A RECEPTORS; INTERFERON-GAMMA; RAT HIPPOCAMPUS; PROLIFERATION; SCHIZOPHRENIA; SEROTONIN; DOPAMINE; NEURONS AB Introduction: Here, we present a stem-cell based study on the de-novo generation of beta-III-tubulin-positive neurons after treatment with the classic antipsychotic drug haloperidol or after treatment with the second-generation antipsychotic (SGA) ziprasidone. Methods: Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in cell culture with basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF). ANSC differentiated upon withdrawal of EGF and bFGF. Results and Discussion: Ziprasidone generated significantly more beta-III-tubulin-positive neurons than haloperidol during the differentiation of adult neural stem cells isolated from murine hippocampus (ANSC). We assume that this net increase in neurogenesis by ziprasidone relies on this drug's 5-HT1A receptor affinity, which is not present in the haloperidol molecule, since the inactivation by WAY100621 impeded this process. These data could possibly suggest a clinical relevance for studying antipsychotic drugs in the stem cell paradigm employed in this study. C1 [Benninghoff, J.; Schindler, C.; Genius, J.; van der Ven, A.; Dehning, S.; Moeller, H. -J.; Rujescu, D.] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Schloesser, R. J.] NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Programm, NIH, Bethesda, MD 20892 USA. [Benninghoff, J.; Wiltfang, J.] Univ Hosp Essen, Dept Psychiat, D-45147 Essen, Germany. RP Benninghoff, J (reprint author), Univ Hosp Essen, Dept Psychiat, Virchowstr 171, D-45147 Essen, Germany. EM jens.benninghoff@lvr.de OI Genius, Just/0000-0003-3270-3491; Wiltfang, Jens/0000-0003-1492-5330; Grunze, Heinz/0000-0003-4712-8979 FU Pfizer Co, New York FX Yes: Funding of this study was provided by an Investigator initiated independent research grant from Pfizer Co, New York. Pfizer had no influence on study design, interpretation of data, or the writing of this report. JB, DR and HG designed the study, wrote the protocol and supervised the experiments. JG, CS, RS and SD assisted during the experiments and HJM served as additional supervisor to the study. All authors approved the final manuscript. HG and HJM have consulted for Pfizer, all other authors declare that they have no conflict of interest. NR 45 TC 8 Z9 8 U1 0 U2 6 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD JAN PY 2013 VL 46 IS 1 BP 10 EP 15 DI 10.1055/s-0032-1311607 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 075JP UT WOS:000313881700002 PM 22592505 ER PT J AU Juon, HS Park, BJ AF Juon, Hee-Soon Park, Byung Joon TI Effectiveness of a culturally integrated liver cancer education in improving HBV knowledge among Asian Americans SO PREVENTIVE MEDICINE LA English DT Article DE Knowledge of HBV infection; Asian Americans; Health disparity ID HEPATITIS-B KNOWLEDGE; SCREENING BEHAVIOR; CHINESE; WOMEN; AGE; DISPARITIES; PREVENTION; WASHINGTON; PROGRAM; VACCINATION AB Objective. The aim of this study was to assess the effectiveness of a hepatitis B virus (HBV) educational program in increasing HBV knowledge. Methods. Using a cluster randomized control trial to recruit participants from the community-based organization in the Baltimore-Washington Metropolitan Area; a total of 877 Asian American participants completed a self-administered pretest. HBV knowledge was the outcome measure. The intervention group received a 30-minute educational program. After the educational program, the intervention group completed a post-education survey. Six months after the education, all participants were followed by phone. Results. The intervention group showed significantly higher knowledge scores than the control group at the 6-month follow-up (between-group difference was 1.44 for knowledge of transmission modes and 0.59 for sequelae, p<0.01). For the intervention group, the increase in knowledge of HBV transmission modes in post-education was much higher than that at the 6-month follow-up (4.18 vs. 2.07), p<0.01) compared to baseline. Age was also an important factor on the educational effect: Those older than 60 years reported the lowest scores in all three points. Conclusions. Findings suggest that this culturally integrated liver cancer educational program increased HBV knowledge. Differential strategies are needed to target age groups, separately educating those younger and those older. (C) 2012 Elsevier Inc. All rights reserved. C1 [Juon, Hee-Soon] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD 21205 USA. [Park, Byung Joon] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA. RP Juon, HS (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, 624 N Broadway,Room 704, Baltimore, MD 21205 USA. EM hjuon@jhsph.edu FU NCI NIH HHS [R25CA129042] FX This research was supported by grant R25CA129042 (NCI NIH HHS). We thank all the participants of this study. We also appreciate the dedicated work of the members of the research team. NR 34 TC 8 Z9 8 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2013 VL 56 IS 1 BP 53 EP 58 DI 10.1016/j.ypmed.2012.11.003 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 077AN UT WOS:000314000400010 PM 23159302 ER PT J AU De Boeck, A Hendrix, A Maynard, D Van Bockstal, M Daniels, A Pauwels, P Gespach, C Bracke, M De Wever, O AF De Boeck, Astrid Hendrix, An Maynard, Dawn Van Bockstal, Mieke Daniels, Annick Pauwels, Patrick Gespach, Christian Bracke, Marc De Wever, Olivier TI Differential secretome analysis of cancer-associated fibroblasts and bone marrow-derived precursors to identify microenvironmental regulators of colon cancer progression SO PROTEOMICS LA English DT Article DE Cancer-associated fibroblasts; Cell Biology; Colon cancer; Mesenchymal stem cells; MS; Secretome ID MESENCHYMAL STROMAL CELLS; PROMOTE TUMOR-GROWTH; PROTEOMIC ANALYSIS; MASS-SPECTROMETRY; GENE-EXPRESSION; BREAST-CANCER; STEM-CELLS; CONDITIONED MEDIA; TISSUE; MYOFIBROBLASTS AB The identification of cancer-associated fibroblast (CAF)-derived proteins that mediate interactions between the tumor stroma and cancer cells is a crucial step toward the discovery of new molecular targets for therapy or molecular signatures that improve tumor classification and predict clinical outcome. CAF are a-smooth muscle actin positive, representing a myofibroblast phenotype that may differentiate from multiple precursor cells, including bone marrow-derived mesenchymal stem cells (MSC). Transforming growth factor-beta 1 (TGF-beta 1) is a crucial inducer of a-smooth muscle actin positive CAFs. In this study, we aimed to identify CAF-derived regulators of colon cancer progression by performing a high-throughput differential secretome profiling between CAF compared to noncancer-activated bone marrow-derived MSC. In addition, we explored the effect of TGF-beta 1 on the secretion of proteins by bone marrow-derived MSC in comparison with the protein secretion profile of CAF. TGF-beta 1 induced de novo secretion of 84 proteins in MSC, of which 16 proteins, including stromal-derived factor-1a and Rantes, were also present in CAF secretome. Immunohistochemistry further validated the expression of selected candidates such as tenascin C, fibronectin ED-A domain and stromal-derived factor-1 in clinical colon cancer specimens. In conclusion, this differential secretome approach enabled us to identify a series of candidate biomarkers for colon cancer that are associated with a CAF-specific phenotype. C1 [De Boeck, Astrid; Hendrix, An; Bracke, Marc; De Wever, Olivier] Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, Bethesda, MD USA. [Maynard, Dawn] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Van Bockstal, Mieke] Ghent Univ Hosp, Dept Pathol, Ghent, Belgium. [Daniels, Annick] Jesse Hosp, Lab Expt Hematol, Hasselt, Belgium. [Pauwels, Patrick] Univ Antwerp, Dept Pathol, Antwerp, Belgium. [Gespach, Christian] Univ Paris 06, Ctr Rech St Antoine, INSERM, UMR S938, Paris, France. RP De Wever, O (reprint author), Ghent Univ Hosp, Dept Radiotherapy & Nucl Med, Lab Expt Canc Res, Pintelaan 185, B-9000 Ghent, Belgium. EM olivier.dewever@ugent.be RI de wever, olivier/J-3094-2013 OI de wever, olivier/0000-0002-5453-760X FU Intramural Research Program of the National Human Genome Research Institute; Centrum voor Gezwelziekten; Flemish community [I.2007.03, T.2009.14, T.2010.14]; France [I.2007.03, T.2009.14, T.2010.14]; INSERM; Vlaamse Liga tegen Kanker; Ghent University; Fund for Scientific Research-Flanders FX This work was supported by the Intramural Research Program of the National Human Genome Research Institute, Centrum voor Gezwelziekten, the Scientific Exchange Program between the Flemish community and France (I.2007.03, T.2009.14, T.2010.14), INSERM (C. G.), Vlaamse Liga tegen Kanker (A. D. B and O. D. W), postdoctoral grant from Special Research Fund, Ghent University (A. H.), travel grant (A. H. and O. D. W.), a doctoral grant (A. D. B.), and a postdoctoral researcher (O. D. W. and A. H.) from Fund for Scientific Research-Flanders. NR 39 TC 30 Z9 30 U1 3 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JAN PY 2013 VL 13 IS 2 SI SI BP 379 EP 388 DI 10.1002/pmic.201200179 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 076TU UT WOS:000313981800018 PM 23175172 ER PT J AU Coleman, CN AF Coleman, C. Norman TI Fukushima and the Future of Radiation Research SO RADIATION RESEARCH LA English DT Editorial Material ID MEDICAL RESPONSE; THERAPY; CANCER; RADIOTHERAPY; EXPOSURE; INDUCE; HEALTH; NIH C1 NCI, Radiat Res Program, Div Canc Treatment & Diag,Dept Hlth & Human Serv, NIH,Off Assistant Secretary Preparendness & Respo, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag,Dept Hlth & Human Serv, NIH,Off Assistant Secretary Preparendness & Respo, 6130 Execut Blvd,EPN Room 6130, Bethesda, MD 20892 USA. EM ccoleman@mail.nih.gov NR 29 TC 5 Z9 5 U1 1 U2 20 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2013 VL 179 IS 1 BP 1 EP 8 DI 10.1667/RR3224.1 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 076AG UT WOS:000313928300001 PM 23231664 ER PT J AU Salas, RE Gamaldo, A Collop, NA Gulyani, S Hsu, M David, PM Rao, A Gamaldo, CE AF Salas, Rachel E. Gamaldo, Alyssa Collop, Nancy A. Gulyani, Seema Hsu, Melanie David, Paula M. Rao, Aruna Gamaldo, Charlene E. TI A step out of the dark: Improving the sleep medicine knowledge of trainees SO SLEEP MEDICINE LA English DT Article DE Sleep medicine; Medical education; Module; Resident; Fatigue; ACGME; Duty hours ID DISORDERS; EDUCATION AB Objective: Over 40-million Americans are undiagnosed, misdiagnosed, or untreated for sleep disorders. Despite the growing need to integrate sleep medicine knowledge into the medical education curriculum, educational leaders have struggled to incorporate contemporary medical topics such as sleep medicine into the already packed curricula. We set out to examine the efficacy of an online, self-paced, sleep medicine learning module as an educational tool for medical students. Methods: We studied 87 Johns Hopkins medical students. Participants were randomly assigned to the sham module (SM, n = 40) or learning module (LM, n = 47). The efficacy of the tool was assessed based on changes in performance (pre- and post-module completion) on a validated sleep knowledge questionnaire (the Dartmouth Sleep Knowledge and Attitude Survey). Results: Improvement in overall sleep knowledge, as measured by the Dartmouth Sleep Knowledge and Attitude Survey, was significantly higher in the LM group compared to the SM group (F(1,84) = 9.71, p < .01, eta(2) = 0.10). Although the SM group's improvement was significantly lower than the LM group, within-subject comparisons did show improvement from their pre- to post-assessment scores as well. Conclusion: A self-paced learning module is an effective educational tool for delivering sleep medicine knowledge to medical students. (C) 2012 Elsevier B. V. All rights reserved. C1 [Salas, Rachel E.; Gulyani, Seema; Hsu, Melanie; David, Paula M.; Rao, Aruna; Gamaldo, Charlene E.] Johns Hopkins Med Inst, Dept Neurol, Neurosleep Div, Baltimore, MD 21287 USA. [Gamaldo, Alyssa] NIA, NIH, Baltimore, MD 21224 USA. [Collop, Nancy A.] Emory Sleep Ctr Atlanta, Emory Sch Med, Atlanta, GA 30322 USA. RP Salas, RE (reprint author), Johns Hopkins Med Inst, Dept Neurol, Neurosleep Div, 600 N Wolfe St,Meyer 6-119, Baltimore, MD 21287 USA. EM rsalas3@jhmi.edu FU American Academy of Neurology; NIH, National Institute on Aging FX This study was funded by an Education Research Grant from the American Academy of Neurology, 2010 Education Research Grant, titled: "Evaluating the Impact of a One-line Mini Sleep Course on Neurology and Medicine Trainees' Sleep Medicine and Clinical Practices and Knowledge." This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The authors would like to thank Nancy Lippi-Woodey for her role as a JHSOM Neurology Clerkship coordinator for facilitating medical student completion of the module. We would also like to thank Drs. Argye Hillis, Charles Weiner, Rafael Llinas, and, Justin McArthur for their support in making this project a success. NR 15 TC 4 Z9 4 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JAN PY 2013 VL 14 IS 1 BP 105 EP 108 DI 10.1016/j.sleep.2012.09.013 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 073EU UT WOS:000313727100018 PM 23127578 ER PT J AU Dong, T Kay, A Artino, AR Gilliland, WR Waechter, DM Cruess, D DeZee, KJ Durning, SJ AF Dong, Ting Kay, Allen Artino, Anthony R., Jr. Gilliland, William R. Waechter, Donna M. Cruess, David DeZee, Kent J. Durning, Steven J. TI Application Essays and Future Performance in Medical School: Are They Related? SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID VALIDITY; RELIABILITY; STUDENTS AB Background: There is a paucity of research on whether application essays are a valid indicator of medical students' future performance. Purpose: The goal is to score medical school application essays systematically and examine the correlations between these essay scores and several indicators of student performance during medical school and internship. Methods: A journalist created a scoring rubric based on the journalism literature and scored 2 required essays of students admitted to our university in 1 year (N = 145). We picked 7 indicators of medical school and internship performance and correlated these measures with overall essay scores: preclinical medical school grade point average (GPA), clinical medical school GPA, cumulative medical school GPA, U.S. Medical Licensing Exam (USMLE) Step 1 and 2 scores, and scores on a program director's evaluation measuring intern professionalism and expertise. We then examined the Pearson and Spearman correlations between essay scores and the outcomes. Results: Essay scores did not vary widely. American Medical College Application Service essay scores ranged from 3.3 to 4.5 (M = 4.11, SD = 0.15), and Uniformed Services University of the Health Sciences essay scores ranged from 2.9 to 4.5 (M = 4.09, SD = 0.17). None of the medical school or internship performance indicators was significantly correlated with the essay scores. Conclusions: These findings raise questions about the utility of matriculation essays, a resource-intensive admission requirement. C1 [Dong, Ting; Gilliland, William R.; DeZee, Kent J.; Durning, Steven J.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Kay, Allen] NIH, Bethesda, MD 20892 USA. RP Dong, T (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM Ting.Dong@usuhs.mil OI Artino, Anthony/0000-0003-2661-7853 NR 5 TC 4 Z9 4 U1 0 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD JAN 1 PY 2013 VL 25 IS 1 BP 55 EP 58 DI 10.1080/10401334.2012.741536 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 072OB UT WOS:000313680600010 PM 23330895 ER PT J AU Klatt, NR Funderburg, NT Brenchley, JM AF Klatt, Nichole R. Funderburg, Nicholas T. Brenchley, Jason M. TI Microbial translocation, immune activation, and HIV disease SO TRENDS IN MICROBIOLOGY LA English DT Review DE HIV; microbial translocation; immune activation; mucosal immunity ID T-CELL-ACTIVATION; SIMIAN IMMUNODEFICIENCY VIRUS; COMBINATION ANTIRETROVIRAL THERAPY; PLASMACYTOID DENDRITIC CELLS; TISSUE FACTOR EXPRESSION; CHRONIC SIV INFECTION; RHESUS MACAQUES; COAGULATION BIOMARKERS; VIROLOGICAL RESPONSES; IL-17 PRODUCTION AB The advent of combination antiretroviral therapy (cART) has significantly improved the prognosis of human immunodeficiency virus (HIV)-infected individuals. However, individuals treated long-term with cART still manifest increased mortality compared to HIV-uninfected individuals. This increased mortality is closely associated with inflammation, which persists in cART-treated HIV-infected individuals despite levels of plasma viremia below detection limits. Chronic, pathological immune activation is a key factor in progression to acquired immunodeficiency syndrome (AIDS) in untreated HIV-infected individuals. One contributor to immune activation is microbial translocation, which occurs when microbial products traverse the tight epithelial barrier of the gastrointestinal tract. Here we review the mechanisms underlying microbial translocation and its role in contributing to immune activation and disease progression in HIV infection. C1 [Klatt, Nichole R.; Brenchley, Jason M.] NIAID, Mol Microbiol Lab, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Funderburg, Nicholas T.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Ctr AIDS Res, Div Infect Dis, Cleveland, OH USA. RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov RI Funderburg, Nicholas/L-8022-2013 FU Intramural NIH HHS [ZIA AI001029-04, Z99 AI999999]; NHLBI NIH HHS [K99 HL108743] NR 104 TC 101 Z9 107 U1 1 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JAN PY 2013 VL 21 IS 1 BP 6 EP 13 DI 10.1016/j.tim.2012.09.001 PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 077FF UT WOS:000314012600002 PM 23062765 ER PT J AU Huh, JR Englund, EE Wang, H Huang, RL Huang, PX Rastinejad, F Inglese, J Austin, CP Johnson, RL Huang, WW Littman, DR AF Huh, Jun R. Englund, Erika E. Wang, Hang Huang, Ruili Huang, Pengxiang Rastinejad, Fraydoon Inglese, James Austin, Christopher P. Johnson, Ronald L. Huang, Wenwei Littman, Dan R. TI Identification of Potent and Selective Diphenylpropanamide ROR gamma Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE retinoic acid-related orphan receptor; ROR gamma antagonist; diphenylpropanamide; T(H)17-related autoimmune diseases ID AUTOIMMUNE INFLAMMATION; CHEMICAL LIBRARIES; ACID; CELLS; IL-17; DIFFERENTIATION; DERIVATIVES; CYTOKINE; LIGANDS; IL-23 AB Retinoic acid-related orphan receptor ROR gamma t plays a pivotal role in the differentiation of T(H)17 cells. Antagonizing ROR gamma t transcriptional activity is a potential means to treat T(H)17-related autoimmune diseases. Herein, we describe the identification of a series of diphenylpropanamides as novel and selective ROR gamma antagonists. Diphenylpropanamide 4n inhibited the transcriptional activity of ROR gamma t, but not ROR alpha, in cells. In addition, it suppressed human T(H)17 cell differentiation at submicromolar concentrations. C1 [Englund, Erika E.; Wang, Hang; Huang, Ruili; Inglese, James; Austin, Christopher P.; Johnson, Ronald L.; Huang, Wenwei] Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Huh, Jun R.; Littman, Dan R.] NYU, Sch Med, Mol Pathogenesis Program, Skirball Inst,Kimmel Ctr Biol & Med, New York, NY 10016 USA. [Littman, Dan R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Huang, Pengxiang; Rastinejad, Fraydoon] Sanford Burnham Med Res Inst Lake Nona, Orlando, FL 32827 USA. RP Huang, WW (reprint author), Natl Ctr Adv Translat Sci, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM huangwe@mail.nih.gov; Dan.Littman@med.nyu.edu FU NIH Roadmap for Medical Research; National Human Genome Research Institute, National Institutes of Health, NIH [K99DK091508, R03DA26211] FX This research was supported by the NIH Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, NIH Grants K99DK091508 (J.R.H.) and R03DA26211 (D.R.L.). NR 23 TC 20 Z9 20 U1 1 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD JAN PY 2013 VL 4 IS 1 BP 79 EP 84 DI 10.1021/ml300286h PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 068ZH UT WOS:000313404200023 PM 24040486 ER PT J AU Algin, O Turkbey, B AF Algin, O. Turkbey, B. TI Intrathecal Gadolinium-Enhanced MR Cisternography: A Comprehensive Review SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID MAGNETIC-RESONANCE CISTERNOGRAPHY; SPONTANEOUS 3RD VENTRICULOSTOMY; CEREBROSPINAL-FLUID RHINORRHEA; INTRACRANIAL HYPOTENSION SYNDROME; PHASE-CONTRAST MRI; GADOPENTETATE DIMEGLUMINE; ARACHNOID CYSTS; ANIMAL-MODEL; CSF LEAKS; CINE MRI AB CE-MRC has been in use for the past 15 years and was reported to be a useful method in the evaluation of CSF disorders and hydrocephalus. The use of CE-MRC in conjunction with other MR imaging techniques has been shown to be effective in selected cases for the evaluation of several disorders of cerebrospinal system. CE-MRC has certain advantages over other cisternographic studies with fewer side effects if performed properly. Although intrathecal Gd administration is not widely accepted yet, several recent studies have reported the safety of small-dose intrathecal gadolinium injection. In this review, we describe CE-MRC and review recent applications in several clinical conditions. C1 [Algin, O.] Ataturk Training & Res Hosp, Dept Radiol, Ankara, Turkey. [Turkbey, B.] NCI, NIH, Bethesda, MD 20892 USA. RP Algin, O (reprint author), Ataturk Training & Res Hosp, Dept Radiol, Ankara, Turkey. EM droktayalgin@gmail.com NR 50 TC 17 Z9 19 U1 1 U2 8 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2013 VL 34 IS 1 BP 14 EP 22 DI 10.3174/ajnr.A2899 PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 070WQ UT WOS:000313545200005 PM 22268089 ER PT J AU Sweeney, EM Shinohara, RT Shea, CD Reich, DS Crainiceanu, CM AF Sweeney, E. M. Shinohara, R. T. Shea, C. D. Reich, D. S. Crainiceanu, C. M. TI Automatic Lesion Incidence Estimation and Detection in Multiple Sclerosis Using Multisequence Longitudinal MRI SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID SEGMENTATION; SUBTRACTION; IMAGES; MS AB BACKGROUND AND PURPOSE: Detecting incidence and enlargement of lesions is essential in monitoring the progression of MS. In clinical trials, lesion load is observed by manually segmenting and comparing serial MR images, which is time consuming, costly, and prone to inter- and intraobserver variability. Subtracting images from consecutive time points nulls stable lesions, leaving only new lesion activity. We propose SuBLIME, an automated method for segmenting incident lesion voxels. MATERIALS AND METHODS: We used logistic regression models incorporating multiple MR imaging sequences and subtraction images from consecutive longitudinal studies to estimate voxel-level probabilities of lesion incidence. We used T1-weighted, T2-weighted, FLAIR, and PD volumes from a total of 110 MR imaging studies from 10 subjects. RESULTS: To assess the performance of the model, we assigned 5 subjects to a training set and the remaining 5 to a validation set. With SuBLIME, lesion incidence is detected and delineated in the validation set with an AUC of 99% (95% CI [97%, 100%]) at the voxel level. CONCLUSIONS: This fully automated and computationally fast method allows sensitive and specific detection of lesion incidence that can be applied to large collections of images. Using the explicit form of the statistical model, SuBLIME can easily be adapted to cases when more or fewer imaging sequences are available. C1 [Sweeney, E. M.; Shinohara, R. T.; Reich, D. S.; Crainiceanu, C. M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Sweeney, E. M.; Shinohara, R. T.; Shea, C. D.; Reich, D. S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Reich, D. S.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Sweeney, EM (reprint author), Johns Hopkins Univ, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM emsweene@jhsph.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Institute of Neurologic Disorders and Stroke; NIH HHS/United States [R1 NS060910-03/NINDS]; NIH; NIH/NINDS [R01N5060910] FX The research was partially supported by the Intramural Research Program of the National Institute of Neurologic Disorders and Stroke. EMS., R.T.S., and C.M.C. were supported by grant R1 NS060910-03/NINDS NIH HHS/United States. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.; Elizabeth Sweeney-RELATED: Grant NIH;* UNRELATED: Patent Johns Hopkins.* Russell Shinohara-RELATED: Grant: NIH, Comments: T32 and RO1 support as a research assistant Fees for Participation in Review Activities Such as Data Monitoring Boards, Statistical Analysis, Endpoint Committees, and the Like: NIH;* Provision of Writing Assistance, Medicines, Equipment, or Administrative Support NIH;* Other: NIH;* UNRELATED: Employment NIH,* Comments: see above; Grants/ Grants Pending: NIH.* Ciprian Crainiceanu-RELATED: Grant NIH/NINDS R01N5060910,* Comments: Statistical methods for multilevel multivariate functional studies; UNRELATED: Consultancy: Merck, On-X Technologies, Comments: Merck: statistical methods for the analysis of EEG data; On-X: design of an adaptive clinical trial for mitral valve surgery; none is related to the work done for this paper, Patents (planned, pending, or issued): The work in the paper was submitted for a US patent application* (*Money paid to institution.) NR 22 TC 14 Z9 15 U1 0 U2 8 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2013 VL 34 IS 1 BP 68 EP 73 DI 10.3174/ajnr.A3172 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 070WQ UT WOS:000313545200013 PM 22766673 ER PT J AU Bailit, E AF Bailit, Ennifer TI Is the use of protocols for obstetric care associated with better outcomes? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Bailit, Ennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S322 EP S322 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500766 ER PT J AU Basraon, S AF Basraon, Sanmaan TI Relationship of early pregnancy waist to hip ratio versus body mass index with gestational diabetes and insulin resistance SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Basraon, Sanmaan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S132 EP S133 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500294 ER PT J AU Catalano, P AF Catalano, Patrick TI Weight loss in overweight and obese pregnant women (OW/OB): what is the effect on fetal growth? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Catalano, Patrick] Eunice Kennedy Shriver Natl Inst Hlth & Human Dev, Maternal Fetal Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S155 EP S155 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500350 ER PT J AU Chaemsaithong, P Romero, R Stampalija, T Dong, Z Yeo, LM Hernandez-Andrade, E Hassan, S Chaiworapongsa, T AF Chaemsaithong, Piya Romero, Roberto Stampalija, Tamara Dong, Zhong Yeo, Lami Hernandez-Andrade, Edgar Hassan, Sonia Chaiworapongsa, Tinnakorn TI Changes in the cytokine TRAIL during pregnancy: a potential explanation for the susceptibility of pregnant women to the effects of infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Chaemsaithong, Piya; Romero, Roberto; Stampalija, Tamara; Dong, Zhong] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RI Stampalija, Tamara/K-4900-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S312 EP S312 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500739 ER PT J AU Chaemsaithong, P Chaiworapongsa, T Stampalija, T Than, NG Dong, Z Yeo, LM Hassan, S Romero, R AF Chaemsaithong, Piya Chaiworapongsa, Tinnakorn Stampalija, Tamara Than, Nandor Gabor Dong, Zhong Yeo, Lami Hassan, Sonia Romero, Roberto TI sTRAIL, a prognostic marker for future death from cardiovascular disease, is decreased in maternal plasma of patients with preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Chaemsaithong, Piya; Stampalija, Tamara; Than, Nandor Gabor; Dong, Zhong; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RI Stampalija, Tamara/K-4900-2014 NR 0 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S275 EP S275 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500648 ER PT J AU Chaiworapongsa, T Korzeniewski, S Schwartz, A Chaemsaithong, P Dong, Z Yeo, L Hassan, S Romero, R AF Chaiworapongsa, Tinnakorn Korzeniewski, Steven Schwartz, Alyse Chaemsaithong, Piya Dong, Zhong Yeo, Lami Hassan, Sonia Romero, Roberto TI Third trimester neutrophil gelatinase-associated lipocalin and angiogenic/anti-angiogenic factors for the identification of late preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Chaemsaithong, Piya; Dong, Zhong; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Korzeniewski, Steven; Schwartz, Alyse; Yeo, Lami; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S277 EP S278 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500655 ER PT J AU Chaiworapongsa, T Korzeniewski, S Schwartz, A Chaemsaithong, P Dong, Z Hernandez-Andrade, E Hassan, S Romero, R AF Chaiworapongsa, Tinnakorn Korzeniewski, Steven Schwartz, Alyse Chaemsaithong, Piya Dong, Zhong Hernandez-Andrade, Edgar Hassan, Sonia Romero, Roberto TI Diagnostic performance of leptin and total adiponectin determined in the third trimester for the identification of late preeclampsia compared to angiogenic/anti-angiogenic and clinical factors SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Chaemsaithong, Piya; Dong, Zhong; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Korzeniewski, Steven; Schwartz, Alyse; Hernandez-Andrade, Edgar; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S278 EP S278 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500656 ER PT J AU Clark, EAS AF Clark, Erin A. S. TI Sex-specific genetic susceptibility to adverse neurodevelopmental outcome after early preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Clark, Erin A. S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S14 EP S14 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500023 ER PT J AU Gilbert, S AF Gilbert, Sharon TI Future consequences of one prior cesarean: a cost-effectiveness analysis of trial of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Gilbert, Sharon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S304 EP S304 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500721 ER PT J AU Graves, S Esplin, S AF Graves, Steven Esplin, Sean TI Association of cord blood digitalis-like factor and necrotizing enterocolitis in the neonate SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Graves, Steven; Esplin, Sean] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S90 EP S90 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500190 ER PT J AU Grobman, W AF Grobman, William TI The frequency and causes of severe maternal morbidity SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S327 EP S328 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500779 ER PT J AU Grobman, W AF Grobman, William TI Short cervix and activity restriction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S227 EP S228 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500532 ER PT J AU Grobman, W AF Grobman, William TI Racial and ethnic disparities in adverse obstetric outcomes and in the provision of obstetric care SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Grobman, William] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S21 EP S21 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500035 ER PT J AU Iams, J AF Iams, Jay TI Transvaginal sonography (TVS) to measure cervical length (CL) in a clinical trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Iams, Jay] NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S163 EP S163 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500371 ER PT J AU Lam, J Romero, R Malshe, A Than, NG Hernandez-Andrade, E Dong, Z Hassan, S Chaiworapongsa, T AF Lam, Jennifer Romero, Roberto Malshe, Amol Than, Nandor Gabor Hernandez-Andrade, Edgar Dong, Zhong Hassan, Sonia Chaiworapongsa, Tinnakom TI Soluble alpha-klotho, an anti-aging protein, is reduced in patients with intra-amniotic infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Romero, Roberto; Malshe, Amol; Than, Nandor Gabor; Dong, Zhong] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Lam, Jennifer; Hernandez-Andrade, Edgar; Hassan, Sonia; Chaiworapongsa, Tinnakom] Wayne State Univ, Sch Med, Dept Obstet & Gyneol, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S344 EP S344 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500820 ER PT J AU Langen, E AF Langen, Elizabeth TI The role of cervical effacement in predicting the rate of cervical change in labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Langen, Elizabeth] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S138 EP S139 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500308 ER PT J AU Laughon, SK Berghella, V Sundaram, R Reddy, U Lu, ZH Hoffman, M AF Laughon, S. Katherine Berghella, Vincenzo Sundaram, Rajeshwari Reddy, Uma Lu, Zhaohui Hoffman, Matt TI Neonatal and maternal outcomes with prolonged second stage of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Laughon, S. Katherine; Sundaram, Rajeshwari; Reddy, Uma; Lu, Zhaohui] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Berghella, Vincenzo] Thomas Jefferson Univ, Dept Obstet & Gynecol, Div MFM, Philadelphia, PA 19107 USA. [Hoffman, Matt] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S149 EP S149 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500335 ER PT J AU Miller, R Smiley, R AF Miller, Russell Smiley, Richard TI The association of beta 2 adrenoceptor genotype with short-cervix mediated preterm birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Miller, Russell; Smiley, Richard] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S255 EP S255 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500597 ER PT J AU Olson, G AF Olson, Gayle TI Head sparing and neonatal outcome in small for gestational age neonates SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Olson, Gayle] NICHHD, Maternal Fetal Med Units Network, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S86 EP S86 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500181 ER PT J AU Paidas, M Triche, E James, A Ballard, T Lowry, S AF Paidas, Michael Triche, Elizabeth James, Andra Ballard, Trina Lowry, Simon TI Recombinant human antithrombin (rhAT) for prevention of venous thromboembolism (VTE) in pregnant patients with hereditary antithrombin deficiency (HD) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Paidas, Michael] Yale Univ, Sch Med, New Haven, CT USA. [Triche, Elizabeth] Brown Univ, Sch Med, Providence, RI 02912 USA. [James, Andra] NHLBI, NIH, Div Blood Dis & Resources, Bethesda, MD 20892 USA. [Ballard, Trina; Lowry, Simon] GTC Biotherapeut Inc, Framingham, MA USA. RI Triche, Elizabeth/I-4986-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S154 EP S154 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500348 ER PT J AU Rice, M AF Rice, Madeline TI Risk factors for maternal placenta-related syndromes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Rice, Madeline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S301 EP S302 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500715 ER PT J AU Rice, M AF Rice, Madeline TI Risk factors for neonatal complications related to placental dysfunction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Rice, Madeline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S301 EP S301 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500714 ER PT J AU Roberson, R Kuddo, T Abebe, D Spong, C AF Roberson, Robin Kuddo, Thea Abebe, Daniel Spong, Catherine TI Alcohol exposure in pregnancy affects phosphorylation of the JNK and p38 cell signaling pathways SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Roberson, Robin; Kuddo, Thea; Abebe, Daniel; Spong, Catherine] NICHD, NIH, UPDN DIR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S196 EP S196 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500450 ER PT J AU Saade, G AF Saade, George TI Cervical funneling or intraamniotic debris and preterm birth in nulliparous women with short cervix SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Saade, George] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S4 EP S4 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500009 ER PT J AU Schisterman, E Silver, R Lesher, L Faraggi, D Waetawski-Wende, J Townsend, J Lynch, A Perkins, N Mumford, S Galai, N AF Schisterman, Enrique Silver, Robert Lesher, Laurie Faraggi, David Waetawski-Wende, Jean Townsend, Janet Lynch, Anne Perkins, Neil Mumford, Sunni Galai, Noya TI Randomized clinical trial of preconception low dose aspirin use to improve pregnancy outcomes: EAGeR (Effects of Aspirin in Gestation and Reproduction) trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Schisterman, Enrique; Perkins, Neil; Mumford, Sunni] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. [Silver, Robert; Lesher, Laurie] Univ Utah, Salt Lake City, UT USA. [Waetawski-Wende, Jean] SUNY Buffalo, Buffalo, NY 14260 USA. [Townsend, Janet] Commonwealth Med Coll, Scranton, PA USA. [Lynch, Anne] Univ Colorado, Denver, CO 80202 USA. [Galai, Noya] Univ Haifa, IL-31999 Haifa, Israel. NR 0 TC 0 Z9 0 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S352 EP S352 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500834 ER PT J AU Stampalija, T Malshe, A Chaiworapongsa, T Chaemsaithong, P Korzeniewski, S Schwartz, A Dong, Z Hassan, S Romero, R AF Stampalija, Tamara Malshe, Amol Chaiworapongsa, Tinnakorn Chaemsaithong, Piya Korzeniewski, Steven Schwartz, Alyse Dong, Zhong Hassan, Sonia Romero, Roberto TI Maternal plasma concentration of sST2 and angiogenic/anti-angiogenic factors at the time of diagnosis of preeclampsia: a link between the immune system and angiogenesis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Stampalija, Tamara; Malshe, Amol; Chaemsaithong, Piya; Dong, Zhong; Romero, Roberto] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA. [Chaiworapongsa, Tinnakorn; Korzeniewski, Steven; Schwartz, Alyse; Hassan, Sonia] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RI Stampalija, Tamara/K-4900-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S262 EP S263 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500615 ER PT J AU Weiner, S AF Weiner, Steven TI Independent validation of a fetal heart rate pattern recognition software SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 33rd Annual Meeting/Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine (SMFM) CY FEB 11-16, 2013 CL San Francisco, CA SP Soc Maternal Fetal Med (SMFM) C1 [Weiner, Steven] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Fetal Med Units Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 SU S BP S316 EP S317 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 068VE UT WOS:000313393500751 ER PT J AU Burg, MB Ferraris, JD AF Burg, Maurice B. Ferraris, Joan D. TI Salt, skeletons, and suicide. Focus on "Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID ACTIVATION C1 [Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov NR 9 TC 1 Z9 1 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 2013 VL 304 IS 2 BP C113 EP C114 DI 10.1152/ajpcell.00319.2012 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 071SS UT WOS:000313615100001 PM 23099642 ER PT J AU Hendler, RW Meuse, CW Smith, PD Kakareka, JW AF Hendler, Richard W. Meuse, Curtis W. Smith, Paul D. Kakareka, John W. TI Further Studies with Isolated Absolute Infrared Spectra of Bacteriorhodopsin Photocycle Intermediates: Conformational Changes and Possible Role of a New Proton-Binding Center SO APPLIED SPECTROSCOPY LA English DT Article DE Conformational changes; FT-IR kinetics; Amides I, II, and III ID SECONDARY STRUCTURE ESTIMATION; INFORMATION-CONTENT; SPECTROSCOPY; PROTEINS AB We recently published procedures describing the isolation of absolute infrared spectra for the intermediates of the bacteriorhodopsin (BR) photocycle and from these, obtaining transitional difference spectra between consecutive intermediates. In that work, we concentrated mainly on proton-binding centers and the route of proton transport across the membrane. In the current study, we used isolated spectra for the amide I, amide II, and amide III envelopes to obtain quantitative information on the extent of conformational change accompanying each transition in the photocycle. Our main finding was that most of the conformational changes occur in the conversion of the M-F intermediate to N. In our earlier publication, a new proton acceptor, absorbing at 1650 cm(-1) was identified, which appeared to accept a proton from Asp96COOH during the transformation of BR dagger to L. Below, we present evidence that supports this interpretation and propose a possible role for this new component. C1 [Hendler, Richard W.] NHLBI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. [Smith, Paul D.] Natl Inst Biomed Imaging & Bioengn, NIH, Laboratoly Cellular Imaging & Macromol Biophys, Bethesda, MD 20892 USA. [Kakareka, John W.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Hendler, Richard W.; Meuse, Curtis W.] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA. RP Hendler, RW (reprint author), NHLBI, NIH, Cell Biol Lab, Bldg 10, Bethesda, MD 20892 USA. EM rwh@helix.nih.gov OI Kakareka, John/0000-0003-0072-0035 FU National Institutes of Health, National Heart Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering; Center for Information Technology FX The authors thank Dr. Ira W. Levin for many helpful discussions and suggestions. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Heart Lung, and Blood Institute; National Institute of Biomedical Imaging and Bioengineering; and the Center for Information Technology. Certain commercial equipment, instruments, or materials are identified in this paper to foster understanding. Such identification does not imply recommendation or endorsement by the National Institutes of Health or the National Institute of Standards and Technology, or that the materials and equipment are necessarily the best available for the purpose. NR 15 TC 0 Z9 0 U1 2 U2 17 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD JAN PY 2013 VL 67 IS 1 BP 73 EP 85 DI 10.1366/12-06662 PG 13 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 071ON UT WOS:000313604200010 PM 23317674 ER PT J AU Horton, BM Hu, YC Martin, CL Bunke, BP Matthews, BS Moore, IT Thomas, JW Maney, DL AF Horton, Brent M. Hu, Yuchen Martin, Christa L. Bunke, Brian P. Matthews, Beth S. Moore, Ignacio T. Thomas, James W. Maney, Donna L. TI Behavioral Characterization of a White-Throated Sparrow Homozygous for the ZAL2(m) Chromosomal Rearrangement SO BEHAVIOR GENETICS LA English DT Article DE Aggression; Alternative phenotypes; Chromosomal inversion; Life history strategies; Polymorphism; White-throated sparrow ID HISTORY TRADE-OFFS; ZONOTRICHIA-ALBICOLLIS GMELIN; GENOMIC ARCHITECTURE; PLUMAGE POLYMORPHISM; CROWNED SPARROWS; SOCIAL-BEHAVIOR; SEX; DOMINANCE; MORPHS; BIRDS AB The white-throated sparrow is rapidly becoming an important model in the genetics of social behavior because of a chromosomal rearrangement that segregates with a behavioral phenotype. Within a population, 50 % of individuals are heterozygous for a rearranged chromosome 2 (ZAL2(m)). These birds sing more and are more aggressive than the other 50 %, who lack the rearrangement. A disassortative mating system, in which heterozygotes almost never interbreed, ensures that ZAL2(m)/2(m) homozygotes are extremely rare. Here, we provide the first systematic characterization of such a homozygote, a hatch-year female. Her plumage was atypical of her age and sex, resembling that of an adult male. She was extremely vocal and aggressive, dominating her opponents in behavioral tests. Her phenotype was thus an exaggerated version of a typical ZAL2/2(m) heterozygote, supporting the hypothesis that alleles inside the ZAL2(m) rearrangement confer high aggression and further emphasizing this species' value as a model of social behavior. C1 [Horton, Brent M.; Hu, Yuchen; Maney, Donna L.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Martin, Christa L.; Bunke, Brian P.; Matthews, Beth S.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA. [Moore, Ignacio T.] Virginia Tech, Dept Biol Sci, Blacksburg, VA 24061 USA. [Thomas, James W.] NHGRI, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Maney, Donna L.] O Wayne Rollins Res Ctr, Atlanta, GA 30322 USA. RP Maney, DL (reprint author), O Wayne Rollins Res Ctr, 1510 Clifton Rd NE,Room 2006,Mail Stop 1940-001-A, Atlanta, GA 30322 USA. EM dmaney@emory.edu RI Maney, Donna/G-3706-2011; OI Moore, Ignacio/0000-0001-8875-8913 FU NIMH [1R01MH082833-01A2]; NHGRI Intramural Research program at the NIH FX The authors would like to thank Demesew Abebe, Jennifer Asher, Erin Baldwin, Anya Grozhik, Christopher Horoszko, Josh Lowman, Lisa Matragrano, Katy Renfro, and Carlos Rodriguez for technical assistance. Christopher Malinsky of the Smithsonian Institution assisted with museum skin preparation. We also thank the Biology Department at Emory University for the use of resources. This work was supported by NIMH 1R01MH082833-01A2 to DLM. JWT was supported by the NHGRI Intramural Research program at the NIH. NR 49 TC 9 Z9 9 U1 3 U2 20 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2013 VL 43 IS 1 BP 60 EP 70 DI 10.1007/s10519-012-9574-6 PG 11 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 074HU UT WOS:000313804300006 PM 23264208 ER PT J AU Ioannidis, JPA Schully, SD Lam, TK Khoury, MJ AF Ioannidis, John P. A. Schully, Sheri D. Lam, Tram Kim Khoury, Muin J. TI Knowledge Integration in Cancer: Current Landscape and Future Prospects SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; OUTCOME REPORTING BIAS; SYSTEMATIC METAANALYSES; REPRODUCIBLE RESEARCH; GENETIC EPIDEMIOLOGY; CUMULATIVE EVIDENCE; EMPIRICAL-EVIDENCE; CONTROLLED-TRIALS; HUMAN-DISEASES; GUIDELINES AB Knowledge integration includes knowledge management, synthesis, and translation processes. It aims to maximize the use of collected scientific information and accelerate translation of discoveries into individual and population health benefits. Accumulated evidence in cancer epidemiology constitutes a large share of the 2.7 million articles on cancer in PubMed. We examine the landscape of knowledge integration in cancer epidemiology. Past approaches have mostly used retrospective efforts of knowledge management and traditional systematic reviews and meta-analyses. Systematic searches identify 2,332 meta-analyses, about half of which are on genetics and epigenetics. Meta-analyses represent 1:89-1:1162 of published articles in various cancer subfields. Recently, there are more collaborative meta-analyses with individual-level data, including those with prospective collection of measurements [e.g., genotypes in genome-wide association studies (GWAS)]; this may help increase the reliability of inferences in the field. However, most meta-analyses are still done retrospectively with published information. There is also a flurry of candidate gene meta-analyses with spuriously prevalent "positive" results. Prospective design of large research agendas, registration of datasets, and public availability of data and analyses may improve our ability to identify knowledge gaps, maximize and accelerate translational progress or-at a minimum-recognize dead ends in a more timely fashion. Cancer Epidemiol Biomarkers Prev; 22(1); 3-10. (c) 2012 AACR. C1 [Ioannidis, John P. A.; Schully, Sheri D.; Lam, Tram Kim; Khoury, Muin J.] NCI, Knowledge Integrat Team, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA. [Ioannidis, John P. A.