FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mittag, T Marsh, J Grishaev, A Orlicky, S Lin, H Sicheri, F Tyers, M Forman-Kay, JD AF Mittag, Tanja Marsh, Joseph Grishaev, Alexander Orlicky, Stephen Lin, Hong Sicheri, Frank Tyers, Mike Forman-Kay, Julie D. TI Structure/Function Implications in a Dynamic Complex of the Intrinsically Disordered Sic1 with the Cdc4 Subunit of an SCF Ubiquitin Ligase SO STRUCTURE LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; UNSTRUCTURED PROTEINS; STRUCTURAL-CHARACTERIZATION; UNFOLDED STATE; SH3 DOMAIN; ENSEMBLES; RECOGNITION; ORIENTATION; SCATTERING; SUGGEST AB Intrinsically disordered proteins can form highly dynamic complexes with partner proteins. One such dynamic complex involves the intrinsically disordered Sic1 with its partner Cdc4 in regulation of yeast cell cycle progression. Phosphorylation of six N-terminal Sic1 sites leads to equilibrium engagement of each phosphorylation site with the primary binding pocket in Cdc4, the substrate recognition subunit of a ubiquitin ligase. ENSEMBLE calculations using experimental nuclear magnetic resonance and small-angle X-ray scattering data reveal significant transient structure in both phosphorylation states of the isolated ensembles (Sic1 and pSic1) that modulates their electrostatic potential, suggesting a structural basis for the proposed strong contribution of electrostatics to binding. A structural model of the dynamic pSic1-Cdc4 complex demonstrates the spatial arrangements in the ubiquitin ligase complex. These results provide a physical picture of a protein that is predominantly disordered in both its free and bound states, enabling aspects of its structure/function relationship to be elucidated. C1 [Mittag, Tanja; Marsh, Joseph; Lin, Hong; Forman-Kay, Julie D.] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada. [Marsh, Joseph; Forman-Kay, Julie D.] Univ Toronto, Dept Biochem, Toronto, ON M5G 1X8, Canada. [Grishaev, Alexander] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Orlicky, Stephen; Sicheri, Frank; Tyers, Mike] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada. [Sicheri, Frank] Univ Toronto, Dept Mol Genet, Toronto, ON M5G 1X8, Canada. [Tyers, Mike] Univ Edinburgh, Sch Biol Sci, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Forman-Kay, JD (reprint author), Hosp Sick Children, Program Mol Struct & Funct, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM forman@sickkids.ca RI Marsh, Joseph/F-2142-2010; Sicheri, Frank/F-8856-2013; OI Marsh, Joseph/0000-0003-4132-0628 FU National Cancer Institute of Canada; Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health (NIH); Canadian Cancer Society; Canadian Institutes of Health Research; Royal Society Wolfson Research Merit; National Cancer Institute (NCI), NIH; U.S. Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-ENG-38] FX We thank L.E. Kay and T. Pawson for many fruitful discussions, A. Bax for access to his Anton Paar SAXSess instrument, and L.E. Kay and R. Muhandiram for assistance with NMR experiments. T.M. acknowledges support by a Terry Fox Post Ph.D. Research Fellowship from the National Cancer Institute of Canada. A.G. acknowledges funding by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), and the Intramural Antiviral Program of the NIH. Additional financial support was provided by funds from the Canadian Cancer Society (to M.T. and J.D.F.-K.) and the Canadian Institutes of Health Research (to F.S. and J.D.F.-K.). M.T. holds a Royal Society Wolfson Research Merit Award and is a Research Professor of the Scottish Universities Life Sciences Alliance. We thank X. Zuo [National Cancer Institute (NCI), NIH] for assistance with SAXS data processing and S. Seifert (Basic Energy Sciences Synchrotron Radiation Center, Advanced Photon Source, Argonne National Laboratory) for his support for the synchrotron experiments. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-ENG-38. The authors thank the NCI for sharing scattering beamline resource allocated under the PUP-77 agreement between the NCI and the Argonne National Laboratory. NR 47 TC 129 Z9 130 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR 14 PY 2010 VL 18 IS 4 BP 494 EP 506 DI 10.1016/j.str.2010.01.020 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 584VL UT WOS:000276781500010 PM 20399186 ER PT J AU Azzato, EM Lee, AJX Teschendorff, A Ponder, BAJ Pharoah, P Caldas, C Maia, AT AF Azzato, E. M. Lee, A. J. X. Teschendorff, A. Ponder, B. A. J. Pharoah, P. Caldas, C. Maia, A. T. TI Common germ-line polymorphism of C1QA and breast cancer survival SO BRITISH JOURNAL OF CANCER LA English DT Article DE C1QA; breast cancer; SNP; risk; differential allelic expression ID SINGLE NUCLEOTIDE POLYMORPHISM; GENE-EXPRESSION; ALLELIC VARIATION; COMPLEMENT; CELLS; COMPONENT; LYMPHOMA; THERAPY; SUBTYPE; GENOME AB BACKGROUND: A synonymous single nucleotide polymorphism (SNP) rs172378 (A > G, Gly- > Gly) in the complement component C1QA has been proposed to be associated with distant breast cancer metastasis. We previously reported overexpression of this gene to be significantly associated with better prognosis in oestrogen-receptor-negative tumours. The purpose of this study was to investigate the association of rs172378 with expression of C1QA and breast cancer survival. METHODS: We analysed the gene expression pattern of rs172378 in normal and tumour tissue samples, and further explored its involvement in relation to mortality in 2270 women with breast cancer participating in Studies of Epidemiology and Risk factors in Cancer Heredity, a population-based case-control study. RESULTS: We found that although rs172378 showed differential allelic expression significantly different between normal (preferentially expressing the G allele) and tumour tissue samples (preferentially expressing the A allele), there was no significant difference in survival by rs172378 genotype (per allele hazard ratio (HR) 1.02, 95% CI: 0.88-1.19, P = 0.78 for all-cause mortality; HR 1.03, 95% CI: 0.87-1.22, P = 0.72 for breast-cancer-specific mortality). CONCLUSION: Our study results show that rs172378 is linked to a cis-regulatory element affecting gene expression and that allelic preferential expression is altered in tumour samples, but do not support an association between genetic variation in C1QA and breast cancer survival. British Journal of Cancer (2010) 102, 1294-1299. doi: 10.1038/sj.bjc.6605625 www.bjcancer.com Published online 23 March 2010 (C) 2010 Cancer Research UK C1 [Lee, A. J. X.; Teschendorff, A.; Ponder, B. A. J.; Caldas, C.; Maia, A. T.] Canc Res UK, Cambridge Res Inst, Cambridge CB2 0RE, England. [Azzato, E. M.; Ponder, B. A. J.; Pharoah, P.] Univ Cambridge, Dept Oncol, Strangeways Res Labs, Cambridge CB1 8RN, England. [Azzato, E. M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Teschendorff, A.; Ponder, B. A. J.; Caldas, C.; Maia, A. T.] Univ Cambridge, Addenbrookes Hosp, Dept Oncol, Cambridge CB2 0XZ, England. [Teschendorff, A.] UCL, UCL Canc Inst, Med Genom Grp, London, England. [Caldas, C.] Li Ka Shing Ctr, Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England. RP Maia, AT (reprint author), Canc Res UK, Cambridge Res Inst, Robinson Way, Cambridge CB2 0RE, England. EM ana-teresa.maia@cancer.org.uk RI Caldas, Carlos/A-7543-2008; Maia, Ana-Teresa/F-4404-2012; Lee, Alvin/A-1047-2017 OI Maia, Ana-Teresa/0000-0002-0454-9207; Lee, Alvin/0000-0002-7427-9142 FU NIH, NCI; DCEG; NIH; Cancer Research UK; University of Cambridge; Hutchison Whampoa Limited; NIHR Cambridge Biomedical Research Centre FX We thank the women who have taken part in the study, the SEARCH study team, the consultants and general practitioners throughout East Anglia for their help in recruiting patients, the staff of ECRIC and North Thames Cancer Registry for providing outcome and clinical data. EA was supported by the Intramural Research Program of the NIH, NCI, DCEG and the NIH-Cambridge Graduate Partnership Program. This work was supported by grants from Cancer Research UK and (ATM, AJXL, AET, CC and BAJP). SEARCH is funded by a programme grant from Cancer Research UK. BAJP is the Li Ka Shing Professor of Oncology at the University of Cambridge. We also acknowledge the support of The University of Cambridge, Cancer Research UK, Hutchison Whampoa Limited and NIHR Cambridge Biomedical Research Centre. NR 24 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 13 PY 2010 VL 102 IS 8 BP 1294 EP 1299 DI 10.1038/sj.bjc.6605625 PG 6 WC Oncology SC Oncology GA 583GZ UT WOS:000276663200012 PM 20332777 ER PT J AU Cuneo, MJ London, RE AF Cuneo, Matthew J. London, Robert E. TI Oxidation state of the XRCC1 N-terminal domain regulates DNA polymerase beta binding affinity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE disulfide switch; DNA repair; scaffolding protein ID STRAND-BREAK REPAIR; RAY SOLUTION SCATTERING; BASE EXCISION-REPAIR; DISULFIDE BONDS; PROTEIN; SWITCHES; PROGRAM; STRESS; SYSTEM; DAMAGE AB Formation of a complex between the XRCC1 N-terminal domain (NTD) and DNA polymerase beta (Pol beta) is central to base excision repair of damaged DNA. Two crystal forms of XRCC1-NTD complexed with Pol beta have been solved, revealing that the XRCC1-NTD is able to adopt a redox-dependent alternate fold, characterized by a disulfide bond, and substantial variations of secondary structure, folding topology, and electrostatic surface. Although most of these structural changes occur distal to the interface, the oxidized XRCC1-NTD forms additional interactions with Pol beta, enhancing affinity by an order of magnitude. Transient disulfide bond formation is increasingly recognized as an important molecular regulatory mechanism. The results presented here suggest a paradigm in DNA repair in which the redox state of a scaffolding protein plays an active role in organizing the repair complex. C1 [Cuneo, Matthew J.; London, Robert E.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov OI Cuneo, Matthew/0000-0002-1475-6656 FU US Department of Energy [DE-AC02-98CH10886] FX The authors would like to thank the laboratory of Sam Wilson (NIEHS) for the human XRCC1 gene and the rat polymerase beta gene, Drs. Eugene DeRose and Joseph Krahn, NIEHS for helpful input on the NMR and crystallography studies, Dr. Lin Yang of the X9 beamline, at the National Synchrotron Light Source at Brookhaven National Laboratory, for assistance with data collection. Use of the X9 beamline is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract DE-AC02-98CH10886. NR 42 TC 27 Z9 28 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6805 EP 6810 DI 10.1073/pnas.0914077107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100046 PM 20351257 ER PT J AU Zhou, J Wang, CG Wang, ZB Dampier, W Wu, KM Casimiro, MC Chepelev, I Popov, VM Quong, A Tozeren, A Zhao, KJ Lisanti, MP Pestell, RG AF Zhou, Jie Wang, Chenguang Wang, Zhibin Dampier, Will Wu, Kongming Casimiro, Mathew C. Chepelev, Iouri Popov, Vladimir M. Quong, Andrew Tozeren, Aydin Zhao, Keji Lisanti, Michael P. Pestell, Richard G. TI Attenuation of Forkhead signaling by the retinal determination factor DACH1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell fate determination; Forkhead protein; transcription factor; tumor suppressor; dachshund homolog 1 ID FATE DETERMINATION FACTOR; ESTROGEN-RECEPTOR-ALPHA; TRANSCRIPTION FACTOR; CYCLIN D1; BREAST-CANCER; GENE-EXPRESSION; CELLULAR MIGRATION; GROWTH; PROLIFERATION; REPRESSION AB The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box-containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets-defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis. C1 [Zhou, Jie; Wang, Chenguang; Wu, Kongming; Casimiro, Mathew C.; Popov, Vladimir M.; Quong, Andrew; Lisanti, Michael P.; Pestell, Richard G.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. [Wang, Chenguang; Lisanti, Michael P.] Thomas Jefferson Univ, Dept Stem Cell Biol & Regenerat Med, Philadelphia, PA 19107 USA. [Zhou, Jie; Wang, Chenguang; Wu, Kongming; Casimiro, Mathew C.; Popov, Vladimir M.; Quong, Andrew; Lisanti, Michael P.; Pestell, Richard G.] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Wang, Zhibin; Chepelev, Iouri; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Dampier, Will; Tozeren, Aydin] Drexel Univ, Ctr Integrated Bioinformat, Sch Biomed Engn Sci & Hlth Syst, Philadelphia, PA 19104 USA. RP Wang, CG (reprint author), Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. EM chenguang.wang@jefferson.edu; richard.pestell@jefferson.edu RI Lisanti, Michael/C-6866-2013 FU Susan Komen Breast Cancer Foundation [BCTR0504227]; National Institutes of Health Cancer Center Core [R01CA70896, R01CA75503, R01CA86072, R01CA080250, R01CA098779, R01CA120876, R01AR055660, 232240, P30CA56036]; Margaret Q. Landenberger Research Foundation; Pennsylvania Department of Health FX This work was supported in part by Award BCTR0504227 from the Susan Komen Breast Cancer Foundation (to C.W.) and National Institutes of Health Grants R01CA70896, R01CA75503, and R01CA86072 (to R.G.P.), R01CA080250, R01CA098779, R01CA120876, and R01AR055660 (to M.P.L.), and 232240 (to A.T.). Work conducted at the Kimmel Cancer Center was supported by National Institutes of Health Cancer Center Core Grant P30CA56036 (to R.G.P.). This project was funded in part by a grant from the Margaret Q. Landenberger Research Foundation (to K.W.), the Pennsylvania Department of Health (to C.W., M.P.L., and R.G.P.), and by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute (K.Z.). NR 34 TC 31 Z9 32 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6864 EP 6869 DI 10.1073/pnas.1002746107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100056 PM 20351289 ER PT J AU Crompton, PD Kayala, MA Traore, B Kayentao, K Ongoiba, A Weiss, GE Molina, DM Burk, CR Waisberg, M Jasinskas, A Tan, XL Doumbo, S Doumtabe, D Kone, Y Narum, DL Liang, XW Doumbo, OK Miller, LH Doolan, DL Baldi, P Felgner, PL Pierce, SK AF Crompton, Peter D. Kayala, Matthew A. Traore, Boubacar Kayentao, Kassoum Ongoiba, Aissata Weiss, Greta E. Molina, Douglas M. Burk, Chad R. Waisberg, Michael Jasinskas, Algis Tan, Xiaolin Doumbo, Safiatou Doumtabe, Didier Kone, Younoussou Narum, David L. Liang, Xiaowu Doumbo, Ogobara K. Miller, Louis H. Doolan, Denise L. Baldi, Pierre Felgner, Philip L. Pierce, Susan K. TI A prospective analysis of the Ab response to Plasmodium falciparum before and after a malaria season by protein microarray SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antigen discovery; naturally acquired immunity; Plasmodium falciparum malaria; prospective cohort study; Mali ID HUMORAL IMMUNE-RESPONSES; MEMORY B-CELLS; ANTIBODY-RESPONSES; SURFACE-ANTIGEN; ERYTHROCYTE-MEMBRANE; ACQUIRED IMMUNITY; VAR GENES; VACCINE; INFECTION; PROTECTION AB Abs are central to malaria immunity, which is only acquired after years of exposure to Plasmodium falciparum (Pf). Despite the enormous worldwide burden of malaria, the targets of protective Abs and the basis of their inefficient acquisition are unknown. Addressing these knowledgegaps could accelerate malaria vaccine development. To this end, we developed a protein microarray containing similar to 23% of the Pf 5,400-protein proteome and used this array to probe plasma from 220 individuals between the ages of 2-10 years and 1825 years in Mali before and after the 6-month malaria season. Episodes of malaria were detected by passive surveillance over the 8month study period. Ab reactivity to Pf proteins rose dramatically in children during the malaria season; however, most of this response appeared to be short-lived based on cross-sectional analysis before the malaria season, which revealed only modest incremental increases in Ab reactivity with age. Ab reactivities to 49 Pf proteins measured before the malaria season were significantly higher in 810- year-old children who were infected with Pf during the malaria season but did not experience malaria (n = 12) vs. those who experienced malaria (n = 29). This analysis also provided insight into patterns of Ab reactivity against Pf proteins based on the life cycle stage at which proteins are expressed, subcellular location, and other proteomic features. This approach, if validated in larger studies and in other epidemiological settings, could prove to be a useful strategy for better understanding fundamental properties of the human immune response to Pf and for identifying previously undescribed vaccine targets. C1 [Crompton, Peter D.; Weiss, Greta E.; Waisberg, Michael; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Kayala, Matthew A.; Baldi, Pierre] Univ Calif Irvine, Sch Informat & Comp Sci, Inst Genom & Bioinformat, Irvine, CA 92697 USA. [Burk, Chad R.; Jasinskas, Algis; Tan, Xiaolin; Felgner, Philip L.] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92697 USA. [Traore, Boubacar; Kayentao, Kassoum; Ongoiba, Aissata; Doumbo, Safiatou; Doumtabe, Didier; Kone, Younoussou; Doumbo, Ogobara K.] Univ Bamako, Malaria Res & Training Ctr, Fac Med Pharm & Dent, Bamako, Mali. [Molina, Douglas M.; Liang, Xiaowu; Felgner, Philip L.] Antigen Discovery Inc, Irvine, CA 92618 USA. [Narum, David L.; Miller, Louis H.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20852 USA. [Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20852 USA. [Doolan, Denise L.] Queensland Inst Med Res, Mol Vaccinol Lab, Brisbane, Qld 4029, Australia. RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM pcrompton@niaid.nih.gov; lmiller@niaid.nih.gov; pfelgner@uci.edu RI Doolan, Denise/F-1969-2015; Crompton, Peter/N-1130-2016 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [1R43AI066791]; National Institutes of Health Biomedical Informatics Training [LM-07443-01]; National Science Foundation [EIA-0321390, IIS-0513376]; Pfizer Australia Research Fellowship FX We thank the residents of Kambila, Mali, for participating in this study. We also thank Dr. Robin Anders for providing MSP-2, Dr. Cheick Tidiane Dabo for clinical laboratory support, Seydou Dia and Tonkoro Diarra for assisting at the study clinic, Bakary Coulibaly and Daouda Kane for helping to prepare the study site, Jozelyn Pablo and Mina Kalantari for cloning and maintaining the clone collection, and Julie Kim, Dr. Richard Sakai, and the Mali Service Center for logistic support. This work was supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by National Institute of Allergy and Infectious Diseases Grant 1R43AI066791 (P.L.F.). M.A.K. and P.B. are supported by National Institutes of Health Biomedical Informatics Training Grant LM-07443-01 and National Science Foundation Grants EIA-0321390 and IIS-0513376 (to P.B.). D.L.D. is supported by a Pfizer Australia Research Fellowship. NR 53 TC 171 Z9 174 U1 3 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6958 EP 6963 DI 10.1073/pnas.1001323107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100072 PM 20351286 ER PT J AU Lev, A Princiotta, MF Zanker, D Takeda, K Gibbs, JS Kumagai, C Waffarn, E Dolan, BP Burgevin, A Van Endert, P Chen, WS Bennink, JR Yewdell, JW AF Lev, Avital Princiotta, Michael F. Zanker, Damian Takeda, Kazuyo Gibbs, James S. Kumagai, Chiharu Waffarn, Elizabeth Dolan, Brian P. Burgevin, Anne Van Endert, Peter Chen, Weisan Bennink, Jack R. Yewdell, Jonathan W. TI Compartmentalized MHC class I antigen processing enhances immunosurveillance by circumventing the law of mass action SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MHC; peptide; translation; virus ID CROSS-PRESENTATION; CYTOSOLIC PEPTIDES; PROTEIN-SYNTHESIS; DENDRITIC CELLS; DEGRADATION; MOLECULES; COMPLEX; GENE AB MHC class I molecules function to display peptides generated from cellular and pathogen gene products for immune surveillance by CD8(+) T cells. Cells typically express similar to 100,000 class I molecules, or similar to 1 per 30,000 cellular proteins. Given "one protein, one peptide" representation, immunosurveillance would be heavily biased toward the most abundant cell proteins. Cells use several mechanisms to prevent this, including the predominant use of defective ribosomal products (DRiPs) to generate peptides from nascent proteins and, as we show here, compartmentalization of DRiP peptide generation to prevent competition from abundant cytosolic peptides. This provides an explanation for the exquisite ability of T cells to recognize peptides generated from otherwise undetected gene products. C1 [Lev, Avital; Takeda, Kazuyo; Gibbs, James S.; Waffarn, Elizabeth; Dolan, Brian P.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Princiotta, Michael F.; Kumagai, Chiharu] SUNY Upstate Med Ctr, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. [Zanker, Damian; Chen, Weisan] Austin Hlth, Ludwig Inst Canc Res, Cell Lab T, Melbourne Ctr Clin Sci, Heidelberg, Vic 3050, Australia. [Burgevin, Anne; Van Endert, Peter] Hop Necker Enfants Malad, INSERM, F-75743 Paris, France. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Chen, Weisan/E-7828-2012; OI van Endert, Peter/0000-0003-3782-0750; Zanker, Damien/0000-0003-1163-9902 NR 20 TC 34 Z9 34 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 6964 EP 6969 DI 10.1073/pnas.0910997107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100073 PM 20351281 ER PT J AU Shirvalkar, PR Rapp, PR Shapiro, ML AF Shirvalkar, Prasad R. Rapp, Peter R. Shapiro, Matthew L. TI Bidirectional changes to hippocampal theta-gamma comodulation predict memory for recent spatial episodes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hippocampus; medial septum; theta-burst stimulation; fimbria-fornix; retrieval ID PHASE PRECESSION; WORKING-MEMORY; CODING SCHEME; OSCILLATIONS; RHYTHM; CODE; RAT; MODULATION; DRIVEN; FIELD AB Episodic memory requires the hippocampus, which is thought to bind cortical inputs into conjunctive codes. Local field potentials (LFPs) reflect dendritic and synaptic oscillations whose temporal structure may coordinate cellular mechanisms of plasticity and memory. We now report that single-trial spatial memory performance in rats was predicted by the power comodulation of theta (4-10 Hz) and low gamma (30-50 Hz) rhythms in the hippocampus. Theta-gamma comodulation (TGC) was prominent during successful memory retrieval but was weak when memory failed or was unavailable during spatial exploration in sample trials. Muscimol infusion into medial septum reduced the probability of TGC and successful memory retrieval. In contrast, patterned electrical stimulation of the fimbria-fornix increased TGC in amnestic animals and partially rescued memory performance in the water maze. The results suggest that TGC accompanies memory retrieval in the hippocampus and that patterned brain stimulation may inform therapeutic strategies for cognitive disorders. C1 [Shirvalkar, Prasad R.; Shapiro, Matthew L.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA. [Rapp, Peter R.] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Shapiro, ML (reprint author), Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA. EM matthew.shapiro@mssm.edu FU National Institute on Aging Intramural Research; National Institutes of Health [MH65658, MH073689, F30 AG034003-01A1]; Mount Sinai School of Medicine FX We thank Alex Morrison and Julius Arijeloye for providing technical assistance, Janina Ferbinteanu, Pamela Kennedy, Amir Bahar, Justin Riceberg, Jake Young, Kimberly Kwei, Marshall Crumiller, and Caroline Dias for their comments on the manuscript, and Maojuan Zhuang for technical work. This work was supported in part by the National Institute on Aging Intramural Research Program, National Institutes of Health Grants MH65658, MH073689, and F30 AG034003-01A1, and the Mount Sinai School of Medicine. NR 37 TC 75 Z9 79 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 7054 EP 7059 DI 10.1073/pnas.0911184107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100088 PM 20351262 ER PT J AU Zhou, XM Gallazzini, M Burg, MB Ferraris, JD AF Zhou, Xiaoming Gallazzini, Morgan Burg, Maurice B. Ferraris, Joan D. TI Contribution of SHP-1 protein tyrosine phosphatase to osmotic regulation of the transcription factor TonEBP/OREBP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hypertonicity; NFAT5; nuclear localization; phosphorylation; siRNA library ID ENHANCER-BINDING PROTEIN; NITRIC-OXIDE PRODUCTION; HIGH NACL; GENE-EXPRESSION; NUCLEOCYTOPLASMIC TRAFFICKING; PHOSPHOLIPASE C-GAMMA-1; NUCLEAR-LOCALIZATION; ACTIVATION; PHOSPHORYLATION; HYPERTONICITY AB Hypertonicity activates the transcription factor TonEBP/OREBP, resulting in increased expression of osmoprotective genes, including those responsible for accumulation of organic osmolytes and heat-shock proteins. Phosphorylation of TonEBP/OREBP contributes to its activation. Several of the kinases that are involved were previously identified, but the phosphatases were not. In the present studies we screened a genomewide human phosphatase siRNA library in human embryonic kidney (HEK)293 cells for effects on TonEBP/OREBP transcriptional activity. We found that siRNAs against 57 phosphatases significantly alter TonEBP/OREBP transcriptional activity during normotonicity (290 mosmol/kg) or hypertonicity (500 mosmol/kg, NaCl added) or both. Most siRNAs increase TonEBP/OREBP activity, implying that the targeted phosphatases normally reduce that activity. We further studied in detail SHP-1, whose knockdown by its specific siRNA increases TonEBP/OREBP transcriptional activity at 500 mosmol/kg. We confirmed that SHP-1 is inhibitory by overexpressing it, which reduces TonEBP/OREBP transcriptional activity at 500 mosmol/kg. SHP-1 dephosphorylates TonEBP/OREBP at a known regulatory site, Y143, both in vivo and in vitro. It inhibits TonEBP/OREBP by both reducing TonEBP/OREBP nuclear localization, which is Y143 dependent, and by lowering high NaCl-induced TonEBP/OREBP transactivating activity. SHP-1 coimmunoprecipitates with TonEBP/OREBP and vice versa, suggesting that they are physically associated in the cell. High NaCl inhibits the effect of SHP-1 on TonEBP/OREBP by increasing phosphorylation of SHP-1 on Ser591, which reduces its phosphatase activity and localization to the nucleus. Thus, TonEBP/OREBP is extensively regulated by phosphatases, including SHP-1, whose inhibition by high NaCl increases phosphorylation of TonEBP/OREBP at Y143, contributing to the nuclear localization and activation of TonEBP/OREBP. C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Dept Med, Div Nephrol, Bethesda, MD 20814 USA. [Gallazzini, Morgan; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, XM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Div Nephrol, Bethesda, MD 20814 USA. EM xiazhou@usuhs.mil; maurice_burg@nih.gov RI Gallazzini, Morgan/E-5465-2011 FU National Heart, Lung, and Blood Institute FX This study was supported in part by the National Heart, Lung, and Blood Institute intramural research program. NR 34 TC 13 Z9 13 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 7072 EP 7077 DI 10.1073/pnas.1002795107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100091 PM 20351292 ER PT J AU Ong, KM Blackford, JA Kagan, BL Simons, SS Chow, CC AF Ong, Karen M. Blackford, John A., Jr. Kagan, Benjamin L. Simons, S. Stoney, Jr. Chow, Carson C. TI A theoretical framework for gene induction and experimental comparisons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dose-response; Michaelis-Menten; gene expression; steroid receptors; glucocorticoids; pharmacology ID DNA-BINDING DOMAIN; GLUCOCORTICOID-RECEPTOR TRANSACTIVATION; DOSE-RESPONSE CURVE; MOLECULAR-MECHANISMS; TRANSCRIPTION FACTOR; SECONDARY MEDIATORS; HORMONE-BINDING; MODULATION; REPRESSION; EXPRESSION AB Ligand-mediated gene induction by steroid receptors is a multistep process characterized by a dose-response curve for gene product that follows a first-order Hill equation. This behavior has classically been explained by steroid binding to receptor being the rate-limiting step. However, this predicts a constant potency of gene induction (EC(50)) for a given receptor-steroid complex, which is challenged by the findings that various cofactors/reagents can alter this parameter in a gene-specificmanner. These properties put strong constraints on the mechanisms of gene induction and raise two questions: How can a first-order Hill dose-response curve (FHDC) arise from a multistep reaction sequence, and how do cofactors modify potency? Here we introduce a theoretical framework in which a sequence of steps yields an FHDC for the final product as a function of the initial agonist concentration. An exact determination of all constants is not required to describe the final FHDC. The theory predicts mechanisms for cofactor/reagent effects on gene-induction potency and maximal activity and it assigns a relative order to cofactors in the sequence of steps. The theory is supported by several observations from glucocorticoid receptor-mediated gene induction. It identifies the mechanism and matches the measured dose-response curves for different concentrations of the combination of cofactor Ubc9 and receptor. It also predicts that an FHDC cannot involve the DNA binding of preformed receptor dimers, which is validated experimentally. The theory is general and can be applied to any biochemical reaction that shows an FHDC. C1 [Blackford, John A., Jr.; Kagan, Benjamin L.; Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Ong, Karen M.; Chow, Carson C.] NIDDK, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM steroids@niddk.nih.gov; carsonc@mail.nih.gov RI Chow, Carson/A-7970-2009 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Jessica Lee for excellent technical assistance and Yunguan Sun for some preliminary experiments. We thank Sankar Adhya, Gordon Hager, Terence Hwa, David Levens, and Ty Voss for helpful comments. This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 43 TC 33 Z9 33 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP 7107 EP 7112 DI 10.1073/pnas.0911095107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100097 PM 20351279 ER PT J AU Zhang, K Jiao, XD Chen, YH Yang, ZL Hennis, A Nemesure, B Hoh, J Hejtmancik, JF AF Zhang, Kang Jiao, Xiaodong Chen, Yuhong Yang, Zhenglin Hennis, Anselm Nemesure, Barbara Hoh, Josephine Hejtmancik, J. Fielding TI Reply to Liu et al.: Differential effects of chromosome 2p16.3 variants on glaucoma in African derived populations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID MODERN HUMAN ORIGINS; OPEN-ANGLE GLAUCOMA; LOCUS C1 [Zhang, Kang; Chen, Yuhong; Yang, Zhenglin] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Zhang, Kang; Chen, Yuhong; Yang, Zhenglin] Univ Calif San Diego, Shiley Eye Ctr, La Jolla, CA 92093 USA. [Jiao, Xiaodong; Hejtmancik, J. Fielding] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. [Jiao, Xiaodong; Hejtmancik, J. Fielding] NIH, Barbados Family Study Grp, Bethesda, MD 20892 USA. [Hennis, Anselm] Univ W Indies, Chron Dis Res Ctr, Res Inst Trop Med, BB-11115 Bridgetown, Barbados. [Hennis, Anselm] Univ W Indies, Barbados Family Study Grp, BB-11115 Bridgetown, Barbados. [Hennis, Anselm] Univ W Indies, Minist Hlth, BB-11115 Bridgetown, Barbados. [Nemesure, Barbara] SUNY Stony Brook, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA. [Nemesure, Barbara] SUNY Stony Brook, Barbados Family Study Grp, Stony Brook, NY 11794 USA. [Hoh, Josephine] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. RP Zhang, K (reprint author), Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. EM kangzhang@ucsd.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 13 PY 2010 VL 107 IS 15 BP E62 EP E62 DI 10.1073/pnas.1000204107 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583AC UT WOS:000276642100103 ER PT J AU Largent, EA Miller, FG Pearson, SD AF Largent, Emily A. Miller, Franklin G. Pearson, Steven D. TI The Pharmacist's Role in Off-label Prescribing Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 [Largent, Emily A.; Miller, Franklin G.; Pearson, Steven D.] NIH, Ctr Clin, Dept Eth, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), NIH, Ctr Clin, Dept Eth, Clin Ctr Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov NR 1 TC 0 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 12 PY 2010 VL 170 IS 7 BP 658 EP 658 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 581XI UT WOS:000276558700021 ER PT J AU Bothmer, A Robbiani, DF Feldhahn, N Gazumyan, A Nussenzweig, A Nussenzweig, MC AF Bothmer, Anne Robbiani, Davide F. Feldhahn, Niklas Gazumyan, Anna Nussenzweig, Andre Nussenzweig, Michel C. TI 53BP1 regulates DNA resection and the choice between classical and alternative end joining during class switch recombination SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DOUBLE-STRAND BREAKS; SITE-SPECIFIC RECOMBINATION; HOMOLOGOUS RECOMBINATION; SOMATIC HYPERMUTATION; CELL-CYCLE; B-CELLS; CHROMOSOMAL REARRANGEMENTS; ANTIBODY DIVERSIFICATION; REGION RECOMBINATION; DEFICIENT MICE AB Class switch recombination (CSR) diversifies antibodies by joining highly repetitive DNA elements, which are separated by 60-200 kbp. CSR is initiated by activation-induced cytidine deaminase, an enzyme that produces multiple DNA double-strand breaks (DSBs) in switch regions. Switch regions are joined by a mechanism that requires an intact DNA damage response and classical or alternative nonhomologous end joining (A-NHEJ). Among the DNA damage response factors, 53BP1 has the most profound effect on CSR. We explore the role of 53BP1 in intrachromosomal DNA repair using I-SceI to introduce paired DSBs in the IgH locus. We find that the absence of 53BP1 results in an ataxia telangiectasia mutated-dependent increase in DNA end resection and that resected DNA is preferentially repaired by microhomology-mediated A-NHEJ. We propose that 53BP1 favors long-range CSR in part by protecting DNA ends against resection, which prevents A-NHEJ-dependent short-range rejoining of intra-switch region DSBs. C1 [Bothmer, Anne; Robbiani, Davide F.; Feldhahn, Niklas; Gazumyan, Anna; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Gazumyan, Anna; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussen@mail.rockefeller.edu FU National Institutes of Health (NIH) [1ROAI072529-01, 5RO1AI037526]; Howard Hughes Medical Institute; Cancer Research Institute; Leukemia and Lymphoma Society FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH; A. Nussenzweig), NIH grants 1ROAI072529-01 and 5RO1AI037526 (to M. C. Nussenzweig), and the Howard Hughes Medical Institute (M. C. Nussenzweig). A. Bothmer is a predoctoral fellow of the Cancer Research Institute. D. F. Robbiani was and N. Feldhahn is a fellow of the Leukemia and Lymphoma Society. NR 74 TC 134 Z9 137 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 12 PY 2010 VL 207 IS 4 BP 855 EP 865 DI 10.1084/jem.20100244 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 581VJ UT WOS:000276552700016 PM 20368578 ER PT J AU Tang, ZS Arjunan, P Lee, C Li, Y Kumar, A Hou, X Wang, B Wardega, P Zhang, F Dong, LJ Zhang, YQ Zhang, SZ Ding, H Fariss, RN Becker, KG Lennartsson, J Nagai, N Cao, YH Li, XR AF Tang, Zhongshu Arjunan, Pachiappan Lee, Chunsik Li, Yang Kumar, Anil Hou, Xu Wang, Bin Wardega, Piotr Zhang, Fan Dong, Lijin Zhang, Yongqing Zhang, Shi-Zhuang Ding, Hao Fariss, Robert N. Becker, Kevin G. Lennartsson, Johan Nagai, Nobuo Cao, Yihai Li, Xuri TI Survival effect of PDGF-CC rescues neurons from apoptosis in both brain and retina by regulating GSK3 beta phosphorylation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; GROWTH-FACTOR CC; ALPHA-RECEPTOR; BETA-RECEPTOR; FAMILY; EXPRESSION; MEMBERS; MEMANTINE; DISEASE; STROKE AB Platelet-derived growth factor CC (PDGF-CC) is the third member of the PDGF family discovered after more than two decades of studies on the original members of the family, PDGF-AA and PDGF-BB. The biological function of PDGF-CC remains largely to be explored. We report a novel finding that PDGF-CC is a potent neuroprotective factor that acts by modulating glycogen synthase kinase 3 beta (GSK3 beta) activity. In several different animal models of neuronal injury, such as axotomy-induced neuronal death, neurotoxin-induced neuronal injury, 6-hydroxydopamine-induced Parkinson's dopaminergic neuronal death, and ischemia-induced stroke, PDGF-CC protein or gene delivery protected different types of neurons from apoptosis in both the retina and brain. On the other hand, loss-of-function assays using PDGF-C null mice, neutralizing antibody, or short hairpin RNA showed that PDGF-CC deficiency/inhibition exacerbated neuronal death in different neuronal tissues in vivo. Mechanistically, we revealed that the neuroprotective effect of PDGF-CC was achieved by regulating GSK3 beta phosphorylation and expression. Our data demonstrate that PDGF-CC is critically required for neuronal survival and may potentially be used to treat neurodegenerative diseases. Inhibition of the PDGF-CC-PDGF receptor pathway for different clinical purposes should be conducted with caution to preserve normal neuronal functions. C1 [Tang, Zhongshu; Arjunan, Pachiappan; Lee, Chunsik; Li, Yang; Kumar, Anil; Hou, Xu; Zhang, Fan; Dong, Lijin; Fariss, Robert N.; Li, Xuri] NEI, NIH, Bethesda, MD 20892 USA. [Wang, Bin; Zhang, Shi-Zhuang] Weifang Med Univ, Dept Radiol, Med Imaging Ctr, Affiliated Hosp, Weifang City 261053, Shandong, Peoples R China. [Wardega, Piotr; Lennartsson, Johan] Uppsala Univ, Ludwig Inst Canc Res, S-75124 Uppsala, Sweden. [Zhang, Yongqing; Becker, Kevin G.] NIA, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Ding, Hao] Univ Manitoba, Dept Biochem & Mol Genet, Winnipeg, MB R3E 3P5, Canada. [Nagai, Nobuo] Kinki Univ, Dept Physiol, Sch Med, Osaka 5898511, Japan. [Cao, Yihai] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. RP Li, XR (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM lixur@nei.nih.gov RI Kumar, Anil/K-8504-2012 FU NIH; National Institute on Aging; National Eye Institute FX This research was supported by the Intramural Research Program of the NIH, the National Institute on Aging, and the National Eye Institute. NR 32 TC 49 Z9 50 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 12 PY 2010 VL 207 IS 4 BP 867 EP 880 DI 10.1084/jem.20091704 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 581VJ UT WOS:000276552700017 PM 20231377 ER PT J AU Yamamoto, Y Moore, R Flavell, RA Lu, BF Negishi, M AF Yamamoto, Yukio Moore, Rick Flavell, Richard A. Lu, Binfeng Negishi, Masahiko TI Nuclear Receptor CAR Represses TNF alpha-Induced Cell Death by Interacting with the Anti-Apoptotic GADD45B SO PLOS ONE LA English DT Article ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CROSS-TALK; LIVER; GENE; ACTIVATION; MICE; METABOLISM; MKK7/JNKK2; INDUCTION AB Background: Phenobarbital (PB) is the most well-known among numerous non-genotoxic carcinogens that cause the development of hepatocellular carcinoma (HCC). PB activates nuclear xenobiotic receptor Constitutive Active/Androstane Receptor ( CAR; NR1I3) and this activation is shown to determine PB promotion of HCC in mice. The molecular mechanism of CAR-mediated tumor promotion, however, remains elusive at the present time. Here we have identified Growth Arrest and DNA Damage-inducible 45 beta (GADD45B) as a novel CAR target, through which CAR represses cell death. Methodology/Principal Findings: PB activation of nuclear xenobiotic receptor CAR is found to induce the Gadd45b gene in mouse liver throughout the development of HCC as well as in liver tumors. Given the known function of GADD45B as a factor that represses Mitogen-activated protein Kinase Kinase 7 - c-Jun N-terminal Kinase (MKK7-JNK) pathway-mediated apoptosis, we have now demonstrated that CAR interacts with GADD45B to repress Tumor Necrosis Factor alpha (TNF alpha)-induced JNK1 phosphorylation as well as cell death. Primary hepatocytes, prepared from Car(+/+), Car(-/-), Gadd45b(+/+) and Gadd45b(-/-) mice, were treated with TNF alpha and Actinomycin D to induce phosphorylation of JNK1 and cell death. Co-treatment with the CAR activating ligand TCPOBOP (1,4 bis[2-(3,5-dichloropyridyloxy)]benzene) has resulted in repression of both phosphorylation and cell death in the primary hepatocytes from Car(+/+) but not Car(-/-) mice. Repression by TCPOBOP was not observed in those prepared from Gadd45b(-/-) mice. In vitro protein-protein interaction and phosphorylation assays have revealed that CAR interacts with MKK7 and represses the MKK7-mediated phosphorylation of JNK1. Conclusions/Significance: CAR can form a protein complex with GADD45B, through which CAR represses MKK7-mediated phosphorylation of JNK1. In addition to activating the Gadd45b gene, CAR may repress death of mouse primary hepatocytes by forming a GADD45B complex and repressing MKK7-mediated phosphorylation of JNK1. The present finding that CAR can repress cell death via its interaction with GADD45B provides an insight for further investigations into the CAR-regulated molecular mechanism by which PB promotes development of HCC. C1 [Yamamoto, Yukio; Moore, Rick; Negishi, Masahiko] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC USA. [Flavell, Richard A.] Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT USA. [Lu, Binfeng] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. RP Yamamoto, Y (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Tokyo, Japan. EM negishi@niehs.nih.gov FU National Institutes of Health (NIH); National Institute of Environmental Health [Z01ES71005-01] FX This study was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health: Z01ES71005-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 28 Z9 29 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 12 PY 2010 VL 5 IS 4 AR e10121 DI 10.1371/journal.pone.0010121 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 583UR UT WOS:000276705900006 PM 20404936 ER PT J AU Gerloff, C Hallett, M AF Gerloff, Christian Hallett, Mark TI Big news from small world networks after stroke SO BRAIN LA English DT Editorial Material ID MOTOR AREAS; RECOVERY; BRAIN; CONNECTIVITY; SYNCHRONIZATION; REORGANIZATION C1 [Gerloff, Christian] Univ Med Ctr Hamburg, Cort Physiol Res Grp, Dept Neurol, Hamburg, Germany. [Hallett, Mark] NINDS, NIH, Human Motor Control Sect, Bethesda, MD 20892 USA. RP Gerloff, C (reprint author), Univ Med Ctr Hamburg, Cort Physiol Res Grp, Dept Neurol, Hamburg, Germany. EM gerloff@uke.de NR 18 TC 11 Z9 12 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR 10 PY 2010 VL 133 BP 952 EP 955 DI 10.1093/brain/awq062 PN 4 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 590KU UT WOS:000277225600002 PM 20375131 ER PT J AU Phan, PAB Tadros, SF Kim, Y Birnbaumer, L Housley, GD AF Phan, Patrick A. B. Tadros, Sherif F. Kim, Youngsoo Birnbaumer, Lutz Housley, Gary D. TI Developmental regulation of TRPC3 ion channel expression in the mouse cochlea SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE Transient receptor potential channel; Hair cells; Hearing; TRPC3 knockout; Spiral ganglion; Immunofluorescence ID OUTER HAIR-CELLS; NONSELECTIVE CATION CONDUCTANCE; SPIRAL GANGLION NEURONS; INTRACELLULAR CA2+; AUDITORY-SYSTEM; GUINEA-PIG; HEARING; RAT; STORE; TRANSDUCTION AB Canonical transient receptor potential type 3 (TRPC3) ion channels assemble from TRPC3 subunits and exhibit multiple activation mechanisms. TRPC3 has been proposed to contribute to Ca(2+) entry supporting Ca(2+) homeostasis in cochlear hair cells and to be activated by G protein-coupled receptor (GPCR) signaling in spiral ganglion neurons. The present study was designed to determine the spatiotemporal profile of TRPC3 expression during mouse cochlear ontogeny. TRPC3 immunofluorescence of cryosectioned cochleae was performed using E16-adult tissue. We found that prior to birth, TRPC3 expression was strongest in epithelial cells that form the cochlear partition. In the early postnatal period, to the onset of hearing (similar to P12), immunofluorescence was strongest in the hair cells, with increased expression in stria vascularis and Reissner's membrane. Afferent neurite labeling in inner spiral plexus and outer spiral bundles developed transiently in the perinatal period, corresponding to the critical period of synaptic consolidation, while signal in the spiral ganglion soma increased from the perinatal period through to adulthood. Compared with the late embryonic/early postnatal levels, hair cell expression was relatively weaker from the third postnatal week, whereas spiral ganglion soma labeling was stronger. In the adult, TRPC3 expression was primarily in the soma of spiral ganglion neurons, the hair cells, and the inner and outer sulcus regions. This spatiotemporal profile of TRPC3 expression was consistent with this ion channel contributing to development of sensory, neural and epithelial cochlear tissues, as well as hair cell Ca(2+) homeostasis and regulation of auditory neurotransmission via GPCR signaling. C1 [Phan, Patrick A. B.; Tadros, Sherif F.; Kim, Youngsoo; Housley, Gary D.] Univ New S Wales, Dept Physiol, Translat Neurosci Facil, Sch Med Sci, Sydney, NSW 2052, Australia. [Birnbaumer, Lutz] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Housley, GD (reprint author), Univ New S Wales, Dept Physiol, Translat Neurosci Facil, Sch Med Sci, Wallace Wurth Bldg,UNSW Kensington Campus, Sydney, NSW 2052, Australia. EM g.housley@unsw.edu.au OI Housley, Gary/0000-0002-8413-588X FU Australian Research Council [DP1097202]; NIH [Z01-ES101684] FX Supported by the Australian Research Council (DP1097202). We also acknowledge the support of the Intramural Research Program of the NIH (Project Z01-ES101684 to LB). NR 42 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD APR 10 PY 2010 VL 133 IS 4 BP 437 EP 448 DI 10.1007/s00418-010-0686-x PG 12 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 573HI UT WOS:000275899500006 PM 20229053 ER PT J AU Ambagala, APN Krogmann, T Qin, J Pesnicak, L Cohen, JI AF Ambagala, Aruna P. N. Krogmann, Tammy Qin, Jing Pesnicak, Lesley Cohen, Jeffrey I. TI A varicella-zoster virus mutant impaired for latency in rodents, but not impaired for replication in cell culture SO VIROLOGY LA English DT Article DE Varicella-zoster Virus; Latency; Shingles; Chickenpox ID HUMAN TRIGEMINAL GANGLIA; HERPES-ZOSTER; VACCINE STRAINS; GENE-EXPRESSION; PROTEIN-KINASE; OKA STRAIN; IN-VITRO; CHILDREN; ESTABLISHMENT; IE62 AB While trying to generate a site-directed deletion in the ORF63 latency-associated gene of varicella-zoster virus (VZV) Oka, we constructed a virus with an unexpected rearrangement. The virus has a small deletion in both copies of ORF63 and two copies of a cassette inserted between ORFs 64/65 and 68/69 containing (a) truncated ORF62, (b) ORF63 with a small deletion, and (c) full-length ORF64. The virus was not impaired for growth in human cells, induced higher levels of neutralizing antibodies in guinea pigs, and was impaired for latency in cotton rats compared with parental virus (p=0.0022). Additional mutants containing the same truncation in ORF62. with or without the ORF63 deletion, were less impaired for latency. A VZV Oka mutant, replicating to similar titers and inducing a comparable immune response as parental virus, but impaired for latency, might serve as a safer vaccine and be less likely to reactivate to cause zoster. (C) 2010 Published by Elsevier Inc. C1 [Ambagala, Aruna P. N.; Krogmann, Tammy; Pesnicak, Lesley; Cohen, Jeffrey I.] NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Qin, Jing] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10,Rm 11N234,10 Ctr Dr,MSC 1888, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This Study was supported by the intramural research program of the National Institute of Allergy and Infectious Diseases. We thank Drs. Paul Kinchington (University of Pittsburgh, Pittsburgh, PA) and William T. Ruyechan (University at Buffalo SUNY, Buffalo, NY) for antibodies to IE62, and Dr. Qingxue Li for assistance with the immunofluorescent focus assay. NR 37 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2010 VL 399 IS 2 BP 194 EP 200 DI 10.1016/j.virol.2010.01.007 PG 7 WC Virology SC Virology GA 566FO UT WOS:000275355700002 PM 20116820 ER PT J AU Ritchie, G Harvey, DJ Feldmann, F Stroeher, U Feldmann, H Royle, L Dwek, RA Rudd, PM AF Ritchie, Gayle Harvey, David J. Feldmann, Friederike Stroeher, Ute Feldmann, Heinz Royle, Louise Dwek, Raymond A. Rudd, Pauline M. TI Identification of N-linked carbohydrates from severe acute respiratory syndrome (SARS) spike glycoprotein SO VIROLOGY LA English DT Article DE SARS; Spike glycoprotein; Glycosylation; N-Linked; Mass Spectrometry; Negative ion fragmentation ID ALPHA-D-MANNOSIDASE; ANGIOTENSIN-CONVERTING ENZYME-2; LASER-DESORPTION IONIZATION; SYNDROME CORONAVIRUS; MASS-SPECTROMETRY; NEGATIVE-IONS; DC-SIGN; FUNCTIONAL RECEPTOR; RAT-LIVER; GLYCANS AB N-glycans were released from the SARS coronavirus (SARS-CoV) spike glycoprotein produced in Vero E6 cells and their structures were determined by a combination of matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, negative ion electrospray collision-induced dissociation time-of-flight mass spectrometry and normal-phase high-performance liquid chromatography with exoglycosidase digestion. Major glycans were high-mannose (Man(5-9)GlcNAC(2)), hybrid and bi-, tri- and tetra-antennary complex with and without bisecting GlcNAc and core fucose. Complex glycans with fewer than the full complement of galactose residues were present and sialyiation was negligible. Treatment with the glucosidase inhibitor N-butyl-deoxynojirimycin (NB-DNJ) inhibited N-glycan processing as evidenced by the appearance of glycans of composition Glc(3)Man(7-9)GlcNAc(2). However, some complex glycans remained suggesting the presence of an alpha-endomannosidase. Our data in tissue culture indicate that inhibition of N-glycan processing may be considered as a therapeutic strategy against SARS CoV infections. (C) 2009 Elsevier Inc. All rights reserved. C1 [Ritchie, Gayle; Harvey, David J.; Dwek, Raymond A.] Univ Oxford, Dept Biochem, Oxford Glycobiol Inst, Oxford OX1 3QU, England. [Feldmann, Friederike; Stroeher, Ute; Feldmann, Heinz] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. [Feldmann, Friederike; Feldmann, Heinz] NIAID, Rocky Mt Labs, Div Intramural Res, NIH, Hamilton, MT 59840 USA. [Stroeher, Ute; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada. [Royle, Louise] Ludger Ltd, Culham Sci Ctr, Abingdon OX14 3EB, Oxon, England. [Rudd, Pauline M.] Univ Coll Dublin, Conway Inst, Natl Inst Bioproc Res & Training, Dublin 4, Ireland. RP Harvey, DJ (reprint author), Univ Oxford, Dept Biochem, Oxford Glycobiol Inst, S Parks Rd, Oxford OX1 3QU, England. EM david.harvey@bioch.ox.ac.uk RI Harvey, David/A-5579-2013 FU Wellcome Trust; Biotechnology and Biological Sciences Research Council; Public Health Agency of Canada (PHAC) FX We thank the Wellcome Trust and the Biotechnology and Biological Sciences Research Council for equipment grants to purchase the Q-TOF and TofSpec mass spectrometers, respectively. We thank the Public Health Agency of Canada (PHAC) for financial support. NR 43 TC 18 Z9 18 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 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2010 VL 399 IS 2 BP 257 EP 269 DI 10.1016/j.virol.2009.12.020 PG 13 WC Virology SC Virology GA 566FO UT WOS:000275355700009 PM 20129637 ER PT J AU Bukreyev, AA DiNapoli, JM Yang, LJ Murphy, BR Collins, PL AF Bukreyev, Alexander A. DiNapoli, Joshua M. Yang, Lijuan Murphy, Brian R. Collins, Peter L. TI Mucosal parainfluenza virus-vectored vaccine against Ebola virus replicates in the respiratory tract of vector-immune monkeys and is immunogenic SO VIROLOGY LA English DT Article DE Virus; Ebola; Vaccine; Mucosal vaccination; Intranasal vaccination; Antibody; Immunity; Vaccine vector; Monkey; Immunogenicity ID INFLUENZA-A VIRUS; PREEXISTING IMMUNITY; NONHUMAN-PRIMATES; SYNCYTIAL VIRUS; T-CELLS; SECONDARY INFECTION; ADENOVIRUS VECTORS; ANTI-AD5 IMMUNITY; IMMUNOGLOBULIN-A; DENDRITIC CELLS AB We previously used human parainfluenza virus type 3 (HPIV3) as a vector to express the Ebola virus (EBOV) GP glycoprotein. The resulting HPIV3/EboGP vaccine was immunogenic and protective against EBOV challenge in a non-human primate model. However, it remained unclear whether the vaccine would be effective in adults due to preexisting immunity to HPIV3. Here, the immunogenicity of HPIV3/EboGP was compared in HPIV3-naive and HPIV3-immune Rhesus monkeys. After a single dose of HPIV3/EboGP, the titers of EBOV-specific serum ELISA or neutralization antibodies were substantially less in HPIV3-immune animals compared to HPIV3-naive animals. However, after two doses, which were previously determined to be required for complete protection against EBOV challenge, the antibody titers were indistinguishable between the two groups. The vaccine virus appeared to replicate, at a reduced level, in the respiratory tract despite the preexisting immunity. This may reflect the known ability of HPIV3 to re-infect and may also reflect the presence of EBOV GP in the vector virion, which confers resistance to neutralization in vitro by HPIV3-specific antibodies. These data suggest that HPIV3/EboGP will be immunogenic in adults as well as children. Published by Elsevier Inc. C1 [Bukreyev, Alexander A.; DiNapoli, Joshua M.; Yang, Lijuan; Murphy, Brian R.; Collins, Peter L.] NIAID, LID, NIH, Bethesda, MD 20892 USA. RP Bukreyev, AA (reprint author), NIAID, LID, NIH, 50 South Dr,Room 6505, Bethesda, MD 20892 USA. EM abukreyev@niaid.nih.gov FU MAID Intramural Program FX We thank Dr. Anthony Sanchez (Centers for Disease Control and Prevention, Atlanta, GA) for providing gamma-irradiated Purified EBOV antigen for ELISA and Dr. Heinz Feldmann (Laboratory of Virology, Rocky Mountain Laboratories, MAID, NIH) for providing VSVAG/ZEBOVGP. We also thank Fatemeh Davoodi (Laboratory of Infectious Diseases, MAID, NIH) for performing HAI assays, as well as Brad Finneyfrock and Dr. Anthony Cook (Bioqual, Inc.), and Stacey Miller (Comparative Medicine Branch, MAID) for their assistance with primate studies. This research was supported by the MAID Intramural Program. NR 43 TC 22 Z9 23 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2010 VL 399 IS 2 BP 290 EP 298 DI 10.1016/j.virol.2010.01.015 PG 9 WC Virology SC Virology GA 566FO UT WOS:000275355700012 PM 20129638 ER PT J AU Pasek, M Boeggeman, E Ramakrishnan, B Qasba, PK AF Pasek, Marta Boeggeman, Elizabeth Ramakrishnan, Boopathy Qasba, Pradman K. TI Galectin-1 as a fusion partner for the production of soluble and folded human beta-1,4-galactosyltransferase-T7 in E. coli SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Protein expression in E coli; Fusion tags; MBP; Galectins; Protein folding; Glycosyltransferases ID MALTOSE-BINDING PROTEIN; ESCHERICHIA-COLI; RECOMBINANT PROTEINS; CATALYTIC DOMAIN; INCLUSION-BODIES; PI INTERACTIONS; EXPRESSION; SOLUBILITY; RECOGNITION; STRATEGIES AB The expression of recombinant proteins in Escherichia coli often leads to inactive aggregated proteins known as the inclusion bodies To date, the best available tool has been the use of fusion tags, including the carbohydrate-binding protein, e g, the maltose-binding protein (MBP) that enhances the solubility of recombinant proteins However, none of these fusion tags work universally with every partner protein We hypothesized that galectins, which are also carbohydrate-binding proteins, may help as fusion partners in folding the mammalian proteins in E coli Here we show for the first time that a small soluble lectin, human galectin-1, one member of a large galectin family, can function as a fusion partner to produce soluble folded recombinant human glycosyltransferase, beta-1,4-galactosyltransferase-7 (beta 4Gal-T7), in E coli. The enzyme beta 4Gal-T7 transfers galactose to xylose during the synthesis of the tetrasaccharide linker sequence attached to a Ser residue of proteoglycans Without a fusion partner. beta 4Gal-T7 is expressed in E colt as inclusion bodies We have designed a new vector construct, pLgals1, from pET-23a that includes the sequence for human galectin-1, followed by the Tev protease cleavage site, a 6 x His-coding sequence, and a multi-cloning site where a cloned gene is inserted After lactose affinity column purification of galectin-1-beta 4Gal-T7 fusion protein, the unique protease cleavage site allows the protein beta 4Gal-T7 to be cleaved from galectin-1 that binds and elutes from UDP-agarose column The eluted protein is enzymatically active, and shows CD spectra comparable to the folded beta 4Gal-T1 The engineered galectin-1 vector could prove to be a valuable tool for expressing other proteins in E coli Published by Elsevier Inc C1 [Pasek, Marta; Boeggeman, Elizabeth; Ramakrishnan, Boopathy; Qasba, Pradman K.] NCI, Struct Glycobiol Sect, SAIC Frederick Inc, CCRNP,CCR, Frederick, MD 21702 USA. [Boeggeman, Elizabeth; Ramakrishnan, Boopathy] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program,Ctr Canc Res, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, SAIC Frederick Inc, CCRNP,CCR, Bldg 469,Room 221, Frederick, MD 21702 USA. FU NCI; NIH [HHSN261200800001E]; CCR FX We thank Dr. Natalia Mercer for the critical reading of the manuscript. This project has been funded in whole or in part with Federal funds from the NCI, NIH under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the view or policies of the Department of HHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. This research was supported [in part] by the Intramural Research Program of the NIH, NCI, CCR. NR 32 TC 11 Z9 11 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 9 PY 2010 VL 394 IS 3 BP 679 EP 684 DI 10.1016/j.bbrc.2010.03.051 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 584WY UT WOS:000276785900042 PM 20226765 ER PT J AU Kotliarov, Y Bozdag, S Cheng, HJ Wuchty, S Zenklusen, JC Fine, HA AF Kotliarov, Yuri Bozdag, Serdar Cheng, Hangjiong Wuchty, Stefan Zenklusen, Jean-Claude Fine, Howard A. TI CNAReporter: a GenePattern pipeline for the generation of clinical reports of genomic alterations SO BMC MEDICAL GENOMICS LA English DT Article ID COPY NUMBER; SNP; HETEROZYGOSITY; ABERRATIONS; MICROARRAYS; ARRAYS; WIDE; CGH AB Background: Genomic copy number alterations are widely associated with a broad range of human tumors and offer the potential to be used as a diagnostic tool. Especially in the emerging era of personalized medicine medical informatics tools that allow the fast visualization and analysis of genomic alterations of a patient's genomic profile for diagnostic and potential treatment purposes increasingly gain importance. Results: We developed CNAReporter, a software tool that allows users to visualize SNP-specific data obtained from Affymetrix arrays and generate PDF-reports as output. We combined standard algorithms for the analysis of chromosomal alterations, utilizing the widely applied GenePattern framework. As an example, we show genome analyses of two patients with distinctly different CNA profiles using the tool. Conclusions: Glioma subtypes, characterized by different genomic alterations, are often treated differently but can be difficult to differentiate pathologically. CNAReporter offers a user-friendly way to visualize and analyse genomic changes of any given tumor genomic profile, thereby leading to an accurate diagnosis and patient-specific treatment. C1 [Kotliarov, Yuri; Bozdag, Serdar; Wuchty, Stefan; Zenklusen, Jean-Claude; Fine, Howard A.] Natl Inst Neurol Disorder & Stroke, Neuro Oncol Branch, NCI, NIH, Bethesda, MD 20892 USA. [Cheng, Hangjiong] NCI, NCI Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD 20852 USA. RP Fine, HA (reprint author), Natl Inst Neurol Disorder & Stroke, Neuro Oncol Branch, NCI, NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Kotliarov, Yuri/B-6938-2017 FU NIH, National Cancer Institute FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute. NR 18 TC 3 Z9 3 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD APR 9 PY 2010 VL 3 AR 11 DI 10.1186/1755-8794-3-11 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 603EG UT WOS:000278190700001 PM 20380730 ER PT J AU Majerciak, V Kruhlak, M Dagur, PK Mccoy, JP Zheng, ZM AF Majerciak, Vladimir Kruhlak, Michael Dagur, Pradeep K. Mccoy, J. Philip, Jr. Zheng, Zhi-Ming TI Caspase-7 Cleavage of Kaposi Sarcoma-associated Herpesvirus ORF57 Confers a Cellular Function against Viral Lytic Gene Expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EFFUSION LYMPHOMA-CELLS; DNA-SEQUENCES; INDUCED APOPTOSIS; PROTEIN; VIRUS; HUMAN-HERPESVIRUS-8; PHOSPHORYLATION; ACTIVATION; PREDICTION; PATHWAYS AB Kaposi sarcoma-associated herpesvirus (KSHV) ORF57 is a viral early protein essential for KSHV multiplication. We found that B cells derived from cavity-based B cell lymphoma with lytic KSHV infection display activation of caspase-8 and cleavage of ORF57 in the cytoplasm by caspase-7 at the aspartate residue at position 33 from the N terminus. Caspase-7 cleavage of ORF57 is prevented by pan-caspase inhibitor z-VAD, caspase-3 and caspase-7 inhibitor z-DEVD, and caspase-7 small interfering RNAs. The caspase-7 cleavage site (30)DETD(33) in ORF57 is not cleavable by caspase-3, although both enzymes use DEXD as a common cleavage site. B cells with lytic KSHV infection and caspase-7 activation exhibited a greatly reduced level of ORF57. A majority of the cells expressing active caspase-7 appeared to have no detectable ORF57 and vice versa. Upon cleavage with caspase-7, ORF57 was deficient in promoting the expression of viral lytic genes. Inhibiting caspase-7 cleavage of ORF57 in KSHV(+) BCBL-1 cells by z-VAD, z-DEVD, or caspase-7 small interfering RNA led to increased expression of viral lytic genes and production of cell-free virus particles. Collectively, our data provide the first compelling evidence that caspase cleavage of ORF57 may represent a cellular function against lytic KSHV infection. C1 [Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Dagur, Pradeep K.; Mccoy, J. Philip, Jr.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), 10 Ctr Dr,Rm 6N106, Bethesda, MD 20892 USA. EM zhengt@mail.nih.gov FU National Cancer Institute, Center for Cancer Research, National Institutes of Health FX This work was supported, in whole or in part, by the National Institutes of Health Intramural Research Program, National Cancer Institute, Center for Cancer Research. NR 50 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 9 PY 2010 VL 285 IS 15 BP 11297 EP 11307 DI 10.1074/jbc.M109.068221 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578IF UT WOS:000276286200036 PM 20159985 ER PT J AU Golden, E Emiliano, A Maudsley, S Windham, BG Carlson, OD Egan, JM Driscoll, I Ferrucci, L Martin, B Mattson, MP AF Golden, Erin Emiliano, Ana Maudsley, Stuart Windham, B. Gwen Carlson, Olga D. Egan, Josephine M. Driscoll, Ira Ferrucci, Luigi Martin, Bronwen Mattson, Mark P. TI Circulating Brain-Derived Neurotrophic Factor and Indices of Metabolic and Cardiovascular Health: Data from the Baltimore Longitudinal Study of Aging SO PLOS ONE LA English DT Article ID CORONARY-ARTERY-DISEASE; BODY-MASS INDEX; PLASMA-CONCENTRATIONS; FUNCTIONAL MODULES; SURVIVAL FACTOR; HUMAN PLATELETS; SEVERE OBESITY; FACTOR BDNF; IN-VITRO; PROTEIN AB Background: Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile. Methodology/Principal Findings: To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age similar to 70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin. Conclusion/Significance: Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined. C1 [Golden, Erin; Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Intramural Res Program, Baltimore, MD 21224 USA. [Emiliano, Ana; Martin, Bronwen] NIA, Metab Unit, Intramural Res Program, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Intramural Res Program, Baltimore, MD 21224 USA. [Windham, B. Gwen; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Carlson, Olga D.; Egan, Josephine M.] NIA, Diabet Sect, Intramural Res Program, Baltimore, MD 21224 USA. [Driscoll, Ira] NIA, Lab Personal & Cognit, Intramural Res Program, Baltimore, MD 21224 USA. RP Golden, E (reprint author), NIA, Cellular & Mol Neurosci Sect, Intramural Res Program, Baltimore, MD 21224 USA. EM martinbro@mail.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural Research Program of the National Institutes of Health (NIH) [5 T32 DK007751-09]; National Institute on Aging FX This work was supported entirely by the Intramural Research Program of the National Institutes of Health (NIH), National Institute on Aging. Ana Emiliano was supported by grant number NIH 5 T32 DK007751-09. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 67 Z9 67 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2010 VL 5 IS 4 AR e10099 DI 10.1371/journal.pone.0010099 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580WU UT WOS:000276482100015 PM 20404913 ER PT J AU Strunk, T Coombs, MRP Currie, AJ Richmond, P Golenbock, DT Stoler-Barak, L Gallington, LC Otto, M Burgner, D Levy, O AF Strunk, Tobias Coombs, Melanie R. Power Currie, Andrew J. Richmond, Peter Golenbock, Douglas T. Stoler-Barak, Liat Gallington, Leighanne C. Otto, Michael Burgner, David Levy, Ofer TI TLR2 Mediates Recognition of Live Staphylococcus epidermidis and Clearance of Bacteremia SO PLOS ONE LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; PHENOL-SOLUBLE MODULIN; CUTTING EDGE; CYTOKINE PRODUCTION; SIGNAL-TRANSDUCTION; IFN-GAMMA; AUREUS; ACTIVATION; CELLS; PHAGOCYTOSIS AB Background: Staphylococcus epidermidis (SE) is a nosocomial pathogen that causes catheter-associated bacteremia in the immunocompromised, including those at the extremes of age, motivating study of host clearance mechanisms. SE-derived soluble components engage TLR2; but additional signaling pathways have also been implicated, and TLR2 can play complex, at times detrimental, roles in host defense against other Staphylococcal spp. The role of TLR2 in responses of primary blood leukocytes to live SE and in clearance of SE bacteremia, the most common clinical manifestation of SE infection, is unknown. Methodology/Principal Findings: We studied TLR2-mediated recognition of live clinical SE strain 1457 employing TLR2-transfected cells, neutralizing anti-TLR antibodies and TLR2-deficient mice. TLR2 mediated SE-induced cytokine production in human embryonic kidney cells, human whole blood and murine primary macrophages, in part via recognition of a soluble TLR2 agonist. After i.v. challenge with SE, early (1 h) cytokine/chemokine production and subsequent clearance of bacteremia (24-48 h) were markedly impaired in TLR2-deficient mice. Conclusions/Significance: TLR2 mediates recognition of live SE and clearance of SE bacteremia in vivo. C1 [Strunk, Tobias; Currie, Andrew J.; Richmond, Peter; Burgner, David] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. [Coombs, Melanie R. Power; Stoler-Barak, Liat; Gallington, Leighanne C.; Levy, Ofer] Childrens Hosp Boston, Div Infect Dis, Boston, MA USA. [Coombs, Melanie R. Power; Levy, Ofer] Harvard Univ, Sch Med, Boston, MA USA. [Golenbock, Douglas T.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Burgner, David] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. RP Strunk, T (reprint author), Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia. EM ofer.levy@childrens.harvard.edu RI Richmond, Peter/G-3379-2012; Gallington, Leighanne/G-9341-2011; Currie, Andrew/C-2778-2015; OI Gallington, Leighanne/0000-0002-0383-7522; Coombs, Melanie/0000-0002-2036-8414; Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [RO1 AI067353-01A1]; Princess Margaret Hospital; Women's and Infants' Research Foundation Western Australia; Clive and Vera Ramaciotti Medical Research Foundation; U. Western Australia; Rebecca Cooper Medical Research Foundation; Channel7 Telethon; European Society for Paediatric Infectious Diseases; National Health and Medical Research Council, Australia; Intramural Research Program of the National Institute of Allergy and Infectious Diseases; U.S. National Institutes of Health; Deutsche Forschungsgemeinschaft [STR1022/1-1]; University of Western Australia; Harvard Club of Australia; Canadian Institutes of Health Research; Children's Health Research Foundation of Western Australia FX Financial support: National Institute of Allergy and Infectious Diseases, National Institutes of Health RO1 AI067353-01A1 (O. L.); Princess Margaret Hospital, Women's and Infants' Research Foundation Western Australia, Clive and Vera Ramaciotti Medical Research Foundation, U. Western Australia, Rebecca Cooper Medical Research Foundation, Channel7 Telethon, European Society for Paediatric Infectious Diseases and the National Health and Medical Research Council, Australia (T. S., A. C., P. R., and D. B.); Intramural Research Program of the National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health (M. O.). T. S. was supported by a Research Fellowship of the Deutsche Forschungsgemeinschaft (STR1022/1-1) and an International Postgraduate Research Scholarship of the University of Western Australia. Support was also provided by fellowships from the Harvard Club of Australia (O. L.), Canadian Institutes of Health Research (M. C.) and the Children's Health Research Foundation of Western Australia (A. J. C.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 30 Z9 30 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 9 PY 2010 VL 5 IS 4 AR e10111 DI 10.1371/journal.pone.0010111 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580WU UT WOS:000276482100022 PM 20404927 ER PT J AU Herbein, G Varin, A AF Herbein, Georges Varin, Audrey TI The macrophage in HIV-1 infection: From activation to deactivation? SO RETROVIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; T-CELL DEPLETION; PERIPHERAL-BLOOD MONOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; GROWTH-FACTOR-BETA; PRIMARY MONONUCLEAR PHAGOCYTES; REGULATES CD4 EXPRESSION; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION AB Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-gamma display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease. C1 [Herbein, Georges; Varin, Audrey] Univ Franche Comte, CHU Besancon, Dept Virol, UPRES EA Pathogens & Inflammat 4266,IFR INSERM 13, F-25030 Besancon, France. [Varin, Audrey] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Herbein, G (reprint author), Univ Franche Comte, CHU Besancon, Dept Virol, UPRES EA Pathogens & Inflammat 4266,IFR INSERM 13, F-25030 Besancon, France. EM georges.herbein@univ-fcomte.fr FU Franche-Comte University; Association for Macrophage and Infection Research (AMIR) FX The work of the authors is supported by institutional funds from the Franche-Comte University and from the Association for Macrophage and Infection Research (AMIR). NR 228 TC 74 Z9 76 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD APR 9 PY 2010 VL 7 AR 33 DI 10.1186/1742-4690-7-33 PG 15 WC Virology SC Virology GA 592VD UT WOS:000277408000001 PM 20380696 ER PT J AU McDaniell, R Lee, BK Song, L Liu, Z Boyle, AP Erdos, MR Scott, LJ Morken, MA Kucera, KS Battenhouse, A Keefe, D Collins, FS Willard, HF Lieb, JD Furey, TS Crawford, GE Iyer, VR Birney, E AF McDaniell, Ryan Lee, Bum-Kyu Song, Lingyun Liu, Zheng Boyle, Alan P. Erdos, Michael R. Scott, Laura J. Morken, Mario A. Kucera, Katerina S. Battenhouse, Anna Keefe, Damian Collins, Francis S. Willard, Huntington F. Lieb, Jason D. Furey, Terrence S. Crawford, Gregory E. Iyer, Vishwanath R. Birney, Ewan TI Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans SO SCIENCE LA English DT Article ID HUMAN GENE-EXPRESSION; PROTEIN CTCF; GENOME; SITES AB The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. C1 [Song, Lingyun; Boyle, Alan P.; Kucera, Katerina S.; Willard, Huntington F.; Furey, Terrence S.; Crawford, Gregory E.] Duke Univ, IGSP, Durham, NC 27708 USA. [McDaniell, Ryan; Lee, Bum-Kyu; Liu, Zheng; Battenhouse, Anna; Iyer, Vishwanath R.] Univ Texas Austin, Ctr Syst & Synthet Biol, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. [Song, Lingyun; Crawford, Gregory E.] Duke Univ, Dept Pediat, Div Med Genet, Durham, NC 27708 USA. [Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Collins, Francis S.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Scott, Laura J.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Keefe, Damian; Birney, Ewan] European Bioinformat Inst, Cambridge CB10 1RQ, England. [Lieb, Jason D.] Univ N Carolina, Dept Biol, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. [Lieb, Jason D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Crawford, GE (reprint author), Duke Univ, IGSP, Durham, NC 27708 USA. EM greg.crawford@duke.edu; vishy@mail.utexas.edu; birney@ebi.ac.uk RI Liu, Zheng/G-2612-2011; Boyle, Alan/I-1848-2014; OI Boyle, Alan/0000-0002-2081-1105; Furey, Terry/0000-0001-5546-9672; Birney, Ewan/0000-0001-8314-8497 FU National Human Genome Research Institute (NHGRI) ENCODE Consortium [U54 HG004563-03]; NHGRI [HG000024] FX We thank T. Severson, F. Ye, and L. Bukovnik at the Duke IGSP Sequencing Core Facility and K. Moon and S. Luo at Illumina for sequencing; S. Tenenbaum and S. Chittur at the State University of New York, Albany, for expression data; J. Lucas and Z. Zhang at Duke for gene expression analysis; the Texas Advanced Computing Center for computational infrastructure; and the 1000 Genomes Project for genotypes. E. B. has been a paid consultant to EagleGenomics, UK. Supported by National Human Genome Research Institute (NHGRI) ENCODE Consortium grant U54 HG004563-03 and NHGRI grant Z01 HG000024. Raw data from this paper are available at Gene Expression Omnibus (GSE15805 and GSE19622) and at the University of California, Santa Cruz (UCSC) Genome Browser. NR 16 TC 190 Z9 193 U1 1 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 9 PY 2010 VL 328 IS 5975 BP 235 EP 239 DI 10.1126/science.1184655 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580OU UT WOS:000276459600044 PM 20299549 ER PT J AU Scruten, E Kovacs-Nolan, J Griebel, PJ Latimer, L Kindrachuk, J Potter, A Babiuk, LA Littel-van den Hurk, SV Napper, S AF Scruten, Erin Kovacs-Nolan, Jennifer Griebel, Philip J. Latimer, Laura Kindrachuk, Jason Potter, Andy Babiuk, Lorne A. Littel-van den Hurk, Sylvia van Drunen Napper, Scott TI Retro-inversion enhances the adjuvant and CpG co-adjuvant activity of host defence peptide Bac2A SO VACCINE LA English DT Article DE Host defence peptides; Vaccine adjuvant; Retro-inversion; Inversion; Peptide stabilization; CpG ODN ID ANTIMICROBIAL PEPTIDES; ANTIBACTERIAL PEPTIDES; CHLAMYDIA-TRACHOMATIS; CATIONIC PEPTIDES; IMMUNE-RESPONSES; LL-37; CATHELICIDIN; RESISTANCE; NEUTROPHILS; MECHANISMS AB Host defence peptides (HDPs) have a variety of potential therapeutic applications, including as vaccine adjuvants, energizing efforts for modification strategies to address their toxicity and instability. Here we compare L, D and RI-Bac2A as vaccine adjuvants. D and RI-Bac2A are equally resistant to proteolytic degradation with no increases in toxicity, however, only RI-Bac2A maintains adjuvant activity of the natural peptide through conserved induction of a Th2 immune response. As HDPs potentiate the adjuvant activity of CpG ODNs, the isomers were also evaluated as co-adjuvants. L-Bac2A has no significant co-adjuvant activity while CpG/RI-Bac2A induces antibody titres significantly higher than CpG (P<0.01), CpG/L-Bac2A (P<0.01) or CpG/D-Bac2A (P<0.01). None of the isomers influence ODN duration or distribution but L and RI-Bac2A promote ODN uptake into B cells and antigen presenting cells. The enhanced adjuvant and co-adjuvant of RI-Bac2A is hypothesized to result from an undefined combination of increased stability and retained biological activity supporting application of retro-inversion to this, and potentially other HDPs. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Scruten, Erin; Kovacs-Nolan, Jennifer; Griebel, Philip J.; Latimer, Laura; Potter, Andy; Littel-van den Hurk, Sylvia van Drunen; Napper, Scott] Univ Saskatchewan, Vaccine & Infect Dis Org, Saskatoon, SK S7N 5E3, Canada. [Babiuk, Lorne A.] Univ Alberta, Edmonton, AB T6G 2J9, Canada. [Kindrachuk, Jason] NIH, Bethesda, MD 20892 USA. RP Napper, S (reprint author), Univ Saskatchewan, Vaccine & Infect Dis Org, 120 Vet Rd, Saskatoon, SK S7N 5E3, Canada. EM scottnapper@usask.ca OI Kindrachuk, Jason/0000-0002-3305-7084 NR 45 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 9 PY 2010 VL 28 IS 17 BP 2945 EP 2956 DI 10.1016/j.vaccine.2010.02.015 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 586CE UT WOS:000276877900005 PM 20193790 ER PT J AU Vaine, M Wang, SX Hackett, A Arthos, J Lu, S AF Vaine, Michael Wang, Shixia Hackett, Anthony Arthos, James Lu, Shan TI Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity SO VACCINE LA English DT Article DE DNA vaccine; Prime-boost; HIV-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODIES; SUBTYPE-B; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEINS; GP120 PROTEIN; VACCINE; INFECTION; CELLS; IMMUNOGENICITY AB Using a gp120 envelope glycoprotein from the JR-FL strain of human immunodeficiency virus-1 (HIV-1) as a model antigen, the goal of the current study was to evaluate the level and quality of antibody responses elicited by different prime-boost vaccination regimens (protein only, DNA only, DNA plus protein) in rabbits. Our data demonstrated that incorporating DNA immunization as a prime in a heterologous prime-boost regimen was able to elicit a more diverse and conformational epitope profile, higher antibody avidity, and improved neutralizing activity than immunization with only protein. Additionally, this improved neutralizing activity was observed in spite of similar antibody specificities and avidities seen when only DNA vaccination was used, providing additional evidence that the use of a combination immunization regimen increases the protective antibody response. Insights gained from the current study confirmed that the heterologous DNA prime-protein boost approach is effective in eliciting not only high level but also improved quality of antigen-specific antibody responses, and thus may offer a new technology platform to develop better and safer subunit vaccines. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Vaine, Michael; Wang, Shixia; Hackett, Anthony; Lu, Shan] Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, Worcester, MA 01605 USA. [Arthos, James] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Lu, S (reprint author), Univ Massachusetts, Sch Med, Dept Med, Lab Nucle Acid Vaccines, Room 304,LRB,364 Plantat St,Lazare Res Bldg, Worcester, MA 01605 USA. EM shan.lu@umassmed.edu OI Lu, Shan/0000-0002-8417-7588 FU US NIH/NIAID [AI065250, AI082274, AI082676]; National Institute of Diabetes and Digestive and Kidney Diseases [5 P30 DK32520] FX This work was supported in part by US NIH/NIAID grants AI065250, AI082274, & AI082676 and grant Number 5 P30 DK32520 from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors would like to acknowledge the generous gifts of mAbs from Drs. Dennis Burton (b12), James Robinson (17b) and Susan Zolla-Pazner (447-52D). Authors would like to thank Dr. Jill M. Grimes Serrano for critical reading and editing of the manuscript. NR 33 TC 52 Z9 54 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 9 PY 2010 VL 28 IS 17 BP 2999 EP 3007 DI 10.1016/j.vaccine.2010.02.006 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 586CE UT WOS:000276877900012 PM 20170767 ER PT J AU Sood, R English, MA Belele, CL Jin, H Bishop, K Haskins, R McKinney, MC Chahal, J Weinstein, BM Wen, ZL Liu, PP AF Sood, Raman English, Milton A. Belele, Christiane L. Jin, Hao Bishop, Kevin Haskins, Rebecca McKinney, Mary Cathleen Chahal, Jagman Weinstein, Brant M. Wen, Zilong Liu, P. Paul TI Development of multilineage adult hematopoiesis in the zebrafish with a runx1 truncation mutation SO BLOOD LA English DT Article ID STEM-CELLS; STEM/PROGENITOR CELLS; TRANSGENIC ZEBRAFISH; DIFFERENTIATION; ENGRAFTMENT; PHENOTYPE; LEUKEMIA; FETAL; AML1 AB Runx1 is required for the emergence of hematopoietic stem cells (HSCs) from hemogenic endothelium during embryogenesis. However, its role in the generation and maintenance of HSCs during adult hematopoiesis remains uncertain. Here, we present analysis of a zebrafish mutant line carrying a truncation mutation, W84X, in runx1. The runx1(W84X/W84X) embryos showed blockage in the initiation of definitive hematopoiesis, but some embryos were able to recover from a larval "bloodless" phase and develop to fertile adults with multilineage hematopoiesis. Using cd41-green fluorescent protein transgenic zebrafish and lineage tracing, we demonstrated that the runx1(W84X/W84X) embryos developed cd41(+) HSCs in the aorta-gonad-mesonephros region, which later migrated to the kidney, the site of adult hematopoiesis. Overall, our data suggest that in zebrafish adult HSCs can be formed without an intact runx1. (Blood. 2010; 115(14): 2806-2809) C1 [Sood, Raman; English, Milton A.; Belele, Christiane L.; Haskins, Rebecca; Liu, P. Paul] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Sood, Raman; Bishop, Kevin; Chahal, Jagman] NHGRI, Zebrafish Core Facil, NIH, Bethesda, MD 20892 USA. [Jin, Hao; Wen, Zilong] Hong Kong Univ Sci & Technol, Dept Biochem, Hong Kong, Hong Kong, Peoples R China. [McKinney, Mary Cathleen; Weinstein, Brant M.] NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Rm 3A26, Bethesda, MD 20892 USA. EM pliu@mail.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU National Human Genome Research Institute; National Institute of Child Health and Human Development, NIH FX This work was supported in part by the Intramural Research Programs of National Human Genome Research Institute and National Institute of Child Health and Human Development, NIH. NR 25 TC 30 Z9 32 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 8 PY 2010 VL 115 IS 14 BP 2806 EP 2809 DI 10.1182/blood-2009-08-236729 PG 4 WC Hematology SC Hematology GA 580MY UT WOS:000276454600014 PM 20154212 ER PT J AU Driscoll, JJ Pelluru, D Lefkimmiatis, K Fulciniti, M Prabhala, RH Greipp, PR Barlogie, B Tai, YT Anderson, KC Shaughnessy, JD Annunziata, CM Munshi, NC AF Driscoll, James J. Pelluru, Dheeraj Lefkimmiatis, Konstantinos Fulciniti, Mariateresa Prabhala, Rao H. Greipp, Philip R. Barlogie, Bart Tai, Yu-Tzu Anderson, Kenneth C. Shaughnessy, John D., Jr. Annunziata, Christina M. Munshi, Nikhil C. TI The sumoylation pathway is dysregulated in multiple myeloma and is associated with adverse patient outcome SO BLOOD LA English DT Article ID NF-KAPPA-B; DNA-REPAIR; SUMO; EXPRESSION; UBIQUITIN; TRANSPLANTATION; DEGRADATION; THERAPY; UBC9; RNF4 AB Multiple myeloma (MM) is a plasma cell neoplasm that proceeds through a premalignant state of monoclonal gammopathy of unknown significance; however, the molecular events responsible for myelomagenesis remain uncharacterized. To identify cellular pathways deregulated in MM, we addressed that sumoylation is homologous to ubiquitination and results in the attachment of the ubiquitin-like protein Sumo onto target proteins. Sumoylation was markedly enhanced in MM patient lysates compared with normal plasma cells and expression profiling indicated a relative induction of sumoylation pathway genes. The Sumo-conjugating enzyme Ube2I, the Sumo-ligase PIAS1, and the Sumo-inducer ARF were elevated in MM patient samples and cell lines. Survival correlated with expression because 80% of patients with low UBE2I and PIAS1 were living 6 years after transplantation, whereas only 45% of patients with high expression survived 6 years. UBE2I encodes the sole Sumo-conjugating enzyme in mammalian cells and cells transfected with a dominant-negative sumoylation-deficient UBE2I mutant exhibited decreased survival after radiation exposure, impaired adhesion to bone marrow stroma cell and decreased bone marrow stroma cell-induced proliferation. UBE2I confers cells with multiple advantages to promote tumorigenesis and predicts decreased survival when combined with PIAS1. The sumoylation pathway is a novel therapeutic target with implications for existing proteasomal-based treatment strategies. (Blood. 2010; 115(14): 2827-2834) C1 [Driscoll, James J.; Annunziata, Christina M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Driscoll, James J.; Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Prabhala, Rao H.; Munshi, Nikhil C.] Vet Adm Boston Healthcare, Dept Res, W Roxbury, MA USA. [Driscoll, James J.; Pelluru, Dheeraj; Fulciniti, Mariateresa; Prabhala, Rao H.; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Driscoll, James J.; Pelluru, Dheeraj; Lefkimmiatis, Konstantinos; Fulciniti, Mariateresa; Prabhala, Rao H.; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Boston, MA USA. [Lefkimmiatis, Konstantinos] Brigham & Womens Hosp, Boston, MA 02115 USA. [Greipp, Philip R.] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Barlogie, Bart; Shaughnessy, John D., Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR 72205 USA. RP Driscoll, JJ (reprint author), NCI, Med Oncol Branch, Bethesda, MD 20892 USA. EM driscollj@mail.nih.gov; nikhil_munshi@dfci.harvard.edu RI Lefkimmiatis, Konstantinos/I-1239-2016; Annunziata, Christina/L-3219-2016 OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866; Annunziata, Christina/0000-0003-2033-6532 FU National Institutes of Health [RO1-124929, P50-100007, PO1-78378]; Myeloma Research Fellow SPORE FX This work was supported in part by the Department of Veterans Affairs Merit Review Awards and the National Institutes of Health (grants RO1-124929, N.C.M.; P50-100007 and PO1-78378, N.C.M., K.C.A.), and a Myeloma Research Fellow SPORE Grant (J.J.D.). NR 38 TC 35 Z9 38 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 8 PY 2010 VL 115 IS 14 BP 2827 EP 2834 DI 10.1182/blood-2009-03-211045 PG 8 WC Hematology SC Hematology GA 580MY UT WOS:000276454600017 PM 19965618 ER PT J AU Jourdan, F Leese, MP Dohle, W Hamel, E Ferrandis, E Newman, SP Purohit, A Reed, MJ Potter, BVL AF Jourdan, Fabrice Leese, Mathew P. Dohle, Wolfgang Hamel, Ernest Ferrandis, Eric Newman, Simon P. Purohit, Atul Reed, Michael J. Potter, Barry V. L. TI Synthesis, Antitubulin, and Antiproliferative SAR of Analogues of 2-Methoxyestradiol-3,17-O,O-bis-sulfamate SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; INHIBITS TUBULIN POLYMERIZATION; ENDOGENOUS MAMMALIAN METABOLITE; MULTITARGETED ANTITUMOR AGENTS; IN-VITRO; STEROID SULFATASE; ANTICANCER ACTIVITY; COLCHICINE SITE; VIVO; ANGIOGENESIS AB The synthesis and antiproliferative activity of analogues of estradiol 3,17-O,O-bis-sulfamates (E2bisMATEs) are discussed. Modifications of the C-17 substituent reveal that an H-bond acceptor is essential for high antiproliferative activity. The local environment in which this H-bond acceptor lies can be varied to an extent. The C-17-oxygen linker can be deleted or substituted with an electronically neutral methylene group, and replacement of the terminal NH(2) with a methyl group is also acceptable. Mesylates 10 and 14 prove equipotent to the E2bisMATEs 2 and 3, while sulfones 20 and 35 display enhanced in vitro antiproliferative activity. In addition, the SAR of 2-substituted estradiol-3-O-sulfamate derivatives as inhibitors of tubulin polymerization has been established for the first time. These agents inhibit the binding of radiolabeled colchicine to tubulin. C1 [Jourdan, Fabrice; Leese, Mathew P.; Dohle, Wolfgang; Potter, Barry V. L.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Jourdan, Fabrice; Leese, Mathew P.; Dohle, Wolfgang; Potter, Barry V. L.] Univ Bath, Sterix Ltd, Bath BA2 7AY, Avon, England. [Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. [Ferrandis, Eric] Inst Rech Henri Beaufour, F-91966 Les Ulis, France. [Purohit, Atul; Reed, Michael J.] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, London W2 1NY, England. RP Potter, BVL (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. EM B.V.L.Potter@bath.ac.uk RI Potter, Barry/A-1845-2012 FU Sterix Ltd. FX This work was supported by Sterix Ltd., a member of the IPSEN Group. We thank Alison Smith for technical support and the NCI DTP program for providing in vitro screening resources. We thank Dr. G. R. Pettit, Arizona State University, for providing CA-4. NR 37 TC 26 Z9 26 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 8 PY 2010 VL 53 IS 7 BP 2942 EP 2951 DI 10.1021/jm9018806 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 575VC UT WOS:000276096300022 PM 20225862 ER PT J AU Pfefferkorn, CM Lee, JC AF Pfefferkorn, Candace M. Lee, Jennifer C. TI Tryptophan Probes at the a-Synuclein and Membrane Interface SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID BOUND ALPHA-SYNUCLEIN; AMPHIPATHIC HELICAL PEPTIDES; ENERGY-TRANSFER KINETICS; PARKINSONS-DISEASE; VESICLE PERMEABILIZATION; ALZHEIMERS-DISEASE; NMR-SPECTROSCOPY; FIBRIL FORMATION; EXTENDED HELIX; PROTEIN-A AB Understanding how environmental factors affect the conformational dynamics of alpha-synuclein (alpha-syn) is of great importance because the accumulation and deposit of aggregated alpha-syn in the brain are intimately connected to Parkinson's disease etiology. Measurements of steady-state and time-resolved fluorescence of single tryptophan-containing alpha-syn variants have revealed distinct phospholipid vesicle and micelle interactions at residues 4, 39, 94, and 125. Our circular dichroism data confirm that Trp mutations do not affect alpha-syn membrane binding properties (apparent association constant K(a)(app) similar to 1 x 10(7) M(-1) for all synucleins) saturating at an estimated lipid-to-protein molar ratio of 380 or approximately 120 proteins covering similar to 7% of the surface area of an 80 nm diameter vesicle. Fluorophores at positions 4 and 94 are the most sensitive to the lipid bilayer with pronounced spectral blue-shifts (W4: Delta lambda(max) similar to 23 nm; W94: Delta lambda(max) similar to 10 nm) and quantum yield increases (W4, W94: similar to 3 fold), while W39 and W125 remain primarily water-exposed. Time-resolved fluorescence data show that all sites (except W125) have subpopulations that interact with the membrane. C1 [Pfefferkorn, Candace M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. EM leej4@mail.nih.gov RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU National Institutes of Health, National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Heart, Lung, and Blood Institute. We thank Dr. Hank Fates (Laboratory of Applied Mass Spectrometry) for technical assistance with ESI-MS, Myoung-Soon Hong (Laboratory of Cell Biology), Dr. Mathew Daniels, and Patricia Connelly (Electron Microscopy Core Facility) for technical assistance with EM, Dr. Grzegorz Piszczek (Biophysical Facility) for assistance with the dynamic light scattering measurements, and Michel de Messieres for assistance with computer modeling. NR 71 TC 35 Z9 35 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 8 PY 2010 VL 114 IS 13 BP 4615 EP 4622 DI 10.1021/jp908092e PG 8 WC Chemistry, Physical SC Chemistry GA 575VF UT WOS:000276096600027 PM 20229987 ER PT J AU Zalzman, M Falco, G Sharova, LV Nishiyama, A Thomas, M Lee, SL Stagg, CA Hoang, HG Yang, HT Indig, FE Wersto, RP Ko, MSH AF Zalzman, Michal Falco, Geppino Sharova, Lioudmila V. Nishiyama, Akira Thomas, Marshall Lee, Sung-Lim Stagg, Carole A. Hoang, Hien G. Yang, Hsih-Te Indig, Fred E. Wersto, Robert P. Ko, Minoru S. H. TI Zscan4 regulates telomere elongation and genomic stability in ES cells SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; SISTER-CHROMATID EXCHANGE; DOUBLE-STRAND BREAKS; MOUSE EMBRYOS; DNA; LINES; RECOMBINATION; EXPRESSION; CULTURE; LENGTH AB Exceptional genomic stability is one of the hallmarks of mouse embryonic stem (ES) cells. However, the genes contributing to this stability remain obscure. We previously identified Zscan4 as a specific marker for two-cell embryo and ES cells. Here we show that Zscan4 is involved in telomere maintenance and long-term genomic stability in ES cells. Only 5% of ES cells express Zscan4 at a given time, but nearly all ES cells activate Zscan4 at least once during nine passages. The transient Zscan4-positive state is associated with rapid telomere extension by telomere recombination and upregulation of meiosis-specific homologous recombination genes, which encode proteins that are colocalized with ZSCAN4 on telomeres. Furthermore, Zscan4 knockdown shortens telomeres, increases karyotype abnormalities and spontaneous sister chromatid exchange, and slows down cell proliferation until reaching crisis by passage eight. Together, our data show a unique mode of genome maintenance in ES cells. C1 [Zalzman, Michal; Falco, Geppino; Sharova, Lioudmila V.; Nishiyama, Akira; Thomas, Marshall; Lee, Sung-Lim; Stagg, Carole A.; Hoang, Hien G.; Yang, Hsih-Te; Ko, Minoru S. H.] NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. [Indig, Fred E.; Wersto, Robert P.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genom & Aging Sect, Genet Lab, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 FU National Institute on Aging, National Institutes of Health FX We would like to thank T. Hamatani, Y. Nakatake, M. Monti, L. Xin, B. Binder and A. A. Sharov for discussion; Y. Piao, C. Nguyen, D. Eckley, I. Goldberg, D. Dudekula and I. Stanghellini for technical assistance; P. Soriano for providing ROSA26-floxed LacZ cells; and H. Niwa for providing ROSA-tet-inducible system. This work was entirely supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 52 TC 123 Z9 124 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 2010 VL 464 IS 7290 BP 858 EP U66 DI 10.1038/nature08882 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579TM UT WOS:000276397300030 PM 20336070 ER PT J AU Wollert, T Hurley, JH AF Wollert, Thomas Hurley, James H. TI Molecular mechanism of multivesicular body biogenesis by ESCRT complexes SO NATURE LA English DT Article ID UBIQUITIN-BINDING DOMAINS; ENDOSOME-ASSOCIATED COMPLEX; III COMPLEX; IN-VITRO; MACHINERY; PROTEINS; ALIX; COMPARTMENT; CLATHRIN; BODIES AB When internalized receptors and other cargo are destined for lysosomal degradation, they are ubiquitinated and sorted by the endosomal sorting complex required for transport (ESCRT) complexes 0, I, II and III into multivesicular bodies. Multivesicular bodies are formed when cargo-rich patches of the limiting membrane of endosomes bud inwards by an unknown mechanism and are then cleaved to yield cargo-bearing intralumenal vesicles. The biogenesis of multivesicular bodies was reconstituted and visualized using giant unilamellar vesicles, fluorescent ESCRT-0, -I, -II and -III complexes, and a membrane-tethered fluorescent ubiquitin fusion as a model cargo. Here we show that ESCRT-0 forms domains of clustered cargo but does not deform membranes. ESCRT-I and ESCRT-II in combination deform the membrane into buds, in which cargo is confined. ESCRT-I and ESCRT-II localize to the bud necks, and recruit ESCRT-0-ubiquitin domains to the buds. ESCRT-III subunits localize to the bud neck and efficiently cleave the buds to form intralumenal vesicles. Intralumenal vesicles produced in this reaction contain the model cargo but are devoid of ESCRTs. The observations explain how the ESCRTs direct membrane budding and scission from the cytoplasmic side of the bud without being consumed in the reaction. C1 [Wollert, Thomas; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov OI Wollert, Thomas/0000-0001-9732-4789 FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Intramural AIDS Targeted Antiviral Program; EMBO FX We thank E. Boura for producing the CFP-Ub and GFP-Ub, J. Lippincott-Schwartz for microscope access, B. Wendland for a yeast strain and advice, and W. Prinz for comments on the manuscript. This work was funded by the Intramural Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and Intramural AIDS Targeted Antiviral Program to J. H. H. and an EMBO long-term fellowship to T. W. NR 52 TC 271 Z9 277 U1 3 U2 58 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 2010 VL 464 IS 7290 BP 864 EP U73 DI 10.1038/nature08849 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579TM UT WOS:000276397300031 PM 20305637 ER PT J AU vonHoldt, BM Pollinger, JP Lohmueller, KE Han, EJ Parker, HG Quignon, P Degenhardt, JD Boyko, AR Earl, DA Auton, A Reynolds, A Bryc, K Brisbin, A Knowles, JC Mosher, DS Spady, TC Elkahloun, A Geffen, E Pilot, M Jedrzejewski, W Greco, C Randi, E Bannasch, D Wilton, A Shearman, J Musiani, M Cargill, M Jones, PG Qian, ZW Huang, W Ding, ZL Zhang, YP Bustamante, CD Ostrander, EA Novembre, J Wayne, RK AF vonHoldt, Bridgett M. Pollinger, John P. Lohmueller, Kirk E. Han, Eunjung Parker, Heidi G. Quignon, Pascale Degenhardt, Jeremiah D. Boyko, Adam R. Earl, Dent A. Auton, Adam Reynolds, Andy Bryc, Kasia Brisbin, Abra Knowles, James C. Mosher, Dana S. Spady, Tyrone C. Elkahloun, Abdel Geffen, Eli Pilot, Malgorzata Jedrzejewski, Wlodzimierz Greco, Claudia Randi, Ettore Bannasch, Danika Wilton, Alan Shearman, Jeremy Musiani, Marco Cargill, Michelle Jones, Paul G. Qian, Zuwei Huang, Wei Ding, Zhao-Li Zhang, Ya-Ping Bustamante, Carlos D. Ostrander, Elaine A. Novembre, John Wayne, Robert K. TI Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication SO NATURE LA English DT Article ID LINKAGE DISEQUILIBRIUM; POPULATION-STRUCTURE; MITOCHONDRIAL-DNA; ANCIENT DNA; WOLVES; ORIGIN; EAST; WILD; ASSOCIATION; SELECTION AB Advances in genome technology have facilitated a new understanding of the historical and genetic processes crucial to rapid phenotypic evolution under domestication(1,2). To understand the process of dog diversification better, we conducted an extensive genome-wide survey of more than 48,000 single nucleotide polymorphisms in dogs and their wild progenitor, the grey wolf. Here we show that dog breeds share a higher proportion of multi-locus haplotypes unique to grey wolves from the Middle East, indicating that they are a dominant source of genetic diversity for dogs rather than wolves from east Asia, as suggested by mitochondrial DNA sequence data(3). Furthermore, we find a surprising correspondence between genetic and phenotypic/functional breed groupings but there are exceptions that suggest phenotypic diversification depended in part on the repeated crossing of individuals with novel phenotypes. Our results show that Middle Eastern wolves were a critical source of genome diversity, although interbreeding with local wolf populations clearly occurred elsewhere in the early history of specific lineages. More recently, the evolution of modern dog breeds seems to have been an iterative process that drew on a limited genetic toolkit to create remarkable phenotypic diversity. C1 [vonHoldt, Bridgett M.; Pollinger, John P.; Knowles, James C.; Novembre, John; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. [Lohmueller, Kirk E.; Degenhardt, Jeremiah D.; Boyko, Adam R.; Auton, Adam; Reynolds, Andy; Bryc, Kasia; Brisbin, Abra; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Han, Eunjung] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 14853 USA. [Parker, Heidi G.; Quignon, Pascale; Mosher, Dana S.; Spady, Tyrone C.; Elkahloun, Abdel; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Earl, Dent A.] Univ Calif Santa Cruz, Dept Biomol Engn, Santa Cruz, CA 95064 USA. [Geffen, Eli] Tel Aviv Univ, Dept Zool, IL-69978 Tel Aviv, Israel. [Pilot, Malgorzata] Polish Acad Sci, Museum Zool, PL-00679 Warsaw, Poland. [Pilot, Malgorzata] Polish Acad Sci, Inst Zool, PL-00679 Warsaw, Poland. [Jedrzejewski, Wlodzimierz] Polish Acad Sci, Mammal Res Inst, PL-17230 Bialowieza, Poland. [Greco, Claudia; Randi, Ettore] ISPRA, I-40064 Ozzano Emilia B, Italy. [Bannasch, Danika] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA. [Wilton, Alan; Shearman, Jeremy] Univ New S Wales, Clive & Vera Ramaciotti Ctr Gene Funct Anal, Sydney, NSW 2052, Australia. [Wilton, Alan; Shearman, Jeremy] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia. [Musiani, Marco] Univ Calgary, Fac Environm Design, Calgary, AB T2N 1N4, Canada. [Cargill, Michelle] Affymetrix Corp, Santa Clara, CA 95051 USA. [Jones, Paul G.] WALTHAM Ctr Pet Nutr, Waltham On The Worlds LE14 4RT, Leics, England. [Qian, Zuwei; Huang, Wei] AZIA Ctr, Affymetrix Asia Pacific Sci Affairs & Collaborat, Shanghai 200120, Peoples R China. [Ding, Zhao-Li] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Kunming 650091, Peoples R China. [Zhang, Ya-Ping] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Peoples R China. [Novembre, John] Univ Calif Los Angeles, Interdepartmental Program Bioinformat, Los Angeles, CA 90095 USA. RP Wayne, RK (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, 621 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM rwayne@ucla.edu RI Shearman, Jeremy/F-1618-2010; Wilton, Alan/C-2430-2011; Novembre, John/G-1339-2011; OI Greco, Claudia/0000-0002-8678-0890; Ostrander, Elaine/0000-0001-6075-9738 FU NSF; NIH; Polish Ministry of Science and Higher Education; European Nature Heritage Fund EURONATUR; National Basic Research Program of China; Chinese Academy of Sciences; Searle Scholars Program; National Human Genome Research Institute; Foundation for Polish Science FX Grants from NSF and NIH (R. K. W.; C. D. B. and J.N.), the Polish Ministry of Science and Higher Education (M. P. and W.J.), European Nature Heritage Fund EURONATUR (W.J.), National Basic Research Program of China (Y.-p.Z.), and Chinese Academy of Sciences (Y.-p.Z.) supported this research. J.N. was supported by the Searle Scholars Program. B.M.vH. was supported by a NIH Training Grant in Genomic Analysis and Interpretation. K. E. L. was supported by a NSF Graduate Research Fellowship. E.A.O., D. S. M., T. C. S., A. E. and H. G. P. are supported by the intramural program of the National Human Genome Research Institute. M. P. was supported by the Foundation for Polish Science. Wolf samples from central and eastern Europe and Turkey were collected as a result of a continuing project on genetic differentiation in Eurasian wolves. We thank the project participants (B. Jedrzejewska, V. E. Sidorovich, M. Shkvyrya, I. Dikiy, E. Tsingarskaya and S. Nowak) for their permission to use 72 samples for this study. We acknowledge R. Hefner and the Zoological collection at Tel Aviv University for Israeli wolf samples. We thank the American Kennel Club (AKC) for the dog images reproduced in Fig. 1. We also gratefully acknowledge the dog owners who generously provided samples, the AKC Canine Health Foundation, and Affymetrix Corporation. We thank B. Van Valkenburgh, K.-P. Koepfli, D. Stahler and D. Smith for reviewing the manuscript. NR 37 TC 277 Z9 284 U1 47 U2 319 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 8 PY 2010 VL 464 IS 7290 BP 898 EP U109 DI 10.1038/nature08837 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579TM UT WOS:000276397300039 PM 20237475 ER PT J AU Roberts, JM Myatt, L Spong, CY Thom, EA Hauth, JC Leveno, KJ Pearson, GD Wapner, RJ Varner, MW Thorp, JM Mercer, BM Peaceman, AM Ramin, SM Carpenter, MW Samuels, P Sciscione, A Harper, M Smith, WJ Saade, G Sorokin, Y Anderson, GB AF Roberts, James M. Myatt, Leslie Spong, Catherine Y. Thom, Elizabeth A. Hauth, John C. Leveno, Kenneth J. Pearson, Gail D. Wapner, Ronald J. Varner, Michael W. Thorp, John M., Jr. Mercer, Brian M. Peaceman, Alan M. Ramin, Susan M. Carpenter, Marshall W. Samuels, Philip Sciscione, Anthony Harper, Margaret Smith, Wendy J. Saade, George Sorokin, Yoram Anderson, Garland B. CA Eunice Kennedy Shriver Natl Inst C TI Vitamins C and E to Prevent Complications of Pregnancy-Associated Hypertension. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID OXIDATIVE STRESS; RANDOMIZED-TRIAL; CLINICAL-TRIALS; PREECLAMPSIA; WOMEN; RISK; PROTEINURIA; RATIO AB Background: Oxidative stress has been proposed as a mechanism linking the poor placental perfusion characteristic of preeclampsia with the clinical manifestations of the disorder. We assessed the effects of antioxidant supplementation with vitamins C and E, initiated early in pregnancy, on the risk of serious adverse maternal, fetal, and neonatal outcomes related to pregnancy-associated hypertension. Methods: We conducted a multicenter, randomized, double-blind trial involving nulliparous women who were at low risk for preeclampsia. Women were randomly assigned to begin daily supplementation with 1000 mg of vitamin C and 400 IU of vitamin E or matching placebo between the 9th and 16th weeks of pregnancy. The primary outcome was severe pregnancy-associated hypertension alone or severe or mild hypertension with elevated liver-enzyme levels, thrombocytopenia, elevated serum creatinine levels, eclamptic seizure, medically indicated preterm birth, fetal-growth restriction, or perinatal death. Results: A total of 10,154 women underwent randomization. The two groups were similar with respect to baseline characteristics and adherence to the study drug. Outcome data were available for 9969 women. There was no significant difference between the vitamin and placebo groups in the rates of the primary outcome (6.1% and 5.7%, respectively; relative risk in the vitamin group, 1.07; 95% confidence interval [CI], 0.91 to 1.25) or in the rates of preeclampsia (7.2% and 6.7%, respectively; relative risk, 1.07; 95% CI, 0.93 to 1.24). Rates of adverse perinatal outcomes did not differ significantly between the groups. Conclusions: Vitamin C and E supplementation initiated in the 9th to 16th week of pregnancy in an unselected cohort of low-risk, nulliparous women did not reduce the rate of adverse maternal or perinatal outcomes related to pregnancy-associated hypertension (ClinicalTrials.gov number, NCT00135707). N Engl J Med 2010;362:1282-91. C1 [Roberts, James M.] Univ Pittsburgh, Dept Obstet, Pittsburgh, PA 15260 USA. [Roberts, James M.] Univ Pittsburgh, Dept Gynecol, Pittsburgh, PA USA. [Myatt, Leslie] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Pearson, Gail D.] NHLBI, Bethesda, MD 20892 USA. [Thom, Elizabeth A.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Hauth, John C.] Univ Alabama, Birmingham, AL USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Wapner, Ronald J.] Columbia Univ, New York, NY USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Mercer, Brian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Carpenter, Marshall W.] Brown Univ, Providence, RI 02912 USA. [Samuels, Philip] Ohio State Univ, Columbus, OH 43210 USA. [Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA. [Smith, Wendy J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Saade, George] Univ Texas Med Branch, Galveston, TX USA. [Anderson, Garland B.] Med Ctr, Galveston, TX USA. RP Roberts, JM (reprint author), Univ Pittsburgh, Dept Obstet, Pittsburgh, PA 15260 USA. RI Samuels, Philip/E-4011-2011; Varner, Michael/K-9890-2013; OI Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR000080, M01 RR000080-45, M01 RR00080, UL1 RR024153, UL1 RR024153-05, UL1 RR024989, UL1 RR024989-03]; NICHD NIH HHS [HD40512, HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40544, HD40545, HD40560, HD53097, HD53118, R24 HD050924, U01 HD036801, U10 HD021410, U10 HD021410-22, U10 HD027860, U10 HD027860-09, U10 HD027869, U10 HD027869-10S1, U10 HD027915, U10 HD027915-19, U10 HD027917, U10 HD027917-18, U10 HD034116, U10 HD034116-13, U10 HD034136, U10 HD034136-10S2, U10 HD034208, U10 HD034208-12, U10 HD036801, U10 HD036801-11, U10 HD040485, U10 HD040485-01, U10 HD040500, U10 HD040500-11, U10 HD040512, U10 HD040512-11, U10 HD040544, U10 HD040544-01, U10 HD040545, U10 HD040545-11, U10 HD040560, U10 HD040560-01, U10 HD053097, U10 HD053097-06, U10 HD053118, U10 HD053118-06, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560, UG1 HD053097] NR 27 TC 181 Z9 191 U1 0 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 8 PY 2010 VL 362 IS 14 BP 1282 EP 1291 DI 10.1056/NEJMoa0908056 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 579SN UT WOS:000276393700007 PM 20375405 ER PT J AU Sun, S Francis, J Sapsford, KE Kostov, Y Rasooly, A AF Sun, Steven Francis, Jesse Sapsford, Kim E. Kostov, Yordan Rasooly, Avraham TI Multi-wavelength spatial LED illumination based detector for in vitro detection of botulinum neurotoxin A activity SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE LED; Electroluminescent excitation; CCD; Fluorescence; Forster Resonance Energy Transfer (FRET); Botulinum neurotoxin A; Biodetection ID LINKED-IMMUNOSORBENT-ASSAY; ARRAY BIOSENSOR; RAPID DETECTION; SEROTYPE-A; NEUROTRANSMITTER RELEASE; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MEMBRANE-PROTEIN; MOUSE BIOASSAY; B NEUROTOXIN AB A portable and rapid detection system for the activity analysis of botulinum neurotoxins (BoNT) is needed for food safety and bio-security applications. To improve BoNT activity detection, a previously designed portable charge-coupled device (CCD) based detector was modified and equipped with a higher intensity more versatile multi-wavelength spatial light-emitting diode (LED) illumination, a faster CCD detector and the capability to simultaneously detect 30 samples. A FITC/DABCYL Forster Resonance Energy Transfer (FRET)-labeled peptide substrate (SNAP-25), with BoNT-A target cleavage site sequence was used to measure BoNT-A light chain (LcA) activity through the FITC fluorescence increase that occurs upon peptide substrate cleavage. For fluorescence excitation, a multi-wavelength spatial LED illuminator was used and compared to our previous electroluminescent (EL) strips. The LED illuminator was equipped with blue, green, red and white LEDs, covering a spectrum of 450-680 nm (red 610-650 nm, green 492-550 nm, blue 450-495 nm, and white LED 440-680 nm). In terms of light intensity, the blue LED was found to be similar to 80-fold higher than the previously used blue EL strips. When measuring the activity of LcA the CCD detector limit of detection (LOD) was found to be 0.08 nM LcA for both the blue LED (2 s exposure) and the blue EL (which require >= 60s exposure) while the limits of quantitation (LOQ) is about 1 nM. The LOD for white LED was higher at 1.4 nM while the white EL was not used for the assay due to a high variable background. Unlike the weaker intensity EL illumination the high intensity LED illumination enabled shorter exposure times and allowed multi-wavelength illumination without the need to physically change the excitation strip, thus making spectrum excitation of multiple fluorophores possible increasing the versatility of the detector platform for a variety of optical detection assays. Published by Elsevier B.V. C1 [Rasooly, Avraham] NCI, Rockville, MD 20892 USA. [Sun, Steven; Sapsford, Kim E.; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Sun, Steven; Francis, Jesse; Kostov, Yordan] Univ Maryland Baltimore Cty, Baltimore, MD 21227 USA. RP Rasooly, A (reprint author), NCI, Rockville, MD 20892 USA. EM rasoolya@mail.nih.gov FU Office of Public Health Emergency Preparedness (OPHEP) [IAG 224-05-655]; FDA [HHSF223200610765P] FX This work was supported in part by the Office of Public Health Emergency Preparedness (OPHEP) IAG 224-05-655 (to A. Rasooly) and by FDA contract HHSF223200610765P (to Dr. Yordan Rostov). NR 50 TC 18 Z9 18 U1 1 U2 10 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD APR 8 PY 2010 VL 146 IS 1 BP 297 EP 306 DI 10.1016/j.snb.2010.02.009 PG 10 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 586UA UT WOS:000276937800046 PM 20498728 ER PT J AU He, YZ Blackford, JA Kohn, EC Simons, SS AF He, Yuanzheng Blackford, John A., Jr. Kohn, Elise C. Simons, S. Stoney, Jr. TI STAMP alters the growth of transformed and ovarian cancer cells SO BMC CANCER LA English DT Article ID DOSE-RESPONSE CURVE; GENE-EXPRESSION; RECEPTOR; TRANSCRIPTION; REPRESSION; STATISTICS; MODULATION; P300; INVOLVEMENT; INDUCTION AB Background: Steroid receptors play major roles in the development, differentiation, and homeostasis of normal and malignant tissue. STAMP is a novel coregulator that not only enhances the ability of p160 coactivator family members TIF2 and SRC-1 to increase gene induction by many of the classical steroid receptors but also modulates the potency (or EC(50)) of agonists and the partial agonist activity of antisteroids. These modulatory activities of STAMP are not limited to gene induction but are also observed for receptor-mediated gene repression. However, a physiological role for STAMP remains unclear. Methods: The growth rate of HEK293 cells stably transfected with STAMP plasmid and overexpressing STAMP protein is found to be decreased. We therefore asked whether different STAMP levels might also contribute to the abnormal growth rates of cancer cells. Panels of different stage human cancers were screened for altered levels of STAMP mRNA. Those cancers with the greatest apparent changes in STAMP mRNA were pursued in cultured cancer cell lines. Results: Higher levels of STAMP are shown to have the physiologically relevant function of reducing the growth of HEK293 cells but, unexpectedly, in a steroid-independent manner. STAMP expression was examined in eight human cancer panels. More extensive studies of ovarian cancers suggested the presence of higher levels of STAMP mRNA. Lowering STAMP mRNA levels with siRNAs alters the proliferation of several ovarian cancer tissue culture lines in a cell line-specific manner. This cell line-specific effect of STAMP is not unique and is also seen for the conventional effects of STAMP on glucocorticoid receptor-regulated gene transactivation. Conclusions: This study indicates that a physiological function of STAMP in several settings is to modify cell growth rates in a manner that can be independent of steroid hormones. Studies with eleven tissue culture cell lines of ovarian cancer revealed a cell line-dependent effect of reduced STAMP mRNA on cell growth rates. This cell-line dependency is also seen for STAMP effects on glucocorticoid receptor-mediated transactivation. These preliminary findings suggest that further studies of STAMP in ovarian cancer may yield insight into ovarian cancer proliferation and may be useful in the development of biomarker panels. C1 [He, Yuanzheng; Blackford, John A., Jr.; Simons, S. Stoney, Jr.] NIDDK, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [He, Yuanzheng] Van Andel Inst, Lab Struct Sci, Grand Rapids, MI 49503 USA. [Kohn, Elise C.] NCI, Mol Signaling Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov FU NIH, NIDDK; Center for Cancer Research, NCI, NIH FX Acknowledgements: We thank Lei Bao (Virginia Tech, Blacksburg, Virginia) for assistance with the GEO and Bruce M. Raaka and Elizabeth Geras-Raaka (NIDDK/NIH) for help with the FACS and cell counting. This research was supported by the Intramural Research Program of the NIH, NIDDK and the Center for Cancer Research, NCI, NIH. NR 32 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 7 PY 2010 VL 10 AR 128 DI 10.1186/1471-2407-10-128 PG 11 WC Oncology SC Oncology GA 587QP UT WOS:000277007800002 PM 20374646 ER PT J AU Chen, M Chen, H Nguyen, A Gupta, D Wang, J Lai, EW Pacak, K Gavrilova, O Quon, MJ Weinstein, LS AF Chen, Min Chen, Hui Nguyen, Annie Gupta, Divakar Wang, Jie Lai, Edwin W. Pacak, Karel Gavrilova, Oksana Quon, Michael J. Weinstein, Lee S. TI G(s)alpha Deficiency in Adipose Tissue Leads to a Lean Phenotype with Divergent Effects on Cold Tolerance and Diet-Induced Thermogenesis SO CELL METABOLISM LA English DT Article ID HIGH-FAT DIETS; GS-ALPHA GENE; INSULIN-RESISTANCE; INDUCED OBESITY; UCP1-INDEPENDENT THERMOGENESIS; MUSCLE MITOCHONDRIA; ENERGY-EXPENDITURE; MICE LACKING; GNAS GENE; PROTEIN AB G(s)alpha, the G protein that mediates receptor-stimulated cAMP generation, has been implicated as a regulator of adipogenesis and adipose tissue function. Heterozygous G(s)alpha mutations lead to obesity in Albright hereditary osteodystrophy (AHO) patients and in mice. In this study, we generated mice with adipose-specific G(s)alpha deficiency. Heterozygotes had 50% loss of G(s)alpha expression in adipose tissue and no obvious phenotype, suggesting that adipose-specific G(s)alpha deficiency is not the cause of obesity in AHO. Homozygotes (FGsKO) had severely reduced adipose tissue, indicating that G(s)alpha is required for adipogenesis. Although FGsKO mice had impaired cold tolerance and reduced responsiveness of brown adipose tissue (BAT) to sympathetic signaling, diet-induced thermogenesis and fatty acid oxidation in skeletal muscle were increased. In normal mice, high-fat diet raised sympathetic nerve activity in muscle, but not in BAT. Our results show that cold- and diet-induced thermogenesis may occur in separate tissues, especially when BAT function is impaired. C1 [Chen, Min; Nguyen, Annie; Gupta, Divakar; Wang, Jie; Weinstein, Lee S.] NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. [Chen, Hui; Quon, Michael J.] Natl Ctr Complementary & Alternat Med, Clin Invest Lab, Diabet Unit, Bethesda, MD 20892 USA. [Lai, Edwin W.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. [Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA. RP Chen, M (reprint author), NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. EM minc@intra.niddk.nih.gov; leew@mail.nih.gov OI Quon, Michael/0000-0002-9601-9915 FU NIDDK, NICHD and NCCAM, NIH FX This study was supported by the Intramural Research Programs of NIDDK, NICHD and NCCAM, NIH. We thank B.B. Kahn for providing aP2-cre mice and W. Jou, S. Pack, and R. Vinitsky for technical support. NR 50 TC 20 Z9 21 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR 7 PY 2010 VL 11 IS 4 BP 320 EP 330 DI 10.1016/j.cmet.2010.02.013 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 581TE UT WOS:000276546700014 PM 20374964 ER PT J AU Stasevich, TJ Mueller, F Brown, DT McNally, JG AF Stasevich, Timothy J. Mueller, Florian Brown, David T. McNally, James G. TI Dissecting the binding mechanism of the linker histone in live cells: an integrated FRAP analysis SO EMBO JOURNAL LA English DT Article DE cooperativity; fluorescence imaging; FRAP; in vivo binding; linker histone ID QUANTITATIVE FLUORESCENCE RECOVERY; NUCLEOSOME REPEAT LENGTH; C-TERMINAL DOMAIN; CHROMATIN IN-VIVO; LIVING CELLS; NUCLEAR PROTEINS; RAPID EXCHANGE; H1; DYNAMICS; TRANSCRIPTION AB The linker histone H1 has a fundamental role in DNA compaction. Although models for H1 binding generally involve the H1 C-terminal tail and sites S1 and S2 within the H1 globular domain, there is debate about the importance of these binding regions and almost nothing is known about how they work together. Using a novel fluorescence recovery after photobleaching (FRAP) procedure, we have measured the affinities of these regions individually, in pairs, and in the full molecule to demonstrate for the first time that binding among several combinations is cooperative in live cells. Our analysis reveals two preferred H1 binding pathways and we find evidence for a novel conformational change required by both. These results paint a complex, highly dynamic picture of H1-chromatin binding, with a significant fraction of H1 molecules only partially bound in metastable states that can be readily competed against. We anticipate the methods we have developed here will be broadly applicable, particularly for deciphering the binding kinetics of other nuclear proteins that, similar to H1, interact with and modify chromatin. The EMBO Journal (2010) 29, 1225-1234. doi:10.1038/emboj.2010.24; Published online 11 March 2010 C1 [Stasevich, Timothy J.; Mueller, Florian; McNally, James G.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. [Brown, David T.] Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov RI Mueller, Florian/C-9075-2012 OI Mueller, Florian/0000-0002-9622-4396 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Dr Tatiana Karpova for imaging assistance and critical reading of the manuscript and Dr Michael Kruhlak for DIC imaging assistance. We thank Dr Michael Bustin and Dr Michael Seidman for reviewing earlier drafts and Dr Davide Mazza and Dr Ariel Michelman-Ribeiro for discussions. We are grateful to Dr Tom Misteli for assistance in obtaining H1 constructs, discussions, and critical reading of the manuscript. This research was supported in part by the intramural program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 40 TC 44 Z9 45 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 7 PY 2010 VL 29 IS 7 BP 1225 EP 1234 DI 10.1038/emboj.2010.24 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 580BP UT WOS:000276422200008 PM 20224551 ER PT J AU Subramanian, J Simon, R AF Subramanian, Jyothi Simon, Richard TI Gene Expression-Based Prognostic Signatures in Lung Cancer: Ready for Clinical Use? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; SURVIVAL; ADENOCARCINOMA; MARKER; CLASSIFICATION; RECURRENCE; MICROARRAY; PREDICTION; GUIDELINES; PROFILE AB A substantial number of studies have reported the development of gene expression-based prognostic signatures for lung cancer. The ultimate aim of such studies should be the development of well-validated clinically useful prognostic signatures that improve therapeutic decision making beyond current practice standards. We critically reviewed published studies reporting the development of gene expression-based prognostic signatures for non-small cell lung cancer to assess the progress made toward this objective. Studies published between January 1, 2002, and February 28, 2009, were identified through a PubMed search. Following hand-screening of abstracts of the identified articles, 16 were selected as relevant. Those publications were evaluated in detail for appropriateness of the study design, statistical validation of the prognostic signature on independent datasets, presentation of results in an unbiased manner, and demonstration of medical utility for the new signature beyond that obtained using existing treatment guidelines. Based on this review, we found little evidence that any of the reported gene expression signatures are ready for clinical application. We also found serious problems in the design and analysis of many of the studies. We suggest a set of guidelines to aid the design, analysis, and evaluation of prognostic signature studies. These guidelines emphasize the importance of focused study planning to address specific medically important questions and the use of unbiased analysis methods to evaluate whether the resulting signatures provide evidence of medical utility beyond standard of care-based prognostic factors. C1 [Subramanian, Jyothi; Simon, Richard] NCI, Biometr Res Branch, Dept Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Dept Canc Treatment & Diag, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@mail.nih.gov RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 38 TC 165 Z9 169 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 7 PY 2010 VL 102 IS 7 BP 464 EP 474 DI 10.1093/jnci/djq025 PG 11 WC Oncology SC Oncology GA 581MN UT WOS:000276527800007 PM 20233996 ER PT J AU Gustafson, AM Soldi, R Anderlind, C Scholand, MB Qian, J Zhang, XH Cooper, K Walker, D McWilliams, A Liu, G Szabo, E Brody, J Massion, PP Lenburg, ME Lam, S Bild, AH Spira, A AF Gustafson, Adam M. Soldi, Raffaella Anderlind, Christina Scholand, Mary Beth Qian, Jun Zhang, Xiaohui Cooper, Kendal Walker, Darren McWilliams, Annette Liu, Gang Szabo, Eva Brody, Jerome Massion, Pierre P. Lenburg, Marc E. Lam, Stephen Bild, Andrea H. Spira, Avrum TI Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID EPITHELIAL GENE-EXPRESSION; PROTEIN-KINASE-C; CELL-LINES; BRONCHIAL EPITHELIUM; SMOKERS; TRANSFORMATION; SIGNATURES; MUTATIONS; 3-KINASE; MYOINOSITOL AB Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically normal proximal airway epithelial cells of smokers at risk for lung cancer. We observed a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal airway before tumorigenesis. Further, PI3K activity is decreased in the airway of high-risk smokers who had significant regression of dysplasia after treatment with the chemopreventive agent myo-inositol, and myo-inositol inhibits the PI3K pathway in vitro. These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy. Our work further suggests that additional lung cancer chemoprevention trials either targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted. C1 [Soldi, Raffaella; Cooper, Kendal; Walker, Darren; Bild, Andrea H.] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. [Gustafson, Adam M.; Anderlind, Christina; Zhang, Xiaohui; Liu, Gang; Brody, Jerome; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Med Ctr, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA. [Gustafson, Adam M.; Anderlind, Christina; Zhang, Xiaohui; Liu, Gang; Brody, Jerome; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Med Ctr, Ctr Pulm, Boston, MA 02118 USA. [Gustafson, Adam M.; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Bioinformat Program, Boston, MA 02118 USA. [Scholand, Mary Beth] Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. [Qian, Jun; Massion, Pierre P.] Vanderbilt Ingram Comprehens Canc Ctr, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA. [Qian, Jun; Massion, Pierre P.] Nashville Vet Affairs Med Ctr, Nashville, TN 37232 USA. [McWilliams, Annette; Lam, Stephen] British Columbia Canc Agcy, Dept Resp Med, Vancouver, BC V5Z 4E6, Canada. [Szabo, Eva] NCI, Lung & Upper Aerodigest Canc Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Lenburg, Marc E.; Spira, Avrum] Boston Univ, Dept Pathol & Lab Med, Sch Med, Boston, MA 02118 USA. RP Bild, AH (reprint author), Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. EM andreab@genetics.utah.edu; aspira@bu.edu RI Lenburg, Marc/B-8027-2008; OI Lenburg, Marc/0000-0002-5760-4708; Liu, Gang/0000-0001-9270-6796 FU NCI NIH HHS [CA90949, P50 CA090949, R01 CA124640, R01CA124640]; NIEHS NIH HHS [U01 ES016035, U01ES016035] NR 56 TC 60 Z9 62 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD APR 7 PY 2010 VL 2 IS 26 AR 26ra25 DI 10.1126/scitranslmed.3000251 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 591MI UT WOS:000277304400001 PM 20375364 ER PT J AU Zheng, XH Mueller, GA Cuneo, MJ DeRose, EF London, RE AF Zheng, Xunhai Mueller, Geoffrey A. Cuneo, Matthew J. DeRose, Eugene F. London, Robert E. TI Homodimerization of the p51 Subunit of HIV-1 Reverse Transcriptase SO BIOCHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; POL POLYPROTEIN PRECURSOR; NONNUCLEOSIDE INHIBITORS; AMINO-ACID; P66/P51 HETERODIMER; SYNTHETIC PEPTIDES; CRYSTAL-STRUCTURES; P66 SUBUNIT; PRIMER GRIP; DIMERIZATION AB The dimerization of HIV reverse transcriptase (RT), required to obtain the active form of the enzyme, is influenced by mutations, non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide substrates, Mg ions, temperature, and specifically designed dimerization inhibitors. In this study, we have utilized nuclear magnetic resonance (NMR) spectroscopy of the [methyl-(13)C]methionine-labeled enzyme and small-angle X-ray scattering (SAXS) to investigate how several of these factors influence the dimerization behavior of the p51 subunit. The (1)H (13)C HSQC spectrum of p51 obtained at micromolar concentrations indicates that a significant fraction of the p51 adopts a "p66-like" conformation. SAXS data obtained for p51 samples were used to determine the fractions of monomer and dimer in the sample and to evaluate the conformation of the fingers/thumb subdomain. All of the p51 monomer observed was found to adopt the compact, "p51C" conformation observed for the p51 subunit in the RT heterodimer. The NMR and SAXS data indicate that the p51 homodimer adopts a structure that is similar to the p66/p51 heterodimer, with one p51C subunit and a second p51 subunit in an extended, "p51E" conformation that resembles the p66 subunit of the heterodimer. The fractional dimer concentration and the fingers/thumb orientation are found to depend strongly on the experimental conditions and exhibit a qualitative dependence on nevirapine and ionic strength (KCl) that is similar to the behavior reported for the heterodimer and the p66 homodimer. The L289K mutation interferes with p51 homodimer formation as it does with formation of the heterodimer, despite its location far from the dimer interface. This effect is readily interpreted in terms of a conformational selection model, in which p51(L289K) has a much greater preference for the compact; PSI C conformation. A reduced level of dimer formation then results from the reduced ratio of the p51E(L289K) to p51C(L289K) monomers. C1 [Zheng, Xunhai; Mueller, Geoffrey A.; Cuneo, Matthew J.; DeRose, Eugene F.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MR-01, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov RI Zheng, Xunhai/G-1187-2015; OI Zheng, Xunhai/0000-0003-0390-2491; Cuneo, Matthew/0000-0002-1475-6656 FU National Institute of Environmental Health Sciences (NIEHS) [HHSN273200700046U]; National Institutes of Health [Z01-ES050147] FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS). E.F. D.'s contribution was funded in whole with Federal funds from NIEHS, under Delivery Order HHSN273200700046U to SRA International, Inc. This research was supported by Research Project Z01-ES050147 (R.E.L..) in the Intramural Research Program of the National Institutes of Health. NR 56 TC 10 Z9 10 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 6 PY 2010 VL 49 IS 13 BP 2821 EP 2833 DI 10.1021/bi902116z PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574HB UT WOS:000275978900008 PM 20180596 ER PT J AU Calaluce, R Gubin, MM Davis, JW Magee, JD Chen, J Kuwano, Y Gorospe, M Atasoy, U AF Calaluce, Robert Gubin, Matthew M. Davis, J. Wade Magee, Joseph D. Chen, Jing Kuwano, Yuki Gorospe, Myriam Atasoy, Ulus TI The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer SO BMC CANCER LA English DT Article ID GENOME-WIDE ANALYSIS; ELAV-LIKE PROTEIN; GENE-EXPRESSION; POSTTRANSCRIPTIONAL REGULATION; GLUT1 EXPRESSION; STABILITY; CELLS; RICH; MICRORNAS; STABILIZATION AB Background: The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs). Methods: The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip), provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE) of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. Results: We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+) and MDA-MB-231 (estrogen receptor negative, ER-) breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. Conclusion: This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER-breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER-breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular environment. C1 [Calaluce, Robert; Gubin, Matthew M.; Magee, Joseph D.; Chen, Jing; Atasoy, Ulus] Univ Missouri, Dept Surg, Columbia, MO 65212 USA. [Kuwano, Yuki; Gorospe, Myriam] NIA, Baltimore, MD 21224 USA. RP Atasoy, U (reprint author), Univ Missouri, Dept Surg, 1 Hosp Dr, Columbia, MO 65212 USA. EM atasoyu@missouri.edu FU NIA-IRP, NIH; Department of Defense [W81XWH-07-1-0406]; University of Missouri FX YK and MG were supported by the NIA-IRP, NIH. UA and JWD were supported by Department of Defense (Idea Award W81XWH-07-1-0406) as well as start up funds from University of Missouri. We wish to thank Dr. Michael McManus (UCSF, California) for his guidance with the lentiviral system. NR 79 TC 28 Z9 30 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 6 PY 2010 VL 10 AR 126 DI 10.1186/1471-2407-10-126 PG 15 WC Oncology SC Oncology GA 585HZ UT WOS:000276817300001 PM 20370918 ER PT J AU Ma, L Yang, J Runesha, HB Tanaka, T Ferrucci, L Bandinelli, S Yang, D AF Ma, Li Yang, Jing Runesha, H. Birali Tanaka, Toshiko Ferrucci, Luigi Bandinelli, Stefania Yang Da TI Genome-wide association analysis of total cholesterol and high-density lipoprotein cholesterol levels using the Framingham Heart Study data SO BMC MEDICAL GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; NEWLY IDENTIFIED LOCI; CARDIOVASCULAR-DISEASE; LIPID CONCENTRATIONS; HDL CHOLESTEROL; VARIANTS; PLASMA; COMMON; SERUM; RISK AB Background: Cholesterol concentrations in blood are related to cardiovascular diseases. Recent genome-wide association studies (GWAS) of cholesterol levels identified a number of single-locus effects on total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. Here, we report single-locus and epistasis SNP effects on TC and HDL-C using the Framingham Heart Study (FHS) data. Results: Single-locus effects and pairwise epistasis effects of 432,096 SNP markers were tested for their significance on log-transformed TC and HDL-C levels. Twenty nine additive SNP effects reached single-locus genome-wide significance (p < 7.2 x 10(-8)) and no dominance effect reached genome-wide significance. Two new gene regions were detected, the RAB3GAP1-R3HDM1-LCT-MCM6 region of chr02 for TC identified by six new SNPs, and the OSBPL8-ZDHHC17 region (chr12) for HDL-C identified by one new SNP. The remaining 22 single-locus SNP effects confirmed previously reported genes or gene regions. For TC, three SNPs identified two gene regions that were tightly linked with previously reported genes associated with TC, including rs599839 that was 10 bases downstream PSRC1 and 3.498 kb downstream CELSR2, rs4970834 in CELSR2, and rs4245791 in ABCG8 that slightly overlapped with ABCG5. For HDL-C, LPL was confirmed by 12 SNPs 8-45 kb downstream, CETP by two SNPs 0.5-11 kb upstream, and the LIPG-ACAA2 region by five SNPs inside this region. Two epistasis effects on TC and thirteen epistasis effects on HDL-C reached the significance of "suggestive linkage". The most significant epistasis effect (p = 5.72 x 10(-13)) was close to reaching "significant linkage" and was a dominance x dominance effect of HDL-C between LMBRD1 (chr06) and the LRIG3 region (chr12), and this pair of gene regions had six other D x D effects with "suggestive linkage". Conclusions: Genome-wide association analysis of the FHS data detected two new gene regions with genome-wide significance, detected epistatic SNP effects on TC and HDL-C with the significance of suggestive linkage in seven pairs of gene regions, and confirmed some previously reported gene regions associated with TC and HDL-C. C1 [Ma, Li; Yang, Jing; Yang Da] Univ Minnesota, Dept Anim Sci, Minneapolis, MN 55455 USA. [Runesha, H. Birali] Univ Minnesota, Inst Supercomp, Minneapolis, MN 55455 USA. [Tanaka, Toshiko] Medstar Hlth Res Inst, Baltimore, MD USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Study Sect, Baltimore, MD 21224 USA. RP Yang, D (reprint author), Univ Minnesota, Dept Anim Sci, Minneapolis, MN 55455 USA. EM yda@umn.edu RI Ma, Li/B-1844-2010 FU Agricultural Experiment Station at the University of Minnesota [MN-16-043]; Minnesota Supercomputer Institute; National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University; Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336] FX This research was supported in part by project MN-16-043 of the Agricultural Experiment Station at the University of Minnesota and by a grant from the Minnesota Supercomputer Institute. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University. This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or the NHLBI. The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336). NR 30 TC 44 Z9 46 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD APR 6 PY 2010 VL 11 AR 55 DI 10.1186/1471-2350-11-55 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 594DQ UT WOS:000277514500001 PM 20370913 ER PT J AU Marcus, FI McKenna, WJ Sherrill, D Basso, C Bauce, B Bluemke, DA Calkins, H Corrado, D Cox, MGPJ Daubert, JP Fontaine, G Gear, K Hauer, R Nava, A Picard, MH Protonotarios, N Saffitz, JE Sanborn, DMY Steinberg, JS Tandri, H Thiene, G Towbin, JA Tsatsopoulou, A Wichter, T Zareba, W AF Marcus, Frank I. McKenna, William J. Sherrill, Duane Basso, Cristina Bauce, Barbara Bluemke, David A. Calkins, Hugh Corrado, Domenico Cox, Moniek G. P. J. Daubert, James P. Fontaine, Guy Gear, Kathleen Hauer, Richard Nava, Andrea Picard, Michael H. Protonotarios, Nikos Saffitz, Jeffrey E. Sanborn, Danita M. Yoerger Steinberg, Jonathan S. Tandri, Harikrishna Thiene, Gaetano Towbin, Jeffrey A. Tsatsopoulou, Adalena Wichter, Thomas Zareba, Wojciech TI Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Proposed Modification of the Task Force Criteria SO CIRCULATION LA English DT Article DE arrhythmias, cardiac; arrhythmogenic right ventricular cardiomyopathy/dysplasia; death, sudden, cardiac; diagnosis; echocardiography; electrocardiography; magnetic resonance imaging ID GENOTYPE-PHENOTYPE ASSESSMENT; MAGNETIC-RESONANCE; NAXOS-DISEASE; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; QUANTITATIVE ASSESSMENT; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; WALL-MOTION; DYSPLASIA/CARDIOMYOPATHY AB Background-In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims-the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results-Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions-The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. C1 [Marcus, Frank I.; Sherrill, Duane; Gear, Kathleen] Univ Arizona, Tucson, AZ USA. [McKenna, William J.] Heart Hosp, London, England. [Basso, Cristina; Bauce, Barbara; Corrado, Domenico; Nava, Andrea; Thiene, Gaetano] Univ Padua, Sch Med, Padua, Italy. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Cox, Moniek G. P. J.; Hauer, Richard] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Daubert, James P.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Zareba, Wojciech] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Steinberg, Jonathan S.] St Lukes Roosevelt Hosp, New York, NY USA. [Fontaine, Guy] Hop La Pitie Salpetriere, Paris, France. [Picard, Michael H.; Sanborn, Danita M. Yoerger] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saffitz, Jeffrey E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Protonotarios, Nikos; Tsatsopoulou, Adalena] Yannis Protonotarios Med Ctr, Hora Naxos, Greece. [Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Wichter, Thomas] Marien Hosp, Osnabruck, Germany. RP Marcus, FI (reprint author), Sarver Heart Ctr, 1501 N Campbell,Rm 5153,Box 245037, Tucson, AZ USA. EM fmarcus@u.arizona.edu RI McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Picard, Michael/0000-0002-9264-3243; Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [R13 HL086825]; National Heart, Lung & Blood Institute; National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, Md [U01-HL65594, U01-HL65652, U01-HL65691, K23-HL093350]; European Commission, Brussels, Belgium [QLG1-CT-2000-01091]; International Society for Holter; Peter French Memorial Foundation; United Desert Charities; Podolsky Family Foundation FX This project was supported by National Institutes of Health research grant R13 HL086825, funded by the National Heart, Lung & Blood Institute and the Office of Rare Disorders, and was supported in part by research grants U01-HL65594, U01-HL65652, U01-HL65691, and K23-HL093350 from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, Md, and by research grant QLG1-CT-2000-01091 5th Framework Programme from the European Commission, Brussels, Belgium. Additional funding was obtained from the International Society for Holter and Noninvasive Electrocardiography and donations from the Peter French Memorial Foundation, United Desert Charities, the Podolsky Family Foundation, and private donors Mr and Mrs L. Becker, Mr and Mrs H. Danz, Mr K. Dorn, Mr T. Livolsi, Mr and Mrs L. Long, and Mr and Mrs H. Wilmerding. NR 59 TC 547 Z9 569 U1 4 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 6 PY 2010 VL 121 IS 13 BP 1533 EP U118 DI 10.1161/CIRCULATIONAHA.108.840827 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 579DX UT WOS:000276348600010 PM 20172911 ER PT J AU Conlan, AJK Rohani, P Lloyd, AL Keeling, M Grenfell, BT AF Conlan, Andrew J. K. Rohani, Pejman Lloyd, Alun L. Keeling, Matthew Grenfell, Bryan T. TI Resolving the impact of waiting time distributions on the persistence of measles SO JOURNAL OF THE ROYAL SOCIETY INTERFACE LA English DT Article DE measles; stochasticity; persistence ID INFECTIOUS-DISEASES; EPIDEMIC MODELS; COMMUNITY SIZE; REALISTIC DISTRIBUTIONS; CHILDHOOD DISEASES; DYNAMICAL-SYSTEMS; VACCINATION; TRANSMISSION; PERIODS; PATTERNS AB Measles epidemics in human populations exhibit what is perhaps the best empirically characterized, and certainly the most studied, stochastic persistence threshold in population biology. A critical community size (CCS) of around 250 000-500 000 separates populations where measles is predominantly persistent from smaller communities where there are frequent extinctions of measles between major epidemics. The fundamental mechanisms contributing to this pattern of persistence, which are long-lasting immunity to re-infection, recruitment of susceptibles, seasonality in transmission, age dependence of transmission and the spatial coupling between communities, have all been quantified and, to a greater or lesser level of success, captured by theoretical models. Despite these successes there has not been a consensus over whether simple models can successfully predict the value of the CCS, or indeed which mechanisms determine the persistence of measles over a broader range of population sizes. Specifically, the level of the CCS has been thought to be particularly sensitive to the detailed stochastic dynamics generated by the waiting time distribution (WTD) in the infectious and latent periods. We show that the relative patterns of persistence between models with different WTDs are highly sensitive to the criterion of comparison-in particular, the statistical measure of persistence that is employed. To this end, we introduce two new statistical measures of persitence-fade-outs post epidemic and fade-outs post invasion. Contrary to previous reports, we demonstrate that, no matter the choice of persistence measure, appropriately parametrized models of measles demonstrate similar predictions for the level of the CCS. C1 [Conlan, Andrew J. K.] Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Cambridge CB3 0ES, England. [Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Program, Raleigh, NC 27695 USA. [Keeling, Matthew] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England. [Keeling, Matthew] Univ Warwick, Math Inst, Coventry CV4 7AL, W Midlands, England. [Rohani, Pejman; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch Publ & Int Affairs, Princeton, NJ 08544 USA. RP Conlan, AJK (reprint author), Univ Cambridge, Dept Vet Med, Cambridge Infect Dis Consortium, Madingley Rd, Cambridge CB3 0ES, England. EM a.j.k.conlan@damtp.cam.ac.uk RI Lloyd, Alun/H-4944-2012; Keeling, Matt/J-9280-2012; OI Keeling, Matt/0000-0003-4639-4765 FU DEFRA [PU/T/WL/07/46 SE3230]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health [R01GM83983] FX A.J.K.C. is funded by DEFRA grant PU/T/WL/07/46 SE3230, sponsored by the Veterinary Laboratories Agency. This research was developed during a Wellcome Trust Prize Studentship at the Department of Zoology, Cambridge. A.J.K.C. thanks CIDC and the Disease Dynamics Group of DAMTP, Cambridge, for helpful discussions and comments on this paper. P.R., A.L.L. and B.T.G. were supported by the RAPIDD Program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. B.T.G. was also supported by NIH grant R01GM83983. NR 75 TC 25 Z9 25 U1 0 U2 8 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1742-5689 J9 J R SOC INTERFACE JI J. R. Soc. Interface PD APR 6 PY 2010 VL 7 IS 45 BP 623 EP 640 DI 10.1098/rsif.2009.0284 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 558ZP UT WOS:000274789400007 PM 19793743 ER PT J AU Chigurupati, S Mughal, MR Chan, SL Arumugam, TV Baharani, A Tang, SC Yu, QS Holloway, HW Wheeler, R Poosala, S Greig, NH Mattson, MP AF Chigurupati, Srinivasulu Mughal, Mohamed R. Chan, Sic L. Arumugam, Thiruma V. Baharani, Akanksha Tang, Sung-Chun Yu, Qian-Sheng Holloway, Harold W. Wheeler, Ross Poosala, Suresh Greig, Nigel H. Mattson, Mark P. TI A Synthetic Uric Acid Analog Accelerates Cutaneous Wound Healing in Mice SO PLOS ONE LA English DT Article ID ISCHEMIC BRAIN-INJURY; DIABETIC FOOT ULCERS; OXIDATIVE STRESS; GROWTH-FACTOR; ANTIOXIDANT DEFENSE; NITRIC-OXIDE; REPAIR; ANGIOGENESIS; PATHOGENESIS; GLUTATHIONE AB Wound healing is a complex process involving intrinsic dermal and epidermal cells, and infiltrating macrophages and leukocytes. Excessive oxidative stress and associated inflammatory processes can impair wound healing, and antioxidants have been reported to improve wound healing in animal models and human subjects. Uric acid (UA) is an efficient free radical scavenger, but has a very low solubility and poor tissue penetrability. We recently developed novel UA analogs with increased solubility and excellent free radical-scavenging properties and demonstrated their ability to protect neural cells against oxidative damage. Here we show that the uric acid analog (6, 8 dithio-UA, but not equimolar concentrations of UA or 1, 7 dimethyl-UA) modified the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in ways consistent with enhancement of the wound healing functions of all three cell types. We further show that 6, 8 dithio-UA significantly accelerates the wound healing process when applied topically (once daily) to full-thickness wounds in mice. Levels of Cu/Zn superoxide dismutase were increased in wound tissue from mice treated with 6, 8 dithio-UA compared to vehicle-treated mice, suggesting that the UA analog enhances endogenous cellular antioxidant defenses. These results support an adverse role for oxidative stress in wound healing and tissue repair, and provide a rationale for the development of UA analogs in the treatment of wounds and for modulation of angiogenesis in other pathological conditions. C1 [Chigurupati, Srinivasulu; Mughal, Mohamed R.; Arumugam, Thiruma V.; Tang, Sung-Chun; Yu, Qian-Sheng; Holloway, Harold W.; Greig, Nigel H.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Chigurupati, Srinivasulu; Poosala, Suresh] NIA, Res Resources Branch, Intramural Res Program, Baltimore, MD 21224 USA. [Wheeler, Ross] Univ Cent Florida, Dept Pathol & Med Educ, Orlando, FL 32816 USA. [Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Chigurupati, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Arumugam, Thiruma/B-4898-2011; Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU National Institute on Aging, National Institutes of Helath (NIH) FX This research was supported by the National Institute on Aging Intramural Research Program of the National Institutes of Helath (NIH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 6 Z9 6 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 6 PY 2010 VL 5 IS 3 AR e10044 DI 10.1371/journal.pone.0010044 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 580BA UT WOS:000276420400015 PM 20386608 ER PT J AU Martin, B Ji, S Maudsley, S Mattson, MP AF Martin, Bronwen Ji, Sunggoan Maudsley, Stuart Mattson, Mark P. TI "Control" laboratory rodents are metabolically morbid: Why it matters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cancer; clinical trials; exercise; insulin resistance; obesity ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; CHRONIC CALORIC RESTRICTION; DIETARY ENERGY RESTRICTION; INDUCED INSULIN-RESISTANCE; TRANSGENIC MOUSE MODEL; WEIGHT-LOSS; ALZHEIMERS-DISEASE; BODY-WEIGHT; BEHAVIORAL DEFICITS; PARKINSONS-DISEASE AB Failure to recognize that many standard control rats and mice used in biomedical research are sedentary, obese, glucose intolerant, and on a trajectory to premature death may confound data interpretation and outcomes of human studies. Fundamental aspects of cellular physiology, vulnerability to oxidative stress, inflammation, and associated diseases are among the many biological processes affected by dietary energy intake and exercise. Although overfed sedentary rodents may be reasonable models for the study of obesity in humans, treatments shown to be efficacious in these animal models may prove ineffective or exhibit novel side effects in active, normal-weight subjects. C1 [Mattson, Mark P.] NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Martin, Bronwen; Ji, Sunggoan] NIA, Metab Unit, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institutes of Health, National Institute on Aging FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 102 TC 134 Z9 138 U1 6 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 6 PY 2010 VL 107 IS 14 BP 6127 EP 6133 DI 10.1073/pnas.0912955107 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579MH UT WOS:000276374400004 PM 20194732 ER PT J AU Jang, H Arce, FT Ramachandran, S Capone, R Azimova, R Kagan, BL Nussinov, R Lal, R AF Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Capone, Ricardo Azimova, Rushana Kagan, Bruce L. Nussinov, Ruth Lal, Ratnesh TI Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atomic force microscopy; molecular dynamics; cell calcium imaging; neurite degeneration and cell death assays; single-channel conductance ID PRION PROTEIN-FRAGMENT; HEPARIN-BINDING DOMAIN; ION CHANNELS; ZN2+-SENSITIVE CHANNEL; COMMON MECHANISM; MOUSE MODELS; GRAMICIDIN-A; 3D STRUCTURE; CONGO RED; IN-VITRO AB Full-length amyloid beta peptides (A beta(1-40/42)) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (A beta(11-42) and A beta(17-42)) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic A beta(9-42) and A beta(17-42) peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated A beta fragments could account for undefined roles played by full length A beta s and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment. C1 [Jang, Hyunbum; Nussinov, Ruth] Natl Canc Inst, SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Azimova, Rushana; Kagan, Bruce L.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Neuropsychiat Inst, Los Angeles, CA 90024 USA. [Azimova, Rushana; Kagan, Bruce L.] Greater Los Angeles Vet Adm Hlth Syst, 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), Natl Canc Inst, SAIC Frederick Inc, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov; rlal@ucsd.edu RI Capone, Ricardo/D-1943-2010 OI Capone, Ricardo/0000-0002-7327-9837 FU National Institutes of Health [IIRG-05-14089]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank Dr. Robert Tycko for providing the A beta9-40 oligomer coordinates, Dr. Jeremy Marks for providing primary hippocampal neurons, Dr Gopal Thinakaran for providing APP-null cells, and Drs. Thinakaran and Sangram Sisodia for invaluable insights, as well as for critical editing of the manuscript. This research was supported by the National Institutes of Health (National Institute on Aging) extramural program (R. L) and Alzheimer's Association Award IIRG-05-14089 (to B.L.K.). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 50 TC 105 Z9 107 U1 3 U2 40 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 6 PY 2010 VL 107 IS 14 BP 6538 EP 6543 DI 10.1073/pnas.0914251107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579MH UT WOS:000276374400074 PM 20308552 ER PT J AU Arana, ME Holmes, SF Fortune, JM Moon, AF Pedersen, LC Kunkel, TA AF Arana, Mercedes E. Holmes, Shannon F. Fortune, John M. Moon, Andrea F. Pedersen, Lars C. Kunkel, Thomas A. TI Functional residues on the surface of the N-terminal domain of yeast Pms1 SO DNA REPAIR LA English DT Article DE Mismatch repair; MutL alpha; DNA binding; Mutator; Mutation rate ID DNA MISMATCH-REPAIR; SITE-DIRECTED MUTAGENESIS; CEREVISIAE MUTL-ALPHA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; CONFORMATIONAL-CHANGES; MUTATOR PHENOTYPES; MAMMALIAN MEIOSIS; NUCLEAR EXTRACTS; ATPASE ACTIVITY AB Saccharomyces cerevisiae MutL alpha is a heterodimer of Mlh1 and Pms1 that participates in DNA mismatch repair (MMR). Both proteins have weakly conserved C-terminal regions (CTDs), with the CTD of Pms1 harboring an essential endonuclease activity. These proteins also have conserved N-terminal domains (NTDs) that bind and hydrolyze ATP and bind to DNA. To better understand Pms1 functions and potential interactions with DNA and/or other proteins, we solved the 2.5 angstrom crystal structure of yeast Pms1 (yPms1) NTD. The structure is similar to the homologous NTDs of Escherichia coli MutL and human PMS2, including the site involved in ATP binding and hydrolysis. The structure reveals a number of conserved, positively charged surface residues that do not interact with other residues in the NTD and are therefore candidates for interactions with DNA, with the CTD and/or with other proteins. When these were replaced with glutamate, several replacements resulted in yeast strains with elevated mutation rates. Two replacements also resulted in NTDs with decreased DNA binding affinity in vitro, suggesting that these residues contribute to DNA binding that is important for mismatch repair. Elevated mutation rates also resulted from surface residue replacements that did not affect DNA binding, suggesting that these conserved residues serve other functions, possibly involving interactions with other MMR proteins. Published by Elsevier B.V. C1 [Arana, Mercedes E.; Holmes, Shannon F.; Fortune, John M.; Kunkel, Thomas A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Arana, Mercedes E.; Holmes, Shannon F.; Fortune, John M.; Moon, Andrea F.; Pedersen, Lars C.; Kunkel, Thomas A.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233-111,TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov FU Division of Intramural Research of the Institutes of Health, National Institute of Environmental Health Sciences [Z01 ES065089] FX The authors thank Alan Clark and Allison Schorzman for thoughtful comments on the manuscript. We thank the NIEHS DNA Sequencing Core Facility for expert assistance in the DNA sequence analysis of Canr mutants. This work was supported in part by Project Z01 ES065089 to TAK from the Division of Intramural Research of the Institutes of Health, National Institute of Environmental Health Sciences. NR 67 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 4 PY 2010 VL 9 IS 4 BP 448 EP 457 DI 10.1016/j.dnarep.2010.01.010 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 594RL UT WOS:000277555000012 PM 20138591 ER PT J AU Motulsky, E Koch, P Janssens, S Lienart, M Vanbellinghen, AM Bolaky, N Chan, CC Caspers, L Martin-Martinez, MD Xu, HP Delporte, C Willermain, F AF Motulsky, Elie Koch, Philippe Janssens, Sarah Lienart, Maite Vanbellinghen, Anne-Marie Bolaky, Nargis Chan, Chi-Chao Caspers, Laure Martin-Martinez, Maria-Dolores Xu, Heping Delporte, Christine Willermain, Francois TI Aquaporin expression in blood-retinal barrier cells during experimental autoimmune uveitis SO MOLECULAR VISION LA English DT Article ID OCULAR INFLAMMATION; PIGMENT EPITHELIUM; GENE DISRUPTION; MACULAR EDEMA; MULLER CELLS; MOUSE RETINA; RAT RETINA; MICE; ASTROCYTES; CHANNELS AB Purpose: Blood-retinal barrier (BRB) breakdown and retinal edema are major complications of autoimmune uveitis and could be related to deregulation of aquaporin (AQP) expression. We have therefore evaluated the expression of AQP1 and AQP4 on BRB cells during experimental autoimmune uveitis (EAU) in mice. Methods: C57Bl6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-16. The disease was graded clinically, and double immunolabeling using glial fibrillary acidic protein (GFAP; a marker of disease activity) and AQP1 or AQP4 antibodies was performed at day 28. AQP1 expression was also investigated in mouse retinal pigment epithelium (RPE) cells (B6-RPE07 cell line) by reverse transcriptase PCR and western blot under basal and tumor necrosis factor alpha (TNF-alpha)-stimulated conditions. Results: In both normal and EAU retina, AQP1 and AQP4 expression were restricted to the photoreceptor layer and to the Muller cells, respectively. Retinal endothelial cells never expressed AQP1. In vasculitis and intraretinal inflammatory infiltrates, decreased AQP1 expression was observed due to the loss of photoreceptors and the characteristic radial labeling of AQP4 was lost. On the other hand, no AQP4 expression was detected in RPE cells. AQP1 was strongly expressed by choroidal endothelial cells, rendering difficult the evaluation of AQP1 expression by RPE cells in vivo. No major differences were found between EAU and controls at this level. Interestingly, B6-RPE07 cells expressed AQP1 in vitro, and TNF-alpha downregulated AQP1 protein expression in those cells. Conclusions: Changes in retinal expression of AQP1 and AQP4 during EAU were primarily due to inflammatory lesions, contrasting with major modulation of AQP expression in BRB detected in other models of BRB breakdown. However, our data showed that TNF-alpha treatment strongly modulates AQP1 expression in B6-RPE07 cells in vitro. C1 [Motulsky, Elie; Janssens, Sarah; Lienart, Maite; Bolaky, Nargis; Delporte, Christine] Univ Libre Bruxelles, Lab Biol Chem & Nutr, B-1070 Brussels, Belgium. [Motulsky, Elie; Koch, Philippe; Janssens, Sarah; Lienart, Maite; Caspers, Laure; Willermain, Francois] CHU St Pierre & Brugmann, Dept Ophthalmol, Brussels, Belgium. [Koch, Philippe; Willermain, Francois] Univ Libre Bruxelles, IRIBHM, B-1070 Brussels, Belgium. [Vanbellinghen, Anne-Marie] Univ Libre Bruxelles, Lab Expt Hormonol, B-1070 Brussels, Belgium. [Chan, Chi-Chao] NEI, Bethesda, MD 20892 USA. [Martin-Martinez, Maria-Dolores] CMP Lab, Brussels, Belgium. [Xu, Heping] Queens Univ Belfast, Ctr Vis & Vasc Sci, Belfast, Antrim, North Ireland. RP Delporte, C (reprint author), Univ Libre Bruxelles, Lab Biol Chem & Nutr, CP 611,Route Lennik 808, B-1070 Brussels, Belgium. EM cdelport@ulb.ac.be RI Xu, Heping/A-4430-2008; Delporte, Christine/A-5733-2012; OI Xu, Heping/0000-0003-4000-931X FU Fund for Medical Scientific Research, Belgium [3.4604.05, 3.4502.09]; Funds for Research in Ophthalmology; ASBL Vesale Award FX We thank Dr. A. Boom and Dr. J. Perret for helpful revision of this manuscript. This work was supported by grants from the Fund for Medical Scientific Research (3.4604.05, 3.4502.09, Belgium) to C. D. and from the Funds for Research in Ophthalmology to E. M. M. L. and S. J. were recipients of an ASBL Vesale Award. NR 26 TC 13 Z9 13 U1 0 U2 1 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 3 PY 2010 VL 16 IS 66-69 BP 602 EP 610 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 619MB UT WOS:000279433200004 PM 20383338 ER PT J AU Conen, D Chae, CU Guralnik, JM Glynn, RJ AF Conen, David Chae, Claudia U. Guralnik, Jack M. Glynn, Robert J. TI Influence of blood pressure and blood pressure change on the risk of congestive heart failure in the elderly SO SWISS MEDICAL WEEKLY LA English DT Article DE hypertension; blood pressure; pulse pressure; heart failure; mortality ID INCREASED PULSE PRESSURE; CARDIOVASCULAR EVENTS; DISEASE RISK; HYPERTENSION; MORTALITY; PROGRESSION; PREDICTORS; RELEVANCE; WOMEN AB Background: While elevated blood pressure (BP) has been consistently associated with incident congestive heart failure (CHF), much less is known about the effect of BP change. We therefore assessed the association of BP change over time with subsequent risk of CHF. Methods: 4655 participants >= 65 years old from the prospective Established Populations for Epidemiologic Studies of the Elderly program who were alive and free of CHF after six years of follow-up were included. Categories of sustained high BP, sustained low BP, BP progression and BP regression were defined according to BP differences between study entry and six years of follow-up. The primary endpoint was incident CHF subsequent to the six year examination. Results: During 4.3 years of follow-up after the six year examination, 642 events occurred. The hazard ratio (HR) (95% confidence interval (CI)) for systolic BP >= 160 compared to <120 mm Hg at six years was 1.39 (1.04-1.86). Conversely, the lowest diastolic BP category at six years was associated with an increased risk of incident CHF (FIR (95% CI) <70 mm Hg versus 70-79 mm Hg 1.42 (1.18-1.71)). Systolic and diastolic BP were better predictors than pulse pressure. The HRs (95% CI) for incident CHF associated with sustained high systolic BP >= 160 mm Fig and systolic BP progression were 1.35 (0.97-1.89) and 1.45 (1.14-1.85), respectively. Conversely, significant associations were found in those with sustained low diastolic BP or diastolic BP regression (HR (95% CI) 1.42 (1.11-1.83) and 1.45 (1.19-1.76), respectively). Conclusion: While persistently elevated systolic BP and systolic BP progression were strong predictors of CHF in the elderly, inverse associations were found with regard to diastolic BP. Systolic and diastolic BP were better predictors of CHF than pulse pressure. C1 [Conen, David] Univ Basel Hosp, Dept Med, CH-4031 Basel, Switzerland. [Conen, David; Chae, Claudia U.; Glynn, Robert J.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. [Chae, Claudia U.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA. RP Conen, D (reprint author), Univ Basel Hosp, Dept Med, Petersgraben 4, CH-4031 Basel, Switzerland. EM conend@uhbs.ch FU National Institute on Aging, Bethesda, Md [AG02107]; Swiss National Science Foundation [PASMA 118586/1] FX This study was supported by contract AG02107 from the National Institute on Aging, Bethesda, Md. David Conen was supported by grants of the Swiss National Science Foundation (PASMA 118586/1). NR 28 TC 6 Z9 7 U1 0 U2 0 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 EI 1424-3997 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD APR 3 PY 2010 VL 140 IS 13-14 BP 202 EP 208 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 583IL UT WOS:000276667500004 PM 20072936 ER PT J AU Schroeder, JL Luger-Hamer, M Pursley, R Pohida, T Chefd'Hotel, C Kellman, P Balaban, RS AF Schroeder, James L. Luger-Hamer, Merav Pursley, Randall Pohida, Tom Chefd'Hotel, Chris Kellman, Peter Balaban, Robert S. TI Subcellular Motion Compensation for Minimally Invasive Microscopy, In Vivo Evidence for Oxygen Gradients in Resting Muscle SO CIRCULATION RESEARCH LA English DT Article DE two-photon excitation microscopy; perivascular mitochondria; NADH fluorescence; mouse skeletal muscle; redox state ID SKELETAL-MUSCLE; FLUORESCENCE MICROSCOPY; NADH FLUORESCENCE; ARTERIOLES; CELLS; ISCHEMIA; VENULES; FIBERS; MODELS; TISSUE AB Rationale: In vivo microscopy seeks to observe dynamic subcellular processes in a physiologically relevant context. A primary limitation of optical microscopy in vivo is tissue motion, which prevents physiological time course observations or image averaging. Objective: To develop and demonstrate motion compensation methods that can automatically track image planes within biological tissues, including the tissue displacements associated with large changes in blood flow, and to evaluate the effect of global hypoxia on the regional kinetics and steady state levels of mitochondrial NAD(P)H. Methods and Results: A dynamic optical microscope, with real-time prospective tracking and retrospective image processing, was used collect high-resolution images through cellular responses to various perturbations. The subcellular metabolic response to hypoxia was examined in vivo. Mitochondria closest to the capillaries were significantly more oxidized at rest (67 +/- 3%) than the intrafibrillar mitochondria (83 +/- 3%; P<0.0001) in the same cell. Conclusions: These data are consistent with the hypothesis that a significant oxygen gradient from capillary to muscle core exists at rest, thereby reducing the oxidative load on the muscle cell. (Circ Res. 2010; 106: 1129-1133.) C1 [Schroeder, James L.; Luger-Hamer, Merav; Kellman, Peter; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. [Pursley, Randall; Pohida, Tom] NIH, Signal Proc & Instrumentat Sect, Ctr Informat Technol, Bethesda, MD 20892 USA. [Chefd'Hotel, Chris] Siemens Res, Dept Imaging & Visualizat, Princeton, NJ USA. RP Balaban, RS (reprint author), 10 Ctr Dr,10-CRC-4-1581, Bethesda, MD 20892 USA. EM balabanr@nhlbi.nih.gov FU NIH/National Heart, Lung, and Blood Institute Division of Intramural Research [HL004610-02] FX Supported by the NIH/National Heart, Lung, and Blood Institute Division of Intramural Research (grant HL004610-02). NR 30 TC 19 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 2 PY 2010 VL 106 IS 6 BP 1129 EP U271 DI 10.1161/CIRCRESAHA.109.211946 PG 23 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 577HQ UT WOS:000276214000016 PM 20167928 ER PT J AU Tanaka, A AF Tanaka, Atsushi TI Parkin-mediated selective mitochondrial autophagy, mitophagy: Parkin purges damaged organelles from the vital mitochondrial network SO FEBS LETTERS LA English DT Review DE Parkin; Parkinson's disease; Mitophagy; Mitochondrial quality control; PINK1 ID RETICULOCYTE MATURATION; PINK1/PARKIN PATHWAY; CELL-DEATH; DISEASE; DEGRADATION; PROTEIN; DYNAMICS; FUSION; STRESS; PINK1 AB Cellular homeostasis is linked tightly to mitochondrial functions. Some damage to mitochondrial proteins and nucleic acids can lead to the depolarization of the inner mitochondrial membrane, thereby sensitizing impaired mitochondria for selective elimination by autophagy. Mitochondrial dysfunction is one of the key aspects of the pathobiology of neurodegenerative disease. Parkin, an E3 ligase located in the cytosol and originally discovered as mutated in monogenic forms of Parkinson's disease (PD), was found recently to translocate specifically to uncoupled mitochondria and to induce their autophagy. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Tanaka, A (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bldg 35,Rm 2C-915,MSC 3704, Bethesda, MD 20892 USA. EM tanakaa@ninds.nih.gov FU NINDS/NIH; JSPS FX I would like to thank Professor Noboru Mizushima (Tokyo Med. Dent. Univ.) for giving me the opportunity of this article. I also thank R. Youle for support and M. Cleland for the critical reading for the manuscript. Our studies are supported by NINDS/NIH intramural program (to R. J. Y.) and JSPS (to A. T.). NR 53 TC 51 Z9 52 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 2 PY 2010 VL 584 IS 7 BP 1386 EP 1392 DI 10.1016/j.febslet.2010.02.060 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 571GD UT WOS:000275738900016 PM 20188730 ER PT J AU Yu, SY Zhao, DM Jothi, R Xue, HH AF Yu, Shuyang Zhao, Dong-Mei Jothi, Raja Xue, Hai-Hui TI Critical Requirement of GABP alpha for Normal T Cell Development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GABP; ADULT HEMATOPOIETIC STEM; CHIP-SEQ DATA; BINDING-PROTEIN; LYMPHOCYTE DEVELOPMENT; GENE-EXPRESSION; NEUROMUSCULAR-JUNCTION; RECEPTOR EXPRESSION; CYCLE PROGRESSION; TARGET GENES AB GA binding protein (GABP) consists of GABP alpha and GABP beta subunits. GABP alpha is a member of Ets family transcription factors and binds DNA via its conserved Ets domain, whereas GABP beta does not bind DNA but possesses transactivation activity. In T cells, GABP has been demonstrated to regulate the gene expression of interleukin-7 receptor alpha chain (IL-7R alpha) and postulated to be critical in T cell development. To directly investigate its function in early thymocyte development, we used GABP alpha conditional knock-out mice where the exons encoding the Ets DNA-binding domain are flanked with LoxP sites. Ablation of GABP alpha with the Lck-Cre transgene greatly diminished thymic cellularity, blocked thymocyte development at the double negative 3 (DN3) stage, and resulted in reduced expression of T cell receptor (TCR) beta chain in DN4 thymocytes. By chromatin immunoprecipitation, we demonstrated in DN thymocytes that GABP alpha is associated with transcription initiation sites of genes encoding key molecules in TCR rearrangements. Among these GABP-associated genes, knockdown of GABP alpha expression by RNA interference diminished expression of DNA ligase IV, Artemis, and Ku80 components in DNA-dependent protein kinase complex. Interestingly, forced expression of prearranged TCR but not IL-7R alpha can alleviate the DN3 block in GABP alpha-targeted mice. Our observations collectively indicate that in addition to regulating IL-7R alpha expression, GABP is critically required for TCR rearrangements and hence normal T cell development. C1 [Yu, Shuyang; Zhao, Dong-Mei; Xue, Hai-Hui] Univ Iowa, Dept Microbiol, Iowa City, IA 52246 USA. [Zhao, Dong-Mei] Univ Iowa, Dept Internal Med, Iowa City, IA 52246 USA. [Xue, Hai-Hui] Univ Iowa, Interdisciplinary Immunol Grad Program, Carver Coll Med, Iowa City, IA 52246 USA. [Jothi, Raja] NIEHS, NIH, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Xue, HH (reprint author), Univ Iowa, Dept Microbiol, Iowa City, IA 52246 USA. EM hai-hui-xue@uiowa.edu RI Jothi, Raja/G-3780-2015 FU National Institutes of Health [AI077504, HL095540]; NIEHS FX This work was supported, in whole or in part, by National Institutes of Health Grants AI077504 and HL095540 (to H. -H. X.). This work was also supported by the Intramural Research Program of the NIEHS, National Institutes of Health (to R. J.). NR 53 TC 16 Z9 16 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10179 EP 10188 DI 10.1074/jbc.M109.088740 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600002 PM 20139079 ER PT J AU Lee, KY Yang, K Cohn, MA Sikdar, N D'Andrea, AD Myung, K AF Lee, Kyoo-young Yang, Kailin Cohn, Martin A. Sikdar, Nilabja D'Andrea, Alan D. Myung, Kyungjae TI Human ELG1 Regulates the Level of Ubiquitinated Proliferating Cell Nuclear Antigen (PCNA) through Its Interactions with PCNA and USP1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPLICATION-FACTOR-C; DNA-POLYMERASE-ETA; GENOME STABILITY; COHESION ESTABLISHMENT; MONOUBIQUITINATED PCNA; COMPLEX-FORMATION; S-PHASE; INSTABILITY; DAMAGE; FORMS AB The level of monoubiquitinated proliferating cell nuclear antigen (PCNA) is closely linked with DNA damage bypass to protect cells from a high level of mutagenesis. However, it remains unclear how the level of monoubiquitinated PCNA is regulated. Here, we demonstrate that human ELG1 protein, which comprises an alternative replication factor C (RFC) complex and plays an important role in preserving genomic stability, as an interacting partner for the USP1 (ubiquitin-specific protease 1)-UAF1 (USP1-associated factor 1) complex, a deubiquitinating enzyme complex for PCNA and FANCD2. ELG1 protein interacts with PCNAs that are localized at stalled replication forks. ELG1 knockdown specifically resulted in an increase in the level of PCNA monoubiquitination without affecting the level of FANCD2 ubiquitination. It is a novel function of ELG1 distinct from its role as an alternative RFC complex because knockdowns of any other RFC subunits or other alternative RFCs did not affect PCNA monoubiquitination. Lastly, we identified a highly conserved N-terminal domain in ELG1 that was responsible for the USP1-UAF1 interaction as well as the activity to down-regulate PCNA monoubiquitination. Taken together, ELG1 specifically directs USP1-UAF1 complex for PCNA deubiquitination. C1 [Lee, Kyoo-young; Sikdar, Nilabja; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Yang, Kailin; Cohn, Martin A.; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Myung, K (reprint author), NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Rm 4A22, Bethesda, MD 20892 USA. EM kmyung@nhgri.nih.gov RI Yang, Kailin/D-7966-2013; Yang, Kailin/L-2205-2013; OI Yang, Kailin/0000-0001-5968-6738; Cohn, Martin/0000-0002-2988-3009 FU National Institutes of Health [RO1-HL52725, RO1-DK43889, PO1-CA092584]; National Institutes of Health, National Human Genome Research Institute, Intramural Research Program [HG012003-07]; Korean Government [KRF-2007-357C00092] FX This work was supported, in whole or in part, by National Institutes of Health Grants RO1-HL52725, RO1-DK43889, and PO1-CA092584 (to A. D.) and National Institutes of Health, National Human Genome Research Institute, Intramural Research Program Grant HG012003-07 (to K. M.). This work was also supported by Korea Research Foundation Grant KRF-2007-357C00092 funded by the Korean Government (to K. Y. L.). NR 34 TC 60 Z9 62 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10362 EP 10369 DI 10.1074/jbc.M109.092544 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600021 PM 20147293 ER PT J AU Yang, YW Petkova, A Huang, K Xu, B Hua, QX Ye, IJ Chu, YC Hu, SQ Phillips, NB Whittaker, J Ismail-Beigi, F Mackin, RB Katsoyannis, PG Tycko, R Weiss, MA AF Yang, Yanwu Petkova, Aneta Huang, Kun Xu, Bin Hua, Qing-xin Ye, I-Ju Chu, Ying-Chi Hu, Shi-Quan Phillips, Nelson B. Whittaker, Jonathan Ismail-Beigi, Faramarz Mackin, Robert B. Katsoyannis, Panayotis G. Tycko, Robert Weiss, Michael A. TI An Achilles' Heel in an Amyloidogenic Protein and Its Repair INSULIN FIBRILLATION AND THERAPEUTIC DESIGN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOTO-CROSS-LINKING; CHEMICAL-SHIFT INDEX; SOLID-STATE NMR; SECONDARY-STRUCTURE; AMINO-ACIDS; A-CHAIN; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; ROTATING SOLIDS; LISPRO INSULIN AB Insulin fibrillation provides a model for a broad class of amyloidogenic diseases. Conformational distortion of the native monomer leads to aggregation-coupled misfolding. Whereas beta-cells are protected from proteotoxicity by hexamer assembly, fibrillation limits the storage and use of insulin at elevated temperatures. Here, we have investigated conformational distortions of an engineered insulin monomer in relation to the structure of an insulin fibril. Anomalous (13)C NMR chemical shifts and rapid (15)N-detected (1)H-(2)H amide-proton exchange were observed in one of the three classical alpha-helices (residues A1-A8) of the hormone, suggesting a conformational equilibrium between locally folded and unfolded A-chain segments. Whereas hexamer assembly resolves these anomalies in accordance with its protective role, solid-state (13)C NMR studies suggest that the A-chain segment participates in a fibril-specific beta-sheet. Accordingly, we investigated whether helicogenic substitutions in the A1-A8 segment might delay fibrillation. Simultaneous substitution of three beta-branched residues (Ile(A2) -> Leu, Val(A3) -> Leu, and Thr(A8) -> His) yielded an analog with reduced thermodynamic stability but marked resistance to fibrillation. Whereas amide-proton exchange in the A1-A8 segment remained rapid, (13)C alpha chemical shifts exhibited a more helical pattern. This analog is essentially without activity, however, as Ile(A2) and Val(A3) define conserved receptor contacts. To obtain active analogs, substitutions were restricted to A8. These analogs exhibit high receptor-binding affinity; representative potency in a rodent model of diabetes mellitus was similar to wild-type insulin. Although (13)C alpha chemical shifts remain anomalous, significant protection from fibrillation is retained. Together, our studies define an "Achilles' heel" in a globular protein whose repair may enhance the stability of pharmaceutical formulations and broaden their therapeutic deployment in the developing world. C1 [Yang, Yanwu; Huang, Kun; Xu, Bin; Hua, Qing-xin; Ye, I-Ju; Hu, Shi-Quan; Phillips, Nelson B.; Whittaker, Jonathan; Weiss, Michael A.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. [Ismail-Beigi, Faramarz; Weiss, Michael A.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Petkova, Aneta; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Chu, Ying-Chi; Katsoyannis, Panayotis G.] NYU, Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY 10029 USA. [Mackin, Robert B.] Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. RP Yang, YW (reprint author), Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. EM yanwu.yang@case.edu; Michael.Weiss@case.edu RI Huang, Kun/H-4427-2012 FU National Institutes of Health [DK52085, DK079233, DK04949, DK054662]; American Heart Association [0530067N]; American Diabetes Association; NIDDK, National Institutes of Health; Independent University of Bangladesh FX This work was supported, in whole or in part, by National Institutes of Health Grants DK52085 (to R. B. M.) and DK079233, DK04949, and DK054662 (to M. A. W.). This work was also supported by Grant 0530067N from the American Heart Association (to Y. Y.) and a grant from the American Diabetes Association (to N. B. P.). This paper is a contribution from the Cleveland Center for Membrane and Structural Biology. M. A. W. has equity in and consults to Thermalin Diabetes, Inc. (Cleveland, OH).; Solid-state NMR measurements were supported by the Intramural Research Program of the NIDDK, National Institutes of Health. We thank Drs. P. Carey, G. M. Clore, G. G. Dodson, R. Levy, D. F. Steiner, and B. Sykes for discussion; and we thank M. Choquette for technical assistance in generating the labeled DKP-proinsulin. M. A. W. thanks Drs. D. Jacobson (Case Western Reserve University Mandel School of Applied Social Sciences), M. R. Miah (Director, Southern Illinois University Carbondale School of Social Work), M. O. Rahman (Provost, Independent University of Bangladesh), and B. M. Chowdhury (Vice Chancellor, Independent University of Bangladesh) for sponsorship of a student-faculty trip to study poverty, micro-finance, and medical needs in the developing world. NR 88 TC 16 Z9 17 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10806 EP 10821 DI 10.1074/jbc.M109.067850 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600066 PM 20106984 ER PT J AU Saha, A Lee, YC Zhang, ZJ Chandra, G Su, SB Mukherjee, AB AF Saha, Arjun Lee, Yi-Ching Zhang, Zhongjian Chandra, Goutam Su, Shao-Bo Mukherjee, Anil B. TI Lack of an Endogenous Anti-inflammatory Protein in Mice Enhances Colonization of B16F10 Melanoma Cells in the Lungs SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCATION END-PRODUCTS; CANCER-CELLS; MICROENVIRONMENTAL REGULATION; SURFACE RECEPTOR; BINDING PROTEINS; METASTASIS; INFLAMMATION; UTEROGLOBIN; EXPRESSION; DISEASE AB Emerging evidence indicates a link between inflammation and cancer metastasis, but the molecular mechanism(s) remains unclear. Uteroglobin (UG), a potent anti-inflammatory protein, is constitutively expressed in the lungs of virtually all mammals. UG-knock-out (UG-KO) mice, which are susceptible to pulmonary inflammation, and B16F10 melanoma cells, which preferentially metastasize to the lungs, provide the components of a model system to determine how inflammation and metastasis are linked. We report here that B16F10 cells, injected into the tail vein of UG-KO mice, form markedly elevated numbers of tumor colonies in the lungs compared with their wild type littermates. Remarkably, UG-KO mouse lungs overexpress two calcium-binding proteins, S100A8 and S100A9, whereas B16F10 cells express the receptor for advanced glycation end products (RAGE), which is a known receptor for these proteins. Moreover, S100A8 and S100A9 are potent chemoattractants for RAGE-expressing B16F10 cells, and pretreatment of these cells with a blocking antibody to RAGE suppressed migration and invasion. Interestingly, in UG-KO mice S100A8/S100A9 concentrations in blood are lowest in tail vein and highest in the lungs, which most likely guide B16F10 cells to migrate to the lungs. Further, B16F10 cells treated with S100A8 or S100A9 overexpress matrix metalloproteinases, which are known to promote tumor invasion. Most notably, the metastasized B16F10 cells in UG-KO mouse lungs express MMP-2, MMP-9, and MMP-14 as well as furin, a pro-protein convertase that activates MMPs. Taken together, our results suggest that a lack of an anti-inflammatory protein leads to increased pulmonary colonization of melanoma cells and identify RAGE as a potential anti-metastatic drug target. C1 [Mukherjee, Anil B.] Eunice Kennedy Shriver NICHD, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Su, Shao-Bo] Sun Yat Sen Univ, State Key Lab Ophthalmol, Zhongshan Ophthalm Ctr, Guangzhou 510060, Guangdong, Peoples R China. RP Mukherjee, AB (reprint author), Eunice Kennedy Shriver NICHD, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Eunice Kennedy Shriver NICHD, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver NICHD, National Institutes of Health. NR 48 TC 30 Z9 33 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10822 EP 10831 DI 10.1074/jbc.M109.083550 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600067 PM 20118237 ER PT J AU Bektas, M Allende, ML Lee, BG Chen, WP Amar, MJ Remaley, AT Saba, JD Proia, RL AF Bektas, Meryem Allende, Maria Laura Lee, Bridgin G. Chen, WeiPing Amar, Marcelo J. Remaley, Alan T. Saba, Julie D. Proia, Richard L. TI Sphingosine 1-Phosphate Lyase Deficiency Disrupts Lipid Homeostasis in Liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPHINGOLIPID METABOLISM; SPHINGOSINE-1-PHOSPHATE LYASE; SALVAGE PATHWAY; BIOSYNTHESIS; INHIBITION; SPHINGOMYELIN; CHOLESTEROL; SPECIFICITY; INSIGHTS; DISEASE AB The cleavage of sphingoid base phosphates by sphingosine-1-phosphate (S1P) lyase to produce phosphoethanolamine and a fatty aldehyde is the final degradative step in the sphingolipid metabolic pathway. We have studied mice with an inactive S1P lyase gene and have found that, in addition to the expected increase of sphingoid base phosphates, other sphingolipids (including sphingosine, ceramide, and sphingomyelin) were substantially elevated in the serum and/or liver of these mice. This latter increase is consistent with a reutilization of the sphingosine backbone for sphingolipid synthesis due to its inability to exit the sphingolipid metabolic pathway. Furthermore, the S1P lyase deficiency resulted in changes in the levels of serum and liver lipids not directly within the sphingolipid pathway, including phospholipids, triacyglycerol, diacylglycerol, and cholesterol. Even though lipids in serum and lipid storage were elevated in liver, adiposity was reduced in the S1P lyase-deficient mice. Microarray analysis of lipid metabolism genes in liver showed that the S1P lyase deficiency caused widespread changes in their expression pattern, with a significant increase in the expression of PPAR gamma, a master transcriptional regulator of lipid metabolism. However, the mRNA expression of the genes encoding the sphingosine kinases and S1P phosphatases, which directly control the levels of S1P, were not significantly changed in liver of the S1P lyase-deficient mice. These results demonstrate that S1P lyase is a key regulator of the levels of multiple sphingolipid substrates and reveal functional links between the sphingolipid metabolic pathway and other lipid metabolic pathways that may be mediated by shared lipid substrates and changes in gene expression programs. The disturbance of lipid homeostasis by altered sphingolipid levels may be relevant to metabolic diseases. C1 [Proia, Richard L.] NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. [Chen, WeiPing] NIDDK, Microarray Core Lab, Bethesda, MD 20892 USA. [Amar, Marcelo J.; Remaley, Alan T.] NIH, Pulm & Vasc Med Branch, NHLBI, Bethesda, MD 20892 USA. [Saba, Julie D.] CHORI, Oakland, CA 94609 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012 FU NIDDK, National Institutes of Health; NHLBI, National Institutes of Health; National Institutes of Health [CA77528, C06 RR018823] FX This work was supported, in whole or in part, by the Intramural Research Program of the NIDDK and NHLBI, National Institutes of Health, and by National Institutes of Health Grants CA77528 (to J. D. S.) and C06 RR018823 (to the MUSC Lipomics Core). NR 39 TC 75 Z9 75 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10880 EP 10889 DI 10.1074/jbc.M109.081489 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600073 PM 20097939 ER PT J AU Sucic, S Dallinger, S Zdrazil, B Weissensteiner, R Jorgensen, TN Holy, M Kudlacek, O Seidel, S Cha, JH Gether, U Newman, AH Ecker, GF Freissmuth, M Sitte, HH AF Sucic, Sonja Dallinger, Stefan Zdrazil, Barbara Weissensteiner, Rene Jorgensen, Trine N. Holy, Marion Kudlacek, Oliver Seidel, Stefan Cha, Joo Hwan Gether, Ulrik Newman, Amy H. Ecker, Gerhard F. Freissmuth, Michael Sitte, Harald H. TI The N Terminus of Monoamine Transporters Is a Lever Required for the Action of Amphetamines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN DOPAMINE TRANSPORTER; HUMAN SEROTONIN TRANSPORTER; ENERGY-TRANSFER MICROSCOPY; INDUCED REVERSE TRANSPORT; NEUROTRANSMITTER TRANSPORTERS; GABA TRANSPORTER-1; NOREPINEPHRINE TRANSPORTERS; OUTWARD TRANSPORT; LIVING CELLS; BINDING-SITE AB The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERT(T81A) and SERT(T81D), suggested structural changes in the inner vestibule indicative of an opening of the inner vestibule. Predictions from this model (e. g. the preferential accumulation of SERT(T81A) in the inward conformation, its reduced turnover number, and a larger distance between its N and C termini) were verified. Most importantly, SERT(T81A) (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERT(T81A) were comparable with those through the wild type transporter. Both abundant Na(+) entry and accumulation of SERT(T81A) in the inward facing conformation ought to favor amphetamine-induced efflux. Thus, we surmised that the N terminus must play a direct role in driving the transporter into a state that supports amphetamine-induced efflux. This hypothesis was verified by truncating the first 64 amino acids and by tethering the N terminus to an additional transmembrane helix. Either modification abolished amphetamine-induced efflux. We therefore conclude that the N terminus of monoamine transporters acts as a lever that sustains reverse transport. C1 [Kudlacek, Oliver; Seidel, Stefan; Sitte, Harald H.] Med Univ Vienna, Ctr Biomol Med & Pharmacol, Inst Pharmacol, A-1090 Vienna, Austria. [Zdrazil, Barbara; Weissensteiner, Rene; Ecker, Gerhard F.] Univ Vienna, Dept Med Chem, A-1090 Vienna, Austria. [Jorgensen, Trine N.; Gether, Ulrik] Univ Copenhagen, Fac Hlth Sci, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. [Cha, Joo Hwan; Newman, Amy H.] NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Sitte, HH (reprint author), Med Univ Vienna, Ctr Biomol Med & Pharmacol, Inst Pharmacol, Waehringerstr 13A, A-1090 Vienna, Austria. EM harald.sitte@meduniwien.ac.at RI Zdrazil, Barbara/F-1021-2013; Sitte, Harald/N-2681-2013; OI Zdrazil, Barbara/0000-0001-9395-1515; Sitte, Harald/0000-0002-1339-7444; Sucic, Sonja/0000-0001-5136-8022; Ecker, Gerhard/0000-0003-4209-6883; Gether, Ulrik/0000-0002-0020-3807 FU National Institutes of Health [P01 DA 12408]; National Institute on Drug Abuse; FWF [P18706, SFB3506, SFB3502, SFB3510] FX This work was supported, in whole or in part, by National Institutes of Health Grant P01 DA 12408 (to U. G.) and the National Institute on Drug Abuse Intramural Research Program (to A. H. N.). This work was also supported by FWF Grants P18706 and SFB3506 (to H. H. S.), SFB3502 (to G. F. E.), and SFB3510 (to M. F.). NR 71 TC 60 Z9 60 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 10924 EP 10938 DI 10.1074/jbc.M109.083154 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600077 PM 20118234 ER PT J AU Wen, J Chiang, YJ Gao, C Xue, H Xu, JY Ning, YH Hodes, RJ Gao, X Chen, YG AF Wen, Jun Chiang, Y. Jeffrey Gao, Chan Xue, Hua Xu, Jingyue Ning, Yuanheng Hodes, Richard J. Gao, Xiang Chen, Ye-Guang TI Loss of Dact1 Disrupts Planar Cell Polarity Signaling by Altering Dishevelled Activity and Leads to Posterior Malformation in Mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURAL-TUBE CLOSURE; CONVERGENT EXTENSION; MESODERM INDUCTION; AXIS FORMATION; PCP PATHWAY; MOUSE; CATENIN; REGULATOR; INHIBITOR; DAPPER1 AB Wnt signaling plays a key role in embryogenesis and cancer development. Dvl (Dishevelled) is a central mediator for both the canonical and noncanonical Wnt pathways. Dact1 (Dapper1, Dpr1), a Dvl interactor, has been shown to negatively modulate Wnt signaling by promoting lysosomal degradation of Dvl. Here we report that Dact1-deficient mice have multiple physiological defects that resemble the human neonate disease congenital caudal regression syndrome, including caudal vertebrae agenesis, anorectal malformation, renal agenesis/dysplasia, fused kidneys, and loss of bladder. These urogenital defects can be traced to impaired hindgut formation starting at embryonic day 8.25. Examination of morphological changes and Wnt target gene expression revealed that the planar cell polarity (PCP) signaling is deregulated, whereas the canonical Wnt/beta-catenin pathway is largely unaffected in mutant embryos. Consistently, the activity of the PCP signal mediators Rho GTPase and c-Jun N-terminal kinase is altered in Dact1(-/-) mouse embryonic fibroblasts. We further observed alterations in the protein level and the cellular distribution of Dvl in the primitive streak of mutant embryos. An increased amount of Dvl2 tends to be accumulated in the cortical regions of the cells, especially at the primitive streak ectoderm close to the posterior endoderm that lately forms the hindgut diverticulum. Together, these data suggest that Dact1 may regulate vertebrate PCP by controlling the level and the cellular localization of Dvl protein. C1 [Wen, Jun; Gao, Chan; Xue, Hua; Ning, Yuanheng; Chen, Ye-Guang] Tsinghua Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. [Chiang, Y. Jeffrey; Hodes, Richard J.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Hodes, Richard J.] NIA, NIH, Bethesda, MD 20892 USA. [Xu, Jingyue; Gao, Xiang] Nanjing Univ, MOE, Key Lab Model Anim Dis Study, Nanjing 210061, Peoples R China. [Xu, Jingyue; Gao, Xiang] Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Peoples R China. RP Chen, YG (reprint author), Tsinghua Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China. EM ygchen@tsinghua.edu.cn RI Gao, Chan/D-7964-2013 FU National Natural Science Foundation of China [30930050, 30921004]; 973 Program [2006CB943401] FX This work was supported, in whole or in part, by a National Institutes of Health Intramural Research Program grant ( to Y.J.C.). This work was also supported by National Natural Science Foundation of China Grants 30930050 and 30921004 and 973 Program Grant 2006CB943401 ( to Y.-G.C.). NR 64 TC 32 Z9 35 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 2 PY 2010 VL 285 IS 14 BP 11023 EP 11030 DI 10.1074/jbc.M109.085381 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 578AC UT WOS:000276264600086 PM 20145239 ER PT J AU Yang, Y Gu, DY Aisa, HA Ito, Y AF Yang, Yi Gu, Dongyu Aisa, Haji Akber Ito, Yoichiro TI Studies on the effect of column angle in centrifugal helix counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Centrifugal counter-current chromatography; Angle between column axis and centrifugal force; Retention of the stationary phase; Resolution; Dipeptide; DNP-amino acid AB The performance of the coiled column of centrifugal counter-current chromatography was investigated by changing the angle between column axis and centrifugal force in the separation of dipeptides or DNP-amino acids each with suitable two-phase solvent systems. In general, retention of the stationary phase (Sf) decreased, and peak resolution (Rs) increased as the column angle was increased. The first series of experiments was performed using a polar two-phase solvent system composed of 1-butanol acetic acid water (4:1:5, v/v/v) to separate two dipeptide samples, Trp-Tyr and Val-Tyr, at a flow rate of 1 ml/min at 1000 rpm. When the column angle was changed from 0 degrees to 90 degrees. Rs increased from 1.05 (Sf = 60.1%) to 1.17 (Sf = 38.7%) with the lower phase mobile and from 1.02 (Sf = 67.8%) to 1.14 (Sf = 47.4%) with the upper phase mobile, respectively. The second series of experiments was similarly performed with a more hydrophobic two-phase solvent system composed of hexane ethyl acetate methanol-0.1 M hydrochloric acid (1:1:1:1, v/v/v/v) to separate three DNP-amino acids. DNP-glu, DNP-beta-ala and DNP-ala, at a flow rate of 1 ml/min at 1000 rpm. When the column angle was changed from 0 degrees to 90 degrees. Rs increased from 1.38 (1st peak/2nd peak) and 1.20 (2nd peak/3rd peak) (Sf = 61.1%) to 1.66 and 1.45 (Sf= 34.4%) with the lower phase mobile and from 1.14 and 0.63 (Sf = 72.2%) to 1.53 and 0.87 (Sf = 51.1%) with the upper phase mobile, respectively. The overall results of our studies indicate that increasing the column angle against the radially acting centrifugal force enhances the mixing of two phases in the column to improve the peak while decreasing the stationary phase retention by interrupting the laminar flow of the mobile phase. Published by Elsevier B.V. C1 [Yang, Yi; Gu, Dongyu; Ito, Yoichiro] NHLBI, NIH, Bioseparat Technol Lab, Biochem & Biophys Ctr, Bethesda, MD 20892 USA. [Yang, Yi; Gu, Dongyu; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Xinjiang Tech Inst Phys & Chem, Urumqi 830011, Peoples R China. [Yang, Yi; Gu, Dongyu] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China. RP Ito, Y (reprint author), NHLBI, NIH, Bioseparat Technol Lab, Biochem & Biophys Ctr, Bldg 10,Room 8N230,10 Ctr Dr,MSC 1762, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov FU Intramural NIH HHS [ZIA HL006022-01] NR 7 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 2 PY 2010 VL 1217 IS 14 BP 2117 EP 2122 DI 10.1016/j.chroma.2010.02.003 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 578HZ UT WOS:000276285600006 PM 20188375 ER PT J AU Stahl, SJ Watts, NR Rader, C DiMattia, MA Mage, RG Palmer, I Kaufman, JD Grimes, JM Stuart, DI Steven, AC Wingfield, PT AF Stahl, Stephen J. Watts, Norman R. Rader, Christoph DiMattia, Michael A. Mage, Rose G. Palmer, Ira Kaufman, Joshua D. Grimes, Jonathan M. Stuart, David I. Steven, Alasdair C. Wingfield, Paul T. TI Generation and Characterization of a Chimeric Rabbit/Human Fab for Co-Crystallization of HIV-1 Rev SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE rabbit antibody; phage display; humanized Fab; scFv; crystallization chaperone ID PHAGE-DISPLAY LIBRARY; ANTIBODY LIBRARIES; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; PROTEIN; FRAGMENTS; CRYSTALLIZATION; REPERTOIRE; MOLECULE; RECEPTOR AB Rev is a key regulatory protein of human immunodeficiency virus type 1. Its function is to bind to viral transcripts and effect export from the nucleus of unspliced mRNA, thereby allowing the synthesis of structural proteins. Despite its evident importance, the structure of Rev has remained unknown, primarily because Rev's proclivity for polymerization and aggregation is an impediment to crystallization. Monoclonal antibody antigen-binding domains (Fabs) have proven useful for the co-crystallization of other refractory proteins. In the present study, a chimeric rabbit/human anti-Rev Fab was selected by phage display, expressed in a bacterial secretion system, and purified from the media. The Fab readily solubilized polymeric Rev. The resulting Fab/Rev complex was purified by metal ion affinity chromatography and characterized by analytical ultracentrifugation, which demonstrated monodispersity and indicated a 1:1 molar stoichiometry. The Fab binds with very high affinity, as determined by surface plasmon resonance, to a conformational epitope in the N-terminal half of Rev. The complex forms crystals suitable for structure determination. The ability to serve as a crystallization aid is a new application of broad utility for chimeric rabbit/human Fab. The corresponding single-chain antibody (scFv) was also prepared, offering the potential of intracellular antibody therapeutics against human immunodeficiency virus type 1. Published by Elsevier Ltd. C1 [Stahl, Stephen J.; Watts, Norman R.; Palmer, Ira; Kaufman, Joshua D.; Wingfield, Paul T.] NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [DiMattia, Michael A.; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. [DiMattia, Michael A.; Grimes, Jonathan M.; Stuart, David I.] Univ Oxford, Div Struct Biol, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Mage, Rose G.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Wingfield, PT (reprint author), NIAMSD, Prot Express Lab, NIH, Bldg 6B,Room 1B130, Bethesda, MD 20892 USA. EM peipw@helix.nih.gov FU Intramural Research Programs of NIAMS; National Cancer Institute; NIAID; Intramural Targeted Antiviral Program of the National Institutes of Health; National Institutes of Health-Oxford Scholars Program; UK Medical Research council; SPINE2COMPLEXES [LSHGCT-2006-031220] FX We thank Dr. J. Vethanayagam [National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)], C. Alexander, and B. Newman [National Institute of Allergy and Infectious Diseases (NIAID)], as well as the staff at the Diamond Light Source, for their expert technical assistance. We also thank Drs. N. Noinaj and S. Buchanan [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)] for advice and provision of resources during the initial crystallization and crystal evaluation experiments and Dr. E. Kandiah (NIAMS) for insightful discussions. This work was supported by the Intramural Research Programs of NIAMS, National Cancer Institute, and NIAID and by the Intramural Targeted Antiviral Program of the National Institutes of Health, as well as by the National Institutes of Health-Oxford Scholars Program. Support was also provided by the UK Medical Research council (D.I.S.) and by SPINE2COMPLEXES (LSHGCT-2006-031220) G.M.G.). NR 39 TC 13 Z9 14 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 2 PY 2010 VL 397 IS 3 BP 697 EP 708 DI 10.1016/j.jmb.2010.01.061 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 576VI UT WOS:000276177300007 PM 20138059 ER PT J AU Mo, C Vire, B Wiestner, A AF Mo, Clifton Vire, Berengere Wiestner, Adrian TI Rituximab: Therapeutic Benefit! Vitamin R? SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOMA; CELLS; CD20 C1 [Mo, Clifton; Vire, Berengere; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Mo, C (reprint author), NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HL999999] NR 6 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2010 VL 47 IS 2 BP 105 EP 106 DI 10.1053/j.seminhematol.2010.02.003 PG 2 WC Hematology SC Hematology GA 580YP UT WOS:000276487300001 PM 20350656 ER PT J AU Dunleavy, K Tay, K Wilson, WH AF Dunleavy, Kieron Tay, Kevin Wilson, Wyndham H. TI Rituximab-Associated Neutropenia SO SEMINARS IN HEMATOLOGY LA English DT Article ID LATE-ONSET NEUTROPENIA; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY THERAPY; B-CELL LYMPHOMA; CHEMOKINE RECEPTOR CXCR4; BONE-MARROW; FACTOR-I; CHEMOTHERAPY; LEUKEMIA; TRANSPLANTATION AB Several recent studies have reported the phenomenon of late-onset neutropenia occurring usually several months following the administration of rituximab or rituximab-based therapies. While it appears that late-onset neutropenia is usually not clinically significant and is self-limited, it is important to recognize its existence given the expanding use of rituximab in both hematologic and nonhematologic disorders. Late-onset neutropenia is intriguing biologically and while its pathogenesis and mechanism are not completely understood, many interesting hypotheses have been proposed to explain its occurrence. Semin Hematol 47:180-186. (C) 2010 Published by Elsevier Inc. C1 [Dunleavy, Kieron; Tay, Kevin; Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), Metab Branch, Bldg 10,Room 4-N-115, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 35 TC 28 Z9 28 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2010 VL 47 IS 2 BP 180 EP 186 DI 10.1053/j.seminhematol.2010.01.009 PG 7 WC Hematology SC Hematology GA 580YP UT WOS:000276487300010 PM 20350665 ER PT J AU Gea-Banacloche, JC AF Gea-Banacloche, Juan C. TI Rituximab-Associated Infections SO SEMINARS IN HEMATOLOGY LA English DT Article ID HEPATITIS-B-VIRUS; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; PNEUMOCYSTIS-JIROVECII PNEUMONIA; ANTI-CD20 MONOCLONAL-ANTIBODY; PHASE-II TRIAL; INTENSIVE IMMUNOSUPPRESSIVE THERAPIES AB After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (NW) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management. Semin Hematol 47:187-198. (C) 2010 Published by Elsevier Inc. C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Gea-Banacloche, JC (reprint author), NCI, Expt Transplantat & Immunol Branch, 10 Ctr Dr,Room 3E-3-3330, Bethesda, MD 20892 USA. EM banacloj@mail.nih.gov NR 123 TC 100 Z9 103 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2010 VL 47 IS 2 BP 187 EP 198 DI 10.1053/j.seminhematol.2010.01.002 PG 12 WC Hematology SC Hematology GA 580YP UT WOS:000276487300011 PM 20350666 ER PT J AU Joyce, MG Radaev, S Sun, PD AF Joyce, M. Gordon Radaev, Sergei Sun, Peter D. TI A rational approach to heavy-atom derivative screening SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID QUICK-SOAK METHOD; BINDING; RESOLUTION; CRYSTALS AB Despite the development in recent times of a range of techniques for phasing macromolecules, the conventional heavy-atom derivatization method still plays a significant role in protein structure determination. However, this method has become less popular in modern high-throughput oriented crystallography, mostly owing to its trial-and-error nature, which often results in lengthy empirical searches requiring large numbers of well diffracting crystals. In addition, the phasing power of heavy-atom derivatives is often compromised by lack of isomorphism or even loss of diffraction. In order to overcome the difficulties associated with the 'classical' heavy-atom derivatization procedure, an attempt has been made to develop a rational crystal-free heavy-atom derivative-screening method and a quick-soak derivatization procedure which allows heavy-atom compound identification. The method includes three basic steps: (i) the selection of likely reactive compounds for a given protein and specific crystallization conditions based on pre-defined heavy-atom compound reactivity profiles, (ii) screening of the chosen heavy-atom compounds for their ability to form protein adducts using mass spectrometry and (iii) derivatization of crystals with selected heavy-metal compounds using the quick-soak method to maximize diffraction quality and minimize non-isomorphism. Overall, this system streamlines the process of heavy-atom compound identification and minimizes the problem of non-isomorphism in phasing. C1 [Joyce, M. Gordon; Radaev, Sergei; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov NR 17 TC 7 Z9 8 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD APR PY 2010 VL 66 BP 358 EP 365 DI 10.1107/S0907444909053074 PN 4 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 573US UT WOS:000275941300004 PM 20382988 ER PT J AU Dauter, Z AF Dauter, Zbigniew TI Carrying out an optimal experiment SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID DIFFRACTION DATA-COLLECTION; RADIATION; STRATEGIES; REFINEMENT; SAD AB Diffraction data collection is the last experimental stage in structural crystallography. It has several technical and theoretical aspects and a compromise usually has to be found between various parameters in order to achieve optimal data quality. The influence and importance of various experimental parameters and their consequences are discussed in the context of different data applications, such as molecular replacement, anomalous phasing, high-resolution refinement or searching for ligands. C1 NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA. EM dauter@anl.gov NR 18 TC 16 Z9 17 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD APR PY 2010 VL 66 BP 389 EP 392 DI 10.1107/S0907444909038578 PN 4 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 573US UT WOS:000275941300008 PM 20382992 ER PT J AU Galkin, A Kulakova, L Wu, R Nash, TE Dunaway-Mariano, D Herzberg, O AF Galkin, Andrey Kulakova, Liudmila Wu, Rui Nash, Theodore E. Dunaway-Mariano, Debra Herzberg, Osnat TI X-ray structure and characterization of carbamate kinase from the human parasite Giardia lamblia SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article DE carbamate kinases; arginine dehydrolase pathway; Giardia lamblia; drug targets ID ARCHAEON PYROCOCCUS-FURIOSUS; PHOSPHATE SYNTHETASE; FUSION PROTEINS; INTESTINALIS; EXPRESSION; ARGININE; ENZYME; SOFTWARE; GENE AB Carbamate kinase catalyzes the reversible conversion of carbamoyl phosphate and ADP to ATP and ammonium carbamate, which is hydrolyzed to ammonia and carbonate. The three-dimensional structure of carbamate kinase from the human parasite Giardia lamblia (glCK) has been determined at 3 A resolution. The crystals belonged to the monoclinic space group P2(1), with unit-cell parameters a = 69.77, b = 85.41, c = 102.1 A, beta = 106.8 degrees. The structure was refined to a final R factor of 0.227. The essentiality of glCK together with its absence in humans makes the enzyme an attractive candidate for anti-Giardia drug development. Steady-state kinetic rate constants have been determined. The k (cat) for ATP formation is 319 +/- 9 s-1. The K (m) values for carbamoyl phosphate and ADP are 85 +/- 6 and 70 +/- 5 mu M, respectively. The structure suggests that three invariant lysine residues (Lys131, Lys216 and Lys278) may be involved in the binding of substrates and phosphoryl transfer. The structure of glCK reveals that a glycerol molecule binds in the likely carbamoyl phosphate-binding site. C1 [Galkin, Andrey; Kulakova, Liudmila; Herzberg, Osnat] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. [Wu, Rui; Dunaway-Mariano, Debra] Univ New Mexico, Dept Chem & Chem Biol, Albuquerque, NM 87131 USA. [Nash, Theodore E.] NIAID, Lab Parasit Dis, NIH, Bethesda, MD USA. RP Herzberg, O (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. EM herzberg@umbi.umd.edu RI Wu, Rui/E-3728-2010 FU National Institutes of Health [R01 AI059733] FX This work was supported by a grant from the National Institutes of Health (R01 AI059733). NR 25 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD APR PY 2010 VL 66 BP 386 EP 390 DI 10.1107/S1744309110004665 PN 4 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 580ZC UT WOS:000276488700003 PM 20383005 ER PT J AU Bloch, M Tong, VT Novotny, TE England, LJ Dietz, PM Kim, SY Samet, JM Tolosa, JE AF Bloch, Michele Tong, Van T. Novotny, Thomas E. England, Lucinda J. Dietz, Patricia M. Kim, Shin Y. Samet, Jonathan M. Tolosa, Jorge E. TI Tobacco use and secondhand smoke exposure among pregnant women in low- and middle-income countries: a call to action SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Editorial Material DE Pregnancy; women's health issues in developing countries; health care policy; maternal mortality and morbidity; preterm birth; tobacco C1 [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Div Maternal Fetal Med, Global Network Perinatal & Reprod Hlth, Portland, OR 97239 USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. [Bloch, Michele] NCI, Bethesda, MD 20892 USA. [Tong, Van T.; England, Lucinda J.; Dietz, Patricia M.; Kim, Shin Y.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Novotny, Thomas E.] San Diego State Univ, San Diego, CA 92182 USA. [Samet, Jonathan M.] Univ So Calif, Inst Global Hlth, Los Angeles, CA USA. RP Tolosa, JE (reprint author), Oregon Hlth & Sci Univ, Div Maternal Fetal Med, Global Network Perinatal & Reprod Hlth, 3181 SW Sam Jackson Pk Rd,L-458, Portland, OR 97239 USA. EM tolosaj@ohsu.edu OI Tong, Van/0000-0002-3970-1440 NR 9 TC 7 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 418 EP 422 DI 10.3109/00016341003605735 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700003 PM 20367426 ER PT J AU Oncken, CA Dietz, PM Tong, VT Belizan, JM Tolosa, JE Berghella, V Goldenberg, RL Lando, HA Samet, JM Bloch, MH AF Oncken, Cheryl A. Dietz, Patricia M. Tong, Van T. Belizan, Jose M. Tolosa, Jorge E. Berghella, Vincenzo Goldenberg, Robert L. Lando, Harry A. Samet, Jonathan M. Bloch, Michele H. TI Prenatal tobacco prevention and cessation interventions for women in low- and middle-income countries SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Review DE Global; tobacco; perinatal and reproductive health ID RANDOMIZED CONTROLLED-TRIAL; NICOTINE REPLACEMENT THERAPY; CIGARETTE WARNING LABELS; SMOKING-CESSATION; PREGNANT-WOMEN; SMOKELESS TOBACCO; INCREASED RISK; CHILD MALNUTRITION; PATERNAL SMOKING; SECONDHAND SMOKE AB Although the prevalence of tobacco use is decreasing in many high-income countries, it is increasing in many low- and middle-income countries. The health and economic burden of increasing tobacco use and dependence is predictable and will have devastating effects in countries with limited resources, particularly for vulnerable populations such as pregnant women. We sought to review effective tobacco prevention and intervention strategies for decreasing tobacco use and secondhand smoke exposure before and during pregnancy in high-, middle-, and low- income countries. We reviewed several types of interventions, including population-level efforts ( increasing tobacco prices, implementing tobacco control policies), community interventions, clinical interventions, and pharmacological treatments. A second purpose of this report is to present findings of an international expert working group that was convened to review the evidence and to establish research priorities in the following areas: ( a) preventing the uptake and reducing tobacco use among girls and women of reproductive age; and (b) reducing tobacco use and secondhand smoke exposure among pregnant women. The working group considered the evidence on existing interventions in terms of burden of disease, intervention impact, intervention costs, feasibility of integration into existing services, uniqueness of the contribution, and overall feasibility. Finally, we present the working group's recommendations for intervention research priorities. C1 [Oncken, Cheryl A.] Univ Connecticut, Sch Med, Dept Med, Farmington, CT 06030 USA. [Oncken, Cheryl A.] Univ Connecticut, Sch Med, Dept Obstet & Gynecol, Farmington, CT 06030 USA. [Dietz, Patricia M.; Tong, Van T.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. [Belizan, Jose M.] Inst Clin Effectiveness & Hlth Policy, Dept Mother & Child Hlth Res, Buenos Aires, DF, Argentina. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Tolosa, Jorge E.; Berghella, Vincenzo] Global Network Perinatal & Reprod Hlth, Portland, OR USA. [Berghella, Vincenzo] Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. [Goldenberg, Robert L.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Lando, Harry A.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Samet, Jonathan M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Bloch, Michele H.] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Oncken, CA (reprint author), Univ Connecticut, Sch Med, Dept Med, MC 3940,263 Farmington Ave, Farmington, CT 06030 USA. EM oncken@nso2.uchc.edu OI Tong, Van/0000-0002-3970-1440; Belizan, Jose/0000-0002-8412-3010; Berghella, Vincenzo/0000-0003-2854-0239 FU NICHD NIH HHS [U01 HD040607] NR 71 TC 18 Z9 19 U1 3 U2 13 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 442 EP 453 DI 10.3109/00016341003678450 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700005 PM 20235895 ER PT J AU England, LJ Kim, SY Tomar, SL Ray, CS Gupta, PC Eissenberg, T Cnattingius, S Bernert, JT Tita, ATN Winn, DM Djordjevic, MV Lambe, M Stamilio, D Chipato, T Tolosa, JE AF England, Lucinda J. Kim, Shin Y. Tomar, Scott L. Ray, Cecily S. Gupta, Prakash C. Eissenberg, Thomas Cnattingius, Sven Bernert, John T. Tita, Alan Thevenet N. Winn, Deborah M. Djordjevic, Mirjana V. Lambe, Mats Stamilio, David Chipato, Tsungai Tolosa, Jorge E. TI Non-cigarette tobacco use among women and adverse pregnancy outcomes SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Review DE Global; smokeless; tobacco; waterpipe; pregnancy ID SMOKELESS TOBACCO; BIRTH-WEIGHT; UNIVERSITY-STUDENTS; ALASKA NATIVES; SMOKING; PREVALENCE; WATERPIPE; INDIA; EXPOSURE; RISK AB Although cigarette smoking remains the most prevalent form of tobacco use in girls and in women of reproductive age globally, use of non-cigarette forms of tobacco is prevalent or gaining in popularity in many parts of the world, especially in low- and middle-income countries. Sparse but growing evidence suggests that the use of some non-cigarette tobacco products during pregnancy increases the risk of adverse pregnancy outcomes. In this paper we review the literature on the prevalence of non-cigarette tobacco product use in pregnant women and in women of reproductive age in high-, middle-, and low- income countries and the evidence that maternal use of these products during pregnancy has adverse health effects. In addition, we communicate findings from an international group of perinatal and tobacco experts that was convened to establish research priorities concerning the use of non-cigarette tobacco products during pregnancy. The working group concluded that attempts to develop a public health response to non-cigarette tobacco use in women are hindered by a lack of data on the epidemiology of use in many parts of the world and by our limited understanding of the type and magnitude of the health effects of these products. We highlight research gaps and provide recommendations for a global research agenda. C1 [England, Lucinda J.; Kim, Shin Y.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30030 USA. [Tomar, Scott L.] Univ Florida, Coll Dent, Dept Community Dent & Behav Sci, Gainesville, FL USA. [Ray, Cecily S.; Gupta, Prakash C.] Healis Sekhsaria Inst Publ Hlth, Navi Mumbai, India. [Eissenberg, Thomas] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Eissenberg, Thomas] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA 23284 USA. [Cnattingius, Sven] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Bernert, John T.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Tita, Alan Thevenet N.] Univ Alabama, Dept Obstet & Gynecol, Ctr Womens Reprod Hlth, Birmingham, AL 35294 USA. [Winn, Deborah M.; Djordjevic, Mirjana V.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Lambe, Mats] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Stamilio, David] St Louis Univ, Sch Med, Washington Univ, Dept Obstet & Gynecol, St Louis, MO USA. [Chipato, Tsungai] Univ Zimbabwe, Coll Hlth Sci, Dept Obstet & Gynecol, Harare, Zimbabwe. [Chipato, Tsungai; Tolosa, Jorge E.] Global Network Perinatal & Reprod Hlth, Portland, OR USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. RP England, LJ (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, 4770 Buford Highway NE,MS K-23, Atlanta, GA 30030 USA. EM lbe9@cdc.gov OI Lambe, Mats/0000-0002-4624-3767 NR 51 TC 20 Z9 21 U1 4 U2 9 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 454 EP 464 DI 10.3109/00016341003605719 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700006 PM 20225987 ER PT J AU Nichter, M Greaves, L Bloch, M Paglia, M Scarinci, I Tolosa, JE Novotny, TE AF Nichter, Mimi Greaves, Lorraine Bloch, Michele Paglia, Michael Scarinci, Isabel Tolosa, Jorge E. Novotny, Thomas E. TI Tobacco use and secondhand smoke exposure during pregnancy in low- and middle-income countries: the need for social and cultural research SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Review DE Women's health issues in developing countries; tobacco; smoking; secondhand smoke; smokeless tobacco ID CIGARETTE-SMOKING; EDUCATIONAL-LEVEL; NATIONAL-SURVEY; YOUNG-PEOPLE; WOMEN; HEALTH; PREVALENCE; GENDER; TRENDS; PERCEPTIONS AB Tobacco use is a leading cause of death and of poor pregnancy outcome in many countries. While tobacco use is decreasing in many high-income countries, it is increasing in many low- and middle-income countries (LMICs), where by the year 2030, 80% of deaths caused by tobacco use are expected to occur. In many LMICs, few women smoke tobacco, but strong evidence indicates this is changing; increased tobacco smoking by pregnant women will worsen pregnancy outcomes, especially in resource-poor settings, and threatens to undermine or reverse hard-won gains in maternal and child health. To date, little research has focused on preventing pregnant women's tobacco use and secondhand smoke (SHS) exposure in LMICs. Research on social and cultural influences on pregnant women's tobacco use will greatly facilitate the design and implementation of effective prevention programs and policies, including the adaptation of successful strategies used in high-income countries. This paper describes pregnant women's tobacco use and SHS exposure and the social and cultural influences on pregnant women's tobacco exposure; it also presents a research agenda put forward by an international workgroup convened to make recommendations in this area. C1 [Nichter, Mimi] Univ Arizona, Tucson, AZ USA. [Greaves, Lorraine] British Columbia Ctr Excellence Womens Hlth, Vancouver, BC, Canada. [Bloch, Michele] NCI, Rockville, MD USA. [Paglia, Michael] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Scarinci, Isabel] Univ Alabama, Birmingham, AL USA. [Tolosa, Jorge E.] Global Network Perinatal & Reprod Hlth, Portland, OR USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. [Novotny, Thomas E.] San Diego State Univ, San Diego, CA 92182 USA. RP Bloch, M (reprint author), NCI, Tobacco Control Res Branch, Execut Plaza N,Room 4038,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM blochm@mail.nih.gov NR 88 TC 26 Z9 28 U1 1 U2 6 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 465 EP 477 DI 10.3109/00016341003592552 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700007 PM 20225988 ER PT J AU Chomba, E Tshefu, A Onyamboko, M Kaseba-Sata, C Moore, J McClure, EM Moss, N Goco, N Bloch, M Goldenberg, RL AF Chomba, Elwyn Tshefu, Antoinette Onyamboko, Marie Kaseba-Sata, Christine Moore, Janet McClure, Elizabeth M. Moss, Nancy Goco, Norman Bloch, Michele Goldenberg, Robert L. TI Tobacco use and secondhand smoke exposure during pregnancy in two African countries: Zambia and the Democratic Republic of the Congo SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE Women's health issues in developing countries; tobacco; smoking; smokeless tobacco; passive smoking ID WARNING LABELS; WOMEN; RISK; DISEASE; BURDEN; COHORT; MUMBAI; INDIA AB Objective. To study pregnant women's knowledge, attitudes and behaviors towards tobacco use and secondhand smoke (SHS) exposure, and exposure to advertising for and against tobacco products in Zambia and the Democratic Republic of the Congo (DRC). Design. Prospective cross-sectional survey between November 2004 and September 2005. Setting. Antenatal care clinics in Lusaka, Zambia, and Kinshasa, DRC. Population. Pregnant women in Zambia ( 909) and the DRC ( 847). Methods. Research staff administered a structured questionnaire to pregnant women attending antenatal care clinics. Main outcome measures. Pregnant women's use of tobacco, exposure to SHS, knowledge of the harms of tobacco and exposure to advertising for and against tobacco products. Results. Only about 10% of pregnant women reported ever having tried cigarettes (6.6% Zambia; 14.1% DRC). However, in the DRC, 41.8% of pregnant women had tried other forms of tobacco, primarily snuff. About 10% of pregnant women and young children were frequently or always exposed to SHS. Pregnant women's knowledge of the hazards of smoking and SHS exposure was extremely limited. About 13% of pregnant women had seen or heard advertising for tobacco products in the last 30 days. Conclusions. Tobacco use and SHS exposure pose serious threats to the health of women, infants and children. In many African countries, maternal and infant health outcomes are often poor and will likely worsen if maternal tobacco use increases. Our findings suggest that a 'window of opportunity' exists to prevent increased tobacco use and SHS exposure of pregnant women in Zambia and the DRC. C1 [Chomba, Elwyn; Kaseba-Sata, Christine] Univ Zambia, Lusaka, Zambia. [Tshefu, Antoinette; Onyamboko, Marie] Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Moore, Janet; McClure, Elizabeth M.; Goco, Norman] Res Triangle Inst, Res Triangle Pk, NC 27709 USA. [Moss, Nancy] NICHHD, Rockville, MD USA. [Bloch, Michele] NCI, Rockville, MD USA. [Goldenberg, Robert L.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. RP Bloch, M (reprint author), NCI, Execut Plaza N,Room 4038,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM blochm@mail.nih.gov FU U.S. National Institute of Child Health and Human Development [UO1 HD043475, UO1 HD043464, UO1 HD040607]; U.S. National Cancer Institute; U.S. Department of Health and Human Services' Office on Women's Health; Bill and Melinda Gates Foundation; National Cancer Institute FX Funding for the study was provided by the U.S. National Institute of Child Health and Human Development (UO1 HD043475, UO1 HD043464 and UO1 HD040607), the U.S. National Cancer Institute, the U.S. Department of Health and Human Services' Office on Women's Health and the Bill and Melinda Gates Foundation. The manuscript was approved for publication by the National Cancer Institute and the National Institute of Child Health and Human Development. The authors appreciate the efforts of the field staff who administered the survey and the pregnant women who participated. NR 43 TC 8 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 531 EP 539 DI 10.3109/00016341003605693 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700014 PM 20230310 ER PT J AU Kadir, MM McClure, EM Goudar, SS Garces, AL Moore, J Onyamboko, M Kaseba, C Althabe, F Castilla, EE Freire, S Parida, S Saleem, S Wright, LL Goldenberg, RL AF Kadir, Muhammad Masood McClure, Elizabeth M. Goudar, Shivaprasad S. Garces, Ana L. Moore, Janet Onyamboko, Marie Kaseba, Christine Althabe, Fernando Castilla, Eduardo E. Freire, Salvio Parida, Sailajanandan Saleem, Sarah Wright, Linda L. Goldenberg, Robert L. CA Global Network Tobacco Study Grp TI Exposure of pregnant women to indoor air pollution: a study from nine low and middle income countries SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE Pregnancy; indoor air pollution; second-hand tobacco smoke exposure; smoking ID ACUTE RESPIRATORY-INFECTIONS; POOR RURAL-AREAS; LOW-BIRTH-WEIGHT; BIOMASS COMBUSTION; CARBON-MONOXIDE; TOBACCO-SMOKE; FETAL HEALTH; GUATEMALA; CHILDREN; INFANT AB Objective. We studied exposure to solid fuel and second-hand tobacco smoke among pregnant women in south Asia, Africa and Latin America. Design. Prospective cross-sectional survey. Setting. Antenatal clinics in Argentina, Brazil, Ecuador, Guatemala, Uruguay, Democratic Republic of Congo, Zambia, India and Pakistan. Sample. A total of 7,961 pregnant women in ten sites in nine countries were interviewed between October 2004 and September 2005. Methods. A standardized questionnaire on exposure to indoor air pollution (IAP) and second-hand smoke was administered to pregnant women during antenatal care. Main outcome measures. Exposure to IAP and second-hand tobacco smoke. Results. South Asian pregnant women commonly reported use of wood (49.1-89.7%), crop residue and animal dung as cooking and heating fuel. African pregnant women reported higher use of charcoal (85.4-93.5%). Latin American pregnant women had greater use of petroleum gas. Among south Asian women, solid fuel use and cooking on an open flame inside the home were common. There was a significant association between solid fuel use and allowing smoking within the home at the Asian sites and in Zambia (p < 0.05). Conclusions. Pregnant women from low/middle income countries were commonly exposed to IAP secondary to use of solid fuels. Among these populations, exposure to second-hand tobacco smoke was also common. This combination of exposures likely increases the risk of poor pregnancy outcomes among the most vulnerable women. Our study highlights the importance of further research on the combined impact of IAP and second-hand tobacco smoke exposures on adverse maternal and perinatal outcomes. C1 [McClure, Elizabeth M.; Moore, Janet] Res Triangle Inst, Dept Stat & Epidemiol, Durham, NC 27709 USA. [Kadir, Muhammad Masood; Saleem, Sarah] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [Goudar, Shivaprasad S.] Jawaharlal Nehru Med Coll, Belgaum, India. [Garces, Ana L.] San Carlos Univ, Guatemala City, Guatemala. [Onyamboko, Marie] Univ Kinshasa, Kinshasa Sch Publ Hlth, Kinshasa, Zaire. [Althabe, Fernando] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Kaseba, Christine] Univ Teaching Hosp, Lusaka, Zambia. [Castilla, Eduardo E.] Estudio Colaborat Latinoamer Malformac Congenitas, Rio De Janeiro, Brazil. [Freire, Salvio] Univ Fed Pernambuco, Recife, PE, Brazil. [Parida, Sailajanandan] SCB Med Coll, Cuttack, Orissa, India. [Wright, Linda L.] NICHHD, Bethesda, MD 20892 USA. [Goldenberg, Robert L.