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Dept Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Dept Stat, Sch Humanities & Sci, Stanford, CA 94305 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. RP Ioannidis, JPA (reprint author), Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Dept Med, 1265 Welch Rd,MSOB X306, Stanford, CA 94305 USA. EM jioannid@stanford.edu FU Intramural CDC HHS [CC999999] NR 55 TC 9 Z9 9 U1 1 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 3 EP 10 DI 10.1158/1055-9965.EPI-12-1144 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900001 PM 23093546 ER PT J AU Siegel, RL Devesa, SS Cokkinides, V Ma, JM Jemal, A AF Siegel, Rebecca L. Devesa, Susan S. Cokkinides, Vilma Ma, Jiemin Jemal, Ahmedin TI State-Level Uterine Corpus Cancer Incidence Rates Corrected for Hysterectomy Prevalence, 2004 to 2008 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; PHYSICAL-ACTIVITY; ENDOMETRIAL; WEIGHT; RISK AB Background: The interpretation of uterine cancer rates is hindered by the inclusion of women whose uterus has been surgically removed in the population at risk. Hysterectomy prevalence varies widely by state and race/ethnicity, exacerbating this issue. Methods: We estimated hysterectomy-corrected, age-adjusted uterine corpus cancer incidence rates by race/ethnicity for 49 states and the District of Columbia during 2004 to 2008 using case counts obtained from population-based cancer registries; population data from the U.S. Census Bureau; and hysterectomy prevalence data from the Behavioral Risk Factor Surveillance System. Corrected and uncorrected incidence rates were compared with regard to geographic and racial/ethnic disparity patterns and the association with obesity. Results: Among non-Hispanic Whites, uterine cancer incidence rates (per 100,000 woman-years) uncorrected for hysterectomy prevalence ranged from 17.1 in Louisiana to 32.1 in New Jersey, mirrored regional hysterectomy patterns, and were not correlated with obesity prevalence (Pearson correlation coefficient, r = 0.06, two-sided P = 0.68). In comparison, hysterectomy-corrected rates were higher by a minimum of 30% (District of Columbia) to more than 100% (Mississippi, Louisiana, Alabama, and Oklahoma), displayed no discernible geographic pattern, and were moderately associated with obesity (r = 0.37, two-sided P = 0.009). For most states, hysterectomy correction diminished or reversed the Black/White deficit and accentuated the Hispanic/White deficit. Conclusion: Failure to adjust uterine cancer incidence rates for hysterectomy prevalence distorts true geographic and racial patterns and substantially underestimates the disease burden, particularly for Southern states. Impact: Correction for hysterectomy is necessary for the accurate evaluation of uterine cancer rates. Cancer Epidemiol Biomarkers Prev; 22(1); 25-31. (c) 2012 AACR. C1 [Siegel, Rebecca L.; Cokkinides, Vilma; Ma, Jiemin; Jemal, Ahmedin] Amer Canc Soc, Atlanta, GA 30303 USA. [Devesa, Susan S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Siegel, RL (reprint author), Amer Canc Soc, 250 Williams St NW,6D 123, Atlanta, GA 30303 USA. EM rebecca.siegel@cancer.org FU Intramural Research Department of the American Cancer Society; Intramural Research Program of the NIH, National Cancer Institute FX This work was supported by the Intramural Research Department of the American Cancer Society and the Intramural Research Program of the NIH, National Cancer Institute. NR 29 TC 10 Z9 10 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 25 EP 31 DI 10.1158/1055-9965.EPI-12-0991 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900004 PM 23125334 ER PT J AU Castle, PE Follansbee, S Borgonovo, S Tokugawa, D Schwartz, LM Lorey, TS LaMere, B Gage, JC Fetterman, B Darragh, TM Rodriguez, AC Wentzensen, N AF Castle, Philip E. Follansbee, Stephen Borgonovo, Sylvia Tokugawa, Diane Schwartz, Lauren M. Lorey, Thomas S. LaMere, Brandon Gage, Julia C. Fetterman, Barbara Darragh, Teresa M. Cecilia Rodriguez, Ana Wentzensen, Nicolas TI A Comparison of Human Papillomavirus Genotype-Specific DNA and E6/E7 mRNA Detection to Identify Anal Precancer among HIV-Infected Men Who Have Sex with Men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARCINOGENIC HUMAN-PAPILLOMAVIRUS; SQUAMOUS INTRAEPITHELIAL LESION; 2-YEAR FOLLOW-UP; CERVICAL-CANCER; AMERICAN SOCIETY; LINEAR-ARRAY; HPV-PROOFER; WOMEN; CYTOLOGY; NEOPLASIA AB Background: Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction. Methods: A total of 363 human immunodeficiency virus (HIV)-positive men who have sex with men had two anal cytology samples taken and were evaluated using high-resolution anoscopy and biopsies of visible lesions. Anal specimens were tested for E6/E7 RNA for five carcinogenic HPV genotypes (HPV16, 18, 31, 33, and 45) and tested for the DNA of 13 carcinogenic HPV genotypes. Results: DNA testing was more likely to be positive than RNA testing (53% vs. 48%; P = 0.02) for the same five HPV genotypes in aggregate. When restricted to five HPV genotypes targeted by the RNA test, the sensitivity to detect anal precancer was the same for DNA and RNA (81%), whereas RNA was more specific than DNA (65% vs. 58%; P = 0.007). In comparison, DNA detection of all 13 carcinogenic HPV genotypes was more sensitive (96% vs. 81%; P = 0.001) but much less specific (65% vs. 33%; P<0.001) as compared with RNA detection of the five HPV genotypes. Conclusion: After controlling for HPV genotypes, RNA was only slightly more specific than DNA detection for anal precancer. Impact: DNA or RNA testing for a subset of the most carcinogenic HPV genotypes may be useful for distinguishing between those HPV-positive men at higher and lower risk of anal precancer and cancer. Cancer Epidemiol Biomarkers Prey; 22(1); 42-49. (C) 2012 AACR. C1 [Castle, Philip E.; Cecilia Rodriguez, Ana] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Darragh, Teresa M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tokugawa, Diane; Lorey, Thomas S.; Fetterman, Barbara] Kaiser Permanente TPMG Reg Lab, Berkeley, CA USA. [LaMere, Brandon] Kaiser Permanente, Womens Hlth Res Inst, Div Res, Oakland, CA USA. [Schwartz, Lauren M.; Gage, Julia C.; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Cecilia Rodriguez, Ana] Fdn Inst Costarricense Invest & Ensenanza Nutr &, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA. EM wentzenn@mail.nih.gov FU Intramural Research Program of NIH/NCI FX The Intramural Research Program of NIH/NCI supported this study. NR 37 TC 9 Z9 9 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 42 EP 49 DI 10.1158/1055-9965.EPI-12-0984 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900006 PM 23155136 ER PT J AU Gu, FY Caporaso, NE Schairer, C Fortner, RT Xu, X Hankinson, SE Eliassen, AH Ziegler, RG AF Gu, Fangyi Caporaso, Neil E. Schairer, Catherine Fortner, Renee T. Xu, Xia Hankinson, Susan E. Eliassen, A. Heather Ziegler, Regina G. TI Urinary Concentrations of Estrogens and Estrogen Metabolites and Smoking in Caucasian Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; CIGARETTE-SMOKING; PREMENOPAUSAL WOMEN; BREAST-CANCER; RISK; ASSOCIATION AB Background: Smoking has been hypothesized to decrease biosynthesis of parent estrogens (estradiol and estrone) and increase their metabolism by 2-hydroxylation. However, comprehensive studies of smoking and estrogen metabolism by 2-, 4-, or 16-hydroxylation are sparse. Methods: Fifteen urinary estrogens and estrogen metabolites (jointly called EM) were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in luteal phase urine samples collected during 1996 to 1999 from 603 premenopausal women in the Nurses' Health Study II (NHSIL 35 current, 140 former, and 428 never smokers). We calculated geometric means and percentage differences of individual EM (pmol/mg creatinine), metabolic pathway groups, and pathway ratios, by smoking status and cigarettes per day (CPD). Results: Total EM and parent estrogens were nonsignificantly lower in current compared with never smokers, with estradiol significant (P-multivariate = 0.02). We observed nonsignificantly lower 16-pathway EM (P = 0.08) and higher 4-pathway EM (P = 0.25) and similar 2-pathway EM in current versus never smokers. EM measures among former smokers were similar to never smokers. Increasing CPD was significantly associated with lower 16-pathway EM (P-trend = 0.04) and higher 4-pathway EM (P-trend = 0.05). Increasing CPD was significantly positively associated with the ratios of 2- and 4-pathway to parent estrogens (P-trend = 0.01 and 0.002), 2- and 4-pathway to 16-pathway (P-trend = 0.02 and 0.003), and catechols to methylated catechols (P-trend = 0.02). Conclusions: As hypothesized, we observed lower urinary levels of total EM and parent estrogens in active smokers. Our results also suggest smoking is associated with altered estrogen metabolism, specifically increased 2- and 4-hydroxylation, decreased 16-hydroxylation, and decreased catechol methylation. Impact: Our study suggests how smoking might influence estrogen-related cancers and conditions. Cancer Epidemiol Biomarkers Prey; 22(1); 58-68. (C) 2012 AACR. C1 [Gu, Fangyi; Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schairer, Catherine] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Xu, Xia] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD USA. [Fortner, Renee T.; Hankinson, Susan E.; Eliassen, A. Heather] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fortner, Renee T.; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Med, Boston, MA USA. [Fortner, Renee T.; Hankinson, Susan E.; Eliassen, A. Heather] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hankinson, Susan E.] Univ Massachusetts, Div Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Gu, FY (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7110, Bethesda, MD 20892 USA. EM guf@mail.nih.gov RI Gu, Fangyi/I-5957-2014; OI Fortner, Renee/0000-0002-1426-8505 FU National Cancer Institute (NCI) [CA67262, CA50385]; Division of Cancer Epidemiology and Genetics of the NCI; NCI [HHSN261200800001E]; [T32 CA09001] FX This study was supported by Research Grants CA67262 and CA50385 from the National Cancer Institute (NCI), the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the NCI, and the NCI federal funds awarded under Contract HHSN261200800001E to SAIC-Frederick, Inc. R.T. Fortner is supported in part by T32 CA09001. NR 26 TC 11 Z9 11 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 58 EP 68 DI 10.1158/1055-9965.EPI-12-0909 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900008 PM 23104668 ER PT J AU Nieminen, MT Novak-Frazer, L Collins, R Dawsey, SP Dawsey, SM Abnet, CC White, RE Freedman, ND Mwachiro, M Bowyer, P Salaspuro, M Rautemaa, R AF Nieminen, Mikko T. Novak-Frazer, Lily Collins, Rebecca Dawsey, Sonja P. Dawsey, Sanford M. Abnet, Christian C. White, Russell E. Freedman, Neal D. Mwachiro, Michael Bowyer, Paul Salaspuro, Mikko Rautemaa, Riina TI Alcohol and Acetaldehyde in African Fermented Milk Mursik-A Possible Etiologic Factor for High Incidence of Esophageal Cancer in Western Kenya SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LACTIC-ACID BACTERIA; ETHANOL-METABOLISM; YOUNG-PEOPLE; BEVERAGES; RISK; YEASTS; KEFIR; DNA; CARCINOGENESIS; IDENTIFICATION AB Background: Esophageal cancer is unusually frequent in Western Kenya, despite the low prevalence of classical risk factors such as heavy drinking and tobacco smoking. Among Kenyans consumption of fermented milk is an old tradition. Our hypothesis is that alcohol and acetaldehyde are produced during the fermentation process and that their carcinogenic potential contributes to the high incidence of esophageal cancer. Methods: Eight samples of mursik milk starter cultures were collected from different Kalenjin families in the Rift Valley province, Western Kenya. A protocol provided by the families was used for milk fermentation. Ethanol and acetaldehyde levels were measured by gas chromatography. The microbial flora in starter cultures was identified by 16S and 18S sequencing. Results: 7/8 starter cultures produced mutagenic (>100 mu mol/L) levels of acetaldehyde and 4/8 starter cultures produced more than 1,000 mu mol/L of acetaldehyde. The highest alcohol levels (mean 79.4 mmol/L) were detected in the four fermented milks with highest acetaldehyde production. The mean number of microbial species in the starter cultures was 5 (range 2-8). Yeasts were identified in all starter cultures (mean 1.5 species/milk) but their proportion of the total microbial count varied markedly (mean 35%, range 7%-90%). A combination of yeast and lactobacilli, especially Candida krusei with Lactobacillus kefiri, with the exclusion of other species, seemed to correlate with higher acetaldehyde and ethanol levels. Conclusions: Significant levels of ethanol and acetaldehyde were produced during mursik fermentation. Impact: When ingested several times daily the repeated exposure to carcinogenic levels of acetaldehyde may contribute to esophageal carcinogenesis. Cancer Epidemiol Biomarkers Prey; 22(1); 69-75. (C) 2012 AACR. C1 [Nieminen, Mikko T.; Salaspuro, Mikko] Univ Helsinki, Res Unit Acetaldehyde & Canc, Fac Med, Helsinki, Finland. [Nieminen, Mikko T.; Rautemaa, Riina] Univ Helsinki, Inst Dent, Dept Oral Med, Helsinki, Finland. [Nieminen, Mikko T.; Rautemaa, Riina] Univ Helsinki, Cent Hosp, Dept Oral & Maxillofacial Dis, Helsinki, Finland. [Nieminen, Mikko T.; Novak-Frazer, Lily; Collins, Rebecca; Bowyer, Paul; Rautemaa, Riina] Univ Manchester, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England. [Nieminen, Mikko T.; Novak-Frazer, Lily; Collins, Rebecca; Bowyer, Paul; Rautemaa, Riina] Wythenshawe Hosp, Univ S Manchester Hosp, Manchester M23 9LT, Lancs, England. [Dawsey, Sanford M.; White, Russell E.; Mwachiro, Michael] Tenwek Hosp, Bomet, Kenya. [Dawsey, Sanford M.; Abnet, Christian C.; Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Rautemaa, R (reprint author), Wythenshawe Hosp, Educ & Res Ctr, 2nd Floor,Southmoor Rd, Manchester M23 9LT, Lancs, England. EM riina.richardson@manchester.ac.uk RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Dawsey, Sonja/0000-0003-1605-3994; Richardson, Riina/0000-0002-1071-6040; Novak Frazer, Lily/0000-0002-1434-3915; Mwachiro, Michael/0000-0002-3779-5324 FU Finnish Dental Society Apollonia [UNID:031510]; Yrjo Jahnsson Foundation [6355]; Sigrid Juselius Foundation [2009/642/Salaspuro]; Helsinki University Hospital [EVOT1020V0017]; Division of Cancer Epidemiology and Genetics of the National Cancer Institute, NIH FX This study project was supported by Grants from Finnish Dental Society Apollonia (UNID:031510), Yrjo Jahnsson Foundation (#6355), Sigrid Juselius Foundation (2009/642/Salaspuro), and Helsinki University Hospital research grant EVOT1020V0017. This study was also supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, NIH. NR 48 TC 5 Z9 5 U1 1 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 69 EP 75 DI 10.1158/1055-9965.EPI-12-0908 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900009 PM 23155139 ER PT J AU Palmer, JR Ruiz-Narvaez, EA Rotimi, CN Cupples, LA Cozier, YC Adams-Campbell, LL Rosenberg, L AF Palmer, Julie R. Ruiz-Narvaez, Edward A. Rotimi, Charles N. Cupples, L. Adrienne Cozier, Yvette C. Adams-Campbell, Lucile L. Rosenberg, Lynn TI Genetic Susceptibility Loci for Subtypes of Breast Cancer in an African American Population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; BLACK WOMENS HEALTH; CONFER SUSCEPTIBILITY; HAPLOTYPE METHOD; COMMON VARIANTS; CHROMOSOME 5P12; TUMOR SUBTYPES; RISK; ADMIXTURE; CONSORTIUM AB Background: Most genome-wide association studies (GWAS) have been carried out in European ancestry populations; no risk variants for breast cancer have been identified solely from African ancestry GWAS data. Few GWAS hits have replicated in African ancestry populations. Methods: In a nested case-control study of breast cancer in the Black Women's Health Study (1,199 cases/1,948 controls), we evaluated index single-nucleotide polymorphisms (SNP) in 21 loci from GWAS of European or Asian ancestry populations, overall, in subtypes defined by estrogen receptor (ER) and progesterone receptor (PR) status (ER+/PR+, n = 336; ER-/PR-, n = 229), and in triple-negative breast cancer (TNBC, N = 81). To evaluate the contribution of genetic factors to population differences in breast cancer subtype, we also examined global percent African ancestry. Results: Index SNPs in five loci were replicated, including three associated with ER-/PR- breast cancer (TERT rs10069690 in 5p15.33, rs704010 in 10q22.3, and rs8170 in 19p13.11): per allele ORs were 1.29 [95% confidence interval (Cl) 1.04-1.59], P = 0.02, 1.52 (95% CI 1.12-2.08), P = 0.01, and 1.30 (95% CI 1.01-1.68), P = 0.04, respectively. Stronger associations were observed for TNBC. Furthermore, cases in the highest quintile of percent African ancestry were three times more likely to have TNBC than ER+/PR+ cancer. Conclusions: These findings provide the first confirmation of the TNBC SNP rs8170 in an African ancestry population, and independent confirmation of the TERT ER SNP. Furthermore, the risk of developing ER breast cancer, particularly TNBC, increased with increasing proportion of global African ancestry. Impact: The findings illustrate the importance of genetic factors in the disproportionately high occurrence of TNBC in African American women. Cancer Epidemiol Biomarkers Prey; 22(1); 127-34. (C) 2012 AACR. C1 [Palmer, Julie R.; Ruiz-Narvaez, Edward A.; Cozier, Yvette C.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA. [Adams-Campbell, Lucile L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Palmer, JR (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM jpalmer@bu.edu OI Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X; Cupples, L. Adrienne/0000-0003-0273-7965; Cozier, Yvette/0000-0003-0625-7256 FU NIH, National Cancer Institute, Division of Cancer Control, and Population Sciences [R01 CA058420, R01 CA098663-06A2]; Susan G. Komen for the Cure Foundation FX This work was supported by grants R01 CA058420 and R01 CA098663-06A2 from the NIH, National Cancer Institute, Division of Cancer Control, and Population Sciences, and a grant from the Susan G. Komen for the Cure Foundation. NR 48 TC 33 Z9 33 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 127 EP 134 DI 10.1158/1055-9965.EPI-12-0769 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900016 PM 23136140 ER PT J AU Miller, JW Sabatino, SA Thompson, TD Breen, N White, MC Ryerson, AB Taplin, S Ballard-Barbash, R AF Miller, Jacqueline W. Sabatino, Susan A. Thompson, Trevor D. Breen, Nancy White, Mary C. Ryerson, A. Blythe Taplin, Stephen Ballard-Barbash, Rachel TI Breast MRI Use Uncommon among U.S. Women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER; MAMMOGRAPHY; RISK; SENSITIVITY; ULTRASOUND AB Background: The goal of breast cancer screening is to reduce breast cancer mortality. Mammography is the standard screening method for detecting breast cancer early. Breast MRI is recommended to be used in conjunction with mammography for screening subsets of women at high risk for breast cancer. We offer the first study to provide national estimates of breast MM use among women in the United States. Methods: We analyzed data from women who responded to questions about having a breast MRI on the 2010 National Health Interview Survey. We assessed report of having a breast MRI and reasons for it by socio-demographic characteristics and access to health care and computed five-year and lifetime breast cancer risk using the Gail model. Results: Among 11,222 women who responded, almost 5% reported ever having a breast MRI and 2% reported having an MM within the 2 years preceding the survey. Less than half of the women who reported having a breast MRI were at increased risk. Approximately 60% of women reported having the breast MRI for diagnostic reasons. Women who ever had a breast MRI were more likely to be older, Black, and insured and to report a usual source of health care as compared with women who reported no MRI. Conclusions: Breast MRI use may be underused or overused in certain subgroups of women. Impact: As access to health care improves, the use of breast MRI and the appropriateness of its use for breast cancer detection will be important to monitor. Cancer Epidemiol Biomarkers Prev; 22(1); 159-66. (C) 2012 AACR. C1 [Miller, Jacqueline W.; Sabatino, Susan A.; Thompson, Trevor D.; White, Mary C.; Ryerson, A. Blythe] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Breen, Nancy; Taplin, Stephen; Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Miller, JW (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Hwy NE,Mailstop K-57, Atlanta, GA 30341 USA. EM JMiller5@cdc.gov RI White, Mary /C-9242-2012 OI White, Mary /0000-0002-9826-3962 FU Intramural NIH HHS [Z99 CA999999] NR 26 TC 2 Z9 2 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2013 VL 22 IS 1 BP 159 EP 166 DI 10.1158/1055-9965.EPI-12-0967 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 070SS UT WOS:000313531900020 PM 23155135 ER PT J AU Rahimi, Z Malek-Khosravi, S Rahimi, Z Jalilvand, F Parsian, A AF Rahimi, Zohreh Malek-Khosravi, Shohreh Rahimi, Ziba Jalilvand, Faranak Parsian, Abbas TI MTHFR C677T and eNOS G894T variants in preeclamptic women: Contribution to lipid peroxidation and oxidative stress SO CLINICAL BIOCHEMISTRY LA English DT Article DE Preeclampsia; MTHFR C677T; eNOS G894T; Lipid peroxidation; TAC ID OXIDE SYNTHASE GENE; FACTOR-V-LEIDEN; PREGNANCY COMPLICATIONS; DIABETIC-NEPHROPATHY; WESTERN IRAN; POLYMORPHISMS; POPULATION; RISK; HOMOCYSTEINE; MUTATION AB Objectives: We aimed to investigate the association between methylenetetrahydrofolate reductase (MTHFR) C677T and endothelial nitric oxide synthase (eNOS) G894T polymorphisms with lipid peroxidation, total antioxidant capacity (TAC) and the risk of preeclampsia in preeclamptic women. Design and Methods: We screened a sample of 198 unrelated women with mild and severe forms of preeclampsia and 101 unrelated women with normal pregnancy with the eNOS and MTHFR variants using PCR-RFLP method. Also, the serum malondialdehyde (MDA) and TAC levels were determined using HPLC and commercial kits, respectively. Results: The frequency of combined genotypes of MTHFR CT and TT (CT + TT) and T allele tended to be higher in severe preeclamptic women compared to controls. There was no significant difference for eNOS G894T genotype and allele frequencies between patients and controls. A significantly higher level of triglycerides was observed in the presence of combined genotypes of MTHFR CT and TT and also eNOS GT and TT (GT + TT) in preeclamptic women compared to controls with the same genotype. Also, the presence of MTHFR TT genotype in severe preeclamptic women was significantly associated with the increased serum MDA level compared to CC genotype. In severe preeclamptic women the presence of CT and combined genotypes of CT and TT was significantly associated with the decreased TAC level compared to CC genotype. Also, a higher MDA level was observed in mild preeclamptic women with eNOS TT genotype compared to those with GG genotype but the difference was not significant. Conclusion: The present study indicates that MTHFR C677T polymorphism through affecting on TG level, lipid peroxidation and oxidative stress might be involved in the pathogenesis of severe preeclampsia. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Rahimi, Zohreh] Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, Kermanshah, Iran. [Rahimi, Zohreh] Kermanshah Univ Med Sci, Dept Biochem, Sch Med, Kermanshah, Iran. [Malek-Khosravi, Shohreh; Jalilvand, Faranak] Kermanshah Univ Med Sci, Dept Obstet & Gynecol, Sch Med, Kermanshah, Iran. [Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Med Biol Res Ctr, Sch Med, Daneshgah Ave,POB 67148-69914, Kermanshah, Iran. EM zrahimi@kums.ac.ir OI Rahimi, Zohreh/0000-0001-7589-3307 FU Kermanshah University of Medical Sciences office of Vice Chancellor for Research, Kermanshah, Iran FX This work was performed in partial fulfillment of the requirements for MD degree of Dr. Faranak Jalilvand, Kermanshah University of Medical Sciences, Kermanshah, Iran and was financially supported by a grant from Kermanshah University of Medical Sciences office of Vice Chancellor for Research, Kermanshah, Iran. NR 37 TC 9 Z9 11 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD JAN PY 2013 VL 46 IS 1-2 BP 143 EP 147 DI 10.1016/j.clinbiochem.2012.10.020 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 069AH UT WOS:000313406800030 PM 23103710 ER PT J AU Srivastava, S AF Srivastava, Sudhir TI The Early Detection Research Network: 10-Year Outlook SO CLINICAL CHEMISTRY LA English DT Review ID PROSTATE-CANCER; VALIDATION; BIOMARKERS AB BACKGROUND: The National Cancer Institute's Early Detection Research Network (EDRN) has made significant progress in developing an organized effort for discovering and validating biomarkers, building resources to support this effort, demonstrating the capabilities of several genomic and proteomic platforms, identifying candidate biomarkers, and undertaking multicenter validation studies. In its first 10 years, the EDRN went from a groundbreaking concept to an operational success. CONTENTS: The EDRN has established clear milestones for reaching a decision of "go" or "no go" during the biomarker development process. Milestones are established on the basis of statistical criteria, performance characteristics of biomarkers, and anticipated clinical use. More than 300 biomarkers have been stopped from further development. To date, the EDRN has prioritized more than 300 biomarkers and has completed more than 10 validation studies. The US Food and Drug Administration has now cleared 5 biomarkers for various clinical endpoints. SUMMARY: The EDRN today combines numerous collaborative and multidisciplinary investigator-initiated projects with a strong national administrative and data infrastructure. The EDRN has created a rigorous peer-review system that ensures that preliminary data-analytical, clinical, and quantitative-are of excellent quality. The process begins with an internal review with clinical, biostatistical, and analytical expertise. The project then receives external peer review and, finally, National Cancer Institute program staff review, resulting in an exceptionally robust and high-quality validation trial. (C) 2012 American Association for Clinical Chemistry C1 NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Canc Prevent Div, 6130 Execut Blvd,Suite 3142,MSC 7362, Rockville, MD 20852 USA. EM ss1a@nih.gov NR 12 TC 11 Z9 11 U1 0 U2 9 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2013 VL 59 IS 1 BP 60 EP 67 DI 10.1373/clinchem.2012.184697 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 070TV UT WOS:000313535100016 PM 23160065 ER PT J AU Feng, ZD Kagan, J Pepe, M Thornquist, M Rinaudo, JA Dahlgren, J Krueger, K Zheng, YY Patriotis, C Huang, Y Sorbara, L Thompson, I Srivastava, S AF Feng, Ziding Kagan, Jacob Pepe, Margaret Thornquist, Mark Rinaudo, Jo Ann Dahlgren, Jackie Krueger, Karl Zheng, Yingye Patriotis, Christos Huang, Ying Sorbara, Lynn Thompson, Ian Srivastava, Sudhir TI The Early Detection Research Network's Specimen Reference Sets: Paving the Way for Rapid Evaluation of Potential Biomarkers SO CLINICAL CHEMISTRY LA English DT Review ID PROSTATE-CANCER DETECTION; PROTEOMIC PATTERNS; SERUM; VALIDATION; SURFACE AB BACKGROUND: The mission of the National Cancer Institute's Early Detection Research Network (EDRN) is to identify and validate cancer biomarkers for clinical use. Since its inception, EDRN investigators have learned a great deal about the process of validating biomarkers for clinical use. Translational research requires a broad spectrum of research expertise, and coordinating collaborative activities can be challenging. The EDRN has developed a robust triage and validation system that serves the roles of both "facilitator" and "brake." CONTENT: The system consists of (a) establishing a reference set of specimens collected under PRoBE (Prospective Specimen Collection Retrospective Blinded Evaluation) design criteria; (b) using the reference set to prevalidate candidate biomarkers before committing to full-scale validation; (c) performing full-scale validation for those markers that pass prevalidation testing; and (d) ensuring that the reference set is sufficiently large in numbers and volumes of sample that it can also be used to study future candidate biomarkers. This system provides rigorous and efficient evaluation of candidate biomarkers and biomarker panels. Reference sets should also be constructed to enable high-quality biomarker-discovery research. SUMMARY: We describe the process of establishing our system in the hope that it will serve as an example of how to validate biomarkers for clinical application. We also hope that this description of the biospecimen reference sets available from the EDRN will encourage the biomarker research community-from academia or industry-to use this resource to advance biomarkers into clinical use. (C) 2012 American Association for Clinical Chemistry C1 [Feng, Ziding; Pepe, Margaret; Thornquist, Mark; Dahlgren, Jackie; Zheng, Yingye; Huang, Ying] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kagan, Jacob; Rinaudo, Jo Ann; Krueger, Karl; Patriotis, Christos; Sorbara, Lynn; Srivastava, Sudhir] NCI, Bethesda, MD 20892 USA. [Thompson, Ian] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Feng, ZD (reprint author), 1100 Fairview Ave N,M2-B500, Seattle, WA 98109 USA. EM zfeng@fhcrc.org FU NCI [U24 CA086368, PSO CA054174, U01 CA86402] FX Z. Feng, NCI (grant no. U24 CA086368); M.S. Pepe, NCI (grant no. U24 CA086368); M. Thorquist, NCI (grant no. U24 CA086368); Y. Zheng, NCI (grant no. U24 CA086368); Y. Huang, NCI (grant no. U24 CA086368); I. Thompson, NCI (grant nos. PSO CA054174 and U01 CA86402). NR 10 TC 19 Z9 19 U1 2 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2013 VL 59 IS 1 BP 68 EP 74 DI 10.1373/clinchem.2012.185140 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 070TV UT WOS:000313535100017 PM 23193062 ER PT J AU Jarrett, SG Novak, M Harris, N Merlino, G Slominski, A Kaetzel, DM AF Jarrett, Stuart G. Novak, Marian Harris, Nathan Merlino, Glenn Slominski, Andrezj Kaetzel, David M. TI NM23 deficiency promotes metastasis in a UV radiation-induced mouse model of human melanoma SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Metastasis suppressor; Melanoma; NM23; Ultraviolet radiation; Mutagenesis; DNA repair; Cell motility; Hepatocyte growth factor; Transgenic mice ID NUCLEOTIDE EXCISION-REPAIR; INDUCED DNA-DAMAGE; ULTRAVIOLET-RADIATION; SUPPRESSOR NM23-H1; CELL-LINES; MICE; GROWTH; GENE; CARCINOGENESIS; EXPRESSION AB Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates of < 5 % for patients presenting with metastatic disease. Mechanisms underlying metastatic spread of UVR-induced melanoma are not well understood, in part due to a paucity of animal models that accurately recapitulate the disease in its advanced forms. We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis. Crossing of the nm23-h1/nm23-h2 knockout in hemizygous-null form ([m1m2](+/-)) to a transgenic mouse strain (hepatocyte growth factor/scatter factor-overexpressing, or HGF(+) strain) vulnerable to poorly-metastatic, UVR-induced melanomas resulted in UVR-induced melanomas with high metastatic potential. Metastasis to draining lymph nodes was seen in almost all cases of back skin melanomas, while aggressive metastasis to lung, thoracic cavity, liver and bone also occurred. Interestingly, no differences were observed in the invasive characteristics of primary melanomas of HGF(+) and HGF(+) x [m1m2](+/-) strains, with both exhibiting invasion into the dermis and subcutis, indicating factors other than simple invasive activity were responsible for metastasis of HGF(+) x [m1m2](+/-) melanomas. Stable cell lines were established from the primary and metastatic melanoma lesions from these mice, with HGF(+) x [m1m2](+/-) lines exhibiting increased single cell migration and genomic instability. These studies demonstrate for the first time in vivo a potent metastasis suppressor activity of NM23 in UVR-induced melanoma, and have provided new tools for identifying molecular mechanisms that underlie melanoma metastasis. C1 [Jarrett, Stuart G.; Novak, Marian; Harris, Nathan; Kaetzel, David M.] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Markey Canc Ctr, Lexington, KY USA. [Merlino, Glenn] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Slominski, Andrezj] Univ Tennessee, Ctr Hlth Sci, Dept Pathol & Lab Med, Memphis, TN 38163 USA. RP Kaetzel, DM (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. EM dmkaetz@uky.edu FU National Institutes of Health, National Cancer Institute [CA83237] FX The authors wish to thank Edith Postel for providing the [m1m2]+/- mouse strain, and John D'Orazio and Kathryn Coyle for their helpful advice over the course of these studies. This work was supported by the National Institutes of Health, National Cancer Institute Grant CA83237 (D.M.K). NR 33 TC 9 Z9 10 U1 0 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 2013 VL 30 IS 1 BP 25 EP 36 DI 10.1007/s10585-012-9495-z PG 12 WC Oncology SC Oncology GA 072YF UT WOS:000313709400003 PM 22699362 ER PT J AU Spano, D Marshall, JC Marino, N De Martino, D Romano, A Scoppettuolo, MN Bello, AM Di Dato, V Navas, L De Vita, G Medaglia, C Steeg, PS Zollo, M AF Spano, Daniela Marshall, Jean-Claude Marino, Natascia De Martino, Daniela Romano, Alessia Scoppettuolo, Maria Nunzia Bello, Anna Maria Di Dato, Valeria Navas, Luigi De Vita, Gennaro Medaglia, Chiara Steeg, Patricia S. Zollo, Massimo TI Dipyridamole prevents triple-negative breast-cancer progression SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Dipyridamole; Metastasis; ERK1/2-MAPK; Wnt; NF-kB; Immune cell infiltration; Tumor microenvironment ID NF-KAPPA-B; PHASE-I; TUMOR-METASTASIS; CYTOTOXICITY; TRIAL; METHOTREXATE; POTENTIATION; TOXICITY; CELLS; 5-FLUOROURACIL AB Dipyridamole is a widely prescribed drug in ischemic disorders, and it is here investigated for potential clinical use as a new treatment for breast cancer. Xenograft mice bearing triple-negative breast cancer 4T1-Luc or MDA-MB-231T cells were generated. In these in vivo models, dipyridamole effects were investigated for primary tumor growth, metastasis formation, cell cycle, apoptosis, signaling pathways, immune cell infiltration, and serum inflammatory cytokines levels. Dipyridamole significantly reduced primary tumor growth and metastasis formation by intraperitoneal administration. Treatment with 15 mg/kg/day dipyridamole reduced mean primary tumor size by 67.5 % (p = 0.0433), while treatment with 30 mg/kg/day dipyridamole resulted in an almost a total reduction in primary tumors (p = 0.0182). Experimental metastasis assays show dipyridamole reduces metastasis formation by 47.5 % in the MDA-MB-231T xenograft model (p = 0.0122), and by 50.26 % in the 4T1-Luc xenograft model (p = 0.0292). In vivo dipyridamole decreased activated beta-catenin by 38.64 % (p < 0.0001), phospho-ERK1/2 by 25.05 % (p = 0.0129), phospho-p65 by 67.82 % (p < 0.0001) and doubled the expression of IkB alpha (p = 0.0019), thus revealing significant effects on Wnt, ERK1/2-MAPK and NF-kB pathways in both animal models. Moreover dipyridamole significantly decreased the infiltration of tumor-associated macrophages and myeloid-derived suppressor cells in primary tumors (p < 0.005), and the inflammatory cytokines levels in the sera of the treated mice. We suggest that when used at appropriate doses and with the correct mode of administration, dipyridamole is a promising agent for breast-cancer treatment, thus also implying its potential use in other cancers that show those highly activated pathways. C1 [Spano, Daniela; Marino, Natascia; De Martino, Daniela; Scoppettuolo, Maria Nunzia; Bello, Anna Maria; Zollo, Massimo] Ctr Ingn Genet CEINGE Biotecnol Avanzate, I-80145 Naples, Italy. [Spano, Daniela; De Martino, Daniela; Romano, Alessia; Scoppettuolo, Maria Nunzia; Bello, Anna Maria; Di Dato, Valeria; De Vita, Gennaro; Medaglia, Chiara; Zollo, Massimo] Univ Naples Federico II, Dipartimento Biochim & Biotecnol Med, I-80131 Naples, Italy. [Marshall, Jean-Claude; Marino, Natascia; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Navas, Luigi] Univ Naples Federico II, Dipartimento Sci Clin Vet, Sez Clin Chirurg, I-80137 Naples, Italy. RP Zollo, M (reprint author), Ctr Ingn Genet CEINGE Biotecnol Avanzate, Via Gaetano Salvatore 486, I-80145 Naples, Italy. EM zollo@ceinge.unina.it RI Di Dato, Valeria/L-2484-2015; Zollo, Massimo/K-5857-2016; OI Di Dato, Valeria/0000-0001-9720-6619; Zollo, Massimo/0000-0002-0970-7243; NAVAS, Luigi/0000-0002-1851-5016 FU National Cancer Institute; Dipartimento di Biochimica e Biotecnologie Mediche, 'Federico II' University of Naples; Fondazione San Paolo; Tumic; Dottorato in Medicina Molecolare, 'Federico II' University of Naples; Dottorato in Produzione e Sanita degli Alimenti di Origine Animale, 'Federico II' University of Naples; Associazione Italiana per la Ricerca sul Cancro FX We would like to thank: Prof. Eugene Lukanidin for sharing the S100A4 antibodies used in this study, Prof. Luigi del Vecchio and Dr. Maddalena Raia for technical advice with the FACS analyses, Dr. Donatella Montanaro for technical advice with histological analyses, and Prof. Francesco Salvatore for supporting the project with the instrumentation required for in vivo imaging in mice. We also thank Viviana Vastolo for technical assistance in in vivo experiments. Associazione Italiana per la ricerca sul Cancro AIRC (MZ), Associazione Italiana per la lotta al Neuroblastoma (MZ). This study was also supported in part by the Intramural Research Program of the National Cancer Institute (PSS). DS was supported by the Dipartimento di Biochimica e Biotecnologie Mediche, 'Federico II' University of Naples; VDD was supported by the Fondazione San Paolo (IM) and Tumic; DMD was supported by a Dottorato in Medicina Molecolare, 'Federico II' University of Naples; GDV was supported by a Dottorato in Medicina Molecolare, 'Federico II' University of Naples; and CM was supported by a Dottorato in Produzione e Sanita degli Alimenti di Origine Animale, 'Federico II' University of Naples. NR 54 TC 17 Z9 17 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 EI 1573-7276 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 2013 VL 30 IS 1 BP 47 EP 68 DI 10.1007/s10585-012-9506-0 PG 22 WC Oncology SC Oncology GA 072YF UT WOS:000313709400005 PM 22760522 ER PT J AU Hochman, J Shen, DF Gottesman, MM Chan, CC AF Hochman, Jacob Shen, DeFen Gottesman, Michael M. Chan, Chi-Chao TI Anti-LFA-1 antibodies enhance metastasis of ocular lymphoma to the brain and contralateral eye SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Metastasis; Lymphoma; Eye; Brain; LFA-1 ID BONE-MARROW-TRANSPLANTATION; ENDOTOXIN-INDUCED UVEITIS; MONOCLONAL-ANTIBODIES; CELL-ADHESION; TRANSENDOTHELIAL MIGRATION; MALIGNANT-LYMPHOMA; IMMUNE FUNCTION; INTEGRIN LFA-1; ICAM-1; CD11A AB Previously we demonstrated that intraperitoneal (IP) inoculation of Rev-2-T-6 mouse lymphoma into syngeneic Balb/c hosts resulted in brain metastasis, migration along the optic nerve sheath, and ocular infiltration. In a second model: intravitreal inoculation of Rev-2-T-6 cells, the developing lymphoma was largely confined within the eye, seldom breaching the retinal pigment epithelium to reside in the choroid and sclera. There was no retrograde infiltration into the brain. Here, we describe a third, complementary model, whereby intravitreal inoculation of Rev-2-T-6 cells into Balb/c mice, followed by repeated IP inoculations of anti-LFA-1/CD11a monoclonal antibodies, results in extensive infiltration of the choroid, sclera, conjunctiva, eyelids and orbit. Furthermore, the lymphoma cells metastasize along the optic nerve sheath into the brain, and through the contralateral optic nerve tract into the contralateral eye. There is no systemic involvement of the lymphoma. Furthermore, anti-LFA-1 treatment results in elevated levels of serum anti-Rev-2-T-6 antibodies. Inoculation of Rev-2-T-6 cells into the vitreous of severe combined immune deficient mice demonstrates a course of clinical signs and histopathological findings similar to those in immune-competent mice treated with anti-LFA-1 antibodies, including invasion of the contralateral eye. Taken together, these findings suggest that confinement of Rev-2-T-6 lymphoma cells to the eye depends on active immune surveillance using a population of effector cells expressing the cell surface integrin LFA-1. Impairing this protection enhances tumor aggressiveness within the eye, and the likelihood of early retrograde lymphoma metastasis into the brain and the contralateral eye. C1 [Hochman, Jacob] Hebrew Univ Jerusalem, Dept Cell & Dev Biol, Alexander Silberman Inst Life Sci, IL-91904 Jerusalem, Israel. [Shen, DeFen; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hochman, J (reprint author), Hebrew Univ Jerusalem, Dept Cell & Dev Biol, Alexander Silberman Inst Life Sci, IL-91904 Jerusalem, Israel. EM hochman@vms.huji.ac.il; chanc@nei.nih.gov FU A.M.N foundation, Jerusalem; National Institute of Health, National Eye Institute; National Institute of Health, National Cancer Institute FX This work was supported by the A.M.N foundation, Jerusalem (JH) and by the Intramural Research Programs of the National Institutes of Health, National Eye Institute (DS, CCC) and National Cancer Institute (JH, MMG). NR 56 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD JAN PY 2013 VL 30 IS 1 BP 91 EP 102 DI 10.1007/s10585-012-9512-2 PG 12 WC Oncology SC Oncology GA 072YF UT WOS:000313709400008 PM 22865235 ER PT J AU Li, MC Tsai, PC Chen, PC Hsieh, CJ Guo, YLL Rogan, WJ AF Li, Ming-Chieh Tsai, Pei-Chien Chen, Pau-Chung Hsieh, Chia-Jung Guo, Yue-Liang Leon Rogan, Walter J. TI Mortality after exposure to polychlorinated biphenyls and dibenzofurans: 30 years after the "Yucheng Accident" SO ENVIRONMENTAL RESEARCH LA English DT Article DE Yucheng; Dioxin; Polychlorinated biphenyls; Polychlorinated dibenzofurans; Standardized mortality ratio ID CAPACITOR MANUFACTURING WORKERS; 24-YEAR FOLLOW-UP; CANCER INCIDENCE; HEART-DISEASE; RICE OIL; COHORT; YUSHO; PCBS; TAIWAN; INCIDENT AB Background: In 1979, approximately 2,000 people in central Taiwan were accidentally exposed to polychlorinated biphenyls and dibenzofurans due to ingestion of contaminated cooking oil. This event was called Yucheng, "oil-syndrome" in Chinese. We followed the exposed persons and compared their cause-specific mortality with that of neighborhood referents 30 years after the accident. Methods: We obtained age- and gender-matched referents from the 1979 neighborhoods of the exposed people. Cause-specific mortality was compared between exposed subjects (N=1803) and their neighborhood referents (N=5170) using standardized mortality ratios (SMR). Total person-years for the Yucheng subjects and neighborhood referents were 48,751 and 141,774, respectively. Results: The SMR for all causes (SMR=1.2, 95% CI: 1.1-1.3), diseases of the circulatory system (SMR=1.3, 95% CI: 1.0-1.6), and diseases of the musculoskeletal system and connective tissue (SMR=6.4, 95% CI: 2.8-12.7) were elevated in Yucheng subjects. Among Yucheng males, the SMRs for diseases of the digestive system (SMR=1.9, 95% CI: 1.2-2.8), malignant neoplasm of stomach (SMR=3.5, 95% CI: 1.5-7.0), and malignant neoplasm of lymphatic and hematopoietic tissue (SMR=3.0, 95% CI: 1.1-6.6) were increased. The SMR for total neoplasms was increased (SMR=1.3, 95% CI: 0.9-1.7). Conclusion: We conclude that exposure to PCBs/PCDFs at levels that produced symptoms in many affects mortality patterns 3 decades after exposure. (c) 2012 Elsevier Inc. All rights reserved. C1 [Li, Ming-Chieh; Chen, Pau-Chung; Hsieh, Chia-Jung] Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei, Taiwan. [Tsai, Pei-Chien] Kaohsiung Med Univ Hosp, Dept Med Res, Kaohsiung, Taiwan. [Guo, Yue-Liang Leon] Natl Taiwan Univ, Coll Med, Dept Environm & Occupat Med, Taipei, Taiwan. [Rogan, Walter J.] NIEHS, Epidemiol Branch, NIH, Bethesda, MD USA. RP Guo, YLL (reprint author), 1,Sect 1,Ren Ai Rd, Taipei 100, Taiwan. EM leonguo@ntu.edu.tw RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; GUO, Yue Leon/0000-0002-8530-4809; Chen, Pau-Chung/0000-0002-6242-5974 FU Department of Health in Taiwan [DOH-98-TD-PH-11, DOH-99-TD-PH-07]; National Science Council in Taiwan [NSC-101-2314-B-002-119]; National Taiwan University Hospital [NTUH.99-P10]; Intramural Research Program of the National Institute of Environmental Health Sciences, US NIH FX This work was supported by the Department of Health in Taiwan (DOH-98-TD-PH-11 and DOH-99-TD-PH-07), the National Science Council in Taiwan (NSC-101-2314-B-002-119), and the National Taiwan University Hospital (NTUH.99-P10). Dr. Rogan is supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, US NIH. NR 33 TC 11 Z9 12 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2013 VL 120 BP 71 EP 75 DI 10.1016/j.envres.2012.09.003 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 071PJ UT WOS:000313606400009 PM 23026800 ER PT J AU Pollack, AZ Mumford, SL Wactawski-Wende, J Yeung, E Mendola, P Mattison, DR Schisterman, EF AF Pollack, A. Z. Mumford, S. L. Wactawski-Wende, J. Yeung, E. Mendola, P. Mattison, D. R. Schisterman, E. F. TI Bone mineral density and blood metals in premenopausal women SO ENVIRONMENTAL RESEARCH LA English DT Article DE Bone mineral density; Cadmium; Lead; Mercury; Women ID NUTRITION EXAMINATION SURVEY; LEVEL CADMIUM EXPOSURE; 3RD NATIONAL-HEALTH; POSTMENOPAUSAL WOMEN; LEAD-EXPOSURE; UNITED-STATES; ENVIRONMENTAL EXPOSURE; URINARY CADMIUM; US WOMEN; OSTEOPOROSIS AB Exposure to metals, specifically cadmium, lead, and mercury, is widespread and is associated with reduced bone mineral density (BMD) in older populations, but the associations among premenopausal women are unclear. Therefore, we evaluated the relationship between these metals in blood and BMD (whole body, total hip, lumbar spine, and non-dominant wrist) quantified by dual energy X-ray absorptiometry in 248 premenopausal women, aged 18-44. Participants were of normal body mass index (mean BMI 24.1), young (mean age 27.4), 60% were white, 20% non-Hispanic black, 15% Asian, and 6% other race group, and were from the Buffalo, New York region. The median (interquartile range) level of cadmium was 0.30 mu g/l (0.19-0.43), of lead was 0.86 mu g/dl (0.68-1.20), and of mercury was 1.10 mu g/l (0.58-2.00). BMD was treated both as a continuous variable in linear regression and dichotomized at the 10th percentile for logistic regression analyses. Mercury was associated with reduced odds of decreased lumbar spine BMD (0.66, 95% confidence interval: 0.44, 0.99), but overall, metals at environmentally relevant levels of exposure were not associated with reduced BMD in this population of healthy, reproductive-aged women. Further research is needed to determine if the blood levels of cadmium, lead, and mercury in this population are sufficiently low that there is no substantive impact on bone, or if effects on bone can be expected only at older ages. Published by Elsevier Inc. C1 [Pollack, A. Z.; Mumford, S. L.; Yeung, E.; Mendola, P.; Mattison, D. R.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. [Wactawski-Wende, J.] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Pollack, AZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B03 Rockville, Rockville, MD 20852 USA. EM pollacka@mail.nih.gov RI Mattison, Donald/L-4661-2013; Yeung, Edwina/F-5992-2015; OI Mattison, Donald/0000-0001-5623-0874; Yeung, Edwina/0000-0002-3851-2613; Pollack, Anna/0000-0002-4313-3298; Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; University at Buffalo; Long-Range Research Initiative Grant of the American Chemistry Council FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The study was also supported in part by the University at Buffalo and Anna Z. Pollack was partially supported by the Long-Range Research Initiative Grant of the American Chemistry Council to Dr. Schisterman, PI. NR 59 TC 9 Z9 9 U1 1 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 2013 VL 120 BP 76 EP 81 DI 10.1016/j.envres.2012.06.001 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 071PJ UT WOS:000313606400010 PM 23122770 ER PT J AU Glauser, TA Cnaan, A Shinnar, S Hirtz, DG Dlugos, D Masur, D Clark, PO Adamson, PC AF Glauser, Tracy A. Cnaan, Avital Shinnar, Shlomo Hirtz, Deborah G. Dlugos, Dennis Masur, David Clark, Peggy O. Adamson, Peter C. CA Childhood Absence Epilepsy Study TI Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy: Initial monotherapy outcomes at 12 months SO EPILEPSIA LA English DT Article DE Randomized clinical trial; Pediatric epilepsy; Epilepsy syndrome treatment ID LONG-TERM PROGNOSIS; FOLLOW-UP; ANTIEPILEPTIC DRUG; WEIGHT-GAIN; CHILDREN; SEIZURES; DIAGNOSIS; ATTENTION AB Purpose: Determine the optimal initial monotherapy for children with newly diagnosed childhood absence epilepsy (CAE) based on 12 months of double-blind therapy. Methods: A double-blind, randomized controlled clinical trial compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed CAE. Study medications were titrated to clinical response, and subjects remained in the trial unless they reached a treatment failure criterion. Maximal target doses were ethosuximide 60 mg/kg/day or 2,000 mg/day, valproic acid 60 mg/kg/day or 3,000 mg/day, and lamotrigine 12 mg/kg/day or 600 mg/day. Original primary outcome was at 1620 weeks and included a videoelectroencephalography (EEG) assessment. For this report, the main effectiveness outcome was the freedom from failure rate 12 months after randomization and included a video-EEG assessment; differential drug effects were determined by pairwise comparisons. The main cognitive outcome was the percentage of subjects experiencing attentional dysfunction at the month 12 visit. Key Findings: A total of 453 children were enrolled and randomized; 7 were deemed ineligible and 446 subjects comprised the overall efficacy cohort. There were no demographic differences between the three cohorts. By 12 months after starting therapy, only 37% of all enrolled subjects were free from treatment failure on their first medication. At the month 12 visit, the freedom-from-failure rates for ethosuximide and valproic acid were similar (45% and 44%, respectively; odds ratio [OR]with valproic acid vs. ethosuximide 0.94; 95% confidence interval [CI] 0.581.52; p = 0.82) and were higher than the rate for lamotrigine (21%; OR with ethosuximide vs. lamotrigine 3.08; 95% CI 1.815.33; OR with valproic acid vs. lamotrigine 2.88; 95% CI 1.685.02; p < 0.001 for both comparisons). The frequency of treatment failures due to lack of seizure control (p < 0.001) and intolerable adverse events (p < 0.037) was significantly different among the treatment groups. Almost two thirds of the 125 subjects with treatment failure due to lack of seizure control were in the lamotrigine cohort. The largest subgroup (42%) of the 115 subjects discontinuing due to adverse events was in the valproic acid group. The previously reported higher rate of attentional dysfunction seen at 1620 weeks in the valproic acid group compared with the ethosuximide or lamotrigine groups persisted at 12 months (p < 0.01). Significance: As initial monotherapy, the superior effectiveness of ethosuximide and valproic acid compared to lamotrigine in controlling seizures without intolerable adverse events noted at 1620 weeks persisted at 12 months. The valproic acid cohort experienced a higher rate of adverse events leading to drug discontinuation as well as significant negative effects on attentional measures that were not seen in the ethosuximide cohort. These 12-month outcome data coupled with the studys prespecified decision-making algorithm indicate that ethosuximide is the optimal initial empirical monotherapy for CAE. This is the first randomized controlled trial meeting International League Against Epilepsy (ILAE) criteria for class I evidence for CAE (or for any type of generalized seizure in adults or children). (NCT00088452.) C1 [Glauser, Tracy A.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Neurol,Comprehens Epilepsy Ctr, Cincinnati, OH 45229 USA. [Cnaan, Avital] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Shinnar, Shlomo; Masur, David] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. [Hirtz, Deborah G.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Dlugos, Dennis; Adamson, Peter C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Glauser, TA (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Neurol,Comprehens Epilepsy Ctr, MLC 2015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM tracy.glauser@cchmc.org FU NIH [NS045911, NS045803, 5 U10 HD031318, 5 U10 HD037249, M01 RR 08084, P30 HD26979]; Eisai; UCB Pharma; Johnson Johnson; Supernus; Sunovion; Questcor; Lundbeck; Upsher Smith; King Pharmaceutical; Abbott Pharmaceutical FX This study was funded by NIH NS045911, NS045803, 5 U10 HD031318, 5 U10 HD037249, M01 RR 08084, and P30 HD26979. The members of the CAE Study Group are listed in the Appendix.; The study was provided study medication free of charge by Pfizer Inc., Abbott Laboratories, and GlaxoSmithKline. Dr. Glauser has received consulting fees from Eisai, UCB Pharma, Johnson & Johnson, Supernus, Sunovion, Questcor, Lundbeck, and Upsher Smith along lecture fees from Eisai, UCB Pharma, Johnson & Johnson, and Questcor. Dr. Cnaan reports consulting for GlaxoSmithKline for non-epilepsy related research. Dr. Shinnar reports receiving consulting fees from Eisai, Johnson & Johnson, King Pharmaceutical, and Questcor along with lecture fees from Eisai, UCB Pharma, and Questcor. Dr. Adamson reports grant support from Abbott Pharmaceutical for oncology-focused research. No other potential conflict of interest relevant to this article was reported. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. NR 52 TC 68 Z9 73 U1 0 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JAN PY 2013 VL 54 IS 1 BP 141 EP 155 DI 10.1111/epi.12028 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA 064ZU UT WOS:000313116500022 PM 23167925 ER PT J AU Scuteri, A Lakatta, EG AF Scuteri, Angelo Lakatta, Edward G. TI Bringing prevention in geriatrics: Evidences from cardiovascular medicine supporting the new challenge SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Arterial aging; Arterial stiffness; Prevention; Cardiovascular disease; Dementia; Cognitive impairment ID SYSTOLIC BLOOD-PRESSURE; LEFT-VENTRICULAR MASS; METABOLIC SYNDROME; UNITED-STATES; COGNITIVE IMPAIRMENT; ARTERIAL STIFFNESS; VASCULAR DEMENTIA; OLDER ADULTS; RISK-FACTORS; AGE AB Aging is a dynamic and systemic process, with high inter-individual heterogeneity, likely partially adaptive. Cardiovascular disease and hypertension are among the leading conditions causing disabilities in older subjects. If, in accordance with most recent definition, prevention is any intervention before the patient receives a diagnosis, prevention is possible at any age. Additionally, disability and CV disease in the elderly may be prevented by targeting factors underlying and modulating the arterial aging process. Cross-talk between arterial and brain aging will be discussed in this context as a paradigmatic clinical model fostering prevention in older subjects. Published by Elsevier Inc. C1 [Scuteri, Angelo; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Scuteri, A (reprint author), IRCCS, INRCA, UOC Geriatria, Via Cassia 1167, I-00189 Rome, Italy. EM angeloelefante@interfree.it FU Intramural NIH HHS [Z01 AG000856-07] NR 70 TC 11 Z9 11 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN PY 2013 VL 48 IS 1 BP 64 EP 68 DI 10.1016/j.exger.2012.02.009 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 071TF UT WOS:000313616500009 PM 22406133 ER PT J AU Alegre, M Lopez-Azcarate, J Obeso, I Wilkinson, L Rodriguez-Oroz, MC Valencia, M Garcia-Garcia, D Guridi, J Artieda, J Jahanshahi, M Obeso, JA AF Alegre, Manuel Lopez-Azcarate, Jon Obeso, Ignacio Wilkinson, Leonora Rodriguez-Oroz, Maria C. Valencia, Miguel Garcia-Garcia, David Guridi, Jorge Artieda, Julio Jahanshahi, Marjan Obeso, Jose A. TI The subthalamic nucleus is involved in successful inhibition in the stop-signal task: A local field potential study in Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Subthalamic nucleus; Stop signal task; Response inhibition; Local field potentials; Parkinson's disease ID DEEP BRAIN-STIMULATION; IMPULSE CONTROL DISORDERS; RESPONSE-INHIBITION; BASAL GANGLIA; REACTION-TIME; OSCILLATORY ACTIVITY; BETA OSCILLATIONS; MOVEMENT; DOPAMINE; LESIONS AB Normal actions and behaviors often require inhibition of unwanted and inadequate movements. Motor inhibition has been studied using the stop signal task, in which participants are instructed to respond to a go signal. Sporadically, a stop signal is also delivered after a short interval following the go signal, prompting participants to inhibit their already started response to the go signal. Functional MRI studies using this paradigm have implicated the activation of the subthalamic nucleus in motor inhibition. We directly recorded subthalamic nucleus activity from bilaterally implanted deep brain stimulation electrodes in a group of 10 patients with Parkinson's disease, during performance of the stop signal task. Response inhibition was associated with specific changes in subthalamic activity in three different frequency bands. Response preparation was associated with a decrease in power and cortico-subthalamic coherence in the beta band (12-30 Hz), which was smaller and shorter when the response was successfully inhibited. In the theta band, we observed an increase in frontal cortico-subthalamic coherence related to the presence of the stop signal, which was highest when response inhibition was unsuccessful. Finally, a specific differential pattern of gamma activity was observed in the "on" motor state. Performance of the response was associated with a significant increase in power and cortico-subthalamic coherence, while successful inhibition of the response was associated with a bilateral decrease in subthalamic power and cortico-subthalamic coherence. Importantly, this inhibition-related decrease in gamma activity was absent in the four patients with dopamine-agonist related impulse-control disorders. Our results provide direct support for the involvement of the subthalamic nucleus in response inhibition and suggest that this function may be mediated by a specific reduction in gamma oscillations in the cortico-subthalamic connection. (c) 2012 Published by Elsevier Inc. C1 [Obeso, Jose A.] Univ Navarra, CIMA, Neurosci Area, Movement Disorders Lab, Pamplona 31008, Spain. [Alegre, Manuel; Rodriguez-Oroz, Maria C.; Guridi, Jorge; Artieda, Julio; Obeso, Jose A.] Univ Navarra Clin, Pamplona, Spain. [Obeso, Ignacio; Wilkinson, Leonora; Jahanshahi, Marjan] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Cognit Motor Neurosci Grp, London WC1N 3BG, England. [Wilkinson, Leonora] Natl Inst Neurol Disorders & Stroke, Behav Neurol Unit, Bethesda, MD USA. [Rodriguez-Oroz, Maria C.; Obeso, Jose A.] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain. RP Obeso, JA (reprint author), Univ Navarra, CIMA, Neurosci Area, Movement Disorders Lab, Pio 12 55, Pamplona 31008, Spain. EM jobeso@unav.es RI Valencia, Miguel/C-3055-2009; Garcia-Garcia, David/I-2105-2015; Artieda, Julio/L-4704-2014; Alegre, Manuel/F-5379-2011 OI Valencia, Miguel/0000-0001-5617-5270; Garcia-Garcia, David/0000-0001-5224-3280; Artieda, Julio/0000-0003-0987-0873; Alegre, Manuel/0000-0003-4985-9724 FU Departamento de Salud, Gobierno de Navarra [14/2009]; UTE project CIMA; Fundacion Caja Madrid; Career Development Fellowship from Parkinson's UK FX This study was supported by a grant from the Departamento de Salud, Gobierno de Navarra (14/2009) and by the UTE project CIMA. Ignacio Obeso was funded by the Fundacion Caja Madrid. Leonora Wilkinson was supported by a Career Development Fellowship from Parkinson's UK. NR 58 TC 41 Z9 42 U1 3 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2013 VL 239 BP 1 EP 12 DI 10.1016/j.expneurol.2012.08.027 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 073TH UT WOS:000313765000002 PM 22975442 ER PT J AU Tweedie, D Rachmany, L Rubovitch, V Lehrmann, E Zhang, YQ Becker, KG Perez, E Miller, J Hoffer, BJ Greig, NH Pick, CG AF Tweedie, David Rachmany, Lital Rubovitch, Vardit Lehrmann, Elin Zhang, Yongqing Becker, Kevin G. Perez, Evelyn Miller, Jonathan Hoffer, Barry J. Greig, Nigel H. Pick, Chaim G. TI Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Mild traumatic brain injury (mTBI); Glucagon-like peptide-1; Exendin-4; Gene expression; Novel object recognition; Alzheimer's disease ID TRAUMATIC BRAIN-INJURY; CONTROLLED CORTICAL IMPACT; NECROSIS-FACTOR-ALPHA; ALZHEIMERS-DISEASE; CELL-CYCLE; AMYLOID-BETA; MOUSE MODEL; A-BETA; COGNITIVE IMPAIRMENT; BINDING-SITES AB Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer's disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury. (c) 2012 Elsevier Inc. All rights reserved. C1 [Tweedie, David] NIA, Translat Gerontol Branch, Intramural Res Program, Drug Design & Dev Sect,Lab Neurosci,NIH, Baltimore, MD 21224 USA. [Rachmany, Lital; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. [Lehrmann, Elin; Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Perez, Evelyn] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Miller, Jonathan; Hoffer, Barry J.] Case Western Reserve Univ, Sch Med, Dept Neurosurg, Cleveland, OH 44106 USA. RP Tweedie, D (reprint author), NIA, Translat Gerontol Branch, Intramural Res Program, Drug Design & Dev Sect,Lab Neurosci,NIH, BRC Room 05C220,251 Bayview Blvd, Baltimore, MD 21224 USA. EM tweedieda@grc.nia.nih.gov; litalrac@post.tau.ac.il; rubovitc@post.tau.ac.il; elehrman@mail.nih.gov; zhangyon@grc.nia.nih.gov; BeckerK@grc.nia.nih.gov; perezev@grc.nia.nih.gov; Jonathan.Miller@UHhospitals.org; bjh82@case.edu; greign@grc.nia.nih.gov; pickc@post.tau.ac.il OI Lehrmann, Elin/0000-0002-9869-9475; Becker, Kevin/0000-0002-6794-6656 FU Sackler School of Medicine, Tel-Aviv University; Intramural Research Program of the National Institute on Aging, National Institutes of Health; Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health FX This research was supported in part by the Sackler School of Medicine, Tel-Aviv University, and the Intramural Research Programs of both the National Institute on Aging and National Institute on Drug Abuse, National Institutes of Health. NR 84 TC 36 Z9 37 U1 0 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2013 VL 239 BP 170 EP 182 DI 10.1016/j.expneurol.2012.10.001 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 073TH UT WOS:000313765000021 PM 23059457 ER PT J AU Manning, VA Pandelova, I Dhillon, B Wilhelm, LJ Goodwin, SB Berlin, AM Figueroa, M Freitag, M Hane, JK Henrissat, B Holman, WH Kodira, CD Martin, J Oliver, RP Robbertse, B Schackwitz, W Schwartz, DC Spatafora, JW Turgeon, BG Yandava, C Young, S Zhou, SG Zeng, QD Grigoriev, IV Ma, LJ Ciuffetti, LM AF Manning, Viola A. Pandelova, Iovanna Dhillon, Braham Wilhelm, Larry J. Goodwin, Stephen B. Berlin, Aaron M. Figueroa, Melania Freitag, Michael Hane, James K. Henrissat, Bernard Holman, Wade H. Kodira, Chinnappa D. Martin, Joel Oliver, Richard P. Robbertse, Barbara Schackwitz, Wendy Schwartz, David C. Spatafora, Joseph W. Turgeon, B. Gillian Yandava, Chandri Young, Sarah Zhou, Shiguo Zeng, Qiandong Grigoriev, Igor V. Ma, Li-Jun Ciuffetti, Lynda M. TI Comparative Genomics of a Plant-Pathogenic Fungus, Pyrenophora tritici-repentis, Reveals Transduplication and the Impact of Repeat Elements on Pathogenicity and Population Divergence SO G3-GENES GENOMES GENETICS LA English DT Article DE wheat (Triticum aestivum); copy number variation; histone H3 transduplication; ToxA; ToxB; anastomosis ID HOST-SELECTIVE TOXIN; BERBERINE BRIDGE ENZYME; NONRIBOSOMAL PEPTIDE SYNTHETASES; BIOSYNTHETIC GENE-CLUSTER; INDUCED POINT MUTATIONS; CELL-WALL DEGRADATION; TAN SPOT; PTR-TOXA; CAUSAL AGENT; COCHLIOBOLUS-CARBONUM AB Pyrenophora tritici-repentis is a necrotrophic fungus causal to the disease tan spot of wheat, whose contribution to crop loss has increased significantly during the last few decades. Pathogenicity by this fungus is attributed to the production of host-selective toxins ( HST), which are recognized by their host in a genotype-specific manner. To better understand the mechanisms that have led to the increase in disease incidence related to this pathogen, we sequenced the genomes of three P. tritici-repentis isolates. A pathogenic isolate that produces two known HSTs was used to assemble a reference nuclear genome of approximately 40 Mb composed of 11 chromosomes that encode 12,141 predicted genes. Comparison of the reference genome with those of a pathogenic isolate that produces a third HST, and a nonpathogenic isolate, showed the nonpathogen genome to be more diverged than those of the two pathogens. Examination of gene-coding regions has provided candidate pathogen-specific proteins and revealed gene families that may play a role in a necrotrophic lifestyle. Analysis of transposable elements suggests that their presence in the genome of pathogenic isolates contributes to the creation of novel genes, effector diversification, possible horizontal gene transfer events, identified copy number variation, and the first example of transduplication by DNA transposable elements in fungi. Overall, comparative analysis of these genomes provides evidence that pathogenicity in this species arose through an influx of transposable elements, which created a genetically flexible landscape that can easily respond to environmental changes. C1 [Manning, Viola A.; Pandelova, Iovanna; Wilhelm, Larry J.; Figueroa, Melania; Holman, Wade H.; Spatafora, Joseph W.; Ciuffetti, Lynda M.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Dhillon, Braham] Univ British Columbia, Dept Forest Sci, Vancouver, BC V6T 1Z4, Canada. [Wilhelm, Larry J.] Oregon Reg Primate Res Ctr, Div Neurosci, Carbone Ferguson Labs, Beaverton, OR 97006 USA. [Goodwin, Stephen B.] Purdue Univ, USDA ARS, W Lafayette, IN 47907 USA. [Berlin, Aaron M.; Kodira, Chinnappa D.; Yandava, Chandri; Young, Sarah; Zeng, Qiandong; Ma, Li-Jun] Broad Inst, Cambridge, MA 02142 USA. [Figueroa, Melania] Oregon State Univ, USDA ARS, Forage Seed & Cereal Res Unit, Corvallis, OR 97331 USA. [Freitag, Michael] Oregon State Univ, Dept Biochem & Biophys, Corvallis, OR 97331 USA. [Freitag, Michael; Ciuffetti, Lynda M.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA. [Hane, James K.] CSIRO, Plant Ind, Ctr Environm & Life Sci, Floreat, WA 6014, Australia. [Henrissat, Bernard] Aix Marseille Univ, CNRS, F-13288 Marseille 9, France. [Kodira, Chinnappa D.] Roche 454, Branford, CT 06405 USA. [Martin, Joel; Schackwitz, Wendy; Grigoriev, Igor V.] US DOE Joint Genome Inst, Walnut Creek, CA 94598 USA. [Oliver, Richard P.] Curtin Univ Technol, Dept Environm & Agr, Australian Ctr Necrotroph Fungal Pathogens, Bentley, WA 6845, Australia. [Robbertse, Barbara] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. [Schwartz, David C.; Zhou, Shiguo] Univ Wisconsin, UW Biotechnol Ctr, Dept Chem, Lab Mol & Computat Genome,Lab Genet, Madison, WI 53706 USA. [Turgeon, B. Gillian] Cornell Univ, Dept Plant Pathol & Plant Microbe Biol, Ithaca, NY 14850 USA. [Ma, Li-Jun] Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. RP Ciuffetti, LM (reprint author), Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. EM lijun@biochem.umass.edu; ciuffetL@science.oregonstate.edu RI Hane, James/A-7062-2011; Henrissat, Bernard/J-2475-2012; OI Hane, James/0000-0002-7651-0977; Ma, Li-Jun/0000-0002-2733-3708; Goodwin, Stephen/0000-0001-5708-9729 FU National Science Foundation under a Minority Postdoctoral Research Fellowship [0706881]; National Research Initiative of the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service [2006-55600-16619]; Office of Science of the U.S. Department of Energy [DE-AC02-05CH11231] FX We thank Cedar Hesse and Jeffrey Kimbrel for helpful discussion about bioinformatics and the Center of Genome Research and Biocomputing, Oregon State University, Corvallis, Oregon, for biocomputing infrastructure. We thank K. Cook, P. Martinez, and S. Ottum for microscopy. We also thank the Colletotrichum genome project (PIs-Lisa Vaillancourt, Michael Thon, and Marty Dickman) for sharing unpublished data. Funding for M. Figueroa was provided by the National Science Foundation under a Minority Postdoctoral Research Fellowship (0706881) awarded in 2007. Sequencing of the reference strain was funded by the National Research Initiative of the U.S. Department of Agriculture Cooperative State Research, Education and Extension Service, grant number (2006-55600-16619), and reviewed through the U.S. Department of Agriculture/National Science Foundation Microbial Genome Sequencing Project. Illumina sequencing work was conducted by the U.S. Department of Energy Joint Genome Institute and supported by the Office of Science of the U.S. Department of Energy (under Contract No. DE-AC02-05CH11231). NR 190 TC 48 Z9 117 U1 3 U2 69 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 2160-1836 J9 G3-GENES GENOM GENET JI G3-Genes Genomes Genet. PD JAN PY 2013 VL 3 IS 1 BP 41 EP 63 DI 10.1534/g3.112.004044 PG 23 WC Genetics & Heredity SC Genetics & Heredity GA 070ZU UT WOS:000313555200006 PM 23316438 ER PT J AU Wu, LT Swartz, MS Pan, JJ Burchett, B Mannelli, P Yang, CM Blazer, DG AF Wu, Li-Tzy Swartz, Marvin S. Pan, Jeng-Jong Burchett, Bruce Mannelli, Paolo Yang, Chongming Blazer, Dan G. TI Evaluating brief screeners to discriminate between drug use disorders in a sample of treatment-seeking adults SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Clinical Trials Network; Item response theory; Receiver operating characteristic curve; Brief screening; Substance use disorders ID CLINICAL-TRIALS NETWORK; ALCOHOL-USE DISORDERS; SUBSTANCE USE DISORDERS; QUALITY-OF-LIFE; ABUSE TREATMENT; PRIMARY-CARE; AUDIT-C; IDENTIFICATION TEST; TREATMENT SERVICES; PROBLEM DRINKING AB Objective: The objective was to identify a potential core set of brief screeners for the detection of individuals with a substance use disorder (SUD) in medical settings. Method: Data were from two multisite studies that evaluated stimulant use outcomes of an abstinence-based contingency management intervention as an addition to usual care (National Drug Abuse Treatment Clinical Trials Network trials 006-007). The sample comprised 847 substance-using adults who were recruited from 12 outpatient substance abuse treatment settings across the United States. Alcohol and drug use disorders were assessed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Checklist. Data were analyzed by factor analysis, item response theory (IRT), sensitivity and specificity procedures. Results: Comparatively prevalent symptoms of dependence, especially inability to cut down for all substances, showed high sensitivity for detecting an SUD (low rate of false negative). IRT-defined severe (infrequent) and low discriminative items, especially withdrawal for alcohol, cannabis and cocaine, had low sensitivity in identifying cases of an SUD. IRT-defined less severe (frequent) and high discriminative items, including inability to cut down or taking larger amounts than intended for all substances and withdrawal for amphetamines and opioids, showed good-to-high values of area under the receiver operating characteristic curve in classifying cases and noncases of an SUD. Conclusion: Findings suggest the feasibility of identifying psychometrically reliable substance dependence symptoms to develop a two-item screen for alcohol and drug disorders. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wu, Li-Tzy; Swartz, Marvin S.; Burchett, Bruce; Mannelli, Paolo; Blazer, Dan G.] Duke Univ, Med Ctr, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Pan, Jeng-Jong] NCI, NIH, Rockville, MD 20852 USA. [Yang, Chongming] Duke Univ, Social Sci Res Inst, Durham, NC 27710 USA. RP Wu, LT (reprint author), Duke Univ, Med Ctr, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. EM litzy.wu@duke.edu FU U.S. National Institute on Drug Abuse of the National Institutes of Health [R21DA027503, R33DA027503, R01DA019623, R01DA019901, U10DA013034]; Eli Lilly; Alkermes, Inc.; AstraZeneca; Bristol-Myers Squibb; Cephalon, Inc.; Forest Research Institute; GlaxoSmithKline; Janssen Pharmaceuticals (Johnson Johnson); Jazz Pharmaceuticals; King Pharmaceuticals, Inc.; Lundbeck McNeil Consumer & Specialty Pharm.; Merck Co. USA; Orphan Medical; Pfizer Inc.; Pondera Pharmaceuticals, Inc.; Reckitt Benckiser; Sunovion Pharm; Titan Pharm FX This work was made possible by research grants from the U.S. National Institute on Drug Abuse of the National Institutes of Health (R21DA027503, R33DA027503, R01DA019623, and R01DA019901 to Li-Tzy Wu; U10DA013034 to Maxine L Stitzer). The Duke University Institutional Review Board approved use of these data for this study. The National Institutes of Health had no role in the design and conduct of the study; analysis and interpretation of the data; and preparation, review, or approval of the manuscript. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.; Marvin Swartz has served as a consultant to Novartis Pharmaceuticals and has received research support from Eli Lilly. Paolo Mannelli has received research support from Alkermes, Inc.; AstraZeneca; Bristol-Myers Squibb; Cephalon, Inc.; Forest Research Institute; GlaxoSmithKline; Janssen Pharmaceuticals (Johnson & Johnson); Jazz Pharmaceuticals; King Pharmaceuticals, Inc.; Lundbeck McNeil Consumer & Specialty Pharm.; Merck & Co. USA; Orphan Medical; Pfizer Inc.; Pondera Pharmaceuticals, Inc.; Reckitt Benckiser; Sunovion Pharm; and Titan Pharm. The other authors have no conflicts of interest to disclose. NR 57 TC 4 Z9 4 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2013 VL 35 IS 1 BP 74 EP 82 DI 10.1016/j.genhosppsych.2012.06.014 PG 9 WC Psychiatry SC Psychiatry GA 072BJ UT WOS:000313643000016 PM 22819723 ER PT J AU Bulea, TC Kobetic, R Audu, ML Schnellenberger, JR Triolo, RJ AF Bulea, Thomas C. Kobetic, Rudi Audu, Musa L. Schnellenberger, John R. Triolo, Ronald J. TI Finite State Control of a Variable Impedance Hybrid Neuroprosthesis for Locomotion After Paralysis SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE Controllable orthosis; functional neuromuscular stimulation (FNS); gait; hybrid neuroprosthesis (HNP); spinal cord injury ID FUNCTIONAL ELECTRICAL-STIMULATION; SPINAL-CORD-INJURY; KNEE FLEXION; GAIT; ORTHOSIS; WALKING; PARAPLEGIA; MECHANISM; RESTORATION; PROSTHESIS AB We have previously reported on a novel variable impedance knee mechanism (VIKM). The VIKM was designed as a component of a hybrid neuroprosthesis to regulate knee flexion. The hybrid neuroprosthesis is a device that uses a controllable brace to support the body against collapse while stimulation provides power for movement. The hybrid neuroprosthesis requires a control system to coordinate the actions of the VIKM with the stimulation system; the development and evaluation of such a controller is presented. Brace mounted sensors and a baseline open loop stimulation pattern are utilized as control signals to activate the VIKM during stance phase while simultaneously modulating muscle stimulation in an on-off fashion. The objective is twofold: reduce the amount of stimulation necessary for walking while simultaneously restoring more biologically correct knee motion during stance using the VIKM. Custom designed hardware and software components were developed for controller implementation. The VIKM hybrid neuroprosthesis (VIKM-HNP) was evaluated during walking in one participant with thoracic level spinal cord injury. In comparison to walking with functional neuromuscular stimulation alone, the VIKM-HNP restored near normal stance phase knee flexion during loading response and pre-swing phases while decreasing knee extensor stimulation by up to 40%. C1 [Bulea, Thomas C.] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA. [Kobetic, Rudi; Schnellenberger, John R.] Louis Stokes Cleveland Dept Vet Affairs Med Ctr, Mot Study Lab, Cleveland, OH 44106 USA. [Audu, Musa L.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Triolo, Ronald J.] Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. RP Bulea, TC (reprint author), NIH, Funct & Appl Biomech Sect, Bldg 10, Bethesda, MD 20892 USA. EM thomas.bulea@nih.gov; rkobetic@fescenter.org; musa.audu@case.edu; jschnel@aptcenter.org; ronald.triolo@case.edu FU U.S. Department of Veterans Affairs, Rehabilitation Research and Development [A6404R]; National Institutes of Health/ National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS) [T32 AR007505] FX This work was supported in part by the U.S. Department of Veterans Affairs, Rehabilitation Research and Development under Grant A6404R. The work of T. C. Bulea was supported by the National Institutes of Health/ National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS) under grant T32 AR007505. NR 45 TC 7 Z9 7 U1 3 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD JAN PY 2013 VL 21 IS 1 BP 141 EP 151 DI 10.1109/TNSRE.2012.2227124 PG 11 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 069GL UT WOS:000313423200017 PM 23193320 ER PT J AU Schuck-Paim, C Shanks, GD Almeida, FEA Alonso, WJ AF Schuck-Paim, Cynthia Shanks, G. Dennis Almeida, Francisco E. A. Alonso, Wladimir J. TI Exceptionally high mortality rate of the 1918 influenza pandemic in the Brazilian naval fleet SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE 1918; Brazil; influenza; navy; pandemic ID EPIDEMIOLOGIC EVIDENCE; RISK-FACTORS; INFECTIONS; PNEUMONIA; VIRUS; ARMY; AGE AB Please cite this paper as: Schuck-Paim et al. (2012) Exceptionally high mortality rate of the 1918 influenza pandemic in the Brazilian naval fleet. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00341.x. Background The naval experience with the 1918 pandemic during World War I remains underexplored despite its key role on the pandemics global diffusion and the epidemiological interest of isolated and relatively homogeneous populations. The pandemic outbreak in the Brazilian naval fleet is of particular interest both because of its severity and the fact that it was the only Latin American military force deployed to war. Objectives To study the mortality patterns of the pandemic in the Brazilian fleet sent to patrol the West African coast in 1918. Method We investigated mortality across vessels, ranks, and occupations based on official population and mortality records from the Brazilian Navy Archives. Results The outbreak that swept this fleet included the highest influenza mortality rate on any naval ship reported to date. Nearly 10% of the crews died, with death rates reaching 1314% on two destroyers. While overall mortality was lower for officers, stokers and engineer officers were significantly more likely to die from the pandemic, possibly due to the pulmonary damage from constant exposure to the smoke and coal dust from the boilers. Conclusions The fatality patterns observed provide valuable data on the conditions that can exacerbate the impact of a pandemic. While the putative lack of exposure to a first pandemic wave may have played a role in the excessive mortality observed in this fleet, our results indicate that strenuous labor conditions, dehydration, and exposure to coal dust were major risk factors. The unequal death rates among vessels remain an open question. C1 [Alonso, Wladimir J.] NIH, DIEPS, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Schuck-Paim, Cynthia; Alonso, Wladimir J.] Origem Sci, Sao Paulo, Brazil. [Shanks, G. Dennis] Australian Army Malaria Inst, Enoggera, Qld, Australia. [Almeida, Francisco E. A.] Naval War Coll, Rio De Janeiro, Brazil. RP Alonso, WJ (reprint author), NIH, DIEPS, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA. EM alonsow@mail.nih.gov RI Valle, Ruben/A-7512-2013; Shanks, George Dennis/F-4056-2014 OI Shanks, George Dennis/0000-0001-5763-8660 NR 30 TC 2 Z9 2 U1 2 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD JAN PY 2013 VL 7 IS 1 BP 27 EP 34 DI 10.1111/j.1750-2659.2012.00341.x PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 058QZ UT WOS:000312650000007 PM 22336427 ER PT J AU Talaat, KR Karron, RA Liang, PH McMahon, BA Luke, CJ Thumar, B Chen, GL Min, JY Lamirande, EW Jin, H Coelingh, KL Kemble, GW Subbarao, K AF Talaat, Kawsar R. Karron, Ruth A. Liang, Philana H. McMahon, Bridget A. Luke, Catherine J. Thumar, Bhagvanji Chen, Grace L. Min, Ji-Young Lamirande, Elaine W. Jin, Hong Coelingh, Kathy L. Kemble, George W. Subbarao, Kanta TI An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE H2N2; human; influenza; influenza vaccine; live attenuated influenza vaccines; neuraminidase inhibition ID AVIAN INFLUENZA; CELL RESPONSES; A VIRUSES; ANTIBODY; CHILDREN; EFFICACY; H3N2; METAANALYSIS; VOLUNTEERS; PROTECTION AB Please cite this paper as: Talaat et al. (2012) An open-label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00350.x. Background Live attenuated influenza vaccines (LAIV) against a variety of strains of pandemic potential are being developed and tested. We describe the results of an open-label phase I trial of a live attenuated H2N2 virus vaccine. Objectives To evaluate the safety, infectivity, and immunogenicity of a live attenuated H2N2 influenza virus vaccine. Participants/methods The A/Ann Arbor/6/60 (H2N2) virus used in this study is the attenuated, cold-adapted, temperature-sensitive strain that provides the genetic backbone of seasonal LAIV (MedImmune). We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of this vaccine administered by nasal spray 4 weeks apart to normal healthy seronegative adults. Results Twenty-one participants received a first dose of the vaccine; 18 participants received a second dose. No serious adverse events occurred during the trial. The most common adverse events after vaccination were headache and musculoskeletal pain. The vaccine was restricted in replication: 24% and 17% had virus detectable by culture or rRT-PCR after the first and second dose, respectively. Antibody responses to the vaccine were also restricted: 24% of participants developed an antibody response as measured by either hemagglutination-inhibition assay (10%), or ELISA for H2 HA-specific serum IgG (24%) or IgA (16%) after either one or two doses. None of the participants had a neutralizing antibody response. Vaccine-specific IgG-secreting cells as measured by enzyme-linked immunospot increased from a mean of 0.5 to 2.0/106 peripheral blood mononuclear cells (PBMCs); vaccine-specific IgA-secreting cells increased from 0.1 to 0.5/106 PBMCs. Conclusions The live attenuated H2N2 1960 AA ca vaccine demonstrated a safety profile consistent with seasonal trivalent LAIV but was restricted in replication and minimally immunogenic in healthy seronegative adults. C1 [Talaat, Kawsar R.; Karron, Ruth A.; Liang, Philana H.; McMahon, Bridget A.; Thumar, Bhagvanji] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Baltimore, MD USA. [Luke, Catherine J.; Chen, Grace L.; Min, Ji-Young; Lamirande, Elaine W.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Baltimore, MD USA. [Jin, Hong; Coelingh, Kathy L.; Kemble, George W.] MedImmune, Mountain View, CA USA. RP Talaat, KR (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Hampton House Room 249,624 N Broadway, Baltimore, MD 21205 USA. EM ktalaat@jhsph.edu FU NIAID, NIH [N01-AI-15444] FX We wish to thank Ruval Comendador, Jasmine Jennings, and Paula Williams-Soro for their expert clinical assistance, Susan DiLorenzo, Nicole Yoder, and Celia Santos for their expert technical assistance. We would also like to thank Bin Lu, Weidong Cui, Silas Nwagwu, Alfred Pan, Lynne Fitch, Patricia Ryan, So-Ching Brazer, David Prichett, Edith Matsuyama, and Zhongying Chen of MedImmune for vaccine manufacturing, testing, and making the reassortant H6 viruses for the NAI assay. This research was supported by the Intramural Research Program of the NIAID, NIH (N01-AI-15444). This research was performed as a Cooperative Research and Development Agreement (CRADA) (CRADA No: AI-0155) between the Laboratory of Infectious Diseases, NIAID and MedImmune. NR 35 TC 17 Z9 17 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD JAN PY 2013 VL 7 IS 1 BP 66 EP 73 DI 10.1111/j.1750-2659.2012.00350.x PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 058QZ UT WOS:000312650000011 PM 22417012 ER PT J AU Pepin, KM Wang, J Webb, CT Smith, GJD Poss, M Hudson, PJ Hong, WS Zhu, HC Riley, S Guan, Y AF Pepin, Kim M. Wang, Jia Webb, Colleen T. Smith, Gavin J. D. Poss, Mary Hudson, Peter J. Hong, Wenshan Zhu, Huachen Riley, Steven Guan, Yi TI Multiannual patterns of influenza A transmission in Chinese live bird market systems SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Avian influenza; coinfection; H5N1; host specificity; live bird market; risk ID AVIAN INFLUENZA; SOUTHERN CHINA; HONG-KONG; POULTRY MARKETS; VIRUS H5N1; INTERSPECIES TRANSMISSION; CONTINUING EVOLUTION; SOUTHEASTERN CHINA; HUMAN INFECTION; FOOD MARKETS AB Please cite this paper as: Pepin et al. (2012) Multiannual patterns of influenza A transmission in Chinese live bird market systems. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2012.00354.x. Background Avian influenza viruses (AIV) cause huge economic losses in poultry industries and pose a substantial threat to human health. However, predicting AIV epizootics and emergence in humans is confounded by insufficient empirical data on the ecology and dynamics of AIV in poultry systems. To address this gap, we quantified incidence patterns for 13 hemagglutinin subtypes of AIV using 6 years of surveillance data that were collected from ten different species of poultry and three different types of poultry holdings (contexts) retail, wholesale, or farms. Methods We collected 42 646 samples in Shantou, China between 2000 and 2006. We screened samples for hemagglutinin subtypes 113 of AIV and Avian Paramyxovirus-type-1 (APMV-1) using monospecific antisera in hemagglutination inhibition tests. We analyzed the data to determine seasonality patterns, subtypehost, and subtypesubtype interactions as well as subtype bias in incidence in different contexts. Results H3, H6, H9, and APMV-1 were the most prevalent. No significant seasonality was found when all subtypes were considered together. For most AIV subtypes and APMV-1, there was subtype specificity for host, context, and coinfection partner. H5 showed the most generalized host usage pattern, followed by H9 and H6. Conclusion Subtype-specific patterns because of host, context, and other subtypes suggest that risk assessments that exclude these details are likely inaccurate. Surveillance should include longitudinal sampling of multiple host species in multiple contexts. Quantitative models of control strategies must consider multiple subtypes, hosts, and source contexts to assess the effectiveness of interventions. C1 [Pepin, Kim M.; Wang, Jia; Webb, Colleen T.; Smith, Gavin J. D.; Hong, Wenshan; Zhu, Huachen; Riley, Steven; Guan, Yi] Shantou Univ, Coll Med, Int Inst Infect & Immun, Shantou, Peoples R China. [Pepin, Kim M.] Colorado State Univ, Ft Collins, CO 80523 USA. [Pepin, Kim M.; Webb, Colleen T.; Poss, Mary; Hudson, Peter J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Wang, Jia; Zhu, Huachen; Guan, Yi] Univ Hong Kong, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. [Smith, Gavin J. D.] Duke NUS Grad Med Sch, Singapore, Singapore. [Poss, Mary; Hudson, Peter J.] Penn State Univ, State Coll, PA USA. [Riley, Steven] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Outbreak Anal & Modelling, London, England. RP Riley, S (reprint author), St Marys Hosp, Sch Med, Dept Infect Dis Epidemiol, Norfolk Pl, London W2 1PG, England. EM s.riley@imperial.ac.uk; yguan@hkucc.hku.hk RI Zhu, Huachen/A-8252-2017; OI Zhu, Huachen/0000-0003-2711-0501; Smith, Gavin JD/0000-0001-5031-468X FU National Institutes of Health (National Institute of Allergy and Infectious Diseases) [HSN266200700005C]; Li Ka Shing Foundation; Area of Excellence Scheme of the UGC of the Hong Kong SAR [AoE/M-12/06]; RAPIDD program of the Science and Technology Directorate, US Department of Homeland Security; Fogarty International Center, NIH; National Science Foundation [0742373]; NIH Fogarty Center [R01 TW008246-01]; US National Institutes of Health MIDAS program; Wellcome Trust FX This work was supported by the National Institutes of Health (National Institute of Allergy and Infectious Diseases contract HSN266200700005C); Li Ka Shing Foundation; Area of Excellence Scheme of the UGC of the Hong Kong SAR (grant AoE/M-12/06), and the RAPIDD program of the Science and Technology Directorate, US Department of Homeland Security, and the Fogarty International Center, NIH. KMP was also supported by National Science Foundation grant 0742373. SR also thanks the NIH Fogarty Center (R01 TW008246-01), US National Institutes of Health MIDAS program, and the Wellcome Trust (University Award). NR 51 TC 18 Z9 20 U1 1 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD JAN PY 2013 VL 7 IS 1 BP 97 EP 107 DI 10.1111/j.1750-2659.2012.00354.x PG 11 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 058QZ UT WOS:000312650000015 PM 22458429 ER PT J AU Forrest, D Wess, J AF Forrest, Douglas Wess, Juergen TI A heartfelt response: new thyroid hormone-sensitive neurons in the hypothalamus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID RECEPTOR-ALPHA GENE; NERVOUS-SYSTEM; MUTATION; MICE AB Thyroid hormone is a well-known regulator of metabolic and cardiovascular functions, and signaling through thyroid receptors has differential effects on cells depending on the receptor isoform that they express. In this issue of the JCI, Mittag et al. provide evidence that thyroid hormone receptors are essential for the formation of a population of parvalbuminergic neurons in the anterior hypothalamus, linking, for the first time, impaired thyroid hormone signaling during development to cellular deficits in the hypothalamus. Since this newly discovered cell group is predicted to play a role in regulating cardiovascular function, these findings suggest that developmental hypothyroidism may be the cause of cardiovascular disorders later in life. C1 [Forrest, Douglas] NIDDK, Nucl Receptor Biol Sect, Lab Endocrinol & Receptor Biol, Bethesda, MD 20892 USA. [Wess, Juergen] NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, Mol Signaling Sect, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov FU Intramural NIH HHS NR 20 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2013 VL 123 IS 1 BP 117 EP 120 DI 10.1172/JCI67448 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500019 PM 23257363 ER PT J AU Jessen, WJ Miller, SJ Jousma, E Wu, JQ Rizvi, TA Brundage, ME Eaves, D Widemann, B Kim, MO Dombi, E Sabo, J Dudley, AH Niwa-Kawakita, M Page, GP Giovannini, M Aronow, BJ Cripe, TP Ratner, N AF Jessen, Walter J. Miller, Shyra J. Jousma, Edwin Wu, Jianqiang Rizvi, Tilat A. Brundage, Meghan E. Eaves, David Widemann, Brigitte Kim, Mi-Ok Dombi, Eva Sabo, Jessica Dudley, Atira Hardiman Niwa-Kawakita, Michiko Page, Grier P. Giovannini, Marco Aronow, Bruce J. Cripe, Timothy P. Ratner, Nancy TI MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NERVE SHEATH TUMORS; PREVIOUSLY TREATED PATIENTS; SCHWANN-CELLS; PLEXIFORM NEUROFIBROMAS; THERAPEUTIC TARGET; SIGNALING PATHWAYS; GENOMIC ANALYSES; HYPERACTIVE RAS; NF1; CANCER AB Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1N(fl/fl);Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials. C1 [Jessen, Walter J.; Miller, Shyra J.; Jousma, Edwin; Wu, Jianqiang; Rizvi, Tilat A.; Brundage, Meghan E.; Eaves, David; Dudley, Atira Hardiman; Cripe, Timothy P.; Ratner, Nancy] Childrens Hosp, Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Widemann, Brigitte; Dombi, Eva; Sabo, Jessica] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Kim, Mi-Ok] Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. [Niwa-Kawakita, Michiko] Inst Natl Sante & Rech Med, Paris, France. [Page, Grier P.] RTI Int, Stat & Epidemiol Unit, S Chamblee, GA USA. [Giovannini, Marco] House Ear Res Inst, Dept Neural Tumor Res, Los Angeles, CA USA. RP Ratner, N (reprint author), Childrens Hosp, Med Ctr, Div Expt Hematol & Canc Biol, 3333 Burnet Ave,MLC 7013, Cincinnati, OH 45229 USA. EM Nancy.Ratner@cchmc.org RI Kim, Mi-Ok/O-9626-2015; OI Jessen, Walter/0000-0003-3840-4337 FU DAMD Program on Neurofibromatosis for the NF1 Microarray Consortium [DODW81XWH- 09-1-0135, W81XWH-04-1-0273]; Children's Tumor Foundation; Bench to Bedside Award for MRI Analyses [NIH-P50-NS05753]; AREA [R01-NS28840] FX We thank Jan Manent for processing human nerve samples, Kevin Shannon (UCSF) for numerous helpful discussions and providing the mutant MEK L115P construct, Pfizer for providing PD0325901 for preclinical testing, and Mila McCurrach for organization of the CTF Preclinical Consortium. We thank Margaret Collins (CCHMC) for providing human tissue samples. We gratefully acknowledge support from the DAMD Program on Neurofibromatosis for the NF1 Microarray Consortium (DODW81XWH- 09-1-0135 and W81XWH-04-1-0273 to N. Ratner) and the Children's Tumor Foundation for support to the NF1 Preclinical Consortium (to T.P. Cripe and N. Ratner), and a Bench to Bedside Award for MRI Analyses (NIH-P50-NS05753). W.J. Jessen was supported in part by an AREA supplement to NIH grant R01-NS28840. NR 62 TC 84 Z9 87 U1 0 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN PY 2013 VL 123 IS 1 BP 340 EP 347 DI 10.1172/JCI60578 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 071MV UT WOS:000313598500038 PM 23221341 ER PT J AU Buckley, A Wingert, K Swedo, S Thurm, A Sato, S Appel, S Rodriguez, AJ AF Buckley, Ashura Wingert, Katherine Swedo, Susan Thurm, Audrey Sato, Susumu Appel, Shmuel Rodriguez, Alcibiades J. TI First Night Effect Analysis in a Cohort of Young Children with Autism Spectrum Disorder SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Autism; first night effect ID SLEEP; DEPRESSION; POLYSOMNOGRAPHY; ADOLESCENTS AB Study Objectives: To evaluate for the first night effect (FNE) in a group of young children with autism. Design: Analysis of polysomnographic data from a 2-night sleep laboratory study. Setting: Clinical Center of the National Institutes of Health. Patients or Participants: 15 children (aged 2-10 years) with a diagnosis of an ASD. Interventions: None. Measurements and Results: Polysomnographic analysis showed the presence of a FNE for wake after sleep onset minutes, stage 2, and sleep efficiency, but not for REM sleep parameters or TST. Conclusions: In this 2-night polysomnographic analysis of sleep stages in young children with autism, we did not find the expected second night increase in total sleep time or REM sleep percentage or a decrease in REM sleep latency. This lack of an FNE for TST and REM parameters suggests that a single-night polysomnogram may be sufficient to evaluate children with an ASD for TST or REM parameters. C1 [Buckley, Ashura; Wingert, Katherine; Swedo, Susan; Thurm, Audrey] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20982 USA. [Sato, Susumu; Appel, Shmuel] NINDS, EEG Sect, Bethesda, MD 20892 USA. [Rodriguez, Alcibiades J.] NYU, Dept Neurol, New York, NY 10016 USA. RP Buckley, A (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,Bldg 10,Room 1C250,MSC 1255, Bethesda, MD 20982 USA. EM Shu.buckley@nih.gov NR 20 TC 2 Z9 2 U1 1 U2 8 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 1 BP 67 EP 70 DI 10.5664/jcsm.2344 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 072DW UT WOS:000313650200011 PM 23319907 ER PT J AU Ojode, T Schneider, EH Tiffany, HL Yung, S Gao, JL Murphy, PM AF Ojode, Teresa Schneider, Erich H. Tiffany, H. Lee Yung, Sunny Gao, Ji-Liang Murphy, Philip M. TI The Major Leukocyte Chemotactic and Activating Factors in the Mouse Gut Lumen Are Not N-Formylpeptide Receptor 1 Agonists SO JOURNAL OF INNATE IMMUNITY LA English DT Article DE Microbiome; Chemotaxis; Inflammation; Formylpeptide; G-protein-coupled receptor ID FORMYL-PEPTIDE RECEPTORS; EPITHELIAL MONOLAYERS; DENDRITIC CELLS; LISTERIA-MONOCYTOGENES; BACTERIAL-DNA; FPR; CHEMOATTRACTANTS; IDENTIFICATION; NEUTROPHILS; MICROBIOTA AB Cultured bacteria release N-formylpeptides, which are potent chemoattractants for phagocytic leukocytes acting at G-protein-coupled receptors FPR1 and FPR2. However, the distribution and immunologic activity of these molecules at mucosal surfaces, where large numbers of bacteria are separated from the immune system by epithelium, remain undefined. To investigate this for the gut, we tested leukocyte responses to cell-free gut luminal contents from C57Bl/6 mice fed a chow diet. Small and large intestine contents were able to compete with labeled N-formylpeptide for binding to FPR1, indicating the presence of FPR1 ligands in the gut lumen. Material from both small and large intestine induced robust calcium flux responses by primary FPR1(+) leukocytes (mouse bone marrow cells and splenocytes and human peripheral blood neutrophils and mononuclear cells), as well as chemotactic responses by both mouse bone marrow cells and human peripheral blood neutrophils. However, unlike defined N-formylpeptides, calcium flux responses induced by gut luminal contents were insensitive both to pertussis toxin treatment of leukocytes and to proteinase K digestion of the samples. Moreover, the gut samples were fully active on neutrophils from mice lacking Fpr1, and the kinetics of the calcium flux response differed markedly for neutrophils and peripheral blood mononuclear cells. The active factor(s) could be dialyzed using a 3.5-kDa pore size membrane. Thus, mouse intestinal lumen contains small, potent and highly efficacious leukocyte chemotactic and activating factors that may be distinct from neutrophils and peripheral blood mononuclear cells and distinct from Fpr1 agonists. Copyright (C) 2012 S. Karger AG, Basel C1 [Ojode, Teresa; Schneider, Erich H.; Tiffany, H. Lee; Yung, Sunny; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signaling Sect, Lab Mol Immunol, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov RI Schneider, Erich/B-9051-2016 OI Schneider, Erich/0000-0002-7905-4276 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; NIH Academy FX This work was supported by funding from the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.; T.O. is a recipient of a post-baccalaureate fellowship of the NIH Academy. NR 28 TC 3 Z9 3 U1 0 U2 11 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1662-811X J9 J INNATE IMMUN JI J. Innate Immun. PY 2013 VL 5 IS 1 BP 2 EP 14 DI 10.1159/000339572 PG 13 WC Immunology SC Immunology GA 070VP UT WOS:000313541600002 PM 22722599 ER PT J AU Zeng, Y Liu, G Ma, Y Chen, XY Ito, Y AF Zeng, Yun Liu, Gang Ma, Ying Chen, Xiaoyuan Ito, Yoichiro TI ORGANIC-HIGH IONIC STRENGTH AQUEOUS SOLVENT SYSTEMS FOR SPIRAL COUNTER-CURRENT CHROMATOGRAPHY: GRAPHIC OPTIMIZATION OF PARTITION COEFFICIENT SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE catecholamines; graphic optimization of partition coefficient; organic-high ionic strength aqueous solvent system series; spiral high-speed counter-current chromatography; sulfonic acids; zwitter ions ID SPEED; SEPARATION AB A new series of organic-high ionic strength aqueous two-phase solvents systems was designed for separation of highly polar compounds by spiral high-speed counter-current chromatography. A total of 21 solvent systems composed of 1-butanol-ethanol-saturated ammonium sulfate-water at various volume ratios are arranged according to an increasing order of polarity. Selection of the two-phase solvent system for a single compound or a multiple sample mixture can be achieved by two steps of partition coefficient measurements using a graphic method. The capability of the method is demonstrated by optimization of partition coefficient for seven highly polar samples including tartrazine (K = 0.77), tryptophan (K = 1.00), methyl green (K = 0.93), tyrosine (0.81), metanephrine (K = 0.89), tyramine (K = 0.98), and normetanephrine (K = 0.96). Three sulfonic acid components in D&C Green No. 8 were successfully separated by HSCCC using the graphic selection of the two-phase solvent system. C1 [Zeng, Yun; Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. [Zeng, Yun; Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen, Peoples R China. [Ma, Ying; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA. [Liu, Gang] N Sichuan Med Coll, Affiliated Hosp, Sichuan Key Lab Med Imaging, Nanchong, Sichuan Provinc, Peoples R China. RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU National Institutes of Health (NIH); Sichuan Province [09ZA036, KFJJ0905/0807, 2011JQ0032]; National Natural Science Foundation of China [81101101] FX This work was supported by the Intramural Research Program (IRP) of the National Institutes of Health (NIH). The work also was partially supported by projects (No. 09ZA036, KFJJ0905/0807, and 2011JQ0032) of Sichuan Province and National Natural Science Foundation of China (81101101). NR 14 TC 5 Z9 5 U1 2 U2 22 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PD JAN 1 PY 2013 VL 36 IS 4 BP 504 EP 512 DI 10.1080/10826076.2012.660725 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 069FF UT WOS:000313420000007 PM 23467197 ER PT J AU Carrington, LB Seifert, SN Willits, NH Lambrechts, L Scott, TW AF Carrington, Lauren B. Seifert, Stephanie N. Willits, Neil H. Lambrechts, Louis Scott, Thomas W. TI Large Diurnal Temperature Fluctuations Negatively Influence Aedes aegypti (Diptera: Culicidae) Life-History Traits SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Aedes aegypti; Thailand; dengue virus; life-history trait; temperature fluctuation ID LARVAL ENVIRONMENTAL-TEMPERATURE; VECTOR COMPETENCE; ADULT LONGEVITY; DENGUE-FEVER; CLIMATE; VIRUS; TRANSMISSION; AUSTRALIA; MOSQUITOS; SURVIVAL AB Seasonal variation in dengue virus transmission in northwestern Thailand is inversely related to the magnitude of diurnal temperature fluctuations, although mean temperature does not vary significantly across seasons. We tested the hypothesis that diurnal temperature fluctuations negatively influence epidemiologically important life-history traits of the primary dengue vector, Aedes aegypti (L.), compared with a constant 26 degrees C temperature. A large diurnal temperature range (DTR) (approximate to 18 degrees C daily swing) extended immature development time (> 1 d), lowered larval survival (approximate to 6%), and reduced adult female reproductive output by 25% 14 d after blood feeding, relative to the constant 26 degrees C temperature. A small DTR (approximate to 8 degrees C daily swing) led to a negligible or slightly positive effect on the life history traits tested. Our results indicate that there is a negative impact of large DTR on mosquito biology and are consistent with the hypothesis that, in at least some locations, large temperature fluctuations contribute to seasonal reduction in dengue virus transmission. C1 [Carrington, Lauren B.; Seifert, Stephanie N.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Willits, Neil H.] Univ Calif Davis, Dept Stat, Davis, CA USA. [Lambrechts, Louis] Inst Pasteur, CNRS, Unite Rech Associee 3012, Paris, France. [Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Carrington, LB (reprint author), Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. EM lbcarrington@ucdavis.edu RI Carrington, Lauren/B-8269-2013; Lambrechts, Louis/A-2057-2010; OI Lambrechts, Louis/0000-0001-5958-2138; Carrington, Lauren Bree/0000-0001-9273-7912 FU National Science Foundation [EF-0914384] FX We thank W. K. Reisen for continued practical and material support; A. Ponlawat for collecting and sending mosquito eggs; S. Olkowski for technical support during experiments, M. V. Armijos, S. A. Juliano, and three anonymous reviewers for providing constructive comments on earlier versions of the manuscript. This research benefited from discussions with working group members in the Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health and was funded by grant EF-0914384 from the Ecology of Infectious Disease program of the National Science Foundation. NR 33 TC 32 Z9 35 U1 3 U2 51 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JAN PY 2013 VL 50 IS 1 BP 43 EP 51 DI 10.1603/ME11242 PG 9 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 071EV UT WOS:000313570600006 PM 23427651 ER PT J AU Betsou, F Gunter, E Clements, J DeSouza, Y Goddard, KAB Guadagni, F Yan, WS Skubitz, A Somiari, S Yeadon, T Chuaqui, R AF Betsou, Fotini Gunter, Elaine Clements, Judith DeSouza, Yvonne Goddard, Katrina A. B. Guadagni, Fiorella Yan, Wusheng Skubitz, Amy Somiari, Stella Yeadon, Trina Chuaqui, Rodrigo TI Identification of Evidence-Based Biospecimen Quality-Control Tools A Report of the International Society for Biological and Environmental Repositories (ISBER) Biospecimen Science Working Group SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID WHOLE-GENOME AMPLIFICATION; POLYMERASE CHAIN-REACTION; PARAFFIN-EMBEDDED TISSUE; PLASMA ASCORBIC-ACID; GENE-EXPRESSION; STORAGE-CONDITIONS; CLINICAL-SAMPLES; STABILITY; RNA; SERUM AB Control of biospecimen quality that is linked to processing is one of the goals of biospecimen science. Consensus is tacking, however, regarding optimal sample quality-control (QC) tools (ie, markers and assays). The aim of this review was to identify QC tools, both for fluid and solid-tissue samples, based on a comprehensive and critical literature review. The most readily applicable tools are those with a known threshold for the preanalytical variation and a known reference range for the QC analyte. Only a few meaningful markers were identified that meet these criteria, such as CD40L for assessing serum exposure at high temperatures and VEGF for assessing serum freeze-thawing. To fully assess biospecimen quality, multiple QC markers are needed. Here we present the most promising biospecimen QC tools that were identified. (J Mal Diagn 2013, 15: 3-16; http://dx.doi.org/10.1016/j.jmoldx.2012.06.008) C1 [Betsou, Fotini] Integrated Biobank Luxembourg, Luxembourg, Luxembourg. [Gunter, Elaine] Specimen Solut LLC, Tucker, GA USA. [Clements, Judith; Yeadon, Trina] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Kelvin Grove, Australia. [DeSouza, Yvonne] Univ Calif San Francisco, AIDS Specimen Bank, San Francisco, CA 94143 USA. [Goddard, Katrina A. B.] Kaiser Permanente NW, Ctr Hlth Res, Portland, OR USA. [Guadagni, Fiorella] IRCCS San Raffaele Pisana, Dept Lab Med & Adv Biotechnol, Interinst Multidisciplinary Biobank BioBIM, Rome, Italy. [Yan, Wusheng] NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Chuaqui, Rodrigo] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Skubitz, Amy] Univ Minnesota, Dept Lab Med & Pathol, BioNet Tissue Procurement Facil, Minneapolis, MN 55455 USA. [Somiari, Stella] Windber Res Inst, Windber, PA USA. RP Betsou, F (reprint author), IBBL Integrated Biobank Luxembourg, 6 Rue Ernest Barble, L-1210 Luxembourg, Luxembourg. EM fay.betsou@ibbl.lu RI Guadagni, Fiorella/J-4432-2013; OI Guadagni, Fiorella/0000-0003-3652-0457; Clements, Judith/0000-0001-6026-1964 FU NIAID NIH HHS [P30 AI027763] NR 61 TC 23 Z9 24 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2013 VL 15 IS 1 BP 3 EP 16 DI 10.1016/j.jmoldx.2012.06.008 PG 14 WC Pathology SC Pathology GA 071PA UT WOS:000313605500002 PM 23195791 ER PT J AU Ahren, E AF Ahren, Eva TI The Lady Anatomist: The Life and Work of Anna Morandi Manzolini SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review DE Bologna; anatomy C1 [Ahren, Eva] Off Hist, NIH, Bethesda, MD USA. RP Ahren, E (reprint author), Off Hist, NIH, Bethesda, MD USA. EM eva.ahren@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JAN PY 2013 VL 68 IS 1 BP 131 EP 133 DI 10.1093/jhmas/jrs040 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 058GT UT WOS:000312622800005 ER PT J AU Chang, R Butman, JA Lonser, RR Sherry, RM Pandalai, PK Horne, MK Lozier, JN AF Chang, Richard Butman, John A. Lonser, Russell R. Sherry, Richard M. Pandalai, Prakash K. Horne, McDonald K., III Lozier, Jay N. TI Treatment of High-risk Venous Thrombosis Patients Using Low-dose Intraclot Injections of Recombinant Tissue Plasminogen Activator and Regional Anticoagulation SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID DEEP-VEIN THROMBOSIS; THROMBOLYTIC THERAPY; LOWER-EXTREMITY; T-PA; ALTEPLASE; HEPARIN; SAFETY; THROMBOEMBOLISM; COMPLICATIONS; UROKINASE AB Seven patients with venous thrombosis and contraindications to traditional thrombolytic therapy, consisting of recent intracranial surgery, recent pineal or retroperitoneal hemorrhage, active genitourinary or gastrointestinal bleeding, epidural procedures, and impending surgery, were successfully treated with a modified thrombolytic regimen. To improve safety, prolonged continuous infusions of tissue plasminogen activator (tPA) was eliminated in favor of once-daily low-dose intraclot injections of tPA to minimize the amount and duration of tPA in the systemic circulation, and low-therapeutic or regional anticoagulation was used to reduce anticoagulant risks. These modifications may allow thrombolytic treatment for selected patients with severe venous thrombosis who are deemed to be at high risk. C1 [Chang, Richard; Butman, John A.] Warren G Magnuson Clin Ctr, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. [Horne, McDonald K., III; Lozier, Jay N.] Warren G Magnuson Clin Ctr, Hematol Serv, Dept Lab Med, Bethesda, MD 20892 USA. [Lonser, Russell R.