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. RP McClure, EM (reprint author), Res Triangle Inst, Dept Stat & Epidemiol, 3040 Cornwallis Dr, Durham, NC 27709 USA. EM mcclure@rti.org OI GOUDAR, SHIVAPRASAD/0000-0002-8680-7053 FU U.S. Eunice Shriver National Institute of Child Health and Human Development; U.S. National Cancer Institute FX This study was funded by grants from the U.S. Eunice Shriver National Institute of Child Health and Human Development and the U.S. National Cancer Institute. NR 33 TC 12 Z9 12 U1 1 U2 9 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD APR PY 2010 VL 89 IS 4 BP 540 EP 548 DI 10.3109/00016340903473566 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 588SR UT WOS:000277094700015 PM 19961275 ER PT J AU Subramaniam, GA Ives, ML Stitzer, ML Dennis, ML AF Subramaniam, Geetha A. Ives, Melissa L. Stitzer, Maxine L. Dennis, Michael L. TI The added risk of opioid problem use among treatment-seeking youth with marijuana and/or alcohol problem use SO ADDICTION LA English DT Article DE Adolescents; clinical characteristics; HIV risk behaviors; opioid-dependent youth; opioid-use risk; problem opioid use; psychiatric comorbidity ID CLINICAL CHARACTERISTICS; HEROIN DEPENDENCE; PROPENSITY SCORE; SUBSTANCE USE; USE DISORDERS; ADOLESCENTS; ADDICTION; OUTCOMES; CAUSAL; TRIAL AB Objectives To determine the added risk of opioid problem use (OPU) in youth with marijuana/alcohol problem use (MAPU). Methods A total of 475 youth (ages 14-21 years) with OPU + MAPU were compared to a weighted sample of 475 youth with MAPU only (i.e. no OPU) before and after propensity score matching on gender, age, race, level of care and weekly use of marijuana/alcohol. Youth were recruited from 88 drug treatment sites participating in eight Center for Substance Abuse Treatment-funded grants. At treatment intake, participants were administered the Global Appraisal of Individual Need to elicit information on demographic, social, substance, mental health, human immunodeficiency virus (HIV), physical and legal characteristics. Odds ratios with confidence intervals were calculated. Results The added risk of OPU among MAPU youth was associated with greater comorbidity; higher rates of psychiatric symptoms and trauma/victimization; greater needle use and sex-related HIV risk behaviours; and greater physical distress. The OPU + MAPU group was less likely to be African American or other race and more likely to be aged 15-17 years, Caucasian; report weekly drug use at home and among peers; engage in illegal behaviors and be confined longer; have greater substance abuse severity and polydrug use; and use mental health and substance abuse treatment services. Conclusions These findings expand upon the existing literature and highlight the substantial incremental risk of OPU on multiple comorbid areas among treatment-seeking youth. Further evaluation is needed to assess their outcomes following standard drug treatment and to evaluate specialized interventions for this subgroup of severely impaired youth. C1 [Subramaniam, Geetha A.; Stitzer, Maxine L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ives, Melissa L.; Dennis, Michael L.] Chestnut Hlth Syst, Normal, IL USA. RP Subramaniam, GA (reprint author), NIDA, Div Clin Neurosci & Behav Res, 6001 Execut Blvd,Room 3129,MSC 9593, Bethesda, MD 20892 USA. EM geetha.subramaniam@nih.gov FU National Institute on Drug Abuse (NIDA) [K12DA000357]; American Academy of Child and Adolescent Psychiatry; Center for Substance Abuse Treatment (CSAT) [TI11424, TI11871, TI11874, TI11888, TI11894, TI13190, TI13305, TI13308, TI13309, TI13313, TI13322, TI13323, TI13340, TI13344, TI3345, TI13354, TI13356, TI13601 TI14090, TI14188, TI14189, TI14196, TI14214, TI14252, TI14254, TI14261, TI14267, TI14271, TI14272]; Substance Abuse and Mental Health Services Administration (SAMHSA) [270-07-0191] FX This development of this paper was supported by research grant K12DA000357 (Subramaniam, Principle Investigator) from the National Institute on Drug Abuse (NIDA) and American Academy of Child and Adolescent Psychiatry, prior to Dr Subramaniam's employment at NIDA. This project was also supported by the Center for Substance Abuse Treatment (CSAT), Substance Abuse and Mental Health Services Administration (SAMHSA) contract 270-07-0191 using data provided by the following grants and contracts from CSAT (TI11424, TI11871, TI11874, TI11888, TI11894, TI13190, TI13305, TI13308, TI13309, TI13313, TI13322, TI13323, TI13340, TI13344, TI3345, TI13354, TI13356, TI13601 TI14090, TI14188, TI14189, TI14196, TI14214, TI14252, TI14254, TI14261, TI14267, TI14271, TI14272, TI14283, TI14311, TI14315, TI14355, TI14376, TI15348, TI15413, TI15415, TI15421, TI15433, TI15446, TI15447, TI15458, TI15461, TI15466, TI15467, TI15469, TI15475, TI15478, TI15479, TI15481, TI15483, TI15485, TI15486, TI15489, TI15511, TI15514, TI15524, TI15527, TI15545, TI15562, TI15577, TI15586, TI15670, TI15671, TI15672, TI15674, TI15677, TI15678, TI15682, TI15686, TI16386, TI16400, TI16414, TI16904, TI16928, TI16939, TI16992, TI17046, TI17055, TI17070, TI17071, TI17433, TI17434, TI17446, TI17476, TI17484, TI17490, TI17523, TI17604, TI17605; TI17638; TI17728; TI17761; TI17763; T17765, TI17769, TI17779, TI17786, TI17788, TI17812, TI17825, TI17830 TI18406; contract 207-98-7047, contract 277-00-6500, contract 270-2003-00006). The authors would like to thank Melinda Tracy for preparation of the manuscript. The content and opinions are those of the authors and do not reflect official positions of the contributing project directors, the National Institute on Drug Abuse, the American Academy of Child and Adolescent Psychiatry or Center for Substance Abuse Treatment/Substance Abuse and Mental Health Services Administration. NR 27 TC 17 Z9 17 U1 3 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2010 VL 105 IS 4 BP 686 EP 698 DI 10.1111/j.1360-0443.2009.02829.x PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 567IX UT WOS:000275441400020 PM 20403020 ER PT J AU Leeman, RF Heilig, M Cunningham, CL Stephens, DN Duka, T O'Malley, SS AF Leeman, Robert F. Heilig, Markus Cunningham, Christopher L. Stephens, David N. Duka, Theodora O'Malley, Stephanie S. TI Ethanol consumption: how should we measure it? Achieving consilience between human and animal phenotypes SO ADDICTION BIOLOGY LA English DT Review DE Alcohol; animal models; biomarkers; genetics; heavy drinking; human laboratory models ID CORTICOTROPIN-RELEASING-FACTOR; CLINICAL LABORATORY PARADIGM; PROGRESSIVE RATIO SCHEDULE; IDENTIFICATION TEST AUDIT; ALCOHOL CUE REACTIVITY; SOCIAL DRINKERS; HEAVY DRINKING; C57BL/6J MICE; USE DISORDERS; OUTCOME EXPECTANCIES AB There is only modest overlap in the most common alcohol consumption phenotypes measured in animal studies and those typically studied in humans. To address this issue, we identified a number of alcohol consumption phenotypes of importance to the field that have potential for consilience between human and animal models. These phenotypes can be broken down into three categories: (1) abstinence/the decision to drink or abstain; (2) the actual amount of alcohol consumed; and (3) heavy drinking. A number of suggestions for human and animal researchers are made in order to address these phenotypes and enhance consilience. Laboratory studies of the decision to drink or to abstain are needed in both human and animal research. In human laboratory studies, heavy or binge drinking that meets cut-offs used in epidemiological and clinical studies should be reported. Greater attention to patterns of drinking over time is needed in both animal and human studies. Individual differences pertaining to all consumption phenotypes should be addressed in animal research. Lastly, improved biomarkers need to be developed in future research for use with both humans and animals. Greater precision in estimating blood alcohol levels in the field, together with consistent measurement of breath/blood alcohol levels in human laboratory and animal studies, provides one means of achieving greater consilience of alcohol consumption phenotypes. C1 [O'Malley, Stephanie S.] Yale Univ, Sch Med, Dept Psychiat, CMHC, New Haven, CT 06519 USA. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, New Haven, CT USA. [Cunningham, Christopher L.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Sch Med, Portland, OR 97201 USA. [Cunningham, Christopher L.] Portland Alcohol Res Ctr, Portland, ME USA. [Stephens, David N.; Duka, Theodora] Univ Sussex, Dept Psychol, Brighton BN1 9RH, E Sussex, England. RP O'Malley, SS (reprint author), Yale Univ, Sch Med, Dept Psychiat, CMHC, Room S202,34 Pk St, New Haven, CT 06519 USA. EM Stephanie.omalley@yale.edu RI Stephens, David/G-2384-2012; OI Heilig, Markus/0000-0003-2706-2482 FU National Institutes of Health [K05 AA014715, P50 AA012870, R01 AA016621, R37 AA007702, U01 AA013479]; United Kingdom Medical Research Council; Connecticut Department of Mental Health and Addiction Services FX We thank John Crabbe and an anonymous reviewer for their helpful comments on an earlier draft of this manuscript. Support for this project was provided by the National Institutes of Health (the NIAAA intramural research program and the following grants: K05 AA014715, P50 AA012870, R01 AA016621, R37 AA007702 and U01 AA013479), by the United Kingdom Medical Research Council, and by the Connecticut Department of Mental Health and Addiction Services. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 116 TC 52 Z9 53 U1 4 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2010 VL 15 IS 2 BP 109 EP 124 DI 10.1111/j.1369-1600.2009.00192.x PG 16 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 554AB UT WOS:000274406800002 PM 20148775 ER PT J AU Stephens, DN Duka, T Crombag, HS Cunningham, CL Heilig, M Crabbe, JC AF Stephens, David N. Duka, Theodora Crombag, Hans S. Cunningham, Christopher L. Heilig, Markus Crabbe, John C. TI Reward sensitivity: issues of measurement, and achieving consilience between human and animal phenotypes SO ADDICTION BIOLOGY LA English DT Review DE Animal models; conditioned place preference; craving; progressive ratio; reward dysregulation; self administration ID CONDITIONED PLACE PREFERENCE; PROGRESSIVE RATIO SCHEDULE; DRUG-SEEKING BEHAVIOR; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; INCENTIVE-SENSITIZATION THEORY; DIMINISHED SOCIAL COMPETENCE; SELF-ADMINISTERED COCAINE; MEDIAL PREFRONTAL CORTEX; ADDICTION-LIKE BEHAVIOR; NONHUMAN PRIMATE MODEL AB Reward is a concept fundamental to discussions of drug abuse and addiction. The idea that altered sensitivity to either drug-reward, or to rewards in general, contributes to, or results from, drug-taking is a common theme in several theories of addiction. However, the concept of reward is problematic in that it is used to refer to apparently different behavioural phenomena, and even to diverse neurobiological processes (reward pathways). Whether these different phenomena are different behavioural expressions of a common underlying process is not established, and much research suggests that there may be only loose relationships among different aspects of reward. Measures of rewarding effects of drugs in humans often depend upon subjective reports. In animal studies, such insights are not available, and behavioural measures must be relied upon to infer rewarding effects of drugs or other events. In such animal studies, but also in many human methods established to objectify measures of reward, many other factors contribute to the behaviour being studied. For that reason, studying the biological (including genetic) bases of performance of tasks that ostensibly measure reward cannot provide unequivocal answers. The current overview outlines the strengths and weaknesses of current approaches that hinder the conciliation of cross-species studies of the genetics of reward sensitivity and the dysregulation of reward processes by drugs of abuse. Some suggestions are made as to how human and animal studies may be made to address more closely homologous behaviours, even if those processes are only partly able to isolate 'reward' from other factors contributing to behavioural output. C1 [Stephens, David N.; Duka, Theodora; Crombag, Hans S.] Univ Sussex, Dept Psychol, Brighton BN1 9QG, E Sussex, England. [Cunningham, Christopher L.; Crabbe, John C.] Oregon Hlth & Sci Univ, Sch Med, Dept Behav Neurosci, Portland, OR 97201 USA. [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Crabbe, John C.] Portland Alcohol Res Ctr, Portland, OR USA. [Crabbe, John C.] Portland VA Med Ctr, Portland, OR USA. RP Stephens, DN (reprint author), Univ Sussex, Dept Psychol, Brighton BN1 9QG, E Sussex, England. EM d.stephens@sussex.ac.uk RI Stephens, David/G-2384-2012; OI Heilig, Markus/0000-0003-2706-2482 FU Medical Research Council [G0400568, G0802642] NR 195 TC 50 Z9 50 U1 4 U2 18 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2010 VL 15 IS 2 BP 145 EP 168 DI 10.1111/j.1369-1600.2009.00193.x PG 24 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 554AB UT WOS:000274406800004 PM 20148777 ER PT J AU Heilig, M Egli, M Crabbe, JC Becker, HC AF Heilig, Markus Egli, Mark Crabbe, John C. Becker, Howard C. TI Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked? SO ADDICTION BIOLOGY LA English DT Review DE Alcoholism; dependence; neuroadaptation; relapse; stress; withdrawal ID CORTICOTROPIN-RELEASING-FACTOR; ACUTE ETHANOL WITHDRAWAL; ANXIETY-LIKE BEHAVIOR; RECEPTOR ANTAGONIST ANTALARMIN; DEPENDENCE-INDUCED INCREASES; ACOUSTIC STARTLE RESPONSE; CROSS-FOSTERING ANALYSIS; NUCLEUS-ACCUMBENS; PHYSICAL-DEPENDENCE; NEUROPEPTIDE-Y AB The role of withdrawal-related phenomena in the development and maintenance of alcohol addiction remains under debate. A 'self-medication' framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol-dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that in most patients, these symptoms abate over 3-6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: (1) are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence?; (2) is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal?; and (3) to what extent is susceptibility to negative affect that persists into protracted abstinence heritable?. C1 [Heilig, Markus] NIAAA, LCTS, Bethesda, MD 20892 USA. [Crabbe, John C.] Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Portland, OR 97201 USA. [Crabbe, John C.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Portland, OR 97201 USA. [Becker, Howard C.] Med Univ S Carolina, Dept Psychiat, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. [Becker, Howard C.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Becker, Howard C.] Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Heilig, M (reprint author), NIAAA, LCTS, 10 Ctr Dr 1-5330, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482 FU NIAAA; NIH [AA10760, AA13519, AA010761, AA014095]; US Department of Veterans Affairs; VA Medical Research FX The authors wish to acknowledge support by the NIAAA intramural research program (MH), NIH grants AA10760, AA13519, and a grant from the US Department of Veterans Affairs (JC), and NIH grants AA010761, AA014095 and VA Medical Research (HB). NR 201 TC 142 Z9 143 U1 6 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 2010 VL 15 IS 2 BP 169 EP 184 DI 10.1111/j.1369-1600.2009.00194.x PG 16 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA 554AB UT WOS:000274406800005 PM 20148778 ER PT J AU Epstein, DH Marrone, GF Heishman, SJ Schmittner, J Preston, KL AF Epstein, David H. Marrone, Gina F. Heishman, Stephen J. Schmittner, John Preston, Kenzie L. TI Tobacco, cocaine, and heroin: Craving and use during daily life SO ADDICTIVE BEHAVIORS LA English DT Article DE Smoking; Nicotine; Cocaine; Heroin; Ecological momentary assessment; Craving ID ECOLOGICAL MOMENTARY ASSESSMENT; SMOKING-CESSATION TREATMENT; SUBSTANCE-ABUSE TREATMENT; ILLICIT DRUG-USE; CIGARETTE-SMOKING; CONTINGENCY MANAGEMENT; DEPENDENT SUBJECTS; NICOTINE; METHADONE; NALTREXONE AB Background: Relationships among tobacco smoking, tobacco craving, and other drug use and craving may have treatment implications in polydrug-dependent individuals. Methods: We conducted the first ecological momentary assessment (EMA) study to investigate how smoking is related to other drug use and craving during daily life. For up to 20 weeks, 106 methadone-maintained outpatients carried PalmPilots (PDAs). They reported their craving, mood, behaviors, environment, and cigarette-smoking status in 2 to 5 random-prompt entries/day and initiated PDA entries when they used cocaine or heroin or had a discrete episode of craving for cocaine or heroin. Results. Smoking frequency increased linearly with random-prompt ratings of tobacco craving, cocaine craving, and craving for both cocaine and heroin. Smoking frequency was greater during discrete episodes of cocaine use and craving than during random-prompt reports of low craving for cocaine. This pattern was also significant for dual cocaine and heroin use and craving. Smoking and tobacco craving were each considerably reduced during periods of urine-verified abstinence from cocaine, and there was a (nonsignificant) tendency for morning smoking to be especially reduced during those periods. Conclusions: This EMA study confirms that smoking and tobacco craving are strongly associated with the use of and craving for cocaine and heroin. Together with prior findings, our data suggest that tobacco and cocaine may each increase craving for (and likelihood of continued use of) themselves and each other. Treatment for tobacco dependence should probably be offered concurrently with (rather than only after) initiation of treatment for other substance-use disorders. Published by Elsevier Ltd. C1 [Epstein, David H.] NIDA, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch,NIH, Baltimore, MD 21224 USA. RP Epstein, DH (reprint author), NIDA, Intramural Res Program, Treatment Sect, Clin Pharmacol & Therapeut Branch,NIH, Room 01B-606,251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM depstein@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU NIDA FX This work was funded by the NIDA Intramural Research Program, which had no further role in the Study design, analysis/interpretation of data, the writing of the report, or the decision to publish. NR 43 TC 50 Z9 51 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 EI 1873-6327 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2010 VL 35 IS 4 BP 318 EP 324 DI 10.1016/j.addbeh.2009.11.003 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 563MF UT WOS:000275135900004 PM 19939575 ER PT J AU Grossman, CI Gordon, CM AF Grossman, Cynthia I. Gordon, Christopher M. TI Mental Health Considerations in Secondary HIV Prevention SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Mental health; Secondary HIV prevention ID CHILDHOOD SEXUAL-ABUSE; STRESS-MANAGEMENT INTERVENTIONS; RANDOMIZED CONTROLLED-TRIAL; TRANSMISSION RISK BEHAVIOR; TRAUMATIC STRESS; POSITIVE PERSONS; SUBSTANCE-ABUSE; UNITED-STATES; METAANALYSIS; HIV/AIDS AB Despite substantial attention in the past decade to the co-morbidity of mental health problems among people living with HIV/AIDS (PLWHA), these problems remain a significant barrier to maintaining health and secondary prevention. To address these issues, program staff from the Center for Mental Health Research on AIDS at the NIMH convened a meeting on 19th and 20th July 2007 to discuss the intersection of mental health and HIV. The conveners brought together leaders in the fields of mental illness and HIV to discuss current gaps in the research related to the prevention, diagnosis, and treatment of mental disorders among PLWHA, and how attention to mental health can affect a variety of health outcomes. Attendees were asked to discuss key questions that, if addressed through empirical investigation, could move the field toward the aim of reducing or alleviating the burden of mental illness for those living with HIV disease. The purpose of this brief report is to summarize this meeting's proceedings, overview key points of discussion, and outline areas that may be useful to consider for clinical researchers in the field. C1 [Grossman, Cynthia I.; Gordon, Christopher M.] NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. RP Grossman, CI (reprint author), NIMH, Ctr Mental Hlth Res AIDS, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM grossmanc@mail.nih.gov NR 37 TC 8 Z9 8 U1 4 U2 8 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 APR PY 2010 VL 14 IS 2 BP 263 EP 271 DI 10.1007/s10461-008-9496-8 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 567EB UT WOS:000275424800004 PM 19057989 ER PT J AU Sueoka, K Goulet, JL Fiellin, DA Rimland, D Butt, AA Gibert, C Rodriguez-Barradas, MC Bryant, K Crystal, S Justice, AC AF Sueoka, Kristen Goulet, Joseph L. Fiellin, David A. Rimland, David Butt, Adeel A. Gibert, Cynthia Rodriguez-Barradas, Maria C. Bryant, Kendall Crystal, Stephen Justice, Amy C. TI Depression Symptoms and Treatment Among HIV Infected and Uninfected Veterans SO AIDS AND BEHAVIOR LA English DT Article DE HIV-infection; Depression; Psychiatric status rating scales; Anti-depressive agents ID PRIMARY-CARE PATIENTS; PATIENT HEALTH QUESTIONNAIRE-9; DISORDERS; VALIDITY; PHQ-9; PHYSICIANS; DIAGNOSIS; SEVERITY; DISEASES AB Depression is one of the most common comorbid conditions affecting persons with HIV. We compared depressive symptoms and depression treatment using data from the Veterans Aging Cohort Study (VACS), a prospective cohort of HIV-infected and uninfected subjects. We identified subjects with a Patient Health Questionnaire score of 10 or greater. Treatment was defined as prescription of a selective serotonin reuptake inhibitor (SSRI) or mental health counseling. Overall, 16% of 4,480 subjects had depressive symptoms, and HIV-infected patients were more likely to have had depressive symptoms (OR = 1.38, 95% CI = 1.18, 1.62). Geographic site of care and having a mental health provider at the clinic was associated with treatment. In multivariable models restricted to 732 patients with depressive symptoms, receipt of depression treatment did not differ by HIV status (Adjusted OR = 1.11, 95% CI = 0.80, 1.54). Non-Hispanic whites were more likely to receive treatment (Adjusted OR = 2.09, 95% CI 1.04, 4.24). Primary care and HIV providers were equally unlikely to treat active depressive symptoms. Treatment variation by race, site, and availability of a mental health provider, suggests targets for intervention. C1 [Goulet, Joseph L.; Justice, Amy C.] VA Connecticut Healthcare Syst, West Haven, CT 06516 USA. [Sueoka, Kristen; Goulet, Joseph L.; Fiellin, David A.; Justice, Amy C.] Yale Univ, Sch Med, New Haven, CT USA. [Rimland, David] VA Med Ctr, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Butt, Adeel A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Butt, Adeel A.] Univ Pittsburgh, Pittsburgh, PA USA. [Gibert, Cynthia] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Rodriguez-Barradas, Maria C.] Michael E De Bakey VAMC, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. [Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, 11ACSLG,Bldg 35A,Room 2-212,950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov OI Goulet, Joseph/0000-0002-0842-804X; Fiellin, David/0000-0002-4006-010X FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U01 AA 13566, U01 AA013566, U10 AA 13566, U10 AA013566, U10 AA013566-08, U10 AA013566-09] NR 25 TC 6 Z9 6 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2010 VL 14 IS 2 BP 272 EP 279 DI 10.1007/s10461-008-9428-7 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 567EB UT WOS:000275424800005 PM 18648927 ER PT J AU Wong, AHW Williams, K Reddy, S Wilson, D Giddy, J Alter, G Ghebremichael, M Carrington, MN Ndung'u, T Walker, BD Altfeld, M Carr, WH AF Wong, Ambrose H. W. Williams, Katie Reddy, Sharon Wilson, Douglas Giddy, Janet Alter, Galit Ghebremichael, Musie Carrington, Mary N. Ndung'u, Thumbi Walker, Bruce D. Altfeld, Marcus Carr, William H. TI Alterations in Natural Killer Cell Receptor Profiles During HIV Type 1 Disease Progression Among Chronically Infected South African Adults SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HLA CLASS-I; HIV-1-INFECTED PATIENTS; CYTOLYTIC FUNCTION; 5 CONTINENTS; NK CLONES; T-CELLS; POPULATIONS; ALLELES; ACTIVATION; RECOGNITION AB Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-naive adult South Africans. These individuals ranged in disease severity from early (CD4 count >500) to advanced HIV-1 disease (CD4 count <50). We found that the frequency of NK cells expressing KIR2DL1, an inhibitory receptor, and/or KIR2DS1, an activating receptor, tended to decrease with increasing HIV-1 viral load. We also discovered a significant increase (p<0.05) in overall NK cell degranulation with disease progression. We found that acutely activated NK cells (CD69(pos)) were deficient in NKp46 expression ex vivo. In conclusion, we observed that with viremia and advanced HIV-1 disease, activated NK cells lack NKp46 expression, and KIR2DS1(pos) and/or KIR2DL1(pos) NK cells are reduced in frequency. These findings suggest that modulation of receptor expression on NK cells may play a role in HIV-1 pathogenesis, and provide new insights on immunological changes in advanced HIV-1 disease. C1 [Wong, Ambrose H. W.; Williams, Katie; Alter, Galit; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA 02129 USA. [Wong, Ambrose H. W.; Reddy, Sharon; Ndung'u, Thumbi; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.] Univ KwaZulu Natal, HIV Pathogenesis Programme, Nelson R Mandela Sch Med, ZA-4013 Durban, South Africa. [Wilson, Douglas] Edendale Hosp, Dept Med, Edendale, South Africa. [Giddy, Janet] McCords Hosp, Durban, South Africa. [Ghebremichael, Musie] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Carrington, Mary N.] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Carr, WH (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, 149 13th St, Charlestown, MA 02129 USA. EM wcarr@partners.org OI Wong, Ambrose/0000-0001-7471-1647; Ndung'u, Thumbi/0000-0003-2962-3992 FU NIH-FIC [K01-TW007703-01A1]; HHMI; Harvard CFAR; NIH [R01-A1067031]; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank Dudu Ndlovu and Pat Bartman for assistance in subject recruitment and sample collection. We thank Karen Bishop and the HPP Blood Processing Core Facility for assistance in sample processing. This work was supported by an NIH-FIC K01-TW007703-01A1 to W. H. C., HHMI Research Fellowship to A. W., Harvard CFAR grant to M. A., and also in part by NIH R01-A1067031 to M. A. M. A. is a Distinguished Clinical Scientist of the Doris Duke Charitable Foundation. This project also has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 39 TC 18 Z9 18 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2010 VL 26 IS 4 BP 459 EP 469 DI 10.1089/aid.2009.0176 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 587XY UT WOS:000277031100011 PM 20380481 ER PT J AU Vazquez, M Maldonado, IM Almodovar, S Lopez, C Colon, MD Hill, M Lorenzo, E AF Vazquez, Manuel Maldonado, Irvin M. Almodovar, Sharilyn Lopez, Carlos Colon, Maria del C. Hill, Martin Lorenzo, Eric TI Short Communication: Human Blood Dendritic Cells Are Infected Separately from Monocytes in HIV Type 1 Patients SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUPPRESSIVE HAART; T-CELLS; IN-VIVO; REPLICATION; MACROPHAGES; SUSCEPTIBILITY; INDIVIDUALS; PERSISTENCE; RESERVOIRS AB Monocytes serve as a systemic reservoir of myeloid precursors for the renewal of tissue macrophages and dendritic cells (DCs). Both monocytes and dendritic cells can be infected with HIV-1. Circulating DCs are believed to be derived from a common precursor of monocytes, or, in the case of inflammatory challenge, from monocytes directly. Because there are fewer infected blood monocytes than infected cells after differentiation, we hypothesized that the majority of HIV-1 infection in circulating DCs occurs via direct viral binding to their CD4 and coreceptors after differentiation. We isolated monocytes at one time point and circulating dendritic cells at a second time point from the blood of HIV-1-infected patients. Proviral DNA was isolated from DCs and monocytes, and the C2-V4 region of the HIV-1 env gene was cloned and sequenced. Phylogeny, nucleotide distances, and glycosylation patterns of the env gene were performed. The phylogenetic trees revealed that viral forms from the monocytes clustered distantly from the quasispecies derived from circulating DCs. The nucleotide distances and differing glycosylation patterns suggest that the infection of DCs is independent of the infection of the monocytes. C1 [Lorenzo, Eric] NIAID Div Extramural Act DEA, Sci Review Program, AIDS Res Review Branch, Bethesda, MD 20892 USA. [Vazquez, Manuel; Lopez, Carlos; Colon, Maria del C.; Hill, Martin; Lorenzo, Eric] Ponce Sch Med, Dept Physiol & Pharmacol, Mol Virol Lab, Ponce, PR 00732 USA. [Maldonado, Irvin M.] San Juan Bautista Sch Med, Dept Biochem & Pharmacol, Caguas, PR USA. [Almodovar, Sharilyn] Univ Colorado, Cardiovasc Pulm Res Lab, Denver, CO 80217 USA. RP Lorenzo, E (reprint author), Ponce Sch Med, Dept Physiol & Pharmacol, Mol Virol Lab, POB 7004, Ponce, PR 00732 USA. EM ericlorenzo@hotmail.com FU NIH [MBRS S06-GM008239, RCMI 2G12RR003050-20] FX We acknowledge Pablo Lopez for assistance in flow cytometric analysis and Drs. Ivan Melendez and Gladys Sepulveda and their clinical staff for patient recruitment, blood collection, and follow-up of the patients. We are also indebted to the patients who donated blood for this study. This work was supported by NIH Grants MBRS S06-GM008239 (to E. L.) and RCMI 2G12RR003050-20 (PSM Molecular Biology Core). Manuel Vazquez and Irvin M. Maldonado contributed equally to this work. NR 33 TC 2 Z9 2 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2010 VL 26 IS 4 BP 471 EP 479 DI 10.1089/aid.2009.0109 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 587XY UT WOS:000277031100012 PM 20380485 ER PT J AU Miranda, RC Pietrzykowski, AZ Tang, YM Sathyan, P Mayfield, D Keshavarzian, A Sampson, W Hereld, D AF Miranda, Rajesh C. Pietrzykowski, Andrzej Z. Tang, Yueming Sathyan, Pratheesh Mayfield, Dayne Keshavarzian, Ali Sampson, Wayne Hereld, Dale TI MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Tolerance; Fetal Alcohol Syndrome; Fetal Alcohol Spectrum Disorders; Neural Stem Cells; Alcoholic Liver Disease; Hepatocellular Carcinoma; Gastrointestinal Cancer; Inflammation; Bone Fracture; miRNA; miR9; miR21; miR153; miR335; miR212; ZO-1 ID ALCOHOLIC LIVER-DISEASE; RAT CEREBRAL-CORTEX; APICAL JUNCTIONAL COMPLEX; INDUCED GUT LEAKINESS; OPIOID RECEPTOR MOR1; EX-VIVO MODEL; GENE-EXPRESSION; PRENATAL EXPOSURE; EPITHELIAL BARRIER; FRONTAL-CORTEX AB Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol's deleterious effects leading to the suggestion that ethanol is a "dirty drug." An important question is, are there cellular "master-switches" that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol-sensitive miRNAs are indeed regulatory master-switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol-sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol's effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol-related disorders. C1 [Miranda, Rajesh C.; Sathyan, Pratheesh] Texas A&M Hlth Sci Ctr, Coll Med, Dept Neurosci & Expt Therapeut, College Stn, TX 77843 USA. [Pietrzykowski, Andrzej Z.] Rutgers State Univ, Dept Anim Sci, New Brunswick, NJ 08903 USA. [Tang, Yueming; Keshavarzian, Ali] Rush Univ, Med Ctr, Dept Gastroenterol, Chicago, IL 60612 USA. [Mayfield, Dayne] Univ Texas Austin, Waggoner Ctr Alcohol & Addict Res, Austin, TX 78712 USA. [Sampson, Wayne] Scott & White Mem Hosp & Clin, Dept Surg, Orthopaed Div, Temple, TX 76508 USA. [Hereld, Dale] NIAAA, Div Metab & Hlth Effects, NIH, Rockville, MD 20852 USA. RP Miranda, RC (reprint author), Texas A&M Hlth Sci Ctr, Coll Med, Dept Neurosci & Expt Therapeut, College Stn, TX 77843 USA. EM miranda@medicine.tamhsc.edu FU NIH/NIAAA [AA13440, AA017481, AA13745] FX This research was supported by grants from NIH/NIAAA, #AA13440 to R.C. Miranda, #AA017481 to A. Pietrzykowski, and #AA13745 to A. Keshavarzian. NR 119 TC 79 Z9 82 U1 2 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 APR PY 2010 VL 34 IS 4 BP 575 EP 587 DI 10.1111/j.1530-0277.2009.01126.x PG 13 WC Substance Abuse SC Substance Abuse GA 573MB UT WOS:000275916900001 PM 20102566 ER PT J AU Miller, AM Wang, H Park, O Horiguchi, N Lafdil, F Mukhopadhyay, P Moh, A Fu, XY Kunos, G Pacher, P Gao, B AF Miller, Andrew M. Wang, Hua Park, Ogyi Horiguchi, Norio Lafdil, Fouad Mukhopadhyay, Partha Moh, Akira Fu, Xin Yuan Kunos, George Pacher, Pal Gao, Bin TI Anti-Inflammatory and Anti-Apoptotic Roles of Endothelial Cell STAT3 in Alcoholic Liver Injury SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE STAT3; Alcoholic Liver Injury; Endothelial Cells; IL-6 ID ETHANOL-INDUCED APOPTOSIS; RAT-LIVER; PRESERVATION INJURY; HYALURONIC-ACID; KUPFFER CELLS; DISEASE; INTERLEUKIN-6; MICE; REGENERATION; HEPATOCYTES AB Background: It is generally believed that the hepatoprotective effect of interleukin-6 (IL-6) is mediated via activation of signal transducer and activator of transcription 3 (STAT3) in hepatocytes. IL-6-deficient mice are more susceptible to alcohol-induced hepatocyte apoptosis and steatosis and elevation of serum alanine transaminase (ALT); however, whereas hepatocyte-specific STAT3 knockout mice are more susceptible to alcohol-induced hepatic steatosis, they have similar hepatocyte apoptosis and serum ALT after alcohol feeding compared with wild-type mice. This suggests that the hepatoprotective effect of IL-6 in alcoholic liver injury may be mediated via activation of STAT3-independent signals in hepatocytes, activation of STAT3 in nonparenchymal cells, or both. We have previously shown that IL-6 also activates STAT3 in sinusoidal endothelial cells (SECs). Thus, the purpose of this study was to investigate whether STAT3 in endothelial cells also plays a protective role in alcoholic liver injury. Methods: Wild-type and endothelial cell-specific STAT3 knockout (STAT3E-/-) mice were pair-fed and fed ethanol containing diet for 4 weeks. Liver injury and inflammation were determined. Results: Feeding mice with ethanol-containing diet for 4 weeks induced greater hepatic injury (elevation of serum ALT) and liver weight in STAT3E-/- mice than wild-type control groups. In addition, ethanol-fed STAT3E-/- mice displayed greater hepatic inflammation and substantially elevated serum and hepatic levels of IL-6 and TNF-alpha compared with wild-type mice. Furthermore, ethanol-fed STAT3E-/- mice displayed a greater abundance of apoptotic SECs and higher levels of serum hyaluronic acid than wild-type controls. Conclusions: These data suggest that endothelial cell STAT3 plays important dual functions of attenuating hepatic inflammation and SEC death during alcoholic liver injury. C1 [Miller, Andrew M.; Wang, Hua; Park, Ogyi; Horiguchi, Norio; Lafdil, Fouad; Gao, Bin] NIAAA, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. [Kunos, George] NIAAA, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. [Mukhopadhyay, Partha; Pacher, Pal] NIAAA, Sect Oxidat Stress, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Moh, Akira; Fu, Xin Yuan] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU NIAAA, NIH FX This work was supported by the intramural program of NIAAA, NIH. No conflicts of interest exist for all authors. NR 37 TC 21 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2010 VL 34 IS 4 BP 719 EP 725 DI 10.1111/j.1530-0277.2009.01141.x PG 7 WC Substance Abuse SC Substance Abuse GA 573MB UT WOS:000275916900016 PM 20102572 ER PT J AU Snow, KK Bonkovsky, HL Fontana, RJ Kim, HY Sterling, RK Di Bisceglie, AM Morgan, TR Dienstag, JL Ghany, MG AF Snow, K. K. Bonkovsky, H. L. Fontana, R. J. Kim, H. -Y. Sterling, R. K. Di Bisceglie, A. M. Morgan, T. R. Dienstag, J. L. Ghany, M. G. CA Halt C Trial Grp TI Changes in quality of life and sexual health are associated with low-dose peginterferon therapy and disease progression in patients with chronic hepatitis C SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHRONIC LIVER-DISEASE; VIRUS-INFECTION; COMBINATION THERAPY; PLUS RIBAVIRIN; BIOPSYCHOSOCIAL PREDICTORS; PEGYLATED INTERFERON; VIROLOGICAL RESPONSE; MAINTENANCE THERAPY; COGNITIVE FUNCTION; WORK PRODUCTIVITY AB P>Background Primary analysis of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) Trial showed long-term peginterferon therapy did not reduce complications in patients with chronic hepatitis C and advanced fibrosis or cirrhosis. Aim To assess the effects of long-term peginterferon therapy and disease progression on health-related quality of life (HRQOL), symptoms and sexual health in HALT-C patients. Methods A total of 517 HALT-C patients received peginterferon alfa-2a (90 mu g/week); 532 received no additional treatment for 3.5 years. Patients were followed up for outcomes of death, hepatocellular carcinoma and hepatic decompensation. Sexual health, SF-36 scores and symptoms were serially assessed by repeated-measures analyses of covariance. Results Patients with cirrhosis (n = 427) reported lower general well-being and more fatigue (P < 0.001) than patients with fibrosis (n = 622). Physical scores declined significantly over time, independent of treatment, and patients with cirrhosis reported lower scores. Vitality scores were lower in those with cirrhosis, and treated patients experienced a greater decline over time than untreated patients; HRQOL rebounded after treatment ended. Patients with a clinical outcome had significantly greater declines in all SF-36 and symptom scores. Among men, Sexual Health scores were significantly worse in treated patients and in those with a clinical outcome. Conclusion Clinical progression of chronic hepatitis C and maintenance peginterferon therapy led to worsening of symptoms, HRQOL and, in men, sexual health in a large patient cohort followed up over 4 years (NCT00006164). C1 [Snow, K. K.; Kim, H. -Y.] New England Res Inst, Watertown, MA 02472 USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, H. L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Fontana, R. J.] Univ Michigan, Med Ctr, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sterling, R. K.] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. [Di Bisceglie, A. M.] St Louis Univ, Div Gastroenterol & Hepatol, Sch Med, St Louis, MO USA. [Morgan, T. R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, T. R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Dienstag, J. L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, J. L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ghany, M. G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Snow, KK (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM ksnow@neriscience.com FU National Institute of Diabetes & Digestive & Kidney Diseases; National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health; Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA); HoffmannLa Roche, Inc. FX Declaration of personal interests: We acknowledge the contribution of Jay H. Hoofnagle, MD, for the design of the symptom and sexual health questionnaires. In addition to the authors of this manuscript, the individuals in Appendix B were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions (see Appendix B). Declaration of funding interests: This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed in Appendix B). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed in Appendix B). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. H. L. Bonkovsky receives research support from HoffmannLa Roche, Inc. R. J. Fontana is on the speaker's bureau for Hoffmann-La Roche, Inc. R. K. Sterling is a consultant, receives research support and is on the speaker's bureau for Hoffmann-La Roche, Inc. A. M. Di Bisceglie is a consultant and receives research support from Hoffmann-La Roche, Inc. T. R. Morgan is a consultant, on the speaker's bureau and receives research support Hoffmann- La Roche, Inc. Authors with no financial relationships related to this project are K. K. Snow, H.-Y. Kim, J. L. Dienstag and M. G. Ghany. NR 48 TC 14 Z9 15 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD APR 1 PY 2010 VL 31 IS 7 BP 719 EP 734 DI 10.1111/j.1365-2036.2010.04235.x PG 16 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 562ZE UT WOS:000275094000004 PM 20070284 ER PT J AU Mark, DB Anstrom, KJ McNulty, SE Flaker, GC Tonkin, AM Smith, WM Toff, WD Dorian, P Clapp-Channing, NE Anderson, J Johnson, G Schron, EB Poole, JE Lee, KL Bardy, GH AF Mark, Daniel B. Anstrom, Kevin J. McNulty, Steven E. Flaker, Greg C. Tonkin, Andrew M. Smith, Warren M. Toff, William D. Dorian, Paul Clapp-Channing, Nancy E. Anderson, Jill Johnson, George Schron, Eleanor B. Poole, Jeanne E. Lee, Kerry L. Bardy, Gust H. TI Quality of life effects of automatic external defibrillators in the home: Results from the Home Automatic External Defibrillator Trial (HAT) SO AMERICAN HEART JOURNAL LA English DT Article ID SUDDEN CARDIAC-ARREST; FAMILY-MEMBERS; THERAPY AB Background Public access automatic external defibrillators (AEDs) can save lives, but most deaths from out-of-hospital sudden cardiac arrest occur at home. The Home Automatic External Defibrillator Trial (HAT) found no survival advantage for adding a home AED to cardiopulmonary resuscitation (CPR) training for 7,001 patients with a prior anterior wall myocardial infarction. Quality of life (QOL) outcomes for both the patient and spouse/companion were secondary end points. Methods A subset of 1,007 study patients and their spouse/companions was randomly selected for ascertainment of QOL by structured interview at baseline and 12 and 24 months after enrollment. The primary QOL measures were the Medical Outcomes Study 36-Item Short-Form psychological well-being (reflecting anxiety and depression) and vitality (reflecting energy and fatigue) subscales. Results For patients and spouse/companions, the psychological well-being and vitality scales did not differ significantly between those randomly assigned an AED plus CPR training and controls who received CPR training only. None of the other QOL measures collected showed a clinically and statistically significant difference between treatment groups. Patients in the AED group were more likely to report being extremely or quite a bit reassured by their treatment assignment. Spouse/companions in the AED group reported being less often nervous about the possibility of using AED/CPR treatment than those in the CPR group. Conclusions Adding access to a home AED to CPR training did not affect QOL either for patients with a prior anterior myocardial infarction or their spouse/companion but did provide more reassurance to the patients without increasing anxiety for spouse/companions. (Am Heart J 2010; 159: 627-634. e7.) C1 [Mark, Daniel B.; Anstrom, Kevin J.; Clapp-Channing, Nancy E.] Outcomes Res Grp, Durham, NC USA. [McNulty, Steven E.; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA. [Flaker, Greg C.] Univ Missouri, Columbia, MO USA. [Tonkin, Andrew M.] Monash Univ, Clayton, Vic 3800, Australia. [Smith, Warren M.] Auckland City Hosp, Auckland, New Zealand. [Toff, William D.] Univ Leicester, Leicester, Leics, England. [Dorian, Paul] Univ Toronto, Toronto, ON, Canada. [Anderson, Jill; Johnson, George; Bardy, Gust H.] Seattle Inst Cardiac Res, Seattle, WA USA. [Schron, Eleanor B.] NIH, Bethesda, MD 20892 USA. [Poole, Jeanne E.] Univ Washington, Seattle, WA 98195 USA. RP Mark, DB (reprint author), Outcomes Res Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM daniel.mark@duke.edu OI Toff, William/0000-0001-5631-4496; Mark, Daniel/0000-0001-6340-8087 FU Medtronic; National Heart, Lung, and Blood Institute/National Institutes of Health, Bethesda, MD [UO1 HL67972] FX Dr Mark reports receiving research support from Medtronic; Dr Smith, having stock options in Cameron Health; Dr Poole, receiving research support from Biotronik, participating in the speaker's bureaus for and receiving honoraria from Medtronic, St. Jude Medical, and Boston Scientific; Dr Bardy, consulting for Philips Medical Systems.; Supported by grant (UO1 HL67972) from the National Heart, Lung, and Blood Institute/National Institutes of Health, Bethesda, MD. NR 18 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2010 VL 159 IS 4 BP 627 EP U156 DI 10.1016/j.ahj.2010.01.013 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 577ZC UT WOS:000276261600017 PM 20362722 ER PT J AU Jain, A Tandri, H Dalal, D Chahal, H Soliman, EZ Prineas, RJ Folsom, AR Lima, JAC Bluemke, DA AF Jain, Aditya Tandri, Harikrishna Dalal, Darshan Chahal, Harjit Soliman, Elsayed Z. Prineas, Ronald J. Folsom, Aaron R. Lima, Joao A. C. Bluemke, David A. TI Diagnostic and prognostic utility of electrocardiography for left ventricular hypertrophy defined by magnetic resonance imaging in relationship to ethnicity: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN HEART JOURNAL LA English DT Article ID MYOCARDIAL-INFARCTION; ECG CRITERIA; MASS; PREVALENCE; SEX; HYPERTENSION; STANDARD; DISEASE; VALUES; COHORT AB Background Left ventricular mass is a strong predictor of cardiovascular disease (CVD), and magnetic resonance imaging (MRI) of the heart is a standard of reference for left ventricular mass measurement. Ethnicity is believed to affect electrocardiographic (ECG) performance. We evaluated the diagnostic and prognostic performance of ECG for left ventricular hypertrophy (LVH) as defined by MRI in relationship to ethnicity. Methods Data were analyzed from 4,967 participants (48% men, mean age 62 +/- 10 years; 39% white, 13% Chinese, 26% African American, 22% Hispanic) enrolled in the Multi-Ethic Study of Atherosclerosis (MESA) who were followed for a median of 4.8 years for incident CVD. Results Thirteen traditional ECG-LVH criteria were assessed, and showed overall and ethnicity-specific low sensitivity (10%-26%) and high specificity (88%-99%) in diagnosing MRI-defined LVH. Ten of 13 ECG-LVH criteria showed superior sensitivity and diagnostic performance in African Americans as compared with whites (P = .02-.001). The sum of amplitudes of S wave in V(1), S wave in V(2), and R wave in V(5) (a MESA-specific ECG-LVH criterion) offered higher sensitivity (40.4%) compared with prior ECG-LVH criteria while maintaining good specificity (90%) and diagnostic performance (receiver operating characteristic area = 0.65). In fully adjusted models, only the MESA-specific ECG-LVH criterion, Romhilt-Estes score, Framingham score, Cornell voltage, Cornell duration product, and Framingham-adjusted Cornell voltage predicted increased CVD risk (P<.05). Conclusions Electrocardiography has low sensitivity but high specificity for detecting MRI-defined LVH. The performance of ECG for LVH detection varies by ethnicity, with African Americans showing higher sensitivity and overall performance compared with other ethnic groups. (Am Heart J 2010; 159: 652-8.) C1 [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Jain, Aditya; Chahal, Harjit; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Tandri, Harikrishna; Dalal, Darshan; Lima, Joao A. C.; Bluemke, David A.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. [Soliman, Elsayed Z.; Prineas, Ronald J.] Wake Forest Univ, Dept Epidemiol, Div Publ Hlth Sci, Sch Med, Winston Salem, NC 27109 USA. [Folsom, Aaron R.; Lima, Joao A. C.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Bluemke, DA (reprint author), NIH, 10 Ctr Dr,Rm 10-1C355, Bethesda, MD 20892 USA. EM bluemked@nih.gov RI Soliman, Elsayed/D-8124-2011; OI Soliman, Elsayed/0000-0001-5632-8150; Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [Z99 CL999999, ZIA CL090019-01, ZIA EB000072-01]; NHLBI NIH HHS [N01 HC095161, N01 HC095159, N01 HC095160, N01 HC095162, N01 HC095163, N01 HC095164, N01 HC095165, N01 HC095166, N01 HC095167, N01 HC095168, N01 HC095169] NR 27 TC 45 Z9 48 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2010 VL 159 IS 4 BP 652 EP 658 DI 10.1016/j.ahj.2009.12.035 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 577ZC UT WOS:000276261600020 PM 20362725 ER PT J AU Howard, BV Curb, JD Eaton, CB Kooperberg, C Ockene, J Kostis, JB Pettinger, M Rajkovic, A Robinson, JG Rossouw, J Sarto, G Shikany, JM Van Horn, L AF Howard, Barbara V. Curb, J. David Eaton, Charles B. Kooperberg, Charles Ockene, Judith Kostis, John B. Pettinger, Mary Rajkovic, Aleksandar Robinson, Jennifer G. Rossouw, Jacques Sarto, Gloria Shikany, James M. Van Horn, Linda TI Low-fat dietary pattern and lipoprotein risk factors: the Women's Health Initiative Dietary Modification Trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BASE-LINE CHARACTERISTICS; GLYCEMIC-INDEX DIET; AD-LIBITUM INTAKE; CARDIOVASCULAR-DISEASE; HDL-CHOLESTEROL; SERUM-LIPIDS; CARBOHYDRATE INTAKE; WEIGHT CHANGE; BODY-WEIGHT; LOAD DIET AB Background: The Women's Health Initiative Dietary Modification Trial tested the effects on chronic disease of a dietary pattern lower in fat and higher in vegetables, fruit, and grains. Objective: The objective was to evaluate the effects of dietary carbohydrate changes on lipids and lipoprotein composition. Design: Postmenopausal women were randomly assigned to an intervention or a comparison group for a mean of 8.1 y. Lipoprotein analyses and subclasses were based on subsamples of 2730 and 209 participants, respectively. Results: At year 6, the total reported fat intake was 7.8% lower and carbohydrate intake was 7.6% higher in the intervention group than in the comparison group. Triglyceride change between groups differed by 2.3, 3.8, and -0.8 mg/dL at 1, 3, and 6 y, respectively, and HDL-cholesterol change differed by -1.6, -0.7, and -1.0 mg/dL at 1, 3, and 6 y, respectively. Changes did not differ by age, ethnicity, or obesity. In diabetic intervention women who were white, the triglyceride difference between the intervention and comparison groups was 33.8 mg/dL, whereas in black women with diabetes (n = 50 in the intervention group; n = 83 in the comparison group), the triglyceride difference was 6.4 mg/dL (P for 3-factor interaction = 0.049). No significant changes were observed in apolipoprotein or lipoprotein particles. Reductions in LDL cholesterol varied by quartile of reported lowering of saturated or trans fat. Conclusions: The replacement of 7-8% of fat intake with complex carbohydrates over 6 y was not associated with clinically adverse effects on triglycerides, HDL cholesterol, or lipoprotein subclasses. Diabetic white women with higher triglyceride concentrations may have greater increases in triglycerides. Am J Clin Nutr 2010; 91: 860-74. C1 [Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA. [Howard, Barbara V.] George Washington Univ, Sch Med, Washington, DC USA. [Curb, J. David] Univ Hawaii, Honolulu, HI 96822 USA. [Eaton, Charles B.] Brown Univ, Providence, RI 02912 USA. [Kooperberg, Charles; Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ockene, Judith] Univ Massachusetts, Fallon Clin, Worcester, MA 01605 USA. [Kostis, John B.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Rajkovic, Aleksandar] Univ Pittsburgh, Pittsburgh, PA USA. [Robinson, Jennifer G.] Univ Iowa, Iowa City, IA USA. [Rossouw, Jacques] NHLBI, Bethesda, MD 20892 USA. [Sarto, Gloria] Univ Wisconsin, Madison, WI USA. [Shikany, James M.] Univ Alabama, Birmingham, AL USA. [Van Horn, Linda] Northwestern Univ, Chicago, IL 60611 USA. RP Howard, BV (reprint author), MedStar Hlth Res Inst, 6525 Belcrest Rd, Hyattsville, MD 20782 USA. EM barbara.v.howard@medstar.net FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221] FX The WHI is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. NR 38 TC 21 Z9 21 U1 0 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2010 VL 91 IS 4 BP 860 EP 874 DI 10.3945/ajcn.2009.28034 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 572BV UT WOS:000275802400006 PM 20164311 ER PT J AU Flegal, KM Ogden, CL Yanovski, JA Freedman, DS Shepherd, JA Graubard, BI Borrud, LG AF Flegal, Katherine M. Ogden, Cynthia L. Yanovski, Jack A. Freedman, David S. Shepherd, John A. Graubard, Barry I. Borrud, Lori G. TI High adiposity and high body mass index-for-age in US children and adolescents overall and by race-ethnic group SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CHILDHOOD OBESITY; PRIMARY-CARE; OVERWEIGHT; PEDIATRICIANS; FATNESS; FAT; DISEASE; GIRLS; YOUNG AB Background: Body mass index (BMI)-for-age has been recommended as a screening test for excess adiposity in children and adolescents. Objective: We quantified the performance of standard categories of BMI-for-age relative to the population prevalence of high adiposity in children and adolescents overall and by race-ethnic group in a nationally representative US population sample by using definitions of high adiposity that are consistent with expert committee recommendations. Design: Percentage body fat in 8821 children and adolescents aged 8-19 y was measured by using dual-energy X-ray absorptiometry in 1999-2004 as part of a health examination survey. Results: With the use of several different cutoffs for percentage fat to define high adiposity, most children with high BMI-for-age (>= 95th percentile of the growth charts) had high adiposity, and few children with normal BMI-for-age (<85th percentile) had high adiposity. The prevalence of high adiposity in intermediate BMI categories varied from 45% to 15% depending on the cutoff. The prevalence of a high BMI was significantly higher in non-Hispanic black girls than in non-Hispanic white girls, but the prevalence of high adiposity was not significantly different. Conclusions: Current BMI cutoffs can identify a high prevalence of high adiposity in children with high BMI-for-age and a low prevalence of high adiposity in children with normal BMI-for-age. By these adiposity measures, less than one-half of children with intermediate BMIs-for-age (85th to <95th percentile) have high adiposity. Differences in high BMI ranges between race-ethnic groups do not necessarily indicate differences in high adiposity. Am J Clin Nutr 2010; 91: 1020-6. C1 [Flegal, Katherine M.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Yanovski, Jack A.] NICHHD, Bethesda, MD 20892 USA. [Freedman, David S.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Shepherd, John A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Graubard, Barry I.] NCI, Bethesda, MD 20892 USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Room 4315,3311 Toledo Rd, Hyattsville, MD 20782 USA. EM kmf2@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Yanovski, Jack/0000-0001-8542-1637; Flegal, Katherine/0000-0002-0838-469X NR 34 TC 99 Z9 100 U1 0 U2 10 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2010 VL 91 IS 4 BP 1020 EP 1026 DI 10.3945/ajcn.2009.28589 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 572BV UT WOS:000275802400024 PM 20164313 ER PT J AU Shao, HP Yuan, CM Xi, LQ Raffeld, M Morris, JC Janik, JE Stetler-Stevenson, M AF Shao, Haipeng Yuan, Constance M. Xi, Liqiang Raffeld, Mark Morris, John C. Janik, John E. Stetler-Stevenson, Maryalice TI Minimal Residual Disease Detection by Flow Cytometry in Adult T-Cell Leukemia/Lymphoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Adult T-cell leukemia/lymphoma; Minimal res dual disease; Flow cytometry; Immunophenotype; CD26; Human T-cell lymphotropic virus-1; HTLV-1; Polymerase chain reaction ID VIRUS TYPE-I; POLYMERASE-CHAIN-REACTION; CD26/DIPEPTIDYL PEPTIDASE-IV; LEUKEMIA-LYMPHOMA; PERIPHERAL-BLOOD; DIFFERENTIAL EXPRESSION; UNITED-STATES; HTLV-I; CD26; TRANSPLANTATION AB Little information exists regarding the detection of minimal residual disease (mRD) in adult T-cell leukemia/lymphoma (ATLL) We evaluated 75 peripheral blood samples from 17 ATLL cases using flow cytometry (FC); 50 of the samples were concurrently evaluated by polymerase chain reaction (PCR) for clonal T-cell receptor gamma chain (TRG) gene rearrangement and the presence of human T-cell lymphotropic virus-1 proviral sequences Residual ATLL cells were identified using a multiparametric approach to identify aberrant T-cell immunophenotypes Malignant T cells were CD4+, CD3 dim+, CD26-, CD25 bright, CD7+, and CD27+, with occasional dim expression of CD2 or CD5. FC exhibited a high sensitivity, detecting as few as 0 29% ATLL cells/WBC (4 9 cells/mu L) in the peripheral blood PCR for TRG gene rearrangement was slightly more sensitive, and FC and PCR complemented each other in detecting MRD In 2 patients, there was complete remission, 4 patients had disease refractory to therapy, and 3 died; 11 others had persistanct disease with variable numbers of ATLL cells in the peripheral blood Higher levels of ATLL cells appeared to correlate with disease severity. FC detection of aberrant T cells permits sensitive and quantitative monitoring of MRD in ATLL. C1 [Shao, Haipeng; Yuan, Constance M.; Xi, Liqiang; Raffeld, Mark; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Morris, John C.; Janik, John E.] NCI, Metab Branch, Ctr Canc Res, Mark O Hatfield Clin Res Ctr,NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A-33,10 Ctr Dr, Bethesda, MD 20892 USA. FU National Institutes of Health, National Cancer Institute FX Supported by the Intramural Program of the National Institutes of Health, National Cancer Institute. NR 38 TC 12 Z9 12 U1 0 U2 3 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2010 VL 133 IS 4 BP 592 EP 601 DI 10.1309/AJCPS1K0OHLJYWWV PG 10 WC Pathology SC Pathology GA 572ID UT WOS:000275821400011 PM 20231613 ER PT J AU Chang, L Tong, K Ameen, V AF Chang, Lin Tong, Kenneth Ameen, Vanessa TI Ischemic Colitis and Complications of Constipation Associated With the Use of Alosetron Under a Risk Management Plan: Clinical Characteristics, Outcomes, and Incidences SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID IRRITABLE-BOWEL-SYNDROME; 5-HT3 RECEPTOR ANTAGONIST; ORAL-CONTRACEPTIVE USE; COLONIC TRANSIT; DOUBLE-BLIND; WOMEN; EFFICACY; METAANALYSIS; TRIALS; SAFETY AB OBJECTIVES: Alosetron is a potent, selective 5-HT(3) receptor antagonist prescribed for women with severe diarrhea-predominant irritable bowel syndrome (IBS-D) under a risk management plan (RMP). The RMP was implemented following cases of ischemic colitis (IC) and complications of constipation (CoC) associated with the use of alosetron. The objectives of this study were to characterize IC and CoC clinical features, outcomes, and incidence rates in the new restricted patient population to evaluate the effectiveness of the RMP in the prevention of serious outcomes. METHODS: Safety data from adverse event reporting from November 2002 through June 2008 were reviewed for probable and possible IC and CoC using the US Food and Drug Administration/sponsor-defined criteria and definitions. Evidence for IC included medical documentation, colonoscopy, and sigmoidoscopy +/- biopsy. Evidence for CoC included medical history and confirmation from health-care professionals. RESULTS: Within the inclusion dates, 29,072 patients received 203,939 alosetron prescriptions. Although the absolute numbers of IC and CoC cases have declined, the incidence rates for IC and CoC (0.95 and 0.36 cases per 1,000 patient-years, respectively) were similar to rates during the postmarketing cycle before alosetron withdrawal. In patients with severe IBS-D receiving alosetron (n = 998) or placebo (n = 411) in clinical trials since reintroduction, incidence rates for IC were 4 and 2 cases per 1,000 patients, respectively. Rates for CoC were 2 and 0 cases per 1,000 patients in the alosetron and placebo groups, respectively. No mesenteric ischemia, surgeries, transfusions, or deaths occurred in patients with IC and no cases of CoC were associated with toxic megacolon, perforation, surgeries, transfusions, or deaths. IC and CoC cases were typically of short duration and all improved on prompt withdrawal of alosetron. CONCLUSIONS: Serious outcomes associated with IC and CoC appear to be mitigated since introduction of alosetron under the RMP. C1 [Chang, Lin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Ctr Neurobiol Stress,Div Digest Dis, Los Angeles, CA 90095 USA. [Tong, Kenneth; Ameen, Vanessa] Prometheus Labs Inc, Clin Dev & Med Affairs, San Diego, CA USA. RP Ameen, V (reprint author), NIDDK, 6707 Democracy Blvd, Bethesda, MD 20892 USA. EM ameenvz@NIDDK.NIH.gov FU Prometheus Laboratories Inc.; Patrice Ferriola, PhD FX Financial support: Support for the study was provided by Prometheus Laboratories Inc. Editorial support, funded by Prometheus for preparation of the paper, was provided by Patrice Ferriola, PhD. NR 48 TC 43 Z9 44 U1 0 U2 7 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 APR PY 2010 VL 105 IS 4 BP 866 EP 875 DI 10.1038/ajg.2010.25 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 582FQ UT WOS:000276582300020 PM 20197759 ER PT J AU Moriyama, B Henning, SA Jin, H Kolf, M Rehak, NN Danner, RL Walsh, TJ Grimes, GJ AF Moriyama, Brad Henning, Stacey A. Jin, Haksong Kolf, Michael Rehak, Nadja N. Danner, Robert L. Walsh, Thomas J. Grimes, George J. TI Physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded hemofiltration solution SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Compounding; Concentration; Dextrose; Diluents; Electrolytes; Filtration; Hydrogen ion concentration; Incompatibilities; Magnesium sulfate; Sodium bicarbonate; Solutions; Stability; Storage ID PARENTERAL-NUTRITION ADMIXTURES; RENAL REPLACEMENT THERAPY; INORGANIC-PHOSPHATE SALTS; ORGANIC CALCIUM AB Purpose. The physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded hemofiltration solution was assessed. Methods. Two bicarbonate-buffered hemofiltration solutions (low- and high-magnesium formulations) were compounded in triplicate. The concentrations of magnesium (15 meq/L) and sodium bicarbonate (50 meq/L) in the high-magnesium formulation were chosen to be somewhat below the concentrations reported as being incompatible in a popular reference. The six hemofiltration bags were stored at 22-25 degrees C without protection from light for 48 hours. Physical compatibility was assessed by visual inspection and microscopy. The pH of the solutions was assayed 3-4 and 52-53 hours after compounding. Electrolyte and glucose concentrations of the solutions were assayed at 3-4 and 50-51 hours after preparation. Results. No particulate matter was observed by visual or microscopic inspection in the compounded hemofiltration solutions at 48 hours. The mean +/- S.D. pH values of the low-magnesium solutions were 8.01 +/- 0.02 and 8.04 +/- 0.02 at 3-4 and 52-53 hours after compounding, respectively. The mean S.D. pH values of the high-magnesium solutions were 7.96 +/- 0.02 and 7.98 +/- 0.01 at 3-4 and 52-53 hours after compounding, respectively. The electrolyte and glucose concentrations in the low- and high-magnesium solutions were similar 3-4 and 50-51 hours after preparation. Conclusion. Magnesium sulfate 1.5 meq/L and sodium bicarbonate 50 meq/L were physically compatible in a pharmacy-compounded hemofiltration solution for 48 hours when stored at 22-25 degrees C without protection from light. C1 [Grimes, George J.] NIH, Dept Pharm, Ctr Clin, Pharmaceut Dev Sect, Bethesda, MD 20892 USA. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Rehak, Nadja N.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Jin, Haksong; Kolf, Michael] NIH, Pharmaceut Dev Sect, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. RP Grimes, GJ (reprint author), NIH, Dept Pharm, Ctr Clin, Pharmaceut Dev Sect, 10 Ctr Dr, Bethesda, MD 20892 USA. EM ggrimes@cc.nih.gov FU National Institutes of Health FX Supported in part by the intramural research program of the National Institutes of Health. NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 1 PY 2010 VL 67 IS 7 BP 562 EP 565 DI 10.2146/ajhp090342 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573AP UT WOS:000275881100014 PM 20237384 ER PT J AU Rasu, RS Hunter, CM Peterson, AL Maruska, HM Foreyt, JP AF Rasu, Rafia S. Hunter, Christine M. Peterson, Alan L. Maruska, Heather M. Foreyt, John P. TI Economic Evaluation of an Internet-Based Weight Management Program SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID COST-EFFECTIVENESS ANALYSIS; AIR-FORCE; INTERVENTION; OVERWEIGHT; GAIN AB Objective: To determine whether a behavioral Internet treatment (BIT) program for weight management is a viable, cost-effective option compared with usual care (UC) in a diverse sample of overweight (average body mass index = 29 kg/m(2)), healthy adults (mean age = 34 years) serving in the US Air Force. Study Design: Two-group parallel randomized controlled trial. Methods: Participants were randomly assigned into 2 groups: UC (n = 215) and UC plus BIT (n = 227). Baseline and 6-month assessments were included in the analyses. Primary outcome measures (changes in body weight, percent body fat, and waist circumference) and secondary outcome measures (Weight Efficacy Lifestyle [WEL] questionnaire) were included in an incremental cost-effectiveness analysis (ICEA) model. Costs were computed using the perspective of an agency wanting to replicate the intervention. Sensitivity analyses were performed to measure the robustness of models. Results: Overall cost for BIT intervention was $11,178.40, or $49.24 per BIT participant. Total staff-time cost was $14.03 per BIT participant. Intervention cost was $25.92 per kilogram of weight loss and $28.96 per centimeter of waist-circumference loss. The cost was $37.88 for each additional point gained on the WEL subscale, where increasing scores indicate increased confidence in managing social pressures to eat. Conclusions: The BIT program is a cost-effective choice for weight management. It may cost more initially, but it results in long-term cost savings. Such cost-effective, Internet-based behavioral interventions for weight management could provide a valuable tool for preventive care aimed at improving individual and societal health. (Am J Manag Care. 2010; 16(4): e98-e104) C1 [Rasu, Rafia S.; Maruska, Heather M.] Univ Missouri, Dept Pharm Practice & Adm, Sch Pharm, Kansas City, MO 64106 USA. [Rasu, Rafia S.] Univ Missouri, Sch Nursing, Kansas City, MO 64106 USA. [Rasu, Rafia S.; Maruska, Heather M.] Univ Missouri, Bloch Sch Business & Publ Adm, Kansas City, MO 64106 USA. [Hunter, Christine M.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Peterson, Alan L.] Wilford Hall USAF Med Ctr, Dept Psychol, San Antonio, TX 78236 USA. [Foreyt, John P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Rasu, RS (reprint author), Univ Missouri, Dept Pharm Practice & Adm, Sch Pharm, 2464 Charlotte St,4247 Hlth Sci Bldg, Kansas City, MO 64106 USA. EM rassur@umkc.edu FU US Army Medical Research and Materiel Command [DAMD17-02-1-0180] FX This study was funded (John P. Foreyt, Principal Investigator) by the US Army Medical Research and Materiel Command's Peer Review Medical Research Program (DAMD17-02-1-0180). The views expressed in this article are those of the authors and are not the official policy of the Department of Defense or the US Air Force. NR 20 TC 15 Z9 15 U1 1 U2 5 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2010 VL 16 IS 4 BP E98 EP E104 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 584ZJ UT WOS:000276793300010 PM 20370312 ER PT J AU Marosy, B Justice, CM Vu, C Zorn, A Nzegwu, N Wilson, AF Miller, NH AF Marosy, Beth Justice, Cristina M. Vu, Cuong Zorn, Andrew Nzegwu, Nneka Wilson, Alexander F. Miller, Nancy H. TI Identification of Susceptibility Loci for Scoliosis in FIS Families With Triple Curves SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE idiopathic scoliosis; triple curve; genomic; chromosomes; familial; loci; screen; identification; spine; genes ID ADOLESCENT IDIOPATHIC SCOLIOSIS; VERTEBRAL ROTATION; LINKAGE ANALYSIS; GENETICS; BOSTON; BRACE; CLASSIFICATION; PREVALENCE; ASSIGNMENT; DEFORMITY AB The triple curve pattern (three lateral curvatures of equal severity) has been recognized as a distinct and unique clinical subtype of scoliosis. As part of a large study of familial idiopathic scoliosis (FIS), a subset of five families with a triple curve pattern (at least one member of each family having a triple curve) was evaluated to determine if this curve pattern was linked to any of the markers previously genotyped as part of the STRP-based previous linkage screen. Model independent linkage analysis (SIBPAL, v4.5) of the initial genomic screen identified candidate regions on chromosomes 6 and 10 when FIS was analyzed both as qualitative and quantitative traits in single- and multipoint linkage analyses. Additional fine mapping analyses of this subgroup with SNPs corroborated the findings in these regions (P < 0.001). These regions have been previously linked to FIS, however, this is the first time these regions have been implicated in a clinically well-defined subgroup and may suggest a unique genetic etiology for the formation of a triple curve. (C) 2010 Wiley-Liss, Inc. C1 [Marosy, Beth; Vu, Cuong; Zorn, Andrew; Nzegwu, Nneka; Miller, Nancy H.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Dept Orthopaed Surg, Baltimore, MD USA. [Justice, Cristina M.; Wilson, Alexander F.] NHGRI, Genometr Sect, NIH, Baltimore, MD USA. [Miller, Nancy H.] Univ Colorado, Hlth Sci Ctr Aurora, Aurora, CO USA. RP Miller, NH (reprint author), 13123 E 16th Ave,B060, Aurora, CO 80045 USA. EM nancy.hadley-miller@ucdenver.edu FU National Human Genome, Research Institute; National Institutes of Health [N01-HG-65403]; National Center for Research Resources [1 P41 RR03655]; Scoliosis Research Society; National Scoliosis Foundation; Scoliosis Association, Inc.; Institute de France Foundation Yves Cotrel; Orthopaedic Pediatric Society of North America; Orthopaedic Research and Education Foundation; NIH [1-R01-AR048862-01A1] FX Grant sponsor: Funding provided in part by International Research Program of the National Human Genome, Research Institute; Grant sponsor: Federal contract N01-HG-65403 from the National Institutes of Health to the Johns Hopkins University; Grant sponsor: National Center for Research Resources; Grant number: 1 P41 RR03655; Grant sponsor: The Scoliosis Research Society; Grant sponsor: National Scoliosis Foundation; Grant sponsor: Scoliosis Association, Inc.; Grant sponsor: Institute de France Foundation Yves Cotrel; Grant sponsor: Orthopaedic Pediatric Society of North America; Grant sponsor: Orthopaedic Research and Education Foundation; Grant sponsor: NIH; Grant number: 1-R01-AR048862-01A1. NR 61 TC 4 Z9 4 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2010 VL 152A IS 4 BP 846 EP 855 DI 10.1002/ajmg.a.33222 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 584LS UT WOS:000276754000009 PM 20358593 ER PT J AU Greenlee, RT Kessel, B Williams, CR Riley, TL Ragard, LR Hartge, P Buys, SS Partridge, EE Reding, DJ AF Greenlee, Robert T. Kessel, Bruce Williams, Craig R. Riley, Thomas L. Ragard, Lawrence R. Hartge, Patricia Buys, Saundra S. Partridge, Edward E. Reding, Douglas J. TI Prevalence, incidence, and natural history of simple ovarian cysts among women > 55 years old in a large cancer screening trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ovarian cancer; ovarian cyst; transvaginal ultrasound ID SIMPLE ADNEXAL CYSTS; POSTMENOPAUSAL WOMEN; MANAGEMENT; ULTRASOUND; DIAGNOSIS; PROSTATE; TUMORS; RISK; LUNG AB OBJECTIVE: The purpose of this study was to measure the occurrence and natural history of simple ovarian cysts in a cohort of older women. STUDY DESIGN: Simple cysts were ascertained among a cohort of 15,735 women from the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial through 4 years of transvaginal ultrasound screening. RESULTS: Simple cysts were seen in 14% of women the first time that their ovaries were visualized. The 1-year incidence of new simple cysts was 8%. Among ovaries with 1 simple cyst at the first screen, 54% retained 1 simple cyst, and 32% had no cyst 1 year later. Simple cysts did not increase risk of subsequent invasive ovarian cancer. CONCLUSION: Simple ovarian cysts are fairly common among postmenopausal women, and most cysts appear stable or resolve by the next annual examination. These findings support recent recommendations to follow unilocular simple cysts in postmenopausal women without intervention. C1 [Greenlee, Robert T.] Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI 54449 USA. [Kessel, Bruce] Univ Hawaii, John A Burns Sch Med, Pacific Hlth Res Inst, Honolulu, HI 96822 USA. [Williams, Craig R.; Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA. [Ragard, Lawrence R.] WESTAT Corp, Rockville, MD 20850 USA. [Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Buys, Saundra S.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Partridge, Edward E.] Univ Alabama, Birmingham, AL USA. [Reding, Douglas J.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. RP Greenlee, RT (reprint author), Marshfield Clin Res Fdn, Epidemiol Res Ctr, 1000 N Oak Ave,Mailstop ML2, Marshfield, WI 54449 USA. EM greenlee.robert@mcrf.mfldclin.edu FU National Cancer Institute [N01-CN-25518] FX This study was supported by National Cancer Institute Grant #N01-CN-25518 to Marshfield Clinic Research Foundation. NR 22 TC 8 Z9 8 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 APR PY 2010 VL 202 IS 4 AR 373.e1 DI 10.1016/j.ajog.2009.11.029 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 575TE UT WOS:000276090400016 PM 20096820 ER PT J AU Moczygemba, CK Paramsothy, P Meikle, S Kourtis, AP Barfield, WD Kuklina, E Posner, SF Whiteman, MK Jamieson, DJ AF Moczygemba, Charmaine K. Paramsothy, Pangaja Meikle, Susan Kourtis, Athena P. Barfield, Wanda D. Kuklina, Elena Posner, Samuel F. Whiteman, Maura K. Jamieson, Denise J. TI Route of delivery and neonatal birth trauma SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT District IV Annual Meeting of the American-College-of-Obstetricians-and-Gynecologists CY SEP 05-07, 2008 CL Orlando, FL SP Amer Coll Obstetricians & Gynecologists DE neonatal birth trauma; patient safety; route of delivery ID CESAREAN DELIVERY; INJURY AB OBJECTIVE: We sought to examine rates of birth trauma in 2 groupings (all International Classification of Diseases, Ninth Revision codes for birth trauma, and as defined by the Agency for Healthcare Research and Quality Patient Safety Indicator [PSI]) among infants born by vaginal and cesarean delivery. STUDY DESIGN: Data on singleton infants were obtained from the 2004-2005 Healthcare Cost and Utilization Project Nationwide Inpatient Sample. RESULTS: The rates of Agency for Healthcare Research and Quality PSI and all birth trauma were 2.45 and 25.85 per 1000 births, respectively. Compared with vaginal, cesarean delivery was associated with increased odds of PSI birth trauma (odds ratio [OR], 1.71), primarily due to an increased risk for "other specified birth trauma" (OR, 2.61). Conversely, cesarean delivery was associated with decreased odds of all birth trauma (OR, 0.55), due to decreased odds of clavicle fractures (OR, 0.07), brachial plexus (OR, 0.10), and scalp injuries (OR, 0.55). CONCLUSION: Infants delivered by cesarean are at risk for different types of birth trauma from infants delivered vaginally. C1 [Moczygemba, Charmaine K.] Emory Univ, Dept Gynecol & Obstet, Emory Sch Med, Atlanta, GA 30303 USA. [Kourtis, Athena P.; Barfield, Wanda D.; Posner, Samuel F.; Whiteman, Maura K.; Jamieson, Denise J.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Kuklina, Elena] Northrop Grumman Civilian Grp, Atlanta, GA USA. [Paramsothy, Pangaja] Contracept Res & Dev Program, Arlington, VA USA. [Meikle, Susan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD USA. RP Moczygemba, CK (reprint author), Emory Univ, Dept Gynecol & Obstet, Emory Sch Med, 69 Jesse Hill Jr Dr,4th Floor, Atlanta, GA 30303 USA. EM cmoczygemba@gmail.com OI Posner, Samuel/0000-0003-1574-585X NR 12 TC 2 Z9 2 U1 1 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 APR PY 2010 VL 202 IS 4 AR 361.e1 DI 10.1016/j.ajog.2009.11.041 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 575TE UT WOS:000276090400011 PM 20079477 ER PT J AU Gazzerro, E Assereto, S Bonetto, A Sotgia, F Scarfi, S Pistorio, A Bonuccelli, G Cilli, M Bruno, C Zara, F Lisanti, MP Minetti, C AF Gazzerro, Elisabetta Assereto, Stefania Bonetto, Andrea Sotgia, Federica Scarfi, Sonia Pistorio, Angela Bonuccelli, Gloria Cilli, Michele Bruno, Claudio Zara, Federico Lisanti, Michael P. Minetti, Carlo TI Therapeutic Potential of Protepsome Inhibition in Duchenne and Becker Muscular Dystrophies SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PROTEASOME INHIBITOR; MDX MOUSE; GLYCOPROTEIN COMPLEX; CA2+-DEPENDENT PROTEOLYSIS; NEUROMUSCULAR DISEASES; MUSCLE DEGENERATION; PEDIATRIC-PATIENTS; PHASE-II; BORTEZOMIB; MICE AB Duchenne muscular dystrophy (DMD) and its milder allelic variant, Becker muscular dystrophy (BMD), result from mutations of the dystrophin gene and lead to progressive muscle deterioration. Enhanced activation of proteasomal degradation underlies critical steps in the pathogenesis of the DMD/BMD dystrophic process. Previously, we demonstrated that treatment with the proteasome inhibitor MG-132 rescues the cell membrane localization of dystrophin and the dystrophin glycoprotein complex in mdx mice, a natural genetic mouse model of DMD. The current work aims to thoroughly define the therapeutic potential in dystrophinopathies of Velcade, a drug that selectively blocks the ubiquitin-proteasome pathway. Velcade is particularly intriguing since it has been approved for the treatment of multiple myeloma. Therefore, its side effects in humans have been explored. Velcade effects were analyzed through two independent methodological approaches. First, we administered the drug systemically in mdx mice over a 2-week period. In this system, Velcade restores the membrane expression of dystrophin and dystrophin glycoprotein complex members and improves the dystrophic phenotype. In a second approach, we treated with the compound explants from muscle biopsies of DMD or BMD patients. We show that the inhibition of the proteasome pathway up-regulates dystrophin, a-sarcoglycan, and P-dystroglycan protein levels in explants from BMD patients, whereas it increases the proteins of the dystrophin glycoprotein complex in DMD cases. (Am J Pathol 2010, 176:1863-1877; DOI: 10.2353/ajpath.2010.090468) C1 [Gazzerro, Elisabetta; Assereto, Stefania; Bonetto, Andrea; Sotgia, Federica; Bruno, Claudio; Zara, Federico; Lisanti, Michael P.; Minetti, Carlo] Univ Genoa, G Gaslini Inst, Muscular & Neurodegenerat Dis Unit, I-16147 Genoa, Italy. [Sotgia, Federica; Bonuccelli, Gloria; Lisanti, Michael P.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA. [Sotgia, Federica; Bonuccelli, Gloria; Lisanti, Michael P.] Thomas Jefferson Univ, Stem Cell Biol & Regenerat Med Ctr, Philadelphia, PA 19107 USA. [Scarfi, Sonia] Univ Genoa, Dept Expt Med, Biochem Sect, I-16126 Genoa, Italy. [Pistorio, Angela] G Gaslini Inst Children, Epidemiol & Biostat Unit, Genoa, Italy. [Cilli, Michele] Natl Canc Inst, Anim Res Facil, Genoa, Italy. RP Gazzerro, E (reprint author), Univ Genoa, G Gaslini Inst, Muscular & Neurodegenerat Dis Unit, Largo G Gaslini 5, I-16147 Genoa, Italy. EM elisabettagazzerro@ospedale-gaslini.ge.it RI Lisanti, Michael/C-6866-2013; Bruno, Claudio/A-3148-2015 OI Bruno, Claudio/0000-0002-3426-2901 FU Association Francaise contre les Myopathies (AFM) [13036, 13771]; Muscular Dystrophy Association FX Supported by the Association Francaise contre les Myopathies (AFM) grant 2007 # 13036 and AFM grant 2008 # 13771 and from funds donated by Prof. R. Bulgarelli. M.P.L., F.S., and G.B. were supported by a grant from the Muscular Dystrophy Association.; E.G. and S.A. contributed equally to this work. NR 44 TC 34 Z9 34 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2010 VL 176 IS 4 BP 1863 EP 1877 DI 10.2353/ajpath.2010.090468 PG 15 WC Pathology SC Pathology GA 580SX UT WOS:000276471500032 PM 20304949 ER PT J AU Xie, LK Hoffert, JD Chou, CL Yu, MJ Pisitkun, T Knepper, MA Fenton, RA AF Xie, Luke Hoffert, Jason D. Chou, Chung-Lin Yu, Ming-Jiun Pisitkun, Trairak Knepper, Mark A. Fenton, Robert A. TI Quantitative analysis of aquaporin-2 phosphorylation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE vasopressin; trafficking; quantitative immunoblot analysis; immunogold electron microscopy ID COLLECTING DUCT; WATER PERMEABILITY; VASOPRESSIN; CHANNEL; KIDNEY; SITES; AQP2; LOCALIZATION; EXPRESSION AB Xie L, Hoffert JD, Chou C, Yu M, Pisitkun T, Knepper MA, AFenton R. Quantitative analysis of aquaporin-2 phosphorylation. Am J Physiol Renal Physiol 298: F1018-F1023, 2010. First published January 20, 2010; doi:10.1152/ajprenal.00580.2009.-The action of vasopressin in rodent collecting ducts to regulate water permeability depends in part on increases in phosphorylation of the water channel aquaporin-2 (AQP2) at three sites: Ser256, Ser264, and Ser269. Previous studies of AQP2 phosphorylation have depended largely on qualitative data using protein mass spectrometry and phospho-specific antibodies. Here, we use a new method employing phospho-specific antibodies to determine the percentage of total AQP2 phosphorylated at each site in the presence and absence of the V2-receptor-selective vasopressin analog dDAVP in rat renal inner medullary collecting duct (IMCD) and cultured mpkCCD cells. Phosphorylation of Ser269, a site previously implicated in plasma membrane retention, was found to increase from 3 to 26% of total AQP2 in rat IMCD cells following dDAVP. Quantification of immunogold labeling of the opposite kidneys from the same rats estimated that 11% of total AQP2 is present in the apical plasma membrane (APM) without injection of dDAVP and 25% is present in the APM after dDAVP. Surprisingly, the baseline level of Ser256 phosphorylation was constitutively high, and there was no increase with dDAVP (confirmed in 2 more sets of rats). In general, Ser264 phosphorylation remained below 5% of total. The pattern of response was similar in cultured mpkCCD cells (large increase in Ser269 phosphorylation following dDAVP, but constitutively high levels of Ser256 phosphorylation). We suggest from these studies that Ser269 phosphorylation may be a more consistent indicator of vasopressin action and AQP2 membrane abundance than is Ser256 phosphorylation. C1 [Fenton, Robert A.] Univ Aarhus, Dept Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. [Xie, Luke; Hoffert, Jason D.; Chou, Chung-Lin; Yu, Ming-Jiun; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), Univ Aarhus, Dept Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. EM rofe@ana.au.dk OI Xie, Luke/0000-0002-3712-5558; Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU Intramural Budget of the National Heart, Lung, and Blood Institute (National Institutes of Health) [ZO1-HL001285]; Danish Medical Research Council; Novo Nordisk Fond; Carlsberg Foundation (Carlsbergfondet); Lundbeck Foundation; Danish National Research Foundation (Danmarks Grundforskningsfond) FX Funding to M. A. Knepper was provided by the Intramural Budget of the National Heart, Lung, and Blood Institute (National Institutes of Health Project ZO1-HL001285). Funding to R. A. Fenton was provided by the Danish Medical Research Council, the Novo Nordisk Fond, the Carlsberg Foundation (Carlsbergfondet), and the Lundbeck Foundation. The Water and Salt Research Center at the University of Aarhus is established and supported by the Danish National Research Foundation (Danmarks Grundforskningsfond). NR 22 TC 24 Z9 24 U1 1 U2 3 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 APR PY 2010 VL 298 IS 4 BP F1018 EP F1023 DI 10.1152/ajprenal.00580.2009 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 572TN UT WOS:000275856100021 PM 20089674 ER PT J AU Shmueli, D Prochaska, JJ Glantz, SA AF Shmueli, Dikla Prochaska, Judith J. Glantz, Stanton A. TI Effect of Smoking Scenes in Films on Immediate Smoking A Randomized Controlled Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ADOLESCENT SMOKING; COLLEGE-STUDENTS; MOVIE SMOKING; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; VIEWING SMOKING; CARBON-MONOXIDE; YOUTH SMOKING; POPULAR FILMS; YOUNG-ADULTS AB Background: The National Cancer Institute has concluded that exposure to smoking in movies causes adolescent smoking and there are similar results for young adults Purpose: This study investigated whether exposure of young adult smokers to images of smoking in films stimulated smoking behavior Methods: 100 cigarette smokers aged 18-25 years were randomly assigned to watch a movie montage composed with or without smoking scenes and paraphernalia followed by a 10-minute recess The outcome was whether or not participants smoked during the recess. Data were collected and analyzed in 2008 and 2009. Results: Smokers who watched the smoking scenes were more likely to smoke during the break (OR=3.06, 9596 CI = 1 01, 9 29). In addition to this acute effect of exposure, smokers who had seen more smoking in movies before the day of the experiment were more likely to smoke during the break (OR = 6.73, 95% CI = 1.00, 45.25, comparing the top to bottom 5th percentiles of exposure) Level of nicotine dependence (OR = 1.71, 95% CI = 1.27, 2 32 per point on the Fagerstrom Test for Nicotine Dependence scale), contemplation (OR = 9.07, 95% CI = 1.71, 47.99) and precontemplation (OR = 7.30, 9596 CI = 1.39, 38.36) stages of change; and impulsivity (OR = 1 21, 9596 CI = 1.03, 1 43) were also associated with smoking during the break. Participants who watched the montage with smoking scenes and those with a higher level of nicotine dependence were also more likely to have smoked within 30 minutes after the study Conclusions: There is a direct link between viewing smoking scenes and immediate subsequent smoking behavior. This finding suggests that individuals attempting to limit or quit smoking should be advised to refrain from or reduce their exposure to movies that contain smoking (Am J Prev Med 2010,38(4) 351-358) (C) 2010 American Journal of Preventive Medicine C1 [Shmueli, Dikla; Prochaska, Judith J.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Glantz, Stanton A.] Univ Calif San Francisco, Ctr Tobacco Control Res & Educ, San Francisco, CA 94143 USA. [Glantz, Stanton A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Shmueli, D (reprint author), Natl Canc Inst, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7326,Room 4083, Rockville, MD 20852 USA. FU State of California Tobacco-Related Disease Research [16FT-0050, 17RT-0077]; National Institute on Drug Abuse [T32 DA007250, K23 DA018691, P50 DA09253]; UCSF Division of Cardiology FX This research was supported by the State of California Tobacco-Related Disease Research Program (16FT-0050 and 17RT-0077) and the National Institute on Drug Abuse (T32 DA007250, K23 DA018691, and P50 DA09253). Dr. Glantz is American Legacy Foundation Distinguished Professor in Tobacco Control and utilized departmental discretionary funds from the UCSF Division of Cardiology to support some of the expenses associated with this study None of the funding agencies played any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, Or approval of the manuscript NR 55 TC 27 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2010 VL 38 IS 4 BP 351 EP 358 DI 10.1016/j.amepre.2009.12.025 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 580AS UT WOS:000276419500001 PM 20307802 ER PT J AU Ashida, S Wilkinson, AV Koehly, LM AF Ashida, Sato Wilkinson, Anna V. Koehly, Laura M. TI Motivation for Health Screening Evaluation of Social Influence Among Mexican-American Adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HIGH BLOOD-PRESSURE; METABOLIC SYNDROME; COLORECTAL-CANCER; CARDIOVASCULAR-DISEASE; MARITAL RELATIONSHIPS; RISK PERCEPTIONS; BEHAVIORS; IMPACT; WOMEN; MAMMOGRAPHY AB Background: Americans of Mexican origin are at high risk for developing cardiovascular disease Purpose: This study aimed to evaluate the associations between the presence of social network members who encourage screening and individuals motivation to undergo three types of health screening blood cholesterol, blood pressure, and blood glucose The distinct roles of encouragers from different generations (older, same, and younger) were evaluated Methods: Adults of Mexican origin (N=452) aged 20-75 years from 162 households in Houston TX were included in this cross-sectional study by completing surveys in 2008 regarding their intentions to screen, health behaviors, illness beliefs, social networks, and family health history in either English or Spanish Data were analyzed in 2009. Results: About one third of the participants reported having at least one same-generation network member who encouraged screening; smaller proportions reported having at least one older- (17% to 19%) and one younger-generation (11% to 12%) encourager The presence of at least one older-generation encourager was associated with higher levels of intention to screen for all three screenings controlling for sociodemographic characteristics and illness beliefs Having at least one same-generation encourager was associated with higher levels of intention to screen for blood cholesterol Conclusions: Social influence may play an important role in motivating individuals to engage in screenings. Network-based intervention involving older individuals to provide encouragement to younger network members should be explored as a means to increase motivation to screen among this population. (Am J Prev Med 2010,38(4) 396-402) Published by Elsevier Inc on behalf of American Journal of Preventive Medicine C1 [Ashida, Sato; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Wilkinson, Anna V.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Ashida, S (reprint author), NHGRI, Social & Behav Res Branch, 31 Ctr Dr,B1B37C MSC 2073, Bethesda, MD 20892 USA. FU National Human Genome Research Institute at the NIH [Z01HG200335]; Caroline W. Law Fund for Cancer Prevention; Dan Duncan Family Institut; National Cancer Institute [CA126988] FX This study was supported by the Intramural Research Program of the National Human Genome Research Institute at the NIH [Z01HG200335 to LMK] We thank Dr. ML Bondy and the Mano a Mano cohort staff for their ongoing work with participant recruitment and follow-up. The Mano a Mano cohort is funded by funds collected pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th legislature to the University of Texas MD Anderson Cancer Center, by the Caroline W. Law Fund for Cancer Prevention, and the Dan Duncan Family Institute. AVW is funded by the National Cancer Institute [CA126988]. We express our gratitude to the participants of this study. In addition, we thank the RAMA research team for their hard work collecting the data for this project. We thank Rick Crux for comments on an earlier draft of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the USDHHS, nor the U.S. Government. NR 57 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2010 VL 38 IS 4 BP 396 EP 402 DI 10.1016/j.amepre.2009.12.028 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 580AS UT WOS:000276419500007 PM 20307808 ER PT J AU Geiss, LS James, C Gregg, EW Albright, A Williamson, DF Cowie, CC AF Geiss, Linda S. James, Cherie Gregg, Edward W. Albright, Ann Williamson, David F. Cowie, Catherine C. TI Diabetes Risk Reduction Behaviors Among US Adults with Prediabetes SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; INCIDENT CARDIOVASCULAR EVENTS; PRIMARY-CARE; PHYSICAL-ACTIVITY; PREVENTION PROGRAM; OBESE-PATIENTS; LIFE-STYLE; MELLITUS; WEIGHT; ADVICE AB Background: Diabetes can be prevented or delayed in high-risk adults through lifestyle modifications, including dietary changes, moderate-intensity exercise, and modest weight loss. However, the extent to which U.S. adults with prediabetes are making lifestyle changes consistent with reducing risk is unknown. Purpose: This study aimed to study lifestyle changes consistent with reducing diabetes risk and factors associated with their adoption among adults with prediabetes Methods: In 2009, data were analyzed from 1402 adults aged years without diabetes who participated in the 2005-2006 National Health and Nutrition Examination Survey and had valid fasting plasma glucose and oral glucose tolerance tests The extent to which adults with prediabetes report that in the past year they tried to control or lose weight, reduced the amount of fat or calories in their diet, or increased physical activity or exercise was estimated and factors associated with the adoption of these behaviors were examined Results: Almost 30% of the U.S. adult population had prediabetes in 2005-2006, but only 7 3% (95% CI=5.596, 92%) were aware they had it. About half of adults with prediabetes reported performing diabetes risk reduction behaviors in the past year, but only about one third of adults with prediabetes had received healthcare provider advice about these behaviors in the past year. In multivariate analyses, provider advice, female gender, and being overweight or obese were positively associated with all three risk reduction behaviors. Conclusions: Adoption of risk reduction behaviors among U.S. adults with prediabetes is suboptimal. Efforts to improve awareness of prediabetes, increase promotion of healthy behaviors, and improve availability of evidence-based lifestyle programs are needed to slow the growth in new cases of diabetes (Am J Prev Med 2010,38(4) 403-409) Published by Elsevier Inc on behalf of American Journal of Preventive Medicine C1 [Geiss, Linda S.; James, Cherie; Gregg, Edward W.; Albright, Ann; Williamson, David F.] Emory Univ, Rollins Sch Publ Hlth, Div Diabet Translat, Atlanta, GA 30322 USA. [Williamson, David F.] Emory Univ, CDC, Hubert Dept Global Hlth, Atlanta, GA 30322 USA. [Cowie, Catherine C.] NIDDK, NIH, Bethesda, MD USA. RP Geiss, LS (reprint author), Diabet Div, MS K10,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 31 TC 71 Z9 71 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2010 VL 38 IS 4 BP 403 EP 409 DI 10.1016/j.amepre.2009.12.029 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 580AS UT WOS:000276419500008 PM 20307809 ER PT J AU Troped, PJ Wilson, JS Matthews, CE Cromley, EK Melly, SJ AF Troped, Philip J. Wilson, Jeffrey S. Matthews, Charles E. Cromley, Ellen K. Melly, Steven J. TI The Built Environment and Location-Based Physical Activity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID COMPUTER-SCIENCE; CARDIOVASCULAR-DISEASE; UNITED-STATES; TIME SPENT; ACCELEROMETER; PREVENTION; COMMUNITY; WALKING; DESIGN; POLICY AB Background: Studies of the built environment and physical activity have implicitly assumed that a substantial amount of activity occurs near home, but in fact the location is unknown Purpose: This study aims to examine associations between built environment variables within home and work buffers and moderate-to-vigorous physical activity (MVPA) occurring within these locations. Methods: Adults (n=148) from Massachusetts wore an accelerometer and GPS unit for up to 4 days Levels of MVPA were quantified within 50-m and I-km home and work buffers. Multiple regression models were used to examine associations between five objective built environment variables within 1-km home and work buffers (intersection density, land use mix, population and housing unit density, vegetation index) and MVPA within those areas Results: The mean daily minutes of MVPA accumulated in all locations=61.1 +/- 32.8, whereas duration within the 1-km home buffers=14.0 +/- 16 4 minutes. Intersection density, land use mix, and population and housing unit density within 1-km home buffers were positively associated with MVPA in the buffer, whereas a vegetation index showed an inverse relationship (all p<0.05) None of these variables showed associations with total MVPA Within I km of work, only population and housing unit density were significantly associated with MVPA within the buffer Conclusions: Findings are consistent with studies showing that certain attributes of the built environment around homes are positively related to physical activity, but in this case only when the outcome was location-based Simultaneous accelerometer-GPS monitoring shows promise as a method to improve understanding of how the built environment influences physical activity behaviors by allowing activity to be quantified in a range of physical contexts and thereby provide a more explicit link between physical activity outcomes and built environment exposures. (Am J Prey Med 2010,38(4) 429 - 438) (C) 2010 American Journal of Preventive Medicine C1 [Troped, Philip J.] Purdue Univ, Dept Hlth & Kinesiol, W Lafayette, IN 47907 USA. [Wilson, Jeffrey S.] Indiana Univ Purdue Univ, Dept Geog, Indianapolis, IN 46202 USA. [Matthews, Charles E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Cromley, Ellen K.] Inst Community Res, Hartford, CT USA. [Melly, Steven J.] Harvard Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA USA. RP Troped, PJ (reprint author), Purdue Univ, Dept Hlth & Kinesiol, Lambert Fieldhouse,Room I06-B,800 W Stadium Ave, W Lafayette, IN 47907 USA. RI matthews, Charles/E-8073-2015 OI matthews, Charles/0000-0001-8037-3103 FU Active Living Research Program; Robert Wood Johnson Foundation; College of Liberal Arts at Purdue University FX This study was supported with funding from the Active Living Research Program, the Robert Wood Johnson Foundation, and additional funding from the College of Liberal Arts at Purdue University. We thank Marcelo Oliveira and Jean Wolf from GeoStats, Inc, Atlanta GA, for their assistance with GPS data collection and processing. In addition, we thank Dr. Bruce Craig from the Department of Statistics, Purdue University, for his recommendations on statistical modeling approaches, Andreana Robertson for SAS programming, and Kosuke Tamura for manuscript preparation NR 29 TC 95 Z9 97 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2010 VL 38 IS 4 BP 429 EP 438 DI 10.1016/j.amepre.2009.12.032 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 580AS UT WOS:000276419500011 PM 20307812 ER PT J AU Hoots, WK AF Hoots, W. Keith TI The Registry and Surveillance in Hemoglobinopathies Improving the Lives of Individuals with Hemoglobinopathies SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material C1 NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Hoots, WK (reprint author), NHLBI, Div Blood Dis & Resources, 6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA. NR 15 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2010 VL 38 IS 4 SU 4 BP S510 EP S511 DI 10.1016/j.amepre.2010.01.005 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 580AV UT WOS:000276419800011 PM 20331951 ER PT J AU Shaw, P AF Shaw, Philip TI The Shape of Things to Come in Attention Deficit Hyperactivity Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; ADOLESCENTS; VOLUME C1 NIMH, Bethesda, MD 20892 USA. RP Shaw, P (reprint author), NIMH, Bldg 10,Rm 3N202, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov NR 10 TC 2 Z9 2 U1 2 U2 3 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 APR PY 2010 VL 167 IS 4 BP 363 EP 365 DI 10.1176/appi.ajp.2010.10010037 PG 3 WC Psychiatry SC Psychiatry GA 577LE UT WOS:000276223800001 PM 20360322 ER PT J AU Bu, LP Fee, E AF Bu, Liping Fee, Elizabeth TI Unite to Fight Malaria! SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Bu, Liping] Alma Coll, Dept Hist, Alma, MI 48801 USA. [Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Bu, LP (reprint author), Alma Coll, Dept Hist, 614 W Superior St, Alma, MI 48801 USA. EM bulipi@alma.edu FU NLM NIH HHS [G13 LM009702, 1G13LM009702-01] NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2010 VL 100 IS 4 BP 608 EP 608 DI 10.2105/AJPH.2009.181743 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 573TG UT WOS:000275937200009 PM 20167882 ER PT J AU Vaisbuch, E Romero, R Erez, O Mazaki-Tovi, S Kusanovic, JP Soto, E Dong, Z Chaiworapongsa, T Kim, SK Ogge, G Pacora, P Yeo, L Hassan, SS AF Vaisbuch, Edi Romero, Roberto Erez, Offer Mazaki-Tovi, Shali Kusanovic, Juan Pedro Soto, Eleazar Dong, Zhong Chaiworapongsa, Tinnakorn Kim, Sun Kwon Ogge, Giovanna Pacora, Percy Yeo, Lami Hassan, Sonia S. TI Activation of the Alternative Pathway of Complement is a Feature of Pre-Term Parturition but not of Spontaneous Labor at Term SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Review DE Inflammation; intra-amniotic infection; microbial invasion of the amniotic cavity; pregnancy; pre-term delivery; pre-term labor ID MANNOSE-BINDING LECTIN; INFLAMMATORY RESPONSE SYNDROME; NORMAL HUMAN-PREGNANCY; FACTOR-H POLYMORPHISM; TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID; MACULAR DEGENERATION; INTRAAMNIOTIC INFECTION; PRE-ECLAMPSIA; PERIODONTAL INFECTION AB Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous pre-term delivery < 34 weeks of gestation. The aim of this study was to determine whether spontaneous pre-term labor (PTL) with intact membranes, intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of study This cross-sectional study included women in the following groups: (i) non-pregnant (n = 40); (ii) normal pregnancy (gestational age range 20-36, 6/7 weeks, n = 63); (iii) women at term not in labor (n = 70); (iv) women at term in spontaneous labor (n = 59); (v) patients with an episode of PTL who delivered at term (n = 62); (vi) PTL without IAI who delivered pre-term (n = 30); and (vii) PTL with IAI who delivered pre-term (n = 67). Maternal plasma FBb concentrations were determined by ELISA. Results (i) Among patients with PTL, those who had a pre-term delivery either with IAI (1.21 mu g/mL, IQR 0.77-2.16) or without IAI (1.13 mu g/mL, IQR 0.92-2.08) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 mu g/mL, IQR 0.64-1.57; P = 0.007 and P = 0.026, respectively); (ii) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered pre-term (P = 0.9); (iii) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (P = 0.8); (iv) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (P = 0.8) and were not correlated with advancing gestational age (r = -0.28, P = 0.8). Conclusion (i) Pre-term parturition is associated with activation of the alternative complement pathway in maternal circulation; (ii) such activation is not detectable in spontaneous labor at term; (iii) IAI does not explain the activation of the alternative pathway of complement in PTL. Collectively, these observations suggest that pre-term and term labors have fundamental differences in the regulation of innate immunity. C1 [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Ogge, Giovanna; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Ogge, Giovanna; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Soto, Eleazar; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. The authors would like to thank Dr. Jane E. Salmon (Hospital for Special Surgery, Weill Medical College, Cornell University, New York, NY) for the thoughtful and valuable advice during the conduction of this work. NR 109 TC 16 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD APR PY 2010 VL 63 IS 4 BP 318 EP 330 DI 10.1111/j.1600-0897.2009.00800.x PG 13 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 567JF UT WOS:000275442200007 PM 20163401 ER PT J AU Garantziotis, S Li, Z Potts, EN Lindsey, JY Stober, VP Polosukhin, VV Blackwell, TS Schwartz, DA Foster, WM Hollingsworth, JW AF Garantziotis, Stavros Li, Zhuowei Potts, Erin N. Lindsey, James Y. Stober, Vandy P. Polosukhin, Vasiliy V. Blackwell, Timothy S. Schwartz, David A. Foster, W. Michael Hollingsworth, John W. TI TLR4 Is Necessary for Hyaluronan-mediated Airway Hyperresponsiveness after Ozone Inhalation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE environmental airways injury; asthma; toll-like receptor; macrophage; TNF-alpha ID TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; LUNG INJURY; TNF-ALPHA; ALVEOLAR MACROPHAGES; EPITHELIAL-CELLS; NITRIC-OXIDE; INFLAMMATION; MICE; EXPOSURE AB Rationale: Ozone is a common environmental air pollutant that contributes to hospitalizations for respiratory illness. The mechanisms, which regulate ozone-induced airway hyperresponsiveness, remain poorly understood. We have previously reported that toll-like receptor 4 (TLR4) deficient animals are protected against ozone-induced airway hyperresponsiveness (AHR) and that hyaluronan (HA) mediates ozone-induced AHR. However, the relation between TLR4 and hyaluronan in the airway response to ozone remains unexplored. Objectives: We hypothesized that HA acts as an endogenous TLR4 ligand for the development of AHR after ozone-induced environmental airway injury. Methods: TLR4-deficient and wild-type C57BL/6 mice were exposed to either inhaled ozone or intratracheal HA and the inflammatory and AHR response was measured. Measurements and Main Results: TLR4-deficient mice have similar levels of cellular inflammation, lung injury, and soluble HA levels as those of C57BL/6 mice after inhaled ozone exposure. However, TLR4-deficient mice are partially protected from AHR after ozone exposure as well as after direct intratracheal instillation of endotoxin-free low molecular weight HA. Similar patterns of TLR4-dependent cytokines were observed in the bronchial alveolar lavage fluid after exposure to either ozone or HA. Exposure to ozone increased immunohistological staining of TLR4 on lung macrophages. Furthermore, in vitro HA exposure of bone marrow derived macrophages induced NF-kappa B and production of a similar pattern of proinflammatory cytokines in a manner dependent on TLR4. Conclusions: Our observations support the observation that extracellular matrix HA contributes to ozone-induced airways disease. Furthermore, our results support that TLR4 contributes to the biological response to HA by mediating both the production of proinflammatory cytokines and the development of ozone-induced AHR. C1 [Li, Zhuowei; Potts, Erin N.; Lindsey, James Y.; Foster, W. Michael; Hollingsworth, John W.] Duke Univ, Div Pulm Allergy & Crit Care Med, Dept Med, Med Ctr, Durham, NC 27710 USA. [Garantziotis, Stavros; Stober, Vandy P.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Polosukhin, Vasiliy V.; Blackwell, Timothy S.] Vanderbilt Univ, Sch Med, Dept Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. [Schwartz, David A.] Natl Jewish Med Ctr, Denver, CO USA. RP Hollingsworth, JW (reprint author), Duke Univ, Div Pulm Allergy & Crit Care Med, Dept Med, Med Ctr, Box 103004, Durham, NC 27710 USA. EM holli017@mc.duke.edu RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU National Institute of Environmental Health Services [ES16347, ES16126, ES16659]; National Institutes of Health, National Institute of Environmental Health Sciences FX Supported by the National Institute of Environmental Health Services (ES16347, ES16126, ES16659). Support is also provided, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 48 TC 47 Z9 49 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2010 VL 181 IS 7 BP 666 EP 675 DI 10.1164/rccm.200903-0381OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 578AR UT WOS:000276266100007 PM 20007931 ER PT J AU Carney, JA Gaillard, RC Bertherat, J Stratakis, CA AF Carney, J. Aidan Gaillard, Rolf C. Bertherat, Jerome Stratakis, Constantine A. TI Familial Micronodular Adrenocortical Disease, Cushing Syndrome, and Mutations of the Gene Encoding Phosphodiesterase 11A4 (PDE11A) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Cushing syndrome; PDE11A mutation; primary pigmented nodular adrenocortical disease; micronodular adrenal hyperplasia; PRKAR1A mutation ID MCCUNE-ALBRIGHT-SYNDROME; CARNEY COMPLEX; ADRENAL-HYPERPLASIA; REGULATORY SUBUNIT; PRKAR1A GENE; PROTEIN; FEATURES; PDE8B AB We present the pathologic findings in the adrenal glands of 4 patients, aged 10 to 38 years, with Cushing syndrome and germline inactivating mutations of the gene PDE11A4 that encodes phosphodiesterase11A4. The gene is expressed in the adrenal cortex and catalyses the hydrolysis of cyclic adenosine monophosphate and cyclic guanosine monophosphate. Two of the patients were mother and daughter; the third had no affected relative; the fourth patient inherited the mutation from her father. Three of the group, including the mother and daughter, had the same pathology, primary pigmented nodular adrenocortical disease, a disorder known to be caused by inactivating mutations of the PRKAR1A gene. In these cases, the adrenal glands were small and the pathologic change was deep in the cortex in which numerous pigmented micronodules developed. In the remaining patient, the glands were slightly enlarged primarily owing to a diffuse hyperplasia of the superficial cortex that extended into the epi-adrenal fat. C1 [Carney, J. Aidan] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Gaillard, Rolf C.] Univ Vaudois, Dept Diabet Endocrinol & Metab, Ctr Hosp, Lausanne, Switzerland. [Bertherat, Jerome] Hop Cochin, Serv Endocrinol, F-75674 Paris, France. [Stratakis, Constantine A.] NICHD, Sect Endocrinol & Genet, PDEGEN, NIH, Bethesda, MD USA. RP Carney, JA (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 SW 1st St, Rochester, MN 55905 USA. EM carney.aidan@mayo.edu FU Agence Nationale pour la Reserche [ANR-08-GENOPAT-002] FX Jerome Bertherat was supported by a grant from Agence Nationale pour la Reserche Grant ANR-08-GENOPAT-002. NR 24 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2010 VL 34 IS 4 BP 547 EP 555 DI 10.1097/PAS.0b013e3181d31f49 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 584CC UT WOS:000276726600014 PM 20351491 ER PT J AU Venkataraman, G McClain, KL Pittaluga, S Rao, VK Jaffe, ES AF Venkataraman, Girish McClain, Kenneth L. Pittaluga, Stefania Rao, V. Koneti Jaffe, Elaine S. TI Development of Disseminated Histiocytic Sarcoma in a Patient With Autoimmune Lymphoproliferative Syndrome and Associated Rosai-Dorfman Disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE histiocytic sarcoma; Rosai-Dorfman disease; sinus histiocytosis with massive lymphadenopathy; apoptosis; autoimmune lymphoproliferative syndrome ID LYMPHOID-TISSUE LYMPHOMA; MASSIVE LYMPHADENOPATHY; SINUS HISTIOCYTOSIS; FOLLICULAR LYMPHOMA; APOPTOSIS; MUTATIONS; CYTOKINE; DISORDER; FEATURES; PROTEIN AB Patients with autoimmune lymphoproliferative syndrome (ALPS) have defective lymphocyte apoptosis with increased risk for lymphoid malignancies. Herein, we report a patient with ALPS who developed histiocytic sarcoma in a background of sinus histiocytosis and massive lymphadenopathy or Rosai-Dorfman disease. This patient had documented ALPS type Ia with a germline missense mutation in exon 9 of the TNFRSF6 gene (973 A > T, D244V) encoding Fas (CD95/Apo-1). He presented at 10 months with hepatosplenomegaly and autoimmune hemolytic anemia and was diagnosed with ALPS. At the age of 6 years, he developed classic Hodgkin lymphoma which was treated using standard chemotherapy. Two years later, a biopsy of a positron emission tomography-positive axillary node showed features of ALPS and focal involvement by sinus histiocytosis and massive lymphadenopathy. Thereafter, the patient continued to have continued lymphadenopathy and progressive splenomegaly, leading to exploratory surgery at the age of 13 years for suspicion of lymphoma. Para-abdominal nodes revealed sheets of malignant-looking histiocytes with increased mitotic activity and areas of necrosis, indicative of histiocytic sarcoma. Spleen and lymph nodes also showed involvement by Rosai-Dorfman disease. Both components had an identical phenotype of S-100+/CD68+/CD163+. The occurrence of malignancies involving 2 separate hematopoietic lineages in ALPS has not been reported earlier. Given the central role of defective Fas signaling in ALPS, histiocytes may be yet another lineage at risk for neoplastic transformation secondary to a block in apoptosis. C1 [Venkataraman, Girish; Pittaluga, Stefania; Jaffe, Elaine S.] NIH, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [McClain, Kenneth L.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Rao, V. Koneti] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. RP Jaffe, ES (reprint author), NIH, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 2B 42, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov OI Venkataraman, Girish/0000-0002-8674-2608; Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute; National Institute of Allergy and Infectious Diseases FX Supported by the intramural research programs of Center for Cancer Research, National Cancer Institute, and the National Institute of Allergy and Infectious Diseases. NR 24 TC 19 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2010 VL 34 IS 4 BP 589 EP 594 DI 10.1097/PAS.0b013e3181d5ddf8 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 584CC UT WOS:000276726600021 PM 20216376 ER PT J AU Meyers, K McDonald, R Smith, J Mathais, R Portale, A Liu, J Morrison, Y Bridges, N Harmon, W AF Meyers, Kevin McDonald, Ruth Smith, Jodi Mathais, Robert Portale, Anthony Liu, Jun Morrison, Yvonne Bridges, Nancy Harmon, William TI A Phase II Exploratory Study To Determine the Safety and Study of the Immunomodulatory Functions of Induction Therapy with Campath-1H (R), Combined with Chronic Immunosuppression with MMF and Sirolimus: A Study of the Pediatric Cooperative Clinical Trials in Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Meyers, Kevin] Univ Penn, CHOP, Philadelphia, PA 19104 USA. [McDonald, Ruth; Smith, Jodi] Univ Washington, Seattle, WA 98195 USA. [Portale, Anthony] UCSF, San Francisco, CA USA. [Morrison, Yvonne; Bridges, Nancy] NIAID, NIH, Bethesda, MD 20892 USA. [Harmon, William] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 74 EP 74 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701115 ER PT J AU Lee, JJ Hurst, FP Abbott, KC Agodoa, LY Jindal, RM AF Lee, Jessica J. Hurst, Frank P. Abbott, Kevin C. Agodoa, Lawrence Y. Jindal, Rahul M. TI Outcomes Associated with Influenza Vaccination in the First Year after Kidney Transplantation: Analysis of USRDS SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Lee, Jessica J.; Hurst, Frank P.; Abbott, Kevin C.; Jindal, Rahul M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 127 EP 127 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701292 ER PT J AU Azimzadeh, AM Kelishadi, S Ezzelarab, M Singh, AK Stoddard, T Zhang, TS Burdorf, L Avon, C Laaris, A Cheng, XF Ayares, D Horvath, K Corcoran, P Mohiuddin, M Cooper, DK Barth, RN Pierson, RN AF Azimzadeh, Agnes M. Kelishadi, Sean Ezzelarab, Mohamed Singh, Avneesh K. Stoddard, Tiffany Zhang, Tianshu Burdorf, Lars Avon, Chris Laaris, Amal Cheng, Xiangfei Ayares, David Horvath, Keith Corcoran, P. Mohiuddin, Muhammad Cooper, David K. Barth, Rolf N. Pierson, Richard N. TI Early Graft Failure of GTKO Pig Organs in Baboons Is Reduced by HCPRP Expression SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Azimzadeh, Agnes M.; Kelishadi, Sean; Stoddard, Tiffany; Zhang, Tianshu; Burdorf, Lars; Avon, Chris; Laaris, Amal; Cheng, Xiangfei; Barth, Rolf N.; Pierson, Richard N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Azimzadeh, Agnes M.; Kelishadi, Sean; Stoddard, Tiffany; Zhang, Tianshu; Burdorf, Lars; Avon, Chris; Laaris, Amal; Cheng, Xiangfei; Barth, Rolf N.; Pierson, Richard N.] Baltimore VAMC, Baltimore, MD USA. [Ezzelarab, Mohamed; Cooper, David K.] Univ Pittsburgh, Starzl Transplantat Inst, Pittsburgh, PA 15260 USA. [Singh, Avneesh K.; Horvath, Keith; Corcoran, P.; Mohiuddin, Muhammad] NHLBI, NIH, Cardiothorac Res Program, Bethesda, MD USA. [Ayares, David] Revivicor, Blacksburg, VA USA. RI Barth, Rolf/B-2542-2014; Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 186 EP 187 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701499 ER PT J AU Mohiuddin, MM Corcoran, PC Singh, AK Hoyt, RF Thomas, ML Eckhaus, MA Azimzadeh, A Pierson, RN Horvath, KA AF Mohiuddin, Muhammad M. Corcoran, Philip C. Singh, Avneesh K. Hoyt, Robert F. Thomas, Marvin L. Eckhaus, Michael A. Azimzadeh, Agnes Pierson, Richard N. Horvath, Keith A. TI Pig to Baboon Cardiac Xenotransplantation: Essential Role of B Cell Depletion in Prolonging Cardiac Xenograft Survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Mohiuddin, Muhammad M.; Corcoran, Philip C.; Singh, Avneesh K.; Hoyt, Robert F.; Horvath, Keith A.] NHLBI, NIH, Bethesda, MD USA. [Thomas, Marvin L.; Eckhaus, Michael A.] DVR, NIH, Bethesda, MD USA. [Azimzadeh, Agnes; Pierson, Richard N.] Univ Maryland, College Pk, MD 20742 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 186 EP 186 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921701498 ER PT J AU Chakkera, H Devarapalli, Y Weil, EJ Mazur, M Hamawi, K Reddy, K Mulligan, M Moss, A Mekeel, K Heilman, R AF Chakkera, Harini Devarapalli, Y. Weil, E. J. Mazur, M. Hamawi, K. Reddy, K. Mulligan, M. Moss, A. Mekeel, K. Heilman, R. TI Predictive Risk of Pre-Transplant Fasting Glucose on the Development of New Onset Diabetes after Kidney Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Weil, E. J.] NIDDK, NIH, Phoenix, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 243 EP 243 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702110 ER PT J AU Hurst, FP Sajjad, I Elster, EA Falta, EM Agodoa, LY Abbott, KC Jindal, RM AF Hurst, Frank P. Sajjad, Imran Elster, Eric A. Falta, Edward M. Agodoa, Lawrence Y. Abbott, Kevin C. Jindal, Rahul M. TI Transplantation of A2 Kidneys into B and O Recipients: USRDS Experience. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Hurst, Frank P.; Elster, Eric A.; Falta, Edward M.; Abbott, Kevin C.; Jindal, Rahul M.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. [Sajjad, Imran] Univ Wisconsin, Madison, WI USA. [Agodoa, Lawrence Y.] NIDDK, Natl Inst Hlth, Bethesda, MD USA. [Jindal, Rahul M.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 282 EP 282 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702254 ER PT J AU Singh, AK Seavey, CN Horvath, KA Mohiuddin, MM AF Singh, Avneesh K. Seavey, Caleb N. Horvath, Keith A. Mohiuddin, Muhammad M. TI Ex-Vivo Expanded CD4+CD25+Treg Cells Suppress T and B Immune Response. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Singh, Avneesh K.; Seavey, Caleb N.; Horvath, Keith A.; Mohiuddin, Muhammad M.] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 298 EP 298 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702307 ER PT J AU Horvath, KA Corcoran, PC Singh, AK Hoyt, RF Thomas, ML Mohiuddin, MM AF Horvath, Keith A. Corcoran, Philip C. Singh, Avneesh K. Hoyt, Robert F. Thomas, Marvin L. Mohiuddin, Muhammad M. TI Left Ventricular Pressure Measurement with Telemetry Offers an Accurate and Convenient Measurement of Cardiac Xenograft Function. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Horvath, Keith A.; Corcoran, Philip C.; Singh, Avneesh K.; Hoyt, Robert F.; Mohiuddin, Muhammad M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Thomas, Marvin L.] DVR NIH, Bethesda, MD USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 299 EP 299 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702308 ER PT J AU Corcoran, PC Horvath, KA Singh, AK Hoyt, RF Thomas, ML Mohiuddin, MM AF Corcoran, Philip C. Horvath, Keith A. Singh, Avneesh K. Hoyt, Robert F. Thomas, Marvin L. Mohiuddin, Muhammad M. TI Recipient Related Surgical and Non Surgical Complications in a Pig to Baboon Cardiac Xenotransplantation Model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 10th American Transplant Congress CY MAY 01-05, 2010 CL San Diego, CA SP Amer Soc Transplantat C1 [Corcoran, Philip C.; Horvath, Keith A.; Singh, Avneesh K.; Hoyt, Robert F.; Mohiuddin, Muhammad M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Thomas, Marvin L.] DVR ORS NIH, Bethesda, MD USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2010 VL 10 SU 4 SI SI BP 300 EP 300 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 573NX UT WOS:000275921702312 ER PT J AU Tian, F Marini, AM Lipsky, RH AF Tian, Feng Marini, Ann M. Lipsky, Robert H. TI NMDA receptor activation induces differential epigenetic modification of Bdnf promoters in hippocampal neurons SO AMINO ACIDS LA English DT Article DE Brain-derived neurotrophic factor; BDNF; Chromatin remodeling; Epigenetic modification; Histone; Methylation; HDAC; MeCP2 ID NEUROTROPHIC FACTOR GENE; METHYL-D-ASPARTATE; LONG-TERM POTENTIATION; MULTIPLE PROMOTERS; SYNAPTIC ACTIVITY; KAPPA-B; BRAIN; EXPRESSION; PLASTICITY; PROTEIN AB Transcriptional regulation of the gene encoding brain-derived neurotrophic factor (BDNF) has been widely studied. However, an understanding of mechanisms modifying chromatin, events that are essential for controlling transcription, is rudimentary. We focused on two activation-dependent regions of the Bdnf gene physically linked to known transcription sites for exons 1 and 4. Using chromatin immunoprecipitation assays, we determined that N-methyl-d-aspartate (NMDA) receptor activation derepressed promoters 1 and 4-mediated transcription. This derepression correlated with reduced occupancy by histone deacetylase 1 and methyl cytosine-binding protein 2 of each promoter region near known transcription start sites in cultured hippocampal neurons. These changes did not occur at all sites upstream of transcription initiation. Taken together, these findings suggest that histone and other DNA-binding proteins are involved in remodeling of chromatin at some, but not all sites, within Bdnf promoters 1 and 4 and are associated with NMDA receptor-dependent increases in transcription. C1 [Tian, Feng] NCI, Sect Canc Genet, Genet Branch, NIH, Bethesda, MD 20892 USA. [Marini, Ann M.; Lipsky, Robert H.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. [Marini, Ann M.; Lipsky, Robert H.] Uniformed Serv Univ Hlth Sci, Program Neurosci, Bethesda, MD 20814 USA. [Lipsky, Robert H.] Inova Fairfax Hosp, Dept Neurosci, Falls Church, VA 22042 USA. RP Lipsky, RH (reprint author), Inova Fairfax Hosp, Dept Neurosci, 3300 Gallows Rd, Falls Church, VA 22042 USA. EM robert.lipsky@inova.org OI Lipsky, Robert/0000-0001-7753-1473 FU NIH [NIAAA Z01-AA00325]; Defense Brain and Spinal Cord Injury Program [F-192EG-C1] FX This study was supported by NIH intramural grant NIAAA Z01-AA00325 (RHL) and extramural grant F-192EG-C1 from the Defense Brain and Spinal Cord Injury Program (AMM). NR 34 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD APR PY 2010 VL 38 IS 4 BP 1067 EP 1074 DI 10.1007/s00726-009-0315-y PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 580CA UT WOS:000276423300011 PM 19565326 ER PT J AU Hunter, C Campbell, MK Kessler, R AF Hunter, Christine Campbell, Marci K. Kessler, Rodger TI TRANSLATION RESEARCH: DESIGN AND METHODOLOGY CONSIDERATIONS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hunter, Christine] NIDDK, Div Diabet Endocrinol & Metab Dis, Arlington, VA 22204 USA. [Campbell, Marci K.] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. [Kessler, Rodger] Univ Vermont, Coll Med, Ctr Clin & Translat Sci, Burlington, VT USA. EM hunterchristine@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 3 EP 3 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700008 ER PT J AU Borowski, LA Arora, NK Smith, AW Oakley-Girvan, I AF Borowski, Laurel A. Arora, Neeraj K. Smith, Ashley Wilder Oakley-Girvan, Ingrid TI CANCER SURVIVORS' USE OF COMPLEMENTARY AND ALTERNATIVE MEDICINE AND DISCLOSURE OF USE TO PHYSICIANS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Borowski, Laurel A.; Arora, Neeraj K.; Smith, Ashley Wilder] NCI, Bethesda, MD 20892 USA. [Oakley-Girvan, Ingrid] No Calif Canc Ctr, Fremont, CA USA. EM borowskil@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 6 EP 6 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700021 ER PT J AU Chou, WYS Wang, L Rutten, LF Moser, R Nelson, D Hesse, B AF Chou, Wen-ying Sylvia Wang, Lin Rutten, Lila Finney Moser, Richard Nelson, David Hesse, Bradford TI FACTORS ASSOCIATED WITH AMERICANS' RATINGS OF HEALTHCARE QUALITY: WHAT DO THEY TELL US ABOUT THE RATERS AND THE HEALTHCARE SYSTEM? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Chou, Wen-ying Sylvia; Rutten, Lila Finney; Hesse, Bradford] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. [Chou, Wen-ying Sylvia; Nelson, David] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Wang, Lin] Georgetown Univ, Sch Med, Washington, DC USA. EM chouws@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 6 EP 6 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700019 ER PT J AU Imayama, I Alfano, C Cadmus, L Duggan, C McTiernan, A AF Imayama, Ikuyo Alfano, Catherine Cadmus, Lisa Duggan, Catherine McTiernan, Anne TI EFFECT OF A 12-MONTH EXERCISE INTERVENTION ON SELF-EFFICACY AND HEALTH-RELATED QUALITY OF LIFE: ROLE OF GENDER AND WEIGHT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Imayama, Ikuyo; Cadmus, Lisa; Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Alfano, Catherine] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. EM iimayama@fhcrc.org NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 32 EP 32 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700122 ER PT J AU Luk, JW Wang, J Simons-Morton, BG AF Luk, Jeremy W. Wang, Jing Simons-Morton, Bruce G. TI GENDER DIFFERENCES IN VICTIMIZATION, DEPRESSION AND SUBSTANCE USE IN A NATIONAL SAMPLE OF US ADOLESCENTS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Luk, Jeremy W.] Univ Washington, Seattle, WA 98195 USA. [Wang, Jing; Simons-Morton, Bruce G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. EM jwluk@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 37 EP 37 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700145 ER PT J AU Kiernan, M Estabrooks, P Gorin, A Autienza, A AF Kiernan, Michaela Estabrooks, Paul Gorin, Amy Autienza, Audie TI A NEW LOOK AT THE ROLE OF SOCIAL SUPPORT FOR LONG-TERM WEIGHT MANAGEMENT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kiernan, Michaela] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA. [Gorin, Amy] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Estabrooks, Paul] Virginia Tech, Dept Human Nutr Foods & Exercise, Roanoke, VA USA. [Autienza, Audie] NCI, HPRB BRP DCCPS, Bethesda, MD 20892 USA. EM mkiernan@stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 40 EP 40 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700153 ER PT J AU Pentz, MA Almanza, E Dunton, G Berrigan, D AF Pentz, Mary Ann Almanza, Estela Dunton, Genevieve Berrigan, David TI SMART GROWTH PLANNING FOR OBESITY PREVENTION IN CHILDREN AND FAMILIES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Pentz, Mary Ann; Almanza, Estela; Dunton, Genevieve] USC, Keck Sch Med, Dept Prevent Med, Alhambra, CA 91803 USA. [Berrigan, David] NCI, Bethesda, MD 20892 USA. EM pentz@usc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 42 EP 42 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700161 ER PT J AU Czajkowski, SM Cella, D Stone, AA Amtmann, D Keefe, F AF Czajkowski, Susan M. Cella, David Stone, Arthur A. Amtmann, Dagmar Keefe, Francis TI PATIENT-REPORTED OUTCOMES MEASUREMENT INFORMATION SYSTEM (PROMIS): USING NEW THEORY AND TECHNOLOGY TO IMPROVE MEASUREMENT OF PATIENT-REPORTED OUTCOMES IN CLINICAL RESEARCH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Czajkowski, Susan M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Cella, David] NW Univ Feinberg, Sch Med, Dept Med Social Sci, Chicago, IL USA. [Stone, Arthur A.] SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. [Amtmann, Dagmar] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Keefe, Francis] Duke Univ, Med Ctr, Durham, NC USA. EM Czajkows@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 46 EP 46 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700178 ER PT J AU Kobrin, S Hall, K Rothman, A Meissner, H Tiro, J Ferrer, R Shmueli, D AF Kobrin, Sarah Hall, Kara Rothman, Alex Meissner, Helen Tiro, Jasmin Ferrer, Rebecca Shmueli, Dikla TI USE OF HEALTH BEHAVIOR THEORY IN NCI-FUNDED CANCER SCREENING INTERVENTION PROPOSALS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kobrin, Sarah; Hall, Kara; Ferrer, Rebecca; Shmueli, Dikla] NCI, Behav Res Program, Rockville, MD 20852 USA. [Rothman, Alex] U Minnesota, Minneapolis, MN USA. [Meissner, Helen] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Tiro, Jasmin] U Texas SW, Dallas, TX USA. EM kobrins@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 64 EP 64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700245 ER PT J AU Waters, EA Freedman, AN Klein, WM Moser, RP AF Waters, Erika A. Freedman, Andrew N. Klein, William M. Moser, Richard P. TI UNREALISTIC OPTIMISM AND UNREALISTIC PESSIMISM OF DEVELOPING BREAST CANCER: A NOVEL METHODOLOGICAL APPROACH TO A BASIC PSYCHOLOGICAL PRINCIPLE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Waters, Erika A.; Freedman, Andrew N.; Klein, William M.; Moser, Richard P.] NCI, Bethesda, MD 20892 USA. EM erika.a.waters@gmail.com NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 64 EP 64 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700247 ER PT J AU Weaver, K Rowland, J Augustson, E Atienza, A AF Weaver, Kathryn Rowland, Julia Augustson, Erik Atienza, Audie TI SMOKING CONCORDANCE IN CANCER PATIENT-CAREGIVER DYADS AND QUALITY OF LIFE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Weaver, Kathryn; Rowland, Julia; Augustson, Erik; Atienza, Audie] NCI, DCCPS, Bethesda, MD 20892 USA. EM keweaver@wfubmc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 69 EP 69 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700265 ER PT J AU Davis, K Koshiol, J Price, RA Tiro, J AF Davis, Kia Koshiol, Jill Price, Rebecca Anhang Tiro, Jasmin TI WHAT DO WOMEN KNOW ABOUT CERVICAL CANCER NOW? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Davis, Kia; Price, Rebecca Anhang] NCI, SAIC, Frederick, MD 21701 USA. [Koshiol, Jill] NCI, Rockville, MD 20852 USA. [Tiro, Jasmin] Univ Texas SW, Dallas, TX USA. EM DavisKia@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 70 EP 70 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700270 ER PT J AU Portnoy, DB Roter, D Erby, LH AF Portnoy, David B. Roter, Debra Erby, Lori H. TI THE COMBINED ROLE OF LOW NUMERACY AND HEALTH LITERACY ON CLIENT LEARNING IN BRCA 1/2 GENETIC COUNSELING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Portnoy, David B.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Roter, Debra; Erby, Lori H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. EM portnoydb@mail.nih.gov RI Roter, Debra/N-8830-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 74 EP 74 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700285 ER PT J AU Vanderpool, RC Studts, J Cohen, E Andyrkowski, M Arnold, S Bright, MA AF Vanderpool, Robin C. Studts, Jamie Cohen, Elisia Andyrkowski, Mike Arnold, Susanne Bright, Mary Anne TI LUNG CANCER CONVERSATIONS: ANALYZING THE CONTENT OF NCI'S LIVEHELP SERVICE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Vanderpool, Robin C.; Studts, Jamie; Cohen, Elisia; Andyrkowski, Mike; Arnold, Susanne] Univ Kentucky, Lexington, KY 40504 USA. [Bright, Mary Anne] NCI, Bethesda, MD 20892 USA. EM robin@cis.uky.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 75 EP 75 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700290 ER PT J AU Kong, A Alfano, CM Beresford, SAA Foster-Schubert, KE Duggan, CR McTiernan, A AF Kong, Angela Alfano, Catherine M. Beresford, Shirley A. A. Foster-Schubert, Karen E. Duggan, Catherine R. McTiernan, Anne TI SELF-MONITORING BEHAVIORS AND EATING HABITS ASSOCIATED WITH 12-MONTH WEIGHT CHANGE IN OVERWEIGHT/OBESE WOMEN IN A LIFESTYLE BEHAVIOR CHANGE TRIAL SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Kong, Angela; Beresford, Shirley A. A.; Foster-Schubert, Karen E.; McTiernan, Anne] Univ Washington, Seattle, WA 98109 USA. [Alfano, Catherine M.] NCI, Bethesda, MD 20892 USA. [Kong, Angela; Beresford, Shirley A. A.; Foster-Schubert, Karen E.; Duggan, Catherine R.; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. EM akong@fhcrc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 87 EP 87 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700338 ER PT J AU King, PS Iannotti, R AF King, Pamela S. Iannotti, Ronald TI LONGITUDINAL TRAJECTORIES OF CHRONIC ILLNESS OUTCOMES ACROSS ADOLESCENCE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [King, Pamela S.] Univ Utah, Salt Lake City, UT USA. [Iannotti, Ronald] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 109 EP 109 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700422 ER PT J AU Meyerowitz, B Penedo, FJ Rowland, JH AF Meyerowitz, Beth Penedo, Frank J. Rowland, Julia H. TI QUALITY OF LIFE AMONG HISPANIC CANCER SURVIVORS: LESSONS LEARNED AND CHALLENGES FOR THE FUTURE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Meyerowitz, Beth] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. [Penedo, Frank J.] Univ Miami, Psychol & Sylvester Comprehens Canc Ctr, Miami, FL USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. EM meyer-ow@usc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 116 EP 116 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700451 ER PT J AU Iannotti, R Plotnick, LP Clark, LM Guttman-Bauman, I AF Iannotti, Ronald Plotnick, Leslie P. Clark, Loretta M. Guttman-Bauman, Ines TI SOCIAL INFLUENCES ON TRANSITION FROM PEDIATRIC TO ADULT DIABETES CARE SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Iannotti, Ronald] NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. [Plotnick, Leslie P.; Clark, Loretta M.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Guttman-Bauman, Ines] Johns Hopkins Univ, Baltimore, MD USA. [Guttman-Bauman, Ines] Mt Washington Hosp Pediat Diabet Clin, Baltimore, MD USA. EM iannottr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 120 EP 120 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700466 ER PT J AU Iannotti, R Wiebe, DJ AF Iannotti, Ronald Wiebe, Deborah J. TI TRANSITION FROM PEDIATRIC TO ADULT CARE FOR ADOLESCENTS WITH CHILDHOOD CHRONIC ILLNESSES SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Iannotti, Ronald] NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. [Wiebe, Deborah J.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Div Psychol, Dallas, TX 75390 USA. EM iannottr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 120 EP 120 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700464 ER PT J AU Wang, J Iannotti, RJ AF Wang, Jing Iannotti, Ronald J. TI IDENTIFYING BULLIES, VICTIMS, AND BULLY-VICTIMS IN TRADITIONAL AND CYBER BULLYING SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Wang, Jing; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. EM wangji2@mail.nih.gov NR 0 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 139 EP 139 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700537 ER PT J AU Stipelman, B Feng, A Hall, K Moser, R Stokols, D Nebeling, L Berger, N Goran, M Jeffery, R McTiernan, A Thomquist, M AF Stipelman, Brooke Feng, Annie Hall, Kara Moser, Richard Stokols, Daniel Nebeling, Linda Berger, Nathan Goran, Michael Jeffery, Robert McTiernan, Anne Thomquist, Mark TI THE RELATIONSHIP BETWEEN COLLABORATIVE READINESS AND SCIENTIFIC PRODUCTIVITY IN THE TRANSDISCIPLINARY RESEARCH ON ENERGETICS AND CANCER (TREC) CENTERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Stipelman, Brooke; Hall, Kara; Moser, Richard; Nebeling, Linda] NCI, Rockville, MD 20852 USA. [Feng, Annie] SAIC Frederick, Frederick, MD USA. [Stokols, Daniel] Univ Calif Irvine, Irvine, CA USA. [Berger, Nathan] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Goran, Michael] Univ So Calif, Los Angeles, CA USA. [Jeffery, Robert] Univ Minnesota, Minneapolis, MN USA. [McTiernan, Anne; Thomquist, Mark] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. EM stipelmanba@mail.nih.gov NR 0 TC 4 Z9 4 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 143 EP 143 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700556 ER PT J AU Farhat, T Simons-Morton, B AF Farhat, Tilda Simons-Morton, Bruce TI STAGE-SPECIFIC PSYCHOSOCIAL CORRELATES OF ADOLESCENT ALCOHOL USE: VARIATIONS BY GENDER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Farhat, Tilda; Simons-Morton, Bruce] NICHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, NIH, Rockville, MD USA. EM farhatti@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 160 EP 160 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700622 ER PT J AU White, DB Koehly, LM Omogbehin, A McBride, CM AF White, Della B. Koehly, Laura M. Omogbehin, Adedamola McBride, Colleen M. TI ASSOCIATION OF AFRICAN AMERICANS' BELIEFS ABOUT DISPARITIES IN LUNG CANCER AND WILLINGNESS TO PARTICIPATE IN CLINICAL GENETICS RESEARCH SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [White, Della B.; Koehly, Laura M.; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Omogbehin, Adedamola] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. EM whitede@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 164 EP 164 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700638 ER PT J AU Moser, RP Arndt, J Han, PK Waters, EA Amsellem, M Hesse, B AF Moser, Richard P. Arndt, Jamie Han, Paul K. Waters, Erika A. Amsellem, Marni Hesse, Bradford TI UNDERUSE OF NEEDED CARE, CANCER-RELATED MORTALITY SALIENCE AND ASSOCIATED FACTORS: US PREVALENCE ESTIMATES FROM A NATIONALLY REPRESENTATIVE SURVEY SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Moser, Richard P.; Waters, Erika A.; Hesse, Bradford] NCI, Bethesda, MD 20892 USA. [Arndt, Jamie] Univ Missouri, Columbia, MO USA. [Han, Paul K.] Maine Med Ctr, Portland, ME 04102 USA. [Amsellem, Marni] SAIC Frederick Inc, Frederick, MD USA. EM moserr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 168 EP 168 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700651 ER PT J AU O'Neill, S McBride, CM Alford, SH Kaphingst, KA AF O'Neill, Suzanne McBride, Colleen M. Alford, Sharon Hensley Kaphingst, Kimberly A. TI DO BEHAVIORAL RISK FACTORS AND GENETIC CAUSAL BELIEFS DIMINISH INTEREST IN SEEKING INFORMATION ABOUT HEALTH HABITS? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [O'Neill, Suzanne] Georgetown Univ, Washington, DC 20007 USA. [McBride, Colleen M.; Kaphingst, Kimberly A.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Detroit, MI USA. EM sco4@georgetown.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 183 EP 183 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700711 ER PT J AU Hunt, Y Augustson, E AF Hunt, Yvonne Augustson, Erik TI USE OF SOCIAL NETWORKING SITES BY PREGNANT SMOKERS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hunt, Yvonne; Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. EM hun-tym@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 193 EP 193 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700753 ER PT J AU Mitchell, S Bevans, M Wehrlen, L Cole, M Silverman, L Prachenko, O Koklanaris, E Wallen, G AF Mitchell, S. Bevans, M. Wehrlen, L. Cole, M. Silverman, L. Prachenko, O. Koklanaris, E. Wallen, G. TI SYMPTOM PROFILES IN SURVIVORS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (AHSCT) SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Mitchell, S.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Cole, M.] Lawrence Technol Univ, Southfield, MI USA. EM mitchlls@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 201 EP 201 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700784 ER PT J AU Basinski, JR Alfano, CM Katon, WJ Syrjala, KL Fann, JR AF Basinski, James R. Alfano, Catherine M. Katon, Wayne J. Syrjala, Karen L. Fann, Jesse R. TI IMPACT OF DELIRIUM ON DISTRESS, HEALTH-RELATED QUALITY OF LIFE, AND COGNITION 6 MONTHS AND 1 YEAR AFTER HEMATOPOIETIC CELL TRANSPLANT SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Basinski, James R.] Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, DHHS, Washington, DC USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Dept Biobehav Sci, Seattle, WA 98104 USA. EM basinski@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 202 EP 202 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700787 ER PT J AU Bellizzi, K Aziz, N Rowland, J Arora, N Weaver, K Hamilton, A Oakley-Girvan, I AF Bellizzi, Keith Aziz, N. Rowland, J. Arora, N. Weaver, K. Hamilton, A. Oakley-Girvan, I. TI DOUBLE JEOPARDY? AGE, RACE AND QOL IN OLDER ADULTS WITH CANCER SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Bellizzi, Keith] Univ Connecticut, Storrs, CT 06269 USA. [Aziz, N.; Rowland, J.; Arora, N.] NCI, Bethesda, MD 20892 USA. [Weaver, K.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hamilton, A.] Univ So Calif, Los Angeles, CA USA. [Oakley-Girvan, I.] No Calif Canc Ctr, Fremont, CA USA. EM keith.m.bellizzi@uconn.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 207 EP 207 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700809 ER PT J AU Hunt, Y Chou, S Augustson, E Finney-Rutten, L AF Hunt, Yvonne Chou, Sylvia Augustson, Erik Finney-Rutten, Lila TI INTERNET USE AMONG SMOKERS IN THE US, 2003 TO 2007 SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Hunt, Yvonne; Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Chou, Sylvia; Finney-Rutten, Lila] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. EM hun-tym@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 219 EP 219 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700856 ER PT J AU Evans, SE Augustson, E Hurd, AL Hunt, YM AF Evans, Sarah E. Augustson, Erik Hurd, Ami L. Hunt, Yvonne M. TI A COMPARISON OF PREGNANT SMOKERS TO OTHER WOMEN: ANALYSIS OF THE NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEYS SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Meeting Abstract C1 [Augustson, Erik] NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Evans, Sarah E.; Hurd, Ami L.] SAIC, Bethesda, MD USA. EM augustse@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD APR PY 2010 VL 39 SU 1 BP 220 EP 220 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 572OF UT WOS:000275841700857 ER PT J AU Micciolo, R Di Francesco, V Fantin, F Canal, L Harris, TB Bosello, O Zamboni, M AF Micciolo, Rocco Di Francesco, Vincenzo Fantin, Francesco Canal, Luisa Harris, Tamara B. Bosello, Ottavio Zamboni, Mauro TI Prevalence of Overweight and Obesity in Italy (2001-2008): Is There a Rising Obesity Epidemic? SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Body Mass Index; Obesity; Overweight; Prevalence ID BODY-MASS INDEX; FACTOR SURVEILLANCE SYSTEM; SELF-REPORTED WEIGHT; MEDITERRANEAN DIET; NATIONAL-HEALTH; TRENDS; ADULTS; NUTRITION; POPULATION; VALIDITY AB PURPOSE: To provide national, population-based estimates of the prevalence of overweight and obesity in the Italian population. METHODS: Prevalence estimates of overweight and obesity were calculated in seven waves (2001-2008) of the cross-sectional Multipurpose Household Survey organized by the Italian National Institute of Statistics, which are representative of the general adult Italian population. Sampling weights were used to estimate prevalence figures as well as their standard errors. Mean-difference plot was used to evaluate changes in the distribution of body mass index across sex and age categories. RESULTS: Almost half of Italian men and about 1 of 3 Italian women are overweight or obese. Between 2001 and 2008 the age-standardized prevalence of overweight (obesity) increased 1.4% (1.9%) in men and 0.4% (0.5%) in women. Mean-difference plots showed an upward shift for body mass index distribution with an increasing skewness. CONCLUSIONS: The obesity epidemic is one of the major issues in United States and other developed countries. However, if for "epidemic" we mean that in Italy obesity is steadily increasing, then our data give little support to this interpretation. In fact, trends observed between 1983 and 2008 suggest that the rates of changes in the prevalence of overweight and/or obesity are not increasing. Ann Epidemiol 2010;20:258-264. (C) 2010 Elsevier Inc. All rights reserved. C1 [Micciolo, Rocco] Univ Trent, Dept Sociol & Social Res, I-38122 Trento, Italy. [Di Francesco, Vincenzo; Fantin, Francesco; Bosello, Ottavio; Zamboni, Mauro] Univ Verona, Dept Med & Surg Sci, I-37100 Verona, Italy. [Canal, Luisa] Univ Trent, Dept Cognit & Educ Sci, I-38122 Trento, Italy. [Harris, Tamara B.] NIA, Off Geriatr Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Micciolo, R (reprint author), Univ Trent, Dept Sociol & Social Res, Via Verdi 26, I-38122 Trento, Italy. EM rocco.miccio-lo@unitn.it OI ZAMBONI, Mauro/0000-0001-6961-9483 FU Intramural NIH HHS [ZIA AG004050-02] NR 30 TC 28 Z9 28 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2010 VL 20 IS 4 BP 258 EP 264 DI 10.1016/j.annepidem.2010.01.006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 578DS UT WOS:000276274300002 PM 20149969 ER PT J AU Kataja-Tuomola, MK Kontto, JP Mannisto, S Albanes, D Virtamo, JR AF Kataja-Tuomola, Merja K. Kontto, Jukka P. Mannisto, Satu Albanes, Demetrius Virtamo, Jarmo R. TI Effect of alpha-tocopherol and beta-carotene supplementation on macrovascular complications and total mortality from diabetes: Results of the ATBC Study SO ANNALS OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VITAMIN-E SUPPLEMENTATION; CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; OXIDATIVE STRESS; RISK; EVENTS; INDIVIDUALS; ANTIOXIDANT; MECHANISMS AB Aim. To determine whether alpha-tocopherol or beta-carotene supplementation affects diabetic macrovascular complications and total mortality. Methods. This study was carried out as part of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a double-blind, randomized trial with a 2x2 factorial design. A total of 29,133 middle-aged male smokers received either vitamin E 50 mg/day or beta-carotene 20 mg/day, or both, or placebo for a median of 6.1 years. At base-line, 1700 men had type 2 diabetes. Of these men, 662 were diagnosed with first-ever macrovascular complication, and 1142 died during the 19-year follow-up. Results. Neither supplementation affected the risk of macrovascular complication or total mortality during the intervention period. For the alpha-tocopherol-supplemented versus no alpha-tocopherol-supplemented, and beta-carotene-supplemented versus no beta-carotene-supplemented we found relative risk (RR) 0.84 (95% confidence interval (CI) 0.65-1.10) and RR 1.15 (95% CI 0.89-1.50) for macrovascular complication, respectively, and RR 1.00 (95% CI 0.80-1.25) and RR 1.06 (95% CI 0.85-1.33) for total mortality, respectively. No essential changes were found in these effects when the follow-up was extended up to 19 years. Conclusion. Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers. C1 [Kataja-Tuomola, Merja K.; Kontto, Jukka P.; Mannisto, Satu; Virtamo, Jarmo R.] Natl Inst Hlth & Welf, FI-00300 Helsinki, Finland. [Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Kataja-Tuomola, MK (reprint author), Natl Inst Hlth & Welf, Mannerheimintie 166, FI-00300 Helsinki, Finland. EM merja.kataja-tuomola@thl.fi RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046; Kontto, Jukka/0000-0003-3899-9852 FU US Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National Cancer Institute; National Institutes of Health FX This ATBC Study was supported by US Public Health Service contracts N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. NR 23 TC 18 Z9 18 U1 0 U2 3 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PD APR PY 2010 VL 42 IS 3 BP 178 EP 186 DI 10.3109/07853890903508887 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 581WM UT WOS:000276556200003 PM 20350251 ER PT J AU Moriyama, B Torabi-Parizi, P Pratt, AK Henning, SA Pennick, G Shea, YR Chowdhuri, SR Rinaldi, MG Barrett, AJ Walsh, TJ AF Moriyama, Brad Torabi-Parizi, Parizad Pratt, Alexandra K. Henning, Stacey A. Pennick, Gennethel Shea, Yvonne R. Chowdhuri, Sinchita Roy Rinaldi, Michael G. Barrett, A. John Walsh, Thomas J. TI Pharmacokinetics of Liposomal Amphotericin B in Pleural Fluid SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PULMONARY ZYGOMYCOSIS; LIPID FORMULATIONS; EMPYEMA-THORACIS; CANCER; MUCORMYCOSIS; PENETRATION; PHYSIOLOGY; PATIENT; FUNGI AB We report the penetration of liposomal amphotericin B into the pleural fluid of a patient with pulmonary zygomycosis and empyema. The ratio of area under the concentration-versus-time curve in pleural fluid (AUC(pleural fluid)) to that in serum (AUC(serum)) for liposomal amphotericin B over 24 h was 9.4%, with pleural fluid concentrations of 2.12 to 4.91 mu g/ml. Given the relatively low level of intrapleural penetration of liposomal amphotericin B, chest tube drainage may be warranted for successful treatment of zygomycotic empyema. C1 [Moriyama, Brad; Henning, Stacey A.] NIH, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Pennick, Gennethel; Rinaldi, Michael G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Torabi-Parizi, Parizad; Pratt, Alexandra K.] Dept Crit Care Med, Bethesda, MD USA. [Shea, Yvonne R.] Dept Lab Med, Bethesda, MD USA. [Chowdhuri, Sinchita Roy; Walsh, Thomas J.] NCI, Bethesda, MD 20892 USA. [Barrett, A. John] NHLBI, Bethesda, MD 20892 USA. RP Moriyama, B (reprint author), NIH, Ctr Clin, Dept Pharm, 10 Ctr Dr, Bethesda, MD 20892 USA. EM bmoriyama@cc.nih.gov FU National Institutes of Health FX This work was supported in part by the intramural research program of the National Institutes of Health. NR 22 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2010 VL 54 IS 4 BP 1633 EP 1635 DI 10.1128/AAC.01438-09 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 570HG UT WOS:000275662700034 PM 20086161 ER PT J AU Yoo, MH Gu, XL Xu, XM Kim, JY Carlson, BA Patterson, AD Cai, HB Gladyshev, VN Hatfield, DL AF Yoo, Min-Hyuk Gu, Xinglong Xu, Xue-Ming Kim, Jin-Young Carlson, Bradley A. Patterson, Andrew D. Cai, Huaibin Gladyshev, Vadim N. Hatfield, Dolph L. TI Delineating the Role of Glutathione Peroxidase 4 in Protecting Cells Against Lipid Hydroperoxide Damage and in Alzheimer's Disease SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID OXIDATIVE STRESS; CHOLESTEROL HYDROPEROXIDES; INDUCED APOPTOSIS; SPERM MATURATION; MICE; GLUTATHIONE-PEROXIDASE-4; REDUCTION; INJURY; PHGPX; IDENTIFICATION AB Numerous studies characterizing the function of glutathione peroxidase 4 (GPx4) have demonstrated that this selenoenzyme is protective against oxidative stress. Herein, we characterized the function of this protein by targeting GPx4 downregulation using RNA interference. Partial knockdown of GPx4 levels resulted in growth retardation and morphological changes. Surprisingly, GPx4 knockdown cells showed virtually unchanged levels of intracellular ROS, yet highly increased levels of oxidized lipid by-products. GPx1, another glutathione peroxidase and a major cellular peroxide scavenging enzyme, did not rescue GPx4-deficient cells and did not reduce lipid peroxide levels. The data established an essential role of GPx4 in protecting cells against lipid hydroperoxide damage, yet a limited role as a general antioxidant enzyme. As oxidized lipid hydroperoxides are a characteristic of neurodegenerative diseases, we analyzed brain tissues of mice suffering from a model of Alzheimer's disease and found that oxidized lipid by-products were enriched, and expression of both GPx4 and guanine-rich sequence-binding factor, which is known to control GPx4 synthesis, was downregulated. Brain tissue from an Alzheimer's diseased human also manifested enhanced levels of one of the oxidized lipid by-products, 4-hydroxynonenal. These data suggest a role of GPx4 in neurodegenerative diseases through its function in removal of lipid hydroperoxides. Antioxid. Redox Signal. 12, 819-827. C1 [Yoo, Min-Hyuk; Xu, Xue-Ming; Kim, Jin-Young; Carlson, Bradley A.; Patterson, Andrew D.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. [Gu, Xinglong; Cai, Huaibin] NIA, OSD, LNG, NIH, Bethesda, MD 20892 USA. [Kim, Jin-Young] Seoul Natl Univ, Sch Biol Sci, Inst Mol Biol & Genet, Seoul, South Korea. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. [Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68583 USA. [Gladyshev, Vadim N.