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Sherry, Richard M.; Pandalai, Prakash K.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Chang, R (reprint author), Warren G Magnuson Clin Ctr, Radiol & Imaging Sci Dept, 9000 Rockville Pk,Bldg 10,Room 1C-338, Bethesda, MD 20892 USA. EM rchang@cc.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU National Institutes of Health FX The treatments described in this study were supported by funding provided through National Institutes of Health research protocols under which the patients were already enrolled. NR 14 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2013 VL 24 IS 1 BP 27 EP 34 DI 10.1016/j.jvir.2012.09.017 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 071MT UT WOS:000313598300005 PM 23273695 ER PT J AU Lipkowitz, MS Freedman, BI Langefeld, CD Comeau, ME Bowden, DW Kao, WHL Astor, BC Bottinger, EP Iyengar, SK Klotman, PE Freedman, RG Zhang, WJ Parekh, RS Choi, MJ Nelson, GW Winkler, CA Kopp, JB AF Lipkowitz, Michael S. Freedman, Barry I. Langefeld, Carl D. Comeau, Mary E. Bowden, Donald W. Kao, W. H. Linda Astor, Brad C. Bottinger, Erwin P. Iyengar, Sudha K. Klotman, Paul E. Freedman, Richard G. Zhang, Weijia Parekh, Rulan S. Choi, Michael J. Nelson, George W. Winkler, Cheryl A. Kopp, Jeffrey B. CA AASK Investigators TI Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans SO KIDNEY INTERNATIONAL LA English DT Article DE AASK (African American Study of Kidney Disease and Hypertension); APOL1; chronic kidney disease; ethnic minority; human genetics; hypertension ID STAGE RENAL-DISEASE; AASK TRIAL; EUROPEAN-AMERICANS; MYH9; NEPHROSCLEROSIS; PROGRESSION; APOL1; RISK; POLYMORPHISMS AB Despite intensive antihypertensive therapy there was a high incidence of renal end points in participants of the African American Study of Kidney Disease and Hypertension (AASK) cohort. To better understand this, coding variants in the apolipoprotein L1 (APOL1) and the nonmuscle myosin heavy chain 9 (MYH9) genes were evaluated for an association with hypertension-attributed nephropathy and clinical outcomes in a case-control study. Clinical data and DNA were available for 675 AASK participant cases and 618 African American non-nephropathy control individuals. APOL1 G1 and G2, and MYH9 El variants along with 44 ancestry informative markers, were genotyped with allele frequency differences between cases and controls analyzed by logistic regression multivariable models adjusting for ancestry, age, and gender. In recessive models, APOL1 risk variants were significantly associated with kidney disease in all cases compared to controls with an odds ratio of 2.57. In AASK cases with more advanced disease, such as a baseline urine protein to creatinine ratio over 0.6 g/g or a serum creatinine over 3 mg/dl during follow-up, the association was strengthened with odds ratios of 6.29 and 4.61, respectively. APOL1 risk variants were consistently associated with renal disease progression across medication classes and blood pressure targets. Thus, kidney disease in AASK participants was strongly associated with APOL1 renal risk variants. Kidney International (2012) 83, 114-120; doi:10.1038/ki.2012.263; published online 25 July 2012 C1 [Lipkowitz, Michael S.] Georgetown Univ, Sch Med, Div Nephrol & Hypertens, Dept Med, Washington, DC 20007 USA. [Freedman, Barry I.; Freedman, Richard G.] Wake Forest Sch Med, Nephrol Sect, Dept Internal Med, Winston Salem, NC USA. [Langefeld, Carl D.; Comeau, Mary E.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Bowden, Donald W.] Wake Forest Sch Med, Ctr Diabet Res, Dept Biochem, Winston Salem, NC USA. [Bowden, Donald W.] Wake Forest Sch Med, Ctr Human Genom & Personalized Med, Dept Biochem, Winston Salem, NC USA. [Kao, W. H. Linda] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Kao, W. H. Linda; Parekh, Rulan S.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Astor, Brad C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Nephrol, Madison, WI USA. [Bottinger, Erwin P.] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA. [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Ophthalmol, Cleveland, OH 44106 USA. [Klotman, Paul E.] Baylor Coll Med, Houston, TX 77030 USA. [Zhang, Weijia] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY USA. [Parekh, Rulan S.] Univ Hlth Network, Hosp Sick Children, Dept Pediat, Toronto, ON, Canada. [Parekh, Rulan S.] Univ Hlth Network, Hosp Sick Children, Dept Med, Toronto, ON, Canada. [Parekh, Rulan S.] Univ Toronto, Toronto, ON, Canada. [Choi, Michael J.] Johns Hopkins Univ, Dept Internal Med, Div Nephrol, Baltimore, MD USA. [Nelson, George W.; Winkler, Cheryl A.] SAIC Frederick, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD USA. [Kopp, Jeffrey B.] Natl Inst Diabet & Digest & Kidney Disorders, Kidney Dis Sect, Bethesda, MD USA. RP Lipkowitz, MS (reprint author), Georgetown Univ, Sch Med, Div Nephrol & Hypertens, Dept Med, Washington, DC 20007 USA. EM Michael.S.Lipkowitz@gunet.georgetown.edu; bfreedma@wake-health.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU National Institutes of Health (NIH) [RO1 DK066358, RO1 DK053591, RO1 HL56266, RO1 DK070941, RO1 DK084149, RO1 DK057867, DK048689, RO1 DK72367]; General Research Center for the Wake Forest School of Medicine [HHSN261200800001E]; Intramural Research Program of NIH, Frederick National Laboratory for Cancer Research FX This work was funded in part by the National Institutes of Health (NIH) grants RO1 DK066358 (DWB), RO1 DK053591 (DWB), RO1 HL56266 (BIF), RO1 DK070941 (BIF), RO1 DK084149 (BIF), RO1 DK057867 (MSL), DK048689 (MSL) and RO1 DK72367 (WHLK and RSP), and in part by the General Research Center for the Wake Forest School of Medicine, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Intramural Research Program of NIH, Frederick National Laboratory for Cancer Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 85 Z9 87 U1 2 U2 11 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 JAN PY 2013 VL 83 IS 1 BP 114 EP 120 DI 10.1038/ki.2012.263 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 068ST UT WOS:000313387200017 PM 22832513 ER PT J AU Kendall, GM Little, MP Wakeford, R Bunch, KJ Miles, JCH Vincent, TJ Meara, JR Murphy, MFG AF Kendall, G. M. Little, M. P. Wakeford, R. Bunch, K. J. Miles, J. C. H. Vincent, T. J. Meara, J. R. Murphy, M. F. G. TI A record-based case-control study of natural background radiation and the incidence of childhood leukaemia and other cancers in Great Britain during 1980-2006 SO LEUKEMIA LA English DT Article DE cancer; childhood; radiation; radon; gamma rays ID IONIZING-RADIATION; UNITED-KINGDOM; DOMESTIC SOURCES; INDOOR RADON; EXPOSURE; RISK; PROPORTION; CHILDREN; ENGLAND; WALES AB We conducted a large record-based case-control study testing associations between childhood cancer and natural background radiation. Cases (27 447) born and diagnosed in Great Britain during 1980-2006 and matched cancer-free controls (36 793) were from the National Registry of Childhood Tumours. Radiation exposures were estimated for mother's residence at the child's birth from national databases, using the County District mean for gamma rays, and a predictive map based on domestic measurements grouped by geological boundaries for radon. There was 12% excess relative risk (ERR) (95% CI 3, 22; two-sided P = 0.01) of childhood leukaemia per millisievert of cumulative red bone marrow dose from gamma radiation; the analogous association for radon was not significant, ERR 3% (95% CI -4, 11; P = 0.35). Associations for other childhood cancers were not significant for either exposure. Excess risk was insensitive to adjustment for measures of socio-economic status. The statistically significant leukaemia risk reported in this reasonably powered study (power similar to 50%) is consistent with high-dose rate predictions. Substantial bias is unlikely, and we cannot identify mechanisms by which confounding might plausibly account for the association, which we regard as likely to be causal. The study supports the extrapolation of high-dose rate risk models to protracted exposures at natural background exposure levels. Leukemia (2013) 27, 3-9; doi:10.1038/leu.2012.151 C1 [Kendall, G. M.; Bunch, K. J.; Vincent, T. J.; Murphy, M. F. G.] Univ Oxford, Childhood Canc Res Grp, Oxford OX3 7LG, England. [Little, M. P.] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Wakeford, R.] Univ Manchester, Dalton Nucl Inst, Manchester, Lancs, England. [Meara, J. R.] Hlth Protect Agcy, Ctr Radiat Chem & Environm, Hazards, Oxon, England. RP Kendall, GM (reprint author), Univ Oxford, Childhood Canc Res Grp, New Richards Bldg,Old Rd Campus, Oxford OX3 7LG, England. EM Gerald.Kendall@ccrg.ox.ac.uk OI Wakeford, Richard/0000-0002-2934-0987; Little, Mark/0000-0003-0980-7567 FU Department of Health for England and Wales, Scottish Government; CHILDREN with CANCER (UK) FX We are grateful for the detailed and helpful comments of the two referees. This work was supported by the Department of Health for England and Wales, Scottish Government and CHILDREN with CANCER (UK), but these organisations had no role in study design, the collection, analysis, and interpretation of data, the writing of the article nor in the decision to submit it for publication. We thank the British Geological Survey for allowing the use of the HPA/BGS radon map and to Royal Mail and Ordnance Survey for making available ADDRESS-POINT data (Crown Copyright. All rights reserved). Colleagues at the Childhood Cancer Research Group undertook the geocoding of addresses and social class codings for occupations. We also thank Dr Gerald Draper and Mr Charles Stiller for advice and to Drs Ethel Gilbert, Colin Muirhead and Mark Pearce for commenting on a draft manuscript. NR 43 TC 55 Z9 61 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2013 VL 27 IS 1 BP 3 EP 9 DI 10.1038/leu.2012.151 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 070MP UT WOS:000313511400002 PM 22766784 ER PT J AU Katzmann, JA Clark, R Kyle, RA Larson, DR Therneau, TM Melton, LJ Benson, JT Colby, CL Dispenzieri, A Landgren, O Kumar, S Bradwell, AR Cerhan, JR Rajkumar, SV AF Katzmann, J. A. Clark, R. Kyle, R. A. Larson, D. R. Therneau, T. M. Melton, L. J., III Benson, J. T. Colby, C. L. Dispenzieri, A. Landgren, O. Kumar, S. Bradwell, A. R. Cerhan, J. R. Rajkumar, S. V. TI Suppression of uninvolved immunoglobulins defined by heavy/light chain pair suppression is a risk factor for progression of MGUS SO LEUKEMIA LA English DT Article DE MGUS; multiple myeloma; prognosis; suppression; heavy/light ID UNDETERMINED SIGNIFICANCE MGUS; SMOLDERING MULTIPLE-MYELOMA; MONOCLONAL GAMMOPATHY; DIAGNOSIS; CRITERIA AB We hypothesized that the suppression of uninvolved immunoglobulin in monoclonal gammopathy of undetermined significance (MGUS) as detected by suppression of the isotype-specific heavy and light chain (HLC-pair suppression) increases the risk of progression to malignancy. This approach required quantitation of individual heavy/light chains (for example, IgG lambda in IgG kappa MGUS patients). Of 1384 MGUS patients from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 999 persons. We identified HLC-pair suppression in 27% of MGUS patient samples compared with 11% of patients with suppression of uninvolved IgG, IgA or IgM. HLC-pair suppression was a significant risk factor for progression (hazard ratio (HR), 2.3; 95% confidence interval (CI) 1.5-3.7; P<0.001). On multivariate analysis, HLC-pair suppression was an independent risk factor for progression to malignancy in combination with serum M-spike size, heavy chain isotype and free light chain ratio (HR, 1.8; 95% CI, 1.1-3.00; P = 0.018). The finding that HLC-pair suppression predicts progression in MGUS and occurs several years before malignant transformation has implications for myeloma biology. Leukemia (2013) 27, 208-212; doi: 10.1038/leu.2012.189 C1 [Katzmann, J. A.; Clark, R.] Mayo Clin, Dept Lab Med, Div Clin Biochem & Immunol, Rochester, MN 55905 USA. [Kyle, R. A.; Dispenzieri, A.; Kumar, S.; Rajkumar, S. V.] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN 55905 USA. [Larson, D. R.; Therneau, T. M.; Benson, J. T.; Colby, C. L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN 55905 USA. [Melton, L. J., III; Cerhan, J. R.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN 55905 USA. [Landgren, O.] NCI, Multiple Myeloma Sect, Bethesda, MD 20892 USA. [Bradwell, A. R.] Binding Site, Birmingham, W Midlands, England. RP Katzmann, JA (reprint author), Mayo Clin, Dept Lab Med, Div Clin Biochem & Immunol, 200 1st St SW, Rochester, MN 55905 USA. EM Katzmann@mayo.edu RI Kumar, Shaji/A-9853-2008; OI Kumar, Shaji/0000-0001-5392-9284; Rajkumar, S. Vincent/0000-0002-5862-1833; Cerhan, James/0000-0002-7482-178X; Bradwell, Arthur/0000-0002-1562-1606; Dispenzieri, Angela/0000-0001-8780-9512 FU National Cancer Institute, National Institutes of Health, US Public Health Service, Bethesda, MD [CA107476, CA100707, CA83724]; Jabbs Foundation, Birmingham, UK; Henry J Predolin Foundation, USA FX This study was supported in part by the National Cancer Institute (CA107476, CA100707, CA83724), National Institutes of Health, US Public Health Service, Bethesda, MD and in part by the Jabbs Foundation, Birmingham, UK and the Henry J Predolin Foundation, USA. NR 16 TC 37 Z9 40 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JAN PY 2013 VL 27 IS 1 BP 208 EP 212 DI 10.1038/leu.2012.189 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 070MP UT WOS:000313511400027 PM 22781594 ER PT J AU Makinde, AY John-Aryankalayil, M Palayoor, ST Cerna, D Coleman, CN AF Makinde, Adeola Y. John-Aryankalayil, Molykutty Palayoor, Sanjeewani T. Cerna, David Coleman, C. Norman TI Radiation Survivors: Understanding and Exploiting the Phenotype following Fractionated Radiation Therapy SO MOLECULAR CANCER RESEARCH LA English DT Review ID FUKUSHIMA NUCLEAR ACCIDENT; IONIZING-RADIATION; CANCER CELLS; IN-VIVO; SINGLE; MICRORNAS; TUMOR; BREAST; RADIOTHERAPY; METABOLISM AB Radiation oncology modalities such as intensity-modulated and image-guided radiation therapy can reduce the high dose to normal tissue and deliver a heterogeneous dose to tumors, focusing on areas deemed at highest risk for tumor persistence. Clinical radiation oncology produces daily doses ranging from 1 to 20 Gy, with tissues being exposed to 30 or more daily fractions. Hypothesizing the cells that survive fractionated radiation therapy have a substantially different phenotype than the untreated cells, which might be exploitable for targeting with molecular therapeutics or immunotherapy, three prostate cancer cell lines (PC3, DU145, and LNCaP) and normal endothelial cells were studied to understand the biology of differential effects of multifraction (MF) radiation of 0.5, 1, and/or 2 Gy fraction to 10 Gy total dose, and a single dose of 5 and 10 Gy. The resulting changes in mRNA, miRNA, and phosphoproteome were analyzed. Significant differences were observed in the MF radiation exposures including those from the 0.5 Gy MF that produces little cell killing. As expected, p53 function played a major role in response. Pathways modified by MF include immune response, DNA damage, cell-cycle arrest, TGF-beta, survival, and apoptotic signal transduction. The radiation-induced stress response will set forth a unique platform for exploiting the effects of radiation therapy as "focused biology" for cancer treatment in conjunction with molecular targeted or immunologically directed therapy. Given that more normal tissue is treated, albeit to lower doses with these newer techniques, the response of the normal tissue may also influence long-term treatment outcome. Mol Cancer Res; 11(1); 5-12. (c) 2012 AACR. C1 [Makinde, Adeola Y.; John-Aryankalayil, Molykutty; Palayoor, Sanjeewani T.; Cerna, David; Coleman, C. Norman] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cerna, David; Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Makinde, AY (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10,B3B406, Bethesda, MD 20892 USA. EM adeola.makinde@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 51 TC 17 Z9 17 U1 1 U2 11 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 JAN PY 2013 VL 11 IS 1 BP 5 EP 12 DI 10.1158/1541-7786.MCR-12-0492 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 073LH UT WOS:000313744000002 PM 23175523 ER PT J AU Horton, JK Wilson, SH AF Horton, Julie K. Wilson, Samuel H. TI Predicting Enhanced Cell Killing through PARP Inhibition SO MOLECULAR CANCER RESEARCH LA English DT Article ID DNA-POLYMERASE-BETA; BASE-EXCISION-REPAIR; POLY(ADP-RIBOSE) POLYMERASE; CYTOTOXICITY; DAMAGE; INTERMEDIATE; TEMOZOLOMIDE; PROTECTION; MECHANISM; CANCER AB PARP inhibitors show promise as combination and single agents in cancer chemotherapy. Here, we evaluate results obtained with mouse fibroblasts and the common laboratory PARP inhibitor 4-amino-1,8-naphthalimide (4-AN) and analyze the potential for enhanced cytotoxicity following the combination of a DNA-damaging agent and a PARP inhibitor. Methylated DNA bases are repaired by the monofunctional glycosylase-initiated single-nucleotide base excision repair (BER) pathway. An intermediate of this process has a single-nucleotide gap in double-stranded DNA containing the 5'-deoxyribose phosphate (dRP) group at one margin. This 5'-dRP group is removed by the lyase activity of pol beta prior to gap filling; then completion of repair is by DNA ligation. PARP-1 binds to and is activated by the 5'-dRP group-containing intermediate, and poly(ADP-ribos)ylation is important for efficient repair. 4-AN-mediated sensitization to the methylating chemotherapeutic agent temozolomide is extreme, producing a level of cytotoxicity not seen with either agent alone. In contrast, with agents producing oxidative DNA damage repaired by bifunctional glycosylase-initiated BER, there is only weak sensitization by cotreatment with PARP inhibitor. Other clinically used DNA-damaging agents repaired by different DNA repair pathways also reveal minimal 4-AN-mediated sensitization. This information has potentially important implications for strategic use of PARP inhibitors in chemotherapy. Mol Cancer Res; 11(1); 13-18. (c) 2012 AACR. C1 [Horton, Julie K.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,MD F1-12, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural Research Program of the NIH, National Institute of Environmental Health Sciences [Z01ES050159] FX This work was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (project number Z01ES050159). NR 21 TC 21 Z9 21 U1 0 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 JAN PY 2013 VL 11 IS 1 BP 13 EP 18 DI 10.1158/1541-7786.MCR-12-0512 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 073LH UT WOS:000313744000003 PM 23193155 ER PT J AU Weldon, JE Xiang, LM Zhang, JL Beers, R Walker, DA Onda, M Hassan, R Pastan, I AF Weldon, John E. Xiang, Laiman Zhang, Jingli Beers, Richard Walker, Dawn A. Onda, Masanori Hassan, Raffit Pastan, Ira TI A Recombinant Immunotoxin against the Tumor-Associated Antigen Mesothelin Reengineered for High Activity, Low Off-Target Toxicity, and Reduced Antigenicity SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID VASCULAR LEAK SYNDROME; PHASE-I TRIAL; PSEUDOMONAS-AERUGINOSA EXOTOXIN; B-CELL MALIGNANCIES; DNA-IMMUNIZED MICE; ANTITUMOR-ACTIVITY; RFB4(DSFV)-PE38 BL22; PHAGE DISPLAY; INTRACELLULAR TRAFFICKING; CYTOTOXIC ACTIVITY AB SS1P is a recombinant immunotoxin (RIT) engineered for the targeted elimination of malignant cells that express the tumor-associated antigen mesothelin. It is composed of an antimesothelin antibody variable fragment (Fv) linked to a cytotoxic fragment of Pseudomonas exotoxin A (PE) that includes domains II and III of native PE. The clinical use of SS1P is limited by its propensity to induce neutralizing antibodies and to cause a dose-limiting capillary leak syndrome (CLS) in patients. In this article, we describe a reengineered SS1P with improved properties that overcome these deficits. The redesign of SS1P consists of (i) removing the bulk of PE domain II (residues 251-273 and 284-394 of native PE), leaving only an 11-residue furin cleavage site, (ii) adding a Gly-Gly-Ser peptide linker after the furin cleavage site, and (iii) replacing eight highly solvent-exposed residues in the catalytic domain of PE. The new molecule, SS1-LR/GGS/8M, has cytotoxic activity comparable with SS1P on several mesothelin-expressing cell lines and remarkably improved activity on primary cells from patients with mesothelioma. In a mouse xenograft tumor model, high doses of SS1-LR/GGS/8M elicit antitumor activity superior to the activity of SS1P at its maximum-tolerated dose. In addition, SS1-LR/GGS/8M has greatly decreased ability to cause CLS in a rat model and reduced antigenicity or reactivity with antibodies to the sera of patients previously treated with SS1P. Mol Cancer Ther; 12(1); 48-57. (C) 2012 AACR. C1 [Weldon, John E.; Xiang, Laiman; Zhang, Jingli; Beers, Richard; Walker, Dawn A.; Onda, Masanori; Hassan, Raffit; Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov OI Weldon, John/0000-0002-6516-9064 FU NIH, NCI, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 50 TC 36 Z9 36 U1 0 U2 6 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 JAN PY 2013 VL 12 IS 1 BP 48 EP 57 DI 10.1158/1535-7163.MCT-12-0336 PG 10 WC Oncology SC Oncology GA 071JI UT WOS:000313588200005 PM 23136186 ER PT J AU Xing, RJ Bhirde, AA Wang, SJ Sun, XL Liu, G Hou, YL Chen, XY AF Xing, Ruijun Bhirde, Ashwinkumar A. Wang, Shouju Sun, Xiaolian Liu, Gang Hou, Yanglong Chen, Xiaoyuan TI Hollow iron oxide nanoparticles as multidrug resistant drug delivery and imaging vehicles SO NANO RESEARCH LA English DT Article DE drug resistance; hollow nanoparticles; doxorubicin; magnetic resonance imaging (MRI); drug delivery ID MAGNETIC NANOPARTICLES; FE3O4 NANOPARTICLES; SOLID TUMORS; CANCER; DOXORUBICIN; RELEASE; TUMORIGENESIS; MECHANISMS; CONTRAST; REVERSAL AB Magnetic nanoparticles have been used as drug delivery vehicles against a number of cancer cells. Most of these theranostic formulations have used solid iron oxide nanoparticles (SIONPs) loaded with chemotherapeutics as nano-carrier formulation for both magnetic resonance imaging (MRI) and cancer therapy. In this study, we applied the dopamine-plus-human serum albumin (HSA) method to modify hollow iron oxide nanoparticles (HIONPs) and encapsuated doxorubicin (DOX) within the hollow porous structure of the nano-carrier. The new delivery system can load more drug than solid iron oxide nanoparticles of the same core size using the same coating strategy. The HIONPs-DOX formulation also has a pH-dependent drug release behaviour. Compared with free DOX, the HIONPs-DOX were more effectively uptaken by the multidrug resistant OVCAR8-ADR cells and consequently more potent in killing drug resistant cancer cells. MRI phantom and cell studies also showed that the HIONPs-DOX can decrease the T (2) MRI signal intensity and can be used as a MRI contrast agent while acting as a drug delivery vehicle. For the first time, the dual application of chemo drug transport and MR imaging using the HIONPs-DOX formulation was achieved against both DOX-sensitive and DOX-resistant cancer cells. C1 [Xing, Ruijun; Bhirde, Ashwinkumar A.; Wang, Shouju; Sun, Xiaolian; Hou, Yanglong; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Xing, Ruijun] Peking Univ, Dept Mat Sci & Engn, Coll Engn, Beijing 100871, Peoples R China. [Liu, Gang] Xiamen Univ, Sch Publ Hlth, Ctr Mol Imaging & Translat Med, Xiamen 361005, Peoples R China. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. EM Shawn.Chen@nih.gov RI Hou, Yanglong/B-8688-2012 FU National Basic Research Program of China (973 Program) [2013CB733802, 2010CB934602]; National Science Foundation of China (NSFC) [81101101, 81201086, 81201129, 81201190, 51273165, 51172005, 81028009]; Chinese Academy of Sciences Professorship for Senior International Scientists [2011T2J06]; Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH); China Scholarship Council FX This research was supported in part by the National Basic Research Program of China (973 Program, Nos. 2013CB733802 and 2010CB934602); the National Science Foundation of China (NSFC, Nos. 81101101, 81201086, 81201129, 81201190, 51273165, 51172005 and 81028009); the Chinese Academy of Sciences Professorship for Senior International Scientists (No. 2011T2J06); and the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). R. X. is partially supported by the China Scholarship Council. NR 35 TC 35 Z9 36 U1 7 U2 168 PU TSINGHUA UNIV PRESS PI BEIJING PA TSINGHUA UNIV, RM A703, XUEYAN BLDG, BEIJING, 10084, PEOPLES R CHINA SN 1998-0124 J9 NANO RES JI Nano Res. PD JAN PY 2013 VL 6 IS 1 BP 1 EP 9 DI 10.1007/s12274-012-0275-5 PG 9 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 072GW UT WOS:000313658800001 ER PT J AU Lakatta, EG Maltsev, VA AF Lakatta, Edward G. Maltsev, Victor A. TI Reprogramming paces the heart SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID PACEMAKER; CELLS C1 [Lakatta, Edward G.; Maltsev, Victor A.] NIA, Lab Cardiovasc Sci, Intramural Res Program, US Natl Inst Hlth, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Lab Cardiovasc Sci, Intramural Res Program, US Natl Inst Hlth, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov; maltsevvi@mail.nih.gov FU Intramural NIH HHS [ZIA AG000260-04] NR 10 TC 3 Z9 3 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2013 VL 31 IS 1 BP 31 EP 32 DI 10.1038/nbt.2480 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 071CP UT WOS:000313563600016 PM 23302930 ER PT J AU Hanada, K Restifo, NP AF Hanada, Ken-ichi Restifo, Nicholas P. TI Double or nothing on cancer immunotherapy SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID T-CELLS; ADOPTIVE IMMUNOTHERAPY; ERBB2 C1 [Hanada, Ken-ichi; Restifo, Nicholas P.] NCI, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hanada, K (reprint author), NCI, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Restifo, Nicholas/A-5713-2008; Hanada, Ken-ichi/L-2481-2013; OI Hanada, Ken-ichi/0000-0003-2959-1257; Restifo, Nicholas P./0000-0003-4229-4580 NR 11 TC 7 Z9 7 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2013 VL 31 IS 1 BP 33 EP 34 DI 10.1038/nbt.2471 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 071CP UT WOS:000313563600017 PM 23302931 ER PT J AU Bianco, P Cao, X Frenette, PS Mao, JJ Robey, PG Simmons, PJ Wang, CY AF Bianco, Paolo Cao, Xu Frenette, Paul S. Mao, Jeremy J. Robey, Pamela G. Simmons, Paul J. Wang, Cun-Yu TI The meaning, the sense and the significance: translating the science of mesenchymal stem cells into medicine SO NATURE MEDICINE LA English DT Article ID BONE-MARROW; HEMATOPOIETIC STEM; OSTEOGENESIS IMPERFECTA; PROGENITOR CELLS; STROMAL CELLS; OSTEOBLAST DIFFERENTIATION; STEM/PROGENITOR CELLS; FIBROUS DYSPLASIA; NICHE; ADULT AB Mesenchymal stem cells (MSCs) are the focus of intensive efforts worldwide directed not only at elucidating their nature and unique properties but also developing cell-based therapies for a diverse range of diseases. More than three decades have passed since the original formulation of the concept, revolutionary at the time, that multiple connective tissues could emanate from a common progenitor or stem cell retained in the postnatal bone marrow. Despite the many important advances made since that time, substantial ambiguities still plague the field regarding the nature, identity, function, mode of isolation and experimental handling of MSCs. These uncertainties have a major impact on their envisioned therapeutic use. C1 [Bianco, Paolo] Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. [Cao, Xu] Johns Hopkins Univ, Dept Orthoped Surg, Baltimore, MD USA. [Frenette, Paul S.] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Dept Cell Biol, Dept Med, New York, NY USA. [Mao, Jeremy J.] Columbia Univ, Coll Dent Med, Ctr Craniofacial Regenerat, New York, NY USA. [Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. [Simmons, Paul J.] Mesoblast Ltd, Melbourne, Vic, Australia. [Wang, Cun-Yu] Univ Calif Los Angeles, Sch Dent, Div Oral Biol, Lab Mol Signaling, Los Angeles, CA 90024 USA. RP Bianco, P (reprint author), Univ Roma La Sapienza, Dept Mol Med, Rome, Italy. EM paolo.bianco@uniroma1.it RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [GGP09227]; Fondazione Roma; Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR); Ministero della Salute; EU (Angioscaff); Fondazione Institut Pasteur-Cenci Bolognetti; US National Institutes of Health (NIH) [R01 DK056638, HL69438, HL097819, HL097700, HL116340]; NIH [DK57501, R01 DE018248, R01 EB009663]; National Institute of Dental and Craniofacial Research (NIDCR), NIH [DE019412, DE016513]; Division of Intramural Research, NIDCR of the Intramural Research Program, NIH, Department of Health and Human Services FX Note that the authors are listed in alphabetical order in the author list. This work was supported in part by grants from Telethon (GGP09227), Fondazione Roma, Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), Ministero della Salute, EU (Angioscaff) and Fondazione Institut Pasteur-Cenci Bolognetti (to P.B.), the US National Institutes of Health (NIH) (R01 DK056638, HL69438, HL097819, HL097700, HL116340 to P.S.F.), NIH DK57501 (to X.C.), the National Institute of Dental and Craniofacial Research (NIDCR), NIH (DE019412 and DE016513 to C.-Y.W.), NIH R01 DE018248 and R01 EB009663 to J.J.M. and the Division of Intramural Research, NIDCR of the Intramural Research Program, NIH, Department of Health and Human Services (to P.G.R.). NR 64 TC 349 Z9 361 U1 16 U2 137 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 JAN PY 2013 VL 19 IS 1 BP 35 EP 42 DI 10.1038/nm.3028 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 066OO UT WOS:000313230300023 PM 23296015 ER PT J AU Natarajan, G Shankaran, S McDonald, SA Das, A Ehrenkranz, RA Goldberg, RN Stoll, BJ Tyson, JE Higgins, RD Schendel, D Hougaard, DM Skogstrand, K Thorsen, P Carlo, WA AF Natarajan, Girija Shankaran, Seetha McDonald, Scott A. Das, Abhik Ehrenkranz, Richard A. Goldberg, Ronald N. Stoll, Barbara J. Tyson, Jon E. Higgins, Rosemary D. Schendel, Diana Hougaard, David M. Skogstrand, Kristin Thorsen, Poul Carlo, Waldemar A. TI Association Between Blood Spot Transforming Growth Factor-beta and Patent Ductus Arteriosus in Extremely Low-Birth Weight Infants SO PEDIATRIC CARDIOLOGY LA English DT Article DE Transforming growth factor; Patent ductus arteriosus; Preterm; Neonate ID EXPRESSION; CELLS; MIGRATION; CYTOKINES AB Permanent ductal closure involves anatomic remodeling, in which transforming growth factor (TGF)-beta appears to play a role. Our objective was to evaluate the relationship, if any, between blood spot TGF-beta on day 3 and day 7 of life and patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants. Prospective observational study involving ELBW infants (n = 968) in the National Institute of Child Health and Human Development Neonatal Research Network who had TGF-beta measured on filter paper spot blood samples using a Luminex assay. Infants with a PDA (n = 493) were significantly more immature, had lower birth weights, and had higher rates of respiratory distress syndrome than those without PDA (n = 475). TGF-beta on days 3 and 7 of life, respectively, were significantly lower among neonates with PDA (median 1,177 pg/ml [range 642-1,896]; median 1,386 pg/ml [range 868-1,913]) compared with others without PDA (median 1,334 pg/ml [range 760-2,064]; median 1,712 pg/ml [range 1,014-2,518 pg/ml]). The significant difference persisted when death or PDA was considered a composite outcome. TGF-beta levels were not significantly different among subgroups of infants with PDA who were not treated (n = 51) versus those who were treated medically (n = 283) or by surgical ligation (n = 159). TGF-beta was not a significant predictor of death or PDA (day 3 odds ratio [OR] 0.99, 95 % confidence interval [CI] 0.83-1.17; day 7 OR 0.88, 95 % CI 0.74-1.04) on adjusted analyses. Our results suggest that blood spot TGF-beta alone is unlikely to be a reliable biomarker of a clinically significant PDA or its responsiveness to treatment. C1 [Natarajan, Girija; Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [McDonald, Scott A.] RTI Int, Dept Stat & Epidemiol, Durham, NC USA. [Das, Abhik] RTI Int, Dept Stat & Epidemiol, Rockville, MD USA. [Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Stoll, Barbara J.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Tyson, Jon E.] Univ Texas Med Sch Houston, Dept Pediat, Houston, TX USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Schendel, Diana] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Hougaard, David M.; Skogstrand, Kristin] Statens Serum Inst, Sect Neonatal Screening & Hormones, Dept Clin Biochem & Immunol, DK-2300 Copenhagen, Denmark. [Thorsen, Poul] Lillebaelt Hosp, Dept Obstet & Gynecol, Kolding, Denmark. [Thorsen, Poul] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. RP Natarajan, G (reprint author), Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. EM gnatara@med.wayne.edu OI Skogstrand, Kristin/0000-0002-0026-3711 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Department of Health and Human Services [U10 HD21385, U10 HD40689, U10 HD 27871, U10 HD21373, U10 HD36790, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851, R03 HD054420]; National Institutes of Health [GCRC M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039, 5 M01 RR00044]; National Institutes of Health; Centers for Disease Control and Prevention FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Department of Health and Human Services (Grants No. U10 HD21385, U10 HD40689, U10 HD 27871, U10 HD21373, U10 HD36790, U10 HD40461, U10 HD34216, U10 HD21397, U10 HD27904, U10 HD40492, U10 HD27856, U10 HD40521, U10 HD27853, U10 HD27880, U10 HD27851, and R03 HD054420) and from the National Institutes of Health (Grants No. GCRC M01 RR 08084, M01 RR 00125, M01 RR 00750, M01 RR 00070, M01 RR 0039-43, M01 RR 00039, and 5 M01 RR00044). The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the Centers for Disease Control and Prevention provided grant support for recruitment for 1999 through 2001 and data analysis for the Neonatal Research Network's Cytokines Study. The funding agencies provided overall oversight for study conduct, but all data analyses and interpretation were independent of the funding agencies. Data collected at participating NRN sites were transmitted to RTI International, the data-coordinating center (DCC) for the NRN, which stored, managed, and analyzed the data for this study. On behalf of the network, Abhik Das (DCC PI) and Scott A. McDonald (DCC statistician) had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis. We are indebted to our medical and nursing colleagues as well as the infants and their parents who agreed to take part in this study. NR 15 TC 0 Z9 0 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0172-0643 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD JAN PY 2013 VL 34 IS 1 BP 149 EP 154 DI 10.1007/s00246-012-0404-7 PG 6 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 070PB UT WOS:000313520600020 PM 22684193 ER PT J AU Pao, M AF Pao, Maryland TI Suicide by Security Blanket and Other Stories from the Child Psychiatry Emergency Service: What Happens to Children with Acute Mental Illness SO PSYCHOSOMATICS LA English DT Book Review C1 [Pao, Maryland] NIMH, Bethesda, MD 20892 USA. [Pao, Maryland] NIH, Psychiat Consultat Liaison Serv, Ctr Clin, Bethesda, MD 20892 USA. RP Pao, M (reprint author), NIMH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 2013 VL 54 IS 1 BP 100 EP 100 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 071QS UT WOS:000313609900017 ER PT J AU Floeter, MK Danielian, LE Kim, YK AF Floeter, Mary Kay Danielian, Laura E. Kim, Yong Kyun TI Effects of motor skill learning on reciprocal inhibition SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Motor skill learning; reciprocal inhibition; electromyography; dual task; spinal plasticity ID ARM MOVEMENT; MUSCLE COORDINATION; FICTIVE LOCOMOTION; VOLUNTARY MOVEMENT; SPINAL REFLEXES; HUMAN FOREARM; H-REFLEX; MODULATION; HUMANS; CONSOLIDATION AB Purpose: Learning a skilled movement is associated with more efficient use of subcortical motor circuits which can coordinate features of the movements such as the timing and patterns of activation of different muscles. Learning a motor skill could strengthen spinal interneuron circuits that facilitate the movement. We hypothesized that learning a simple, alternating movement would produce changes in spinal circuits that mediate reciprocal inhibition between antagonist muscles. Methods: Sixteen healthy adult subjects were trained to perform a wrist flexion and extension task to control the movement of a cursor between targets appearing on a computer display. The goal of the task was to hit the targets. Subjects practiced for 15 minutes daily until reaching the acquisition criterion. Surface EMG recordings from wrist flexor and extensor muscles showed reduced co-contraction during acquisition of the task. Results: Compared to the initial session, in the final session short-latency reciprocal inhibition was enhanced during the late-extension phase in the final session. This phase-dependent increase in short-latency reciprocal inhibition is likely to facilitate switching activation between wrist antagonistic muscles. Conclusions: Learning a motor skill can produce alterations in spinal reflex circuits that facilitate the desired movement. C1 [Floeter, Mary Kay; Danielian, Laura E.] NINDS, Human Spinal Physiol Unit, NIH, Bethesda, MD 20892 USA. [Kim, Yong Kyun] Kwandong Univ, Dept Phys Med & Rehabil, Myongji Hosp, Coll Med, Koyang, Kyunggi, South Korea. RP Kim, YK (reprint author), Kwandong Univ, Dept Phys Med & Rehabil, Myongji Hosp, Coll Med, 697-24 Hwajung Dong, Koyang, Kyunggi, South Korea. EM yongkyunk@gmail.com FU Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke FX This research was supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 39 TC 4 Z9 4 U1 3 U2 21 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2013 VL 31 IS 1 BP 53 EP 62 DI 10.3233/RNN-120247 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 073JY UT WOS:000313740500005 PM 23142814 ER PT J AU Kang, DH Jo, HJ Jung, WH Kim, SH Jung, YH Choi, CH Lee, US An, SC Jang, JH Kwon, JS AF Kang, Do-Hyung Jo, Hang Joon Jung, Wi Hoon Kim, Sun Hyung Jung, Ye-Ha Choi, Chi-Hoon Lee, Ul Soon An, Seung Chan Jang, Joon Hwan Kwon, Jun Soo TI The effect of meditation on brain structure: cortical thickness mapping and diffusion tensor imaging SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE LA English DT Article DE cortical thickness; diffusion tensor imaging; medial prefrontal cortex; meditation ID LONG-TERM MEDITATION; GRAY-MATTER DENSITY; VOXEL-BASED MORPHOMETRY; HUMAN CEREBRAL-CORTEX; PLASMA-CATECHOLAMINES; ANTERIOR CINGULATE; PRACTITIONERS; FMRI; CONNECTIVITY; MINDFULNESS AB A convergent line of neuroscientific evidence suggests that meditation alters the functional and structural plasticity of distributed neural processes underlying attention and emotion. The purpose of this study was to examine the brain structural differences between a well-matched sample of long-term meditators and controls. We employed whole-brain cortical thickness analysis based on magnetic resonance imaging, and diffusion tensor imaging to quantify white matter integrity in the brains of 46 experienced meditators compared with 46 matched meditation-naive volunteers. Meditators, compared with controls, showed significantly greater cortical thickness in the anterior regions of the brain, located in frontal and temporal areas, including the medial prefrontal cortex, superior frontal cortex, temporal pole and the middle and interior temporal cortices. Significantly thinner cortical thickness was found in the posterior regions of the brain, located in the parietal and occipital areas, including the postcentral cortex, inferior parietal cortex, middle occipital cortex and posterior cingulate cortex. Moreover, in the region adjacent to the medial prefrontal cortex, both higher fractional anisotropy values and greater cortical thickness were observed. Our findings suggest that long-term meditators have structural differences in both gray and white matter. C1 [Kang, Do-Hyung; Jang, Joon Hwan; Kwon, Jun Soo] Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul 110744, South Korea. [Jo, Hang Joon] NIMH, Sci & Stat Comp Core, NIH, Bethesda, MD 20892 USA. [Jung, Wi Hoon; Jung, Ye-Ha; Kwon, Jun Soo] SNU MRC, Clin Cognit Neurosci Ctr, Inst Neurosci, Seoul 110744, South Korea. [Kim, Sun Hyung] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Choi, Chi-Hoon] Natl Med Ctr, Dept Diagnost Radiol, Seoul 100799, South Korea. [Lee, Ul Soon; An, Seung Chan] Korea Inst Brain Sci, Seoul 135894, South Korea. [Kwon, Jun Soo] Seoul Natl Univ, Coll Nat Sci, World Class Univ Program, Dept Brain & Cognit Sci, Seoul 151742, South Korea. RP Kwon, JS (reprint author), Seoul Natl Univ, Coll Med, Dept Psychiat, 101 Daehak Ro, Seoul 110744, South Korea. EM kwonjs@snu.ac.kr RI Kwon, Jun Soo/J-2734-2012; JO, HANG JOON/D-1775-2011 OI JO, HANG JOON/0000-0002-9180-3831 FU National Research Foundation [20110015639]; World Class University through the Korea Science and Engineering Foundation [R31-10089]; Ministry of Education, Science and Technology, Republic of Korea; National Institute of Mental Health (NIMH); National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH) FX The authors give special thanks to Korea Institute of Brain Science for the assistance in the present study and Daniel Glen for his amazing support with data analysis. The authors also thank Ji Yeon Han for all her work in data acquisition, the clinical and nursing staff of the Clinical Cognitive Neuroscience Center for the help with recruitment, and Robert Cox and Ziad Saad for their development of AFNI and SUMA. This research was supported by Mid-career Research Program through National Research Foundation grant (20110015639) and by World Class University program through the Korea Science and Engineering Foundation (R31-10089) funded by the Ministry of Education, Science and Technology, Republic of Korea. Hang Joon Jo was supported by the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Programs of the National Institutes of Health (NIH). NR 56 TC 36 Z9 37 U1 7 U2 63 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1749-5016 J9 SOC COGN AFFECT NEUR JI Soc. Cogn. Affect. Neurosci. PD JAN PY 2013 VL 8 IS 1 SI SI BP 27 EP 33 DI 10.1093/scan/nss056 PG 7 WC Neurosciences; Psychology; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 072DR UT WOS:000313649700004 PM 22569185 ER PT J AU Locatis, C Ackerman, M AF Locatis, Craig Ackerman, Michael TI Three Principles for Determining the Relevancy of Store-and-Forward and Live Interactive Telemedicine: Reinterpreting Two Telemedicine Research Reviews and Other Research SO TELEMEDICINE AND E-HEALTH LA English DT Article DE telemedicine; technology; telecommunications ID GRADING DIABETIC-RETINOPATHY; ACUTE MYOCARDIAL-INFARCTION; CONGENITAL HEART-DISEASE; REAL-TIME TELEMEDICINE; DIGITAL RETINAL IMAGES; TELE-ENDOSCOPY; DIAGNOSIS; OTOLARYNGOLOGY; TELECOLPOSCOPY; CONSULTATIONS AB The Agency for Healthcare Research and Quality sponsored two telemedicine research reviews. The latest review concluded that telemedicine is most relevant to specialties, such as psychiatry and neurology, where high levels of patient interaction are crucial to assessment. Telemedicine research studies cited in the reviews having positive findings in the specialties of ophthalmology, otolaryngology, obstetrics and gynecology, gastroenterology, and cardiology and more recent research in these areas are reviewed to identify criteria other than degree of interaction for determining the appropriateness of telemedicine interventions. These criteria include congruity or the extent that procedures used in telemedicine are similar to those of in-person examination, fidelity or the degree to which the information used for assessment in remote examinations is of similar quality to that used in-person, and reliability or the consistency with which information can be gathered and transmitted. C1 [Locatis, Craig] NIH, Off High Performance Comp & Commun, Natl Lib Med, Bethesda, MD 20894 USA. RP Locatis, C (reprint author), NIH, Off High Performance Comp & Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM locatis@nlm.nih.gov FU National Institutes of Health Intramural Research Program FX This review was supported through the National Institutes of Health Intramural Research Program. NR 38 TC 4 Z9 4 U1 2 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD JAN PY 2013 VL 19 IS 1 BP 19 EP 23 DI 10.1089/tmj.2012.0063 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 071BX UT WOS:000313561800005 PM 23186085 ER PT J AU Bernstein, DI Kashon, M Lummus, ZL Johnson, VJ Fluharty, K Gautrin, D Malo, JL Cartier, A Boulet, LP Sastre, J Quirce, S Germolec, D Tarlo, SM Cruz, MJ Munoz, X Luster, MI Yucesoy, B AF Bernstein, David I. Kashon, Michael Lummus, Zana L. Johnson, Victor J. Fluharty, Kara Gautrin, Denyse Malo, Jean-Luc Cartier, Andre Boulet, Louis-Philippe Sastre, Joaquin Quirce, Santiago Germolec, Dori Tarlo, Susan M. Cruz, Maria-Jesus Munoz, Xavier Luster, Michael I. Yucesoy, Berran TI CTNNA3 (alpha-Catenin) Gene Variants Are Associated With Diisocyanate Asthma: A Replication Study in a Caucasian Worker Population SO TOXICOLOGICAL SCIENCES LA English DT Article DE diisocyanate asthma; CTNNA3; alpha-T catenin; occupational asthma ID OCCUPATIONAL ASTHMA; EXPOSURE; POLYMORPHISMS; ISOCYANATES; RESPONSES; GENOTYPES; PATTERNS; DISEASE; IL-13; RISK AB Recently, a genome-wide association study (GWAS) conducted in Korean subjects identified four CTNNA3 (alpha-T catenin) single nucleotide polymorphisms (SNPs) (rs10762058, rs7088181, rs1786929, and rs4378283) associated with diisocyanate-induced occupational asthma (DA). The CTNNA3 gene codes for a cadherin involved in formation of stretch-resistant cell-cell adhesions. We conducted a candidate gene association study to replicate these findings in Caucasian workers. Genotyping was performed on DNA using a 5 nuclease PCR assay collected from 410 diisocyanate-exposed and predominantly Canadian workers including 132 workers with DA confirmed by a specific inhalation challenge (DA); 131 symptomatic workers in whom DA was excluded by a negative challenge (DA); and 147 hexamethylene diisocyanateexposed asymptomatic workers (AWs). As in the Korean study, highly linked CTNNA3 rs7088181 and rs10762058 SNPs (but not rs4378283 and rs1786929) were significantly associated with DA when compared with AWs but not in comparison with DA workers (p 0.05). After adjusting for potentially confounding variables of age, smoking status, and duration of exposure, minor allele homozygotes of rs7088181 and rs10762058 SNPs were at increased risk for DA compared with AWs (OR 9.05 [95% CI: 1.69, 48.54] and OR 6.82 [95% CI: 1.65, 28.24], respectively). In conclusion, we replicated results from the only reported GWAS study of DA demonstrating an association between two closely linked CTNNA3 gene SNPs and DA. These findings lend further support to the clinical relevance of these genotypes in predicting susceptibility to DA and the potential importance of catenins in the disease process. C1 [Bernstein, David I.] Univ Cincinnati, Dept Internal Med, Div Immunol Allergy & Rheumatol, Coll Med, Cincinnati, OH 45267 USA. [Kashon, Michael; Fluharty, Kara; Luster, Michael I.; Yucesoy, Berran] CDC Natl Inst Occupat Safety & Hlth, Hlth Effects Lab Div, Morgantown, WV 26505 USA. [Johnson, Victor J.] BRT Burleson Res Technol, Morrisville, NC 27560 USA. [Gautrin, Denyse; Malo, Jean-Luc; Cartier, Andre] Univ Montreal, Hop Sacre Coeur Montreal, Montreal, PQ H4J 1C5, Canada. [Boulet, Louis-Philippe] Univ Laval, Hop Laval, Ste Foy, PQ G1Y 4G5, Canada. [Sastre, Joaquin] Fdn Jimenez Diaz, Dept Allergy, E-28040 Madrid, Spain. [Quirce, Santiago] Hosp La Paz, IdiPAZ, Dept Allergy, Madrid 28046, Spain. [Germolec, Dori] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Tarlo, Susan M.] Univ Toronto, Toronto, ON M5G 1Z5, Canada. [Cruz, Maria-Jesus; Munoz, Xavier] Hosp Valle De Hebron, Madrid 08035, Spain. RP Bernstein, DI (reprint author), Univ Cincinnati, Dept Internal Med, Div Immunol Allergy & Rheumatol, Coll Med, 3255 Eden Ave,Suite 350, Cincinnati, OH 45267 USA. EM bernstdd@ucmail.uc.edu RI Munoz, Xavier/I-9009-2014; Cruz, Maria Jesus/I-9073-2014 OI Cruz, Maria Jesus/0000-0001-9759-5466 FU National Institute of Environmental Health Sciences; National Institute for Occupational Safety and Health [Y1-ES0001]; NIOSH/CDC [R01 OH 008795] FX National Institute of Environmental Health Sciences and National Institute for Occupational Safety and Health (Agreement No.Y1-ES0001) and NIOSH/CDC R01 OH 008795. NR 20 TC 19 Z9 20 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2013 VL 131 IS 1 BP 242 EP 246 DI 10.1093/toxsci/kfs272 PG 5 WC Toxicology SC Toxicology GA 072EV UT WOS:000313652900022 PM 22977168 ER PT J AU Lukacik, P Barnard, TJ Hinnebusch, BJ Buchanan, SK AF Lukacik, Petra Barnard, Travis J. Hinnebusch, B. Joseph Buchanan, Susan K. TI Specific targeting and killing of Gram-negative pathogens with an engineered phage lytic enzyme SO VIRULENCE LA English DT Editorial Material C1 [Lukacik, Petra; Barnard, Travis J.; Buchanan, Susan K.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Buchanan, SK (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM skbuchan@helix.nih.gov FU Intramural NIH HHS NR 0 TC 4 Z9 5 U1 1 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD JAN PY 2013 VL 4 IS 1 BP 90 EP 91 DI 10.1073/pnas.1203472109 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 071DL UT WOS:000313566000007 PM 23314572 ER PT J AU Taylor, CL Carriquiry, AL Bailey, RL Sempos, CT Yetley, EA AF Taylor, Christine L. Carriquiry, Alicia L. Bailey, Regan L. Sempos, Christopher T. Yetley, Elizabeth A. TI Appropriateness of the probability approach with a nutrient status biomarker to assess population inadequacy: a study using vitamin D SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID INTAKE DISTRIBUTIONS; VARIANCE; ENERGY AB Background: There are questions about the appropriate method for the accurate estimation of the population prevalence of nutrient inadequacy, on the basis of a biomarker of nutrient status (BNS). Objective: We determined the applicability of a statistical probability method to a BNS, specifically serum 25-hydroxyvitamin D [25(OH)D]. The ability to meet required statistical assumptions was the central focus. Design: Data on serum 25(OH)D concentrations in adults aged 19-70 y from the 2005-2006 NHANES were used (n = 3871). An Institute of Medicine report provided reference values. We analyzed key assumptions of symmetry, differences in variance, and the independence of distributions. We also corrected observed distributions for within-person variability (WPV). Estimates of vitamin D inadequacy were determined. Results: We showed that the BNS [serum 25(OH)D] met the criteria to use the method for the estimation of the prevalence of inadequacy. The difference between observations corrected compared with uncorrected for WPV was small for serum 25(OH)D but, nonetheless, showed enhanced accuracy because of correction. The method estimated a 19% prevalence of inadequacy in this sample, whereas misclassification inherent in the use of the more traditional 97.5th percentile high-end cutoff inflated the prevalence of inadequacy (36%). Conclusions: When the prevalence of nutrient inadequacy for a population is estimated by using serum 25(OH)D as an example of a BNS, a statistical probability method is appropriate and more accurate in comparison with a high-end cutoff. Contrary to a common misunderstanding, the method does not overlook segments of the population. The accuracy of population estimates of inadequacy is enhanced by the correction of observed measures for WPV. Am J Clin Nutr 2013;97:72-8. C1 [Taylor, Christine L.] NIH, Off Dietary Supplements, Off Director, Bethesda, MD 20892 USA. [Carriquiry, Alicia L.] Iowa State Univ, Dept Stat, Ames, IA USA. RP Taylor, CL (reprint author), NIH, Off Dietary Supplements, Off Director, 6100 Execut Blvd,Room 3B01, Bethesda, MD 20892 USA. EM taylorc13@od.nih.gov FU Office of Dietary Supplements FX Supported by the Office of Dietary Supplements. NR 23 TC 19 Z9 20 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2013 VL 97 IS 1 BP 72 EP 78 DI 10.3945/ajcn.112.046094 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 065GD UT WOS:000313135600011 PM 23097269 ER PT J AU Bastian, LA Fish, LJ Peterson, BL Biddle, AK Garst, J Lyna, P Molner, S Bepler, G Kelley, M Keefe, FJ McBride, CM AF Bastian, Lori A. Fish, Laura J. Peterson, Bercedis L. Biddle, Andrea K. Garst, Jennifer Lyna, Pauline Molner, Stephanie Bepler, Gerold Kelley, Mike Keefe, Francis J. McBride, Colleen M. TI Assessment of the Impact of Adjunctive Proactive Telephone Counseling to Promote Smoking Cessation Among Lung Cancer Patients' Social Networks SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE Tobacco Use Cessation; Lung Neoplasms; Social Support; Proactive Telephone Counseling; Prevention Research ID CES-D; FAMILY; DEPRESSION; TRIAL; CARE; INTERVENTION; RECRUITMENT; INTENTION; DIAGNOSIS; SYMPTOMS AB Purpose. When a patient is diagnosed with lung cancer, members of his/her social network may be more likely to engage in smoking cessation efforts. Proactive telephone counseling combined with a tailored self-directed intervention may be more effective at promoting smoking cessation than a tailored self-directed intervention alone. Design. Randomized controlled trial. Setting. Four clinical sites. Subjects. Current smokers who are family members and close friends of patients with lung cancer. Intervention. Six counselor-initiated counseling calls using motivational interviewing techniques and focusing on teaching adaptive coping skills based on the transactional model of stress and coping along with tailored self-directed materials (including nicotine patches, if not contraindicated) (n = 245) vs. tailored self-directed materials (including nicotine patches, if not contraindicated) (n = 251). Measures. Participants were surveyed at baseline and at 2 weeks, 6 months, and 12 months postintervention. The outcome was 7-day point prevalent abstinence. Analysis. The objective of this study was to test for arm differences in smoking cessation rates at 2 weeks and 6 months postintervention (primary) and at 12 months postintervention (secondary). Results. We found no overall effect of the proactive intervention on cessation rates. Among younger participants (age <50), the cessation rate in the intervention group was higher than in the control group at 2 weeks postintervention (16% vs. 4%, p = .046). For older participants (age >50), there were no group differences. Conclusion. Proactive telephone counseling focusing on adaptive coping skills was difficult to implement among smokers in lung cancer patients' social network. Although this study did not demonstrate any added benefit to cessation rates, this null finding may be a result of an intervention that was weaker than intended, owing to difficulties in completing the counseling phone calls. We-discuss lessons learned and areas for future research in this special population. (Am J Health Promot 2013;27[3]:181-190.) C1 [Bastian, Lori A.; Garst, Jennifer; Molner, Stephanie; Kelley, Mike] Duke Univ, Dept Med, Durham, NC USA. [Fish, Laura J.] Duke Univ, Dept Family & Community Med, Durham, NC USA. [Peterson, Bercedis L.] Duke Univ, Dept Biostat, Durham, NC USA. [Lyna, Pauline] Duke Univ, Canc Prevent & Detect Program, Durham, NC USA. [Keefe, Francis J.] Duke Univ, Dept Psychiat, Durham, NC 27706 USA. [Bastian, Lori A.; Kelley, Mike] Durham Vet Affairs Med Ctr, Durham, NC USA. [Biddle, Andrea K.] Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC USA. [Bepler, Gerold] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Thorac Oncol, Tampa, FL 33612 USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Bastian, LA (reprint author), Durham VA, 508 Fulton St 152, Durham, NC 27705 USA. EM lori.bastian@va.gov OI Biddle, Andrea/0000-0003-0273-7439 FU Intramural NIH HHS; NCI NIH HHS [5U01-CA-92622] NR 41 TC 7 Z9 8 U1 0 U2 4 PU AMER JOURNAL HEALTH PROMOTION INC PI TROY PA PO BOX 1254, TROY, MI 48099-1254 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD JAN-FEB PY 2013 VL 27 IS 3 BP 181 EP 190 DI 10.4278/ajhp.101122-QUAN-387 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068YX UT WOS:000313403200008 PM 23286595 ER PT J AU Kuhn, JH Radoshitzky, SR Bavari, S Jahrling, PB AF Kuhn, Jens H. Radoshitzky, Sheli R. Bavari, Sina Jahrling, Peter B. TI The International Code of Virus Classification and Nomenclature (ICVCN): proposal to delete Rule 3.41 SO ARCHIVES OF VIROLOGY LA English DT Article AB It is proposed to delete Rule 3.41 of the International Code of Virus Classification and Nomenclature, which requires the name of a virus taxon to precede the term for the taxonomic unit. C1 [Kuhn, Jens H.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, Frederick, MD USA. [Radoshitzky, Sheli R.; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD USA. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, Frederick, MD USA. EM kuhnjens@mail.nih.gov RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]; NIAID [HHSN272200200016I] FX The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was funded by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T) to SB and SRR. JHK performed this work as an employee of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute, and FKM as an employee of Battelle Memorial Institute, under its prime contract with NIAID, under Contract No. HHSN272200200016I. NR 2 TC 4 Z9 4 U1 0 U2 5 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD JAN PY 2013 VL 158 IS 1 BP 297 EP 299 DI 10.1007/s00705-012-1453-1 PG 3 WC Virology SC Virology GA 067KY UT WOS:000313294200041 PM 22932924 ER PT J AU Kuhn, JH Bao, YM Bavari, S Becker, S Bradfute, S Brister, JR Bukreyev, AA Chandran, K Davey, RA Dolnik, O Dye, JM Enterlein, S Hensley, LE Honko, AN Jahrling, PB Johnson, KM Kobinger, G Leroy, EM Lever, MS Muhlberger, E Netesov, SV Olinger, GG Palacios, G Patterson, JL Paweska, JT Pitt, L Radoshitzky, SR Saphire, EO Smither, SJ Swanepoel, R Towner, JS van der Groen, G Volchkov, VE Wahl-Jensen, V Warren, TK Weidmann, M Nichol, ST AF Kuhn, Jens H. Bao, Yiming Bavari, Sina Becker, Stephan Bradfute, Steven Brister, J. Rodney Bukreyev, Alexander A. Chandran, Kartik Davey, Robert A. Dolnik, Olga Dye, John M. Enterlein, Sven Hensley, Lisa E. Honko, Anna N. Jahrling, Peter B. Johnson, Karl M. Kobinger, Gary Leroy, Eric M. Lever, Mark S. Muehlberger, Elke Netesov, Sergey V. Olinger, Gene G. Palacios, Gustavo Patterson, Jean L. Paweska, Janusz T. Pitt, Louise Radoshitzky, Sheli R. Saphire, Erica Ollmann Smither, Sophie J. Swanepoel, Robert Towner, Jonathan S. van der Groen, Guido Volchkov, Viktor E. Wahl-Jensen, Victoria Warren, Travis K. Weidmann, Manfred Nichol, Stuart T. TI Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae SO ARCHIVES OF VIROLOGY LA English DT Article ID TAXONOMY; NAMES; IDENTIFICATION; VIROLOGISTS; EBOLAVIRUS; PROPOSAL AB The task of international expert groups is to recommend the classification and naming of viruses. The International Committee on Taxonomy of Viruses Filoviridae Study Group and other experts have recently established an almost consistent classification and nomenclature for filoviruses. Here, further guidelines are suggested to include their natural genetic variants. First, this term is defined. Second, a template for full-length virus names (such as "Ebola virus H.sapiens-tc/COD/1995/Kikwit-9510621") is proposed. These names contain information on the identity of the virus (e.g., Ebola virus), isolation host (e.g., members of the species Homo sapiens), sampling location (e.g., Democratic Republic of the Congo (COD)), sampling year, genetic variant (e.g., Kikwit), and isolate (e.g., 9510621). Suffixes are proposed for individual names that clarify whether a given genetic variant has been characterized based on passage zero material (-wt), has been passaged in tissue/cell culture (-tc), is known from consensus sequence fragments only (-frag), or does (most likely) not exist anymore (-hist). We suggest that these comprehensive names are to be used specifically in the methods section of publications. Suitable abbreviations, also proposed here, could then be used throughout the text, while the full names could be used again in phylograms, tables, or figures if the contained information aids the interpretation of presented data. The proposed system is very similar to the well-known influenzavirus nomenclature and the nomenclature recently proposed for rotaviruses. If applied consistently, it would considerably simplify retrieval of sequence data from electronic databases and be a first important step toward a viral genome annotation standard as sought by the National Center for Biotechnology Information (NCBI). Furthermore, adoption of this nomenclature would increase the general understanding of filovirus-related publications and presentations and improve figures such as phylograms, alignments, and diagrams. Most importantly, it would counter the increasing confusion in genetic variant naming due to the identification of ever more sequences through technological breakthroughs in high-throughput sequencing and environmental sampling. C1 [Kuhn, Jens H.; Jahrling, Peter B.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, Frederick, MD USA. [Bao, Yiming; Brister, J. Rodney] Natl Lib Med, Informat Engn Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. [Bavari, Sina; Dye, John M.; Honko, Anna N.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] USA, Med Res Inst Infect Dis, Frederick, MD USA. [Becker, Stephan; Dolnik, Olga] Univ Marburg, Inst Virol, D-35032 Marburg, Germany. [Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA. [Bukreyev, Alexander A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Enterlein, Sven] Integrated BioTherapeut Inc, Gaithersburg, MD USA. [Hensley, Lisa E.] Fed Drug Adm, Med Countermeasure Initiat, Silver Spring, MD USA. [Kobinger, Gary] Publ Hlth Agcy Canada, Natl Microbiol Lab, Special Pathogens Program, Winnipeg, MB, Canada. [Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon. [Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Porton Down, Salisbury, Wilts, England. [Muehlberger, Elke] Univ Sch Med, Natl Emerging Infect Dis Lab, Boston, MA USA. [Netesov, Sergey V.] Novosibirsk State Univ, Novosibirsk 630090, Novosibirsk Obl, Russia. [Paweska, Janusz T.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Ctr Emerging & Zoonot Dis, Johannesburg, Gauteng, South Africa. [Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa. [Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent, Viral Special Pathogens Branch, Div High Consequence Pathogens Pathol, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium. [Volchkov, Viktor E.] Univ Lyon, Lab Filovirus, Ecole Normale Super Lyon, INSERM,U758,UCB Lyon 1, Lyon, France. [Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, Div Clin Res DCR, NIH, B-8200 Res Plaza, Frederick, MD USA. EM kuhnjens@mail.nih.gov; stn1@cdc.gov RI Netesov, Sergey/A-3751-2013; Volchkov, Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; LEROY, Eric/I-4347-2016; Becker, Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Weidmann, Manfred/G-1817-2015 OI Netesov, Sergey/0000-0002-7786-2464; Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045; Olinger, Gene/0000-0001-7338-0292; LEROY, Eric/0000-0003-0022-0890; Muhlberger, Elke/0000-0003-3547-9376; Honko, Anna/0000-0001-9165-148X; Becker, Stephan/0000-0002-2794-5659; Palacios, Gustavo/0000-0001-5062-1938; Weidmann, Manfred/0000-0002-7063-7491 FU Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]; NIAID [HHSN272200200016I]; NIH, National Library of Medicine FX The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was funded in part by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T to SB). JHK and VWJ performed this work as employees of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200200016I. This research was also supported in part by the Intramural Research Program of the NIH, National Library of Medicine (YB and JRB). NR 36 TC 49 Z9 50 U1 2 U2 32 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD JAN PY 2013 VL 158 IS 1 BP 301 EP 311 DI 10.1007/s00705-012-1454-0 PG 11 WC Virology SC Virology GA 067KY UT WOS:000313294200042 PM 23001720 ER PT J AU Nualart-Marti, A Solsona, C Fields, RD AF Nualart-Marti, Anna Solsona, Caries Fields, R. Douglas TI Gap junction communication in myelinating glia SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE Gap junction; Hemichannel; Myelinating glia; Intercellular communication; CMTX; PMLD ID MARIE-TOOTH-DISEASE; CENTRAL-NERVOUS-SYSTEM; MERZBACHER-LIKE-DISEASE; SCHMIDT-LANTERMAN INCISURES; RAT OPTIC-NERVE; SCHWANN-CELLS; CONNEXIN 32; PANNEXIN 1; OLIGODENDROCYTE CONNEXINS; WHITE-MATTER AB Gap junction communication is crucial for myelination and axonal survival in both the peripheral nervous system (PNS) and central nervous system (CNS). This review examines the different types of gap junctions in myelinating glia of the PNS and CNS (Schwann cells and oligodendrocytes respectively), including their functions and involvement in neurological disorders. Gap junctions mediate intercellular communication among Schwann cells in the PNS, and among oligodendrocytes and between oligodendrocytes and astrocytes in the CNS. Reflexive gap junctions mediating transfer between different regions of the same cell promote communication between cellular compartments of myelinating glia that are separated by layers of compact myelin. Gap junctions in myelinating glia regulate physiological processes such as cell growth, proliferation, calcium signaling, and participate in extracellular signaling via release of netirotransmitters from hemijunctions. In the CNS, gap junctions form a glial network between oligodendrocytes and astrocytes. This transcellular communication is hypothesized to maintain homeostasis by facilitating restoration of membrane potential after axonal activity via electrical coupling and the re-distribution of potassium ions released from axons. The generation of transgenic mice for different subsets of connexins has revealed the contribution of different connexins in gap junction formation and illuminated new subcellular mechanisms underlying demyelination and cognitive defects. Alterations in metabolic coupling have been reported in animal models of X-linked Charcot-Marie-Tooth disease (CMTX) and Pelizaeus-Merzbarcher-like disease (PMLD), which are caused by mutations in the genes encoding for connexin 32 and connexin 47 respectively. Future research identifying the expression and regulation of gap junctions in myelinating glia is likely to provide a better understanding of myelinating glia in nervous system function, plasticity, and disease. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions. (C) 2012 Published by Elsevier B.V. C1 [Nualart-Marti, Anna; Solsona, Caries] Univ Barcelona, Lab Cellular & Mol Neurobiol, Dept Pathol & Expt Therapeut, Barcelona 08907, Spain. [Nualart-Marti, Anna] Inst Invest Biomed Bellvitge IDIBELL, Barcelona 08908, Spain. [Nualart-Marti, Anna; Fields, R. Douglas] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Nervous Syst Dev & Plast Sect, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM annanualart@ub.edu; solsona@ub.edu; fieldsd@mail.nih.gov FU Intramural NIH HHS [ZIA HD000713-15] NR 132 TC 31 Z9 33 U1 1 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JAN PY 2013 VL 1828 IS 1 SI SI BP 69 EP 78 DI 10.1016/j.bbamem.2012.01.024 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 068XD UT WOS:000313398600007 PM 22326946 ER PT J AU Ma, CX Ellis, MJC Petroni, GR Guo, ZF Cai, SR Ryan, CE Lockhart, AC Naughton, MJ Pluard, TJ Brenin, CM Picus, J Creekmore, AN Mwandoro, T Yarde, ER Reed, J Ebbert, M Bernard, PS Watson, M Doyle, LA Dancey, J Piwnica-Worms, H Fracasso, PM AF Ma, Cynthia X. Ellis, Matthew J. C. Petroni, Gina R. Guo, Zhanfang Cai, Shi-rong Ryan, Christine E. Lockhart, A. Craig Naughton, Michael J. Pluard, Timothy J. Brenin, Christiana M. Picus, Joel Creekmore, Allison N. Mwandoro, Tibu Yarde, Erin R. Reed, Jerry Ebbert, Mark Bernard, Philip S. Watson, Mark Doyle, Laurence A. Dancey, Janet Piwnica-Worms, Helen Fracasso, Paula M. TI A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Irinotecan; UCN-01; Chk1; Metastatic triple negative breast cancer; TP53; p53 ID DNA-DAMAGE; CHECKPOINT KINASE-1; REPLICATION STRESS; SOLID TUMORS; CELL LINES; CHK1; P53; PROTEIN; CYTOTOXICITY; ABROGATION AB Mutations in TP53 lead to a defective G1 checkpoint and the dependence on checkpoint kinase 1 (Chk1) for G2 or S phase arrest in response to DNA damage. In preclinical studies, Chk1 inhibition resulted in enhanced cytotoxicity of several chemotherapeutic agents. The high frequency of TP53 mutations in triple negative breast cancer (TNBC: negative for estrogen receptor, progesterone receptor, and HER2) make Chk1 an attractive therapeutic target. UCN-01, a non-selective Chk1 inhibitor, combined with irinotecan demonstrated activity in advanced TNBC in our Phase I study. The goal of this trial was to further evaluate this treatment in women with TNBC. Patients with metastatic TNBC previously treated with anthracyclines and taxanes received irinotecan (100-125 mg/m(2) IV days 1, 8, 15, 22) and UCN-01 (70 mg/m(2) IV day 2, 35 mg/m(2) day 23 and subsequent doses) every 42-day cycle. Peripheral blood mononuclear cells (PBMC) and tumor specimens were collected. Twenty five patients were enrolled. The overall response (complete response (CR) + partial response (PR)) rate was 4 %. The clinical benefit rate (CR + PR + stable disease a parts per thousand yen6 months) was 12 %. Since UCN-01 inhibits PDK1, phosphorylated ribosomal protein S6 (pS6) in PBMC was assessed. Although reduced 24 h post UCN-01, pS6 levels rose to baseline by day 8, indicating loss of UCN-01 bioavailability. Immunostains of gamma H2AX and pChk1(S296) on serial tumor biopsies from four patients demonstrated an induction of DNA damage and Chk1 activation following irinotecan. However, Chk1 inhibition by UCN-01 was not observed in all tumors. Most tumors were basal-like (69 %), and carried mutations in TP53 (53 %). Median overall survival in patients with TP53 mutant tumors was poor compared to wild type (5.5 vs. 20.3 months, p = 0.004). This regimen had limited activity in TNBC. Inconsistent Chk1 inhibition was likely due to the pharmacokinetics of UCN-01. TP53 mutations were associated with a poor prognosis in metastatic TNBC. C1 [Ma, Cynthia X.; Ellis, Matthew J. C.; Guo, Zhanfang; Naughton, Michael J.; Pluard, Timothy J.] Washington Univ, Sch Med, Dept Med, Sect Breast Oncol,Div Oncol, St Louis, MO 63110 USA. [Ma, Cynthia X.; Ellis, Matthew J. C.; Lockhart, A. Craig; Naughton, Michael J.; Pluard, Timothy J.; Picus, Joel; Creekmore, Allison N.; Mwandoro, Tibu; Watson, Mark; Piwnica-Worms, Helen] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. [Petroni, Gina R.] Univ Virginia, Ctr Canc, Dept Publ Hlth Sci, Div Translat Res & Appl Stat, Charlottesville, VA 22908 USA. [Cai, Shi-rong; Ryan, Christine E.; Piwnica-Worms, Helen] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. [Cai, Shi-rong; Ryan, Christine E.; Piwnica-Worms, Helen] Washington Univ, Sch Med, Bright Inst, St Louis, MO 63110 USA. [Lockhart, A. Craig; Picus, Joel; Piwnica-Worms, Helen] Washington Univ, Sch Med, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA. [Brenin, Christiana M.; Yarde, Erin R.; Fracasso, Paula M.] Univ Virginia, Sch Med, Dept Med, Div Hematol Oncol, Charlottesville, VA 22908 USA. [Reed, Jerry] Washington Univ, Sch Med, Genome Inst, St Louis, MO 63110 USA. [Ebbert, Mark; Bernard, Philip S.] ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA. [Bernard, Philip S.] Univ Utah, Hlth Sci Ctr, Dept Pathol, Huntsman Canc Inst, Salt Lake City, UT 84132 USA. [Watson, Mark] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Doyle, Laurence A.; Dancey, Janet] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Ma, CX (reprint author), Washington Univ, Sch Med, Dept Med, Sect Breast Oncol,Div Oncol, Campus Box 8056,660 S Euclid Ave, St Louis, MO 63110 USA. EM cma@dom.wustl.edu RI Piwnica-Worms, Helen/C-5214-2012 FU NIH [R21 CA128369, U01 CA114722]; Susan G. Komen Foundation [KG08155] FX We wish to thank the patients and their families for participation in this study. We also thank the nurses, clinical research and regulatory coordinators at Washington University Siteman Cancer Center and the Emily Couric Clinical Cancer Center at the University of Virginia Health System for their care of the patients on this study. Dr. Mark A. Watson, Director, Tissue Procurement Core; Alvin J. Siteman Cancer Center at Washington University School of Medicine; and Barnes-Jewish Hospital and his staff members, especially Ms. Vicky Holtschlag, for tissue acquisition and processing. We would like to thank Ms. Jennifer Stratman and Ms. Shelly Audrain from the Laboratory and Genomic Medicine, Department of Pathology at Washington University School of Medicine for tumor TP53 sequencing. We would like to thank Dr. Katherine Deschryver for reviewing the pathology slides. We would like to thank members of the SPECS team, Sherri Davies, Elaine Mardis, Jacqueline Snider, and Tammi Vickery, for assistance with the PAM50 Breast Cancer Intrinsic Classifer (TM) molecular subtype analysis. Grant Support: NIH R21 CA128369 (P. M. F.), Susan G. Komen Foundation KG08155 (C. X. M. and H.P.-W.), and NIH U01 CA114722 (M.J.E). NR 47 TC 50 Z9 51 U1 0 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2013 VL 137 IS 2 BP 483 EP 492 DI 10.1007/s10549-012-2378-9 PG 10 WC Oncology SC Oncology GA 066DT UT WOS:000313201100015 PM 23242585 ER PT J AU Forsythe, LP Alfano, CM George, SM McTiernan, A Baumgartner, KB Bernstein, L Ballard-Barbash, R AF Forsythe, Laura P. Alfano, Catherine M. George, Stephanie M. McTiernan, Anne Baumgartner, Kathy B. Bernstein, Leslie Ballard-Barbash, Rachel TI Pain in long-term breast cancer survivors: the role of body mass index, physical activity, and sedentary behavior SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Cancer; Pain; Body mass index; Physical activity; Sedentary behavior ID QUALITY-OF-LIFE; TELEVISION VIEWING TIME; ALL-CAUSE MORTALITY; CARCINOMA IN-SITU; GENERAL-POPULATION; UNITED-STATES; OLDER-ADULTS; FOLLOW-UP; FUNCTIONAL LIMITATIONS; RECREATIONAL EXERCISE AB Although pain is common among post-treatment breast cancer survivors, studies that are longitudinal, identify a case definition of clinically meaningful pain, or examine factors contributing to pain in survivors are limited. This study describes longitudinal patterns of pain in long-term breast cancer survivors, evaluating associations of body mass index (BMI), physical activity, sedentary behavior with mean pain severity and above-average pain. Women newly diagnosed with stages 0-IIIA breast cancer (N = 1183) were assessed, on average, 6 months (demographic/clinical characteristics), 30 months (demographics), 40 months (demographics, pain), 5 years (BMI, physical activity, and sedentary behavior), and 10 years (demographics, pain, BMI, physical activity, and sedentary behavior) post-diagnosis. This analysis includes survivors who completed pain assessments 40 months post-diagnosis (N = 801), 10 years post-diagnosis (N = 563), or both (N = 522). Above-average pain was defined by SF-36 bodily pain scores a parts per thousand yen1/2 standard deviation worse than age-specific population norms. We used multiple regression models to test unique associations of BMI, physical activity, and sedentary behavior with pain adjusting for demographic and clinical factors. The proportion of survivors reporting above-average pain was higher at 10 years than at 40 months (32.3 vs. 27.8 %, p < 0.05). Approximately one-quarter of survivors reported improved pain, while 9.0 % maintained above-average pain and 33.1 % reported worsened pain. Cross-sectionally at 10 years, overweight and obese survivors reported higher pain than normal-weight survivors and women meeting physical activity guidelines were less likely to report above-average pain than survivors not meeting these guidelines (p < 0.05). Longitudinally, weight gain (> 5 %) was positively associated, while meeting physical activity guidelines was inversely associated, with above-average pain (OR, 95 % CI = 1.76, 1.03-3.01 and 0.40, 0.20-0.84, respectively) (p < 0.05). Weight gain and lack of physical activity place breast cancer survivors at risk for pain long after treatment ends. Weight control and exercise interventions should be tested for effects on long-term pain in these women. C1 [Forsythe, Laura P.; Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [George, Stephanie M.; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth, Seattle, WA 98104 USA. [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. RP Forsythe, LP (reprint author), Patient Centered Outcomes Res Inst, 1828 L St NW,Suite 900, Washington, DC 20036 USA. EM lforsythe@pcori.org FU National Cancer Institute [N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010] FX The HEAL study is supported by the National Cancer Institute (Grants N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010). We would also like to thank the HEAL study managers, Todd Gibson of Information Management Systems, and the HEAL study participants. NR 69 TC 23 Z9 23 U1 2 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2013 VL 137 IS 2 BP 617 EP 630 DI 10.1007/s10549-012-2335-7 PG 14 WC Oncology SC Oncology GA 066DT UT WOS:000313201100029 PM 23242613 ER PT J AU Dinglas, VD Gifford, JM Husain, N Colantuoni, E Needham, DM AF Dinglas, Victor D. Gifford, Jeneen M. Husain, Nadia Colantuoni, Elizabeth Needham, Dale M. TI Quality of Life Before Intensive Care Using EQ-5D: Patient Versus Proxy Responses SO CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; adult; critical care; health status; proxy; quality of life; respiratory distress syndrome ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY ILL PATIENTS; CRITICAL ILLNESS; HEALTH; AGREEMENT; SURVIVORS; PERSPECTIVES; RELIABILITY; POPULATION; DIFFERENCE AB Objective: To compare patients' retrospectively reported baseline quality of life before intensive care hospitalization with population norms and proxy reports. Design: Prospective cohort study. Setting: Thirteen ICUs at four teaching hospitals in Baltimore, MD. Patients: One hundred forty acute lung injury survivors and their designated proxies. Interventions: Around the time of hospital discharge, both patients and proxies were asked to retrospectively estimate patients' baseline quality of life before hospital admission using the EQ-5D quality-of-life instrument. Measurements and Main Results: Mean patient-rated EQ-5D visual analog scale scores and utility scores were significantly lower than population norms but were significantly higher than proxy ratings. However, the magnitude of difference in average utility scores between patients and either population norms or proxies was not clinically important. For the five individual EQ-5D domains, kappa statistics revealed slight to fair agreement between patients and proxies. Bland-Altman plots demonstrated that for both the visual analog scale and utility scores, proxies underestimated scores when patients reported high ratings and overestimated scores for low patient ratings. Conclusions: Patients retrospectively reported worse baseline health status before acute lung injury than population norms and better status than proxy reports; however, the magnitude of these differences in health status may not be clinically important. Proxies had only slight to fair agreement with patients in all five EQ-5D domains, attenuating patients' more extreme ratings toward moderate scores. Caution is required when interpreting proxy retrospective reports of baseline health status for survivors of acute lung injury. (Crit Care Med 2013; 41:9-14) C1 [Dinglas, Victor D.; Needham, Dale M.] Johns Hopkins Univ, Outcomes Crit Illness & Surg Grp, Div Pulm & Crit Care Med, Baltimore, MD 21218 USA. [Gifford, Jeneen M.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Husain, Nadia; Colantuoni, Elizabeth] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Needham, Dale M.] Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD USA. RP Needham, DM (reprint author), Johns Hopkins Univ, Outcomes Crit Illness & Surg Grp, Div Pulm & Crit Care Med, Baltimore, MD 21218 USA. EM dale.needham@jhmi.edu FU National Institutes of Health (Acute Lung Injury SCCOR Grant) [P050 HL 73994]; Canadian Institutes of Health Research FX This research was supported by the National Institutes of Health (Acute Lung Injury SCCOR Grant # P050 HL 73994). Dr. Needham was supported by a Clinician-Scientist Award from the Canadian Institutes of Health Research. The funding bodies had no role in the study design, manuscript writing, or decision to submit the manuscript for publication. NR 36 TC 12 Z9 13 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2013 VL 41 IS 1 BP 9 EP 14 DI 10.1097/CCM.0b013e318265f340 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 065LR UT WOS:000313150300002 PM 23232287 ER PT J AU Barrett, J AF Barrett, John TI Progress and change for Cytotherapy SO CYTOTHERAPY LA English DT Editorial Material C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Hematol Branch, 10,CRC Room 3E-5330,10 Ctr Dr, Bethesda, MD 20892 USA. EM cytotherapyjournal@gmail.com NR 0 TC 0 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD JAN PY 2013 VL 15 IS 1 BP 1 EP 1 DI 10.1016/j.jcyt.2012.10.001 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 068RF UT WOS:000313383200001 PM 23260080 ER PT J AU Shechner, T Jarcho, JM Britton, JC Leibenluft, E Pine, DS Nelson, EE AF Shechner, Tomer Jarcho, Johanna M. Britton, Jennifer C. Leibenluft, Ellen Pine, Daniel S. Nelson, Eric E. TI ATTENTION BIAS OF ANXIOUS YOUTH DURING EXTENDED EXPOSURE OF EMOTIONAL FACE PAIRS: AN EYE-TRACKING STUDY SO DEPRESSION AND ANXIETY LA English DT Article DE anxiety; threat-bias; orienting; eye tracking ID GENERALIZED ANXIETY DISORDER; SOCIAL ANXIETY; TIME-COURSE; FACIAL EXPRESSIONS; THREAT; CHILDREN; ADOLESCENTS; MOVEMENTS; GAZE; TASK AB Background Previous studies demonstrate that anxiety is characterized by biased attention toward threats, typically measured by differences in motor reaction time to threat and neutral cues. Using eye-tracking methodology, the current study measured attention biases in anxious and nonanxious youth, using unrestricted free viewing of angry, happy, and neutral faces. Methods Eighteen anxious and 15 nonanxious youth (817 years old) passively viewed angry-neutral and happy-neutral face pairs for 10 s while their eye movements were recorded. Results Anxious youth displayed a greater attention bias toward angry faces than nonanxious youth, and this bias occurred in the earliest phases of stimulus presentation. Specifically, anxious youth were more likely to direct their first fixation to angry faces, and they made faster fixations to angry than neutral faces. Conclusions Consistent with findings from earlier, reaction-time studies, the current study shows that anxious youth, like anxious adults, exhibit biased orienting to threat-related stimuli. This study adds to the existing literature by documenting that threat biases in eye-tracking patterns are manifest at initial attention orienting. Depression and Anxiety 30: 14-21, 2013. Published 2012. C1 [Shechner, Tomer] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA. RP Shechner, T (reprint author), NIMH, Sect Dev Affect Neurosci, 9000 Rockville Pike,Bldg 15K,Room 208, Bethesda, MD 20892 USA. EM shechnert@mail.nih.gov RI Britton, Jennifer/J-4501-2013; OI Jarcho, Johanna/0000-0001-9075-6968; Nelson, Eric/0000-0002-3376-2453 FU NIMH FX Contract grant sponsor: NIMH. NR 30 TC 19 Z9 19 U1 5 U2 68 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2013 VL 30 IS 1 BP 14 EP 21 DI 10.1002/da.21986 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 066VY UT WOS:000313250600003 PM 22815254 ER PT J AU Lebowitz, ER Woolston, J Bar-Haim, Y Calvocoressi, L Dauser, C Warnick, E Scahill, L Chakir, AR Shechner, T Hermes, H Vitulano, LA King, RA Leckman, JF AF Lebowitz, Eli R. Woolston, Joseph Bar-Haim, Yair Calvocoressi, Lisa Dauser, Christine Warnick, Erin Scahill, Lawrence Chakir, Adi R. Shechner, Tomer Hermes, Holly Vitulano, Lawrence A. King, Robert A. Leckman, James F. TI FAMILY ACCOMMODATION IN PEDIATRIC ANXIETY DISORDERS SO DEPRESSION AND ANXIETY LA English DT Article DE family accommodation; anxiety disorders; family members; treatment outcomes; obsessive compulsive disorder; cognitive behavioral therapy ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; PARENT-CHILD INTERACTIONS; DISRUPTIVE BEHAVIORS; CONTROLLED-TRIAL; PSYCHOMETRIC PROPERTIES; COERCIVE; PREDICTORS; SYMPTOMS; OCD AB Background Family accommodation has been studied in obsessive compulsive disorder using the Family Accommodation Scale (FAS) and predicts greater symptom severity, more impairment, and poorer treatment outcomes. However, family accommodation has yet to be systematically studied among families of children with other anxiety disorders. We developed the Family Accommodation ScaleAnxiety (FASA) that includes modified questions from the FAS to study accommodation across childhood anxiety disorders. The objectives of this study were to report on the first study of family accommodation across childhood anxiety disorders and to test the utility of the FASA for assessing the phenomenon. Methods Participants were parents (n = 75) of anxious children from two anxiety disorder specialty clinics (n = 50) and a general outpatient clinic (n = 25). Measures included FASA, structured diagnostic interviews, and measures of anxiety and depression. Results Accommodation was highly prevalent across all anxiety disorders and particularly associated with separation anxiety. Most parents reported participation in symptoms and modification of family routines as well as distress resulting from accommodation and undesirable consequences of not accommodating. The FASA displayed good internal consistency and convergent and divergent validity. Accommodation correlated significantly with anxious but not depressive symptoms, when controlling for the association between anxiety and depression. Factor analysis of the FASA pointed to a two-factor solution; one relating to modifications, the other to participation in symptoms. Conclusions Accommodation is common across childhood anxiety disorders and associated with severity of anxiety symptoms. The FASA shows promise as a means of assessing family accommodation in childhood anxiety disorders. Depression and Anxiety 30: 47-54, 2013. (C) 2012 Wiley Periodicals, Inc. C1 [Lebowitz, Eli R.; Woolston, Joseph; Dauser, Christine; Warnick, Erin; Scahill, Lawrence; Hermes, Holly; Vitulano, Lawrence A.; King, Robert A.; Leckman, James F.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Bar-Haim, Yair; Chakir, Adi R.] Tel Aviv Univ, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Calvocoressi, Lisa] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Shechner, Tomer] NIMH, Bethesda, MD 20892 USA. RP Lebowitz, ER (reprint author), POB 207900, New Haven, CT 06520 USA. EM eli.lebowitz@yale.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU Messer Anxiety Program at the Yale Child Study Center; John Wiley and Sons; National Institutes of Health; Tourette Syndrome Association; McGraw Hill; Oxford University Press FX Eli Lebowitz is grateful for the support of the Messer Anxiety Program at the Yale Child Study Center. Dr. Lebowitz has received royalties from John Wiley and Sons. Dr. Leckman has received research support from the National Institutes of Health and the Tourette Syndrome Association. He has received royalties from John Wiley and Sons, McGraw Hill, and Oxford University Press. Dr. Scahill serves as a consultant for BioMarin, Boehringer-Ingelheim, Neruosearch, and Pfizer. All other authors have no conflicts to disclose. NR 38 TC 40 Z9 40 U1 4 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD JAN PY 2013 VL 30 IS 1 BP 47 EP 54 DI 10.1002/da.21998 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 066VY UT WOS:000313250600007 PM 22965863 ER PT J AU Sacks, DB AF Sacks, David B. TI Hemoglobin A(1c) in Diabetes: Panacea or Pointless? SO DIABETES LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; GLYCATED HEMOGLOBIN; GLYCEMIC CONTROL; NATIONAL-HEALTH; IRON-DEFICIENCY; GLUCOSE CONTROL; BLOOD; GLYCOHEMOGLOBIN; STANDARDIZATION; COMPLICATIONS C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Sacks, DB (reprint author), NIH, Dept Lab Med, Bldg 10, Bethesda, MD 20892 USA. EM sacksdb@mail.nih.gov OI Sacks, David/0000-0003-3100-0735 FU Intramural NIH HHS NR 26 TC 11 Z9 11 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2013 VL 62 IS 1 BP 41 EP 43 DI 10.2337/db12-1485 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061CM UT WOS:000312824700012 PM 23258914 ER PT J AU Hodgin, JB Nair, V Zhang, H Randolph, A Harris, RC Nelson, RG Weil, EJ Cavalcoli, JD Patel, JM Brosius, FC Kretzler, M AF Hodgin, Jeffrey B. Nair, Viji Zhang, Hongyu Randolph, Ann Harris, Raymond C. Nelson, Robert G. Weil, E. Jennifer Cavalcoli, James D. Patel, Jignesh M. Brosius, Frank C., III Kretzler, Matthias TI Identification of Cross-Species Shared Transcriptional Networks of Diabetic Nephropathy in Human and Mouse Glomeruli SO DIABETES LA English DT Article ID EXPRESSION; MICE; PODOCYTES; ALBUMINURIA; MICROARRAYS; DISEASE; MARKERS AB Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations of human DN, limiting their utility. To define the molecular similarities and differences between human and murine DN, we performed a cross-species comparison of glomerular transcriptional networks. Glomerular gene expression was profiled in patients with early type 2 DN and in three mouse models (streptozotocin DBA/2, C57BLKS db/db, and eNOS-deficient C57BLKS db/db mice). Species-specific transcriptional networks were generated and compared with a novel network-matching algorithm. Three shared human-mouse cross-species glomerular transcriptional networks containing 143 (Human-DBA STZ), 97 (Human-BKS db/db), and 162 (Human-BKS eNOS(-/-) db/db) gene nodes were generated. Shared nodes across all networks reflected established pathogenic mechanisms of diabetes complications, such as elements of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and vascular endothelial growth factor receptor (VEGFR) signaling pathways. In addition, novel pathways not previously associated with DN and cross-species gene nodes and pathways unique to each of the human-mouse networks were discovered. The human-mouse shared glomerular transcriptional networks will assist DN researchers in selecting mouse models most relevant to the human disease process of interest. Moreover, they will allow identification of new pathways shared between mice and humans. Diabetes 62:299-308, 2013 C1 [Nair, Viji; Zhang, Hongyu; Randolph, Ann; Brosius, Frank C., III; Kretzler, Matthias] Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Hodgin, Jeffrey B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Harris, Raymond C.] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Nelson, Robert G.; Weil, E. Jennifer] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Cavalcoli, James D.; Kretzler, Matthias] Univ Michigan, Dept Bioinformat & Computat Med, Ann Arbor, MI 48109 USA. [Patel, Jignesh M.] Univ Wisconsin, Dept Comp Sci, Madison, WI 53706 USA. [Brosius, Frank C., III] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. RP Brosius, FC (reprint author), Univ Michigan, Dept Internal Med, Div Nephrol, Ann Arbor, MI 48109 USA. EM fbrosius@umich.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01-DK-076139, U24-DK-076169, 20497-16, R01-DK-054639-14, R01-DK-079912, R24-DK-082841]; Juvenile Diabetes Research Foundation; Applied Systems Biology Core of University of Michigan O'Brien Kidney Center [P30-DK-081943] FX This work was supported by grants U01-DK-076139, U24-DK-076169/subaward 20497-16, R01-DK-054639-14, R01-DK-079912, and R24-DK-082841 from the National Institute of Diabetes and Digestive and Kidney Diseases and by funds from the Juvenile Diabetes Research Foundation. Support for informational analysis was provided by the Applied Systems Biology Core of the University of Michigan O'Brien Kidney Center (P30-DK-081943). NR 27 TC 40 Z9 40 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JAN PY 2013 VL 62 IS 1 BP 299 EP 308 DI 10.2337/db11-1667 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061CM UT WOS:000312824700039 PM 23139354 ER PT J AU Gunay-Aygun, M Font-Montgomery, E Lukose, L Gerstein, MT Piwnica-Worms, K Choyke, P Daryanani, KT Turkbey, B Fischer, R Bernardini, I Sincan, M Zhao, XC Sandler, NG Roque, A Douek, DC Graf, J Huizing, M Bryant, JC Mohan, P Gahl, WA Heller, T AF Gunay-Aygun, Meral Font-Montgomery, Esperanza Lukose, Linda Gerstein, Maya Tuchman Piwnica-Worms, Katie Choyke, Peter Daryanani, Kailash T. Turkbey, Baris Fischer, Roxanne Bernardini, Isa Sincan, Murat Zhao, Xiongce Sandler, Netanya G. Roque, Annelys Douek, Daniel C. Graf, Jennifer Huizing, Marjan Bryant, Joy C. Mohan, Parvathi Gahl, William A. Heller, Theo TI Characteristics of Congenital Hepatic Fibrosis in a Large Cohort of Patients With Autosomal Recessive Polycystic Kidney Disease SO GASTROENTEROLOGY LA English DT Article DE Ductal Plate Malformation; Noncirrhotic Portal Hypertension; Genetics; Hepatorenal Fibrocystic Disease ID INTRAHEPATIC BILE-DUCTS; NORMAL VALUES; LIVER VOLUME; CHILDREN; SPLEEN; LENGTH; ABNORMALITIES; DIMENSIONS; EXPERIENCE; OUTCOMES AB BACKGROUND & AIMS: Autosomal recessive polycystic kidney disease (ARPKD), the most common ciliopathy of childhood, is characterized by congenital hepatic fibrosis and progressive cystic degeneration of kidneys. We aimed to describe congenital hepatic fibrosis in patients with ARPKD, confirmed by detection of mutations in PKHD1. METHODS: Patients with ARPKD and congenital hepatic fibrosis were evaluated at the National Institutes of Health from 2003 to 2009. We analyzed clinical, molecular, and imaging data from 73 patients (age, 1-56 years; average, 12.7 +/- 13.1 years) with kidney and liver involvement (based on clinical, imaging, or biopsy analyses) and mutations in PKHD1. RESULTS: Initial symptoms were liver related in 26% of patients, and others presented with kidney disease. One patient underwent liver and kidney transplantation, and 10 others received kidney transplants. Four presented with cholangitis and one with variceal bleeding. Sixty-nine percent of patients had enlarged left lobes on magnetic resonance imaging, 92% had increased liver echogenicity on ultrasonography, and 65% had splenomegaly. Splenomegaly started early in life; 60% of children younger than 5 years had enlarged spleens. Spleen volume had an inverse correlation with platelet count and prothrombin time but not with serum albumin level. Platelet count was the best predictor of spleen volume (area under the curve of 0.88905), and spleen length corrected for patient's height correlated inversely with platelet count (R-2 = 0.42, P < .0001). Spleen volume did not correlate with renal function or type of PKHD1 mutation. Twenty-two of 31 patients who underwent endoscopy were found to have varices. Five had variceal bleeding, and 2 had portosystemic shunts. Forty-percent had Caroli syndrome, and 30% had an isolated dilated common bile duct. CONCLUSIONS: Platelet count is the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with ARPKD. Seventy percent of patients with ARPKD have biliary abnormalities. Kidney and liver disease are independent, and variability in severity is not explainable by type of PKHD1 mutation; ClinicalTrials.gov number, NCT00068224. C1 [Gunay-Aygun, Meral; Font-Montgomery, Esperanza; Lukose, Linda; Gerstein, Maya Tuchman; Piwnica-Worms, Katie; Fischer, Roxanne; Bernardini, Isa; Sincan, Murat; Graf, Jennifer; Huizing, Marjan; Bryant, Joy C.; Gahl, William A.; Heller, Theo] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gunay-Aygun, Meral; Gahl, William A.] Off Rare Dis, Intramural Program, Bethesda, MD USA. [Choyke, Peter; Turkbey, Baris] NCI, Mol Imaging Program, Bethesda, MD 20892 USA. [Daryanani, Kailash T.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA. [Zhao, Xiongce] NIDDK, Liver Dis Branch, Bethesda, MD USA. [Sandler, Netanya G.; Roque, Annelys; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Mohan, Parvathi] George Washington Univ, Dept Pediat Gastroenterol, Washington, DC USA. RP Gunay-Aygun, M (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov OI Utay, Netanya/0000-0002-6407-8670 FU Intramural Research Programs of the National Human Genome Research Institute; National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases; NIH Clinical Center FX Supported by the Intramural Research Programs of the National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and NIH Clinical Center. NR 41 TC 30 Z9 35 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP 112 EP U218 DI 10.1053/j.gastro.2012.09.056 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100032 PM 23041322 ER PT J AU di Magliano, MP Forsmark, C Freedman, S Hebrok, M Pasricha, PJ Saluja, A Stanger, BZ Holt, J Serrano, J James, SP Rustgi, AK AF di Magliano, Marina Pasca Forsmark, Christopher Freedman, Steven Hebrok, Matthias Pasricha, Pankaj J. Saluja, Ashok Stanger, Ben Z. Holt, Jane Serrano, Jose James, Stephen P. Rustgi, Anil K. TI Advances in Acute and Chronic Pancreatitis: From Development to Inflammation and Repair SO GASTROENTEROLOGY LA English DT Article ID SHWACHMAN-DIAMOND-SYNDROME; HEREDITARY PANCREATITIS; MOUSE PANCREAS; CHYMOTRYPSIN C; RAS ACTIVITY; ADULT-MOUSE; TRYPSINOGEN; CELLS; MICE; ACTIVATION C1 [di Magliano, Marina Pasca] Univ Michigan, Sch Med, Dept Surg, Div Surg Oncol,Dept Cell & Dev Biol, Ann Arbor, MI USA. [Forsmark, Christopher] Univ Florida, Coll Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Gainesville, FL USA. [Freedman, Steven] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Translat Res,Pancreas Ctr, Boston, MA 02215 USA. [Hebrok, Matthias] Univ Calif San Francisco, San Francisco Med Sch, Ctr Diabet, San Francisco, CA 94143 USA. [Pasricha, Pankaj J.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol,Ctr Motil Disorders &, Baltimore, MD 21205 USA. [Saluja, Ashok] Univ Minnesota, Sch Med, Dept Surg, Minneapolis, MN 55455 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Abramson Family Canc Res Inst, Div Gastroenterol,Dept Med & Cell & Dev Biol, Philadelphia, PA 19104 USA. [Stanger, Ben Z.] Univ Penn, Perelman Sch Med, Ctr Canc, Philadelphia, PA 19104 USA. [Holt, Jane] Natl Pancreas Fdn, Boston, MA USA. [Serrano, Jose; James, Stephen P.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA. [Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Div Gastroenterol,Dept Med, Philadelphia, PA 19104 USA. [Rustgi, Anil K.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Div Gastroenterol,Dept Genet, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, Perelman Sch Med, Abramson Canc Ctr, GI Div,Dept Med, 415 Curie Blvd,600 CRB, Philadelphia, PA 19104 USA. EM anil2@mail.med.upenn.edu NR 20 TC 4 Z9 4 U1 1 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2013 VL 144 IS 1 BP E1 EP E4 DI 10.1053/j.gastro.2012.11.018 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 062ZY UT WOS:000312965100001 ER PT J AU Kimonis, VE Singh, KE Zhong, R Pastakia, B DiGiovanna, JJ Bale, SJ AF Kimonis, Virginia E. Singh, Kathryn E. Zhong, Rocksheng Pastakia, Behram DiGiovanna, John J. Bale, Sherri J. TI Clinical and radiological features in young individuals with nevoid basal cell carcinoma syndrome SO GENETICS IN MEDICINE LA English DT Article DE basal cell nevus syndrome; Gorlin syndrome; nevoid basal cell carcinoma syndrome; pediatric diagnostic criteria ID GORLIN-SYNDROME; NEVUS SYNDROME; HUMAN HOMOLOG; MUTATIONS; MEDULLOBLASTOMA; IRRADIATION; DIAGNOSIS; PATIENT; GENE AB Purpose: Nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, jaw cysts, palmar/plantar pits, spine and rib anomalies, and falx cerebri calcification. Current diagnostic criteria are suboptimal when applied to pediatric populations, as most common symptoms often do not begin to appear until teenage years. Methods: We studied minor and major clinical features in 30 children/teenagers and compared the findings with 75 adults from 26 families with nevoid basal cell carcinoma syndrome. Results: Fifty percent of children/teenagers and 82% of adults had at least one basal cell carcinoma. Jaw cysts occurred in 60% of children/teenagers and 81% of adults. Palmar/plantar pits were the most frequent feature seen in affected individuals at all ages. Macrocephaly was seen in 50% of affected and 8% of unaffected children/teenagers. Frontal bossing, hypertelorism, Sprengel deformity, pectus deformity, and cleft lip/palate were seen among affected children/teenagers but not among their unaffected siblings. Falx calcification, the most frequent radiological feature, was present in 37% of individuals <20 and 79% of those >20 years. Conclusion: We report clinical and radiological manifestations of nevoid basal cell carcinoma syndrome in children/teenagers, many of whom lacked major features such as basal cell carcinomas, jaw cysts, and falx calcification. Evaluations for palmar/plantar pits, craniofacial features, and radiological manifestations permit early diagnosis and optimum surveillance. Genet Med 2013:15(1):79-83 C1 [Kimonis, Virginia E.; Singh, Kathryn E.] Univ Calif Irvine, Div Genet & Metab, Irvine, CA 92717 USA. [Zhong, Rocksheng] Yale Univ, Sch Med, New Haven, CT USA. [Pastakia, Behram] Vet Adm Hosp, Washington, DC USA. [DiGiovanna, John J.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Bale, Sherri J.] GeneDx Inc, Gaithersburg, MD USA. RP Kimonis, VE (reprint author), Univ Calif Irvine, Div Genet & Metab, Irvine, CA 92717 USA. EM vkimonis@uci.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institutes of Health FX Funding was provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health. We thank the participating patients, families, and their physicians whose contributions have made this study possible. NR 29 TC 9 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD JAN PY 2013 VL 15 IS 1 BP 79 EP 83 DI 10.1038/gim.2012.96 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 069TV UT WOS:000313460900009 PM 22918513 ER PT J AU Sherafat-Kazemzadeh, R Yanovski, SZ Yanovski, JA AF Sherafat-Kazemzadeh, R. Yanovski, S. Z. Yanovski, J. A. TI Pharmacotherapy for childhood obesity: present and future prospects SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Review DE clinical trials; obesity drug therapy; anti-obesity agents; child; adolescent; review ID PRADER-WILLI-SYNDROME; PLACEBO-CONTROLLED TRIAL; BODY-MASS INDEX; POLYCYSTIC-OVARY-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; INADEQUATE GLYCEMIC CONTROL; TYPE-2 DIABETES-MELLITUS; LIFE-STYLE INTERVENTION; CONGENITAL LEPTIN DEFICIENCY; CONTROLLED CLINICAL-TRIAL AB Pediatric obesity is a serious medical condition associated with significant comorbidities during childhood and adulthood. Lifestyle modifications are essential for treating children with obesity, yet many have insufficient response to improve health with behavioral approaches alone. This review summarizes the relatively sparse data on pharmacotherapy for pediatric obesity and presents information on obesity medications in development. Most previously studied medications demonstrated, at best, modest effects on body weight and obesity-related conditions. It is to be hoped that the future will bring new drugs targeting specific obesity phenotypes that will allow clinicians to use etiology-specific, and therefore more effective, anti-obesity therapies. International Journal of Obesity (2013) 37, 1-15; doi: 10.1038/ijo.2012.144; published online 28 August 2012 C1 [Yanovski, J. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. [Yanovski, S. Z.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. RP Yanovski, JA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,Hatfield Clin Res Ctr, 10 Ctr Dr,Room 1E-3330,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU NICHD [1ZIAHD000641]; Obecure FX RS-K and SZY declare no conflict of interest. JAY is a Commissioned Officer in the United States Public Health Service, Department of Health and Human Services. JAY was the principal investigator for NICHD-sponsored clinical studies using metformin, orlistat and betahistine, and has received orlistat and matching placebo from Roche Pharmaceuticals and betahistine and matching placebo plus research support for clinical research studies from Obecure.; The conduct of this research was supported by Intramural Research Program Grant 1ZIAHD000641 from the NICHD (to JA Yanovski). NR 295 TC 11 Z9 11 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JAN PY 2013 VL 37 IS 1 BP 1 EP 15 DI 10.1038/ijo.2012.144 PG 15 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 068HW UT WOS:000313358100001 PM 22929210 ER PT J AU Beneri, CA Zeldow, B Nachman, S Van der Linde, M Pillay, E Dittmer, S Kim, S Jean-Philippe, P Coetzee, J Bobat, R Hawkins, E Violari, A AF Beneri, C. A. Zeldow, B. Nachman, S. Van der Linde, M. Pillay, E. Dittmer, S. Kim, S. Jean-Philippe, P. Coetzee, J. Bobat, R. Hawkins, E. Violari, A. CA P1041 Team TI Loss to follow-up among infants in a study of isoniazid prophylaxis (P1041) in South Africa SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE retention; children; tuberculosis ID HIV-INFECTED PATIENTS; TUBERCULOSIS; CHILDREN AB OBJECTIVE: To assess risk factors for loss to follow-up (LFU) from the IMPAACT P1041 study, an isoniazid (INH) prophylaxis study conducted in southern Africa. DESIGN: Infants in two cohorts, human immunodeficiency virus-infected (HIV+) and HIV-exposed but noninfected (HIV-), were randomized to INH or placebo for 96 weeks. LFU was evaluated at week 96. RESULTS: Of 1351 infants, 12.9% were LFU (10.4% HIV+, 14.7% HIV-); 65% of the HIV+ cohort was asymptomatic. Among HIV+ infants, large household size (>6 vs. <4 members, P = 0.035) and presence of an elder (>= 55 years, P = 0.05) were associated with better retention. Although attenuated in adjusted analysis, these associations held among HIV- infants. Among HIV- infants, having a younger mother increased the risk (P = 0.008) and maternal history of TB reduced the risk of LFU, the latter by nearly 70% (P = 0.048 univariate, 0.09 adjusted). LFU was largely due to inability to contact the participant (58% HIV+, 30% HIV-), and inability to attend the clinic and withdrawal of consent (HIV-). CONCLUSIONS: Household support was an important factor in participant retention, particularly for the non-HIV-infected cohort, as young maternal age was a risk factor for LFU. Retaining study participants from this mobile population can be challenging and may warrant additional support. C1 [Beneri, C. A.; Nachman, S.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Zeldow, B.; Kim, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Van der Linde, M.; Coetzee, J.] Tygerberg Hosp, Cape Town, South Africa. [Pillay, E.; Bobat, R.] Univ KwaZulu Natal, Durban, South Africa. [Dittmer, S.; Violari, A.] Univ Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South Africa. [Jean-Philippe, P.] NIAID, Henry Jackson Fdn, Bethesda, MD 20892 USA. [Hawkins, E.] Social & Sci Syst, Silver Spring, MD USA. RP Beneri, CA (reprint author), SUNY Stony Brook, HSC T11 Rm 030, Stony Brook, NY 11794 USA. EM christy.beneri@stonybrook.edu FU Statistical and Data Analysis Center at Harvard School of Public Health, under NIAID [5 U01 A141110, 1 U01 AI068616]; Pediatric AIDS Clinical Trials Group; IMPAACT Group; NICHD [N01-DK-9-001/HHSN267200800001C]; National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health [AI068632] FX This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under NIAID cooperative agreement #5 U01 A141110 with the Pediatric AIDS Clinical Trials Group and #1 U01 AI068616 with the IMPAACT Group. Support of the sites was provided by NIAID and the NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C).; Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health [AI068632]. NR 13 TC 1 Z9 1 U1 0 U2 0 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JAN PY 2013 VL 17 IS 1 BP 32 EP 38 DI 10.5588/ijtld.12.0282 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 066NN UT WOS:000313227600008 PM 23232002 ER PT J AU Muldoon, LL Alvarez, JI Begley, DJ Boado, RJ del Zoppo, GJ Doolittle, ND Engelhardt, B Hallenbeck, JM Lonser, RR Ohlfest, JR Prat, A Scarpa, M Smeyne, RJ Drewes, LR Neuwelt, EA AF Muldoon, Leslie L. Alvarez, Jorge I. Begley, David J. Boado, Ruben J. del Zoppo, Gregory J. Doolittle, Nancy D. Engelhardt, Britta Hallenbeck, John M. Lonser, Russell R. Ohlfest, John R. Prat, Alexandre Scarpa, Maurizio Smeyne, Richard J. Drewes, Lester R. Neuwelt, Edward A. TI Immunologic privilege in the central nervous system and the blood-brain barrier SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE blood-brain barrier; multiple sclerosis; neuroimaging; neuroinflammation; neurovascular unit ID FOCAL CEREBRAL-ISCHEMIA; ADVANCE TRANSLATIONAL RESEARCH; CONVECTION-ENHANCED DELIVERY; LYSOSOMAL STORAGE DISORDERS; RAT CHOROID-PLEXUS; PARKINSONS-DISEASE; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; T-CELLS; MUCOPOLYSACCHARIDOSIS IIIB AB The brain is in many ways an immunologically and pharmacologically privileged site. The blood-brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 13-21; doi:10.1038/jcbfm.2012.153; published online 17 October 2012 C1 [Muldoon, Leslie L.; Doolittle, Nancy D.; Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Muldoon, Leslie L.] Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97239 USA. [Alvarez, Jorge I.; Prat, Alexandre] Univ Montreal, Hop Notre Dame, CRCHUM, Dept Med & Neurol,Ctr Excellence Neur, Montreal, PQ H3C 3J7, Canada. [Begley, David J.] Kings Coll London, Inst Pharmaceut Sci, London WC2R 2LS, England. [Boado, Ruben J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [del Zoppo, Gregory J.] Univ Washington, Dept Med & Neurol, Seattle, WA 98195 USA. [Engelhardt, Britta] Univ Bern, Theodor Kocher Inst, Bern, Switzerland. [Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Ohlfest, John R.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Scarpa, Maurizio] Univ Padua, Dept Pediat, Padua, Italy. [Smeyne, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Drewes, Lester R.] Univ Minnesota, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. [Neuwelt, Edward A.] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA. [Neuwelt, Edward A.] Dept Vet Affairs Med Ctr, Off Res & Dev, Portland, OR USA. RP Neuwelt, EA (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, 3181 Sam Jackson Pk Rd,L603, Portland, OR 97239 USA. EM neuwelte@ohsu.edu RI Scarpa, Maurizio/E-2539-2016 OI Smeyne, Richard/0000-0002-8459-5472; FU NIH R13 Meeting grant [9R13NS076353]; Walter S and Lucienne Driskill Foundation FX Funding was provided by an NIH R13 Meeting grant (9R13NS076353) and by the Walter S and Lucienne Driskill Foundation to EAN. NR 113 TC 71 Z9 75 U1 3 U2 60 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2013 VL 33 IS 1 BP 13 EP 21 DI 10.1038/jcbfm.2012.153 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 066MJ UT WOS:000313224600002 PM 23072749 ER PT J AU Kreisl, WC Jenko, KJ Hines, CS Lyoo, CH Corona, W Morse, CL Zoghbi, SS Hyde, T Kleinman, JE Pike, VW McMahon, FJ Innis, RB AF Kreisl, William C. Jenko, Kimberly J. Hines, Christina S. Lyoo, Chul Hyoung Corona, Winston Morse, Cheryl L. Zoghbi, Sarni S. Hyde, Thomas Kleinman, Joel E. Pike, Victor W. McMahon, Francis J. Innis, Robert B. CA Biomarkers Consortium PET Radiolig TI A genetic polymorphism for translocator protein 18 kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE neuroinflammation; PBR28; schizophrenia; translocator protein ID PERIPHERAL BENZODIAZEPINE-RECEPTORS; POSITRON-EMISSION-TOMOGRAPHY; CHRONIC-SCHIZOPHRENICS; MICROGLIAL ACTIVATION; PET RADIOLIGAND; TEMPORAL-LOBES; AFFINITY; LIGANDS; QUANTIFICATION; INFLAMMATION AB Second-generation radioligands for translocator protein (TSPO), an inflammation marker, are confounded by the codominant rs6971 polymorphism that affects binding affinity. The resulting three groups are homozygous for high-affinity state (HH), homozygous for low-affinity state (LL), or heterozygous (HL). We tested if in vitro binding to leukocytes distinguished TSPO genotypes and if genotype could affect clinical studies using the TSPO radioligand [C-11]PBR28. In vitro binding to leukocytes and [C-11]PBR28 brain imaging were performed in 27 human subjects with known TSPO genotype. Specific [H-3]PBR28 binding was measured in prefrontal cortex of 45 schizophrenia patients and 47 controls. Leukocyte binding to PBR28 predicted genotype in all subjects. Brain uptake was similar to 40% higher in HH than HL subjects. Specific [H-3]PBR28 binding in LL controls was negligible, while HH controls had similar to 80% higher binding than HL controls. After excluding LL subjects, specific binding was 16% greater in schizophrenia patients than controls. This difference was insignificant by itself (P=0.085), but was significant after correcting for TSPO genotype (P=0.011). Our results show that TSPO genotype influences PBR28 binding in vitro and in vivo. Correcting for this genotype increased statistical power in our postmortem study and is recommended for in vivo positron emission tomography studies. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 53-58; doi:10.1038/jcbfm.2012.131; published online 12 September 2012 C1 [Kreisl, William C.; Jenko, Kimberly J.; Hines, Christina S.; Lyoo, Chul Hyoung; Morse, Cheryl L.; Zoghbi, Sarni S.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Corona, Winston; McMahon, Francis J.] NIMH, Human Genet Branch, Bethesda, MD 20892 USA. [Hyde, Thomas] Lieber Inst Brain Dev, Div Dev Neurobiol & Funct Genom, Baltimore, MD USA. [Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Kreisl, WC (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr,Room B1-D43,MSC 1026, Bethesda, MD 20892 USA. EM kreislw@mail.nih.gov OI McMahon, Francis/0000-0002-9469-305X FU Intramural Research Program of the National Institute of Mental Health-National Institutes of Health (IRP-NIMH-NIH); NIMH; Foundation for the NIH Biomarkers Consortium; EMD Serono; Glaxo Smith Kline; Lilly; Merck; Pfizer, Inc.; Roche FX This project was funded by the Intramural Research Program of the National Institute of Mental Health-National Institutes of Health (IRP-NIMH-NIH), and as a public-private partnership supported by the NIMH and the Foundation for the NIH Biomarkers Consortium (www.biomarkersconsortium.org). This work was supported by EMD Serono, Glaxo Smith Kline, Lilly, Merck, Pfizer, Inc., and Roche. Additional support was provided by the American Academy of Neurology Foundation (to WCK). NR 33 TC 75 Z9 76 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2013 VL 33 IS 1 BP 53 EP 58 DI 10.1038/jcbfm.2012.131 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 066MJ UT WOS:000313224600007 PM 22968319 ER PT J AU Cheng, BT Brinkmann, M Forkert, ND Treszl, A Ebinger, M Kohrmann, M Wu, O Kang, DW Liebeskind, DS Tourdias, T Singer, OC Christensen, S Luby, M Warach, S Fiehler, J Fiebach, JB Gerloff, C Thomalla, G AF Cheng, Bastian Brinkmann, Mathias Forkert, Nils D. Treszl, Andras Ebinger, Martin Koehrmann, Martin Wu, Ona Kang, Dong-Wha Liebeskind, David S. Tourdias, Thomas Singer, Oliver C. Christensen, Soren Luby, Marie Warach, Steven Fiehler, Jens Fiebach, Jochen B. Gerloff, Christian Thomalla, Goetz CA STIR Imaging Investigator VISTA Imaging Investigator TI Quantitative measurements of relative fluid-attenuated inversion recovery (FLAIR) signal intensities in acute stroke for the prediction of time from symptom onset SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE acute stroke; diffusion-weighted imaging; fluid-attenuated inversion recovery; magnetic resonance imaging ID ACUTE ISCHEMIC-STROKE; CEREBRAL-ISCHEMIA; PULSE SEQUENCES; MANAGEMENT; BRAIN; RAT; MR; GUIDELINES; EVOLUTION; DIFFUSION AB In acute stroke magnetic resonance imaging, a 'mismatch' between visibility of an ischemic lesion on diffusion-weighted imaging (DWI) and missing corresponding parenchymal hyperintensities on fluid-attenuated inversion recovery (FLAIR) data sets was shown to identify patients with time from symptom onset <= 4.5 hours with high specificity. However, moderate sensitivity and suboptimal interpreter agreement are limitations of a visual rating of FLAIR lesion visibility. We tested refined image analysis methods in patients included in the previously published PREFLAIR study using refined visual analysis and quantitative measurements of relative FLAIR signal intensity (rSI) from a three-dimensional, segmented stroke lesion volume. A total of 399 patients were included. The 61 of FLAIR lesions showed a moderate correlation with time from symptom onset (r=0.382, P<0.001). A FLAIR rSI threshold of <1.0721 predicted symptom onset <= 4.5 hours with slightly increased specificity (0.85 versus 0.78) but also slightly decreased sensitivity (0.47 versus 0.58) as compared with visual analysis. Refined visual analysis differentiating between 'subtle' and 'obvious' FLAIR hyperintensities and classification and regression tree algorithms combining information from visual and quantitative analysis also did not improve diagnostic accuracy. Our results raise doubts whether the prediction of stroke onset time by visual image judgment can be improved by quantitative rSI measurements. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 76-84; doi:10.1038/jcbfm.2012.129; published online 10 October 2012 C1 [Cheng, Bastian; Brinkmann, Mathias; Gerloff, Christian; Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Neurol Klin & Poliklin, Kopf & Neurozentrum, D-20246 Hamburg, Germany. [Forkert, Nils D.] Univ Klinikum Hamburg Eppendorf, Inst Computat Neurosci, D-20246 Hamburg, Germany. [Treszl, Andras] Univ Klinikum Hamburg Eppendorf, Inst Med Biometrie & Epidemiol, D-20246 Hamburg, Germany. [Ebinger, Martin; Fiebach, Jochen B.] Charite, Ctr Schlaganfallforsch Berlin, D-13353 Berlin, Germany. [Koehrmann, Martin] Univ Erlangen Nurnberg, Neurol Klin, D-91054 Erlangen, Germany. [Wu, Ona] Harvard Univ, Sch Med, Dept Radiol,Massachusetts GeneralHosp, Athinoula A MartinosCtr Biomed Imaging, Boston, MA 02115 USA. [Kang, Dong-Wha] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Liebeskind, David S.] Univ Calif, Dept Neurol, Oakland, CA USA. [Tourdias, Thomas] Univ Bordeaux, CHU Bordeaux, Serv NeuroImagerie Diagnost Therapeut, Bordeaux, France. [Singer, Oliver C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neororadiol, Erlangen, Germany. [Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia. [Luby, Marie; Warach, Steven] NINDS, Bethesda, MD 20892 USA. [Fiehler, Jens] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neuroradiol Diagnost & Intervent, D-20246 Hamburg, Germany. RP Cheng, BT (reprint author), Univ Klinikum Hamburg Eppendorf, Neurol Klin & Poliklin, Kopf & Neurozentrum, Martinistr 52, D-20246 Hamburg, Germany. EM b.cheng@uke.uni-hamburg.de RI Forkert, Nils Daniel/K-6273-2012; OI Forkert, Nils Daniel/0000-0003-2556-3224; Fiebach, Jochen B./0000-0002-7936-6958 FU Boehringer Ingelheim; Lundbeck; Siemens; Syngis; Synarc; Bayer Vital; EBS technologies; Glaxo Smith Kline; Pfizer; Sanofi Aventis; Silk Road Medical; UCB; CoAxia; Concentric Medical; National Institutes of Health; ACRIN; Biogen; Genzyme; Mitsubishi; Else Kroner-Fresenius-Stiftung; French Government (PHRC); National Institutes of Health [R01NS059775, R01NS063925, P50NS051343]; GE; Olea; Imaging Biometrics; Else Kroner-Fresenius-Stiftung [2009_A36]; Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin [01 EO 0801]; National Health and Medical Research Council (Australia); National Stroke Foundation (Australia); Heart Foundation of Australia; French national grant PHRC; National Institute of Neurological Disorders and Stroke (NINDS); European Union [202213, 223153]; Volkswagen Foundation; Deutsche Forschungsgemeinschaft FX Jochen B Fiebach has received fees as a board member, consultant, or lecturer from Boehringer Ingelheim, Lundbeck, Siemens, Syngis, and Synarc. Christian Gerloff has received fees as a consultant or lecture fees from Bayer Vital, Boehringer Ingelheim, EBS technologies, Glaxo Smith Kline, Lundbeck, Pfizer, Sanofi Aventis, Silk Road Medical, and UCB. David S Liebeskind has received fees as a consultant for CoAxia and Concentric Medical. A Gregory Sorensen was supported by grants from the National Institutes of Health and has received fees as a board member, consultant, or lecturer from ACRIN, Biogen, Genzyme, Mitsubishi, and has received royalties from GE and Olea. Gotz Thomalla has received a research grant from the Else Kroner-Fresenius-Stiftung. Thomas Tourdias has received a national grant from the French Government (PHRC). Ona Wu was supported in part by grants from the National Institutes of Health (R01NS059775, R01NS063925, and P50NS051343) and has received royalties and licensing fees from GE, Olea, and Imaging Biometrics. The other authors report no conflict of interest.; PRE-FLAIR has received funding from the Else Kroner-Fresenius-Stiftung (2009_A36). In Berlin, data were collected within the 1,000+ study, which has received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801). EPITHET was a phase II prospective, randomized, double-blinded, placebo-controlled, multinational trial funded by the National Health and Medical Research Council (Australia), the National Stroke Foundation (Australia), and the Heart Foundation of Australia. VIRAGE is a national multicenter study supported by French national grant PHRC.; This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), and also by the European Union's Seventh Framework Programme grant agreement No. 202213 and No. 223153 (European Stroke Network), the Volkswagen Foundation, and the Deutsche Forschungsgemeinschaft. NR 31 TC 26 Z9 27 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JAN PY 2013 VL 33 IS 1 BP 76 EP 84 DI 10.1038/jcbfm.2012.129 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 066MJ UT WOS:000313224600010 PM 23047272 ER PT J AU Nguyen, VA Boyd-Graber, J Altschul, SF AF Viet-An Nguyen Boyd-Graber, Jordan Altschul, Stephen F. TI Dirichlet Mixtures, the Dirichlet Process, and the Structure of Protein Space SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE alignment; computational molecular biology; dynamic programming; multiple alignment; sequence analysis ID NONPARAMETRIC PROBLEMS; ALIGNMENT; MODELS; PRIORS AB The Dirichlet process is used to model probability distributions that are mixtures of an unknown number of components. Amino acid frequencies at homologous positions within related proteins have been fruitfully modeled by Dirichlet mixtures, and we use the Dirichlet process to derive such mixtures with an unbounded number of components. This application of the method requires several technical innovations to sample an unbounded number of Dirichlet-mixture components. The resulting Dirichlet mixtures model multiple-alignment data substantially better than do previously derived ones. They consist of over 500 components, in contrast to fewer than 40 previously, and provide a novel perspective on the structure of proteins. Individual protein positions should be seen not as falling into one of several categories, but rather as arrayed near probability ridges winding through amino acid multinomial space. C1 [Viet-An Nguyen] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Viet-An Nguyen; Boyd-Graber, Jordan] Univ Maryland, UMIACS, College Pk, MD 20742 USA. [Boyd-Graber, Jordan] Univ Maryland, iSch, College Pk, MD 20742 USA. [Altschul, Stephen F.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Rm 6N-605, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.inh.gov RI Boyd-Graber, Jordan/A-9976-2016 OI Boyd-Graber, Jordan/0000-0002-7770-4431 FU National Science Foundation [1018625]; National Library of Medicine at the National Institutes of Health FX Jordan Boyd-Graber is supported by National Science Foundation grant #1018625. Stephen Altschul is supported by the Intramural Research Program of the National Library of Medicine at the National Institutes of Health. NR 30 TC 6 Z9 6 U1 1 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD JAN PY 2013 VL 20 IS 1 BP 1 EP 18 DI 10.1089/cmb.2012.0244 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 068HZ UT WOS:000313358400001 PM 23294268 ER PT J AU Haggstrom, DA Klabunde, CN Smith, JL Yuan, G AF Haggstrom, David A. Klabunde, Carrie N. Smith, Judith Lee Yuan, Gigi TI Variation in Primary Care Physicians' Colorectal Cancer Screening Recommendations by Patient Age and Comorbidity SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cancer screening; health services; colorectal cancer; primary care physicians ID TASK-FORCE; QUALITY; VIGNETTES; IMPACT AB Screening patterns among primary care physicians (PCPs) may be influenced by patient age and comorbidity. Colorectal cancer (CRC) screening has little benefit among patients with limited life expectancy. To characterize the extent to which PCPs modify their recommendations for CRC screening based upon patients' increasing age and/or worsening comorbidity Cross-sectional, nationally representative survey. The study comprised primary care physicians (n = 1,266) including general internal medicine, family practice, and obstetrics-gynecology physicians. Physician CRC screening recommendations among patients of varying age and comorbidity were measured based upon clinical vignettes. Independent variables in adjusted models included physician and practice characteristics. For an 80-year-old patient with unresectable non-small cell lung cancer (NSCLC), 25 % of PCPs recommended CRC screening. For an 80-year-old patient with ischemic cardiomyopathy (New York Heart Association, Class II), 71 % of PCPs recommended CRC screening. PCPs were more likely to recommend fecal occult blood testing than colonoscopy as the preferred screening modality for a healthy 80-year-old, compared to healthy 50- or 65-year-old patients (19 % vs. 5 % vs. 2 % p < 0.001). For an 80-year-old with unresectable NSCLC, PCPs who were an obstetrics-gynecology physician were more likely to recommend CRC screening, while those with a full electronic medical record were less likely to recommend screening. PCPs consider comorbidity when screening older patients for CRC and may change the screening modality from colonoscopy to FOBT. However, a sizable proportion of PCPs would recommend screening for patients with advanced cancer who would not benefit. Understanding the mechanisms underlying these patterns will facilitate the design of future medical education and policy interventions to reduce unnecessary care. C1 [Haggstrom, David A.] Richard L Roudebush VA Med Ctr, VA Hlth Serv Res, Indianapolis, IN 46202 USA. [Haggstrom, David A.] Richard L Roudebush VA Med Ctr, Dev Ctr Excellence Implementing Evidence Based Pr, Indianapolis, IN 46202 USA. [Haggstrom, David A.] Indiana Univ Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA. [Haggstrom, David A.] Regenstrief Inst Inc, IU Ctr Hlth Serv & Outcomes Res, Indianapolis, IN USA. [Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Smith, Judith Lee] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. [Yuan, Gigi] Informat Management Serv Inc, Silver Spring, MD USA. RP Haggstrom, DA (reprint author), Richard L Roudebush VA Med Ctr, VA Hlth Serv Res, 1481 W 10th St 11H, Indianapolis, IN 46202 USA. EM dahaggst@iupui.edu FU National Cancer Institute [N02-PC-51308]; Agency for Healthcare Research and Quality [Y3-PC-5019-01, Y3-PC-5019-02]; Centers for Disease Control and Prevention [Y3-PC-6017-01]; VA HSR&D Career Development Award [CD207016-2] FX Funding support for this study was provided by the National Cancer Institute (contract number N02-PC-51308), the Agency for Healthcare Research and Quality (inter-agency agreement numbers Y3-PC-5019-01 and Y3-PC-5019-02), and the Centers for Disease Control and Prevention (inter-agency agreement number Y3-PC-6017-01). Dr. Haggstrom is the recipient of VA HSR&D Career Development Award CD207016-2. NR 21 TC 10 Z9 10 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JAN PY 2013 VL 28 IS 1 BP 18 EP 24 DI 10.1007/s11606-012-2093-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 066GL UT WOS:000313208500006 PM 22653380 ER PT J AU Shepperd, JA Lipkus, IM Sanderson, SC McBride, CM O'Neill, SC Docherty, S AF Shepperd, James A. Lipkus, Isaac M. Sanderson, Saskia C. McBride, Colleen M. O'Neill, Suzanne C. Docherty, Sharron TI Testing Different Communication Formats on Responses to Imagined Risk of Having Versus Missing the GSTM1 Gene SO JOURNAL OF HEALTH COMMUNICATION LA English DT Article ID LUNG-CANCER RISK; SMOKING-CESSATION; DECISION-MAKING; BEHAVIOR-CHANGE; HEALTH; FEEDBACK; SMOKERS; SUSCEPTIBILITY; POLYMORPHISMS; AVOIDANCE AB Genetic markers of lung cancer susceptibility, such as the common variant of the glutathione S-transferase Mu 1 gene (GSTM1-null), confer small probabilities of disease risk. The authors explored the influence of different approaches to communicating the small variations in risk associated with this biomarker. College smokers (N = 128) imagined that they had the GSTM1 wild-type variant versus the GSTM1 null-type variant. The authors presented lung cancer risk in 6 ways that varied the risk format (absolute risk vs. incremental risk) and the presentation style of the information (no graphics vs. graphic display of foreground only vs. graphic display of foreground + background). Presentation style had minor effects. However, absolute risk information increased negative emotions more than did incremental risk information. Perceptions of risk and negative emotions were most profoundly affected by the difference between having the GSTM1 wild-type variant versus the GSTM1 null-type variant. The authors discuss implications for conveying small probabilities related to genetic risk. C1 [Shepperd, James A.] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA. [Lipkus, Isaac M.; Docherty, Sharron] Duke Univ, Sch Nursing, Durham, NC USA. [Sanderson, Saskia C.] Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [O'Neill, Suzanne C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Shepperd, JA (reprint author), Univ Florida, Dept Psychol, POB 112250, Gainesville, FL 32611 USA. EM shepperd@ufl.edu FU NCI NIH HHS [P30 CA051008, R01 CA121922-01A2, R01 CA121922] NR 35 TC 5 Z9 5 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1081-0730 J9 J HEALTH COMMUN JI J. Health Commun. PD JAN 1 PY 2013 VL 18 IS 1 BP 124 EP 137 DI 10.1080/10810730.2012.688245 PG 14 WC Communication; Information Science & Library Science SC Communication; Information Science & Library Science GA 069DR UT WOS:000313416000009 PM 22888806 ER PT J AU Zhang, G Ding, HQ Chen, HL Ye, XW Li, HX Lin, X Ke, ZJ AF Zhang, Geng Ding, Hanqing Chen, Honglei Ye, Xingwang Li, Huaixing Lin, Xu Ke, Zunji TI Thiamine Nutritional Status and Depressive Symptoms Are Inversely Associated among Older Chinese Adults SO JOURNAL OF NUTRITION LA English DT Article ID ERYTHROCYTE TRANSKETOLASE ACTIVITY; ALZHEIMERS-DISEASE; ELDERLY-PEOPLE; DEFICIENCY; BLOOD; NEURODEGENERATION; SUPPLEMENTATION; PYROPHOSPHATE; DIPHOSPHATE; IMPAIRMENT AB Thiamine has been hypothesized to play an important role in mental health; however, few studies have investigated the association between thiamine nutritional status and depression in the general population. Concentrations of free thiamine and its phosphate esters [thiamine monophosphate (TMP) and thiamine diphosphate (TDP)] in erythrocytes were measured by HPLC among 1587 Chinese men and women aged 50-70 y. The presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score of >= 16. The median erythrocyte concentration (nmol/L) was 3.73 for free thiamine, 3.74 for TMP, and 169 for TDP. The overall prevalence of depressive symptoms was 11.3%. Lower concentrations of all 3 erythrocyte thiamine biomarkers were monotonically associated with a higher prevalence of depressive symptoms: the multivariable adjusted ORs comparing the lowest with the highest quartiles were 2.97 (95% CI = 1.87, 4.72; P-trend < 0.001) for free thiamine, 3.46 (95% CI = 1.99, 6.02; P-trend < 0.001) for TMP, and 1.98 (95% CI = 1.22, 3.21; P-trend = 0.002) for TDP. In conclusion, poorer thiamine nutritional status and higher odds of depressive symptoms were associated among older Chinese adults. This finding should be further investigated in prospective or interventional studies. J. Nutr. 143: 53-58, 2013. C1 [Zhang, Geng; Ding, Hanqing; Ye, Xingwang; Li, Huaixing; Lin, Xu; Ke, Zunji] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. [Zhang, Geng; Ding, Hanqing; Ye, Xingwang; Li, Huaixing; Lin, Xu; Ke, Zunji] Chinese Acad Sci, Grad Sch, Shanghai, Peoples R China. [Chen, Honglei] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Lin, X (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China. EM xlin@sibs.ac.cn; zjke@sibs.ac.cn RI Ke, Zunji/E-4822-2010; Ke, Zun-Ji/N-5689-2014; OI Ke, Zunji/0000-0003-4038-2456; Ke, Zun-Ji/0000-0003-4038-2456; Chen, Honglei/0000-0003-3446-7779 FU National Natural Science Foundation of China [30930081, 31271142, 81021002]; National Basic Research 973 Program [2010CB912000, 2011CB504002, 2012CB524900]; Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences [SIBS2008006]; Chinese Academy of Sciences [KSCX2-EW-R-10]; Key Discipline of Shanghai Public Health-Food and Nutritional Sciences [12GWZX0702]; Program of Clinical Research Center, Institute for Nutritional Sciences and Shanghai Xuhui Central Hospital [CRC20100010]; Intramural Program of the NIH, the National Institute of Environmental Health Sciences FX Supported by the National Natural Science Foundation of China (30930081, 31271142, and 81021002), the National Basic Research 973 Program (2010CB912000, 2011CB504002, and 2012CB524900), the Chief Scientist Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences (SIBS2008006), the Chinese Academy of Sciences (KSCX2-EW-R-10), Key Discipline of Shanghai Public Health-Food and Nutritional Sciences (12GWZX0702), and Program of Clinical Research Center, Institute for Nutritional Sciences and Shanghai Xuhui Central Hospital (CRC20100010). Dr. Chen is supported by the Intramural Program of the NIH, the National Institute of Environmental Health Sciences. NR 48 TC 14 Z9 17 U1 6 U2 15 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 2013 VL 143 IS 1 BP 53 EP 58 DI 10.3945/jn.112.167007 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 065MV UT WOS:000313153500008 PM 23173173 ER PT J AU Ono, F AF Ono, Fumihito TI Big answers from a small fly with a cultured brain SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material C1 NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ono, F (reprint author), NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EM onof@mail.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN PY 2013 VL 591 IS 1 BP 3 EP 3 DI 10.1113/jphysiol.2012.246538 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 067CV UT WOS:000313271300002 PM 23281482 ER PT J AU Scimemi, A AF Scimemi, Annalisa TI A TRP among the astrocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Review ID EXTRASYNAPTIC GABA(A) RECEPTORS; LONG-TERM POTENTIATION; TONIC INHIBITION; MOLECULAR ARCHITECTURE; POSTNATAL-DEVELOPMENT; HIPPOCAMPAL-NEURONS; ELECTRON-MICROSCOPY; GLUTAMATE UPTAKE; CEREBRAL-CORTEX; NERVOUS-SYSTEM AB TRP channels were first identified as membrane proteins mediating phototransduction in fruit flies. Astrocytes were initially referred to as the silent elements of the nervous system. At the time these discoveries were made, few would have suspected TRP channels and astrocytes could contribute significantly to our understanding of brain signalling. Recent findings, however, put TRP channels and astrocytes in the spotlight, describe their ability to modulate the activity of specific sets of synapses, and raise some interesting questions. What makes astrocytes capable of exerting cell-specific effects on interneuronal signals? How do different synapses respond to changes in astrocytic function and in the local micro-structure of the neuropil? Can astrocytes be considered good candidate targets for therapeutic intervention to treat neurological diseases? Here I discuss the recent developments on TRP channels and astrocytes that have made us aware of the many structural and functional features of synapses that still need to be discovered and that could lead a new avant-garde in decoding the cellular and molecular basis of brain (dys)function. C1 NINDS, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Scimemi, A (reprint author), NINDS, Synapt Physiol Sect, NIH, 35 Convent Dr 3C316, Bethesda, MD 20892 USA. EM scimemia@ninds.nih.gov RI Scimemi, Annalisa/O-5396-2014 OI Scimemi, Annalisa/0000-0003-4975-093X FU NIH/NINDS [NS002986] FX This work was supported by the NIH/NINDS Intramural Research Program (NS002986). NR 68 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JAN PY 2013 VL 591 IS 1 BP 9 EP 15 DI 10.1113/jphysiol.2012.237883 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 067CV UT WOS:000313271300005 PM 23045334 ER PT J AU Lippman, ME Cassidy, J Wesley, M Young, RC AF Lippman, Marc E. Cassidy, Jane Wesley, Margaret Young, Robert C. TI Increasing the response rate to cytotoxic chemotherapy by endocrine means (Retraction of vol 23, pg 1173, 1985) SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Correction C1 [Lippman, Marc E.; Cassidy, Jane; Young, Robert C.] NCI, Med Branch 10 12N226, NIH, Bethesda, MD 20205 USA. [Wesley, Margaret] NCI, Biometr Res Branch, NIH, Bethesda, MD 20205 USA. RP Lippman, ME (reprint author), NCI, Med Branch 10 12N226, NIH, Bethesda, MD 20205 USA. NR 1 TC 0 Z9 0 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JAN PY 2013 VL 133 BP 141 EP 141 DI 10.1016/j.jsbmb.2012.09.020 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 067LS UT WOS:000313296600017 ER PT J AU Lawrence, YR Vikram, B Dignam, JJ Chakravarti, A Machtay, M Freidlin, B Takebe, N Curran, WJ Bentzen, SM Okunieff, P Coleman, CN Dicker, AP AF Lawrence, Yaacov Richard Vikram, Bhadrasain Dignam, James J. Chakravarti, Arnab Machtay, Mitchell Freidlin, Boris Takebe, Naoko Curran, Walter J., Jr. Bentzen, Soren M. Okunieff, Paul Coleman, C. Norman Dicker, Adam P. TI NCIRTOG Translational Program Strategic Guidelines for the Early-Stage Development of Radiosensitizers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RANDOMIZED PHASE-II; CELL LUNG-CANCER; CONTINUAL REASSESSMENT METHOD; STEREOTACTIC BODY RADIATION; GROWTH-FACTOR RECEPTOR; CLINICAL-TRIAL-DESIGN; LATE-ONSET TOXICITIES; ANTI-ANGIOGENIC THERAPY; DRUG STEERING COMMITTEE; LOCALLY ADVANCED HEAD AB The addition of chemotherapeutic agents to ionizing radiation has improved survival in many malignancies. Cure rates may be further improved by adding novel targeted agents to current radiotherapy or radiochemotherapy regimens. Despite promising laboratory data, progress in the clinical development of new drugs with radiation has been limited. To define and address the problems involved, a collaborative effort between individuals within the translational research program of the Radiation Oncology Therapy Group and the National Cancer Institute was established. We discerned challenges to drug development with radiation including: 1) the limited relevance of preclinical work, 2) the pharmaceutical industry's diminished interest, and 3) the important individual skills and institutional commitments required to ensure a successful program. The differences between early-phase trial designs with and without radiation are noted as substantial. The traditional endpoints for early-phase clinical trialsuacute toxicity and maximum-tolerated doseuare of limited value when combining targeted agents with radiation. Furthermore, response rate is not a useful surrogate marker of activity in radiation combination trials.Consequently, a risk-stratified model for drug-dose escalation with radiation is proposed, based upon the known and estimated adverse effects. The guidelines discuss new clinical trial designs, such as the time-to-event continual reassessment method design for phase I trials, randomized phase II screening trials, and the use of surrogate endpoints, such as pathological response. It is hoped that by providing a clear pathway, this article will accelerate the rate of drug development with radiation. C1 [Lawrence, Yaacov Richard] Chaim Sheba Med Ctr, Dept Radiat Oncol, IL-52621 Tel Hashomer, Israel. [Lawrence, Yaacov Richard; Dicker, Adam P.] Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19107 USA. [Vikram, Bhadrasain] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Freidlin, Boris] NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. [Dignam, James J.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Chakravarti, Arnab] Ohio State Univ, Coll Med, Dept Radiat Oncol, Columbus, OH 43210 USA. [Machtay, Mitchell] Case Western Reserve Univ, Sch Med, Dept Radiat Oncol, Seidman Canc Ctr, Cleveland, OH USA. [Takebe, Naoko] NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Invest Drug Branch,NIH, Rockville, MD USA. [Curran, Walter J., Jr.] Emory Univ, Winship Canc Ctr, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Bentzen, Soren M.] Univ Wisconsin, Dept Human Oncol, Madison, WI USA. [Bentzen, Soren M.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Okunieff, Paul] Univ Florida, Dept Radiat Oncol, Gainesville, FL USA. [Coleman, C. Norman] NCI, Radiat Res Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Lawrence, YR (reprint author), Chaim Sheba Med Ctr, Dept Radiat Oncol, IL-52621 Tel Hashomer, Israel. EM yaacovla@gmail.com RI Bentzen, Soren/E-3997-2012; OI Bentzen, Soren/0000-0002-7444-7564; Dicker, Adam/0000-0003-0733-3337 FU NCI NIH HHS [P30 CA014520, P30 CA016058, P30CA56036, R01CA108633, RC2CA148190, U10 CA032115, U10 CA21661, U10 CA32115, U10 CA37422] NR 125 TC 21 Z9 21 U1 1 U2 9 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 JAN PY 2013 VL 105 IS 1 BP 11 EP 24 DI 10.1093/jnci/djs472 PG 14 WC Oncology SC Oncology GA 066JN UT WOS:000313217100006 PM 23231975 ER PT J AU Kohaar, I Porter-Gill, P Lenz, P Fu, YP Mumy, A Tang, W Apolo, AB Rothman, N Baris, D Schned, AR Ylaya, K Schwenn, M Johnson, A Jones, M Kida, M Silverman, DT Hewitt, SM Moore, LE Prokunina-Olsson, L AF Kohaar, Indu Porter-Gill, Patricia Lenz, Petra Fu, Yi-Ping Mumy, Adam Tang, Wei Apolo, Andrea B. Rothman, Nathaniel Baris, Dalsu Schned, Alan R. Ylaya, Kris Schwenn, Molly Johnson, Alison Jones, Michael Kida, Masatoshi Silverman, Debra T. Hewitt, Stephen M. Moore, Lee E. Prokunina-Olsson, Ludmila TI Genetic Variant as a Selection Marker for AntiProstate Stem Cell Antigen Immunotherapy of Bladder Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RESISTANT PROSTATE-CANCER; GENOME-WIDE ASSOCIATION; GASTRIC-CANCER; URINARY-BLADDER; SUSCEPTIBILITY LOCI; MONOCLONAL-ANTIBODY; CHINESE POPULATION; TUMOR-GROWTH; PSCA GENE; IN-VIVO AB A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multivariable linear regression (P 6.4610(11); n 278). The association pattern is similar in non-muscle-invasive tumors, stages Ta (P 3.1010(5); n 173) and T1 (P 2.6410(5); n 60), and muscle-invasive tumors, stages T2 (P .01; n 23) and T3/4 (P .03; n 22). The study suggests that anti-PSCA immunotherapy might be beneficial for bladder cancer patients with high tumor PSCA expression, which is statistically significantly associated with the presence of CT and TT genotypes of a common genetic variant, rs2294008. Future clinical studies will be needed to validate PSCA as a therapeutic target for bladder cancer. C1 [Kohaar, Indu; Porter-Gill, Patricia; Fu, Yi-Ping; Mumy, Adam; Tang, Wei; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Apolo, Andrea B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ylaya, Kris; Hewitt, Stephen M.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Rothman, Nathaniel; Baris, Dalsu; Silverman, Debra T.; Moore, Lee E.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rothman, Nathaniel; Baris, Dalsu; Silverman, Debra T.; Moore, Lee E.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Lenz, Petra] SAIC Frederick, Natl Lab Canc Res, Clin Monitoring Res Program, Frederick, MD USA. [Schned, Alan R.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pathol, Hanover, NH 03756 USA. [Schwenn, Molly] Maine Canc Registry, Augusta, ME USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. [Jones, Michael] Maine Med Ctr, Dept Pathol & Lab Med, Portland, ME 04102 USA. [Kida, Masatoshi] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, 8717 Grovemont Cir, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov RI Tang, Wei/H-7103-2013; OI Tang, Wei/0000-0002-7089-4391; Prokunina-Olsson, Ludmila/0000-0002-9622-2091; Hewitt, Stephen/0000-0001-8283-1788 FU National Institutes of Health, National Cancer Institute [HHSN261200800001E]; Division of Cancer Epidemiology and Genetics, Intramural Research Program of the National Institutes of Health, National Cancer Institute; National Cancer Institute [NCI N02-CP-01037] FX This work was supported in whole or in part with federal funds from the Intramural Research Program of the National Institutes of Health, National Cancer Institute (contract HHSN261200800001E). The New England Bladder Cancer study, the National Cancer Institute bladder cancer genome-wide association studies, and follow-up studies are supported by the Division of Cancer Epidemiology and Genetics, Intramural Research Program of the National Institutes of Health, National Cancer Institute. The New England Bladder Cancer study is also supported by a National Cancer Institute contract (NCI N02-CP-01037). This work was supported by a National Cancer Institute Director's Career Development Award (to Y-PF). NR 40 TC 13 Z9 15 U1 0 U2 13 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 JAN PY 2013 VL 105 IS 1 BP 69 EP 73 DI 10.1093/jnci/djs458 PG 5 WC Oncology SC Oncology GA 066JN UT WOS:000313217100011 PM 23266392 ER PT J AU Strong, R Miller, RA Astle, CM Baur, JA de Cabo, R Fernandez, E Guo, W Javors, M Kirkland, JL Nelson, JF Sinclair, DA Teter, B Williams, D Zaveri, N Nadon, NL Harrison, DE AF Strong, Randy Miller, Richard A. Astle, Clinton M. Baur, Joseph A. de Cabo, Rafael Fernandez, Elizabeth Guo, Wen Javors, Martin Kirkland, James L. Nelson, James F. Sinclair, David A. Teter, Bruce Williams, David Zaveri, Nurulain Nadon, Nancy L. Harrison, David E. TI Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Longevity; Aging; Mice; Diet; Interventions ID INTERVENTIONS TESTING PROGRAM; CAENORHABDITIS-ELEGANS; EXTENDING LIFE; RATS; ANTIOXIDANT; LONGEVITY; RESTRICTION; RAPAMYCIN; SURVIVAL; CATECHIN AB The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin. oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only. C1 [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth; Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78245 USA. [Strong, Randy; Fernandez, Elizabeth; Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. [Astle, Clinton M.; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Baur, Joseph A.] Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. [Baur, Joseph A.] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA 19104 USA. [de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. [Guo, Wen] Boston Univ, Dept Med, Evans Biomed Res Ctr, Boston, MA 02215 USA. [Javors, Martin] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78245 USA. [Kirkland, James L.] Mayo Clin, Robert & Arlene Kogod Ctr Aging, Sw Rochester, MN USA. [Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78245 USA. [Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Teter, Bruce] VA Greater Angeles Healthcare Syst, Dept Med, Sepulveda, CA USA. [Williams, David] Univ Calif Los Angeles, Sch Med, Dept Ophthalmol, Los Angeles, CA 90024 USA. [Williams, David] Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. [Zaveri, Nurulain] Astraea Therapeut LLC, Mountain View, CA USA. [Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA. RP Strong, R (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM strong@uthscsa.edu RI Kirkland, James/F-9159-2016; de Cabo, Rafael/J-5230-2016; OI , rafael/0000-0003-2830-5693; de Cabo, Rafael/0000-0002-3354-2442; Baur, Joseph/0000-0001-8262-6549; Sinclair, David/0000-0002-9936-436X FU National Institute on Aging at the National Institutes of Health [U01-AG022303, U01-AG025707, U01-AG022308, AG13925, U01-AG022307, P30-AG13319]; Department of Veterans Affairs; Intramural Research Program of the National Institute on Aging FX This work was supported by the National Institute on Aging at the National Institutes of Health (U01-AG022303 to RAM., U01-AG025707 and U01-AG022308 to D.E.H., AG13925 to J.L.K., and U01-AG022307 and P30-AG13319 to R.S.) and the Department of Veterans Affairs (R.S.). R.d.C. is supported by the Intramural Research Program of the National Institute on Aging. NR 44 TC 48 Z9 48 U1 3 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2013 VL 68 IS 1 BP 6 EP 16 DI 10.1093/gerona/gls070 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400002 PM 22451473 ER PT J AU Rodriguez-Manas, L Feart, C Mann, G Vina, J Chatterji, S Chodzko-Zajko, W Harmand, MGC Bergman, H Carcaillon, L Nicholson, C Scuteri, A Sinclair, A Pelaez, M Van der Cammen, T Beland, F Bickenbach, J Delamarche, P Ferrucci, L Fried, LP Gutierrez-Robledo, LM Rockwood, K Artalejo, FR Serviddio, G Vega, E AF Rodriguez-Manas, Leocadio Feart, Catherine Mann, Giovanni Vina, Jose Chatterji, Somnath Chodzko-Zajko, Wojtek Gonzalez-Colaco Harmand, Magali Bergman, Howard Carcaillon, Laure Nicholson, Caroline Scuteri, Angelo Sinclair, Alan Pelaez, Martha Van der Cammen, Tischa Beland, Francois Bickenbach, Jerome Delamarche, Paul Ferrucci, Luigi Fried, Linda P. Miguel Gutierrez-Robledo, Luis Rockwood, Kenneth Rodriguez Artalejo, Fernando Serviddio, Gaetano Vega, Enrique CA FOD-CC Grp TI Searching for an Operational Definition of Frailty: A Delphi Method Based Consensus Statement. The Frailty Operative Definition-Consensus Conference Project SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Frailty; Consensus definition; Older people; Biomarkers ID DISABILITY; PHENOTYPE; HEALTH; PEOPLE AB Background. There is no consensus regarding the definition of frailty for clinical uses. Methods. A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. Results. Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. Conclusions. There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established. C1 [Rodriguez-Manas, Leocadio] Hosp Univ Getafe, Jefe Serv Geriatria, Getafe 28905, Spain. [Feart, Catherine] Univ Bordeaux, F-33000 Bordeaux, France. [Feart, Catherine] INSERM, ISPED, Ctr INSERM, Epidemiol Biostat U897, F-33000 Bordeaux, France. [Mann, Giovanni; Nicholson, Caroline] Kings Coll London, London WC2R 2LS, England. [Vina, Jose] Univ Valencia, Valencia, Spain. [Chatterji, Somnath] World Hlth Org, Geneva, Switzerland. [Chodzko-Zajko, Wojtek] Univ Illinois, Chicago, IL 60680 USA. [Bergman, Howard] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Carcaillon, Laure] Ctr Res Epidemiol & Populat Hlth, Villejuif, France. [Scuteri, Angelo] UO Geriatria, INRCA IRCCS, Rome, Italy. [Sinclair, Alan] Univ Bedfordshire, Bedford, England. [Pelaez, Martha] Hlth Fdn S Florida, Miami, FL USA. [Van der Cammen, Tischa] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Beland, Francois] Lady Davis Hop Gen Juif, Montreal, PQ, Canada. [Bickenbach, Jerome] Leiter Unit Disabil Policy Schweizer, Nottwill, Switzerland. [Delamarche, Paul] Univ Rennes 2, F-35043 Rennes, France. [Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. [Fried, Linda P.] Columbia Univ, Med Ctr, New York, NY USA. [Miguel Gutierrez-Robledo, Luis] Inst Geriatria, Mexico City, DF, Mexico. [Rockwood, Kenneth] Dalhousie Univ, Halifax, NS, Canada. [Rodriguez Artalejo, Fernando] Univ Autonoma Madrid, E-28049 Madrid, Spain. [Serviddio, Gaetano] Univ Foggia, Foggia, Italy. [Vega, Enrique] World Hlth Org, Pan Amer Hlth Org, Reg Advisory Ageing & Hlth, Washington, DC USA. RP Rodriguez-Manas, L (reprint author), Hosp Univ Getafe, Jefe Serv Geriatria, Carretera Toledo,Km 12,5, Getafe 28905, Spain. EM lrodriguez.hugf@salud.madrid.org RI Pamplona, Reinald/A-7359-2010; FEART, Catherine/A-3339-2016; OI Pamplona, Reinald/0000-0003-4337-6107; FEART, Catherine/0000-0002-7959-1610; serviddio, gaetano/0000-0002-6424-7841 FU EU [HEALTH.2010.2.2.2-5, 261270]; Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad [RD06/0013]; Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain; Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA FX Supported by EU HEALTH.2010.2.2.2-5 (Grant agreement no.: 261270) program, Red Tematica de Investigacion Cooperativa en Envejecimiento y Fragilidad (RD06/0013), Instituto de Salud Carlos III, Ministry of Science and Innovation, Spain and by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA. NR 16 TC 155 Z9 157 U1 6 U2 49 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2013 VL 68 IS 1 BP 62 EP 67 DI 10.1093/gerona/gls119 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400008 PM 22511289 ER PT J AU Metti, AL Cauley, JA Newman, AB Ayonayon, HN Barry, LC Kuller, LM Satterfield, S Simonsick, EM Yaffe, K AF Metti, Andrea L. Cauley, Jane A. Newman, Anne B. Ayonayon, Hilsa N. Barry, Lisa C. Kuller, Lewis M. Satterfield, Suzanne Simonsick, Eleanor M. Yaffe, Kristine TI Plasma Beta Amyloid Level and Depression in Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Depression; Epidemiology; Plasma beta amyloid ID MILD COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE; APOLIPOPROTEIN-E; CES-D; RISK; SYMPTOMS; DEMENTIA; ASSOCIATION; HISTORY; DECLINE AB Background. Older adults with depression have an increased risk of developing dementia. Low plasma beta-amyloid 42 (A beta 42) and A beta 42/A beta 40 have emerged as promising biomarkers of dementia. The association between depression and plasma A beta is unclear. Methods. In this longitudinal study of 988 community-dwelling elders from the Health Aging and Body Composition study, depression was assessed with the Center for Epidemiologic Studies-Depression Scale 10-item version. We determined the association between A beta 42 and A beta 42/A beta 40 tertile and depression at baseline and over 9 years. We also stratified the models to determine if apolipoprotein E e4 allele status modified the associations. Results. Mean baseline age was 74.0 +/- 3.0 years, 51(5.2%) participants had depression, 545 (55.2%) were women, 531 (53.7%) were black, and 286(30.7%) had one or more apolipoprotein E e4 allele. At baseline, there was no association between A beta 42/A beta 40 or A beta 42 and depression. Over 9 years, 220 (23.5%) participants developed depression. In adjusted Cox proportional hazards models, among those with one or more e4 allele, low A beta 42/A beta 40 was associated with an increased risk of developing depression over time (low 10.8% vs high 3.2%, hazard ratio = 2.38, 95% confidence interval: 1.15-4.92). Among those with no e4 allele, there was no association between A beta 42/A beta 40 and risk of depression over time (13.3% vs 17.5%, hazard ratio = 0.80, 95% confidence interval: 0.52-1.23; p value for interaction = .003). Conclusions. The association between low plasma A beta 42/A beta 40 and increased risk of incident depression among those with one or more apolipoprotein E e4 allele implies a synergistic relationship similar to that found with dementia. Future work should investigate the interrelationships among plasma A beta 42/A beta 40, depression, and dementia. C1 [Metti, Andrea L.] Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Ayonayon, Hilsa N.; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Barry, Lisa C.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Simonsick, Eleanor M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metti, AL (reprint author), Univ Pittsburgh, Ctr Aging & Populat Hlth, Dept Epidemiol, Grad Sch Publ Hlth, 130 N Bellefield,Room 434, Pittsburgh, PA 15213 USA. EM alw111@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane A/0000-0003-0752-4408 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; National Institute of Nursing Research [R01-NR012459]; Intramural Research Program on the National Institutes of Health (NIH), NIA FX This work was supported by National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and National Institute of Nursing Research grant R01-NR012459. This research was supported in part by the Intramural Research Program on the National Institutes of Health (NIH), NIA. NR 31 TC 15 Z9 15 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JAN PY 2013 VL 68 IS 1 BP 74 EP 79 DI 10.1093/gerona/gls093 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 065MU UT WOS:000313153400010 PM 22499763 ER PT J AU Shiloh, S Wade, CH Roberts, JS Alford, SH Biesecker, BB AF Shiloh, Shoshana Wade, Christopher H. Roberts, J. Scott Alford, Sharon Hensley Biesecker, Barbara B. TI On Averages and Peaks: How Do People Integrate Attitudes about Multiple Diseases to Reach a Decision about Multiplex Genetic Testing? SO MEDICAL DECISION MAKING LA English DT Article DE cognitive psychology; judgment and decision psychology; patient choice modeling; social judgment theory ID HEREDITARY CANCER; GENOMIC MEDICINE; INFORMED CHOICE; INCREASED RISK; SUSCEPTIBILITY; INFORMATION; PERCEPTIONS; INTENTION; INDIVIDUALS; PARTICIPATE AB Background. The aim of the current study was to learn how people integrate attitudes about multiple health conditions to make a decision about genetic testing uptake. Methods. This study recruited 294 healthy young adults from a parent research project, the Multiplex Initiative, conducted in a large health care system in Detroit, Michigan. All participants were offered a multiplex genetic test that assessed risk for 8 common health conditions (e. g., type 2 diabetes). Data were collected from a baseline survey, a web-based survey, and at the time of testing. Results. Averaging attitudes across diseases predicted test uptake but did not contribute beyond peak attitudes, the highest attitude toward testing for a single disease in the set. Peak attitudes were found sufficient to predict test uptake. Limitations. The effects of set size and mode of presentation could not be examined because these factors were constant in the multiplex test offered. Conclusions. These findings support theories suggesting that people use representative evaluations in attitude formation. The implication of these findings for further developments in genetic testing is that the communication and impact of multiplex testing may need to be considered in the light of a bias toward peak attitudes. C1 [Shiloh, Shoshana] Tel Aviv Univ, Dept Psychol, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. [Wade, Christopher H.] Univ Washington Bothell, Dept Nursing, Bothell, WA USA. [Roberts, J. Scott] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI USA. [Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Shiloh, S (reprint author), Tel Aviv Univ, Dept Psychol, Sch Psychol Sci, IL-69978 Tel Aviv, Israel. EM shoshi@freud.tau.ac.il FU National Human Genome Research Institute, National Institutes of Health; National Cancer Institute [U19CA 079689]; National Institutes of Health [HHSN268200782096C]; National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The research was made possible through a collaboration with the Cancer Research Network funded by the National Cancer Institute (U19CA 079689). Group Health Research Institute and Henry Ford Hospital provided additional resources. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (HHSN268200782096C). In addition, this research was supported in part by an appointment to the Senior Fellowship Program at the National Institutes of Health. This program is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the National Institutes of Health. Revision accepted for publication 19 June 2012. NR 49 TC 1 Z9 1 U1 0 U2 20 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 JAN PY 2013 VL 33 IS 1 SI SI BP 71 EP 77 DI 10.1177/0272989X12464432 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 067BR UT WOS:000313268100007 PM 23128581 ER PT J AU Jaffe, ES Nicolae, A Pittaluga, S AF Jaffe, Elaine S. Nicolae, Alina Pittaluga, Stefania TI Peripheral T-cell and NK-cell lymphomas in the WHO classification: pearls and pitfalls SO MODERN PATHOLOGY LA English DT Article DE anaplastic large cell lymphoma; Epstein Barr virus; NK-cell lymphoma; peripheral T-cell lymphoma; T-follicular helper cells; T regulatory cells ID EPSTEIN-BARR-VIRUS; NATURAL-KILLER-CELL; DISTINCT CLINICOPATHOLOGICAL ENTITY; LYMPHADENOPATHY-LIKE LYMPHOMA; GAMMA-DELTA; ANGIOIMMUNOBLASTIC LYMPHADENOPATHY; LYMPHOPROLIFERATIVE DISORDER; MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; B-CELL AB Peripheral T-cell and NK-cell lymphomas are functionally, pathologically, and clinically complex. Most nodal T-cell lymphomas belong to the adaptive immune system, whereas many extranodal T-cell and NK-cell lymphomas are derived from innate immune cells. The pathological manifestations often reflect the functional attributes of the neoplastic cells. Several forms of peripheral T-cell lymphoma are derived from T-follicular helper cells (T-FH), and include angioimmunoblastic T-cell lymphoma, the follicular variant of peripheral T-cell lymphoma, not otherwise specified, and primary cutaneous small/medium CD4-positive T-cell lymphoma. T-FH-derived neoplasms are often associated with atypical and clonal B-cell proliferations, which take a number of forms, sometimes mimicking classical Hodgkin's lymphoma, and sometimes showing marked plasmacytic differentiation. Most extranodal T-cell lymphomas are cytotoxic and often arise in mucosal-associated sites. They can be derived from either alpha beta or gamma delta cytotoxic T cells, and include subcutaneous panniculitis-like T-cell lymphoma, and enteropathy-associated T-cell lymphomas, both Type I and Type II. Type I enteropathy-associated lymphomas occur in association with celiac disease, whereas Type II lymphomas are more often sporadic. For some T-cell lymphomas, such as hepatosplenic T-cell lymphoma, immunophenotypic heterogeneity is seen within a single disease entity. New data are emerging on the molecular pathogenesis of T-cell and NK-cell lymphoma, but most tumor types remain poorly characterized. Modern Pathology (2013) 26, S71-S87; doi:10.1038/modpathol.2012.181 C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH,Ctr Canc Res, Bldg 10,Room 2B 42,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Jaffe, Elaine/0000-0003-4632-0301 NR 118 TC 33 Z9 35 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 2013 VL 26 SU 1 BP S71 EP S87 DI 10.1038/modpathol.2012.181 PG 17 WC Pathology SC Pathology GA 067PH UT WOS:000313307100006 PM 23281437 ER PT J AU Qazi, S Liepold, LO Abedin, MJ Johnson, B Prevelige, P Frank, JA Douglas, T AF Qazi, Shefah Liepold, Lars O. Abedin, Md Joynal Johnson, Ben Prevelige, Peter Frank, Joseph A. Douglas, Trevor TI P22 Viral Capsids as Nanocomposite High-Relaxivity MRI Contrast Agents SO MOLECULAR PHARMACEUTICS LA English DT Article DE viral capsid; VLP; bacteriophage P22; magnetic resonance imaging; MRI; imaging agent; contrast agent; T1; relaxivity; gadolinium; DTPA-Gd; azide-alkyne click chemistry; nanoparticle; nanocomposite; protein cages; payload ID AZIDE-ALKYNE CYCLOADDITION; NANOPARTICLES; COMPLEXES; COAT; MATURATION; WATER; BACTERIOPHAGE-P22; POLYMERIZATION; MECHANISMS; STRATEGIES AB Attachment of multiple chelated Gd3+ ions to the interior of bacteriophage P22 viral capsids affords nanoscale MRI contrast agents with extremely high relaxivity values. Highly fenestrated "wiffleball" morphology is unique to P22 and assures water exchange between the environment and interior cavity of the capsid. The cavity of P22 "wiffleball" was functionalized with a branched oligomer comprising multiple DTPA-Gd complexes resulting in an impressive payload of 1,900 Gd3+ ions inside each 64 nm capsid. High relaxivities of r(l,ionic) = 21.7 mM(-1) s(-1) and r(l,particle) = 41,300 mM(-1) s(-1) at 298 K, 0.65 T (28 MHz) are reported, with r(1)/r(2) ratio of 0.80 and optimized rotational correlation time for this system. Specific design modifications are suggested for future improvements of viral capsid-based MRI contrast agents directed toward clinical translation. C1 [Qazi, Shefah; Liepold, Lars O.; Abedin, Md Joynal; Johnson, Ben; Douglas, Trevor] Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. [Qazi, Shefah; Liepold, Lars O.; Abedin, Md Joynal; Johnson, Ben; Douglas, Trevor] Montana State Univ, Ctr Bioinspired Nanomat, Bozeman, MT 59717 USA. [Prevelige, Peter] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Frank, Joseph A.] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA. [Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Douglas, T (reprint author), Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. EM tdouglas@chemistry.montana.edu RI Douglas, Trevor/F-2748-2011 FU National Institutes of Health [R01-EB012027] FX This research was supported in part by grants from the National Institutes of Health (R01-EB012027). NR 36 TC 25 Z9 25 U1 3 U2 45 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 JAN PY 2013 VL 10 IS 1 BP 11 EP 17 DI 10.1021/mp300208g PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 065NV UT WOS:000313156100003 PM 22656692 ER PT J AU Gaitan, MI de Alwis, MP Sati, P Nair, G Reich, DS AF Gaitan, Maria I. de Alwis, Manori P. Sati, Pascal Nair, Govind Reich, Daniel S. TI Multiple sclerosis shrinks intralesional, and enlarges extralesional, brain parenchymal veins SO NEUROLOGY LA English DT Article ID CEREBROSPINAL VENOUS INSUFFICIENCY; MS LESIONS; VISIBILITY; ATROPHY; VASCULATURE; IMPAIRMENT; VENOGRAPHY; MATTER; 3T AB Objectives: Many multiple sclerosis (MS) lesions develop around small veins that are surrounded by perivenular inflammatory cells, but whether veins in the brains of people with MS are smaller or larger than similar veins in healthy volunteers or people with other neurologic diseases remains unknown. This question can be addressed by high-resolution, high-field-strength MRI. Methods: In a cross-sectional study performed on a standard 3 T clinical scanner, we acquired whole-brain T2*-weighted images with 0.55 mm isotropic voxels and reconstructed the courses of deep and superficial veins within the white matter. We compared the apparent diameters of intralesional and perilesional veins to those of extralesional MS veins, veins in healthy volunteers, and veins in individuals with other neurologic diseases. Results: We studied veins in 19 MS cases, 9 healthy volunteers, and 8 individuals with other neurologic diseases, analyzing a total of 349 veins. The mean diameter of intralesional veins (0.76 +/- 0.14 mm) was smaller than that of perilesional (1.18 +/- 0.13 mm; p < 0.001) and extralesional (1.13 +/- 0.14 mm; p, 0.001) veins, regardless of lesion size and location. Perilesional and extralesional MS veins were larger than non-MS veins (0.94 +/- 0.14 mm; p < 0.001), and intralesional MS veins were smaller (p < 0.001). Conclusions: The small apparent size of intralesional MS veins may reflect compression by the perivascular inflammatory cuff within active lesions or hardening of the vascular wall in chronic lesions. The finding that extralesional veins are larger than similar veins in non-MS lesions may result from diffuse disease-related processes. Neurology (R) 2013;80:145-151 C1 [Gaitan, Maria I.; de Alwis, Manori P.; Sati, Pascal; Nair, Govind; Reich, Daniel S.] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [de Alwis, Manori P.] Cornell Univ, Ithaca, NY USA. RP Reich, DS (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM daniel.reich@nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Intramural Research Program of the National Institute of Neurological Disorders of Stroke, NIH FX Supported by the Intramural Research Program of the National Institute of Neurological Disorders of Stroke, NIH. NR 32 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN PY 2013 VL 80 IS 2 BP 145 EP 151 DI 10.1212/WNL.0b013e31827b916f PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 068DM UT WOS:000313344700010 PM 23255828 ER PT J AU Pemberton, VL Browning, B Webster, A Dean, JM Moler, FW AF Pemberton, Victoria L. Browning, Brittan Webster, Angie Dean, J. Michael Moler, Frank W. TI Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials: The Vanguard Phase Experience and Implications for Other Trials SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE cardiopulmonary resuscitation; induced hypothermia; pediatric intensive care ID RANDOMIZED CONTROLLED-TRIALS; CONGENITAL HEART-DISEASE; CLINICAL-TRIALS; NEONATAL ENCEPHALOPATHY; MODERATE HYPOTHERMIA; MULTICENTER COHORT; CHILDREN; CHALLENGES; BARRIERS; OUTCOMES AB Objective: To determine whether an 18-month vanguard phase, in the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials, confirmed study feasibility and patient safety, a prerequisite to continued funding by the sponsor. Design: Randomized controlled trial. Setting: Pediatric intensive care and pediatric cardiac care units in 15 clinical sites in the United States and Canada. Patients: Children aged 48 hrs to 18 yrs of age, with return of circulation after cardiac arrest. Interventions: Therapeutic hypothermia vs. therapeutic normothermia. Measurements and Main Results: The first 15 of 20 potential sites to obtain Institutional Review Board and subcontract approvals were selected as vanguard sites. Institutional Review Board approvals were obtained 92 days (median, interquartile range 65-114) and subcontracts signed 34 days (interquartile range 20-48) after distribution. Sites screened subjects at 13 days (interquartile range 9-21) and enrolled the first subjects 64 days (interquartile range 13-154) after study launch. The recruitment milestone was reached 4 months ahead of schedule, with no safety concerns identified. Overall recruitment in this ongoing trial remains on target. Conclusions: The Therapeutic Hypothermia after Pediatric Cardiac Arrest vanguard phase proved beneficial for the investigators and funding agency. Because complex multicenter trials are rarely ready to launch when grant funds are received, the vanguard allowed time to refine the protocol and recruitment approaches. Competition for vanguard positions led to expedient Institutional Review Board and subcontract completion. Early success and sustained momentum contributed to recruitment at or above goals. Financial risks to the sponsor were minimized by tying funding for the full trial to achieving pre-specified milestones. A vanguard phase may be a desirable strategy for the successful conduct of other complex clinical trials. Clinical Trial Registration: NCT00880087 and NCT00878644 (http://clinicaltrials.gov/ct2/show/NCT00880087?term=pediatric+hypothermia & rank=4; http://clinicaltrials.gov/ct2/show/NCT00878644?term=pediatric+hypothermia&rank=5). (Pediatr Crit Care Med 2013; 14:19-26) C1 [Pemberton, Victoria L.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Browning, Brittan; Webster, Angie; Dean, J. Michael] Univ Utah, Dept Pediat, Div Crit Care, Salt Lake City, UT USA. [Moler, Frank W.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. RP Pemberton, VL (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. EM pembertonv@nhlbi.nih.gov FU [NIH U01 HL094339]; [U01 HL094345] FX Supported, in part, by grants NIH U01 HL094339 and U01 HL094345. NR 37 TC 13 Z9 13 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2013 VL 14 IS 1 BP 19 EP 26 DI 10.1097/PCC.0b013e31825b860b PG 8 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 068FS UT WOS:000313352200009 PM 23295834 ER PT J AU Anand, KJS Clark, AE Willson, DF Berger, J Meert, KL Zimmerman, JJ Harrison, R Carcillo, JA Newth, CJL Bisping, S Holubkov, R Dean, JM Nicholson, CE AF Anand, Kanwaljeet J. S. Clark, Amy E. Willson, Douglas F. Berger, John Meert, Kathleen L. Zimmerman, Jerry J. Harrison, Rick Carcillo, Joseph A. Newth, Christopher J. L. Bisping, Stephanie Holubkov, Richard Dean, J. Michael Nicholson, Carol E. CA Eunice Kennedy Shriver Natl Inst TI Opioid Analgesia in Mechanically Ventilated Children: Results From the Multicenter Measuring Opioid Tolerance Induced by Fentanyl Study SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE agitation; anxiolysis; child; clinical practices; infant; intensive care; pain; variability ID PEDIATRIC INTENSIVE-CARE; CRITICALLY-ILL CHILDREN; CLINICAL-PRACTICE GUIDELINES; CONSENSUS GUIDELINES; PROLONGED SEDATION; PAIN-CONTROL; SPINAL-CORD; WITHDRAWAL; MIDAZOLAM; UNIT AB Objective: To examine the clinical factors associated with increased opioid dose among mechanically ventilated children in the pediatric intensive care unit. Design: Prospective, observational study with 100% accrual of eligible patients. Setting: Seven pediatric intensive care units from tertiary-care children's hospitals in the Collaborative Pediatric Critical Care Research Network. Patients: Four hundred nineteen children treated with morphine or fentanyl infusions. Interventions: None. Measurements and Main Results: Data on opioid use, concomitant therapy, demographic and explanatory variables were collected. Significant variability occurred in clinical practices, with up to 100-fold differences in baseline opioid doses, average daily or total doses, or peak infusion rates. Opioid exposure for 7 or 14 days required doubling of the daily opioid dose in 16% patients (95% confidence interval 12%-19%) and 20% patients (95% confidence interval 16%-24%), respectively. Among patients receiving opioids for longer than 3 days (n = 225), this occurred in 28% (95% confidence interval 22%-33%) and 35% (95% confidence interval 29%-41%) by 7 or 14 days, respectively. Doubling of the opioid dose was more likely to occur following opioid infusions for 7 days or longer (odds ratio 7.9, 95% confidence interval 4.3-14.3; p < 0.001) or co-therapy with midazolam (odds ratio 5.6, 95% confidence interval 2.4-12.9; p < 0.001), and it was less likely to occur if morphine was used as the primary opioid (vs. fentanyl) (odds ratio 0.48, 95% confidence interval 0.25-0.92; p = 0.03), for patients receiving higher initial doses (odds ratio 0.96, 95% confidence interval 0.95-0.98; p < 0.001), or if patients had prior pediatric intensive care unit admissions (odds ratio 0.37, 95% confidence interval 0.15-0.89; p = 0.03). Conclusions: Mechanically ventilated children require increasing opioid doses, often associated with prolonged opioid exposure or the need for additional sedation. Efforts to reduce prolonged opioid exposure and clinical practice variation may prevent the complications of opioid therapy. (Pediatr Crit Care Med 2013; 14:28-36) C1 [Anand, Kanwaljeet J. S.] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Le Bonheur Childrens Hosp, Memphis, TN 38163 USA. [Anand, Kanwaljeet J. S.] Univ Tennessee, Ctr Hlth Sci, Dept Anesthesiol, Le Bonheur Childrens Hosp, Memphis, TN 38163 USA. [Anand, Kanwaljeet J. S.] Univ Tennessee, Ctr Hlth Sci, Dept Neurobiol, Le Bonheur Childrens Hosp, Memphis, TN 38163 USA. [Clark, Amy E.; Bisping, Stephanie; Holubkov, Richard; Dean, J. Michael] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Willson, Douglas F.] Univ Virginia, Dept Pediat, Childrens Hosp, Charlottesville, VA USA. [Berger, John] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA. [Meert, Kathleen L.] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA. [Zimmerman, Jerry J.] Univ Washington, Sch Med, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Harrison, Rick] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Carcillo, Joseph A.] Childrens Hosp Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Newth, Christopher J. L.] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, Los Angeles, CA 90027 USA. [Nicholson, Carol E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Bethesda, MD USA. RP Anand, KJS (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Le Bonheur Childrens Hosp, Memphis, TN 38163 USA. EM kanand@uthsc.edu OI Anand, Kanwaljeet/0000-0001-6498-1483 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Health and Human Services [U10HD500009, U10HD050096, U10HD049981, U10HD049945, U10HD049983, U10HD050012, U01HD049934] FX This work was supported, in part, by cooperative agreements (U10HD500009, U10HD050096, U10HD049981, U10HD049945, U10HD049983, U10HD050012, and U01HD049934) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Department of Health and Human Services. NR 53 TC 21 Z9 21 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2013 VL 14 IS 1 BP 27 EP 36 DI 10.1097/PCC.0b013e318253c80e PG 10 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 068FS UT WOS:000313352200010 PM 23132396 ER PT J AU Ni, C Zhang, DM Beyer, LA Halsey, KE Fukui, H Raphael, Y Dolan, DF Hornyak, TJ AF Ni, Christina Zhang, Deming Beyer, Lisa A. Halsey, Karin E. Fukui, Hideto Raphael, Yehoash Dolan, David F. Hornyak, Thomas J. TI Hearing dysfunction in heterozygous Mitf(Mi-wh)/+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Article DE cochlea; development; melanocyte; intermediate cell; deafness ID TRANSCRIPTION FACTOR; STRIA VASCULARIS; MITF GENE; MELANOCYTE DEVELOPMENT; MICROPHTHALMIA GENE; HUMAN HOMOLOG; NEURAL CREST; HAIR-CELLS; INNER-EAR; MUTATIONS AB The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh)/+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh)/+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh)/+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh)/+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. C1 [Ni, Christina; Zhang, Deming; Hornyak, Thomas J.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Beyer, Lisa A.; Halsey, Karin E.; Fukui, Hideto; Raphael, Yehoash; Dolan, David F.] Univ Michigan, Kresge Hearing Res Inst, Dept Otolaryngol, Sch Med, Ann Arbor, MI 48109 USA. [Hornyak, Thomas J.] VA Maryland Hlth Care Syst, Baltimore, MD USA. [Hornyak, Thomas J.] Univ Maryland, Sch Med, Dept Dermatol, Baltimore, MD 21201 USA. [Hornyak, Thomas J.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. RP Hornyak, TJ (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM thornyak@som.umaryland.edu FU NIH [R01-AR047951, P30-DC05188]; NIH, National Cancer Institute, Center for Cancer Research FX The technical assistance of Lisa Kabara is appreciated. We acknowledge Lynn Lamoreux for originally providing Mitf mutant mice, and Ronna Hertzano for assistance with cochlear dissections. This work was supported by NIH R01-AR047951 (to T.J.H.) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The work was also supported by NIH P30-DC05188 (D.F.D., Y.R.). NR 35 TC 5 Z9 6 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD JAN PY 2013 VL 26 IS 1 BP 78 EP 87 DI 10.1111/pcmr.12030 PG 10 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 058QL UT WOS:000312648600011 PM 23020089 ER PT J AU Pringle, B Colpe, LJ Heinssen, RK Schoenbaum, M Sherrill, JT Claassen, CA Pearson, JL AF Pringle, Beverly Colpe, Lisa J. Heinssen, Robert K. Schoenbaum, Michael Sherrill, Joel T. Claassen, Cynthia A. Pearson, Jane L. TI A Strategic Approach for Prioritizing Research and Action to Prevent Suicide SO PSYCHIATRIC SERVICES LA English DT Article ID CONTROLLED-TRIAL; RISK-FACTORS; INTERVENTIONS; MILITARY; PROGRAMS AB It is time to strategically apply science and accountability to the public health problem of preventable suicide. U.S. suicide rates have remained stable for decades. More than 36,000 individuals now die by suicide each year. A public health based approach to quickly and substantially reduce suicides requires strategic deployment of existing evidence-based interventions, rapid development of new interventions, and measures to increase accountability for results. The purpose of this Open Forum is to galvanize researchers to further develop and consolidate knowledge needed to guide these actions. As researchers overcome data limitations and methodological challenges, they enable better prioritization of high-risk subgroups for targeted suicide prevention efforts, identification of effective interventions ready for deployment, estimation of the implementation impact of effective interventions in real-world settings, and assessment of time horizons for taking implementation to scale. This new knowledge will permit decision makers to take strategic action to reduce suicide and stake-holders to hold them accountable for results. (Psychiatric Services 64:71-75, 2013; doi: 10.1176/appi.ps.005122011) C1 [Pringle, Beverly; Colpe, Lisa J.; Heinssen, Robert K.; Schoenbaum, Michael; Sherrill, Joel T.; Pearson, Jane L.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Claassen, Cynthia A.] Univ N Texas Hlth Sci Ctr, Dept Psychiat, Ft Worth, TX USA. RP Pringle, B (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM bpringle@mail.nih.gov NR 28 TC 15 Z9 15 U1 1 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 JAN PY 2013 VL 64 IS 1 BP 71 EP 75 DI 10.1176/appi.ps.005122011 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 067MV UT WOS:000313299500013 PM 23280458 ER PT J AU Sarenmalm, EK Browall, M Persson, LO Fall-Dickson, J Gaston-Johansson, F AF Sarenmalm, Elisabeth Kenne Browall, Maria Persson, L. -O. Fall-Dickson, J. Gaston-Johansson, Fanny TI Relationship of sense of coherence to stressful events, coping strategies, health status, and quality of life in women with breast cancer SO PSYCHO-ONCOLOGY LA English DT Article DE sense of coherence; stressful events; coping strategies; health status; quality of life; distress; breast cancer ID PSYCHOLOGICAL DISTRESS; POSTMENOPAUSAL WOMEN; ANTONOVSKYS SENSE; ANXIETY; COHORT; SALUTOGENESIS; CHEMOTHERAPY; DIAGNOSIS; SYMPTOMS; SCALE AB Objective To test the hypothesis that Antonovsky's concept of sense of coherence (SOC) predicts stressful events, coping strategies, health status, and quality of life (QoL) in a cohort of postmenopausal women (n?=?131) with newly diagnosed primary or recurrent breast cancer. Methods Regression analyses of longitudinal data at baseline through 6?months following breast cancer diagnosis examined the relationships between SOC (13-item version), daily assessment of coping with stressful events, health status, and QoL (EORTC QLQ-30). Results The findings support Antonovsky's concept of SOC. Women with strong SOC reported fewer stressful events and more days without stressful events. They used more coping strategies and more frequently used distraction, situation redefinition, direct action, and relaxation, but seldom religion, to cope with stressful events, and reported better health status and QoL. Women with weak SOC experienced more distress and used fewer coping strategies, and they more frequently used coping strategies such as catharsis and seeking social and spiritual support, but seldom acceptance of the situation. They reported worse health status and QoL, regardless of disease stage or treatment. The relationships between SOC and health status and QoL were linear. Conclusions Sense of coherence significantly predicts distress, number and type of coping strategies such as direct action and relaxation, health status, and QoL in women with breast cancer. Our data suggest that the SOC scale may be a useful screening tool to identify individuals particularly vulnerable to distress and unable to cope adequately. Assessing SOC strength may assist health care providers to provide individualized patient interventions. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Sarenmalm, Elisabeth Kenne] Skaraborg Hosp, Ctr Res & Dev, SE-54185 Skovde, Sweden. [Sarenmalm, Elisabeth Kenne; Persson, L. -O.] Gothenburg Univ, Sahlgrenska Acad, Inst Hlth & Caring Sci, Gothenburg, Sweden. [Sarenmalm, Elisabeth Kenne; Browall, Maria; Gaston-Johansson, Fanny] Johns Hopkins Sch Nursing, Baltimore, MD USA. [Browall, Maria] Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden. [Browall, Maria] Univ Skovde, Sch Life Sci, Skovde, Sweden. [Fall-Dickson, J.] NINR, NIH, Bethesda, MD 20892 USA. RP Sarenmalm, EK (reprint author), Skaraborg Hosp, Ctr Res & Dev, SE-54185 Skovde, Sweden. EM elisabeth.kenne.sarenmalm@vgregion.se RI Brovall, Maria/K-5489-2013 OI Brovall, Maria/0000-0003-0976-531X FU Western Region Research and Development Unit; King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg, Sweden FX We thank all the patients who participated in this study and willingly completed the diaries and questionnaires. The authors would also like to express their sincere gratitude to Salmir Nasic for expert assistance in statistical analyses. This study was supported by a grant from the Western Region Research and Development Unit and the King Gustav V Jubilee Clinic Cancer Research Foundation, Gothenburg, Sweden. The authors have declared that there is no conflict of interest. NR 40 TC 17 Z9 18 U1 3 U2 40 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2013 VL 22 IS 1 BP 20 EP 27 DI 10.1002/pon.2053 PG 8 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 065EV UT WOS:000313132100004 ER PT J AU Park, J Piknova, B Schechter, AN AF Park, Jiwon Piknova, Barbora Schechter, Alan N. TI Nitric oxide levels increase during platelet concentrate production from buffy coats, but not during storage Reply SO TRANSFUSION LA English DT Letter ID THROMBOTIC THROMBOCYTOPENIC PURPURA C1 [Park, Jiwon; Piknova, Barbora; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Park, J (reprint author), NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM alans@intra.niddk.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2013 VL 53 IS 1 BP 235 EP 235 DI 10.1111/j.1537-2995.2012.03933.x PG 1 WC Hematology SC Hematology GA 068ET UT WOS:000313348900036 PM 23294214 ER PT J AU Resnik, DB AF Resnik, David B. TI Plagiarism among Collaborators SO ACCOUNTABILITY IN RESEARCH-POLICIES AND QUALITY ASSURANCE LA English DT Article C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Mail Drop CU 03,Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-04] NR 6 TC 2 Z9 2 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0898-9621 J9 ACCOUNT RES JI Account. Res. PD JAN 1 PY 2013 VL 20 IS 1 BP 1 EP 4 DI 10.1080/08989621.2013.749738 PG 4 WC Medical Ethics SC Medical Ethics GA 063FH UT WOS:000312981100001 PM 23281580 ER PT J AU Dauter, Z AF Dauter, Zbigniew TI Placement of molecules in (not out of) the cell SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Editorial Material AB To uniquely describe a crystal structure, it is sufficient to specify the crystal unit cell and symmetry, and describe the unique structural motif which is repeated by the space-group symmetry throughout the whole crystal. It is somewhat arbitrary how such a unique motif can be defined and positioned with respect to the unit-cell origin. As a result of such freedom, some isomorphous structures are presented in the Protein Data Bank in different locations and appear as if they have different atomic coordinates, despite being completely equivalent structurally. This may easily confuse those users of the PDB who are less familiar with crystallographic symmetry transformations. It would therefore be beneficial for the community of PDB users to introduce standard rules for locating crystal structures of macromolecules in the unit cells of various space groups. C1 NCI, Synchrotron Radiat Res Sect, Argonne Natl Lab, Argonne, IL 60439 USA. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, Argonne Natl Lab, Argonne, IL 60439 USA. EM dauter@anl.gov NR 5 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JAN PY 2013 VL 69 BP 2 EP 4 DI 10.1107/S0907444912044794 PN 1 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 061RU UT WOS:000312866500002 PM 23275157 ER PT J AU Xu, XQ Chang, BCW Mans, BJ Ribeiro, JMC Andersen, JF AF Xu, Xueqing Chang, Bianca W. Mans, Ben J. Ribeiro, Jose M. C. Andersen, John F. TI Structure and ligand-binding properties of the biogenic amine-binding protein from the saliva of a blood-feeding insect vector of Trypanosoma cruzi SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID BUG RHODNIUS-PROLIXUS; NITRIC-OXIDE BINDING; HEME PROTEIN; BLOODSUCKING INSECT; NITROPHORIN 2; DENSITY MODIFICATION; CRYSTAL-STRUCTURES; HISTAMINE-BINDING; SOFT TICKS; POCKET AB Proteins that bind small-molecule mediators of inflammation and hemostasis are essential for blood-feeding by arthropod vectors of infectious disease. In ticks and triatomine insects, the lipocalin protein family is greatly expanded and members have been shown to bind biogenic amines, eicosanoids and ADP. These compounds are potent mediators of platelet activation, inflammation and vascular tone. In this paper, the structure of the amine-binding protein (ABP) from Rhodnius prolixus, a vector of the trypanosome that causes Chagas disease, is described. ABP binds the biogenic amines serotonin and norepinephrine with high affinity. A complex with tryptamine shows the presence of a binding site for a single ligand molecule in the central cavity of the beta-barrel structure. The cavity contains significant additional volume, suggesting that this protein may have evolved from the related nitrophorin proteins, which bind a much larger heme ligand in the central cavity. C1 [Xu, Xueqing; Chang, Bianca W.; Mans, Ben J.; Ribeiro, Jose M. C.; Andersen, John F.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Mans, Ben J.] Agr Res Council, Onderstepoort Vet Inst, ZA-0110 Onderstepoort, South Africa. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM jandersen@niaid.nih.gov RI Ribeiro, Jose/J-7011-2015; OI Mans, Ben/0000-0002-0177-0029; Ribeiro, Jose/0000-0002-9107-0818 FU US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38]; NIAID, National Institutes of Health FX The authors thank D. Garboczi and A. Gittis for discussions and R. Hearn for technical assistance. We also thank the staffs of the Southeast Regional Collaborative Access Team and the Structural Biology Center, Advanced Photon Source, Argonne National Laboratory for assistance with X-ray data collection. Use of the Advanced Photon Source beamlines was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract No. W-31-109-Eng-38. This work was supported by the intramural research program of the NIAID, National Institutes of Health. NR 41 TC 6 Z9 6 U1 1 U2 52 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JAN PY 2013 VL 69 BP 105 EP 113 DI 10.1107/S0907444912043326 PN 1 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 061RU UT WOS:000312866500013 PM 23275168 ER PT J AU Furst, DO Goldfarb, LG Kley, RA Vorgerd, M Olive, M van der Ven, PFM AF Fuerst, Dieter O. Goldfarb, Lev G. Kley, Rudolf A. Vorgerd, Matthias Olive, Montse van der Ven, Peter F. M. TI Filamin C-related myopathies: pathology and mechanisms SO ACTA NEUROPATHOLOGICA LA English DT Review DE Filamin C; Filaminopathy; Myofibrillar myopathy; Distal myopathy; Limb-girdle muscular dystrophy; Pathomechanism ID EARLY RESPIRATORY-FAILURE; Z-DISC PROTEINS; MYOFIBRILLAR MYOPATHY; MUSCULAR-DYSTROPHY; BINDING PROTEIN; SKELETAL-MUSCLE; DISTAL MYOPATHY; HEREDITARY MYOPATHY; ACTININ-BINDING; GAMMA-FILAMIN AB The term filaminopathy was introduced after a truncating mutation in the dimerization domain of filamin C (FLNc) was shown to be responsible for a devastating muscle disease. Subsequently, the same mutation was found in patients from diverse ethnical origins, indicating that this specific alteration is a mutational hot spot. Patients initially present with proximal muscle weakness, while distal and respiratory muscles become affected with disease progression. Muscle biopsies of these patients show typical signs of myofibrillar myopathy, including disintegration of myofibrils and aggregation of several proteins into distinct intracellular deposits. Highly similar phenotypes were observed in patients with other mutations in Ig-like domains of FLNc that result in expression of a noxious protein. Biochemical and biophysical studies showed that the mutated domains acquire an abnormal structure causing decreased stability and eventually becoming a seed for abnormal aggregation with other proteins. The disease usually presents only after the fourth decade of life possibly as a result of ageing-related impairments in the machinery that is responsible for disposal of damaged proteins. This is confirmed by mutations in components of this machinery that cause a highly similar phenotype. Transfection studies of cultured muscle cells reflect the events observed in patient muscles and, therefore, may provide a helpful model for testing future dedicated therapeutic strategies. More recently, FLNC mutations were also found in families with a distal myopathy phenotype, caused either by mutations in the actin-binding domain of FLNc that result in increased actin-binding and non-specific myopathic abnormalities without myofibrillar myopathy pathology, or a nonsense mutation in the rod domain that leads to RNA instability, haploinsufficiency with decreased expression levels of FLNc in the muscle fibers and myofibrillar abnormalities, but not to the formation of desmin-positive protein aggregates required for the diagnosis of myofibrillar myopathy. C1 [Fuerst, Dieter O.; van der Ven, Peter F. M.] Univ Bonn, Inst Cell Biol, D-53121 Bonn, Germany. [Goldfarb, Lev G.] NIH, Bethesda, MD 20892 USA. [Kley, Rudolf A.; Vorgerd, Matthias] Ruhr Univ Bochum, Univ Hosp Bergmannsheil, Neuromuscular Ctr Ruhrgebiet, Dept Neurol, Bochum, Germany. [Olive, Montse] IDIBELL Hosp Univ Bellvitge, Dept Pathol, Inst Neuropathol, Barcelona, Spain. [Olive, Montse] IDIBELL Hosp Univ Bellvitge, Dept Neurol, Neuromuscular Unit, Barcelona, Spain. RP Furst, DO (reprint author), Univ Bonn, Inst Cell Biol, Ulrich Haberland Str 61A, D-53121 Bonn, Germany. EM dfuerst@uni-bonn.de; GoldfarbL@ninds.nih.gov; rudolf.kley@rub.de; matthias.vorgerd@bergmannsheil.de; 25169mop@comb.cat; pvdven@uni-bonn.de OI Olive, Montse/0000-0001-5727-0165 FU National Institute of Neurological Disorders and Stroke, NIH; German Research foundation [KL 2487/1-1, FOR1228, FOR1352]; German Ministry of Education and Research [01GM0887]; Ruhr-University Bochum [FoRUM K042-09]; Spanish Instituto de Salud Carlos III [PI08-574] FX This research was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH [L. G. G], the German Research foundation [KL 2487/1-1 to R. A. K., FOR1228 to M. V., D.O.F., FOR1352 to D.O.F.], the German Ministry of Education and Research [01GM0887 to R. A. K., P.F.M.v.d. V., M. V., D.O.F.], the Ruhr-University Bochum [FoRUM K042-09 to R. A. K.], and the Spanish Instituto de Salud Carlos III [PI08-574 to M.O.]. NR 61 TC 21 Z9 21 U1 1 U2 33 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2013 VL 125 IS 1 BP 33 EP 46 DI 10.1007/s00401-012-1054-9 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 063MD UT WOS:000313002300004 PM 23109048 ER PT J AU Prada, CE Jousma, E Rizvi, TA Wu, JQ Dunn, RS Mayes, DA Cancelas, JA Dombi, E Kim, MO West, BL Bollag, G Ratner, N AF Prada, Carlos E. Jousma, Edwin Rizvi, Tilat A. Wu, Jianqiang Dunn, R. Scott Mayes, Debra A. Cancelas, Jose A. Dombi, Eva Kim, Mi-Ok West, Brian L. Bollag, Gideon Ratner, Nancy TI Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition SO ACTA NEUROPATHOLOGICA LA English DT Article DE Macrophages; Neurofibromatosis type 1; Neurofibromin; Fms; c-kit; Minocycline; Mouse model ID PERIPHERAL-NERVE; MAST-CELLS; SCHWANN-CELLS; GLIOMA GROWTH; TYPE-1; MICROGLIA; HYPERACTIVATION; RECRUITMENT; EXPRESSION; PLEXIFORM AB Neurofibromatosis type 1 (NF1) is a common genetic disease that predisposes 30-50 % of affected individuals to develop plexiform neurofibromas. We found that macrophage infiltration of both mouse and human neurofibromas correlates with disease progression. Macrophages accounted for almost half of neurofibroma cells, leading us to hypothesize that nerve macrophages are inflammatory effectors in neurofibroma development and/or growth. We tested the effects of PLX3397, a dual kit/fms kinase inhibitor that blocks macrophage infiltration, in the Dhh-Cre; Nf1 (flox/flox) mouse model of GEM grade I neurofibroma. In mice aged 1-4 months, prior to development of nerve pathology and neurofibroma formation, PLX3397 did not impair tumor initiation and increased tumor volume compared to controls. However, in mice aged 7-9 months, after tumor establishment, a subset of mice demonstrating the largest reductions in macrophages after PLX3397 exhibited cell death and tumor volume regression. Macrophages are likely to provide an initial line of defense against developing tumors. Once tumors are established, they become tumor permissive. Macrophage depletion may result in impaired tumor maintenance and represent a therapeutic strategy for neurofibroma therapy. C1 [Jousma, Edwin; Rizvi, Tilat A.; Wu, Jianqiang; Mayes, Debra A.; Cancelas, Jose A.; Ratner, Nancy] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA. [Prada, Carlos E.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Dunn, R. Scott] Cincinnati Childrens Hosp Med Ctr, Div Imaging Resource Ctr, Cincinnati, OH 45229 USA. [Kim, Mi-Ok] Cincinnati Childrens Hosp Med Ctr, Div Biostat, Cincinnati, OH 45229 USA. [Prada, Carlos E.] Cardiovasc Fdn Colombia, Ctr Genom Med & Metab, Floridablanca, Colombia. [Dombi, Eva] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [West, Brian L.; Bollag, Gideon] Plexxikon Inc, Berkeley, CA 94710 USA. RP Ratner, N (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, 3333 Burnet Ave,ML 7013, Cincinnati, OH 45229 USA. EM nancy.ratner@cchmc.org RI Kim, Mi-Ok/O-9626-2015 FU NIH [NS28840, P50-NS057531]; Department of Defense [W81XWH-11-1-0057] FX This work was supported by grants from the NIH (NS28840 and P50-NS057531), and the Department of Defense Program on Neurofibromatosis (W81XWH-11-1-0057) to NR. We thank Margaret Collins, MD for providing human tissue sections. NR 39 TC 25 Z9 26 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JAN PY 2013 VL 125 IS 1 BP 159 EP 168 DI 10.1007/s00401-012-1056-7 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 063MD UT WOS:000313002300012 PM 23099891 ER PT J AU Ghitza, UE Gore-Langton, RE Lindblad, R Shide, D Subramaniam, G Tai, B AF Ghitza, Udi E. Gore-Langton, Robert E. Lindblad, Robert Shide, David Subramaniam, Geetha Tai, Betty TI Common data elements for substance use disorders in electronic health records: the NIDA Clinical Trials Network experience SO ADDICTION LA English DT Review DE Addiction; common data elements; drug abuse; electronic health record; electronic medical record; NIDA Clinical Trials Network; SBIRT; screening ID ABUSE SCREENING-TEST; PSYCHOMETRIC PROPERTIES; INFORMATION-TECHNOLOGY; CARE AB Aims Electronic health records (EHRs) are essential in improving quality and enhancing efficiency of health-care delivery. By 2015, medical care receiving service reimbursement from US Centers for Medicare and Medicaid Services (CMS) must show meaningful use of EHRs. Substance use disorders (SUD) are grossly under-detected and under-treated in current US medical care settings. Hence, an urgent need exists for improved identification of and clinical intervention for SUD in medical settings. The National Institute on Drug Abuse Clinical Trials Network (NIDA CTN) has leveraged its infrastructure and expertise and brought relevant stakeholders together to develop consensus on brief screening and initial assessment tools for SUD in general medical settings, with the objective of incorporation into US EHRs. Methods Stakeholders were identified and queried for input and consensus on validated screening and assessment for SUD in general medical settings to develop common data elements to serve as shared resources for EHRs on screening, brief intervention and referral to treatment (SBIRT), with the intent of supporting interoperability and data exchange in a developing Nationwide Health Information Network. Results Through consensus of input from stakeholders, a validated screening and brief assessment instrument, supported by Clinical Decision Support tools, was chosen to be used at out-patient general medical settings. Conclusions The creation and adoption of a core set of validated common data elements and the inclusion of such consensus-based data elements for general medical settings will enable the integration of SUD treatment within mainstream health care, and support the adoption and meaningful use of the US Office of the National Coordinator for Health Information Technology (ONC)-certified EHRs, as well as CMS reimbursement. C1 [Ghitza, Udi E.; Subramaniam, Geetha; Tai, Betty] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. [Gore-Langton, Robert E.; Lindblad, Robert; Shide, David] EMMES Corp, Rockville, MD USA. RP Tai, B (reprint author), NIDA, Ctr Clin Trials Network, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM btai@nida.nih.gov NR 15 TC 12 Z9 12 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 J9 ADDICTION JI Addiction PD JAN PY 2013 VL 108 IS 1 BP 3 EP 8 DI 10.1111/j.1360-0443.2012.03876.x PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 061XU UT WOS:000312884400002 PM 22563741 ER PT J AU Tai, B Gore-Langton, RE Ghitza, UE Lindblad, R Subramaniam, G Shide, D AF Tai, Betty Gore-Langton, Robert E. Ghitza, Udi E. Lindblad, Robert Subramaniam, Geetha Shide, David TI TOO MANY RATING SCALES: NOT ENOUGH VALIDATION RESPONSE SO ADDICTION LA English DT Editorial Material DE Addiction; brief; common data elements; drug abuse; drug dependence; electronic health record; electronic medical record; NIDA Clinical Trials Network; SBIRT; screening C1 [Tai, Betty; Ghitza, Udi E.; Subramaniam, Geetha] NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. [Gore-Langton, Robert E.; Lindblad, Robert; Shide, David] EMMES Corp, Rockville, MD 20850 USA. RP Tai, B (reprint author), NIDA, Ctr Clin Trials Network, NIH, Bethesda, MD 20892 USA. EM btai@nida.nih.gov FU Center for the Clinical Trials Network of the National Institute on Drug Abuse, National Institutes of Health FX Several authors are employees of the Center for the Clinical Trials Network of the National Institute on Drug Abuse, National Institutes of Health, the funding agency for the National Drug Abuse Treatment Clinical Trials Network. The opinions in this manuscript are those of the authors and do not represent the official position of the US Government. NR 7 TC 0 Z9 0 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 EI 1360-0443 J9 ADDICTION JI Addiction PD JAN PY 2013 VL 108 IS 1 BP 12 EP 13 DI 10.1111/j.1360-0443.2012.03979.x PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 061XU UT WOS:000312884400006 PM 23279355 ER PT J AU Schindler, CW Justinova, Z Lafleur, D Woods, D Roschke, V Hallak, H Sklair-Tavron, L Redhi, GH Yasar, S Bergman, J Goldberg, SR AF Schindler, Charles W. Justinova, Zuzana Lafleur, David Woods, Doug Roschke, Viktor Hallak, Hussein Sklair-Tavron, Liora Redhi, Godfrey H. Yasar, Sevil Bergman, Jack Goldberg, Steven R. TI Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys SO ADDICTION BIOLOGY LA English DT Article DE Cocaine; discrimination; hydrolase; reinstatement; self-administration; squirrel monkeys ID HUMAN BUTYRYLCHOLINESTERASE; RATS; DEPENDENCE; METABOLISM; TOXICITY; ESTERASE; PLASMA AB Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced 2 hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hours following Albu-CocH administration. In behavioral experiments in monkeys, pre-treatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 mu g/kg/injection) for over 24 hours. Pre-treatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative-stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted. C1 [Schindler, Charles W.; Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Intramural Res Program, Baltimore, MD 21224 USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, MPRC, Baltimore, MD 21201 USA. [Lafleur, David; Roschke, Viktor] Zyngenia Inc, Gaithersburg, MD USA. [Yasar, Sevil] Johns Hopkins Univ, Div Geriatr Med & Gerontol, Sch Med, Baltimore, MD USA. [Bergman, Jack] Harvard Univ, McLean Hosp, Sch Med, Belmont, MA USA. RP Schindler, CW (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM cschindl@helix.nih.gov RI Justinova, Zuzana/A-9109-2011 OI Justinova, Zuzana/0000-0001-5793-7484 FU NIH, National Institute on Drug Abuse; NIDA Residential Research Support Services [N01 DA59909] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Drug Abuse and NIDA Residential Research Support Services Contract N01 DA59909. NR 24 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2013 VL 18 IS 1 BP 30 EP 39 DI 10.1111/j.1369-1600.2011.00424.x PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 059YB UT WOS:000312740500004 PM 22264200 ER PT J AU Lessov-Schlaggar, CN Lepore, RL Kristjansson, SD Schlaggar, BL Barnes, KA Petersen, SE Madden, PAF Heath, AC Barch, DM AF Lessov-Schlaggar, Christina N. Lepore, Rebecca L. Kristjansson, Sean D. Schlaggar, Bradley L. Barnes, Kelly Anne Petersen, Steven E. Madden, Pamela A. F. Heath, Andrew C. Barch, Deanna M. TI Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking SO ADDICTION BIOLOGY LA English DT Article DE Cigarette smoking; co-twin control; cognitive control; discordant; fMRI; reward ID DIAGNOSTIC INTERVIEW; SEPARATING PROCESSES; REWARD; ADDICTION; SMOKERS; SYSTEM; RELIABILITY; NONSMOKERS; INVENTORY; NETWORKS AB Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (2434 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked =100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems. C1 [Lessov-Schlaggar, Christina N.; Kristjansson, Sean D.; Madden, Pamela A. F.; Heath, Andrew C.; Barch, Deanna M.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Lepore, Rebecca L.; Schlaggar, Bradley L.; Petersen, Steven E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Barnes, Kelly Anne] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Petersen, Steven E.; Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA. RP Lessov-Schlaggar, CN (reprint author), 660 S Euclid,Campus Box 8134, St Louis, MO 63110 USA. EM schlaggc@psychiatry.wustl.edu RI Barch, Deanna/G-8638-2013 FU McDonnell Center for Systems Neuroscience at Washington University (CNLS); Alvin J. Siteman Cancer Center at Washington University School of Medicine; NCI Cancer Center Support Grant [P30 CA91842]; Barnes-Jewish Hospital in St. Louis, Missouri; NIH [DA027046, AA009022]; Washington University School of Medicine FX The authors would like to thank Layne Simpson for initial recruitment and screening of the twins; Rebecca Coalson, Kelly McVey and Joshua Siegel for help with fMRI data collection; and Steve Nelson, Jessica Church, Alecia Vogel and Fran Miezin for help with setting up task parameters in Psyscope software. The authors are indebted to the twins for their commitment to the study. The study design and conduct, as well as data collection, management and analysis was supported by the Barnes-Jewish Hospital Foundation in Saint Louis, Missouri, and by grants from the McDonnell Center for Systems Neuroscience at Washington University (CNLS), the Alvin J. Siteman Cancer Center (supported in part by an NCI Cancer Center Support Grant #P30 CA91842) at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, Missouri, for use of the Prevention and Control Research Program, which provided pilot funding (CNLS) and by NIH grant DA027046 (CNLS), which also supported preparation of this manuscript. Diagnostic interview surveys of the total twin cohort were supported by NIH grant AA009022 (ACH). NR 45 TC 10 Z9 10 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD JAN PY 2013 VL 18 IS 1 BP 98 EP 108 DI 10.1111/j.1369-1600.2012.00435.x PG 11 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 059YB UT WOS:000312740500011 PM 22340136 ER PT J AU Brooks, PJ Zakhari, S AF Brooks, Philip J. Zakhari, Samir TI Moderate Alcohol Consumption and Breast Cancer in Women: From Epidemiology to Mechanisms and Interventions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Breast Cancer; Alcohol Metabolism; Epidemiology; Mechanism ID EPITHELIAL-MESENCHYMAL TRANSITION; POSTMENOPAUSAL WOMEN; MEDIATED CARCINOGENESIS; MOLECULAR-MECHANISMS; DRINKING PATTERNS; OXIDATIVE STRESS; MAMMARY-TUMOR; GROWTH-RATE; RISK; DISEASE AB Epidemiologic studies indicate that moderate alcohol consumption increases breast cancer risk in women. Understanding the mechanistic basis of this relationship has important implications for women's health and breast cancer prevention. In this commentary, we focus on some recent epidemiologic studies linking moderate alcohol consumption to breast cancer risk and place the results of those studies within the framework of our current understanding of the temporal and mechanistic basis of human carcinogenesis. This analysis supports the hypothesis that alcohol acts as a weak cumulative breast carcinogen and may also be a tumor promoter. We discuss the implications of these mechanisms for the prevention and treatment of alcohol-related breast cancer and present some considerations for future studies. Moderate alcohol consumption has been shown to benefit cardiovascular health and recently been associated with healthy aging. Therefore, a better understanding of how moderate alcohol consumption impacts breast cancer risk will allow women to make better informed decisions about the risks and benefits of alcohol consumption in the context of their overall health and at different stages of their life. Such mechanistic information is also important for the development of rational clinical interventions to reduce ethanol-related breast cancer mortality. C1 [Brooks, Philip J.; Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Div Metab & Hlth Effects, 5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z99 AA999999, ZIA AA000083-17] NR 50 TC 27 Z9 27 U1 2 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 IS 1 BP 23 EP 30 DI 10.1111/j.1530-0277.2012.01888.x PG 8 WC Substance Abuse SC Substance Abuse GA 064ZN UT WOS:000313115200005 PM 23072454 ER PT J AU Narasimhan, M Rathinam, M Riar, A Patel, D Mummidi, S Yang, HS Colburn, NH Henderson, GI Mahimainathan, L AF Narasimhan, Madhusudhanan Rathinam, Marylatha Riar, Amanjot Patel, Dhyanesh Mummidi, Srinivas Yang, Hsin-Shen Colburn, Nancy H. Henderson, George I. Mahimainathan, Lenin TI Programmed Cell Death 4 (PDCD4): A Novel Player in Ethanol-Mediated Suppression of Protein Translation in Primary Cortical Neurons and Developing Cerebral Cortex SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE EtOH; Protein Synthesis; PDCD4; Primary Cortical Neurons; eIF4A; Cerebral Cortex ID PRENATAL ALCOHOL EXPOSURE; INITIATION-FACTOR 4A; EUKARYOTIC TRANSLATION; SYNAPTIC PLASTICITY; ELONGATION-FACTORS; OXIDATIVE STRESS; APOPTOTIC DEATH; BINDING-PROTEIN; SKELETAL-MUSCLE; GENE-EXPRESSION AB Background Prenatal exposure to ethanol (EtOH) elicits a range of neuro-developmental abnormalities, microcephaly to behavioral deficits. Impaired protein synthesis has been connected to pathogenesis of EtOH-induced brain damage and abnormal neuron development. However, mechanisms underlying these impairments of protein synthesis are not known. In this study, we illustrate the effects of EtOH on programmed cell death protein 4 (PDCD4), a tumor and translation repressor. Methods Primary cortical neurons (PCNs) were treated with 2.5 and 4 mg/ml EtOH for different time points (4 to 24 hours), and PDCD4 expression was detected by Western blotting. Protein synthesis was determined using [35S] methionine incorporation assay. Methyl cap pull-down assay was performed to establish the effect of EtOH on association of eukaryotic initiation factor 4A (eIF4A) with capped mRNA. Luciferase assay was performed to determine the in vivo translation. A 2-day acute 5-dose binge model with EtOH (4 g/kg body wt, 25% v/v) was performed in SpragueDawley rats at 12-hour intervals and analyzed for PDCD4, eIF4A, and eIF4Amethyl cap association. Results EtOH increased PDCD4 expression in a time- and dose-dependent manner in PCNs, which inhibited the association of eIF4A with methyl cap. EtOH and ectopic PDCD4 expression suppressed in vivo translation in PCNs and RNAi targeting of PDCD4 blocked the inhibitory effect of EtOH on protein synthesis. In utero exposure of pregnant rats to EtOH resulted in a significant increase in PDCD4 in fetal cerebral cortex along with the inhibition of methyl capassociated eIF4A, compared with isocaloric controls. Increased PDCD4 also occurred in pooled fractions of remaining brain regions. Conclusions Our data, for the first time, illustrate that PDCD4 mediates inhibitory effects of EtOH on protein synthesis in PCNs and developing brain. C1 [Narasimhan, Madhusudhanan; Rathinam, Marylatha; Riar, Amanjot; Patel, Dhyanesh; Henderson, George I.; Mahimainathan, Lenin] Texas Tech Univ, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Narasimhan, Madhusudhanan; Henderson, George I.; Mahimainathan, Lenin] Texas Tech Univ, S Plains Alcohol & Addict Res Ctr, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Mummidi, Srinivas] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Mummidi, Srinivas] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA. [Yang, Hsin-Shen] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. [Yang, Hsin-Shen] Univ Kentucky, Lucille P Markey Canc Ctr, Lexington, KY USA. [Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA. RP Mahimainathan, L (reprint author), Texas Tech Univ, Dept Pharmacol & Neurosci, Hlth Sci Ctr, 3601 4th St,STOP 6592, Lubbock, TX 79430 USA. EM lenin.mahimainathan@ttuhsc.edu OI /0000-0001-5077-3552 FU Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development [1I01BX000975]; NIH [RO1AI043279]; [RO1 AA010114] FX This work was supported by RO1 AA010114 (to GIH). SM is supported by grants awarded by the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development (1I01BX000975) and by NIH (RO1AI043279). We thank Dr. Michele Pagano, NYUMC, New York, for PDCD4 plasmid. NR 61 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2013 VL 37 IS 1 BP 96 EP 109 DI 10.1111/j.1530-0277.2012.01850.x PG 14 WC Substance Abuse SC Substance Abuse GA 064ZN UT WOS:000313115200013 PM 22757755 ER PT J AU Lewis, M Ghassemi, P Hibbeln, J AF Lewis, Michael Ghassemi, Parviz Hibbeln, Joseph TI Therapeutic use of omega-3 fatty acids in severe head trauma SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; BRAIN-INJURY; ENTERAL NUTRITION; AXONAL INJURY; MODEL; SUPPLEMENTATION; TRANSIENT; APOPTOSIS; ISCHEMIA AB Traumatic brain injury (TBI) has long been recognized as the leading cause of traumatic death and disability. Tremendous advances in surgical and intensive care unit management of the primary injury, including maintaining adequate oxygenation, controlling intracranial pressure, and ensuring proper cerebral perfusion pressure, have resulted in reduced mortality. However, the secondary injury phase of TBI is a prolonged pathogenic process characterized by neuroinflammation, excitatory amino acids, free radicals, and ion imbalance. There are no approved therapies to directly address these underlying processes. Here, we present a case that was intentionally treated with substantial amounts of omega-3 fatty acids (n-3FA) to provide the nutritional foundation for the brain to begin the healing process following severe TBI. Recent animal research supports the use of n-3FA, and clinical experience suggests that benefits may be possible from substantially and aggressively adding n-3FA to optimize the nutritional foundation of severe TBI patients and must be in place if the brain is to be given the opportunity to repair itself to the best possible extent. Administration early in the course of treatment, in the emergency department or sooner, has the potential to improve outcomes from this potentially devastating public health problem. C1 [Lewis, Michael] Brain Hlth Educ & Res Fdn, Arlington, VA 22206 USA. [Hibbeln, Joseph] NIAAA, NIH, Rockville, MD 20852 USA. RP Lewis, M (reprint author), Brain Hlth Educ & Res Fdn, Arlington, VA 22206 USA. EM dr.michael.lewis@gmail.com; peter@arctelcom.com; Joseph.hibbeln@nih.gov FU Intramural NIH HHS [ZIA AA000115-12] NR 29 TC 4 Z9 5 U1 2 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2013 VL 31 IS 1 AR 273.e5 DI 10.1016/j.ajem.2012.05.014 PG 4 WC Emergency Medicine SC Emergency Medicine GA 062WM UT WOS:000312954600077 PM 22867826 ER PT J AU Chaturvedi, AK Moore, SC Hildesheim, A AF Chaturvedi, Anil K. Moore, Steven C. Hildesheim, Allan TI Invited Commentary: Circulating Inflammation Markers and Cancer Risk - Implications for Epidemiologic Studies SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE cardiovascular disease; circulating markers; inflammation; multiplexed assays; neoplasms; reproducibility ID C-REACTIVE PROTEIN; GLOBAL CARDIOVASCULAR RISK; MOLECULAR EPIDEMIOLOGY; CYTOKINE LEVELS; HEART-DISEASE; LUNG-CANCER; PREDICTION; DESIGN; WOMEN; ASSOCIATIONS AB Chronic inflammation, an established risk factor for cardiovascular disease, is increasingly being recognized as an etiologic factor in several cancers. In this issue of the Journal, Touvier et al. (Am J Epidemiol. 2013;177(1):313) report on the association of 7 markers of inflammation, adiposity, and endothelial function with risk of overall cancer and breast and prostate cancers in a nested case-control study carried out within the SU.VI.MAX cohort (France, 19942007). Consistent with previous reports on this topic, Touvier et al. focused on a limited number of markers. Future studies of inflammation and cancer should be able to capitalize on emerging multiplexed methods for the simultaneous detection of larger numbers of inflammatory markers in low-volume specimens. This should allow a more comprehensive evaluation of the role of inflammation in cancer development. In this commentary, the authors review emerging methods for measurement of multiplexed inflammation markers, the design and analytic implications of the use of these methods in epidemiologic studies, and potential public health implications of such studies. Given that many large prospective cohort studies have already collected and banked serum/plasma samples, rapid gains in our understanding of chronic inflammation and its role in cancer etiology are possible. C1 [Chaturvedi, Anil K.; Hildesheim, Allan] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Moore, Steven C.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Chaturvedi, AK (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Hildesheim, Allan/B-9760-2015; Chaturvedi, Anil/J-2024-2015; Moore, Steven/D-8760-2016 OI Hildesheim, Allan/0000-0003-0257-2363; Chaturvedi, Anil/0000-0003-2696-8899; Moore, Steven/0000-0002-8169-1661 FU Intramural NIH HHS NR 40 TC 8 Z9 8 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2013 VL 177 IS 1 BP 14 EP 19 DI 10.1093/aje/kws357 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 061WT UT WOS:000312881600003 PM 23171878 ER PT J AU Desai, CS Colangelo, LA Liu, K Jacobs, DR Cook, NL Lloyd-Jones, DM Ogunyankin, KO AF Desai, Chintan S. Colangelo, Laura A. Liu, Kiang Jacobs, David R., Jr. Cook, Nakela L. Lloyd-Jones, Donald M. Ogunyankin, Kofo O. TI Prevalence, Prospective Risk Markers, and Prognosis Associated With the Presence of Left Ventricular Diastolic Dysfunction in Young Adults The Coronary Artery Risk Development in Young Adults Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CARDIA study; clinical outcomes; diastolic dysfunction; left ventricle ID SOCIETY-OF-CARDIOLOGY; HEART-FAILURE; MASS; ECHOCARDIOGRAPHY; COMMUNITY; DIAGNOSIS; CARDIA AB The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (19851986), and echocardiography was done at year 5 when the participants were 2335 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1 and abnormal relaxation was present in 9.3. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95 confidence interval: 2.0, 9.3) and 1.6 (95 confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts. C1 [Desai, Chintan S.; Colangelo, Laura A.; Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [Cook, Nakela L.] NHLBI, Bethesda, MD 20892 USA. [Lloyd-Jones, Donald M.] Northwestern Univ, Div Cardiol, Chicago, IL 60611 USA. [Ogunyankin, Kofo O.] First Cardiol Consultants, Lagos, Nigeria. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM dlj@northwestern.edu FU National Heart, Lung, and Blood Institute; University of Alabama at Birmingham [N01-HC95095, N01-HC48047]; University of Minnesota [N01-HC48048]; Northwestern University [N01-HC48049]; Kaiser Foundation Research Institute [N01-HC48050]; National Institutes of Health [T32 HL 69771-8] FX The Coronary Artery Risk Development in Young Adults (CARDIA) Study was conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (grants N01-HC95095 and N01-HC48047), the University of Minnesota (grant N01-HC48048), Northwestern University (grant N01-HC48049), and the Kaiser Foundation Research Institute (grant N01-HC48050). Dr. Desai was supported by National Institutes of Health grant T32 HL 69771-8. This manuscript has been reviewed by CARDIA for scientific content and consistency of data interpretation with previous CARDIA publications. NR 21 TC 8 Z9 8 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2013 VL 177 IS 1 BP 20 EP 32 DI 10.1093/aje/kws224 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 061WT UT WOS:000312881600004 PM 23211639 ER PT J AU Koutros, S Freeman, LEB Lubin, JH Heltshe, SL Andreotti, G Barry, KH DellaValle, CT Hoppin, JA Sandler, DP Lynch, CF Blair, A Alavanja, MCR AF Koutros, Stella Freeman, Laura E. Beane Lubin, Jay H. Heltshe, Sonya L. Andreotti, Gabriella Barry, Kathryn Hughes DellaValle, Curt T. Hoppin, Jane A. Sandler, Dale P. Lynch, Charles F. Blair, Aaron Alavanja, Michael C. R. TI Risk of Total and Aggressive Prostate Cancer and Pesticide Use in the Agricultural Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aggressive prostate cancer; cohort study; farming; organophosphate insecticides; pesticide exposure; prostate cancer ID IN-VITRO; OCCUPATIONAL-EXPOSURE; PROSPECTIVE COHORT; 3A4 METABOLISM; UNITED-STATES; DNA-DAMAGE; MALE RATS; APPLICATORS; MALATHION; CHEMICALS AB Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (19932007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95 confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed 1.63, 95 confidence interval (CI): 1.22, 2.17; P-trend 0.001); malathion (RR for Q4 vs. nonexposed 1.43, 95 CI: 1.08, 1.88; P-trend 0.04); and terbufos (RR for Q4 vs. nonexposed 1.29, 95 CI: 1.02, 1.64; P-trend 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed 1.49, 95 CI: 1.03, 2.18; P-trend 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer. C1 [Koutros, Stella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Heltshe, Sonya L.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. [Lynch, Charles F.] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. RP Koutros, S (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8115,MSC 7240, Rockville, MD 20852 USA. EM KoutrosS@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Sandler, Dale/0000-0002-6776-0018 FU National Institutes of Health; Division of Cancer Epidemiology and Genetics; National Cancer Institute [Z01CP010119]; National Institute of Environmental Health Sciences [Z01ES0490300] FX This work was supported by the Intramural Research Program of the National Institutes of Health; the Division of Cancer Epidemiology and Genetics, National Cancer Institute (Z01CP010119); and the National Institute of Environmental Health Sciences (Z01ES0490300). NR 51 TC 40 Z9 41 U1 2 U2 53 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2013 VL 177 IS 1 BP 59 EP 74 DI 10.1093/aje/kws225 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 061WT UT WOS:000312881600008 PM 23171882 ER PT J AU Pollack, AZ Perkins, NJ Mumford, SL Ye, A Schisterman, EF AF Pollack, A. Z. Perkins, N. J. Mumford, S. L. Ye, A. Schisterman, E. F. TI Correlated Biomarker Measurement Error: An Important Threat to Inference in Environmental Epidemiology SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE biomarkers; cadmium; environmental epidemiology; lead; measurement error; reliability ID EXPOSURE MEASUREMENT ERROR; LOGISTIC-REGRESSION MODELS; REPRODUCTIVE HORMONES; EXPLANATORY VARIABLES; PREMENOPAUSAL WOMEN; STRONG CONFOUNDERS; LINEAR-REGRESSION; DETECTION LIMITS; CADMIUM; LEAD AB Utilizing multiple biomarkers is increasingly common in epidemiology. However, the combined impact of correlated exposure measurement error, unmeasured confounding, interaction, and limits of detection (LODs) on inference for multiple biomarkers is unknown. We conducted data-driven simulations evaluating bias from correlated measurement error with varying reliability coefficients (R), odds ratios (ORs), levels of correlation between exposures and error, LODs, and interactions. Blood cadmium and lead levels in relation to anovulation served as the motivating example, based on findings from the BioCycle Study (20052007). For most scenarios, main-effect estimates for cadmium and lead with increasing levels of positively correlated measurement error created increasing downward or upward bias for OR 1.00 and OR 1.00, respectively, that was also a function of effect size. Some scenarios showed bias for cadmium away from the null. Results subject to LODs were similar. Bias for main and interaction effects ranged from 130 to 36 and from 144 to 84, respectively. A closed-form continuous outcome case solution provides a useful tool for estimating the bias in logistic regression. Investigators should consider how measurement error and LODs may bias findings when examining biomarkers measured in the same medium, prepared with the same process, or analyzed using the same method. C1 [Pollack, A. Z.; Perkins, N. J.; Mumford, S. L.; Ye, A.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Pollack, A. Z.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Pollack, AZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM pollacka@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Pollack, Anna/0000-0002-4313-3298; Schisterman, Enrique/0000-0003-3757-641X FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Long-Range Research Initiative of the American Chemistry Council; Congress of Epidemiology FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by the Long-Range Research Initiative of the American Chemistry Council.; This paper was a finalist for the 2011 Reuel A. Stallones Student Prize Paper, awarded by the Congress of Epidemiology. NR 36 TC 7 Z9 8 U1 1 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2013 VL 177 IS 1 BP 84 EP 92 DI 10.1093/aje/kws209 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 061WT UT WOS:000312881600010 PM 23221725 ER PT J AU Acosta, MT Bearden, CE Castellanos, XF Cutting, L Elgersma, Y Gioia, G Gutmann, DH Lee, YS Legius, E Muenke, M North, K Parada, LF Ratner, N Hunter-Schaedle, K Silva, AJ AF Acosta, Maria T. Bearden, Carrie E. Castellanos, Xavier F. Cutting, Laurie Elgersma, Ype Gioia, Gerard Gutmann, David H. Lee, Yong-Seok Legius, Eric Muenke, Maximillian North, Kathryn Parada, Luis F. Ratner, Nancy Hunter-Schaedle, Kim Silva, Alcino J. TI The Learning Disabilities Network (LeaDNet): Using Neurofibromatosis Type 1 [NF1] as a Paradigm for Translational Research (vol 158A, pg 2225, 2012) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Correction C1 [Acosta, Maria T.; Gioia, Gerard] Childrens Natl Med Ctr, Gilbert Neurofibromatosis Inst, Washington, DC 20010 USA. [Acosta, Maria T.; Muenke, Maximillian] NHGRI, NIH, Bethesda, MD 20892 USA. [Bearden, Carrie E.; Lee, Yong-Seok; Silva, Alcino J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Castellanos, Xavier F.] NYU, New York, NY USA. [Cutting, Laurie] Vanderbilt Univ, Nashville, TN USA. [Elgersma, Ype] Erasmus Univ, Rotterdam, Netherlands. [Gutmann, David H.] Washington Univ, Sch Med, St Louis, MO USA. [Legius, Eric] Katholieke Univ Leuven, Louvain, Belgium. [North, Kathryn] Univ Sydney, Childrens Hosp Westmead, Sydney, NSW 2006, Australia. [Parada, Luis F.] Univ Texas SW, Dallas, TX USA. [Ratner, Nancy] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Hunter-Schaedle, Kim] Childrens Tumor Fdn, New York, NY USA. RP Acosta, MT (reprint author), Childrens Natl Med Ctr, Gilbert Neurofibromatosis Inst, Washington, DC 20010 USA. RI Parada, luis/B-9400-2014; North, Kathryn/K-6476-2012 OI North, Kathryn/0000-0003-0841-8009 NR 1 TC 0 Z9 0 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JAN PY 2013 VL 161A IS 1 BP 236 EP 236 DI 10.1002/ajmg.a.35667 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 062RO UT WOS:000312939200042 ER PT J AU Conde-Agudelo, A Romero, R Nicolaides, K Chaiworapongsa, T O'Brien, JM Cetingoz, E da Fonseca, E Creasy, G Soma-Pillay, P Fusey, S Cam, C Alfirevic, Z Hassan, SS AF Conde-Agudelo, Agustin Romero, Roberto Nicolaides, Kypros Chaiworapongsa, Tinnakorn O'Brien, John M. Cetingoz, Elcin da Fonseca, Eduardo Creasy, George Soma-Pillay, Priya Fusey, Shalini Cam, Cetin Alfirevic, Zarko Hassan, Sonia S. TI Vaginal progesterone vs cervical cerclage for the prevention of preterm birth in women with a sonographic short cervix, previous preterm birth, and singleton gestation: a systematic review and indirect comparison metaanalysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE birthweight; cervix; neonatal intensive care unit; perinatal mortality; perinatal morbidity; premature; prematurity; progestin; 17 alpha-hydroxyprogesterone caproate; 17P ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; ELECTROSURGICAL EXCISION PROCEDURE; CERVICOVAGINAL FETAL FIBRONECTIN; CONNECTIVE TISSUE CHANGES; PREMATURE LABOR; DOUBLE-BLIND; UTERINE CERVIX; INTACT MEMBRANES; PROPHYLACTIC CERCLAGE AB OBJECTIVE: No randomized controlled trial has compared vaginal progesterone and cervical cerclage directly for the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous spontaneous preterm birth. We performed an indirect comparison of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. STUDY DESIGN: Adjusted indirect metaanalysis of randomized controlled trials. RESULTS: Four studies that evaluated vaginal progesterone vs placebo (158 patients) and 5 studies that evaluated cerclage vs no cerclage (504 patients) were included. Both interventions were associated with a statistically significant reduction in the risk of preterm birth at <32 weeks of gestation and composite perinatal morbidity and mortality compared with placebo/no cerclage. Adjusted indirect metaanalyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes. CONCLUSION: Based on state-of-the-art methods for indirect comparisons, either vaginal progesterone or cerclage are equally efficacious in the prevention of preterm birth in women with a sonographic short cervix in the mid trimester, singleton gestation, and previous preterm birth. Selection of the optimal treatment needs to consider adverse events, cost and patient/clinician preferences. C1 [Conde-Agudelo, Agustin; Romero, Roberto; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Conde-Agudelo, Agustin; Romero, Roberto; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Nicolaides, Kypros] Kings Coll Hosp London, Dept Obstet & Gynecol, London, England. [Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Hutzel Hosp, Detroit, MI USA. [O'Brien, John M.] Univ Kentucky, Perinatal Diagnost Ctr, Cent Baptist Hosp, Lexington, KY USA. [O'Brien, John M.] Univ Kentucky, Dept Obstet & Gynecol, Lexington, KY USA. [Cetingoz, Elcin; Cam, Cetin] Zeynep Kamil Women & Children Dis Educ & Res Hosp, Dept Obstet & Gynecol, Istanbul, Turkey. [da Fonseca, Eduardo] Univ Sao Paulo, Dept Obstet & Ginecol, Hosp Servidor Publ Estadual Francisco Morato de O, Sao Paulo, Brazil. [da Fonseca, Eduardo] Univ Sao Paulo, Sch Med, Sao Paulo, Brazil. [Creasy, George] Columbia Labs Inc, Livingston, NJ USA. [Soma-Pillay, Priya] Steve Biko Acad Hosp, Dept Obstet & Gynaecol, Pretoria, South Africa. [Soma-Pillay, Priya] Univ Pretoria, ZA-0002 Pretoria, South Africa. [Alfirevic, Zarko] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RP Conde-Agudelo, A (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. RI Fonseca, Eduardo/A-2490-2013; OI Creasy, George/0000-0002-6645-4238 FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Department of Health and Human Services, Bethesda, MD; Columbia Laboratories, Inc; Watson Pharmaceuticals FX Supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD.; Most of the authors report no conflict of interest, except as stated in this paragraph. J.M.O. was involved in studies of progesterone gel treatment for preterm birth prevention sponsored by Columbia Laboratories, Inc (which is the manufacturer of the preparation used in the PREGNANT trial) and a previous trial of vaginal progesterone in women at risk for preterm delivery, serves on advisory boards, and is a consultant for Watson Pharmaceuticals (which is a company with a financial interest in marketing vaginal progesterone gel for the prevention of preterm birth). He and others are listed in the patent on the use of all progesterone compounds to prevent preterm birth (US Patent Number 7,884,093: Progesterone for the Treatment and Prevention of Spontaneous Preterm Birth). G.C. is an employee of Columbia Laboratories, Inc. NR 236 TC 11 Z9 15 U1 2 U2 18 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2013 VL 208 IS 1 AR 42.e1 DI 10.1016/j.ajog.2012.10.877 PG 18 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 063QT UT WOS:000313015600012 PM 23157855 ER PT J AU Andric, SA Kojic, Z Bjelic, MM Mihajlovic, AI Baburski, AZ Sokanovic, SJ Janjic, MM Stojkov, NJ Stojilkovic, SS Kostic, TS AF Andric, Silvana A. Kojic, Zvezdana Bjelic, Maja M. Mihajlovic, Aleksandar I. Baburski, Aleksandar Z. Sokanovic, Srdjan J. Janjic, Marija M. Stojkov, Natasa J. Stojilkovic, Stanko S. Kostic, Tatjana S. TI The opposite roles of glucocorticoid and alpha(1)-adrenergic receptors in stress triggered apoptosis of rat Leydig cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE Leydig cells; immobilization stress; corticosterone; adrenaline; testis; apoptosis ID REPEATED IMMOBILIZATION STRESS; BETA-HYDROXYSTEROID DEHYDROGENASE; PROTEIN-KINASE-A; ADULT MALE-RATS; TESTICULAR STEROIDOGENESIS; IN-VITRO; ANDROGEN PRODUCTION; HORMONAL-REGULATION; ADAPTIVE RESPONSE; STEM-CELLS AB Andric SA, Kojic Z, Bjelic MM, Mihajlovic AI, Baburski AZ, Sokanovic SJ, Janjic MM, Stojkov NJ, Stojilkovic SS, Kostic TS. The opposite roles of glucocorticoid and alpha(1)-adrenergic receptors in stress triggered apoptosis of rat Leydig cells. Am J Physiol Endocrinol Metab 304: E51-E59, 2013. First published November 13, 2012; doi:10.1152/ajpendo.00443.2012.-The stress-induced initiation of proapoptotic signaling in Leydig cells is relatively well defined, but the duration of this signaling and the mechanism(s) involved in opposing the stress responses have not been addressed. In this study, immobilization stress (IMO) was applied for 2 h daily, and animals were euthanized immediately after the first (IMO1), second (IMO2), and 10th (IMO10) sessions. In IMO1 and IMO2 rats, serum corticosterone and adrenaline were elevated, whereas serum androgens and mRNA transcription of insulin-like factor-3 in Leydig cells were inhibited. Reduced oxygen consumption and the mitochondrial membrane potential coupled with a leak of cytochrome c from mitochondria and increased caspase-9 expression, caspase-3 activity, and number of apoptotic Leydig cells was also observed. Corticosterone and adrenaline were also elevated in IMO10 rats but were accompanied with a partial recovery of androgen secretion and normalization of insulin-like factor-3 transcription coupled with increased cytochrome c expression, abolition of proapoptotic signaling, and normalization of the apoptotic events. Blockade of intratesticular glucocorticoid receptors diminished proapoptotic effects without affecting antiapoptotic effects, whereas blockade of intratesticular alpha(1)-adrenergic receptors diminished the antiapoptotic effects without affecting proapoptotic effects. These results confirmed a critical role of glucocorticoids in mitochondria-dependent apoptosis and showed for the first time the relevance of stress-induced upregulation of alpha(1)-adrenergic receptor expression in cell apoptotic resistance to repetitive IMOs. The opposite role of two hormones in control of the apoptotic rate in Leydig cells also provides a rationale for a partial recovery of androgen production in chronically stressed animals. C1 [Andric, Silvana A.; Bjelic, Maja M.; Mihajlovic, Aleksandar I.; Baburski, Aleksandar Z.; Sokanovic, Srdjan J.; Janjic, Marija M.; Stojkov, Natasa J.; Kostic, Tatjana S.] Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Reprod Endocrinol & Signaling Grp, Novi Sad 21000, Serbia. [Kojic, Zvezdana] Univ Belgrade, Sch Med, Inst Physiol, Belgrade, Serbia. [Stojilkovic, Stanko S.] NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Kostic, TS (reprint author), Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Reprod Endocrinol & Signaling Grp, 2 Dositeja Obradovica Sq, Novi Sad 21000, Serbia. EM tatjana.kostic@dbe.uns.ac.rs FU Autonomic Province of Vojvodina Grant [2570]; Serbian Ministry of Science and Technological Development Grant [173057]; Intramural Research Program of the National Institute of Child Health and Human Development FX This work was supported by the Autonomic Province of Vojvodina Grant (no. 2570), the Serbian Ministry of Science and Technological Development Grant (no. 173057), and the Intramural Research Program of the National Institute of Child Health and Human Development. NR 56 TC 4 Z9 4 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2013 VL 304 IS 1 BP E51 EP E59 DI 10.1152/ajpendo.00443.2012 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 063YO UT WOS:000313038300006 PM 23149620 ER PT J AU Nayeem, MA Pradhan, I Mustafa, SJ Morisseau, C Falck, JR Zeldin, DC AF Nayeem, Mohammed A. Pradhan, Isha Mustafa, S. Jamal Morisseau, Christophe Falck, John R. Zeldin, Darryl C. TI Adenosine A(2A) receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPAR gamma SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE soluble epoxide hydrolase; adenosine A(2a) receptor; adenosine A(1) receptor; CYP2J5-epoxgenase; omega-hydroxylase; contraction; relaxation ID PROLIFERATOR-ACTIVATED RECEPTORS; EPOXYEICOSATRIENOIC ACIDS EETS; REDUCES RENAL INFLAMMATION; BLOOD-PRESSURE REGULATION; ARTERY ENDOTHELIAL-CELLS; CORONARY-HEART-DISEASE; SMOOTH-MUSCLE CELLS; NITRIC-OXIDE; GENETIC-VARIATION; SKELETAL-MUSCLE AB Nayeem MA, Pradhan I, Mustafa SJ, Morisseau C, Falck JR, Zeldin DC. AdenosineA(2A) receptor modulates vascular response in soluble epoxide hydrolase-null mice through CYP-epoxygenases and PPAR gamma. Am J Physiol Regul Integr Comp Physiol 304: R23-R32, 2013. First published November 14, 2012; doi:10.1152/ajpregu.00213.2012.-The interaction between adenosine and soluble epoxide hydrolase (sEH) in vascular response is not known. Therefore, we hypothesized that lack of sEH in mice enhances adenosine-induced relaxation through A(2A) adenosine receptors (AR) via CYP-epoxygenases and peroxisome proliferator-activated receptor gamma (PPAR gamma). sEH(-/-) showed an increase in A(2A) AR, CYP2J, and PPAR gamma by 31%, 65%, and 36%, respectively, and a decrease in A(1)AR and PPAR gamma (30% and 27%, respectively) vs. sEH(-/-). 5=-N-ethylcarboxamidoadenosine (NECA, an adenosine receptor agonist), CGS 21680 (A2A AR-agonist), and GW 7647 (PPAR gamma-agonist)-induced responses were tested with nitro-L-arginine methyl ester (L-NAME) (NO-inhibitor; 10(-4) M), ZM-241385, SCH58261 (A(2A) AR-antagonists; 10(-6) M), 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, an epoxyeicosatrienoic acid-antagonist; 10(-5) M), 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA; 10 mu M) or trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB, sEH-inhibitors; 10(-5) M), and T0070907 (PPAR gamma-antagonist; 10(-7) M). In sEH(-/-) mice, ACh response was not different from sEH(-/-) (P < 0.05), and L-NAME blocked ACh-responses in both sEH(-/-) and sEH(-/-) mice (P < 0.05). NECA (10(-6) M)-induced relaxation was higher in sEH(-/-) (+12.94 +/- 3.2%) vs. sEH(-/-) mice (-5.35 +/- 5.2%); however, it was blocked by ZM-241385 (- 22.42 +/- 1.9%) and SCH-58261(-30.04 +/- 4.2%). CGS-21680 (10(-6) M)-induced relaxation was higher in sEH(-/-) (+37.4 +/- 5.4%) vs. sEH(-/-) (-2.14 +/- 2.8%). L-NAME (sEH(-/-), +30.28 +/- 4.8%, P < 0.05) did not block CGS-21680-induced response, whereas 14,15-EEZE (-7.1 +/- 3.7%, P > 0.05) did. Also, AUDA and t-AUCB did not change CGS-21680-induced response in sEH(-/-) (P < 0.05), but reversed in sEH(-/-) (from +2.14 +/- 2.8% to +45.33 +/- 4.1%, and + 63.37 +/- 7.2, respectively). PPAR gamma-agonist did not relax as CGS 21680 (-2.48 +/- 1.1 vs. + 37.4 +/- 5.4%) in sEH(-/-), and PPAR gamma-antagonist blocked (from + 37.4 +/- 5.4% to + 9.40 +/- 3.1) CGS 21680-induced relaxation in sEH(-/-). Our data suggest that adenosine-induced relaxation in sEH(-/-) may depend on the upregulation of A(2A) AR, CYP2J, and PPAR gamma, and the downregulation of A(1) AR and PPAR alpha. C1 [Nayeem, Mohammed A.] W Virginia Univ, Robert C Byrd Hlth Sci Ctr N 3051, Ctr Cardiovasc & Resp Sci, Dept Physiol & Pharmacol, Morgantown, WV 26506 USA. [Morisseau, Christophe] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. [Morisseau, Christophe] Univ Calif Davis, UC Davis Canc Ctr, Davis, CA 95616 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Nayeem, MA (reprint author), W Virginia Univ, Robert C Byrd Hlth Sci Ctr N 3051, Ctr Cardiovasc & Resp Sci, Dept Physiol & Pharmacol, 1 Med Ctr Dr,POB 9229, Morgantown, WV 26506 USA. EM mnayeem@hsc.wvu.edu RI Nayeem, Mohammed/A-3949-2017 OI Nayeem, Mohammed/0000-0002-7827-4760 FU West Virginia University (WVU); National Institutes of Health Grant [HL-027339, HL-094447]; NIH [GM-31278]; National Institute of Environmental Health Sciences Grant [z01 ES025034] FX This work was supported by Bridge Grant funding [West Virginia University WVU)] and startup funding (WVU) to M. A. Nayeem, National Institutes of Health Grant HL-027339 and HL-094447 to S. J. Mustafa, NIH Grant GM-31278 to J. R. Falck and National Institute of Environmental Health Sciences Grant z01 ES025034 to D. C. Zeldin. NR 66 TC 5 Z9 5 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 2013 VL 304 IS 1 BP R23 EP R32 DI 10.1152/ajpregu.00213.2012 PG 10 WC Physiology SC Physiology GA 064DN UT WOS:000313051200003 PM 23152114 ER PT J AU ElZarrad, MK Eckstein, ET Glasgow, RE AF ElZarrad, M. Khair Eckstein, Erin T. Glasgow, Russell E. TI Applying Chronic Illness Care, Implementation Science, and Self-Management Support to HIV SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Review ID ANTIRETROVIRAL THERAPY; PREEXPOSURE PROPHYLAXIS; IMPROVE ADHERENCE; HEALTH-SERVICES; PREVENTION; INTERVENTIONS; MODEL; LITERACY; TRANSMISSION; INFECTION C1 [ElZarrad, M. Khair; Eckstein, Erin T.; Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [ElZarrad, M. Khair] NCI, Canc Prevent Fellowship Program, Rockville, MD 20852 USA. [ElZarrad, M. Khair] US FDA, Interagcy Oncol Task Force Joint Fellowship Progr, Silver Spring, MD USA. RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 6144, Rockville, MD 20852 USA. EM glasgowre@mail.nih.gov FU Division of Cancer Control and Population Sciences; Cancer Prevention Fellowship Program; National Cancer Institute, Rockville; Interagency Oncology Task Force Joint Fellowship Program; U.S. Food and Drug Administration, Silver Spring, Maryland; CDC through the Association for Prevention Teaching and Research (CDC-APTR) [11-NCHHSTP-01] FX From the Division of Cancer Control and Population Sciences (ElZarrad, Eckstein, Glasgow) and the Cancer Prevention Fellowship Program (ElZarrad), National Cancer Institute, Rockville; and Interagency Oncology Task Force Joint Fellowship Program (ElZarrad), U.S. Food and Drug Administration, Silver Spring, Maryland; Publication of this article was supported by the CDC through the Association for Prevention Teaching and Research (CDC-APTR) Cooperative Agreement number 11-NCHHSTP-01. NR 60 TC 8 Z9 8 U1 3 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 EI 1873-2607 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2013 VL 44 IS 1 SU 2 BP S99 EP S107 DI 10.1016/j.amepre.2012.09.046 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 056YL UT WOS:000312528000008 PM 23253770 ER PT J AU Suarez-Jimenez, B Hathaway, A Waters, C Vaughan, K Suomi, SJ Noble, PL Pine, DS Fox, NA Nelson, EE AF Suarez-Jimenez, Benjamin Hathaway, Amanda Waters, Carlos Vaughan, Kelli Suomi, Stephen J. Noble, Pamela L. Pine, Daniel S. Fox, Nathan A. Nelson, Eric E. TI Effect of Mother's Dominance Rank on Offspring Temperament in Infant Rhesus Monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE development; dominance; hierarchy; infant; temperament ID FEAR-POTENTIATED STARTLE; BEHAVIORAL-INHIBITION; SOCIAL HIERARCHY; PRIMATE; MACAQUES; STRESS; BABOONS; NUCLEUS; ANXIETY; PSYCHOPATHOLOGY AB In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies. Am. J. Primatol. 75:65-73, 2013. Published 2012 by Wiley Periodicals, Inc. C1 [Suomi, Stephen J.; Nelson, Eric E.] NIMH, Sect Dev Affect Neurosci, Bethesda, MD 20892 USA. [Suarez-Jimenez, Benjamin; Hathaway, Amanda; Waters, Carlos; Vaughan, Kelli; Noble, Pamela L.] NIMH, DIRP Nonhuman Primate Core, Bethesda, MD 20892 USA. [Pine, Daniel S.; Nelson, Eric E.] NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. [Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. RP Nelson, EE (reprint author), NIMH, Sect Dev Affect Neurosci, Bldg 15K, Bethesda, MD 20892 USA. EM nelsone@mail.nih.gov OI Nelson, Eric/0000-0002-3376-2453; Vaughan, Kelli/0000-0001-5274-582X FU NIMH Intramural Research Program FX Contract grant sponsor: NIMH Intramural Research Program. NR 37 TC 4 Z9 4 U1 3 U2 67 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JAN PY 2013 VL 75 IS 1 BP 65 EP 73 DI 10.1002/ajp.22081 PG 9 WC Zoology SC Zoology GA 057CF UT WOS:000312538800007 PM 23042298 ER PT J AU Nierenberg, AA Friedman, ES Bowden, CL Sylvia, LG Thase, ME Ketter, T Ostacher, MJ Leon, AC Reilly-Harrington, N Iosifescu, DV Pencina, M Severe, JB Calabrese, JR AF Nierenberg, Andrew A. Friedman, Edward S. Bowden, Charles L. Sylvia, Louisa G. Thase, Michael E. Ketter, Terence Ostacher, Michael J. Leon, Andrew C. Reilly-Harrington, Noreen Iosifescu, Dan V. Pencina, Michael Severe, Joanne B. Calabrese, Joseph R. TI Lithium Treatment Moderate-Dose Use Study (LiTMUS) for Bipolar Disorder: A Randomized Comparative Effectiveness Trial of Optimized Personalized Treatment With and Without Lithium SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PSYCHOTROPIC-DRUG PRESCRIPTION; COMORBIDITY SURVEY REPLICATION; PATTERN-MIXTURE MODELS; LOW SERUM LEVELS; DOUBLE-BLIND; I-DISORDER; MAINTENANCE TREATMENT; MOOD DISORDERS; DSM-IV AB Objective: Lithium salts, once the mainstay of therapy for bipolar disorder, have tolerability issues at a higher dosage that often limit adherence. The authors investigated the comparative effectiveness of more tolerable dosages of lithium as part of optimized personalized treatment (OPT). Method: The authors randomly assigned 283 bipolar disorder outpatients to 6 months of open, flexible, moderate dosages of lithium plus OPT or to 6 months of OPT alone. The primary outcome measures were the Clinical Global Impression Scale for Bipolar Disorder-Severity (CGI-BP-S) and "necessary clinical adjustments" (medication adjustments per month). Secondary outcome measures included mood symptoms and functioning. The authors also assessed sustained remission (defined as a CGI-BPS score <= 2 for 2 months) and treatment with second-generation antipsychotics. The authors hypothesized that lithium plus OPT would result in greater clinical improvement and fewer necessary clinical adjustments. Results: The authors observed no statistically significant advantage of lithium plus OPT on CGI-BP-S scores, necessary clinical adjustments, or proportion with sustained remission. Both groups had similar outcomes across secondary clinical and functional measures. Fewer patients in the lithium-plus-OPT group received second-generation antipsychotics compared with the OPT-only group (48.3% and 62.5%, respectively). Conclusions: In this pragmatic comparative effectiveness study, a moderate but tolerated dosage of lithium plus OPT conferred no symptomatic advantage when compared with OPT alone, but the lithium-plus-OPT group had less exposure to second-generation antipsychotics. Only about one-quarter of patients in both groups achieved sustained remission of symptoms. These findings highlight the persistent and chronic nature of bipolar disorder as well as the magnitude of unmet needs in its treatment. (Am J Psychiatry 2013; 170:102-110) C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Stanford Univ, Stanford, CA 94305 USA. Weill Cornell Med Coll, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Harvard Clin Res Inst, Boston, MA USA. NIMH, Rockville, MD 20857 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM anierenberg@partners.org OI Ostacher, Michael/0000-0003-0353-7535 FU American Drug Utilization Review; American Professional Society of ADHD and Related Disorders; American Psychiatric Association; American Society for Clinical Psychopharmacology; Appliance Computing (Mindsite); AstraZeneca; Basliea; Baystate Medical Center; Belvoir Publishing; Brain Cells; Brandeis University; Bristol-Myers Squibb; Columbia University; Corcept; Dainippon Sumitomo; Eli Lilly; EpiQ; Forest Pharmaceuticals, Hillside Hospital; IMEDEX; International Society for Bipolar Disorders; Johnson Johnson; MJ Consulting; Medscape; MBL Publishing, New York State; NIMH; Novartis; PamLabs; Pfizer; PGx Health; Physicians Postgraduate Press; Ridge Diagnostics; Schering-Plough; SciMed; ShireSUNY Buffalo; Takeda/Lundbeck; Targacept; Teva Pharmaceuticals; University of Texas Southwestern Dallas; University of Wisconsin; University of Pisa; GlaxoSmithKline; Wyeth; Solvay; Schering-Plough,; Sanofi-Aventis; Merck FX Dr. Nierenberg has received consulting fees, advisory board fees, research support, or speakers honoraria from American Drug Utilization Review, American Professional Society of ADHD and Related Disorders, American Psychiatric Association, American Society for Clinical Psychopharmacology, Appliance Computing (Mindsite), AstraZeneca, Basliea, Baystate Medical Center, Belvoir Publishing, Brain Cells, Brandeis University, Bristol-Myers Squibb, Columbia University, Corcept, Dainippon Sumitomo, Eli Lilly, EpiQ, Forest Pharmaceuticals, Hillside Hospital, IMEDEX, International Society for Bipolar Disorders, Johnson & Johnson, MJ Consulting, Medscape, MBL Publishing, New York State, NIMH, Novartis, PamLabs, Pfizer, PGx Health, Physicians Postgraduate Press, Ridge Diagnostics, Schering-Plough, SciMed, Shire, SUNY Buffalo, Takeda/Lundbeck, Targacept, Teva Pharmaceuticals, University of Texas Southwestern Dallas, University of Wisconsin, and University of Pisa; has consulted through the MGH Clinical Trials Network and Institute for Brain Cells, Dianippon Sumitomo/Sepracor, Johnson & Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Schering-Plough, Shire, Targacept, and Takeda/Lundbeck Pharmaceuticals; and owns stock options in Appliance Computing and Brain Cells. Through Massachusetts General Hospital, Dr. Nierenberg is named for copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery-Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute. Dr. Nierenberg is a presenter for the Massachusetts General Hospital Psychiatry Academy (MGHPA). The education programs conducted by the MGHPA were supported through Independent Medical Education grants from Astra Zeneca, Bristol-Myers Squibb, Eli Lilly, and Janssen Pharmaceuticals. Dr. Friedman has received consulting fees, advisory board fees, research support, royalties, or speakers honoraria from Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cyberonics, Indevus, Medtronics, the NIMH Agency for Healthcare Research and Quality, NorthStar/St. Jude Medical, Novartis, Respironics, Sanofi-Aventis, Springer, and Wyeth-Ayerst. Dr. Bowden has received consulting fees, advisory board fees, research support, or speakers honoraria from Bristol-Myers Squibb, Johnson & Johnson, Merck Pfizer, NIMH, Repligen, and Sanofi-Aventis. Dr. Sylvia has received consulting fees from Bracket Global and Clintara, was a shareholder for Concordant Rater Systems, has received royalties from New Harbinger Publisher, and has presented for the MGHPA. Dr. Thase has received consulting fees, advisory board fees, research support, or speakers honoraria from AstraZeneca, Bristol-Myers Squibb, Dey Pharma, Eli Lilly, Forest Pharmaceuticals, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, H. Lundbeck A/S, MedAvante, Merck, Neuronetics, the NIMH Agency for Healthcare Research Quality, Novartis, Ortho-McNeil Pharmaceuticals, Otsuka, PamLab, Pfizer, Schering-Plough, Sepracor, Shire, Supernus Pharmaceuticals, Takeda (Lundbeck), and Transcept Pharmaceuticals; has equity holdings in MedAvante; and has received royalty income from American Psychiatric Foundation, Guilford Publications, Herald House, Oxford University Press, and W.W. Norton. Dr. Thase's spouse is employed by Embryon (formerly Advogent). Dr.; Ketter has received consulting fees, advisory board fees, research support, royalties, or speakers honoraria from American Psychiatric Publishing, AstraZeneca, Astellas Pharmaceuticals, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Merck, the NIMH Agency for Healthcare Research and Quality, Hoven Pharmaceuticals, Pfizer, Sunovion, and XenoPort. Dr. Ketter's spouse is an employee with and holds stock in Johnson & Johnson. Dr. Ostacher has served as a consultant to Sunovion. Dr. Leon has served on independent data and safety monitoring boards for AstraZeneca, Pfizer, and Sunovion; has received consulting fees from the Food and Drug Administration, MedAvante, NIMH, and Roche; and held equity in MedAvante. Dr. Reilly-Harrington has received royalties from the American Psychological Association and Oxford University Press, was a shareholder in Concordant Rater Systems, and has received consulting fees from Bracket Global. Dr. losifescu has received consulting or advisory board fees from Aspect Medical, Forest Pharmaceuticals, Ortho-McNeil, and Reed Medical (sponsor of the Massachusetts General Hospital Psychiatry Academy). Dr. Pencina consults for Pamlab and RCT Logic. Ms. Severe is a former employee of NIMH. Dr. Calabrese has received consulting fees, advisory board fees, research support, or speakers honoraria from Abbott, Astra-Zeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Dainippon Sumitomo, Eli Lilly, EPI-Q, Forest Pharmaceuticals, France Foundation, GlaxoSmithKline, Health Resources Services Administration. Janssen, Johnson SE Johnson, Lundbeck, Merck, NARSAD, Neurosearch, NIMH, Ortho-McNeil, Otsuka, Pfizer, Rep ligen, Schering-Plough, Servier, Solvay, Stanley Medical Research Institute, Supernus, Synosia, Takeda, the US Department of Defense, and Wyeth, and has provided CME lectures supported by AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson bz Johnson, Merck, Pfizer, Sanofi-Aventis, Schering-Plough, Solvay, and Wyeth. NR 40 TC 31 Z9 31 U1 6 U2 30 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2013 VL 170 IS 1 BP 102 EP 110 DI 10.1176/appi.ajp.2012.12060751 PG 9 WC Psychiatry SC Psychiatry GA 064OZ UT WOS:000313086200013 PM 23288387 ER EF