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. EM hatfield@mail.nih.gov RI gu, xinglong/A-3054-2011; Patterson, Andrew/G-3852-2012; Gladyshev, Vadim/A-9894-2013; Cai, Huaibin/H-3359-2013 OI gu, xinglong/0000-0002-0437-5606; Patterson, Andrew/0000-0003-2073-0070; Cai, Huaibin/0000-0002-8596-6108 FU National Institutes of Health [GM065204, CA080946] FX This work was supported by the National Institutes of Health NCI Intramural Research Program and the Center for Cancer Research (to DLH), the intramural program of the National Institute on Aging (to HC) and by National Institutes of Health Grants GM065204 and CA080946 (to VNG). We thank Barbara J Taylor and Subhadra Banerjee, FACS Core Facility, CCR, and Susan Garfield, CCR Confocal Microscopy Core Facility, NCI, NIH, for their kind assistance with FACS analysis and confocal microscopy. NR 38 TC 42 Z9 44 U1 2 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2010 VL 12 IS 7 BP 819 EP 827 DI 10.1089/ars.2009.2891 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 562KX UT WOS:000275050200004 PM 19769463 ER PT J AU Novoselov, SV Kim, HY Hua, DM Lee, BC Astle, CM Harrison, DE Friguet, B Moustafa, ME Carlson, BA Hatfield, DL Gladyshev, VN AF Novoselov, Sergey V. Kim, Hwa-Young Hua, Deame Lee, Byung Cheon Astle, Clinton M. Harrison, David E. Friguet, Bertrand Moustafa, Mohamed E. Carlson, Bradley A. Hatfield, Dolph L. Gladyshev, Vadim N. TI Regulation of Selenoproteins and Methionine Sulfoxide Reductases A and B1 by Age, Calorie Restriction, and Dietary Selenium in Mice SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID GLUTATHIONE-PEROXIDASE; LIFE-SPAN; SELENOCYSTEINE INSERTION; ANTIOXIDANT DEFENSE; OXIDATIVE STRESS; GENE-EXPRESSION; TRANSGENIC MICE; PROTEIN; MITOCHONDRIAL; RATS AB Methionine residues are susceptible to oxidation, but this damage may be reversed by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the major methionine sulfoxide reductase in liver of mice and it is among the proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA activities, were reduced with age, and the selenium regulation of MsrB1 was preserved in the aging liver, suggesting that MsrB1 could account for the impaired methionine sulfoxide reduction in aging animals. We also examined regulation of Msr and selenoprotein expression by a combination of dietary selenium and calorie restriction and found that, under calorie restriction conditions, selenium regulation was preserved. In addition, mice overexpressing a mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed in selenium deficiency, whereas MsrA activity was elevated in these animals. Finally, we show that selenium regulation in inbred mouse strains is preserved in an outbred aging model. Taken together, these findings better define dietary regulation of methionine sulfoxide reduction and selenoprotein expression in mice with regard to age, calorie restriction, dietary Se, and a combination of these factors. Antioxid. Redox Signal. 12, 829-838. C1 [Lee, Byung Cheon; Gladyshev, Vadim N.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Novoselov, Sergey V.; Kim, Hwa-Young; Hua, Deame; Lee, Byung Cheon; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. [Novoselov, Sergey V.] Russian Acad Sci, Inst Cell Biophys, Pushchino 142292, Russia. [Kim, Hwa-Young] Yeungnam Univ, Coll Med, Dept Biochem & Mol Biol, Taegu, South Korea. [Lee, Byung Cheon; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Astle, Clinton M.; Harrison, David E.] Jackson Lab, Bar Harbor, ME 04609 USA. [Friguet, Bertrand] Lab Biol & Biochim Cellulaire Vieillissement, Paris, France. [Moustafa, Mohamed E.; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Sect Mol Biol Selenium, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU National Institutes of Health [AG021518, GM065204, CA080946, GM061603]; Korean Science and Engineering Foundation via the AgingAssociated Vascular Disease Research Center at Yeungnam University [R13-2005-005-01004-0]; Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We would like to thank Vyacheslav Labunskyy, Mikalai Malinovski, Anton Turanov, and Yukiho Shinogawa for their help with processing of mouse samples, and Alexey Lobanov for help with statistical analysis. This work was supported by National Institutes of Health AG021518 and in part by GM065204, CA080946 and GM061603 to VNG, by the Korean Science and Engineering Foundation via the AgingAssociated Vascular Disease Research Center at Yeungnam University (R13-2005-005-01004-0) to HYK, and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research to DLH. NR 51 TC 27 Z9 27 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2010 VL 12 IS 7 BP 829 EP 838 DI 10.1089/ars.2009.2895 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 562KX UT WOS:000275050200005 PM 19769460 ER PT J AU Shchedrina, VA Zhang, Y Labunskyy, VM Hatfield, DL Gladyshev, VN AF Shchedrina, Valentina A. Zhang, Yan Labunskyy, Vyacheslav M. Hatfield, Dolph L. Gladyshev, Vadim N. TI Structure-Function Relations, Physiological Roles, and Evolution of Mammalian ER-Resident Selenoproteins SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID SELENOCYSTEINE INSERTION SYSTEM; ENDOPLASMIC-RETICULUM MEMBRANE; THIOREDOXIN-LIKE FAMILY; MISFOLDED PROTEINS; GLYCOPROTEIN GLUCOSYLTRANSFERASE; IODOTHYRONINE SELENODEIODINASES; DROSOPHILA-MELANOGASTER; 15-KDA SELENOPROTEIN; SELENIUM METABOLISM; MUSCULAR-DYSTROPHY AB Selenium is an essential trace element in mammals. The major biological form of this micronutrient is the amino acid selenocysteine, which is present in the active sites of selenoenzymes. Seven of 25 mammalian selenoproteins have been identified as residents of the endoplasmic reticulum, including the 15-kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins K, M, N, S, and T. Most of these proteins are poorly characterized. However, recent studies implicate some of them in quality control of protein folding in the ER, retrotranslocation of misfolded proteins from the ER to the cytosol, metabolism of the thyroid hormone, and regulation of calcium homeostasis. In addition, some of these proteins are involved in regulation of glucose metabolism and inflammation. This review discusses evolution and structure-function relations of the ER-resident selenoproteins and summarizes recent findings on these proteins, which reveal the emerging important role of selenium and selenoproteins in ER function. Antioxid. Redox Signal. 12, 839-849. C1 [Shchedrina, Valentina A.; Zhang, Yan; Labunskyy, Vyacheslav M.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Shchedrina, Valentina A.; Zhang, Yan; Labunskyy, Vyacheslav M.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA USA. [Shchedrina, Valentina A.; Zhang, Yan; Labunskyy, Vyacheslav M.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE USA. [Shchedrina, Valentina A.; Zhang, Yan; Labunskyy, Vyacheslav M.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. [Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Brigham & Womens Hosp, Div Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013 FU NIH; NCI Intramural Research Program; Center for Cancer Research FX We thank Dr. Dmitri Fomenko for providing a modeled SelT structure. This work was supported by NIH grants to V. N. G., and NCI Intramural Research Program and the Center for Cancer Research to D. L. H. NR 80 TC 63 Z9 66 U1 1 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2010 VL 12 IS 7 BP 839 EP 849 DI 10.1089/ars.2009.2865 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 562KX UT WOS:000275050200006 PM 19747065 ER PT J AU Keith, K Harden, E Gill, R Marquez, V Kern, E Prichard, M AF Keith, Kathy Harden, Emma Gill, Rachel Marquez, Victor Kern, Earl Prichard, Mark TI Efficacy of N-methanocarbathymidine Against Herpes Simplex Virus is Cell Cycle Dependent SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 23rd International Conference on Antiviral Research CY APR 25-28, 2010 CL San Francisco, CA SP Int Soc Antiviral Res C1 [Keith, Kathy; Harden, Emma; Gill, Rachel; Kern, Earl; Prichard, Mark] Univ Alabama, Sch Med, Birmingham, AL USA. [Marquez, Victor] Natl Canc Inst, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2010 VL 86 IS 1 MA 135 BP A58 EP A58 DI 10.1016/j.antivira1.2010.02.445 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 598CH UT WOS:000277809600114 ER PT J AU Meier, C Reichardt, B Svenja, W Mahler, M Hughes, S Boyer, P AF Meier, Chris Reichardt, Bastian Svenja, Warnecke Mahler, Miriam Hughes, Stephen Boyer, Paul TI D-carba-dT as a Promising New Antiviral Compounds? SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 23rd International Conference on Antiviral Research CY APR 25-28, 2010 CL San Francisco, CA SP Int Soc Antiviral Res C1 [Meier, Chris; Reichardt, Bastian; Svenja, Warnecke; Mahler, Miriam] Univ Hamburg, Dept Chem, Hamburg, Germany. [Hughes, Stephen; Boyer, Paul] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2010 VL 86 IS 1 MA 145 BP A62 EP A62 DI 10.1016/j.antivira1.2010.02.455 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 598CH UT WOS:000277809600124 ER PT J AU Selvam, P Maddali, K Marchand, C Pommier, Y AF Selvam, Periyasamy Maddali, Kasthuraiah Marchand, Christophe Pommier, Yves TI Studies of HIV lntegrase Inhibitory Activity of Morinda citrifolia L Noni Fruit Extracts SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 23rd International Conference on Antiviral Research CY APR 25-28, 2010 CL San Francisco, CA SP Int Soc Antiviral Res C1 [Selvam, Periyasamy] Devaki Amma Mem Coll Pharm, Malapuram 676364, India. [Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2010 VL 86 IS 1 MA 98 BP A45 EP A46 DI 10.1016/j.antivira1.2010.02.408 PG 2 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 598CH UT WOS:000277809600078 ER PT J AU Selvam, P Maddali, K Pommier, Y AF Selvam, Periyasamy Maddali, Kasthuraiah Pommier, Yves TI Studies of HIV-1 Integrase Inhibitory Activity of Wrightia tinctoria SO ANTIVIRAL RESEARCH LA English DT Meeting Abstract CT 23rd International Conference on Antiviral Research CY APR 25-28, 2010 CL San Francisco, CA SP Int Soc Antiviral Res C1 [Selvam, Periyasamy] Devaki Amma Mem Coll Pharm, Chelembra, Malapuram, India. [Maddali, Kasthuraiah; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2010 VL 86 IS 1 MA 47 BP A28 EP A28 DI 10.1016/j.antiviral.2010.02.357 PG 1 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 598CH UT WOS:000277809600028 ER PT J AU Yadav, M Lavania, A Tomar, R Prasad, GBKS Jain, S Yadav, H AF Yadav, Mukesh Lavania, Amita Tomar, Radha Prasad, G. B. K. S. Jain, Shalini Yadav, Hariom TI Complementary and Comparative Study on Hypoglycemic and Antihyperglycemic Activity of Various Extracts of Eugenia jambolana Seed, Momordica charantia Fruits, Gymnema sylvestre, and Trigonella foenum graecum Seeds in Rats SO APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY LA English DT Article DE Eugenia jambolana; Momordica charantia; Gymnema sylvestre; Trigonella foenum graecum; Hypoglycemia; Glucose-infused diabetes; Herbal; Glimepiride ID DIABETES-MELLITUS; CUCURBITACIN GLYCOSIDES; DEVELOPING-COUNTRIES; IMMATURE FRUITS; CONSTITUENTS; GALACTOMANNAN; HYPERGLYCEMIA; SAPONINS; L. AB In present study, we investigated hypoglycemic and antihyperglycemic potential of five extracts (water, ethanol, methanol, hexane, and chloroform) of four plants (i.e., seeds of Eugenia jambolana, fruits of Momordica charantia, leaves of Gymnema sylvestre, and seeds of Trigonella foenum graecum) alone and/or in combination with glimepiride in rats. Ethanol extract of E. jambolana, water extract of M. charantia, ethanol extract of G. sylvestre, and water extract of T. graecum exhibited highest hypoglycemic and antihyperglycemic activity (most active) in rats among all the extracts, while hexane extracts exhibited least activities. Most active extracts were further studied to dose-dependent (200, 100, and 50 mg/kg body weight (bw)) hypoglycemic and antihyperglycemic effects alone and in combination with glimepiride (20, 10, and 5 mg/kg bw). The combination of most active extracts (200 mg/kg bw) and lower dose of glimepiride (5 mg/kg bw) showed safer and potent hypoglycemic as well as antihyperglycemic activities without creating severe hypoglycemia in normal rats, while higher doses (200 mg/kg bw of most active extracts, and 10 and 20 mg/kg bw of glimepiride) were generated lethal hypoglycemia in normal rats. From this study, it may be concluded that the ethanol extract of E. jambolana seeds, water extract of M. charantia fruits, ethanol extract of G. sylvestre leaves, and water extract of T. graecum seeds have higher hypoglycemic and antihyperglycemic potential and may use as complementary medicine to treat the diabetic population by significantly reducing dose of standard drugs. C1 [Yadav, Mukesh] Coll Adv Studies, Datia, Madhya Pradesh, India. [Yadav, Mukesh; Lavania, Amita; Tomar, Radha] Jiwaji Univ, Sch Studies Chem, Gwalior 474011, MP, India. [Prasad, G. B. K. S.] Jiwaji Univ, Sch Studies Biochem, Gwalior 474011, MP, India. [Jain, Shalini] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Yadav, Hariom] NIH, Clin Res Ctr, Diabet Branch, Bethesda, MD 20892 USA. RP Yadav, M (reprint author), Coll Adv Studies, Datia, Madhya Pradesh, India. EM mukeshyadav2009@gmail.com OI Yadav, Hariom/0000-0003-4504-1597 NR 37 TC 17 Z9 19 U1 2 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0273-2289 J9 APPL BIOCHEM BIOTECH JI Appl. Biochem. Biotechnol. PD APR PY 2010 VL 160 IS 8 BP 2388 EP 2400 DI 10.1007/s12010-009-8799-1 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 576NX UT WOS:000276152700019 PM 19904502 ER PT J AU Hida, K Won, SY Di Pasquale, G Hanes, J Chiorini, JA Ostermeier, M AF Hida, Kaoru Won, Sang Y. Di Pasquale, Giovanni Hanes, Justin Chiorini, John A. Ostermeier, Marc TI Sites in the AAV5 capsid tolerant to deletions and tandem duplications SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Directed evolution; AAV; Viral gene delivery ID ADENOASSOCIATED VIRUS TYPE-2; GENE-TRANSFER; AIRWAY EPITHELIA; INSERTIONAL MUTAGENESIS; EFFICIENT TRANSDUCTION; DIRECTED EVOLUTION; VECTORS; THERAPY; SEROTYPE-5; INFECTION AB Gene therapy vectors based on adeno-associated virus (AAV) have shown much promise in clinical trials for the treatment of a variety of diseases. However, the ability to manipulate and engineer the viral surface for enhanced efficiency is necessary to overcome such barriers as pre-existing immunity and transduction of non-target cells that currently limit AAV applications. Although single amino acid changes and peptide insertions at select sites have been explored previously, the tolerance of AAV to small deletions and tandem duplications of sequence has not been globally addressed. Here, we have generated a large, diverse library of >10(5) members containing deletions and tandem duplications throughout the viral capsid of AAV5. Four unique mutants were identified that maintain the ability to form viral particles, with one showing improved transduction on both 2931 and BEAS-2B cells. This approach may find potential use for the generation of novel variants with improved and altered properties or in the identification of sites that are tolerant to insertions of targeting ligands. (C) 2010 Elsevier Inc. All rights reserved. C1 [Won, Sang Y.; Hanes, Justin; Ostermeier, Marc] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA. [Hida, Kaoru] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. [Hanes, Justin; Ostermeier, Marc] Johns Hopkins Univ, Inst NanoBioTechnol, Baltimore, MD 21218 USA. [Di Pasquale, Giovanni; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Ostermeier, M (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, 3400 N Charles St,221 MD Hall, Baltimore, MD 21218 USA. EM oster@jhu.edu RI Ostermeier, Marc/A-2697-2010 OI Ostermeier, Marc/0000-0003-0900-3665 FU NIH; NIDCR FX This research was supported in part by the Intramural Research Program of the NIH and NIDCR to J.A.C. NR 35 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR 1 PY 2010 VL 496 IS 1 BP 1 EP 8 DI 10.1016/j.abb.2010.01.009 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 574GE UT WOS:000275976500001 PM 20102698 ER PT J AU Levine, KE Stout, MD Ross, GT Essader, AS Weber, FX Grohse, PM Fernando, RA Milstein, LS Hooth, MJ Collins, BJ AF Levine, Keith E. Stout, Matthew D. Ross, Glenn T. Essader, Amal S. Weber, Frank X. Grohse, Peter M. Fernando, Reshan A. Milstein, Lisa S. Hooth, Michelle J. Collins, Bradley J. TI Validation and Application of a Method for the Determination of Total Chromium in Rat Tissues by Inductively Coupled Plasma Mass Spectrometry SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID ICP-MS; HEXAVALENT CHROMIUM; CARCINOGENICITY; TOXICITY; HUMANS; VANADIUM; CELL AB The validation of a method for the determination of chromium (Cr) in F-344/N rat tissues by inductively coupled plasma-mass spectrometry is described. Samples were analyzed after a rapid, open-vessel microwave digestion procedure. Performance of the method was evaluated using kidney tissue across a concentration range of 0.50-5.00 mu g Cr/g tissue. Data for method linearity, accuracy, precision, digest stability, and storage stability are presented along with limits of detection and quantitation data. Data from a method cross-validation for B6C3F1 mouse kidney tissue are also presented. After validation, the method was applied to analyze samples collected in support of two chronic toxicity and carcinogenesis studies conducted by the National Toxicology Program. C1 [Levine, Keith E.; Ross, Glenn T.; Essader, Amal S.; Weber, Frank X.; Grohse, Peter M.; Fernando, Reshan A.; Milstein, Lisa S.] RTI Int, Res Triangle Pk, NC 27709 USA. [Stout, Matthew D.; Hooth, Michelle J.; Collins, Bradley J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Levine, KE (reprint author), RTI Int, Res Triangle Pk, NC 27709 USA. EM levine@rti.org FU National Institute of Environmental Health Sciences, National Institute of Health [N01-ES-05455, N01-ES-65554] FX This work was funded in full by the National Institute of Environmental Health Sciences, National Institute of Health, Contract Nos. N01-ES-05455 and N01-ES-65554. NR 28 TC 3 Z9 3 U1 3 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD APR PY 2010 VL 58 IS 3 BP 883 EP 891 DI 10.1007/s00244-009-9397-5 PG 9 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 581GV UT WOS:000276510700042 PM 19798462 ER PT J AU ElMasri, WM Tran, TH Mulla, ZD AF ElMasri, Wafic M. Tran, Therese H. Mulla, Zuber D. TI A Case-Control Study of Asthma and Ovarian Cancer SO ARCHIVES OF ENVIRONMENTAL & OCCUPATIONAL HEALTH LA English DT Article DE asthma; case-control study; epidemiology; hospital databases; ovarian cancer; Florida ID EPITHELIAL OVARIAN; RISK; ALLERGY; SMOKING; OBESITY; COHORT; TUMORS AB Epidemiologic studies have found inverse associations between allergy and the development of certain tumors. The authors sought to determine if there was an association between asthma and ovarian cancer. A case-control study was conducted using Florida hospital data (year 2001). Discharge diagnoses were coded using the ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification). Cases were 1,582 women whose principal discharge diagnosis was a malignant neoplasm of the ovary. Two control series were used: 4,744 women whose principal diagnosis was an upper limb bone fracture, and 21,830 women whose principal diagnosis was an acute myocardial infarction. Odds ratios (ORs) adjusted for age, race-ethnicity. Medicaid status, obesity, and smoking were calculated. Cases were 30% less likely than fracture control to be asthmatics (adjusted OR = 0.70, 95% confidence interval [CI]: 0.49-0.99, p = .04). Similarly, cases when compared to acute myocardial infarction controls were significantly less likely to have asthma (adjusted OR = 0.62, 95% CI: 0.45-0.87, p = .005). The results of this statewide exploratory study suggest that individuals with asthma may have a lower risk of developing ovarian cancer than nonasthmatics. C1 [ElMasri, Wafic M.; Tran, Therese H.; Mulla, Zuber D.] Texas Tech Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, Paul L Foster Sch Med, El Paso, TX 79905 USA. [Mulla, Zuber D.] Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA. [ElMasri, Wafic M.] NCI, NIH, Bethesda, MD 20892 USA. RP Mulla, ZD (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, Paul L Foster Sch Med, 4800 Alberta Ave, El Paso, TX 79905 USA. EM zuber.mulla@ttuhsc.edu FU Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso FX This study was supported by the Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, El Paso. NR 20 TC 5 Z9 5 U1 0 U2 4 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 1933-8244 J9 ARCH ENVIRON OCCUP H JI Arch. Environ. Occup. Health PD APR-JUN PY 2010 VL 65 IS 2 BP 101 EP 105 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 602HT UT WOS:000278130800008 PM 20439229 ER PT J AU Lindell, SG Schwandt, ML Sun, H Sparenborg, JD Bjork, K Kasckow, JW Sommer, WH Goldman, D Higley, JD Suomi, SJ Heilig, M Barr, CS AF Lindell, Stephen G. Schwandt, Melanie L. Sun, Hui Sparenborg, Jeffrey D. Bjork, Karl Kasckow, John W. Sommer, Wolfgang H. Goldman, David Higley, J. Dee Suomi, Stephen J. Heilig, Markus Barr, Christina S. TI Functional NPY Variation as a Factor in Stress Resilience and Alcohol Consumption in Rhesus Macaques SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NEUROPEPTIDE-Y GENE; CORTICOTROPIN-RELEASING HORMONE; SINGLE NUCLEOTIDE POLYMORPHISM; NONHUMAN PRIMATE MODEL; OPIOID-RECEPTOR GENE; WISTAR RATS; ACID CONCENTRATIONS; NONPREFERRING RATS; POPULATION-SAMPLE; EARLY EXPERIENCE AB Context: Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence. Objective: To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity ( peer rearing). Design: We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for -1002 T > G, and the data were analyzed using analysis of variance. Setting: National Institutes of Health Animal Center. Subjects: Ninety-six rhesus macaques. Main Outcome Measure: Behavior arousal during social separation stress and ethanol consumption. Results: The G allele altered binding of regulatory proteins in all nuclear extracts tested, and -1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. Conclusions: Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans. C1 [Lindell, Stephen G.; Schwandt, Melanie L.; Sun, Hui; Sparenborg, Jeffrey D.; Bjork, Karl; Sommer, Wolfgang H.; Heilig, Markus; Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Kasckow, John W.] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. [Higley, J. Dee] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. [Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD USA. RP Barr, CS (reprint author), NIAAA, Clin Studies Lab, Primate Sect, Div Intramural Clin & Biol Res, POB 529, Poolesville, MD 20837 USA. EM cbarr@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Heilig, Markus/0000-0003-2706-2482 FU Intramural NIH HHS [Z99 AA999999, Z01 AA000301-10, Z99 HD999999] NR 60 TC 35 Z9 36 U1 3 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2010 VL 67 IS 4 BP 423 EP 431 PG 9 WC Psychiatry SC Psychiatry GA 578RM UT WOS:000276312800013 PM 20368518 ER PT J AU Pellicano, C Gallo, A Li, XB Ikonomidou, VN Evangelou, IE Ohayon, JM Stern, SK Ehrmantraut, M Cantor, F McFarland, HF Bagnato, F AF Pellicano, Clelia Gallo, Antonio Li, Xiaobai Ikonomidou, Vasiliki N. Evangelou, Iordanis E. Ohayon, Joan M. Stern, Susan K. Ehrmantraut, Mary Cantor, Fredric McFarland, Henry F. Bagnato, Francesca TI Relationship of Cortical Atrophy to Fatigue in Patients With Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID DEEP GRAY-MATTER; QUALITY-OF-LIFE; BASAL GANGLIA; BRAIN ATROPHY; PARIETAL CORTEX; RATING-SCALES; DEPRESSION; DISABILITY; VOLUME; FMRI AB Background: Fatigue is a common and disabling symptom of multiple sclerosis (MS). Previous studies reported that damage of the corticostriatothalamocortical circuit is critical in its occurrence. Objective: To investigate the relationship between fatigue in MS and regional cortical and subcortical gray matter atrophy. Design: Case-control study. Setting: National Institutes of Health. Participants: Twenty-four patients with MS and 24 matched healthy volunteers who underwent 3.0-T magnetic resonance imaging and evaluations of fatigue (Modified Fatigue Impact Scale) and depression (Center for Epidemiologic Studies Depression Scale). Main Outcome Measures: Relationship between thalamic and basal ganglia volume, cortical thickness of frontal and parietal lobes, and, in patients, T2 lesion volume and normal-appearing white matter volume and the extent of fatigue. Results: Patients were more fatigued than healthy volunteers (P=.04), while controlling for the effect of depression. Modified Fatigue Impact Scale score correlated with cortical thickness of the parietal lobe (r=-0.50, P=.01), explaining 25% of its variance. The posterior parietal cortex was the only parietal area significantly associated with the Modified Fatigue Impact Scale scores. Conclusions: Cortical atrophy of the parietal lobe had the strongest relationship with fatigue. Given the implications of the posterior parietal cortex in motor planning and integration of information from different sources, our preliminary results suggest that dysfunctions in higher-order aspects of motor control may have a role in determining fatigue in MS. C1 [Pellicano, Clelia; Gallo, Antonio; Ikonomidou, Vasiliki N.; Evangelou, Iordanis E.; Ohayon, Joan M.; Stern, Susan K.; Ehrmantraut, Mary; Cantor, Fredric; McFarland, Henry F.; Bagnato, Francesca] NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Li, Xiaobai] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5C103, Bethesda, MD 20892 USA. RI Pellicano, Clelia/K-1062-2016 OI Pellicano, Clelia/0000-0002-3272-1094 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 43 TC 60 Z9 61 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2010 VL 67 IS 4 BP 447 EP 453 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 581XQ UT WOS:000276559500012 PM 20385911 ER PT J AU Klein, R Knudtson, MD Klein, BEK Wong, TY Cotch, MF Barr, G AF Klein, Ronald Knudtson, Michael D. Klein, Barbara E. K. Wong, Tien Y. Cotch, Mary Frances Barr, Graham TI Emphysema, Airflow Limitation, and Early Age-Related Macular Degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; RAY CT IMAGES; ATHEROSCLEROSIS MESA; COMPUTED-TOMOGRAPHY; PULMONARY-DISEASE; CARDIAC CT; LUNG; MACULOPATHY; SEGMENTATION; ASSOCIATION AB Objective: To describe the associations of lung function and emphysema, measured with spirometry and computed tomography (CT), with early age-related macular degeneration (AMD) in a sample of white, black, Hispanic, and Chinese subjects. Methods: Three thousand three hundred ninety-nine persons aged 45 to 84 years residing in 6 US communities participated in a period cross-sectional study. Age-related macular degeneration was measured from digital retinal photographs at the second Multi-Ethnic Study of Atherosclerosis (MESA) examination. Forced expiratory volume in 1 second (FEV1) and FEV1 to forced vital capacity (FVC) ratio were measured at the third or fourth MESA examination. Percent emphysema was measured from cardiac CT scans at baseline. Apical and basilar lung segments were defined as the cephalad or caudal regions of the lung on the cardiac CT scan. Logistic regression models were used to examine the association of lung function and structure with AMD, controlling for age, sex, and other factors. Results: The prevalence of early AMD was 3.7%. Early AMD was not associated with FEV1 (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.58-1.15; P=.25), FEV1: FVC ratio (OR, 0.92; 95% CI, 0.76-1.12; P=.43), percent emphysema (OR, 1.13; 95% CI, 0.91-1.40; P=.26), and apical-basilar difference in percent emphysema (OR, 1.14; 95% CI, 0.95-1.37; P=.17). Associations were stronger in smokers. Apical-basilar difference in percent emphysema was significantly associated with early AMD among those whoever smoked (OR, 1.28; 95% CI, 1.02-1.60; P=.03). Associations were not modified by race/ethnicity. Conclusions: Lung function and emphysema on CT scan were not cross-sectionally associated with AMD; this might be explained by the relatively low smoking exposure in this cohort. C1 [Klein, Ronald; Knudtson, Michael D.; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53726 USA. [Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia. [Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Barr, Graham] Columbia Univ, Div Gen Med, Dept Med, Med Ctr, New York, NY USA. [Barr, Graham] Columbia Univ, Dept Epidemiol, Med Ctr, New York, NY USA. RP Klein, R (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, 610 N Walnut St,450 WARF, Madison, WI 53726 USA. EM kleinr@epi.ophth.wisc.edu OI Cotch, Mary Frances/0000-0002-2046-4350 FU National Heart, Lung and Blood Institute [N01-HC-95159, N01-HC-95165, N01-HC-95169]; National Eye Institute [Z01000403]; National Institutes of Health [HL69979-03, HL077612] FX This research was supported by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung and Blood Institute; National Institutes of Health Intramural Research program award Z01000403 from the National Eye Institute (Dr Cotch); and grants HL69979-03 (Drs R. Klein and Wong) and HL077612 (Dr Barr) from the National Institutes of Health. NR 27 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2010 VL 128 IS 4 BP 472 EP 477 PG 6 WC Ophthalmology SC Ophthalmology GA 581YC UT WOS:000276560800013 PM 20385944 ER PT J AU Washington, MK Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE Vauthey, JN AF Washington, Mary Kay Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. Vauthey, Jean-Nicolas CA Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Carcinoma of the Perihilar Bile Ducts SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HILAR CHOLANGIOCARCINOMA; RESECTION C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Dept Pathol, Med Ctr, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Vauthey, Jean-Nicolas] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu NR 15 TC 3 Z9 4 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2010 VL 134 IS 4 BP E19 EP E24 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 580EK UT WOS:000276429800004 PM 20367295 ER PT J AU Washington, MK Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE Vauthey, JN AF Washington, Mary Kay Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. Vauthey, Jean-Nicolas CA Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Carcinoma of the Intrahepatic Bile Ducts SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID RISK-FACTORS; CHOLANGIOCARCINOMA; PROGNOSIS C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Jessup, J. Milburn] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Frankel, Wendy L.] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Vauthey, Jean-Nicolas] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu NR 14 TC 2 Z9 6 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2010 VL 134 IS 4 BP E14 EP E18 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 580EK UT WOS:000276429800003 PM 20367294 ER PT J AU Washington, MK Berlin, J Branton, PA Burgart, LJ Carter, DK Compton, CC Fitzgibbons, PL Frankel, WL Jessup, JM Kakar, S Minsky, B Nakhleh, RE Vauthey, JN AF Washington, Mary Kay Berlin, Jordan Branton, Philip A. Burgart, Lawrence J. Carter, David K. Compton, Carolyn C. Fitzgibbons, Patrick L. Frankel, Wendy L. Jessup, J. Milburn Kakar, Sanjay Minsky, Bruce Nakhleh, Raouf E. Vauthey, Jean-Nicolas CA Canc Comm Coll Amer Pathologists TI Protocol for the Examination of Specimens From Patients With Carcinoma of the Distal Extrahepatic Bile Ducts SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CHOLANGIOCARCINOMA C1 [Washington, Mary Kay] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Berlin, Jordan] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Branton, Philip A.] Inova Fairfax Hosp, Dept Pathol, Falls Church, VA USA. [Burgart, Lawrence J.] Abbott NW Hosp, Allina Labs, Minneapolis, MN 55407 USA. [Carter, David K.] St Marys Duluth Clin Hlth Syst, Dept Pathol, Duluth, MN USA. [Compton, Carolyn C.] NIH, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Jessup, J. Milburn] NIH, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Fitzgibbons, Patrick L.] St Jude Med Ctr, Dept Pathol, Fullerton, CA USA. [Frankel, Wendy L.] Ohio State Univ, Dept Pathol, Med Ctr, Columbus, OH 43210 USA. [Kakar, Sanjay] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. [Kakar, Sanjay] Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Minsky, Bruce] Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. [Nakhleh, Raouf E.] Mayo Clin, Dept Pathol, Jacksonville, FL 32224 USA. [Vauthey, Jean-Nicolas] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. RP Washington, MK (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C-3316 MCN, Nashville, TN 37232 USA. EM kay.washington@vanderbilt.edu NR 14 TC 2 Z9 4 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2010 VL 134 IS 4 BP E8 EP E13 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 580EK UT WOS:000276429800002 PM 20367298 ER PT J AU Nelson, KB Richardson, AK He, JP Lateef, TM Khoromi, S Merikangas, KR AF Nelson, Karin B. Richardson, Amanda Kalaydjian He, Jianping Lateef, Tarranum M. Khoromi, Suzan Merikangas, Kathleen R. TI Headache and Biomarkers Predictive of Vascular Disease in a Representative Sample of US Children SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; CORONARY-HEART-DISEASE; TENSION-TYPE HEADACHE; IHS CRITERIA; FOLLOW-UP; PEDIATRIC MIGRAINE; METABOLIC SYNDROME; PRESCHOOL AGE; ADOLESCENTS AB Objective: To examine the association of childhood headache disorders with markers of risk for cardiovascular and cerebrovascular disease. Design: Information was collected on severe or recurrent headache or migraine in childhood or adolescence and on biomarkers predictive of vascular disease. Setting: The National Health and Nutrition Survey, a nationally representative health survey. Participants: Children or adolescents aged 4 to 19 years (n = 11 770) who took part in the National Health and Nutrition Survey in 1999 through 2004. Main Exposure: Headache. Main Outcome Measures: Body mass index; levels of C-reactive protein, homocysteine, serum and red blood cell folate, vitamin B(12), methylmalonic acid, total cholesterol, high-density lipoprotein cholesterol, non high-density lipoprotein cholesterol, triglycerides, and uric acid; and platelet count. Results: Mean values for body mass index, C-reactive protein, and homocysteine were higher in children with than without headaches, and more children with headaches were in the highest quintile of risk for these factors. Serum and red blood cell folate levels were lower in children with headache. More children with headache were in the highest quintile of risk for 3 or more of these factors. Conclusions: Several important risk factors for long-term vascular morbidity cluster in children and adolescents with severe or recurrent headache or migraine. Further study and screening of children with headaches may permit improved preventive management. Arch Pediatr Adolesc Med. 2010; 164(4):358-362 C1 [Nelson, Karin B.] NINDS, Washington, DC USA. [Nelson, Karin B.; Lateef, Tarranum M.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Richardson, Amanda Kalaydjian; He, Jianping; Lateef, Tarranum M.; Khoromi, Suzan; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA. RP Nelson, KB (reprint author), NINDS, NIH, Bldg 31,Room 8A03, Bethesda, MD 20892 USA. EM nelsonk@ninds.nih.gov FU National Institute of Mental Health; National Institute of Neurological Disorders and Stroke FX This study was supported by the National Institute of Mental Health and National Institute of Neurological Disorders and Stroke intramural research programs. NR 42 TC 11 Z9 11 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2010 VL 164 IS 4 BP 358 EP 362 PG 5 WC Pediatrics SC Pediatrics GA 578RL UT WOS:000276312700010 PM 20368489 ER PT J AU Kuhn, JH Jahrling, PB AF Kuhn, Jens H. Jahrling, Peter B. TI Clarification and guidance on the proper usage of virus and virus species names SO ARCHIVES OF VIROLOGY LA English DT Review ID FELINE CALICIVIRUS DISEASE; INTERNATIONAL-COMMITTEE; ORDER MONONEGAVIRALES; TAXONOMY; NOMENCLATURE; CLASSIFICATION; VIROLOGISTS; PROPOSAL; LATIN AB A pivotal step in the development of a consistent nomenclature for virus classification was the introduction of the virus species concept by the International Committee on Taxonomy of Viruses (ICTV) in 1991. Yet, almost two decades later, many virologists still are unable to differentiate between virus species and actual viruses. Here we attempt to explain the origin of this confusion, clarify the difference between taxa and physical entities, and suggest simple measures that could be implemented by ICTV Study Groups to make virus taxonomy and nomenclature more accessible to laboratory virologists. C1 [Kuhn, Jens H.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA. [Kuhn, Jens H.] IRF Frederick, King Of Prussia, PA 19406 USA. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. EM kuhnjens@mail.nih.gov RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU Intramural NIH HHS [Z01 AI001025-02] NR 46 TC 18 Z9 18 U1 0 U2 19 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 APR PY 2010 VL 155 IS 4 SI SI BP 445 EP 453 DI 10.1007/s00705-010-0600-9 PG 9 WC Virology SC Virology GA 576EA UT WOS:000276125900001 PM 20204430 ER PT J AU Gong, TX Jiang, Y Wang, YL Yang, D Li, WY Zhang, Q Feng, W Wang, BN Jiang, ZH Li, MY AF Gong, Tianxiang Jiang, Yan Wang, Yueling Yang, De Li, Wanyi Zhang, Qiang Feng, Wei Wang, Baoning Jiang, Zhonghua Li, Mingyuan TI Recombinant mouse beta-defensin 2 inhibits infection by influenza A virus by blocking its entry SO ARCHIVES OF VIROLOGY LA English DT Article ID ALPHA-DEFENSIN; ESCHERICHIA-COLI; INNATE IMMUNITY; PROTEINS; PEPTIDE; FUSION AB Human influenza A virus (IAV) is a major cause of life-threatening respiratory tract disease worldwide. Defensins are small cationic peptides of about 2-6 kDa that are known for their broad-spectrum antimicrobial activity. Here, we focused on the anti-influenza A activity of mouse beta-defensin 2 (mBD2). The prokaryotic expression plasmid pET32a-mBD2 was constructed and introduced into Escherichia coli Rosseta gami (2) to produce recombinant mBD2 (rmBD2). Purified rmBD2 showed strong antiviral activity against IAV in vitro. The protective rate for Madin-Darby canine kidney cells was 93.86% at an rmBD2 concentration of 100 mu g/ml. Further studies demonstrated that rmBD2 prevents IAV infection by inhibiting viral entry. In addition, both pretreatment and postinfection treatment with rmBD2 provided protection against lethal virus challenge with IAV in experimental mice, with protection rates of 70 and 30%, respectively. These results suggest that the mBD2 might have important effects on influenza A virus invasion. C1 [Gong, Tianxiang; Jiang, Yan; Wang, Yueling; Li, Wanyi; Zhang, Qiang; Feng, Wei; Wang, Baoning; Jiang, Zhonghua; Li, Mingyuan] Sichuan Univ, W China Sch Preclin & Forens Med, Dept Microbiol, Chengdu 610041, Peoples R China. [Yang, De] SAIC Frederick, Basic Res Program, Frederick, MD 21720 USA. [Yang, De] NCI, Mol Immunoregulat Lab, NCI FCRDC, NIH, Frederick, MD 21720 USA. [Li, Mingyuan] Sichuan Univ, State Key Lab Oral Dis, Chengdu 610041, Peoples R China. RP Li, MY (reprint author), Sichuan Univ, W China Sch Preclin & Forens Med, Dept Microbiol, Chengdu 610041, Peoples R China. EM lmy3985@sina.com FU National Natural Science Foundation of China [30671964] FX This work was financially supported by National Natural Science Foundation of China (No. 30671964, People's Republic of China). NR 24 TC 15 Z9 22 U1 2 U2 10 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 APR PY 2010 VL 155 IS 4 SI SI BP 491 EP 498 DI 10.1007/s00705-010-0608-1 PG 8 WC Virology SC Virology GA 576EA UT WOS:000276125900006 PM 20195655 ER PT J AU Martinez, M Amarilla, AA Galeano, ME Aquino, VH Farina, N Russomando, G Parra, GI AF Martinez, Magaly Amarilla, Alberto A. Galeano, Maria E. Aquino, Victor H. Farina, Norma Russomando, Graciela Parra, Gabriel I. TI Predominance of rotavirus G2P[4] and emergence of G12P[9] strains in Asuncion, Paraguay, 2006-2007 SO ARCHIVES OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUSES; VACCINATED POPULATION; PHYLOGENETIC ANALYSIS; CHILDREN; G12; DIARRHEA; BRAZIL; ARGENTINA; GENE AB Rotavirus is the most common cause of severe diarrhea in children worldwide. Monitoring the diversity of rotavirus strains is of great importance for current and future vaccination programs. To determine the diversity of rotavirus circulating in Asuncion, Paraguay, between 2006 and 2007, we carried out a molecular characterization of rotaviruses detected in children <5 years old and adults (>18 years old). We found that the most common circulating strain was G2P[4] (69/143), followed by G9P[8] (37/143). The temporal distribution of strains showed that, in children, G2P[4] was predominant in 2006, and that G2P[4] and G9P[8] were co-predominant in 2007, whereas in adults, G2P[4] was predominant in both years. Additionally, one G9P[6] and three G12P[9] strains were found in adult samples, making this the first report of these strains circulating in Paraguay. Sequence analysis of the G12P[9] strains suggests across-border migration of this strain within the southern cone of America. C1 [Martinez, Magaly; Amarilla, Alberto A.; Galeano, Maria E.; Farina, Norma; Russomando, Graciela; Parra, Gabriel I.] Natl Univ Asunc, IICS, Dept Mol Biol, Asuncion 2511, Paraguay. [Amarilla, Alberto A.; Aquino, Victor H.] USP, Ribeirao Preto Sch Med, Virol Res Ctr, BR-3900 Ribeirao Preto, SP, Brazil. [Farina, Norma] San Roque Private Hosp, Clin Lab, Asuncion, Paraguay. RP Parra, GI (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike,Bldg 50,Room 6316, Bethesda, MD 20892 USA. EM parrag@niaid.nih.gov RI Amarilla, Alberto/C-3112-2012; OI Amarilla, Alberto/0000-0002-4151-2024; Aquino, Victor Hugo/0000-0003-1910-0776; Parra, Gabriel/0000-0002-1102-4740 NR 39 TC 19 Z9 19 U1 0 U2 3 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 APR PY 2010 VL 155 IS 4 SI SI BP 525 EP 533 DI 10.1007/s00705-010-0617-0 PG 9 WC Virology SC Virology GA 576EA UT WOS:000276125900010 PM 20213281 ER PT J AU Almeida, MQ AF Almeida, Madson Q. TI Idiopathic central diabetes insipidus: the challenge remains SO ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA LA English DT Editorial Material ID VASOPRESSIN; AUTOIMMUNITY; ANTIBODIES C1 [Almeida, Madson Q.] Univ Sao Paulo HCFMUSP, Fac Med, Hosp Clin, Lab Hormonios & Genet Mol LIM 42,Unidade Endocrin, Sao Paulo, Brazil. [Almeida, Madson Q.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA. RP Almeida, MQ (reprint author), Av Dr Eneas de Carvalho Aguiar,155,20 Ander,Bloco, BR-05403900 Sao Paulo, Brazil. EM madsonalmeida@usp.br NR 10 TC 0 Z9 0 U1 0 U2 1 PU SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA PI RIO DE JANEIRO, RJ PA RUA HUMAITA, 85 CJ 501, RIO DE JANEIRO, RJ, 22261-000, BRAZIL SN 0004-2730 J9 ARQ BRAS ENDOCRINOL JI Arq. Bras. Endocrinol. Metabol. PD APR PY 2010 VL 54 IS 3 BP 251 EP 252 DI 10.1590/S0004-27302010000300001 PG 2 GA 601NO UT WOS:000278067300001 PM 20520953 ER PT J AU Giles, JT Malayeri, AA Fernandes, V Post, W Blumenthal, RS Bluemke, D Vogel-Claussen, J Szklo, M Petri, M Gelber, AC Brumback, L Lima, J Bathon, JM AF Giles, Jon T. Malayeri, Ashkan A. Fernandes, Veronica Post, Wendy Blumenthal, Roger S. Bluemke, David Vogel-Claussen, Jens Szklo, Moyses Petri, Michelle Gelber, Allan C. Brumback, Lyndia Lima, Joao Bathon, Joan M. TI Left Ventricular Structure and Function in Patients With Rheumatoid Arthritis, As Assessed by Cardiac Magnetic Resonance Imaging SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CONGESTIVE-HEART-FAILURE; TUMOR-NECROSIS-FACTOR; RISK-FACTORS; FACTOR-ALPHA; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS MESA; CIRCULATING LEVELS; EJECTION FRACTION; DISEASE; MASS AB Objective. Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. Methods. With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. Results. Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. Conclusion. These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume. C1 [Bathon, Joan M.] Johns Hopkins Univ, Div Rheumatol, Baltimore, MD 21224 USA. [Bluemke, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Brumback, Lyndia] Univ Washington, Seattle, WA 98195 USA. RP Bathon, JM (reprint author), Johns Hopkins Univ, Div Rheumatol, 5200 Eastern Ave,Suite 4100, Baltimore, MD 21224 USA. EM jbathon@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [AR-050026]; National Heart, Lung, and Blood Institute, NIH [N01-HC-95159, N01-HC-95166, N01-HC-95169]; Arthritis National Research Foundation FX Supported by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR-050026 and National Heart, Lung, and Blood Institute contracts N01-HC-95159 through N01-HC-95166 and N01-HC-95169) and by grant support from the Arthritis National Research Foundation. NR 50 TC 38 Z9 41 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD APR PY 2010 VL 62 IS 4 BP 940 EP 951 DI 10.1002/art.27349 PG 12 WC Rheumatology SC Rheumatology GA 619LS UT WOS:000279432300004 PM 20131277 ER PT J AU Rider, LG Koziol, D Giannini, EH Jain, MS Smith, MR Whitney-Mahoney, K Feldman, BM Wright, SJ Lindsley, CB Pachman, LM Villalba, ML Lovell, DJ Bowyer, SL Plotz, PH Miller, FW Hicks, JE AF Rider, Lisa G. Koziol, Deloris Giannini, Edward H. Jain, Minal S. Smith, Michaele R. Whitney-Mahoney, Kristi Feldman, Brian M. Wright, Susan J. Lindsley, Carol B. Pachman, Lauren M. Villalba, Maria L. Lovell, Daniel J. Bowyer, Suzanne L. Plotz, Paul H. Miller, Frederick W. Hicks, Jeanne E. TI Validation of Manual Muscle Testing and a Subset of Eight Muscles for Adult and Juvenile Idiopathic Inflammatory Myopathies SO ARTHRITIS CARE & RESEARCH LA English DT Article ID DISEASE-ACTIVITY; OUTCOME ASSESSMENT; DAMAGE INDEXES; DERMATOMYOSITIS; POLYMYOSITIS; CHILDHOOD; SCALE AB Objective. To validate manual muscle testing (MMT) for strength assessment in juvenile and adult dermatomyositis (DM) and polymyositis (PM). Methods. Patients with PM/DM (73 children and 45 adults) were assessed at baseline and reevaluated 6-9 months later. We compared Total MMT (a group of 24 proximal, distal, and axial muscles) and Proximal MMT (7 proximal muscle groups) tested bilaterally on a 0-10 scale with 144 subsets of 6 and 96 subsets of 8 muscle groups tested unilaterally. Expert consensus was used to rank the best abbreviated MMT subsets for face validity and ease of assessment. Results. The Total, Proximal, and best MMT subsets had excellent internal reliability (Total MMT r(s) = 0.91-0.98), and consistency (Cronbach's alpha = 0.78-0.97). Inter-and intrarater reliability were acceptable (Kendall's W 0.68-0.76, r(s) = 0.84-0.95). MMT subset scores correlated highly with Total and Proximal MMT scores and with the Childhood Myositis Assessment Scale, and correlated moderately with physician global activity, functional disability, magnetic resonance imaging, and axial and distal MMT scores, and, in adults, with creatine kinase level. The standardized response mean for Total MMT was 0.56 in juveniles and 0.75 in adults. Consensus was reached to use a subset of 8 muscles (neck flexors, deltoids, biceps, wrist extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors) that performed as well as the Total and Proximal MMT, and had good face validity and ease of assessment. Conclusion. These findings aid in standardizing the use of MMT for assessing strength as an outcome measure for myositis. C1 [Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Off Clin Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Koziol, Deloris; Jain, Minal S.; Smith, Michaele R.; Hicks, Jeanne E.] NIH, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Giannini, Edward H.; Lovell, Daniel J.] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Whitney-Mahoney, Kristi; Feldman, Brian M.] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Wright, Susan J.; Lindsley, Carol B.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Pachman, Lauren M.] Childrens Mem Hosp, Chicago, IL 60614 USA. [Pachman, Lauren M.] Northwestern Univ, Chicago, IL 60611 USA. [Villalba, Maria L.; Plotz, Paul H.] NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bowyer, Suzanne L.] Indiana Univ, Sch Med, Indianapolis, IN USA. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Off Clin Res, NIH,Dept Hlth & Human Serv, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIH; National Institute of Environmental Health Sciences; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Rehabilitation Medicine Department; NIH Clinical Center FX Supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Rehabilitation Medicine Department, and the NIH Clinical Center. Dr. Feldman holds a Canada Research Chair in Childhood Arthritis. NR 27 TC 68 Z9 68 U1 0 U2 6 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD APR PY 2010 VL 62 IS 4 BP 465 EP 472 DI 10.1002/acr.20035 PG 8 WC Rheumatology SC Rheumatology GA 639MR UT WOS:000280979400006 PM 20391500 ER PT J AU Yates, JW Kirch, R AF Yates, Jerome W. Kirch, Rebecca TI Regulatory Barriers for Adequate Pain Control SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Article DE Single Convention on Narcotic Drugs; regulatory barriers; international responsibility ID CANCER PAIN; MANAGEMENT; PREVALENCE; POLICY; OUTPATIENTS AB In 1961 the "Single Convention on Narcotic Drugs" was adopted by the United Nations to explicitly address the need for narcotic drugs to curtail suffering and keep the distribution of these drugs in the control of health professionals. Fifty years later, neither goal has been reached for a variety of reasons. Governments have avoided putting in place systems to assure adequate supplies to relieve the suffering of those with severe pain, drug enforcement agencies maintain restrictive regulations and physicians are intimidated by threats of legal action if their prescribing patterns do not conform to arbitrary standards. There is a shortage of pain control consultants and the training for most health care providers is deficient when it comes to the management of chronic pain. Some of the regulatory barriers have been successfully addressed through advocacy efforts and the expertise deficiencies improved through targeted educational programs. C1 [Yates, Jerome W.] SUNY Buffalo, RPCI, Buffalo, NY 14260 USA. [Yates, Jerome W.] NIA, NIH, Bethesda, MD 20892 USA. [Kirch, Rebecca] Amer Canc Soc, Canc Act Network, Atlanta, GA 30329 USA. RP Yates, JW (reprint author), SUNY Buffalo, RPCI, Buffalo, NY 14260 USA. EM jeromey@aol.com NR 27 TC 0 Z9 1 U1 0 U2 1 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI NAGOYA PA 4-84 JOTO-CHO, KITA-KU, NAGOYA, 462-0831, JAPAN SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PD APR PY 2010 VL 11 SU 1 BP 17 EP 21 PG 5 WC Oncology SC Oncology GA 682DK UT WOS:000284379900004 PM 20590343 ER PT J AU Terry, S Austin, C Inglese, J Meeker, D Terry, P AF Terry, Sharon Austin, Christopher Inglese, James Meeker, David Terry, Patrick TI Assay, Preclinical, and Clinical Brick Walls and Opportunities for System Change Through GRANDRx SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Editorial Material C1 [Terry, Sharon] Genet Alliance, Washington, DC 20008 USA. [Austin, Christopher; Inglese, James] NHGRI, NCGC, NIH, Rockville, MD USA. [Meeker, David] Genzyme Corp, Therapeut Biosurg & Corp Operat, Cambridge, MA USA. [Terry, Patrick] Grand Therapeut Fdn, Washington, DC USA. RP Terry, S (reprint author), Genet Alliance, 4301 Connecticut Ave NW,Suite 404, Washington, DC 20008 USA. EM sterry@geneticalliance.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD APR PY 2010 VL 8 IS 2 BP 128 EP 134 DI 10.1089/adt.2010.0802.rt PG 7 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 591FD UT WOS:000277283900002 PM 20307201 ER PT J AU Yasgar, A Shultz, J Zhou, WH Wang, H Huang, F Murphy, N Abel, EL DiGiovanni, J Inglese, J Simeonov, A AF Yasgar, Adam Shultz, John Zhou, Wenhui Wang, Hui Huang, Fen Murphy, Nancy Abel, Erika L. DiGiovanni, John Inglese, James Simeonov, Anton TI A High-Throughput 1,536-Well Luminescence Assay for Glutathione S-Transferase Activity SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID INHIBITORS; LIBRARIES; BIOTRANSFORMATION; CONJUGATION; EXPRESSION; TOXICOLOGY; MECHANISM; DRUGS; A1-1 AB Glutathione S-transferases (GSTs) constitute a family of detoxification enzymes that catalyze the conjugation of glutathione with a variety of hydrophobic compounds, including drugs and their metabolites, to yield water-soluble derivatives that are excreted in urine or bile. Profiling the effect of small molecules on GST activity is an important component in the characterization of drug candidates and compound libraries. Additionally, specific GST isozymes have been implicated in drug resistance, especially in cancer, and thus represent potential targets for intervention. To date, there are no sensitive miniaturized high-throughput assays available for GST activity detection. A series of GST substrates containing a masked luciferin moiety have been described recently, offering the potential for configuring a sensitive screening assay via coupled luciferase reaction and standard luminescence detection. We report on the optimization and miniaturization of this homogeneous method to 1,536-well format using GSTs from 3 different species: mouse isozyme A4-4, human isozymes A1-1, M1-1, and P1-1, and the major GST from the parasitic worm Schistosoma japonicum. C1 [Yasgar, Adam; Inglese, James; Simeonov, Anton] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Shultz, John; Huang, Fen; Murphy, Nancy] Promega Corp, Madison, WI USA. [Zhou, Wenhui; Wang, Hui] Promega Biosci Inc, San Luis Obispo, CA USA. [Abel, Erika L.; DiGiovanni, John] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Div Res, Smithville, TX USA. RP Simeonov, A (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. EM asimeono@mail.nih.gov OI Abel, Erika/0000-0001-8791-825X FU NIH Roadmap for Medical Research [ES016623]; NHGRI FX This research was supported in part by the Molecular Libraries Initiative of the NIH Roadmap for Medical Research, the Intramural Research Program of the NHGRI, NIH, and NIH grant ES016623 (to E.A. and J.D.). NR 35 TC 9 Z9 9 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD APR PY 2010 VL 8 IS 2 BP 200 EP 211 DI 10.1089/adt.2009.0248 PG 12 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 591FD UT WOS:000277283900006 PM 20085484 ER PT J AU Koh, KK Han, SH Oh, PC Shin, EK Quon, MJ AF Koh, Kwang Kon Han, Seung Hwan Oh, Pyung Chun Shin, Eak Kyun Quon, Michael J. TI Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction SO ATHEROSCLEROSIS LA English DT Review DE Combination therapy; Atherosclerosis; Endothelial dysfunction; Insulin resistance; Risk factors ID ACTIVATED-RECEPTOR-GAMMA; RANDOMIZED CONTROLLED-TRIAL; SMOOTH-MUSCLE-CELLS; SPONTANEOUSLY HYPERTENSIVE-RATS; CONVERTING ENZYME-INHIBITORS; LOW-DENSITY-LIPOPROTEIN; INTIMA-MEDIA THICKNESS; II TYPE-1 RECEPTOR; HIGH-RISK PATIENTS; ANGIOTENSIN-II AB Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by similar to 30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin-angiotensin-aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin-angiotensin-aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon] Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, Div Cardiol, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, Div Cardiol, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Gil Medical Center, Gachon University, Incheon, Korea [2007-1]; NCCAM, NIH FX This study was partly supported by grants from established investigator award (2007-1) (K.K. Koh), Gil Medical Center, Gachon University, Incheon, Korea. This work was supported, in part, by the Intramural Research Program, NCCAM, NIH (M.J. Quon). NR 106 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2010 VL 209 IS 2 BP 307 EP 313 DI 10.1016/j.atherosclerosis.2009.09.007 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 576PS UT WOS:000276158000001 PM 19800624 ER PT J AU Kim, NH Pavkov, ME Nelson, RG Hanson, RL Bennett, PH Curtis, JM Sievers, ML Knowler, WC AF Kim, Nan Hee Pavkov, Meda E. Nelson, Robert G. Hanson, Robert L. Bennett, Peter H. Curtis, Jeffrey M. Sievers, Maurice L. Knowler, William C. TI The separate and joint effects of prolonged QT interval and heart rate on mortality SO ATHEROSCLEROSIS LA English DT Article DE Cardiovascular disease; Heart rate; Mortality; QT interval ID SUDDEN CARDIAC DEATH; CARDIOVASCULAR MORTALITY; GENERAL-POPULATION; DIABETES-MELLITUS; QT(C) INTERVAL; PIMA-INDIANS; FOLLOW-UP; ALL-CAUSE; DISEASE; MEN AB Objectives: Understanding why prolonged Bazett-corrected QT interval (QTc) is a risk factor for mortality is difficult, because QTc is positively correlated with heart rate. To optimally distinguish the effects of QT interval and heart rate on mortality, QT interval and heart rate were modeled separately and jointly in Pima Indians. Methods: The effects of QT and heart rate on all-cause and cause-specific mortality were assessed in the overall study population and according to the presence or absence of diabetes using multivariable time-dependent proportional hazards models. Results: Among 1488 nondiabetic and 990 diabetic subjects >= 25 years old, 81 nondiabetic and 149 diabetic subjects died during a median follow-up of 7.3 years. When included in the same regression model, QT and heart rate each predicted all-cause mortality [hazard ratios per standard deviation (SD) (95% confidence interval) = 1.31 (1.10-1.57) and 1.57 (1.32-1.87) respectively]. In nondiabetic subjects, hazard ratios for all-cause mortality were 1.54 (1.19-1.99) for QT and 1.86 (1.46-2.37) for heart rate. In diabetic subjects, hazard ratios for all-cause mortality were lower, 1.27 (1.00-1.62) for QT and 1.41 (1.12-1.78) for heart rate. In the overall study population, neither QT nor heart rate significantly predicted cardiovascular disease (CVD) mortality [hazard ratios = 1.13 (0.77-1.64) and 1.46 (0.98-2.19)] when adjusted for each other. Heart rate unadjusted for QT, however, predicted CVD mortality [hazard ratio = 1.34 (1.00-1.79)] in a separate model. Conclusions: QT prolongation and high heart rate both predict all-cause mortality in Pima Indians, but heart rate was consistently the stronger predictor of the two. Published by Elsevier Ireland Ltd. C1 [Kim, Nan Hee] Korea Univ, Sch Med, Seoul, South Korea. [Pavkov, Meda E.; Nelson, Robert G.; Hanson, Robert L.; Bennett, Peter H.; Curtis, Jeffrey M.; Sievers, Maurice L.; Knowler, William C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ USA. RP Kim, NH (reprint author), Korea Univ, Ansan Hosp, Gojan 1 Dong, Ansan 425707, South Korea. EM nhkendo@gmail.com RI Max, Mad/E-5238-2010; Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Max, Mad/0000-0001-6966-6829; Hanson, Robert/0000-0002-4252-7068 FU National Institute of Diabetes and Digestive and Kidney Diseases; American Diabetes Association FX This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases and by the American Diabetes Association. NR 40 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2010 VL 209 IS 2 BP 539 EP 544 DI 10.1016/j.atherosclerosis.2009.09.026 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 576PS UT WOS:000276158000037 PM 19878945 ER PT J AU Karasik, LB Adolph, KE Tamis-LeMonda, CS Bornstein, MH AF Karasik, Lana B. Adolph, Karen E. Tamis-LeMonda, Catherine S. Bornstein, Marc H. TI WEIRD walking: Cross-cultural research on motor development SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material AB Motor development - traditionally studied in WEIRD populations - falls victim to assumptions of universality similar to other domains described by Henrich et al. However, cross-cultural research illustrates the extraordinary diversity that is normal in motor skill acquisition. Indeed, motor development provides an important domain for evaluating cultural challenges to a general behavioral science. C1 [Karasik, Lana B.; Bornstein, Marc H.] Natl Inst Child Hlth & Human Dev NICHD, Bethesda, MD 20892 USA. [Adolph, Karen E.; Tamis-LeMonda, Catherine S.] NYU, Dept Psychol, New York, NY 10003 USA. RP Karasik, LB (reprint author), Natl Inst Child Hlth & Human Dev NICHD, Bethesda, MD 20892 USA. EM lana.karasik@nih.gov; karen.adolph@nyu.edu; catherine.tamis-lemonda@nyu.edu; Marc_H_Bornstein@nih.gov FU Intramural NIH HHS [Z01 HD001119-20]; NICHD NIH HHS [R37 HD033486] NR 0 TC 10 Z9 10 U1 1 U2 12 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD APR-JUN PY 2010 VL 33 IS 2-3 BP 95 EP + DI 10.1017/S0140525X10000117 PG 15 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 626NR UT WOS:000279973200014 PM 20546664 ER PT J AU Auchampach, JA Gizewski, ET Wan, TC de Castro, S Brown, GG Jacobson, KA AF Auchampach, John A. Gizewski, Elizabeth T. Wan, Tina C. de Castro, Sonia Brown, Garth G., Jr. Jacobson, Kenneth A. TI Synthesis and pharmacological characterization of [I-125]MRS5127, a high affinity, selective agonist radioligand for the A(3) adenosine receptor SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Nucleoside; G protein-coupled receptor; Adenosine receptor; Radioligand binding ID RHEUMATOID-ARTHRITIS; KAPPA-B; ANTAGONIST RADIOLIGAND; LIGANDS; TARGET; NUCLEOSIDES; DERIVATIVES; INHIBITION; ACTIVATION; CARCINOMA AB A recently reported selective agonist of the human A(3) adenosine receptor (hA(3)AR), MRS5127 (1'R,2'R,3'S,4'R,5'S)-4'-[2-chloro-6-(3-iodobenzylamino)-purine]-2',3'-O-dihydroxy-bicyclo-[3.1.0]hexane, was radioiodinated and characterized pharmacologically. It contains a rigid bicyclic ring system in place of a 5'-truncated ribose moiety, and was selected for radiolabeling due to its nanomolar binding affinity at both human and rat A(3)ARs. The radioiodination of the N-6-3-iodobenzyl substituent by iododestannylation of a 3-(trimethylstannyl)benzyl precursor was achieved in 73% yield, measured after purification by HPLC. [I-125]MRS5127 bound to the human A(3)AR expressed in membranes of stably transfected HEK 293 cells. Specific binding was saturable, competitive, and followed a one-site binding model, with a K-d value of 5.74 +/- 0.97 nM. At a concentration equivalent to its K-d, non-specific binding comprised 27 +/- 2% of total binding. In kinetic studies, [I-125]MRS5127 rapidly associated with the hA(3)AR (t(1/2) =0.514 +/- 0.014 min), and the affinity calculated from association and dissociation rate constants was 3.50 +/- 1.46 nM. The pharmacological profile of ligands in competition experiments with [I-125]MRS5127 was consistent with the known structure-activity-relationship profile of the hA(3)AR. [I-125]MRS5127 bound with similar high affinity (K-d, nM) to recombinant A(3)ARs from mouse (4.90 +/- 0.77), rabbit (2.53 +/- 0.11), and dog (3.35 +/- 0.54). For all of the species tested, MRS5127 exhibited A(3)AR agonist activity based on negative coupling to cAMP production. Thus, [I-125]MRS5127 represents a new species-independent agonist radioligand for the A3AR. The major advantage of [I-125]MRS5127 compared with previously used A(3)AR radioligands is its high affinity, low degree of non-specific binding, and improved A(3)AR selectivity. (C) 2009 Elsevier Inc. All rights reserved. C1 [Auchampach, John A.; Gizewski, Elizabeth T.; Wan, Tina C.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA. [de Castro, Sonia; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Brown, Garth G., Jr.] PerkinElmer Inc, Waltham, MA 02451 USA. RP Auchampach, JA (reprint author), Med Coll Wisconsin, Dept Pharmacol & Toxicol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jauchamp@mcw.edu; kajacobs@helix.nih.gov RI de castro, sonia/E-7303-2012; Jacobson, Kenneth/A-1530-2009 OI de castro, sonia/0000-0002-3838-6856; Jacobson, Kenneth/0000-0001-8104-1493 FU NIH [R01 HL077707]; National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (KAJ) and by NIH R01 HL077707 (JAA). We thank Dr. Artem Melman (Clarkson University) for preparation of synthetic intermediates, and Dr. Zhan-Guo Gao and Dr. Athena Keene-Klutz for helpful discussion. NR 34 TC 9 Z9 10 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 1 PY 2010 VL 79 IS 7 BP 967 EP 973 DI 10.1016/j.bcp.2009.11.009 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 557JQ UT WOS:000274665800004 PM 19917269 ER PT J AU Gao, JH Chen, K Xie, RG Xie, J Yan, YJ Cheng, Z Peng, XG Chen, XY AF Gao, Jinhao Chen, Kai Xie, Renguo Xie, Jin Yan, Yongjun Cheng, Zhen Peng, Xiaogang Chen, Xiaoyuan TI In Vivo Tumor-Targeted Fluorescence Imaging Using Near-Infrared Non-Cadmium Quantum Dots SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MULTIFUNCTIONAL MAGNETIC NANOPARTICLES; GROWTH-FACTOR RECEPTOR; PHOSPHOLIPID MICELLES; LIVING SUBJECTS; BREAST-CANCER; INTEGRIN; VASCULATURE; PEPTIDE; BIODISTRIBUTION; CYTOTOXICITY AB This article reported the high tumor targeting efficacy of RGD peptide labeled near-infrared (NIR) non-cadmium quantum dots (QDs). After using poly(ethylene glycol) to encapsulate InAs/InP/ZnSe QDs (emission maximum at about 800 nm), QD800-PEG dispersed well in PBS buffer with the hydrodynamic diameter (HD) of 15.9 nm and the circulation half-life of similar to 29 min. After coupling QD800-PEG with arginine glycine aspartic acid (RGD) or arginine-alanine-aspartic acid (RAD) peptides, we used nude mice bearing subcutaneous U87MG tumor as models to test tumor-targeted fluorescence imaging. The results indicated that the tumor uptake of QD800-RGD is much higher than those of QD800-PEG and QD800-RAD. The semiquantitative analysis of the region of interest (ROI) showed a high tumor uptake of 10.7 +/- 1.5% ID/g in mice injected with QD800-RGD, while the tumor uptakes of QD800-PEG and QD800-RAD were 2.9 +/- 0.3% ID/g and 4.0 0.5%ID/g, respectively, indicating the specific tumor targeting of QD800-RGD. The high reproducibility of bioconjunction between QDs and the RGD peptide and the feasibility of QD-RGD bioconjugates as tumor-targeted fluorescence probes warrant the successful application of QDs for in vivo molecular imaging. C1 [Gao, Jinhao; Chen, Kai; Xie, Jin; Yan, Yongjun; Cheng, Zhen; Chen, Xiaoyuan] Stanford Univ, Mol Imaging Program Stanford, Dept Radiol, Sch Med, Stanford, CA 94305 USA. [Gao, Jinhao; Chen, Kai; Xie, Jin; Yan, Yongjun; Cheng, Zhen; Chen, Xiaoyuan] Stanford Univ, Sch Med, BioX Program, Stanford, CA 94305 USA. [Xie, Renguo; Peng, Xiaogang] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. RP Gao, JH (reprint author), Stanford Univ, Mol Imaging Program Stanford, Dept Radiol, Sch Med, 1201 Welch Rd, Stanford, CA 94305 USA. EM gaojh@stanford.edu; shawn.chen@nih.gov RI Gao, Jinhao/F-5092-2010; Xie, Jin/E-8193-2010; Cheng, Zhen/K-2843-2012; peng, xiaogang/R-6184-2016 OI Gao, Jinhao/0000-0003-3215-7013; peng, xiaogang/0000-0002-5606-8472 FU NCI/NIH [R21 CA 121842, U54 CA119367] FX This work was partially supported by NCI/NIH R21 CA 121842 and U54 CA119367. NR 45 TC 92 Z9 98 U1 10 U2 128 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 APR PY 2010 VL 21 IS 4 BP 604 EP 609 DI 10.1021/bc900323v PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 585IE UT WOS:000276817800006 PM 20369817 ER PT J AU Vattikuti, S Chow, CC AF Vattikuti, Shashaank Chow, Carson C. TI A Computational Model for Cerebral Cortical Dysfunction in Autism Spectrum Disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Cognitive shifting; cortical circuit; fragile X syndrome; minicolumn; saccade; synaptic balance ID LATERAL INTRAPARIETAL AREA; FRAGILE-X-SYNDROME; GABAERGIC INHIBITION; DOWN-REGULATION; NETWORK MODEL; MOUSE MODEL; OCULOMOTOR; ABNORMALITIES; CATATONIA; DEFICITS AB Background: Perturbations to the microscopic level balance between synaptic excitation and inhibition and neuron organization in the cerebral cortex are suggested to underlie autism spectrum disorder (ASD) traits. The mechanism linking these perturbations to cognitive behaviors in ASD is unknown. This study strives to bridge this gap by generating clinically testable diagnostic and pharmacological predictions based on the effect of synaptic imbalance and neuron distribution on a computational local circuit model of the cerebral cortex. Methods: We use a computational microscopic model of the cerebral cortex that incorporates N-methyl-D-aspartate and gamma-aminobutyric acid synaptic kinetics. We employ the model circuit during model tasks similar to visually guided and gap oculomotor saccade tasks and interpret qualitative model predictions of saccade hypometria and dysmetria. We consider the effects of varying the excitatory to inhibitory synaptic balance, neuron density, and neuron clustering in this model. Results: An increase of synaptic excitation over synaptic inhibition results in increased hypometria and dysmetria. Similar effects by either reduced inhibition or increased excitation suggest that a variety of pharmacological compounds can be used for both screening and medical management. On the other hand, any change to the microscopic neuron anatomy that increases the effective maximum distance between excitatory neurons decreases hypometria but has no affect on dysmetria. Conclusions: Perturbations to a computational model of a local cerebral cortical circuit can account for saccade hypometria and dysmetria reported in ASD studies. This approach may provide a direct link between cerebral cortical function and ASD behaviors. C1 [Vattikuti, Shashaank; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Chow, CC (reprint author), NIDDK, Lab Biol Modeling, NIH, Bldg 12A,Room 4007, Bethesda, MD 20892 USA. EM carsonc@mail.nih.gov RI Chow, Carson/A-7970-2009 FU National Institutes of Health/National Institute of Diabetes and Digestive and kidney Diseases FX This work was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Diabetes and Digestive and kidney Diseases. NR 45 TC 30 Z9 30 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2010 VL 67 IS 7 BP 672 EP 678 DI 10.1016/j.biopsych.2009.09.008 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 574QY UT WOS:000276008700011 PM 19880095 ER PT J AU Stiff, PJ Agovi, MA Antman, KH Blaise, D Camitta, BM Cairo, MS Childs, RW Edwards, JR Gale, RP Hale, GA Lazarus, HM Arora, M AF Stiff, Patrick J. Agovi, Manza-A. Antman, Karen H. Blaise, Didier Camitta, Bruce M. Cairo, Mitchell S. Childs, Richard W. Edwards, John R. Gale, Robert Peter Hale, Gregory A. Lazarus, Hillard M. Arora, Mukta TI High-Dose Chemotherapy with Blood or Bone Marrow Transplants for Rhabdomyosarcoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Rhabdomyosarcoma; Autotransplant; Soft-tissue sarcoma ID STEM-CELL RESCUE; METASTATIC RHABDOMYOSARCOMA; INTERGROUP RHABDOMYOSARCOMA; PROGNOSTIC-FACTORS; RECURRENT RHABDOMYOSARCOMA; EWINGS-SARCOMA; CHILDREN; THERAPY; RISK; ADOLESCENTS AB Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, the 5-year survival for those who relapse is about 30%, and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone marrow (BM) transplants for RMS between 1989 and 2003, and reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR). Histologic subtype was confirmed by reviewing pathology reports. Treatment-related mortality (TRM), progression-free survival (PFS), and overall survival (OS) were evaluated. Overall, 73% of subjects were <20 years; 39% had cancer bulk >5 cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant, and 67% were in first remission. The I-year TRM was 5% (95% confidence interval [CI], 1%-12%) and the 5-year PFS and OS were 29% (95% CI, 18%41%) and 32% (95% CI, 21%-44%), respectively. There was only a 4% relapse rate after the first year. There were no differences in 5-year PFS or survival based on histological subtype, transplant in first remission versus relapse (36% versus 29%; P = .5), or transplantation for poor-risk histologies in first remission versus relapse (34% versus 33%; P = .9). Our data indicate that autotransplants for RMS disease are typically done in patients with disease responsive to chemotherapy pretransplant, with approximately one-third long-term survivors. Despite high-risk factors, we also found a low TRM, perhaps reflecting the migration from marrow to blood stem cells as the graft source. Even when performed after relapse for alveolar/undifferentiated histologies, long-term survivals were seen seemingly better than results with conventional therapies. Biol Blood Marrow Transplant 16: 525-532 (2010) (C) 2010 American Society for Blood Marrow Transplantation C1 [Stiff, Patrick J.] Loyola Univ, Med Ctr, Blood & Marrow Stem Cell Transplant Program, Maywood, IL 60153 USA. [Agovi, Manza-A.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Antman, Karen H.] Boston Univ, Boston, MA 02215 USA. [Blaise, Didier] Inst J Paoli I Calmettes, F-13009 Marseille, France. [Camitta, Bruce M.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Ctr Canc & Blood Disorders, Milwaukee, WI 53226 USA. [Cairo, Mitchell S.] Columbia Univ, Med Ctr, New York, NY USA. [Childs, Richard W.] NIH, Bethesda, MD 20892 USA. [Edwards, John R.] Florida Hosp Canc Inst, Orlando, FL USA. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Hale, Gregory A.] All Childrens Hosp, Tampa, FL USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RP Stiff, PJ (reprint author), Loyola Univ, Med Ctr, Blood & Marrow Stem Cell Transplant Program, 2160 S 1st Ave, Maywood, IL 60153 USA. EM pstiff@lumc.edu OI Antman, Karen/0000-0002-1093-8356 FU National Cancer Institute (NCI) [U24-CA76518, 5U01HL069294]; National Heart, Lung and Blood Institute (NFILBI); National Institute of Allergy and Infectious Diseases (MAID); NHLBI [5U01HL069294]; HRSA/DHHS [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter international, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CvtoTherm; DOR BioPharma, Inc.; Dynal Biotech; Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; Leukemia & Lymphoma Society; Merck Company; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; Teva Pharmaceutical Industries; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NFILBI) and the National Institute of Allergy and Infectious Diseases (MAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter international, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CvtoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; Teva Pharmaceutical Industries; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the U.S. Government. NR 19 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2010 VL 16 IS 4 BP 525 EP 532 DI 10.1016/j.bbmt.2009.11.020 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 578JC UT WOS:000276288600008 PM 19961947 ER PT J AU Kalaycio, ME Kukreja, M Woolfrey, AE Szer, J Cortes, J Maziarz, RT Bolwell, BJ Buser, A Copelan, E Gale, RP Gupta, V Maharaj, D Marks, DI Pavletic, SZ Horowitz, MM Arora, M AF Kalaycio, Matt E. Kukreja, Manisha Woolfrey, Ann E. Szer, Jeffrey Cortes, Jorge Maziarz, Richard T. Bolwell, Brian J. Buser, Andreas Copelan, Edward Gale, Robert Peter Gupta, Vikas Maharaj, Dipnarine Marks, David I. Pavletic, Steven Z. Horowitz, Mary M. Arora, Mukta TI Allogeneic Hematopoietic Cell Transplant for Prolymphocytic Leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Prolymphocytic leukemia; Allogeneic stem cell transplantation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MALIGNANCIES; CLADRIBINE; DISORDERS AB The poor prognosis of patients with prolymphocytic leukemia (PLL) has led some clinicians to recommend allogeneic hematopoietic cell transplant (HCT). However, the data to support this approach is limited to case-reports and small case series. We reviewed the database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to determine outcomes after allotransplant for patients with PLL. We identified 47 patients with a median age of 54 years (range: 30-75 years). With a median follow-up of 13 months, progression-free survival (PFS) was 33% (95% confidence interval [CI] 20%-47%) at 1 year. The most common cause of death was relapse or progression in 49%. The cumulative incidence of treatment-related mortality (TRM) at I-year posttransplant was 28%. The small patient population prohibited prognostic factor analysis, but these data support consideration of allotransplant for PLL. Further study of a larger population of patients is needed to determine which patients are more likely to benefit. Biol Blood Marrow Transplant 16: 543-547 (2010) (C) 2010 American Society for Blood Marrow Transplantation C1 [Kalaycio, Matt E.; Bolwell, Brian J.; Copelan, Edward] Taussig Canc Inst, Cleveland, OH USA. [Kukreja, Manisha; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Woolfrey, Ann E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Szer, Jeffrey] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Cortes, Jorge] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Buser, Andreas] Blutspendezentrum, Basel, Switzerland. [Gale, Robert Peter] Celgene Corp, Summit, NJ USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Maharaj, Dipnarine] S Florida Bone Marrow Stem Cell Transplant Inst, Boynton Beach, FL USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. [Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. RP Kalaycio, ME (reprint author), Cleveland Clin, Taussig Canc Inst R35, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM kalaycm@ccf.org RI Buser, Andreas/A-2660-2008; OI Buser, Andreas/0000-0002-7942-6746; Szer, Jeff/0000-0001-6783-2301 FU NCI NIH HHS [U24 CA076518-12, U24 CA076518, U24 CA76518]; NHLBI NIH HHS [5U01HL069294, U01 HL069294] NR 21 TC 10 Z9 10 U1 0 U2 1 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 APR PY 2010 VL 16 IS 4 BP 543 EP 547 DI 10.1016/j.bbmt.2009.11.021 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 578JC UT WOS:000276288600010 PM 19961946 ER PT J AU Xie, J Chen, K Huang, J Lee, S Wang, JH Gao, J Li, XG Chen, XY AF Xie, Jin Chen, Kai Huang, Jing Lee, Seulki Wang, Jinhua Gao, Jinhao Li, Xingguo Chen, Xiaoyuan TI PET/NIRF/MRI triple functional iron oxide nanoparticles SO BIOMATERIALS LA English DT Article DE Iron oxide nanoparticle (IONP); Magnetic resonance imaging (MRI); Positron emission tomography (PET); Near-infrared fluorescence (NIRF) imaging; Enhanced permeability and retention (EPR) effect; Multiple imaging ID ALBUMIN-BOUND PACLITAXEL; IN-VIVO; MAGNETIC NANOPARTICLES; MONOCLONAL-ANTIBODY; DRUG-DELIVERY; TUMOR-CELLS; CANCER; PROBES; RGD; PERMEABILITY AB Engineered nanoparticles with theranostic functions have attracted a lot of attention for their potential role in the dawning era of personalized medicine. Iron oxide nanoparticles (IONPs), with their advantages of being non-toxic, biodegradable and inexpensive, are candidate platforms for the buildup of theranostic nanostructures; however, progress in using them has been limited largely due to inefficient drug loading and delivery. In the current study, we utilized dopamine to modify the surface of IONPs, yielding nanoconjugates that can be easily encapsulated into human serum albumin (HSA) matrices (clinically utilized drug carriers). This nanosystem is well-suited for dual encapsulation of IONPs and drug molecules, because the encapsulation is achieved in a way that is similar to common drug loading. To assess the biophysical characteristics of this novel nanosystem, the HSA coated IONPs (HSA-IONPs) were dually labeled with (64)Cu-DOTA and Cy5.5, and tested in a subcutaneous U87MG xenograft mouse model. In vivo positron emission tomography (PET)/near-infrared fluorescence (NIRF)/magnetic resonance imaging (MRI) tri-modality imaging, and ex vivo analyses and histological examinations were carefully conducted to investigate the in vivo behavior of the nanostructures. With the compact HSA coating, the HSA-IONPs manifested a prolonged circulation half-life; more impressively, they showed massive accumulation in lesions, high extravasation rate, and low uptake of the particles by macrophages at the tumor area. Published by Elsevier Ltd. C1 [Xie, Jin; Lee, Seulki; Chen, Xiaoyuan] NIBIB, LOMIN, NIH, Bethesda, MD 20892 USA. [Xie, Jin; Chen, Kai; Huang, Jing; Lee, Seulki; Wang, Jinhua; Gao, Jinhao; Chen, Xiaoyuan] Stanford Univ, Dept Radiol Biophys & Biox Program, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Huang, Jing; Li, Xingguo] Beijing Univ, Dept Chem, Beijing 100871, Peoples R China. RP Chen, XY (reprint author), NIBIB, LOMIN, NIH, Bldg 31,Room 1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Gao, Jinhao/F-5092-2010; Xie, Jin/E-8193-2010 OI Gao, Jinhao/0000-0003-3215-7013; FU Intramural NIH HHS [Z99 EB999999, ZII EB000066-01] NR 35 TC 225 Z9 236 U1 23 U2 185 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2010 VL 31 IS 11 BP 3016 EP 3022 DI 10.1016/j.biomaterials.2010.01.010 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 573WR UT WOS:000275946500008 PM 20092887 ER PT J AU Pastorin, G Federico, S Paoletta, S Corradino, M Cateni, F Cacciari, B Klotz, KN Gao, ZG Jacobson, KA Spalluto, G Moro, S AF Pastorin, Giorgia Federico, Stephanie Paoletta, Silvia Corradino, Marta Cateni, Francesca Cacciari, Barbara Klotz, Karl-Norbert Gao, Zhan-Guo Jacobson, Kenneth A. Spalluto, Giampiero Moro, Stefano TI Synthesis and pharmacological characterization of a new series of 5,7-disubstituted-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives as adenosine receptor antagonists: A preliminary inspection of ligand-receptor recognition process SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE G Protein-coupled receptors; Adenosine receptor antagonists; Triazolo-triazine; Ligand-receptor modeling studies ID HUMAN A(3); A(3)-ADENOSINE RECEPTOR; PARKINSONS-DISEASE; A(2B) RECEPTOR; HIGHLY POTENT; HIGH-AFFINITY; FORCE-FIELD; RAT-BRAIN; A(2A); ZM241385 AB A new series of triazolotriazines variously substituted at the C5 and N7 (5-25) positions was synthesized and fully characterized at the four adenosine receptor (AR) subtypes. In particular, arylacetyl or arylcarbamoyl moieties were introduced at the N7 position, which enhanced affinity at the hA(2B) and hA(3) ARs, respectively, when utilized on the pyrazolo-triazolopyrimidine nucleus as we reported in the past. In general, compounds with a free amino group at the 7 position (5, 6), showed good affinity at the rat (r) A(2A) AR (range 18.3-96.5 nM), while the introduction of a phenylcarbamoyl moiety at the N7 position (12, 19, 24) slightly increased the affinity at the hA3 AR (range 311-633 nM) with respect to the unsubstituted derivatives. The binding profiles of the synthesized analogues seemed to correlate with the substitutions at the C5 and N7 positions. At the hA2B AR, derivative 5, which contained a free amino group at the 7 position, was the most potent (EC50 3.42 mu M) and could represent a starting point for searching new non-xanthine hA2B AR antagonists. Molecular models of the rA(2A) and hA3 ARs were constructed by homology to the recently reported crystallographic structure of the hA(2A) AR. A preliminary receptor-driven structure-activity relationship (SAR) based on the analysis of antagonist docking has been provided. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Federico, Stephanie; Cateni, Francesca; Spalluto, Giampiero] Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy. [Pastorin, Giorgia] Natl Univ Singapore, Dept Pharm, Singapore 117548, Singapore. [Paoletta, Silvia; Corradino, Marta; Moro, Stefano] Univ Padua, Dipartimento Sci Farmaceut, MMS, I-35131 Padua, Italy. [Cacciari, Barbara] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. [Klotz, Karl-Norbert] Univ Wurzburg, Inst Pharmakol & Toxikol, D-97078 Wurzburg, Germany. [Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, MRS, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Spalluto, G (reprint author), Univ Trieste, Dipartimento Sci Farmaceut, Piazzale Europa 1, I-34127 Trieste, Italy. EM spalluto@univ.trieste.it; stefano.moro@unipd.it RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Pastorin, Giorgia/B-5907-2015 OI Federico, Stephanie/0000-0003-2800-5287; Klotz, Karl-Norbert/0000-0003-3553-3205; Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; FU University of Padova, Italy; Italian Ministry for University and Research (MIUR), Rome, Italy; NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX The molecular modeling work coordinated by S. M. was carried out with financial support from the University of Padova, Italy, and the Italian Ministry for University and Research (MIUR), Rome, Italy. S. M. is also very grateful to Chemical Computing Group for the scientific and technical partnership. This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. NR 57 TC 19 Z9 19 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR PY 2010 VL 18 IS 7 BP 2524 EP 2536 DI 10.1016/j.bmc.2010.02.039 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 577YA UT WOS:000276258700017 PM 20304654 ER PT J AU Kim, JE Chung, WY Chun, KS Lee, CK Park, HJ Kim, WB Park, KK AF Kim, Jin-Eun Chung, Won-Yoon Chun, Kyung-Soo Lee, Chang Ki Park, Hee-Juhn Kim, Won-Bae Park, Kwang-Kyun TI Pleurospermum kamtschaticum Extract Induces Apoptosis via Mitochondrial Pathway and NAG-1 Expression in Colon Cancer Cells SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE Pleurospermum kamtschaticum; apoptosis; Bax/Bcl-2; caspases; NAG-1 ID ACTIVATED GENE NAG-1; COLORECTAL-CANCER; CYTOCHROME-C; GROWTH ARREST; PROTEINS; BCL-2; ANGIOGENESIS; RELEASE; CASCADE; DEATH AB To evaluate the anticarcinogenic activity of methanol extract of Pleurospermum kamischaticum (PKE), we assessed its apoptosis-inducing capability in HT-29 colon carcinoma cells. PKE treatment for 2 h reduced cell viability in a dose-related manner, and induced apoptotic morphological changes. Flow cytometric analysis indicated that PKE treatment at 0.05 mg/ml induced early apoptosis in 66.2% of HT-29 cells. Additionally, Bcl-2 expression was substantially reduced in PKE-treated HT-29 cells, increasing the Bax/Bcl-2 ratio. The protein levels of procaspase-9 and procaspase-3 were decreased markedly, reflecting caspase-9 and caspase-3 activation, and resulting PARP cleavage was noted in the PKE-treated HT-29 cells. Furthermore, we detected increased NAG-1 expression in the PKE-treated HT-29 cells. In an in vivo study, intraperitoneal PKE administration suppressed the formation of tumor nodules in the lungs of mice. These results indicate that PKE can serve as a beneficial supplement in the treatment and the prevention of colon cancer. C1 [Kim, Jin-Eun; Chung, Won-Yoon; Lee, Chang Ki; Park, Kwang-Kyun] Yonsei Univ, Coll Dent, Dept Oral Biol, Seoul 120752, South Korea. [Chung, Won-Yoon; Lee, Chang Ki; Park, Kwang-Kyun] Yonsei Univ, Coll Dent, Brain Korea Project 21, Seoul 120752, South Korea. [Chung, Won-Yoon; Lee, Chang Ki; Park, Kwang-Kyun] Yonsei Univ, Coll Dent, Oral Canc Res Inst, Oral Sci Res Inst, Seoul 120752, South Korea. [Chun, Kyung-Soo] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Park, Hee-Juhn] Sangji Univ, Dept Bot Resources, Wonju 220702, South Korea. [Kim, Won-Bae] RDA, Natl Alpine Agr Expt Stn, Pyohgchang 232950, South Korea. RP Park, KK (reprint author), Yonsei Univ, Coll Dent, Dept Oral Biol, 250 Seongsanno, Seoul 120752, South Korea. FU Ministry for Health, Welfare & Family Affairs, Republic of Korea [A060197] FX This study was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A060197). NR 31 TC 5 Z9 5 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD APR PY 2010 VL 74 IS 4 BP 788 EP 792 DI 10.1271/bbb.90826 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 599GW UT WOS:000277900200016 PM 20378978 ER PT J AU Han, SS Chang, JT AF Han, Summer S. Chang, Joseph T. TI Reconsidering the asymptotic null distribution of likelihood ratio tests for genetic linkage in multivariate variance components models under complete pleiotropy SO BIOSTATISTICS LA English DT Article DE Asymptotic null distribution; Likelihood ratio test; Mixing probabilities; Multivariate linkage; Nonstandard boundary condition; Single-factor model; Variance components ID QUANTITATIVE TRAITS; POWER; SIMULATION; PEDIGREES; QTL AB Accurate knowledge of the null distribution of hypothesis tests is important for valid application of the tests. In previous papers and software, the asymptotic null distribution of likelihood ratio tests for detecting genetic linkage in multivariate variance components models has been stated to be a mixture of chi-square distributions with binomial mixing probabilities. For variance components models under the complete pleiotropy assumption, we show by simulation and by theoretical arguments based on the geometry of the parameter space that all aspects of the previously stated asymptotic null distribution are incorrect-both the binomial mixing probabilities and the chi-square components. Correcting the null distribution gives more conservative critical values than previously stated, yielding P values that can easily be 10 times larger. The true mixing probabilities give the highest probability to the case where all variance parameters are estimated positive, and the mixing components show severe departures from chi-square distributions. Thus, the asymptotic null distribution has complex features that raise challenges for the assessment of significance of multivariate linkage findings. We propose a method to generate an asymptotic null distribution that is much faster than other empirical methods such as permutation, enabling us to obtain P values with higher precision more efficiently. C1 [Han, Summer S.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chang, Joseph T.] Yale Univ, Dept Stat, New Haven, CT 06520 USA. RP Han, SS (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM summer.han@nih.gov FU Yale Center for High Performance Computation in Biology and Biomedicine (National Institutes of Health [NIH]) [RR19895-02]; NIH [R01 DC007665] FX Yale Center for High Performance Computation in Biology and Biomedicine (National Institutes of Health [NIH] grant RR19895-02); NIH (R01 DC007665). NR 27 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2010 VL 11 IS 2 BP 226 EP 241 DI 10.1093/biostatistics/kxp054 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 564US UT WOS:000275243900004 PM 20029057 ER PT J AU Fay, MP AF Fay, Michael P. TI Confidence intervals that match Fisher's exact or Blaker's exact tests SO BIOSTATISTICS LA English DT Article DE Conditional Exact Test; Confidence Set; Fisher's Exact Test; Odds Ratio; Two-by-Two Table AB When analyzing a 2 x 2 table, the two-sided Fisher's exact test and the usual exact confidence interval (CI) for the odds ratio may give conflicting inferences; for example, the test rejects but the associated CI contains an odds ratio of 1. The problem is that the usual exact CI is the inversion of the test that rejects if either of the one-sided Fisher's exact tests rejects at half the nominal significance level. Further, the confidence set that is the inversion of the usual two-sided Fisher's exact test may not be an interval, so following Blaker (2000, Confidence curves and improved exact confidence intervals for discrete distributions. Canadian Journal of Statistics 28, 783-798), we define the "matching" interval as the smallest interval that contains the confidence set. We explore these 2 versions of Fisher's exact test as well as an exact test suggested by Blaker (2000) and provide the R package exact2 x2 which automatically assigns the appropriate matching interval to each of the 3 exact tests. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 NR 2 TC 35 Z9 36 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2010 VL 11 IS 2 BP 373 EP 374 DI 10.1093/biostatistics/kxp050 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 564US UT WOS:000275243900014 PM 19948745 ER PT J AU Ajiboye, S Sissung, TM Sharifi, N Figg, WD AF Ajiboye, Seun Sissung, Tristan M. Sharifi, Nima Figg, William D. TI More than an accessory: implications of type III transforming growth factor-beta receptor loss in prostate cancer SO BJU INTERNATIONAL LA English DT Review DE betaglycan; TGF beta III receptor; prostate cancer; testosterone ID TUMOR-SUPPRESSOR; CELL-MIGRATION; BETAGLYCAN; ACTIVINS; INHIBINS; ACTIVATION; EXPRESSION AB The type III transforming growth factor-beta receptor (TGF beta R3, betaglycan), a tumour suppressor, is the most frequently lost TGF beta pathway component. This event appears to be very important in the transition of the TGF beta pathway from having tumour-suppressor activity in early prostate tumour development, to having tumour-promoting activity in metastatic disease. Moreover, loss of the TGF beta R3 can also affect the cellular response towards testosterone, inhibin/activin, and dysregulate growth-factor pathways that mediate growth and angiogenesis. In this review we discuss how TGF beta R3 normally functions as an accessory protein in the TGF beta pathway, how its loss is related to tumour progression, and the treatment implications of TGF beta R3 loss in individuals with prostate cancer. C1 [Figg, William D.] NCI, Clin Pharmacol Program, Med Oncol Clin Res Unit, Med Oncol Branch,Ctr Canc Res, Bethesda, MD 20892 USA. [Ajiboye, Seun; Figg, William D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. [Sharifi, Nima] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hematol & Oncol, Dallas, TX USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Clin Res Unit, Med Oncol Branch,Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU National Institutes of Health, National Cancer Institute, Bethesda, MD; Prostate Cancer Foundation; Howard Hughes Medical Institute FX This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Bethesda, MD and Prostate Cancer Foundation Young Investigator Award, Howard Hughes Medical Institute Physician Scientist Early Career Award. NR 21 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2010 VL 105 IS 7 BP 913 EP 916 DI 10.1111/j.1464-410X.2009.08999.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 564HW UT WOS:000275204900007 PM 20067462 ER PT J AU Lapalombella, R Andritsos, L Liu, Q May, SE Browning, R Pham, LV Blum, KA Blum, W Ramanunni, A Raymond, CA Smith, LL Lehman, A Mo, XK Jarjoura, D Chen, CS Ford, R Rader, C Muthusamy, N Johnson, AJ Byrd, JC AF Lapalombella, Rosa Andritsos, Leslie Liu, Qing May, Sarah E. Browning, Rebekah Pham, Lan V. Blum, Kristie A. Blum, William Ramanunni, Asha Raymond, Chelsey A. Smith, Lisa L. Lehman, Amy Mo, Xiaokui Jarjoura, David Chen, Ching-Shih Ford, Richard, Jr. Rader, Christoph Muthusamy, Natarajan Johnson, Amy J. Byrd, John C. TI Lenalidomide treatment promotes CD154 expression on CLL cells and enhances production of antibodies by normal B cells through a PI3-kinase-dependent pathway SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NF-KAPPA-B; IMMUNOGLOBULIN REPLACEMENT THERAPY; DEPENDENT CELLULAR CYTOTOXICITY; CD40 LIGAND; SERUM IMMUNOGLOBULINS; MULTIPLE-MYELOMA; T-CELLS; GENE; ACTIVATION AB Chronic lymphocytic leukemia (CLL) involves a profound humoral immune defect and tumor-specific humoral tolerance that directly contribute to disease morbidity and mortality. CD154 gene therapy can reverse this immune defect, but attempts to do this pharmacologically have been unsuccessful. The immune-modulatory agent lenalidomide shows clinical activity in CLL, but its mechanism is poorly understood. Here, we demonstrate that lenalidomide induces expression of functional CD154 antigen on CLL cells both in vitro and in vivo. This occurs via enhanced CD154 transcription mediated by a Nuclear Factor of Activated T cells c1 (NFATc1)/Nuclear Factor-kappa B (NF kappa B) complex and also through phosphoinositide-3 (PI3)-kinase pathway-dependent stabilization of CD154 mRNA. Importantly, CD154-positive CLL cells upregulate BID, DR5, and p73, become sensitized to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis, and promote costimulatory activation of normal B cells to produce antibodies. In CLL patients receiving lenalidomide, similar evidence of CD154 activation is observed including BID, DR5, and p73 induction and also development of anti-ROR1 tumor-directed antibodies. Our data demonstrate that lenalidomide promotes CD154 expression on CLL cells with subsequent activation phenotype, and may therefore reverse the humoral immune defect observed in this disease. This study is registered at http://clinicaltrials.gov as NCT00466895. (Blood. 2010;115(13):2619-2629) C1 [Lapalombella, Rosa; Andritsos, Leslie; Liu, Qing; May, Sarah E.; Browning, Rebekah; Blum, Kristie A.; Blum, William; Ramanunni, Asha; Raymond, Chelsey A.; Smith, Lisa L.; Chen, Ching-Shih; Muthusamy, Natarajan; Johnson, Amy J.; Byrd, John C.] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA. [Liu, Qing] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Pham, Lan V.; Ford, Richard, Jr.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lehman, Amy; Mo, Xiaokui; Jarjoura, David] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. [Chen, Ching-Shih; Byrd, John C.] Ohio State Univ, Coll Pharm, Div Med Chem, Columbus, OH 43210 USA. [Rader, Christoph] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Byrd, JC (reprint author), B302 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM amy.johnson@osumc.edu; amy.johnson@osumc.edu RI Johnson, Amy/A-5662-2009; Blum, Kristie/E-2768-2011; Lapalombella, Rosa/C-2837-2014; Blum, William/E-2769-2011 FU Cancer and Leukemia Group B Foundation; D. Warren Brown Foundation; Leukemia & Lymphoma Society; National Cancer Institute [P50-CA140158, 1K12 CA133250, P01 CA95426, P01 CA101956] FX This work was supported by the Cancer and Leukemia Group B Foundation, D. Warren Brown Foundation, Specialized Center of Research from the Leukemia & Lymphoma Society, and P50-CA140158, 1K12 CA133250, P01 CA95426, and P01 CA101956 from the National Cancer Institute. NR 51 TC 79 Z9 80 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2010 VL 115 IS 13 BP 2619 EP 2629 DI 10.1182/blood-2009-09-242438 PG 11 WC Hematology SC Hematology GA 577DI UT WOS:000276201000011 PM 19965642 ER PT J AU Bjorklund, AT Schaffer, M Fauriat, C Ringden, O Remberger, M Hammarstedt, C Barrett, AJ Ljungman, P Ljunggren, HG Malmberg, KJ AF Bjorklund, Andreas T. Schaffer, Marie Fauriat, Cyril Ringden, Olle Remberger, Mats Hammarstedt, Christina Barrett, A. John Ljungman, Per Ljunggren, Hans-Gustaf Malmberg, Karl-Johan TI NK cells expressing inhibitory KIR for non-self-ligands remain tolerant in HLA-matched sibling stem cell transplantation SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; UNRELATED DONOR TRANSPLANTATION; MHC CLASS-I; MISSING SELF; HEMATOPOIETIC TRANSPLANTS; RECEPTOR REPERTOIRE; PERIPHERAL-BLOOD; INCOMPATIBILITY; RECONSTITUTION; MOLECULES AB Natural killer (NK)-cell alloreactivity in recipients of hematopoietic stem cell grafts from HLA-identical siblings is intriguing and has suggested breaking of NK-cell tolerance during the posttransplantation period. To examine this possibility, we analyzed clinical outcomes in a cohort of 105 patients with myeloid malignancies who received T cell-replete grafts from HLA-matched sibling donors. Presence of inhibitory killer cell immunoglobulin-like receptors (KIRs) for nonself HLA class I ligands had no effect on disease-free survival, incidence of relapse, or graft-versus-host disease. A longitudinal analysis of the NK-cell repertoire and function revealed a global hyporesponsiveness of NK cells early after transplantation. Functional responses recovered at approximately 6 months after transplantation. Importantly, NKG2A(-) NK cells expressing KIRs for nonself HLA class I ligands remained tolerant at all time points. Furthermore, a direct comparison of NK-cell reconstitution in T cell-replete and T cell-depleted HLA-matched sibling stem cell transplantation (SCT) revealed that NKG2A(+) NK cells dominated the functional repertoire early after transplantation, with intact tolerance of NKG2A(-) NK cells expressing KIRs for nonself ligands in both settings. Our results provide evidence against the emergence of alloreactive NK cells in HLA-identical allogeneic SCT. (Blood. 2010;115(13):2686-2694) C1 [Bjorklund, Andreas T.; Fauriat, Cyril; Hammarstedt, Christina; Ljunggren, Hans-Gustaf; Malmberg, Karl-Johan] Karolinska Univ Hosp, Karolinska Inst, Dept Med, CIM, S-14186 Stockholm, Sweden. [Bjorklund, Andreas T.; Ljungman, Per; Malmberg, Karl-Johan] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Ctr Hematol, S-14186 Stockholm, Sweden. [Schaffer, Marie; Ringden, Olle; Remberger, Mats] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Div Clin Immunol, S-14186 Stockholm, Sweden. [Fauriat, Cyril] Univ Aix Marseille 2, INSERM, Ctr Immunol Marseille Luminy, U631, Marseille, France. [Ringden, Olle; Remberger, Mats] Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Ctr Allogene Stem Cell Transplantat, S-14186 Stockholm, Sweden. [Barrett, A. John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Malmberg, KJ (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Med, CIM, F59, S-14186 Stockholm, Sweden. EM kalle.malmberg@ki.se RI Fauriat, Cyril/D-4285-2017; OI Malmberg, Karl-Johan/0000-0002-8718-9373 FU Swedish Foundation for Strategic Research; Swedish Research Council; Swedish Cancer Society; Swedish Children's Cancer Foundation; Cancer Society of Stockholm; Royal Swedish Academy of Sciences; Tobias Foundation; Soderberg Foundation; Belven Foundation; Ake Wiberg Foundation; Stockholm County Council; Karolinska Institutet FX This work was supported by grants from the Swedish Foundation for Strategic Research, the Swedish Research Council, the Swedish Cancer Society, the Swedish Children's Cancer Foundation, the Cancer Society of Stockholm, the Royal Swedish Academy of Sciences, the Tobias Foundation, the Soderberg Foundation, The Belven Foundation, the Ake Wiberg Foundation, an ALF-project grant from the Stockholm County Council, and the Karolinska Institutet. NR 34 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2010 VL 115 IS 13 BP 2686 EP 2694 DI 10.1182/blood-2009-07-229740 PG 9 WC Hematology SC Hematology GA 577DI UT WOS:000276201000019 PM 20097883 ER PT J AU Morales, J Villa, K Gattis, J Castro, W Colon, K Lubkowski, J Sanabria, P Hunter, R Washington, AV AF Morales, Jessica Villa, Karina Gattis, Jim Castro, William Colon, Katiria Lubkowski, Jacek Sanabria, Priscilla Hunter, Robert Washington, A. Valance TI Soluble TLT-1 modulates platelet-endothelial cell interactions and actin polymerization SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE alpha-granules; actin polymerization; adhesion; endothelium; platelets; P-selectin; soluble triggering receptor expressed on myeloid cells like transcript-1; triggering receptor expressed on myeloid cells; triggering receptor expressed on myeloid cells-1; triggering receptor expressed on myeloid cells like transcript-1 ID TREM; INFLAMMATION; MICROPARTICLES; AGGREGATION; HEMORRHAGE; THROMBOSIS; RESPONSES; ADHESION; RECEPTOR; SEPSIS AB Triggering receptor expressed on myeloid cells (TREM) like transcript-1 (TLT-1) is a membrane protein receptor found in alpha-granules of platelets and megakaryocytes. Upon platelet activation TLT-1 is rapidly brought to the surface of platelets. Recently, we demonstrated that activated platelets release a soluble form of TLT-1 (sTLT-1) that is found in serum but not in the plasma of healthy individuals and can enhance platelet aggregation in vitro. Furthermore, evaluation of patients diagnosed with inflammatory diseases, such as sepsis, show that these patients have significantly elevated levels of sTLT-1 in their blood. Accordingly, mice deficient in TLT-1 are predisposed to bleeding in response to an inflammatory challenge; however, the mechanism of TLT-1 function remains unknown. In this investigation, we demonstrate an increase in the amount of platelets that adhere to endothelial cell monolayers in the presence of recombinant sTLT-1 (rsTLT-1). Additionally, we present evidence that rsTLT-1 increases platelet adherence to glass slides by stimulating actin polymerization in platelets, as determined by increased staining of rodamine phalloidin. These results suggest that during inflammation, sTLT-1 may mediate hemostasis by enhancing actin polymerization, resulting in increased platelet aggregation and adherence to the endothelium. Blood Coagul Fibrinolysis 21:229-236 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Morales, Jessica; Gattis, Jim; Castro, William; Washington, A. Valance] Univ Cent Caribe, Lab Anat & Cell Biol, Bayamon, PR USA. [Villa, Karina; Hunter, Robert] Univ Cent Caribe, Sch Med, Ctr Retrovirus Res, Bayamon, PR USA. [Lubkowski, Jacek] NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21701 USA. [Colon, Katiria; Sanabria, Priscilla] Univ Cent Caribe, Dept Physiol, Bayamon, PR USA. [Washington, A. Valance] Univ Puerto Rico Mayaguez, Dept Biol, Mayaguez, PR USA. RP Washington, AV (reprint author), Univ Puerto Rico Mayaguez, Dept Biol, POB 60327, Bayamon, PR 00681 USA. EM valancew@gmail.com RI Rinaldi2, Carlos/D-4479-2011 FU NIH; National Cancer Institute; Center for Cancer Research; National Center for Research Resources (NCRR) [2G12RR3035]; National Institute of General Medical Sciences [SC2GM081237]; Aniara Corp; [N01-Co-12400] FX The authors would like to thank the staff of the Protein and Nucleic Acid and Optical Imaging Facilities at Universidad Central del Caribe. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and under contract N01-Co-12400. Additional funding was obtained through grants from the National Center for Research Resources (NCRR), a component of the NIH (2G12RR3035), the National Institute of General Medical Sciences (SC2GM081237), and the Aniara Corp. The content of this publication neither necessarily reflects 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 NIH or the United States government. NR 26 TC 6 Z9 8 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD APR PY 2010 VL 21 IS 3 BP 229 EP 236 DI 10.1097/MBC.0b013e3283358116 PG 8 WC Hematology SC Hematology GA 585OY UT WOS:000276836900005 PM 20093931 ER PT J AU Pedone, C Napoli, N Pozzilli, P Lauretani, F Bandinelli, S Ferrucci, L Antonelli-Incalzi, R AF Pedone, Claudio Napoli, Nicola Pozzilli, Paolo Lauretani, Fulvio Bandinelli, Stefania Ferrucci, Luigi Antonelli-Incalzi, Raffaele TI Quality of diet and potential renal acid load as risk factors for reduced bone density in elderly women SO BONE LA English DT Article DE Bone mineral density; Potential renal acid load; Aged; Women; Nutrition ID PHYSICAL-ACTIVITY; MINERAL DENSITY; PROTEIN; CALCIUM; ADULTS; OLDER; NUTRITION; ASSOCIATION; POPULATIONS; ULTRASOUND AB Background: Bone mineral density (BMD) may be influenced by the general dietary pattern and the potential renal acid load (PRAL). Methods: We compared the dietary intake (estimated using the European Prospective Investigation into Cancer and nutrition questionnaire) of 497 community-living women (60 years of age and older) grouped according to tertiles of baseline total, trabecular and cortical BMD estimated using tibial peripheral quantitative computed tomography (pQCT), and of BMD variation over 6 years. Results: None of the nutrients taken into account nor PRAL was associated with total BMD, with the exception that the intake of polyunsaturated fatty acids (PUFA) was slightly higher among women with the highest total BMD. Similar results were found for trabecular BMD. Cortical BMD was associated with serum 25-OH vitamin D (38.8, 43.2, and 49.5 nmol/L in the first, second, and third tertiles, respectively; P = 0.042). In the longitudinal analysis, a lower BMI was associated with greater loss of total BMD, while lower serum 25-OH vitamin D at baseline was associated with smaller loss of cortical BMD. Conclusions: We found no relationship between dietary acid load and BMD. We also confirmed the role of well-recognized risk factor for osteoporosis. (C) 2009 Elsevier Inc. All rights reserved. C1 [Pedone, Claudio; Antonelli-Incalzi, Raffaele] Univ Campus Biomed, Area Geriatria, I-00128 Rome, Italy. [Pedone, Claudio; Napoli, Nicola; Pozzilli, Paolo] Fdn Alberto Sordi Onlus, Rome, Italy. [Napoli, Nicola; Pozzilli, Paolo] Univ Campus Biomed, Area Endocrinol & Malattie Metab, I-00128 Rome, Italy. [Lauretani, Fulvio] Tuscany Reg Hlth Agcy, Florence, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Antonelli-Incalzi, Raffaele] Fdn San Raffaele Cittadella Carita, Taranto, Italy. RP Pedone, C (reprint author), Univ Campus Biomed, Area Geriatria, Via Alvaro Portillo 21, I-00128 Rome, Italy. EM c.pedone@unicampus.it RI Pedone, Claudio/F-9488-2010; Antonelli Incalzi, Raffaele/G-3978-2012; Lauretani, Fulvio/K-5115-2016; OI Pedone, Claudio/0000-0003-1847-9032; Antonelli Incalzi, Raffaele/0000-0003-2100-2075; Lauretani, Fulvio/0000-0002-5287-9972; Napoli, Nicola/0000-0002-3091-8205 FU NIA NIH HHS [N01 AG916413] NR 29 TC 15 Z9 15 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2010 VL 46 IS 4 BP 1063 EP 1067 DI 10.1016/j.bone.2009.11.031 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 574RD UT WOS:000276009400028 PM 20005315 ER PT J AU Meguro, A Ozaki, K Oh, I Hatanaka, K Matsu, H Tatara, R Sato, K Leonard, WJ Ozawa, K AF Meguro, A. Ozaki, K. Oh, I. Hatanaka, K. Matsu, H. Tatara, R. Sato, K. Leonard, W. J. Ozawa, K. TI IL-21 is critical for GVHD in a mouse model SO BONE MARROW TRANSPLANTATION LA English DT Article DE GVHD; IL-21; hematopoietic SCT ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CELL-DIFFERENTIATION; CYTOKINE RECEPTOR; T-CELLS; INTERLEUKIN-21; MICE; IMMUNODEFICIENCY; ACTIVATION; MECHANISMS AB Immunological effects of IL-21 on T, B and natural killer (NK) cells have been reported, but the role of IL-21 in GVHD remains obscure. Here, we demonstrate that morbidity and mortality of GVHD was signi. cantly reduced after BMT with splenocytes from IL-21R(-/-) mice compared with those from wild type mice. To further con. rm our observation, we generated a decoy receptor for IL-21. GVHD was again less severe in mice receiving BM cells transduced with the IL-21 decoy receptor than control mice These results suggest that IL-21 critically regulates GVHD, and that blockade of the IL-21 signal may represent a novel strategy for the prophylaxis for GVHD. Bone Marrow Transplantation (2010) 45, 723-729; doi:10.1038/bmt.2009.223; published online 31 August 2009 C1 [Meguro, A.; Ozaki, K.; Oh, I.; Hatanaka, K.; Matsu, H.; Tatara, R.; Sato, K.; Ozawa, K.] Jichi Med Univ, Dept Med, Div Hematol, Shimotsuke, Tochigi 3290498, Japan. [Leonard, W. J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Ozaki, K (reprint author), Jichi Med Univ, Dept Med, Div Hematol, 3311-1 Yakushiji, Shimotsuke, Tochigi 3290498, Japan. EM ozakikat@jichi.ac.jp FU Ministry of Health, Labor and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan; Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health (Bethesda, MD, USA),; Jichi Medical University, Tochigi, Japan FX We thank Dr Kitamura (Institute of Medical Science, University of Tokyo, Tokyo) for donating PLAT-E, a packaging cell line. This work was supported in part by grants from the Ministry of Health, Labor and Welfare of Japan, by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health (Bethesda, MD, USA), and by an Intramural Research Grant from Jichi Medical University, Tochigi, Japan. NR 26 TC 13 Z9 16 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2010 VL 45 IS 4 BP 723 EP 729 DI 10.1038/bmt.2009.223 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 579ME UT WOS:000276373900017 PM 19718060 ER PT J AU Mitchell, SA Leidy, NK Mooney, KH Dudley, WN Beck, SL LaStayo, PC Cowen, EW Palit, P Comis, LE Krumlauf, MC Avila, DN Atlam, N Fowler, DH Pavletic, SZ AF Mitchell, S. A. Leidy, N. Kline Mooney, K. H. Dudley, W. N. Beck, S. L. LaStayo, P. C. Cowen, E. W. Palit, P. Comis, L. E. Krumlauf, M. C. Avila, D. N. Atlam, N. Fowler, D. H. Pavletic, S. Z. TI Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD) SO BONE MARROW TRANSPLANTATION LA English DT Article DE functional status; chronic graft-versus-host disease; symptoms; survivorship; late effects; allogeneic hematopoietic stem cell transplantation ID QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; HEALTH SURVEY SF-36; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; 2-MINUTE WALK TEST; MYELOID-LEUKEMIA; SYMPTOM EXPERIENCE; COMORBIDITY INDEX; PHYSICAL FUNCTION AB This study examined factors accounting for functional performance limitations in 100 long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Functional performance, measured by the SF-36 physical component summary score, was substantially lower (mean = 36.8 +/- 10.7) than the US population norm of 50 (P < 0.001). The most severe decrements were in physical function (mean = 38.8 +/- 10.9) and physical role function (mean = 37.88 +/- 11.88); 68% of respondents exceeded the five-point threshold of minimum clinically important difference below the norm on these subscales. Controlling for age and gender, six variables explained 56% of the variance in functional performance: time since cGVHD diagnosis, cGVHD severity, intensity of immunosuppression, comorbidity, functional capacity (distance walked in 2min, grip strength, and range of motion), and cGVHD symptom bother (F = 11.26; P < 0.001). Significant independent predictors of impaired performance were intensive systemic immunosuppression, reduced capacity for ambulation, and greater cGVHD symptom bother (P < 0.05). Symptom bother had a direct effect on functional performance, as well as an indirect effect partially mediated by functional capacity (Sobel test, P = 0.004). Results suggest two possible mechanisms underlying impaired functional performance in survivors with cGVHD and underscore the importance of testing interventions to enhance functional capacity and reduce symptom bother. Bone Marrow Transplantation (2010) 45, 762-769; doi:10.1038/bmt.2009.238; published online 28 September 2009 C1 [Mitchell, S. A.; Palit, P.; Krumlauf, M. C.] NIH, Ctr Clin, Rockville, MD 20852 USA. [Leidy, N. Kline] United BioSource Ctr Hlth Outcomes Res Corp, Sci Affairs, Bethesda, MD USA. [Mooney, K. H.; Beck, S. L.] Univ Utah, Coll Nursing, Salt Lake City, UT 84112 USA. [Dudley, W. N.] Univ N Carolina, Sch Hlth & Human Performance, Greensboro, NC 27412 USA. [LaStayo, P. C.] Univ Utah, Dept Phys Therapy, Salt Lake City, UT USA. [Cowen, E. W.] NCI, Dermatol Branch, Bethesda, MD 20892 USA. [Comis, L. E.] NIH, Ctr Clin, Bethesda, MD USA. [Avila, D. N.; Fowler, D. H.; Pavletic, S. Z.] NCI, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA. [Atlam, N.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Mitchell, SA (reprint author), NIH, Ctr Clin, Room 2B11,10 Ctr Dr, Rockville, MD 20852 USA. EM mitchlls@mail.nih.gov FU National Institutes of Health; Clinical Center; Nursing and Patient Care Services FX We gratefully acknowledge Marjorie Pett, PhD, MSW, University of Utah College of Nursing, and N Lynn Gerber, MD, George Mason University, for advice and valuable critique of an early version of this manuscript, and Li Li, MD, National Institutes of Health, Clinical Center, Department of Rehabilitation Medicine, for assistance in obtaining the measures of functional capacity. The investigators wish to acknowledge all members of the National Institutes of Health cGVHD Clinic and Study Group, Bethesda, MD, for their expert care of these study participants and for assistance with data collection. We thank the two anonymous journal reviewers for their helpful critique. This work was supported by the National Institutes of Health, Clinical Center, Nursing and Patient Care Services. NR 52 TC 43 Z9 46 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2010 VL 45 IS 4 BP 762 EP 769 DI 10.1038/bmt.2009.238 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 579ME UT WOS:000276373900022 PM 19784078 ER PT J AU Luo, JF Gao, YT Chow, WH Shu, XO Li, HL Yang, G Cai, QY Rothman, N Cai, H Shrubsole, MJ Franke, AA Zheng, W Dai, Q AF Luo, Jianfeng Gao, Yu-Tang Chow, Wong-Ho Shu, Xiao-Ou Li, Honglan Yang, Gong Cai, Qiuyin Rothman, Nathaniel Cai, Hui Shrubsole, Martha J. Franke, Adrian A. Zheng, Wei Dai, Qi TI Urinary polyphenols and breast cancer risk: results from the Shanghai Women's Health Study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Urinary polyphenols; Flavanols; Flavonols ID CATECHOL-O-METHYLTRANSFERASE; ASIAN-AMERICAN WOMEN; GREEN TEA; CHINESE WOMEN; GENETIC POLYMORPHISMS; BLACK TEA; FLAVONOID INTAKE; FOOD SOURCES; EXCRETION; MECHANISMS AB Polyphenols, the most abundant dietary antioxidants, also possess many other anticarcinogenic activities. Urinary metabolites of polyphenols could complement dietary assessment of the bioavailability of these nutrients. We conducted a study of 353 incident breast cancer cases and 701 individually matched controls nested within the Shanghai Women's Health Study cohort of women aged 40-70 years at baseline. Liquid chromatography photo-diode array electrospray mass spectrometry was used to measure tea polyphenols (epicatechin, epigallocatechin, and their metabolites) and flavonols (e.g., quercetin and kaempferol). Multivariate conditional logistic regression analyses were used to assess associations between breast cancer risk and urinary excretion rates of polyphenols. Urinary excretion of tea polyphenols increased with increasing tea leaves consumed among controls, but not among breast cancer cases. Compared with cases, controls had higher levels of urinary total polyphenols and tea polyphenols, particularly epicatechin. In contrast, we did not find any dose-response relationship between urinary polyphenols and breast cancer risk. Urinary excretion of epicatechin was inversely associated with breast cancer risk [odds ratio (OR) and 95% confidence interval (CI) of 0.59 (0.39-0.88) for the intermediate tertile]. In spline regression, we found an overall dose-response relationship between epicatechin level and risk of breast cancer, although it was not apparent in low and middle urinary excretion range. In conclusion, high epicatechin may be related to a reduced risk of breast cancer. Further studies are warranted to confirm our findings. C1 [Luo, Jianfeng; Shu, Xiao-Ou; Yang, Gong; Cai, Qiuyin; Cai, Hui; Shrubsole, Martha J.; Zheng, Wei; Dai, Qi] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Inst Med & Publ Hlth,Dept Med,Sch Med, Nashville, TN 37203 USA. [Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Gao, Yu-Tang; Li, Honglan] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Franke, Adrian A.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Luo, Jianfeng] Fudan Univ, Sch Publ Hlth, Dept Hlth Stat & Social Med, Shanghai 200032, Peoples R China. RP Dai, Q (reprint author), Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Vanderbilt Ingram Canc Ctr, Inst Med & Publ Hlth,Dept Med,Sch Med, 6th Floor,Suite 600,2525 W End Ave, Nashville, TN 37203 USA. EM qi.dai@vanderbilt.edu RI Shrubsole, Martha/K-5052-2015 OI Shrubsole, Martha/0000-0002-5591-7575 FU NIH [S10 RR020890-01, N02 CP1101066]; USPHS [R01CA106591, R01CA70867] FX The authors would like to thank the study participants. The authors also thank Laurie Custer for the skillful performance of LC/MS assays. We acknowledge the support by NIH grant S10 RR020890-01. Sources of support: This study was supported by USPHS grant R01CA106591 as well as USPHS grant R01CA70867 and NIH intramural program (N02 CP1101066) for the parent study. NR 65 TC 16 Z9 19 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD APR PY 2010 VL 120 IS 3 BP 693 EP 702 DI 10.1007/s10549-009-0487-x PG 10 WC Oncology SC Oncology GA 571LH UT WOS:000275752800017 PM 19653095 ER PT J AU Miller, TW Isenberg, JS Roberts, DD AF Miller, Thomas W. Isenberg, Jeff S. Roberts, David D. TI Thrombospondin-1 is an inhibitor of pharmacological activation of soluble guanylate cyclase SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE thrombospondin-1; CD47; soluble guanylate cyclase; nitric oxide; cardiovascular disease ID SMOOTH-MUSCLE RELAXATION; ISCHEMIC TISSUE SURVIVAL; NITRIC-OXIDE; CELL RESPONSES; SODIUM-NITROPRUSSIDE; PLATELET-AGGREGATION; BOVINE LUNG; CD47; BINDING; HEME AB Background and purpose: Soluble guanylate cyclase (sGC) is the signal transduction enzyme most responsible for mediating the effects of nitric oxide (NO). Recently, NO-independent small molecule activators of sGC have been developed that have promising clinical activities. We have shown that the secreted matrix protein thrombospondin-1 (TSP-1) binds to CD47 and potently inhibits NO stimulation of sGC in endothelial and vascular smooth muscle cells (VSMCs) and platelets. Here we show that TSP-1 signalling via CD47 inhibits sGC activation by NO-independent sGC activating small molecules. Experimental approach: Vascular smooth muscle cells and washed human platelets were pretreated with TSP-1 (2.2 nM) in the presence of haeme-dependent sGC activators (YC-1, BAY 41-2272), and a haeme-independent activator (meso-porphyrin IX), and cGMP levels were measured. The effect of sGC activators on platelet aggregation and contraction of VSMC embedded in collagen gels was also assayed in the presence and absence of TSP-1. Key results: Thrombospondin-1 inhibited sGC activator-dependent increase in cGMP in VSMC and platelets. TSP-1 pretreatment also inhibited the ability of these agents to delay thrombin-induced platelet aggregation. TSP-1 pretreatment reduced the ability of sGC activating agents to abrogate VSMC contraction in vitro. Conclusions and implications: This work demonstrates that TSP-1 is a universal inhibitor of sGC, blocking both haeme-dependent and haeme-independent activation. These data coupled with the reported increases in TSP-1 with age, diabetes, ischaemia/reperfusion, and atherosclerosis implies that the therapeutic potential of all drugs that activate sGC could be compromised in disease states where TSP-1/CD47 signalling is elevated. C1 [Miller, Thomas W.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Isenberg, Jeff S.] Univ Pittsburgh, Dept Med, Vasc Med Inst, Pittsburgh, PA USA. [Isenberg, Jeff S.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011 OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785 FU NIH/NCI; [K22 CA128616] FX The authors would like to thank Conor S. Norris for helpful discussions regarding this work. This work was supported by Intramural Research Program of the NIH/NCI (D.D.R.) and K22 CA128616 (J.S.I.). NR 47 TC 29 Z9 29 U1 1 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 2010 VL 159 IS 7 BP 1542 EP 1547 DI 10.1111/j.1476-5381.2009.00631.x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 572YK UT WOS:000275873700017 PM 20233213 ER PT J AU Gomez-Acevedo, H Li, MY Jacobson, S AF Gomez-Acevedo, Horacio Li, Michael Y. Jacobson, Steven TI Multistability in a Model for CTL Response to HTLV-I Infection and Its Implications to HAM/TSP Development and Prevention SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE HTLV-I; HAM/TSP; CD4 T cells; CD8 T cells; Global dynamics; Lyapunov functions ID CELL LEUKEMIA-VIRUS; TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; CD8(+) T-CELLS; PERIPHERAL-BLOOD; CEREBROSPINAL-FLUID; IMMUNE-RESPONSE; PROVIRAL DNA; DYNAMICS; MYELOPATHY AB Human T-cell leukaemia/lymphoma virus type I (HTLV-I) is a retrovirus that has been identified as the causative agent of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other illnesses. HTLV-I infects primarily CD4(+) T cells and the transmission occurs through direct cell-to-cell contact. HAM/TSP patients harbor higher proviral loads in peripheral blood lymphocytes than asymptomatic carriers. Also, HAM/TSP patients exhibit a remarkably high number of circulating HTLV-I-specific CD8(+) cytotoxic T lymphocytes (CTLs) in the peripheral blood. While CTLs have a protective role by killing the infected cells and lowering the proviral load, a high level of CTLs and their cytotoxicity are believed to be a main cause of the development of HAM/TSP. A mathematical model for HTLV-I infection of CD4(+) T cells that incorporates the CD8(+) cytotoxic T-cell (CTL) response is investigated. Our mathematical analysis reveals that the system can stabilize at a carrier steady-state with persistent viral infection but no CTL response, or at a HAM/TSP steady-state at which both the viral infection and CTL response are persistent. We also establish two threshold parameters R (0) and R (1), the basic reproduction numbers for viral persistence and for CTL response, respectively. We show that the parameter R (1) can be used to distinguish asymptomatic carriers from HAM/TSP patients, and as an important control parameter for preventing the development of HAM/TSP. C1 [Li, Michael Y.] Univ Alberta, Dept Math & Stat Sci, Edmonton, AB T6G 2G1, Canada. [Gomez-Acevedo, Horacio] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. [Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Li, MY (reprint author), Univ Alberta, Dept Math & Stat Sci, Edmonton, AB T6G 2G1, Canada. EM mli@math.ualberta.ca RI Li, Michael/G-3628-2013 FU Intramural NIH HHS [Z01 NS003040-01, Z01 NS002817-19, Z01 NS002817-18] NR 35 TC 19 Z9 20 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD APR PY 2010 VL 72 IS 3 BP 681 EP 696 DI 10.1007/s11538-009-9465-z PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 571WO UT WOS:000275786900007 PM 20041353 ER PT J AU Hayashi, Y Lagarde, F Tsuda, N Funamoto, S Preston, DL Koyama, K Mabuchi, K Ron, E Kodama, K Tokuoka, S AF Hayashi, Yuzo Lagarde, Frederic Tsuda, Nobuo Funamoto, Sachiyo Preston, Dale L. Koyama, Kojiro Mabuchi, Kiyohiko Ron, Elaine Kodama, Kazunori Tokuoka, Shoji TI Papillary Microcarcinoma of the Thyroid Among Atomic Bomb Survivors Tumor Characteristics and Radiation Risk SO CANCER LA English DT Article DE thyroid; papillary microcarcinoma; atomic bombs; radiation ID CANCER INCIDENCE; INCREASING INCIDENCE; IONIZING-RADIATION; BREAST-CANCER; SOLID CANCER; CARCINOMA; HIROSHIMA; NAGASAKI; AUTOPSY; PREVALENCE AB BACKGROUND: Radiation exposure is an established cause of clinical thyroid cancer, but little is known about radiation effects on papillary microcarcinoma (PMC) of the thyroid, a relatively common subclinical thyroid malignancy. Because the incidence of these small thyroid cancers has been increasing, it is important to better understand them and their relation to radiation. METHODS: PMCs were identified in a subset of 7659 members of the Life Span Study of atomic bomb survivors who had archived autopsy or surgical materials. We conducted a pathology review of these specimens and evaluated the histological features of the tumors and the association between PMCs and thyroid radiation dose. RESULTS: From 1958 to 1995, 458 PMCs were detected among 313 study subjects. The majority of cancers exhibited pathologic features of papillary thyroid cancers. Overall, 81% of the PMCs were of the sclerosing variant and 91% were nonencapsulated, psammoma bodies that occurred in 13% and calcification was observed in 23%. Over 95% had papillary or papillary-follicular architecture and most displayed nuclear overlap, clear nuclei, and nuclear grooves. Several of these features increased with increasing tumor size, but no association was found with radiation dose. A significant radiation-dose response was found for the prevalence of PMCs (estimated excess odds ratio/Gy = 0.57; 95% confidence interval, 0.01-1.55), with the excess risk observed primarily among women. CONCLUSIONS: Exposure to low-to-moderate doses of ionizing radiation appears to increase the risk of thyroid PMCs, even when exposure occurs during adulthood. Cancer 2010;116:1646-55. (C) 2010 American Cancer Society C1 [Tokuoka, Shoji] Radiat Effects Res Fdn, Minami Ku, Hiroshima 7320815, Japan. [Hayashi, Yuzo] Hiroshima Asa Citizens Hosp, Dept Pathol, Hiroshima, Japan. [Lagarde, Frederic; Funamoto, Sachiyo] Radiat Effects Res Fdn, Dept Stat, Hiroshima 7320815, Japan. [Tsuda, Nobuo] Nagasaki Gen Hlth Ctr, Dept Pathol, Nagasaki, Japan. [Preston, Dale L.] Hirosoft Int, Eureka, CA USA. [Koyama, Kojiro] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 7320815, Japan. [Mabuchi, Kiyohiko; Ron, Elaine] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tokuoka, S (reprint author), Radiat Effects Res Fdn, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM tokuoka@rerf.or.jp FU RERF Research Protocol [RP 6-91]; GNCI [NO1-CP-31, 012-66]; NIH, NCI, Division of Cancer Epidemiology and Genetics FX Sources of support: RERF Research Protocol RP 6-91; GNCI contact number NO1-CP-31, 012-66; Intramural Research Program of the NIH, NCI, Division of Cancer Epidemiology and Genetics. NR 39 TC 10 Z9 13 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1646 EP 1655 DI 10.1002/cncr.24872 PG 10 WC Oncology SC Oncology GA 574IV UT WOS:000275983500006 PM 20120034 ER PT J AU Ogbureke, KUE Abdelsayed, RA Kushner, H Li, L Fisher, LW AF Ogbureke, Kalu U. E. Abdelsayed, Rafik A. Kushner, Harvey Li, Li Fisher, Larry W. TI Two Members of the SIBLING Family of Proteins, DSPP and BSP, May Predict the Transition of Oral Epithelial Dysplasia to Oral Squamous Cell Carcinoma SO CANCER LA English DT Article DE SIBLINGs; oral cancer; oral premalignant lesions; dysplasia; biomarkers; BSP; DSPP; OPN; transition ID MALIGNANT-TRANSFORMATION; PREMALIGNANT LESIONS; NATURAL-HISTORY; LEUKOPLAKIA; EXPRESSION; CANCER; CAVITY; DIAGNOSIS; MMPS AB BACKGROUND: Patients with oral premalignant lesions (OPL) present with oral squamous cell carcinomas (OSCC) at a much higher rate than the general population. There are currently no useful markers that indicate specifically which OPLs are most likely to progress. Three small integrin binding ligands N-linked glycoprotein (SIBLING) family proteins, bone sialoprotein (BSP), osteopontin (OPN), and dentin sialophosphoprotein (DSPP), have been shown to be up-regulated in many cancers, including OSCC. The status of SIBLING expression in OPLs and their correlation to transition to oral cancer are unknown. METHODS: Sixty archival surgical biopsies of dysplastic OPLs were evaluated by immunohistochemistry for expression of BSP, DSPP, and OPN and correlated with local transformation to OSCC at sites adjacent to surgically removed dysplastic OPL. RESULTS: The OPL patient population was representative of previous studies with 20% progressing to OSCC, and no correlation between degree of dysplasia and progression. Eighty-seven percent were positive for at least 1 SIBLING protein. OPN expression had no correlation with progression. The BSP+/DSPP- expression pattern however correlated with decreased transformation to OSCC (point prevalence = 0%; 95% confidence interval [CI], 0-20.6), whereas the BSP-/DSPP+ pattern was associated with more frequent progression (point prevalence = 77.8%; 95%CI, 47.8-95.4). Incrementally higher expression scores (0 to 3) of BSP and DSPP were also associated with increased predictive values (odds ratio, 25.53; 95% CI, 2.14-304.7 and 10.13; 95% CI, 2.0-50.0, respectively, for each increment). CONCLUSIONS: BSP and DSPP are excellent candidate markers for successful OPL surgical intervention and may be predictors of OPL-OSCC progression. Cancer 2010;116:1709-17. (C) 2010 American Cancer Society. C1 [Ogbureke, Kalu U. E.; Abdelsayed, Rafik A.] Med Coll Georgia, Sch Dent, Augusta, GA 30912 USA. [Kushner, Harvey] BioMed Comp Res Inst, Philadelphia, PA USA. [Li, Li; Fisher, Larry W.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Ogbureke, KUE (reprint author), Med Coll Georgia, Sch Dent, 1120 15th St, Augusta, GA 30912 USA. EM kogbureke@mail.mcg.edu FU NIH [K23DE017791-01A1]; MCGRI [STP00105W005]; Wendy Will Cancer Fund; NIH, NIDCR FX NIH grant no. K23DE017791-01A1 (KUO); MCGRI grant no. STP00105W005 (KUO); Wendy Will Cancer Fund (KUO). This research was supported in part by the Intramural Research Program of the NIH, NIDCR (LWF). NR 30 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1709 EP 1717 DI 10.1002/cncr.24938 PG 9 WC Oncology SC Oncology GA 574IV UT WOS:000275983500013 PM 20186700 ER PT J AU Iwamoto, FM Kreisl, TN Kim, L Duic, JP Butman, JA Albert, PS Fine, HA AF Iwamoto, Fabio M. Kreisl, Teri N. Kim, Lyndon Duic, J. Paul Butman, John A. Albert, Paul S. Fine, Howard A. TI Phase 2 Trial of Talampanel, a Glutamate Receptor Inhibitor, for Adults With Recurrent Malignant Gliomas SO CANCER LA English DT Article DE glioma; glioblastoma; talampanel; glutamate receptors ID PROGRESSION-FREE SURVIVAL; PRIMARY BRAIN-TUMORS; HUMAN GLIOBLASTOMA; CELL-LINES; II TRIAL; GROWTH; EXPRESSION; PROLIFERATION; TEMOZOLOMIDE; APOPTOSIS AB BACKGROUND: Glioma cells secrete glutamate and also express alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionate (AMPA) glutamate receptors, which contribute to the proliferation, migration, and neurotoxicity of malignant gliomas. Talampanel is an oral AMPA receptor inhibitor with excellent central nervous system penetration and good tolerability in clinical trials for epilepsy and other neurologic disorders. METHODS: A phase 2 trial was conducted to evaluate the efficacy of talampanel in patients with recurrent malignant glioma as measured by 6-month progression-free survival (PFS6). RESULTS: Thirty patients (22 with glioblastomas [GBMs] and 8 with anaplastic gliomas [AGs]; 63% men) with median age of 51 years (range, 20-67 years) and a median Karnofsky performance scale of 80 were included. Patients tolerated treatment well, and most adverse events were mild and reversible; the most common toxicities were fatigue (27%), dizziness (23%), and ataxia (17%). There was only 1 partial response (5%) reported in the GBM stratum and none among AG patients. At a median follow-up of 13 months, 28 patients (93%) had died. The PFS6 was 4.6% for the initial 22 GBM patients, and the study was terminated early due to treatment futility; the PFS6 was 0% for 8 AG patients. The median PFS was 5.9 weeks for GBM and 8.9 weeks for AG patients. The median overall survival was 13 weeks for GBM patients and 14 months for AG patients. CONCLUSIONS: Talampanel was well-tolerated but had no significant activity as a single agent in unselected recurrent malignant gliomas. Cancer 2010;116:1776-82. Published 2010 by the American Cancer Society C1 [Iwamoto, Fabio M.; Kreisl, Teri N.; Kim, Lyndon; Duic, J. Paul; Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Albert, Paul S.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd,Bloch Bldg 82,Room 225, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov RI Butman, John/A-2694-2008; Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS [Z99 CA999999, ZID BC011098-02] NR 31 TC 39 Z9 39 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2010 VL 116 IS 7 BP 1776 EP 1782 DI 10.1002/cncr.24957 PG 7 WC Oncology SC Oncology GA 574IV UT WOS:000275983500021 PM 20143438 ER PT J AU de Kluyver, RL Sayers, TJ AF de Kluyver, Rachel L. Sayers, Thomas J. TI Breast cancer bone metastases Combination therapy targeting cancer cells and the tumor microenvironment SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE RANKL; Apo2L/TRAIL; breast cancer; bone metastases; osteolysis; apoptosis ID DIFFERENTIATION; CHEMOTHERAPY; INVOLVEMENT; APOPTOSIS; SIGNALS; LINES C1 [de Kluyver, Rachel L.; Sayers, Thomas J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. [Sayers, Thomas J.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Sayers, TJ (reprint author), NCI, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD 21701 USA. RI Sayers, Thomas/G-4859-2015 FU Intramural NIH HHS NR 17 TC 2 Z9 2 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD APR 1 PY 2010 VL 9 IS 7 BP 551 EP 553 DI 10.4161/cbt.9.7.11580 PG 3 WC Oncology SC Oncology GA 645WW UT WOS:000281497900013 PM 20234180 ER PT J AU Lenters, V Basinas, I Beane-Freeman, L Boffetta, P Checkoway, H Coggon, D Portengen, L Sim, M Wouters, IM Heederik, D Vermeulen, R AF Lenters, Virissa Basinas, Ioannis Beane-Freeman, Laura Boffetta, Paolo Checkoway, Harvey Coggon, David Portengen, Lutzen Sim, Malcolm Wouters, Inge M. Heederik, Dick Vermeulen, Roel TI Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers SO CANCER CAUSES & CONTROL LA English DT Article DE Endotoxins; Textile industry; Farmers; Lung cancer; Meta-analysis ID NEW-YORK-STATE; ORGANIC DUSTS; OCCUPATIONAL-EXPOSURE; PROPORTIONATE MORTALITY; RESPONSE RELATIONSHIP; FINNISH FARMERS; FEMALE FARMERS; DECREASED RISK; UNITED-STATES; MILL WORKERS AB To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer. C1 [Lenters, Virissa; Portengen, Lutzen; Wouters, Inge M.; Heederik, Dick; Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3508 TD Utrecht, Netherlands. [Basinas, Ioannis] Aarhus Univ, Inst Publ Hlth, Dept Environm & Occupat Med, Aarhus, Denmark. [Beane-Freeman, Laura] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Checkoway, Harvey] Univ Washington, Sch Publ Hlth & Community Med, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. [Coggon, David] Univ Southampton, Epidemiol Resource Ctr, MRC, Southampton, Hants, England. [Sim, Malcolm] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia. [Heederik, Dick; Vermeulen, Roel] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. RP Vermeulen, R (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, POB 80178, NL-3508 TD Utrecht, Netherlands. EM R.C.H.Vermeulen@uu.nl RI Vermeulen, Roel/F-8037-2011; Beane Freeman, Laura/C-4468-2015; OI Vermeulen, Roel/0000-0003-4082-8163; Beane Freeman, Laura/0000-0003-1294-4124; Lenters, Virissa/0000-0002-0444-9150; Basinas, Ioannis/0000-0001-7708-3017 FU Medical Research Council [MC_U147574248, MC_UP_A620_1018, U.1475.00.005.00006.03(74248)] NR 107 TC 34 Z9 34 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2010 VL 21 IS 4 BP 523 EP 555 DI 10.1007/s10552-009-9483-z PG 33 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 569VY UT WOS:000275631900005 PM 20012774 ER PT J AU Yu, CL Falk, RT Kimlin, MG Rajaraman, P Sigurdson, AJ Horst, RL Cosentino, LM Linet, MS Freedman, DM AF Yu, Chu-Ling Falk, Roni T. Kimlin, Michael G. Rajaraman, Preetha Sigurdson, Alice J. Horst, Ronald L. Cosentino, Louis M. Linet, Martha S. Freedman, D. Michal TI The impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25-hydroxyvitamin D concentrations SO CANCER CAUSES & CONTROL LA English DT Article DE Vitamin D; 25-hydroxyvitamin D; Specimen handling; Time factors; Epidemiologic methods ID VITAMIN-D STATUS; PROSTATE-CANCER; PLASMA 25-HYDROXYVITAMIN-D; SUBSEQUENT RISK; UNITED-STATES; SERUM; 1,25-DIHYDROXYVITAMIN-D; MORTALITY; MEN AB Studies have examined the associations between cancers and circulating 25-hydroxyvitamin D [25(OH)D], but little is known about the impact of different laboratory practices on 25(OH)D concentrations. We examined the potential impact of delayed blood centrifuging, choice of collection tube, and type of assay on 25(OH)D concentrations. Blood samples from 20 healthy volunteers underwent alternative laboratory procedures: four centrifuging times (2, 24, 72, and 96 h after blood draw); three types of collection tubes (red top serum tube, two different plasma anticoagulant tubes containing heparin or EDTA); and two types of assays (DiaSorin radioimmunoassay [RIA] and chemiluminescence immunoassay [CLIA/LIAISON(A (R))]). Log-transformed 25(OH)D concentrations were analyzed using the generalized estimating equations (GEE) linear regression models. We found no difference in 25(OH)D concentrations by centrifuging times or type of assay. There was some indication of a difference in 25(OH)D concentrations by tube type in CLIA/LIAISON(A (R))-assayed samples, with concentrations in heparinized plasma (geometric mean, 16.1 ng ml(-1)) higher than those in serum (geometric mean, 15.3 ng ml(-1)) (p = 0.01), but the difference was significant only after substantial centrifuging delays (96 h). Our study suggests no necessity for requiring immediate processing of blood samples after collection or for the choice of a tube type or assay. C1 [Yu, Chu-Ling; Falk, Roni T.; Rajaraman, Preetha; Sigurdson, Alice J.; Linet, Martha S.; Freedman, D. Michal] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Kimlin, Michael G.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Australian Sun & Hlth Res Lab, Brisbane, Qld 4001, Australia. [Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA. [Cosentino, Louis M.] NCI, Lab Biospecimen & Biorepository Res, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Yu, CL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Mailstop 7238, Rockville, MD 20852 USA. EM yuchu@mail.nih.gov OI Kimlin, Michael/0000-0002-9536-8646 FU Intramural NIH HHS [ZIA CP010133-14]; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 21 TC 5 Z9 5 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2010 VL 21 IS 4 BP 643 EP 648 DI 10.1007/s10552-009-9485-x PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 569VY UT WOS:000275631900014 PM 20020320 ER PT J AU Jacobs, S McCully, CL Murphy, RF Bacher, J Balis, FM Fox, E AF Jacobs, Shana McCully, Cynthia L. Murphy, Robert F. Bacher, John Balis, Frank M. Fox, Elizabeth TI Extracellular fluid concentrations of cisplatin, carboplatin, and oxaliplatin in brain, muscle, and blood measured using microdialysis in nonhuman primates SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Platinum analogs; CNS penetration; Microdialysis ID IN-VIVO MICRODIALYSIS; 9L MALIGNANT GLIOMA; CEREBROSPINAL-FLUID; RHESUS-MONKEY; PHARMACOKINETICS; PLASMA; PLATINUM; TRANSPORTERS; IRRADIATION; CALIBRATION AB Cisplatin, carboplatin, and oxaliplatin are chemically reactive anticancer drugs with modest activity in brain tumors. Previously, we have demonstrated that drug exposure in cerebrospinal fluid (CSF) for these platinum analogs is < 5% of the plasma ultrafiltrate (UF) drug exposure in nonhuman primates. Microdialysis is a minimally invasive in vivo method for sampling small molecules in the blood and tissue extracellular fluid (ECF). The purpose of this study was to estimate the penetration of platinum analogs into the brain ECF. We measured free concentrations of cisplatin, carboplatin, and oxaliplatin in ECF of brain, muscle, and blood of nonhuman primates using microdialysis and compared ECF platinum concentrations in blood and brain to plasma UF and CSF concentrations obtained using conventional sampling methods. For all three platinum analogs, AUC(0-4h) for microdialysis sampling from the vein was similar to standard plasma UF sampling. The median AUC(0-4h) ratio for vein to plasma UF was 1.1 (range, 0.9-1.4). The platinum analogs had limited distribution (< 5%) to the CSF and brain ECF. CSF penetration predicts for the limited penetration of the platinum analogs into brain ECF, but concordance between CSF and brain ECF measurements was poor. CSF oxaliplatin concentrations (AUC(0-4h), 0.4-0.9 mu M h) were substantially lower than brain ECF concentrations (AUC(0-4h), 2.0-8.6 mu M h). The penetration of platinum analogs into CSF and brain is limited. The differences in the CNS penetrations among the three platinum analogs are not clinically significant. For cisplatin and carboplatin, CSF penetration appears to be a surrogate for brain extracellular free drug exposure. C1 [Jacobs, Shana; McCully, Cynthia L.; Murphy, Robert F.; Balis, Frank M.; Fox, Elizabeth] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bacher, John] NIH, Div Vet Resources, ORS, Bethesda, MD 20892 USA. [Jacobs, Shana] Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, NIH, Bldg 10 CRC Rm 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM foxb@mail.nih.gov FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 32 TC 29 Z9 29 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2010 VL 65 IS 5 BP 817 EP 824 DI 10.1007/s00280-009-1085-7 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 557FR UT WOS:000274655500001 PM 19662415 ER PT J AU Rakowski, W Wyn, R Breen, N Meissner, H Clark, MA AF Rakowski, William Wyn, Roberta Breen, Nancy Meissner, Helen Clark, Melissa A. TI Prevalence and correlates of recent and repeat mammography among California women ages 55-79 SO CANCER EPIDEMIOLOGY LA English DT Article DE Mammography; Behavioral science; Women's health; Preventive health services; Cancer screening ID BREAST-CANCER; SCREENING MAMMOGRAPHY; PATIENT; CARE; MULTILEVEL; RISK AB Objective: Data on repeat mammography rates are less available than for recent screening. Two large, population-based state surveys provide the opportunity to investigate repeat and recent mammography prevalence and correlates among California's diverse population. Methods: Data were from women aged 55-79, using the 2001 and 2005 California Health Interview Surveys. The study assessed the prevalence and correlates of recent mammography (within the past two years) and repeat mammography (mammogram within the past two years and 3-11 mammograms within the past six years). Results: Prevalence was 82.4% (recent) and 73.8% (repeat) in 2001, and 87.1% (recent) and 77.5% (repeat) in 2005. Correlates of lower rates were insurance status, no usual source of care, being a smoker, age 65-79, being Asian with no English proficiency, being never married, and lower absolute risk for breast cancer. Especially low ratios of repeat-to-recent mammography existed for the uninsured, and those using the emergency room or with no source of care. Unexpected findings in which unadjusted results were inconsistent with multivariable adjusted results occurred for Latinas with no English proficiency and women at 200-299% of poverty level. Conclusions: Several groups of women in California remain at-risk of lower mammography utilization. However, investigators should also be alert for instances where multivariable analyses seem particularly discrepant with crude rates. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Rakowski, William; Clark, Melissa A.] Brown Univ, Dept Community Hlth, Program Publ Hlth, Providence, RI 02912 USA. [Wyn, Roberta] Univ Calif Los Angeles, Ctr Hlth Policy, Los Angeles, CA 90024 USA. [Breen, Nancy] Natl Canc Inst, Appl Res Program, Rockville, MD 20852 USA. [Meissner, Helen] Natl Canc Inst, Appl Canc Screening Res Program, Rockville, MD 20852 USA. RP Rakowski, W (reprint author), Brown Univ, Dept Community Hlth, Program Publ Hlth, Box G-S121,2nd Floor,121 S Main St, Providence, RI 02912 USA. EM william_rakowski@brown.edu; rwyn@ucla.edu; breenn@mail.nih.gov; hm36d@nih.gov; melissa_clark@brown.edu FU NIH [K05-CA90485, K07-CA87070] FX Partial support for the preparation of this paper was provided by NIH grants K05-CA90485 (Dr. Rakowski), and K07-CA87070 (Dr. Clark). NR 34 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD APR PY 2010 VL 34 IS 2 BP 168 EP 177 DI 10.1016/j.canep.2010.02.005 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 594NB UT WOS:000277543300010 PM 20303844 ER PT J AU Vaught, JB Hsing, AW AF Vaught, Jimmie B. Hsing, Ann W. TI Methodologic Data: Important Foundation for Molecular and Biomarker Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BIOSPECIMEN C1 [Vaught, Jimmie B.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Vaught, JB (reprint author), NCI, Off Biorepositories & Biospecimen Res, 31 Ctr Dr,Room 10A03, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov; hsinga@mail.nih.gov NR 6 TC 1 Z9 1 U1 0 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 APR PY 2010 VL 19 IS 4 BP 901 EP 902 DI 10.1158/1055-9965.EPI-10-0057 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400001 PM 20332254 ER PT J AU Stanczyk, FZ Jurow, J Hsing, AW AF Stanczyk, Frank Z. Jurow, Jordan Hsing, Ann W. TI Limitations of Direct Immunoassays for Measuring Circulating Estradiol Levels in Postmenopausal Women and Men in Epidemiologic Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HORMONE REPLACEMENT THERAPY; SERUM ESTRADIOL; DIRECT RADIOIMMUNOASSAYS; KITS; ASSAYS AB Serum estradiol (E(2)) serves as an important diagnostic marker in a variety of clinical conditions. In epidemiologic studies, E(2) is commonly used to define the etiologic role of estrogen in hormone-related cancers and chronic conditions. Having an accurate and reliable E(2) assay is of critical importance in these studies, especially when measuring the very low E(2) levels (<30 pg/mL) common in postmenopausal women and men, and for discerning the relatively small (usually <20%) case-control differences in E(2) levels. Because E(2) is metabolized to >100 metabolites in the body, some of which cross-react with E(2) antibodies, direct RIAs without purification steps lack specificity for E(2) and can substantially overestimate E(2) levels. Although direct E(2) RIAs using commercial kits are simpler, less time consuming, and less expensive and require less sample volume than conventional RIAs with preceding purification steps, their lack of sensitivity and specificity makes them invalid for measuring circulating E(2) levels in epidemiologic studies of postmenopausal women or men. Instead, we recommend the use of a well-validated RIA with purification steps to improve sensitivity and specificity and to help achieve the necessary accuracy and reliability needed for epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 19(4); 903-6. (C)2010 AACR. C1 [Stanczyk, Frank Z.; Jurow, Jordan] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. [Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Stanczyk, FZ (reprint author), Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Livingston Res Bldg,1321 N Mission Rd, Los Angeles, CA 90033 USA. EM fstanczyk@socal.rr.com NR 14 TC 32 Z9 34 U1 0 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 APR PY 2010 VL 19 IS 4 BP 903 EP 906 DI 10.1158/1055-9965.EPI-10-0081 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400002 PM 20332268 ER PT J AU Koshiol, J Wang, E Zhao, YD Marincola, F Landi, MT AF Koshiol, Jill Wang, Ena Zhao, Yingdong Marincola, Francesco Landi, Maria Teresa TI Strengths and Limitations of Laboratory Procedures for MicroRNA Detection SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TOTAL RNA; RT-PCR; EXPRESSION DISTINGUISHES; CAENORHABDITIS-ELEGANS; CIGARETTE-SMOKE; CELL CARCINOMA; OVARIAN-CANCER; MICROARRAY; SIGNATURES; GENES AB Background: MicroRNAs (miR) are endogenous, noncoding RNAs involved in many cellular processes and have been associated with the development and progression of cancer. There are many different ways to evaluate miRs. Methods: We described some of the most commonly used and promising miR detection methods. Results: Each miR detection method has benefits and limitations. Microarray profiling and quantitative real-time reverse-transcription PCR are the two most common methods to evaluate miR expression. However, the results from microarray and quantitative real-time reverse-transcription PCR do not always agree. High-throughput, high-resolution next-generation sequencing of small RNAs may offer the opportunity to quickly and accurately discover new miRs and confirm the presence of known miRs in the near future. Conclusions: All of the current and new technologies have benefits and limitations to consider when designing miR studies. Results can vary across platforms, requiring careful and critical evaluation when interpreting findings. Impact: Although miR detection and expression analyses are rapidly improving, there are still many technical challenges to overcome. The old molecular epidemiology tenet of rigorous biomarker validation and confirmation in independent studies remains essential. Cancer Epidemiol Biomarkers Prev; 19(4); 907-11. (C)2010 AACR. C1 [Koshiol, Jill] NCI, Infect & Immunepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20852 USA. [Wang, Ena; Marincola, Francesco] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Wang, Ena; Marincola, Francesco] NIH, Ctr Human Immunol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Koshiol, J (reprint author), NCI, Infect & Immunepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7070, Rockville, MD 20852 USA. EM koshiolj@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 50 TC 55 Z9 60 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 907 EP 911 DI 10.1158/1055-9965.EPI-10-0071 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400003 PM 20332265 ER PT J AU Vaught, JB Caboux, E Hainaut, P AF Vaught, Jimmie B. Caboux, Elodie Hainaut, Pierre TI International Efforts to Develop Biospecimen Best Practices SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID BIOBANKING; CANCER; BIAS AB Variables introduced during the processes involved in biospecimen collection, processing, storage, and analysis are among the potential sources of bias in biomarker research. International efforts are under way to develop best practices to standardize biospecimen handling protocols. In general, documents on best practices address three major recurring themes: technical best practices on infrastructure and specimen handling, recommendations on informatics and data management, and recommendations on ethical, legal, and social issues. There are many areas of agreement among various international efforts, but no single set of practices has emerged as a unifying document. The ethical, legal, and social issues are particularly difficult to harmonize due to the many country-specific issues that are governed by a variety of local and federal rules and regulations. Given the increasingly international nature of research involving biomarkers and biospecimens, it will be necessary to continue to cooperate in the development of harmonized evidence-based best practices. Several international organizations including the International Cancer Genome Consortium are engaged in such efforts. Cancer Epidemiol Biomarkers Prev;19(4); 912-5. (C)2010 AACR. C1 [Vaught, Jimmie B.] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Caboux, Elodie; Hainaut, Pierre] Int Agcy Res Canc, F-69372 Lyon, France. RP Vaught, JB (reprint author), NCI, Off Biorepositories & Biospecimen Res, 31 Ctr Dr,Room 10A03, Bethesda, MD 20892 USA. EM vaughtj@mail.nih.gov RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 NR 10 TC 25 Z9 31 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 912 EP 915 DI 10.1158/1055-9965.EPI-10-0058 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400004 PM 20233852 ER PT J AU Cortes, B Schiffman, M Herrero, R Hildesheim, A Jimenez, S Shea, K Gonzalez, P Porras, C Fallas, G Rodriguez, AC AF Cortes, Bernal Schiffman, Mark Herrero, Rolando Hildesheim, Allan Jimenez, Silvia Shea, Katheryn Gonzalez, Paula Porras, Carolina Fallas, Greivin Cecilia Rodriguez, Ana TI Establishment and Operation of a Biorepository for Molecular Epidemiologic Studies in Costa Rica SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GUANACASTE; INFECTION; WOMEN AB Background: The Proyecto Epidemiologico Guanacaste (PEG) has conducted several large studies related to human papillomavirus (HPV) and cervical cancer in Guanacaste, Costa Rica in a long-standing collaboration with the U.S . National Cancer Institute. To improve molecular epidemiology efforts and save costs, we have gradually transferred technology to Costa Rica, culminating in state-of-the-art laboratories and a bio-repository to support a phase III clinical trial investigating the efficacy of HPV 16/18 vaccine. Objective: Here, we describe the rationale and lessons learned in transferring molecular epidemiologic and biorepository technology to a developing country. Results: At the outset of the PEG in the early 1990s, we shipped all specimens to repositories and laboratories in the United States, which created multiple problems. Since then, by intensive personal interactions between experts from the United States and Costa Rica, we have successfully transferred liquid-based cytology, HPV DNA testing and serology, chlamydia and gonorrhea testing, PCR-safe tissue processing, and viable cryopreservation. To accommodate the vaccine trial, a state-of-the-art repository opened in mid-2004. Approximately 15,000 to 50,000 samples are housed in the repository on any given day, and >500,000 specimens have been shipped, many using a custom-made dry shipper that permits exporting >20,000 specimens at a time. Quality control of shipments received by the NCI biorepository has revealed an error rate of <0.2%. Recently, the PEG repository has incorporated other activities; for example, large-scale aliquotting and longterm, cost-efficient storage of frozen specimens returned from the United States. Using Internet-based specimen tracking software has proven to be efficient even across borders. Conclusion: For long-standing collaborations, it makes sense to transfer the molecular epidemiology expertise toward the source of specimens. The successes of the PEG molecular epidemiology laboratories and biorepository prove that the physical and informatics infrastructures of a modern biorepository can be transferred to a resource-limited and weather-challenged region. Technology transfer is an important and feasible goal of international collaborations. Cancer Epidemiol Biomarkers Prev; 19(4); 916-22. (C)2010 AACR. C1 [Cortes, Bernal; Herrero, Rolando; Jimenez, Silvia; Gonzalez, Paula; Fallas, Greivin; Cecilia Rodriguez, Ana] Fdn INCIENSA, San Jose, Costa Rica. [Schiffman, Mark; Hildesheim, Allan; Porras, Carolina] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA. [Shea, Katheryn] SeraCare Life Sci, Frederick, MD USA. RP Cortes, B (reprint author), Fdn INCIENSA, 7Mo Piso, San Jose, Costa Rica. EM bcortes@proyectoguanacaste.org RI Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU NIH [N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023]; NCI [N01CP-11005]; NIH Office for Research on Women's Health FX The population-based natural history study of HPV infection and cervical neoplasia in Guanacaste, Costa Rica was supported by the NIH (N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP81023). The HPV Vaccine trial is sponsored and funded by NCI (N01CP-11005) with support from the NIH Office for Research on Women's Health. NR 7 TC 8 Z9 8 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 916 EP 922 DI 10.1158/1055-9965.EPI-10-0066 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400005 PM 20332271 ER PT J AU Hofmann, JN Yu, K Horst, RL Hayes, RB Purdue, MP AF Hofmann, Jonathan N. Yu, Kai Horst, Ronald L. Hayes, Richard B. Purdue, Mark P. TI Long-term Variation in Serum 25-Hydroxyvitamin D Concentration among Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID VITAMIN-D STATUS; UNITED-STATES; RISK; PREVENTION; MORTALITY AB Molecular epidemiologic studies of vitamin D and risk of cancer and other health outcomes usually involve a single measurement of the biomarker 25-hydroxyvitamin D [25(OH) D] in serum or plasma. However, the extent to which 25(OH) D concentration at a single time point is representative of an individual's long-term vitamin D status is unclear. To address this question, we evaluated within-person variability in 25(OH) D concentrations across serum samples collected at three time points over a 5-year period among 29 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Blood collection took place year-round, although samples for a given participant were collected in the same month each year. The within-person coefficient of variation and intraclass correlation coefficient were calculated using variance components estimated from random effects models. Spearman rank correlation coefficients were calculated to evaluate agreement between measurements at different collection times (baseline, +1 year, +5 years). The within-subject coefficient of variation was 14.9% [95% confidence interval (CI), 12.4-18.1%] and the intraclass correlation coefficient was 0.71 (95% CI, 0.63-0.88). Spearman rank correlation coefficients comparing baseline to +1 year, +1 year to +5 years, and baseline to +5 years were 0.65 (95% CI, 0.37-0.82), 0.61 (0.29-0.81), and 0.53 (0.17-0.77), respectively. Slightly stronger correlations were observed after restricting to non-Hispanic Caucasian subjects. These findings suggest that serum 25(OH) D concentration at a single time point may be a useful biomarker of long-term vitamin D status in population-based studies of various diseases. Cancer Epidemiol Biomarkers Prev; 19(4); 927-31. (C)2010 AACR. C1 [Hofmann, Jonathan N.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Horst, Ronald L.] Heartland Assays Inc, Ames, IA USA. [Hayes, Richard B.] NYU, Dept Environm Med, Sch Med, New York, NY 10016 USA. [Hayes, Richard B.] NYU, Inst Canc, Sch Med, New York, NY 10016 USA. RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM hofmannjn@mail.nih.gov RI Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Hayes, Richard/0000-0002-0918-661X FU NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 20 TC 75 Z9 75 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 927 EP 931 DI 10.1158/1055-9965.EPI-09-1121 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400007 PM 20332255 ER PT J AU Hsing, AW Meyer, TE Niwa, S Quraishi, SM Chu, LW AF Hsing, Ann W. Meyer, Tamra E. Niwa, Shelley Quraishi, Sabah M. Chu, Lisa W. TI Measuring Serum Melatonin in Epidemiologic Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKINS-LYMPHOMA; BREAST-CANCER RISK; PROSTATE-CANCER; SLEEP DURATION; SHIFT-WORK; NURSES HEALTH; OHSAKI COHORT; HUMAN-PLASMA; GENE NPAS2; NIGHT WORK AB Background: Epidemiologic data on serum melatonin, a marker of circadian rhythms, and cancer are sparse due largely to the lack of reliable assays with high sensitivity to detect relatively low melatonin levels in serum collected during daylight, as commonly available in most epidemiologic studies. Methods: To help expand epidemiologic research on melatonin, we assessed the reproducibility and refined a currently available melatonin RIA, and evaluated its application to epidemiologic investigations by characterizing melatonin levels in serum, urine, and/or plasma in 135 men from several ethnic groups. Results: Reproducibility was high for the standard 1.0-mL serum [mean coefficient of variation (CV), 6.9%; intraclass correlation coefficient (ICC), 97.4%; n = 2 serum pools in triplicate] and urine-based (mean CV, 3.5%; ICC, 99.9%) assays. Reproducibility for the 0.5-mL refined-serum assay was equally good (mean CV, 6.6%; ICC, 99.0%). There was a positive correlation between morning serum melatonin and 6-sulfatoxymelatonin in 24-hour urine (r = 0.46; P = 0.008; n = 49 subjects). Melatonin levels in serum-plasma pairs had a high correlation (r = 0.97; P < 1x10(-4); n = 20 pairs). Morning serum melatonin levels were five times higher than those from the afternoon (before 9 a.m. mean, 11.0 pg/mL, versus after 11 a. m. mean, 2.0 pg/mL). Chinese men had lower melatonin levels (mean, 3.4 pg/mL), whereas Caucasian, African-American, and Ghanaian men had similar levels (mean, 6.7-8.6 pg/mL). Conclusions: These results suggest that melatonin can be detected reliably in serum samples collected in epidemiologic studies in various racial groups. Impact: With improved assays, it may be possible to investigate the role of melatonin and the emerging circadian rhythm hypothesis in cancer etiology in epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 19(4); 932-7. (C)2010 AACR. C1 [Hsing, Ann W.; Meyer, Tamra E.; Quraishi, Sabah M.; Chu, Lisa W.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Niwa, Shelley] Westat Corp, Rockville, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 5024,MSC 7234, Rockville, MD 20852 USA. EM hsinga@mail.nih.gov FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services FX Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services. NR 32 TC 17 Z9 17 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 APR PY 2010 VL 19 IS 4 BP 932 EP 937 DI 10.1158/1055-9965.EPI-10-0004 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400008 PM 20332275 ER PT J AU Sherman, ME Howatt, W Blows, FM Pharoah, P Hewitt, SM Garcia-Closas, M AF Sherman, Mark E. Howatt, Will Blows, Fiona M. Pharoah, Paul Hewitt, Stephen M. Garcia-Closas, Montserrat TI Molecular Pathology in Epidemiologic Studies: A Primer on Key Considerations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID PARAFFIN-EMBEDDED TISSUES; POPULATION-BASED ANALYSIS; BREAST-CANCER; HORMONE-RECEPTOR; MICROARRAYS; EXPRESSION; FIXATION; PROTEIN; RISK; IMMUNOHISTOCHEMISTRY AB The development of molecular pathologic components in epidemiologic studies offers opportunities to relate etiologic factors to specific tumor types, which in turn may allow the development of better overall risk prediction and provide clues about mechanisms that mediate risk factors. In addition, this research may help identify or validate tissue biomarkers related to prognosis and prediction of treatment responses. In this mini review, we highlight specific considerations related to the incorporation of pathology in epidemiologic studies, using breast cancer research as a model. Issues related to ensuring the representativeness of cases for which research tissue is available and understanding limitations resulting from variable procedures for tissue collection, fixation, and processing are discussed. The growing importance of molecular pathology in clinical medicine has led to increased emphasis on optimized tissue preparation, which should enhance this type of research. In addition, the availability of new technologies including tissue microarrays, image scanning, and automated analysis to achieve high-throughput standardized assessment of immunohistochemical markers, and potentially other assays, is enabling consistent scoring of a growing list of markers in large studies. Concurrently, methodologic research to extend the range of assays that can be done on fixed tissues is expanding possibilities for molecular pathologic studies in epidemiologic research. Cancer Epidemiol Biomarkers Prev; 19(4); 966-72. (C)2010 AACR. C1 [Sherman, Mark E.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, Rockville, MD 20852 USA. [Hewitt, Stephen M.] Ctr Canc Res, Pathol Lab, Bethesda, MD USA. [Howatt, Will; Blows, Fiona M.; Pharoah, Paul] Cambridge Res Inst, Cambridge, England. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd, Rockville, MD 20852 USA. EM shermanm@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Hewitt, Stephen/0000-0001-8283-1788 FU National Cancer Institute; Applied Molecular Pathology laboratory; Breast Cancer Association Consortium; Tissue Array Research Program FX Intramural Research Program of the National Cancer Institute, the Applied Molecular Pathology laboratory, and the Tissue Array Research Program. Also supported by the Breast Cancer Association Consortium. NR 43 TC 17 Z9 19 U1 0 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 APR PY 2010 VL 19 IS 4 BP 966 EP 972 DI 10.1158/1055-9965.EPI-10-0056 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400013 PM 20332257 ER PT J AU Huang, WY Sheehy, TM Moore, LE Hsing, AW Purdue, MP AF Huang, Wen-Yi Sheehy, Timothy M. Moore, Lee E. Hsing, Ann W. Purdue, Mark P. TI Simultaneous Recovery of DNA and RNA from Formalin-Fixed Paraffin-Embedded Tissue and Application in Epidemiologic Studies (Retracted article. See vol. 23, pg. 1132, 2014) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review; Retracted Publication ID EXPRESSION ANALYSIS; GENE-EXPRESSION; COPY NUMBER; MICROARRAYS; VALIDATION; EXTRACTION; TUMORS; ASSAY AB Analysis of DNA, RNA, and protein extracted from tissue specimens in epidemiologic studies is useful for assessing etiologic heterogeneity, mechanisms of carcinogenesis, and biomarkers for prognosis and prediction of treatment responses. Fresh-frozen tissue samples may provide optimal quality nucleic acids, but pose multiple logistical considerations, including rapid access to tissues before histopathologic examination and specialized equipment for freezing, transport, and storage; in addition, morphology is often compromised. In contrast, formalin-fixed paraffin-embedded (FFPE) tissue samples, including enormous archives of existing specimens, represent a valuable source of retrospective biological material for epidemiologic research, although presenting different limitations compared with frozen samples. Recent efforts have made progress toward enhancing the utility of FFPE specimens for molecular analyses, including DNA studies, and increasingly for RNA and other macromolecules. Here, we report the method that we used to simultaneously recover DNA and RNA from FFPE tissue specimens with appreciable quantity and quality and discuss briefly the application of tumor markers in epidemiologic studies. Cancer Epidemiol Biomarkers Prev; 19(4); 973-7. (C)2010 AACR. C1 [Huang, Wen-Yi; Moore, Lee E.; Hsing, Ann W.; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Sheehy, Timothy M.] Sci Applicat Int Corp Frederick Inc, DNA Extract & Staging Lab, NCI Frederick, Frederick, MD USA. RP Huang, WY (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, 6120 Execut Blvd,EPS 8110,MSC 7240, Bethesda, MD 20892 USA. EM huangw@mail.nih.gov FU National Cancer Institute; National Cancer Institute, NIH [HHSN261200800001E] FX Intramural Research Program of the National Cancer Institute and federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 17 TC 23 Z9 23 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 973 EP 977 DI 10.1158/1055-9965.EPI-10-0091 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400014 PM 20332269 ER PT J AU Shebl, FM Pinto, LA Garcia-Pineres, A Lempicki, R Williams, M Harro, C Hildesheim, A AF Shebl, Fatma M. Pinto, Ligia A. Garcia-Pineres, Alfonso Lempicki, Richard Williams, Marcus Harro, Clayton Hildesheim, Allan TI Comparison of mRNA and Protein Measures of Cytokines following Vaccination with Human Papillomavirus-16 L1 Virus-like Particles SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENE-EXPRESSION; MULTIPLEX; PATTERNS; ASSAYS AB Background: mRNA expression signatures are frequently used as surrogate measures of cellular function and pathway changes. Few studies have directly compared results obtained using gene expression and multiplex protein assays for corresponding gene products. Methods: We used data available from a clinical trial of a human papillomavirus-16 vaccine that tracked gene expression and cytokine/chemokine production by peripheral blood mononuclear cells stimulated in culture with various antigens to evaluate the degree to which gene expression levels reflect observed levels of cytokines/chemokines. Twenty-six women enrolled in a phase II clinical trial of a human papillomavirus-16 vaccine were evaluated for gene expression (using the Affymetrix Human Genome Focus Array) and cytokine/chemokine levels (using a bead-based 22-plex cytokine assay developed by Linco Research, Inc.) before and after vaccination. Results: Our results suggest the presence of a wide range of correlations between mRNA expression and secreted protein levels. The strongest correlation was observed for IFN-gamma (R = 0.90 overall levels; R = 0.69 when vaccine induced changes were evaluated). More modest overall correlations ranging from 0.40 to 0.80 were observed for MIP1A, IP10, TNF-alpha, MCP1, IL-2, GM-CSF, IL-5, RANTES, and IL-8. Weaker or no correlation was observed between gene expression and protein levels for the remaining cytokines/chemokines evaluated. Conclusion: The degree of correlation between gene expression and protein levels varied among different cytokines/chemokines. Impact: Researchers should be cautious when using mRNA expression array results as a proxy for protein levels using existing technologies. Cancer Epidemiol Biomarkers Prev;19 (4); 978-81. (C)2010 AACR. C1 [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Pinto, Ligia A.; Garcia-Pineres, Alfonso; Williams, Marcus] Sci Applicat Int Corp, HPV Immunol Lab, NCI, NIH, Frederick, MD USA. [Lempicki, Richard] Sci Applicat Int Corp, Lab Bioinformat & Immunopathogenesis, NCI, NIH, Frederick, MD USA. [Harro, Clayton] Johns Hopkins Univ, Ctr Immunizat Res, Baltimore, MD USA. RP Shebl, FM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7074, Rockville, MD 20852 USA. EM sheblf@mail.nih.gov RI Lempicki, Richard/E-1844-2012; Hildesheim, Allan/B-9760-2015 OI Lempicki, Richard/0000-0002-7059-409X; Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] 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. NR 24 TC 40 Z9 40 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 978 EP 981 DI 10.1158/1055-9965.EPI-10-0064 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400015 PM 20332253 ER PT J AU Bolton, KL Garcia-Closas, M Pfeiffer, RM Duggan, MA Howat, WJ Hewitt, SM Yang, XHR Cornelison, R Anzick, SL Meltzer, P Davis, S Lenz, P Figueroa, JD Pharoah, PDP Sherman, ME AF Bolton, Kelly L. Garcia-Closas, Montserrat Pfeiffer, Ruth M. Duggan, Maire A. Howat, William J. Hewitt, Stephen M. Yang, Xiaohong R. Cornelison, Robert Anzick, Sarah L. Meltzer, Paul Davis, Sean Lenz, Petra Figueroa, Jonine D. Pharoah, Paul D. P. Sherman, Mark E. TI Assessment of Automated Image Analysis of Breast Cancer Tissue Microarrays for Epidemiologic Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-RECEPTOR STATUS; IN-SITU HYBRIDIZATION; IMMUNOHISTOCHEMICAL ANALYSIS; CARCINOMA; RISK; VALIDATION; EXPRESSION; IMMUNOREACTIVITY; METAANALYSIS; SYSTEM AB Background: A major challenge in studies of etiologic heterogeneity in breast cancer has been the limited throughput, accuracy, and reproducibility of measuring tissue markers. Computerized image analysis systems may help address these concerns, but published reports of their use are limited. We assessed agreement between automated and pathologist scores of a diverse set of immunohistochemical assays done on breast cancer tissue microarrays (TMA). Methods: TMAs of 440 breast cancers previously stained for estrogen receptor (ER)-alpha, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), ER-beta, and aromatase were independently scored by two pathologists and three automated systems (TMALab II, TMAx, and Ariol). Agreement between automated and pathologist scores of negative/positive was measured using the area under the receiver operating characteristics curve (AUC) and weighted. statistics for categorical scores. We also investigated the correlation between immunohistochemical scores and mRNA expression levels. Results: Agreement between pathologist and automated negative/positive and categorical scores was excellent for ER-alpha and PR (AUC range = 0.98-0.99; kappa range = 0.86-0.91). Lower levels of agreement were seen for ER-beta categorical scores (AUC = 0.99-1.0; kappa = 0.80-0.86) and both negative/positive and categorical scores for aromatase (AUC = 0.85-0.96; kappa = 0.41-0.67) and HER2 (AUC = 0.94-0.97; kappa = 0.53-0.72). For ER-alpha and PR, there was a strong correlation between mRNA levels and automated (rho = 0.67-0.74) and pathologist immunohistochemical scores (rho = 0.67-0.77). HER2 mRNA levels were more strongly correlated with pathologist (rho = 0.63) than automated immunohistochemical scores (rho = 0.41-0.49). Conclusions: Automated analysis of immunohistochemical markers is a promising approach for scoring large numbers of breast cancer tissues in epidemiologic investigations. This would facilitate studies of etiologic heterogeneity, which ultimately may allow improved risk prediction and better prevention approaches. Cancer Epidemiol Biomarkers Prev; 19(4); 992-9. (C)2010 AACR. C1 [Bolton, Kelly L.; Pharoah, Paul D. P.] Univ Cambridge, Canc Res UK, Dept Oncol, Strangeways Res Lab, Cambridge CB1 8RN, England. [Bolton, Kelly L.; Garcia-Closas, Montserrat; Pfeiffer, Ruth M.; Yang, Xiaohong R.; Figueroa, Jonine D.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Hewitt, Stephen M.; Lenz, Petra] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Cornelison, Robert; Anzick, Sarah L.; Meltzer, Paul; Davis, Sean] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Duggan, Maire A.] Univ Calgary, Calgary, AB, Canada. [Howat, William J.] Li Ka Shing Ctr, Canc Res UK, Cambridge Res Inst, Cambridge, England. RP Bolton, KL (reprint author), Univ Cambridge, Canc Res UK, Dept Oncol, Strangeways Res Lab, Worts Causeway, Cambridge CB1 8RN, England. EM boltonk@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Hewitt, Stephen/0000-0001-8283-1788; Davis, Sean/0000-0002-8991-6458 FU National Cancer Institute Intramural; National Cancer Institute Intramural Research Program; University of Calgary; Cancer Research UK FX K.L. Bolton, M. Garcia-Closas, R.M. Pfeiffer, S.M. Hewitt, X.R. Yang, R. Cornelison, S.L. Anzick, P. Meltzer, S. Davis, P. Lenz, J.D. Figueroa, and M.E. Sherman were funded by the National Cancer Institute Intramural Research Program, including resources of the Applied Molecular Pathology Laboratory. M. A. Duggan was funded by the University of Calgary. P. D. P. Pharaoh and W.J. Howat were funded by Cancer Research UK. NR 29 TC 27 Z9 27 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 992 EP 999 DI 10.1158/1055-9965.EPI-09-1023 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400017 PM 20332278 ER PT J AU Yassin, R Lockhart, N del Riego, MG Pitt, K Thomas, JW Weiss, L Compton, C AF Yassin, Rihab Lockhart, Nicole del Riego, Mariana Gonzalez Pitt, Karen Thomas, Jeffrey W. Weiss, Linda Compton, Carolyn TI Custodianship as an Ethical Framework for Biospecimen-Based Research SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OWNERSHIP AB Human biological specimens (biospecimens) are increasingly important for research that aims to advance human health. Yet, despite significant proliferation in specimen- based research and discoveries during the past decade, research remains challenged by the inequitable access to high- quality biospecimens that are collected under rigorous ethical standards. This is primarily caused by the complex level of control and ownership exerted by the myriad of stakeholders involved in the biospecimen research process. This article discusses the ethical model of custodianship as a framework for biospecimen- based research to promote fair research access and resolve issues of control and potential conflicts between biobanks, investigators, human research participants (human subjects), and sponsors. Custodianship is the caretaking obligation for biospecimens frominitial collection to final dissemination of research findings. It endorses key practices and operating principles for responsible oversight of biospecimens collected for research. Embracing the custodial model would ensure transparency in research, fairness to human research participants, and shared accountability among all stakeholders involved in biospecimen- based research. Cancer Epidemiol Biomarkers Prev; 19(4); 1012-5. (C)2010 AACR. C1 [Yassin, Rihab] NCI, Div Canc Biol, Bethesda, MD 20892 USA. [Lockhart, Nicole; Compton, Carolyn] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [Pitt, Karen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Thomas, Jeffrey W.] NCI, Technol Transfer Ctr, Bethesda, MD 20892 USA. [Weiss, Linda] NCI, Off Canc Ctr, Bethesda, MD 20892 USA. [del Riego, Mariana Gonzalez] Sci Applicat Int Corp Frederick Inc, Rose Li & Associates Inc, NCI Frederick, Frederick, MD USA. RP Yassin, R (reprint author), NCI, Div Canc Biol, 6130 Execut Blvd,Suite 5000, Bethesda, MD 20892 USA. EM ry38k@NIH.gov FU Intramural NIH HHS [Z99 CA999999]; PHS HHS [HHSN261200800001E] NR 13 TC 22 Z9 22 U1 0 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 APR PY 2010 VL 19 IS 4 BP 1012 EP 1015 DI 10.1158/1055-9965.EPI-10-0029 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400020 PM 20332272 ER PT J AU Sidelnikov, E Bostick, RM Flanders, WD Long, Q Fedirko, V Shaukat, A Daniel, CR Rutherford, RE AF Sidelnikov, Eduard Bostick, Roberd M. Flanders, W. Dana Long, Qi Fedirko, Veronika Shaukat, Aasma Daniel, Carrie R. Rutherford, Robin E. TI Effects of Calcium and Vitamin D on MLH1 and MSH2 Expression in Rectal Mucosa of Sporadic Colorectal Adenoma Patients SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPITHELIAL-CELL PROLIFERATION; DNA MISMATCH REPAIR; CONTROLLED CLINICAL-TRIAL; NORMAL COLON MUCOSA; MICROSATELLITE INSTABILITY; D SUPPLEMENTATION; DIETARY CALCIUM; 25-HYDROXYVITAMIN D; LIFE-STYLE; CANCER AB To further clarify and develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans and develop modifiable biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3), alone and in combination, on key DNA mismatch repair proteins in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D(3), alone or in combination, versus placebo over 6 months. Colorectal crypt overall expression and distribution of MSH2 and MLH1 proteins in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, MSH2 expression along the full lengths of crypts increased by 61% (P = 0.11) and 30% (P = 0.36) in the vitamin D and calcium groups, respectively, relative to the placebo group. The estimated calcium and vitamin D treatment effects were more pronounced in the upper 40% of crypts (differentiation zone) in which MSH2 expression increased by 169% (P = 0.04) and 107% (P = 0.13) in the vitamin D and calcium groups, respectively. These findings suggest that higher calcium and vitamin D intakes may result in increased DNA MMR system activity in the normal colorectal mucosa of sporadic adenoma patients and that the strongest effects may be vitamin D related and in the differentiation zone of the colorectal crypt. Cancer Epidemiol Biomarkers Prev; 19(4); 1022-32. (C)2010 AACR. C1 [Sidelnikov, Eduard; Bostick, Roberd M.; Flanders, W. Dana; Fedirko, Veronika] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Fedirko, Veronika] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Rutherford, Robin E.] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA 30322 USA. [Shaukat, Aasma] Univ Minnesota, Dept Med, GI Div, Minneapolis, MN 55455 USA. [Daniel, Carrie R.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bostick, RM (reprint author), Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM rmbosti@sph.emory.edu FU National Cancer Institute, NIH [R01 CA104637]; Georgia Cancer Coalition Distinguished Scholar award; Franklin Foundation FX National Cancer Institute, NIH R01 CA104637 (R.M. Bostick), Georgia Cancer Coalition Distinguished Scholar award (R.M. Bostick), and the Franklin Foundation. The National Cancer Institute, the Georgia Cancer Coalition, and the Franklin Foundation had no influence on the design of the study; the collection, analysis, and interpretation of the data; the decision to submit the manuscript for publication; or the writing of the manuscript. NR 47 TC 18 Z9 18 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 1022 EP 1032 DI 10.1158/1055-9965.EPI-09-0526 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400022 PM 20332274 ER PT J AU Slager, SL Goldin, LR Strom, SS Lanasa, MC Spector, LG Rassenti, L Leis, JF Camp, NJ Kay, NE Vachon, CM Glenn, M Weinberg, JB Rabe, KG Cunningham, JM Achenbach, SJ Hanson, CA Marti, GE Call, TG Caporaso, NE Cerhan, JR AF Slager, Susan L. Goldin, Lynn R. Strom, Sara S. Lanasa, Mark C. Spector, Logan G. Rassenti, Laura Leis, Jose F. Camp, Nicola J. Kay, Neil E. Vachon, Celine M. Glenn, Martha Weinberg, J. Brice Rabe, Kari G. Cunningham, Julie M. Achenbach, Sara J. Hanson, Curtis A. Marti, Gerald E. Call, Timothy G. Caporaso, Neil E. Cerhan, James R. TI Genetic Susceptibility Variants for Chronic Lymphocytic Leukemia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKIN-LYMPHOMA; TRANSCRIPTION FACTORS; FAMILIES; RISK; LOCI; MUM1/IRF4; SCAN C1 [Slager, Susan L.; Leis, Jose F.; Kay, Neil E.; Vachon, Celine M.; Rabe, Kari G.; Cunningham, Julie M.; Achenbach, Sara J.; Hanson, Curtis A.; Call, Timothy G.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Goldin, Lynn R.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA. [Spector, Logan G.] Univ Minnesota, Minneapolis, MN USA. [Rassenti, Laura] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Salt Lake City, UT USA. [Marti, Gerald E.] US FDA, Bethesda, MD 20014 USA. RP Slager, SL (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM slager@mayo.edu OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU NIH [CA118444, CA92153]; Intramural Research Program of the NIH, National Cancer Institute; CLL Research Consortium; NCI [N01-PC-35141]; Utah State Department of Health; University of Utah FX NIH grants CA118444 and CA92153; Intramural Research Program of the NIH, National Cancer Institute; and CLL Research Consortium. Data collection in Utah was made possible by the Utah Population Database and the Utah Cancer Registry. Partial support for all data in the Utah Population Database was provided by the University of Utah Huntsman Cancer Institute. The Utah Cancer Registry is funded by contract N01-PC-35141 from the NCI's SEER program with additional support from the Utah State Department of Health and the University of Utah. NR 15 TC 21 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 1098 EP 1102 DI 10.1158/1055-9965.EPI-09-1217 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400030 PM 20332261 ER PT J AU Woolcott, CG Courneya, KS Boyd, NF Yaffe, MJ Terry, T McTiernan, A Brant, R Ballard-Barbash, R Irwin, ML Jones, CA Brar, S Campbell, KL McNeely, ML Karvinen, KH Friedenreich, CM AF Woolcott, Christy G. Courneya, Kerry S. Boyd, Norman F. Yaffe, Martin J. Terry, Tim McTiernan, Anne Brant, Rollin Ballard-Barbash, Rachel Irwin, Melinda L. Jones, Charlotte A. Brar, Sony Campbell, Kristin L. McNeely, Margaret L. Karvinen, Kristina H. Friedenreich, Christine M. TI Mammographic Density Change with 1 Year of Aerobic Exercise among Postmenopausal Women: A Randomized Controlled Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; BODY-MASS INDEX; RECREATIONAL PHYSICAL-ACTIVITY; HORMONE-THERAPY; ENERGY-BALANCE; SEX-HORMONES; ESTROGEN; PATTERNS; HEALTH; COHORT AB Background: The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk. Mammographic density, a secondary outcome, is reported here. Methods: The ALPHA Trial was a parallel group randomized controlled trial conducted between May 2003 and July 2007. Postmenopausal, sedentary women ages 50 to 74 years (n = 320) were evenly randomized to aerobic exercise (45 minutes, 5 days per week) or control (usual life-style) for 1 year. Dense fibroglandular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computerassisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements. Results: Nondense volume decreased in the exercise group relative to the control group (difference between groups = -38.5 cm3; 95% confidence interval, -61.6 to 15.4; P = 0.001). Changes in total body fat accounted for this decrease. Changes in dense area and dense volume, measures that have previously been associated with breast cancer risk, were not significantly different between the groups (P = 0.26). Conclusions: Achieving changes in mammographic measures may require more exercise or a study population with higher baseline levels of sex hormones or a wider range of mammographic density. The data from this study, however, suggest that the protective effect of exercise on breast cancer risk may operate through a mechanism other than mammographic density. Cancer Epidemiol Biomarkers Prev; 19(4); 1112-21. (C) 2010 AACR. C1 [Friedenreich, Christine M.] Alberta Hlth Serv, Calgary, AB T2N 4N2, Canada. [Karvinen, Kristina H.] E Carolina Univ, Dept Exercise & Sport Sci, Greenville, NC USA. [Terry, Tim] Alberta Canc Board, Cross Canc Inst, Edmonton, AB, Canada. [Courneya, Kerry S.] Univ Alberta, Fac Phys Educ & Recreat, Edmonton, AB T6G 2M7, Canada. [McNeely, Margaret L.] Univ Alberta, Dept Phys Therapy, Edmonton, AB T6G 2M7, Canada. [McNeely, Margaret L.] Univ Alberta, Dept Oncol, Edmonton, AB T6G 2M7, Canada. [Jones, Charlotte A.; Brar, Sony] Univ Calgary, Dept Med, Calgary, AB T2N 1N4, Canada. [Irwin, Melinda L.] Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Brant, Rollin] Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. [Campbell, Kristin L.] Univ British Columbia, Dept Phys Therapy, Vancouver, BC V6T 1W5, Canada. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Yaffe, Martin J.] Sunnybrook Res Inst, Toronto, ON, Canada. [Boyd, Norman F.] Ontario Canc Inst, Campbell Family Inst Breast Canc Res, Toronto, ON M4X 1K9, Canada. [Woolcott, Christy G.] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. RP Friedenreich, CM (reprint author), Alberta Hlth Serv, 1331-29 St NW, Calgary, AB T2N 4N2, Canada. EM Christine.friedenreich@albertahealthservices.ca OI Brant, Rollin/0000-0002-8026-2451 FU Canadian Institutes of Health Research; NCI NIH HHS [R25 CA90956, R25 CA090956, R25 CA090956-05] NR 44 TC 21 Z9 22 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 1112 EP 1121 DI 10.1158/1055-9965.EPI-09-0801 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400032 PM 20332266 ER PT J AU Koshiol, J Wei, WQ Kreimer, AR Ren, JS Gravitt, P Chen, W Kim, E Abnet, CC Zhang, Y Kamangar, F Lin, DM Wang, GQ Roth, MJ Dong, ZW Taylor, PR Qiao, YL Dawsey, SM AF Koshiol, Jill Wei, Wen-Qiang Kreimer, Aimee R. Ren, Jian-Song Gravitt, Patti Chen, Wen Kim, Esther Abnet, Christian C. Zhang, Yu Kamangar, Farin Lin, Dong-Mei Wang, Guo-Qing Roth, Mark J. Dong, Zhi-Wei Taylor, Philip R. Qiao, You-Lin Dawsey, Sanford M. TI The Gastric Cardia Is Not a Target for Human Papillomavirus-Induced Carcinogenesis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENITAL HUMAN PAPILLOMAVIRUSES; RISK; CANCERS; HEAD; DNA; PCR; E6 AB Background: Thousands of people in central Asia die every year from gastric cardia adenocarcinoma (GCA). GCA arises in the transformation zone between the esophagus and the stomach, similar to cervical and oropharyngeal carcinoma, which arise in areas with transformation zone characteristics. The analogous biology of the gastric cardia to the cervix and oropharynx, where human papillomavirus (HPV) is known to cause cancer, raises the possibility that GCA could be a HPV-associated cancer. Given the availability of an effective HPV vaccine and its potential to prevent HPV-associated cancer, we decided to evaluate the prevalence of HPV DNA in GCA. Methods: We collected tumor tissue from 144 histopathologically confirmed GCA patients at Yaocun Commune Hospital (Linxian, China), with rigorous attention to prevent DNAcontamination. We tested for the presence of HPV DNA in fresh-frozen tumor specimens using PCR with sensitive L1-, E6-, and E7-based primers. Results: DNA was adequate, as indicated by beta-globin positivity, in 108 cases. Of these, all (100%; 95% confidence interval, 97-100%) were negative for HPV DNA. Conclusions: These results suggest that HPV does not contribute to gastric cardia carcinogenesis in north central China. Impact: Because GCA does not seem to be a HPV-associated cancer, prophylactic HPV vaccination is unlikely to affect rates of GCA in China. Cancer Epidemiol Biomarkers Prev; 19(4); 1137-9. (C) 2010 AACR. C1 [Koshiol, Jill; Kreimer, Aimee R.; Abnet, Christian C.; Kamangar, Farin; Roth, Mark J.; Taylor, Philip R.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. [Wei, Wen-Qiang; Ren, Jian-Song; Chen, Wen; Zhang, Yu; Wang, Guo-Qing; Dong, Zhi-Wei; Qiao, You-Lin] Peking Union Med Coll, Inst Canc, Dept Epidemiol, Beijing 100021, Peoples R China. [Lin, Dong-Mei] Peking Union Med Coll, Inst Canc, Dept Pathol, Beijing 100021, Peoples R China. [Gravitt, Patti; Kim, Esther] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Gravitt, Patti; Kim, Esther] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21218 USA. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Kim, Esther] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, James Canc Hosp, Columbus, OH 43210 USA. [Kim, Esther] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. RP Koshiol, J (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7070, Rockville, MD 20852 USA. EM koshiolj@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Kreimer, Aimee/H-1687-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; FU CCR NIH HHS [N01RC47702]; Intramural NIH HHS [Z99 CA999999] NR 18 TC 5 Z9 7 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 1137 EP 1139 DI 10.1158/1055-9965.EPI-10-0089 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400035 PM 20332262 ER PT J AU Azzato, EM Pharoah, PDP Harrington, P Easton, DF Greenberg, D Caporaso, NE Chanock, SJ Hoover, RN Thomas, G Hunter, DJ Kraft, P AF Azzato, Elizabeth M. Pharoah, Paul D. P. Harrington, Patricia Easton, Douglas F. Greenberg, David Caporaso, Neil E. Chanock, Stephen J. Hoover, Robert N. Thomas, Gilles Hunter, David J. Kraft, Peter TI A Genome-Wide Association Study of Prognosis in Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GERMLINE GENETIC-VARIATION; EXPRESSION SIGNATURE; DATA SETS; SURVIVAL; POLYMORPHISMS; SUSCEPTIBILITY; DIAGNOSIS; PATTERNS; CYP19A1; ALLELES AB Background: Traditional clinicopathologic features of breast cancer do not account for all the variation in survival. Germline genetic variation may provide additional prognostic information. Materials and Methods: We conducted a genome-wide association study of survival after a diagnosis of breast cancer by obtaining follow-up data and genotyping information on 528,252 single-nucleotide polymorphisms for 1,145 postmenopausal women with invasive breast cancer (7,711 person-years at risk) from the Nurses' Health Study scanned in the Cancer Genetic Markers of Susceptibility initiative. We genotyped the 10 most statistically significant loci (most significant single-nucleotide polymorphism located in ARHGAP10; P = 2.28 x 10(-7)) in 4,335 women diagnosed with invasive breast cancer (38,148 years at risk) in the SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity) breast cancer study. Results: None of the loci replicated in the SEARCH study (all P > 0.10). Assuming a minimum of 10 associated loci, the power to detect at least one with a minor allele frequency of 0.2 conferring a relative hazard of 2.0 at genome-wide significance (P = 5 x 10(-8)) was 99%. Conclusion: We did not identify any common germline variants associated with breast cancer survival overall. Impact: Our data suggest that it is unlikely that there are common germline variants with large effect sizes for breast cancer survival overall (hazard ratio > 2). Instead, it is plausible that common variants associated with survival could be specific to tumor subtypes or treatment approaches. New studies, sufficiently powered, are needed to discover new regions associated with survival overall or by subtype or treatment subgroups. Cancer Epidemiol Biomarkers Prev; 19(4); 1140-3. (C) 2010 AACR. C1 [Azzato, Elizabeth M.; Pharoah, Paul D. P.; Harrington, Patricia] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Cambridge CB2 1TN, England. [Easton, Douglas F.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. [Greenberg, David] Eastern Canc Registrat & Informat Ctr, Unit C Magog Court, Cambridge, England. [Azzato, Elizabeth M.; Caporaso, Neil E.; Chanock, Stephen J.; Hoover, Robert N.; Thomas, Gilles] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. RP Azzato, EM (reprint author), 6120 Execut Plaza,Room 7106, Rockville, MD 20852 USA. EM azzatoe2@mail.nih.gov FU Cancer Research UK [, 10118, 10124, A10119, A10124]; Intramural NIH HHS [NIH0013008807, ZIA CP010187-05]; NCI NIH HHS [P01 CA087969-039003, P01 CA087969, P01 CA087969-019003, P01 CA087969-029003, P01 CA087969-03S19003, P01 CA087969-049003, P01 CA087969-059003, P01 CA087969-069007, P01 CA087969-079007, P01 CA087969-089007, P01 CA087969-099007, P01 CA087969-109007, R21 CA165920] NR 19 TC 37 Z9 37 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2010 VL 19 IS 4 BP 1140 EP 1143 DI 10.1158/1055-9965.EPI-10-0085 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 607FL UT WOS:000278484400036 PM 20332263 ER PT J AU Prindiville, SA Ried, T AF Prindiville, Sheila A. Ried, Thomas TI Interphase Cytogenetics of Sputum Cells for the Early Detection of Lung Carcinogenesis SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID IN-SITU HYBRIDIZATION; AIR-FLOW OBSTRUCTION; INSITU HYBRIDIZATION; CHROMOSOME-ABERRATIONS; TUMOR-CELLS; CANCER; CARCINOMA; ABNORMALITIES; PREDICTOR; CYTOLOGY AB This perspective on Varella-Garcia et al. (beginning on p. 447 in this issue of the journal) examines the role of interphase fluorescence in situ hybridization for the early detection of lung cancer. This work is an important step toward identifying and validating a molecular marker in sputum samples for lung cancer early detection and highlights the value of establishing cohort studies with biorepositories of samples collected from participants followed over time for disease development. Cancer Prev Res; 3(4); 416-9. (C)2010 AACR. C1 [Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20852 USA. RP Prindiville, SA (reprint author), NCI, Coordinating Ctr Clin Trials, Ctr Canc Res, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd, Bethesda, MD 20852 USA. EM sheila.prindiville@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 36 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2010 VL 3 IS 4 BP 416 EP 419 DI 10.1158/1940-6207.CAPR-10-0045 PG 4 WC Oncology SC Oncology GA 577ZS UT WOS:000276263600006 PM 20332302 ER PT J AU Hoque, A Ambrosone, CB Till, C Goodman, PJ Tangen, C Kristal, A Lucia, S Wang, Q Kappil, M Thompson, I Hsing, AW Parnes, H Santella, RM AF Hoque, Ashraful Ambrosone, Christine B. Till, Cathee Goodman, Phyllis J. Tangen, Cathy Kristal, Alan Lucia, Scott Wang, Qiao Kappil, Maya Thompson, Ian Hsing, Ann W. Parnes, Howard Santella, Regina M. TI Serum Oxidized Protein and Prostate Cancer Risk within the Prostate Cancer Prevention Trial SO CANCER PREVENTION RESEARCH LA English DT Article ID OXIDATIVELY MODIFIED PROTEINS; SUPEROXIDE-DISMUTASE; PLASMA; DISEASE; SMOKERS; FRUIT; MARKERS; STRESS AB To evaluate the role of oxidative stress in prostate cancer risk, we analyzed serum levels of protein carbonyl groups in 1,808 prostate cancer cases and 1,805 controls, nested in the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial that found finasteride decreased prostate cancer risk. There were no significant differences in protein carbonyl levels in baseline samples between those later diagnosed with prostate cancer and those without at the end of study biopsy. Adjusted odds ratios and 95% confidence intervals (95% CI) for the 4th quartile of protein carbonyl level for the combined, placebo, and finasteride arms were 1.03 (95% CI, 0.85-1.24), 0.88 (95% CI, 0.69-1.12), and 1.27 (95% CI, 0.94-1.71), respectively. There were no significant associations between carbonyl level and risk when analyzing high-grade and low-grade disease separately, nor did finasteride affect protein oxidation levels. The results of this large nested case-control study do not support the hypothesis that oxidative stress, at least as measured by protein carbonyl level, plays a role in prostate cancer. Cancer Prev Res; 3(4); 478-83. (C)2010 AACR. C1 [Santella, Regina M.] Columbia Univ, Div Environm Hlth Sci, New York, NY 10032 USA. [Hoque, Ashraful] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Till, Cathee; Goodman, Phyllis J.; Tangen, Cathy; Kristal, Alan] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lucia, Scott] Univ Colorado Denver, Aurora, CO USA. [Hsing, Ann W.; Parnes, Howard] NCI, Bethesda, MD 20892 USA. [Thompson, Ian] Univ Texas San Antonio, San Antonio, TX USA. RP Santella, RM (reprint author), Columbia Univ, Div Environm Hlth Sci, 630 W 168th St, New York, NY 10032 USA. EM rps1@columbia.edu OI Kristal, Alan/0000-0002-7329-1617; , Maya/0000-0003-2913-2392 FU National Cancer Institute and the National Institute of Environmental Health Sciences [P01 CA108964, CA37429, P30 ES009089, R03 CA117490, P30 CA013696] FX Grants P01 CA108964, CA37429, P30 ES009089, R03 CA117490, and P30 CA013696 from the National Cancer Institute and the National Institute of Environmental Health Sciences. NR 18 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2010 VL 3 IS 4 BP 478 EP 483 DI 10.1158/1940-6207.CAPR-09-0201 PG 6 WC Oncology SC Oncology GA 577ZS UT WOS:000276263600013 PM 20332306 ER PT J AU Gamero, AM Young, MR Mentor-Marcel, R Bobe, G Scarzello, AJ Wise, J Colburn, NH AF Gamero, Ana M. Young, Matthew R. Mentor-Marcel, Roycelynn Bobe, Gerd Scarzello, Anthony J. Wise, Jennifer Colburn, Nancy H. TI STAT2 Contributes to Promotion of Colorectal and Skin Carcinogenesis SO CANCER PREVENTION RESEARCH LA English DT Article ID COLITIS-ASSOCIATED CANCER; NF-KAPPA-B; SIGNALING PATHWAY; ALPHA-INTERFERON; MOUSE MODELS; IFN-GAMMA; MICE; INFLAMMATION; TUMORIGENESIS; CELLS AB Signal transducer and activator of transcription 2 (STAT2) is an essential transcription factor in the type I IFN (IFN-alpha/beta) signal transduction pathway and known for its role in mediating antiviral immunity and cell growth inhibition. Unlike other members of the STAT family, IFNs are the only cytokines known to date that can activate STAT2. Given the inflammatory and antiproliferative dual nature of IFNs, we hypothesized that STAT2 prevents inflammation-induced colorectal and skin carcinogenesis by altering the inflammatory immune response. Contrary to our hypothesis, deletion of STAT2 inhibited azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis as measured by prolonged survival, lower adenoma incidence, smaller polyps, and less chronic inflammation. STAT2 deficiency also inhibited 7,12-dimethylbenz( a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis as indicated by reduced papilloma multiplicity. A potential mechanism by which STAT2 promotes carcinogenesis is through activation of proinflammatory mediators. Deletion of STAT2 decreased azoxymethane/dextran sodium sulfate-induced expression and release of proinflammatory mediators, such as interleukin-6 and CCL2, and decreased interleukin-6 release from skin carcinoma cells, which then decreased STAT3 activation. Our findings identify STAT2 as a novel contributor to colorectal and skin carcinogenesis that may act to increase the gene expression and secretion of proinflammatory mediators, which in turn activate the oncogenic STAT3 signaling pathway. Cancer Prev Res; 3(4); 495-504. (C)2010 AACR. C1 [Gamero, Ana M.; Scarzello, Anthony J.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Young, Matthew R.; Mentor-Marcel, Roycelynn; Bobe, Gerd; Colburn, Nancy H.] NCI, Lab Canc Prevent, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Wise, Jennifer] NCI, Lab Anim Sci Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. RP Gamero, AM (reprint author), Temple Univ, Sch Med, Philadelphia, PA 19140 USA. EM gameroa@temple.edu FU National Cancer Institute [K22CA095326]; NIH [01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX National Cancer Institute, NIH Contract No. N01-CO-12400; National Cancer Institute Award Number K22CA095326 ( A. M. Gamero); and Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 41 TC 16 Z9 20 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2010 VL 3 IS 4 BP 495 EP 504 DI 10.1158/1940-6207.CAPR-09-0105 PG 10 WC Oncology SC Oncology GA 577ZS UT WOS:000276263600015 PM 20233899 ER PT J AU Toll, L Jimenez, L Polgar, W Green, C Gow, J O'Loughlin, K Bernier, M Wainer, IW AF Toll, Lawrence Jimenez, Lucita Polgar, Willma Green, Carol Gow, Jason O'Loughlin, Kathleen Bernier, Michel Wainer, Irving W. TI Selective beta(2)-adrenergic receptor agonists inhibit the proliferation of 1321N1 astrocytoma cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Toll, Lawrence; Jimenez, Lucita; Polgar, Willma; Green, Carol; Gow, Jason; O'Loughlin, Kathleen] SRI Int, Menlo Pk, CA 94025 USA. [Bernier, Michel; Wainer, Irving W.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR PY 2010 VL 70 SU 8 MA 724 DI 10.1158/1538-7445.AM10-724 PG 3 WC Oncology SC Oncology GA V45NR UT WOS:000209823800081 ER PT J AU Andreotti, G Boffetta, P Rosenberg, PS Berndt, SI Karami, S Menashe, I Yeager, M Chanock, SJ Zaridze, D Matteev, V Janout, V Kollarova, H Bencko, V Navratilova, M Szeszenia-Dabrowska, N Mates, D Rothman, N Brennan, P Chow, WH Moore, LE AF Andreotti, Gabriella Boffetta, Paolo Rosenberg, Philip S. Berndt, Sonja I. Karami, Sara Menashe, Idan Yeager, Meredith Chanock, Stephen J. Zaridze, David Matteev, Vsevolod Janout, Vladimir Kollarova, Hellena Bencko, Vladimir Navratilova, Marie Szeszenia-Dabrowska, Neonilia Mates, Dana Rothman, Nathaniel Brennan, Paul Chow, Wong-Ho Moore, Lee E. TI Variants in blood pressure genes and the risk of renal cell carcinoma SO CARCINOGENESIS LA English DT Article ID CANCER-RISK; KIDNEY CANCER; ANGIOTENSINOGEN GENE; VEGETABLE INTAKE; CANDIDATE GENES; FAMILY HISTORY; HYPERTENSION; POLYMORPHISMS; ASSOCIATION; MEDICATIONS AB Hypertension is a known risk factor for renal cell carcinoma (RCC), although the underlying biological mechanisms of its action are unknown. To clarify the role of hypertension in RCC, we examined the risk of RCC in relation to 142 single-nucleotide polymorphisms (SNPs) in eight genes having a role in blood pressure control. We analyzed 777 incident and histologically confirmed RCC cases and 1035 controls who completed an in-person interview as part of a multi-center, hospital-based case-control study in Central Europe. Genotyping was conducted with an Illumina (R) GoldenGate (R) Oligo Pool All assay using germ line DNA. Of the eight genes examined, AGT (angiotensinogen) was most strongly associated with RCC (minimum P-value permutation test = 0.02). Of the 17 AGT tagging SNPs considered, associations were strongest for rs1326889 [odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.15-1.58] and rs2493137 (OR = 1.31, 95% CI = 1.12-1.54), which are located in the promoter. Stratified analysis revealed that the effects of the AGT SNPs were statistically significant in participants with hypertension or high body mass index (BMI) (>= 25 kg/m(2)), but not in subjects without hypertension and with a normal BMI (< 25 kg/m(2)). Also, haplotypes with risk-conferring alleles of markers located in the promoter and intron 1 regions of AGT were significantly associated with RCC compared with the common haplotype in subjects with hypertension or high BMI (global P = 0.003). Our findings suggest that common genetic variants of AGT, particularly those in the promoter, increase RCC risk among subjects who are hypertensive or overweight. C1 [Andreotti, Gabriella; Rosenberg, Philip S.; Berndt, Sonja I.; Karami, Sara; Menashe, Idan; Rothman, Nathaniel; Chow, Wong-Ho; Moore, Lee E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Boffetta, Paolo; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. [Zaridze, David; Matteev, Vsevolod] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. [Janout, Vladimir; Kollarova, Hellena] Palacky Univ, Fac Med, Dept Prevent Med, CR-77147 Olomouc, Czech Republic. [Bencko, Vladimir] Inst Hyg & Epidemiol, CR-10042 Prague, Czech Republic. [Navratilova, Marie] Masaryk Mem Canc Inst, Brno, Czech Republic. [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Lodz, Poland. [Mates, Dana] Inst Publ Hlth, Bucharest, Romania. RP Andreotti, G (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, EPS, 6120 Execut Blvd,Room 8011,MSC 7240, Rockville, MD 20852 USA. EM andreotg@mail.nih.gov RI Zaridze, David/K-5605-2013; Janout, Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; OI mates, dana/0000-0002-6219-9807 FU National Cancer Institute; National Institutes of Health; Department of Health and Human Services FX Federal funds from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services. NR 30 TC 18 Z9 19 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2010 VL 31 IS 4 BP 614 EP 620 DI 10.1093/carcin/bgp321 PG 7 WC Oncology SC Oncology GA 578HV UT WOS:000276285200010 PM 20047954 ER PT J AU Truong, T Sauter, W McKay, JD Hosgood, HD Gallagher, C Amos, CI Spitz, M Muscat, J Lazarus, P Illig, T Wichmann, HE Bickeboller, H Risch, A Dienemann, H Zhang, ZF Naeim, BP Yang, P Zienolddiny, S Haugen, A Le Marchand, L Hong, YC Kim, JH Duell, EJ Andrew, AS Kiyohara, C Shen, HB Matsuo, K Suzuki, T Seow, A Ng, DPK Lan, Q Zaridze, D Szeszenia-Dabrowska, N Lissowska, J Rudnai, P Fabianova, E Constantinescu, V Bencko, V Foretova, L Janout, V Caporaso, NE Albanes, D Thun, M Landi, MT Trubicka, J Lener, M Lubinski, J Wang, Y Chabrier, A Boffetta, P Brennan, P Hung, RJ AF Truong, Therese Sauter, Wiebke McKay, James D. Hosgood, H. Dean, III Gallagher, Carla Amos, Christopher I. Spitz, Margaret Muscat, Joshua Lazarus, Philip Illig, Thomas Wichmann, H. Erich Bickeboeller, Heike Risch, Angela Dienemann, Hendrik Zhang, Zuo-Feng Naeim, Behnaz Pezeshki Yang, Ping Zienolddiny, Shanbeh Haugen, Aage Le Marchand, Loic Hong, Yun-Chul Kim, Jin Hee Duell, Eric J. Andrew, Angeline S. Kiyohara, Chikako Shen, Hongbing Matsuo, Keitaro Suzuki, Takeshi Seow, Adeline Ng, Daniel P. K. Lan, Qing Zaridze, David Szeszenia-Dabrowska, Neonilia Lissowska, Jolanta Rudnai, Peter Fabianova, Eleonora Constantinescu, Vali Bencko, Vladimir Foretova, Lenka Janout, Vladimir Caporaso, Neil E. Albanes, Demetrius Thun, Michael Landi, Maria Teresa Trubicka, Joanna Lener, Marcin Lubinski, Jan Wang, Ying Chabrier, Amelie Boffetta, Paolo Brennan, Paul Hung, Rayjean J. CA EPIC-Lung TI International Lung Cancer Consortium: Coordinated association study of 10 potential lung cancer susceptibility variants SO CARCINOGENESIS LA English DT Article ID METHYLENE-TETRAHYDROFOLATE REDUCTASE; GENE POLYMORPHISMS; METHYLENETETRAHYDROFOLATE REDUCTASE; CHINESE POPULATION; SEQUENCE VARIANTS; INCREASED RISK; CENTRAL-EUROPE; DNA-REPAIR; XUAN-WEI; CELL AB Background. Analysis of candidate genes in individual studies has had only limited success in identifying particular gene variants that are conclusively associated with lung cancer risk. In the International Lung Cancer Consortium (ILCCO), we conducted a coordinated genotyping study of 10 common variants selected because of their prior evidence of an association with lung cancer. These variants belonged to candidate genes from different cancer-related pathways including inflammation (IL1B), folate metabolism (MTHFR), regulatory function (AKAP9 and CAMKK1), cell adhesion (SEZL6) and apoptosis (FAS, FASL, TP53, TP53BP1 and BAT3). Methods. Genotype data from 15 ILCCO case-control studies were available for a total of 8431 lung cancer cases and 11 072 controls of European descent and Asian ethnic groups. Unconditional logistic regression was used to model the association between each variant and lung cancer risk. Results. Only the association between a non-synonymous variant of TP53BP1 (rs560191) and lung cancer risk was significant (OR = 0.91, P = 0.002). This association was more striking for squamous cell carcinoma (OR = 0.86, P = 6 x 10(-4)). No heterogeneity by center, ethnicity, smoking status, age group or sex was observed. In order to confirm this association, we included results for this variant from a set of independent studies (9966 cases/11 722 controls) and we reported similar results. When combining all these studies together, we reported an overall OR = 0.93 (0.89-0.97) (P = 0.001). This association was significant only for squamous cell carcinoma [OR = 0.89 (0.85-0.95), P = 1 x 10(-4)]. Conclusion. This study suggests that rs560191 is associated to lung cancer risk and further highlights the value of consortia in replicating or refuting published genetic associations. C1 [Truong, Therese; McKay, James D.; Duell, Eric J.; Chabrier, Amelie; Boffetta, Paolo; Brennan, Paul; Hung, Rayjean J.] Int Agcy Res Canc, F-69008 Lyon, France. [Truong, Therese] INSERM, U1018, CESP, Ctr Res Epidemiol & Populat Hlth, F-94807 Villejuif, France. [Sauter, Wiebke; Illig, Thomas; Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany. [Sauter, Wiebke; Wichmann, H. Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany. [Hosgood, H. Dean, III; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Gallagher, Carla; Muscat, Joshua; Lazarus, Philip] Penn State Coll Med, Hershey, PA 17033 USA. [Amos, Christopher I.; Spitz, Margaret] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wichmann, H. Erich] Klinikum Grosshadern, D-81377 Munich, Germany. [Bickeboeller, Heike] Univ Gottingen, Sch Med, D-37073 Gottingen, Germany. [Risch, Angela] German Canc Res Ctr, DKFZ, D-69120 Heidelberg, Germany. [Dienemann, Hendrik] Univ Heidelberg, Thoraxklin Heidelberg, D-69126 Heidelberg, Germany. [Zhang, Zuo-Feng; Naeim, Behnaz Pezeshki] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Yang, Ping] Mayo Clin, Ctr Canc, Rochester, MN 55905 USA. [Zienolddiny, Shanbeh; Haugen, Aage] Natl Inst Occupat Hlth, N-0167 Oslo, Norway. [Le Marchand, Loic] Univ Hawaii, Honolulu, HI 96822 USA. [Hong, Yun-Chul; Kim, Jin Hee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. [Hong, Yun-Chul; Kim, Jin Hee] Seoul Natl Univ, Med Res Ctr, Inst Environm Med, Seoul 110799, South Korea. [Duell, Eric J.; Andrew, Angeline S.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. [Duell, Eric J.; Andrew, Angeline S.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA. [Duell, Eric J.] Catalan Inst Oncol, Unit Nutr Environm & Canc, Canc Epidemiol Res Programme, Barcelona 08907, Spain. [Kiyohara, Chikako] Kyushu Univ, Fukuoka 8128582, Japan. [Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Nanjing 210029, Peoples R China. [Matsuo, Keitaro; Suzuki, Takeshi] Aichi Canc Ctr, Res Inst, Aichi 4648681, Japan. [Seow, Adeline; Ng, Daniel P. K.] Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117597, Singapore. [Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow 115478, Russia. [Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, PL-90950 Lodz, Poland. [Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr & Inst Oncol, PL-02781 Warsaw, Poland. [Rudnai, Peter] Natl Inst Environm Hlth, H-1097 Budapest, Hungary. [Fabianova, Eleonora] Specialized Inst Hyg & Epidemiol, Banska 97556, Bystrica, Slovakia. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska 97556, Bystrica, Slovakia. [Constantinescu, Vali] Inst Publ Hlth, Bucharest 050463, Romania. [Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, CZ-12800 Prague, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno 65653, Czech Republic. [Janout, Vladimir] Palacky Univ, Olomouc 77515, Czech Republic. [Caporaso, Neil E.; Albanes, Demetrius; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Thun, Michael] Amer Canc Soc, Atlanta, GA 30301 USA. [Trubicka, Joanna; Lener, Marcin; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathomorphol, Int Hereditary Canc Ctr, PL-70204 Szczecin, Poland. [Wang, Ying; Hung, Rayjean J.] Samuel Lunenfeld Res Inst, Toronto, ON M5T 3L9, Canada. RP Brennan, P (reprint author), Int Agcy Res Canc, Genet Epidemiol Grp, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM brennan@iarc.fr RI Hung, Rayjean/A-7439-2013; Zaridze, David/K-5605-2013; Clavel-Chapelon, Francoise/G-6733-2014; Janout, Vladimir/M-5133-2014; Albanes, Demetrius/B-9749-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010; Zienolddiny, Shanbeh/O-7392-2015; Krogh, Vittorio/K-2628-2016; Risch, Angela/H-2669-2013; OI Matsuo, Keitaro/0000-0003-1761-6314; Krogh, Vittorio/0000-0003-0122-8624; Risch, Angela/0000-0002-8026-5505; Duell, Eric J/0000-0001-5256-0163; Lissowska, Jolanta/0000-0003-2695-5799 FU US National Institutes of Health; National Cancer Institute [R03 CA133939-01]; Central Europe study-World Cancer Research Fund; European Commission's INCO-COPERNICUS Program [IC15-CT98-0332]; Norvegian study-The Norwegian Research Council; Norwegian Cancer Society FX US National Institutes of Health, National Cancer Institute (R03 CA133939-01); Central Europe study-World Cancer Research Fund and European Commission's INCO-COPERNICUS Program (IC15-CT98-0332); Norvegian study-The Norwegian Research Council; Norwegian Cancer Society; Aichi Cancer Center study-Grants- in-Aid for Scientific Research, Ministry of Education, Science, Sports, Culture and Technology of Japan; MD Anderson study-National Institutes of Health (CA127219, CA55769, CA121197); Penn State study-Public Health Service grants (K99 CA131477), National Institutes of Health (P01 CA68384, K07 CA104231); NCI-China study-Intramural National Cancer Institute program (N01 CO12400); Singapore study-Singapore National Medical Research Council; Seoul study-Eco-technopia 21 project, Ministry of Environment, Republic of Korea; `` Deutsche Krebshilfe'' (70-2387, 70-2919); Mayo Clinic study-National Institutes of Health (CA77118, CA80127, CA84354); Norris Cotton Cancer Center study-National Center for Research Resources, National Institutes of Health (P20RR018787). Environment and Genetics in Lung Cancer Etiology, Prostate, Lung, Colon, Ovary Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention studies, genotyping of Alpha-Tocopherol, Beta-Carotene Cancer Prevention study, Cancer Prevention Study II Nutrition Cohort and part of Prostate, Lung, Colon, Ovary Screening Trial-Intramural Research Program, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; AlphaTocopherol, Beta-Carotene Cancer Prevention study-US Public Health Service contracts, National Cancer Institute (N01-CN-45165, N01-RC-45035, N01-RC-37004); PLCO study was also supported by individual contracts from the National Cancer Institute to the University of Colorado Denver (NO1-CN-25514); Georgetown University (NO1-CN-25522); Pacific Health Research Institute (NO1-CN25515); Henry Ford Health System (NO1-CN-25512); University of Minnesota (NO1-CN-25513); Washington University (NO1-CN25516); University of Pittsburgh (NO1-CN-25511); University of Utah (NO1-CN-25524); Marshfield Clinic Research Foundation (NO1-CN-25518); University of Alabama at Birmingham (NO1CN- 75022); Westat (NO1-CN-25476); University of California, Los Angeles (NO1-CN-25404); The Cancer Prevention Study II Nutrition Cohort was supported by the American Cancer Society; The NIH Genes, Environment and Health Initiative partly funded DNA extraction and statistical analyses (HG-06-033-NCI-01, RO1HL09117201); genotyping at the Johns Hopkins University Center for Inherited Disease Research (U01HG004438, NIH HHSN268200782096C); study coordination at the GENEVA Coordination Center (U01 HG004446) for Environment and Genetics in Lung Cancer Etiology and part of PLCO studies. German study-BMBF, Germany (Competence Network Radiation Research, project: individual susceptibility and genomic instability); KORA research platform-the Helmholtz Center Munich, German Research Center for Environmental Health. NR 55 TC 29 Z9 30 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2010 VL 31 IS 4 BP 625 EP 633 DI 10.1093/carcin/bgq001 PG 9 WC Oncology SC Oncology GA 578HV UT WOS:000276285200012 PM 20106900 ER PT J AU Lam, TK Rotunno, M Lubin, JH Wacholder, S Consonni, D Pesatori, AC Bertazzi, PA Chanock, SJ Burdette, L Goldstein, AM Tucker, MA Caporaso, NE Subar, AF Landi, MT AF Lam, Tram Kim Rotunno, Melissa Lubin, Jay H. Wacholder, Sholom Consonni, Dario Pesatori, Angela C. Bertazzi, Pier Alberto Chanock, Stephen J. Burdette, Laurie Goldstein, Alisa M. Tucker, Margaret A. Caporaso, Neil E. Subar, Amy F. Landi, Maria Teresa TI Dietary quercetin, quercetin-gene interaction, metabolic gene expression in lung tissue and lung cancer risk SO CARCINOGENESIS LA English DT Article ID FLAVONOL QUERCETIN; CIGARETTE-SMOKING; DNA-ADDUCTS; INHIBITION; HEALTH; CELLS; POLYMORPHISMS; INDUCTION; ENZYMES; ISOTHIOCYANATES AB Epidemiological and mechanistic evidence on the association of quercetin-rich food intake with lung cancer risk and carcinogenesis are inconclusive. We investigated the role of dietary quercetin and the interaction between quercetin and P450 and glutathione S-transferase (GST) polymorphisms on lung cancer risk in 1822 incident lung cancer cases and 1991 frequency-matched controls from the Environment And Genetics in Lung cancer Etiology study. In non-tumor lung tissue from 38 adenocarcinoma patients, we assessed the correlation between quercetin intake and messenger RNA expression of the same P450 and GST metabolic genes. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific quintiles of intake were calculated using unconditional logistic regression adjusting for putative risk factors. Frequent intake of quercetin-rich foods was inversely associated with lung cancer risk (OR = 0.49; 95% CI: 0.37-0.67; P-trend < 0.001) and did not differ by P450 or GST genotypes, gender or histological subtypes. The association was stronger in subjects who smoked > 20 cigarettes per day (OR = 0.35; 95% CI: 0.19-0.66; P-trend = 0.003). Based on a two-sample t-test, we compared gene expression and high versus low consumption of quercetin-rich foods and observed an overall upregulation of GSTM1, GSTM2, GSTT2, and GSTP1 as well as a downregulation of specific P450 genes (P-values < 0.05, adjusted for age and smoking status). In conclusion, we observed an inverse association of quercetin-rich food with lung cancer risk and identified a possible mechanism of quercetin-related changes in the expression of genes involved in the metabolism of tobacco carcinogens in humans. Our findings suggest an interplay between quercetin intake, tobacco smoking, and lung cancer risk. Further research on this relationship is warranted. C1 [Lam, Tram Kim; Rotunno, Melissa; Goldstein, Alisa M.; Tucker, Margaret A.; Caporaso, Neil E.; Landi, Maria Teresa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lubin, Jay H.; Wacholder, Sholom] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lam, Tram Kim] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Univ Milan, EPOCA, Epidemiol Res Ctr, Milan, Italy. [Consonni, Dario; Pesatori, Angela C.; Bertazzi, Pier Alberto] Osped Maggiore Policlin Mangiagalli & Regina Elen, Fdn IRCCS, Epidemiol Unit, Milan, Italy. [Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Chanock, Stephen J.; Burdette, Laurie] NCI, Core Genotyping Facil, NIH, Gaithersburg, MD 20877 USA. [Chanock, Stephen J.; Burdette, Laurie] NCI, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA. [Subar, Amy F.] NCI, Risk Factor Monitoring & Method Branch, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI bertazzi, pietro alberto/D-5039-2017; OI bertazzi, pietro alberto/0000-0003-3475-2449; pesatori, angela/0000-0002-0261-3252 FU Intramural Research Program of National Institutes of Health; National Cancer Institute; Division of Cancer Epidemiology and Genetics FX Intramural Research Program of National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 52 TC 28 Z9 29 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2010 VL 31 IS 4 BP 634 EP 642 DI 10.1093/carcin/bgp334 PG 9 WC Oncology SC Oncology GA 578HV UT WOS:000276285200013 PM 20044584 ER PT J AU Nussenzweig, A Nussenzweig, MC AF Nussenzweig, Andre Nussenzweig, Michel C. TI Origin of Chromosomal Translocations in Lymphoid Cancer SO CELL LA English DT Review ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; INDUCED CYTIDINE DEAMINASE; END-JOINING PATHWAY; B-CELL LYMPHOMA; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION; DNA-REPAIR; MAMMALIAN-CELLS; GENOMIC INSTABILITY AB Aberrant fusions between heterologous chromosomes are among the most prevalent cytogenetic abnormalities found in cancer cells. Oncogenic chromosomal translocations provide cells with a proliferative or survival advantage. They may either initiate transformation or be acquired secondarily as a result of genomic instability. Here, we highlight recent advances toward understanding the origin of chromosomal translocations in incipient lymphoid cancers and how tumor-suppressive pathways normally limit the frequency of these aberrant recombination events. Deciphering the mechanisms that mediate chromosomal fusions will open new avenues for developing therapeutic strategies aimed at eliminating lesions that lead to the initiation, maintenance, and progression of cancer. C1 [Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Labs Mol Immunol, New York, NY 10065 USA. [Nussenzweig, Michel C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov; nussen@mail.rockefeller.edu FU National Institutes of Health (NIH) [AI037526] FX We thank E. Callen for drawing the figures, and A. Bothmer, S. Bunting, J. Danial, E. Callen, S. Deroubaix, M. Di Virgilio, N. Feldhan, A. Gazumyan, M. Jankovic, I. Klein, K. McBride, R. Pavri, A. Ramiro, B. Reina San- Martin, and D. Robbiani for comments on the manuscript. M. C. N. is a Howard Hughes Medical Institute investigator and is supported by National Institutes of Health (NIH) grant AI037526. A. N. is supported by the Intramural Research program of the NIH, National Cancer Institute, Center for Cancer Research. NR 121 TC 146 Z9 148 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 1 PY 2010 VL 141 IS 1 BP 27 EP 38 DI 10.1016/j.cell.2010.03.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 577GS UT WOS:000276211100010 PM 20371343 ER PT J AU Huang, Y Guigon, CJ Fan, J Cheng, SY Zhu, GZ AF Huang, Yue Guigon, Celine J. Fan, Jun Cheng, Sheue-yann Zhu, Guo-Zhang TI Pituitary homeobox 2 (PITX2) promotes thyroid carcinogenesis by activation of cyclin D2 SO CELL CYCLE LA English DT Article DE thyroid cancer; PITX2; homeodomain transcription factor; cyclin D2; beta-catenin signaling ID BETA-CATENIN; MOLECULAR-GENETICS; MOUSE MODEL; EXPRESSION; PATHWAY; RECEPTOR; HORMONE; TRANSCRIPTION; CARCINOMA; CANCER AB pituitary homeobox 2 (PITX2), a Paired-like homeodomain transcription factor and a downstream effector of beta-catenin signaling, plays substantial roles in normal embryonic development but its possible involvement in tumorigenesis was unknown. In this study, we extend its function in human cancer. Remarkably, we found that PITX2 was frequently expressed in human follicular cell-derived (papillary, follicular and anaplastic) thyroid cancer tissues but not in normal thyroids, indicating for the first time that overactivated PITX2 may contribute to thyroid cancer. Cell-based and biochemical studies were performed to uncover the molecular mechanism of PITX2 action in thyroid cancer. Knockdown of PITX2 gene expression in human thyroid cancer cells significantly reduced cell proliferation and soft-agar colony formation. Biochemical analysis of cell cycle regulators upon PITX2 knockdown revealed downregulation of Cyclin D1, Cyclin D2 and dephosphorylation of Rb. Chromatin immunoprecipitation and promoter reporter assay indicated that Cyclin D2 was a direct target gene of PITX2. Consistently, we observed that high expression levels of Cyclin D2 were frequently associated with PITX2 expression in follicular cell-derived thyroid cancer tissues. to confirm our results in vivo, we took advantage of a mouse model of thyroid cancer (TRbeta(PV/PV) mouse). Consistently, the aberrant elevation of PITX2 levels in the thyroid cancer of TRbeta(PV/PV) mice was accompanied by upregulation of Cyclin D1, Cyclin D2 and increased phosphorylation of Rb. Collectively, our findings demonstrate that the overactivated PITX2-Cyclin D2 pathway promotes thyroid tumorigenesis, and they provide the first evidence implicating an oncogenic role of PITX2 in human cancer. C1 [Huang, Yue; Zhu, Guo-Zhang] Marshall Univ, Biomed Sci Grad Program, Huntington, WV 25755 USA. [Fan, Jun] Marshall Univ, Dept Biochem & Microbiol, Huntington, WV USA. [Zhu, Guo-Zhang] Marshall Univ, Dept Biol Sci, Huntington, WV USA. [Zhu, Guo-Zhang] Marshall Univ, Cell Differentiat & Dev Ctr, Huntington, WV USA. [Guigon, Celine J.; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Zhu, GZ (reprint author), Marshall Univ, Biomed Sci Grad Program, Huntington, WV 25755 USA. EM zhu4@marshall.edu RI HUANG, YUE/A-9694-2009 FU NIDCR/NIH [5P50DE019032] FX West Virginia Experimental Program to Stimulate Competitive Research (EPSCoR)-Research Challenge Fund to G.-Z. Zhu and SPORE # 5P50DE019032 from NIDCR/NIH to Dr. David Sidransky, Johns Hopkins University. NR 32 TC 22 Z9 22 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2010 VL 9 IS 7 BP 1333 EP 1341 PG 9 WC Cell Biology SC Cell Biology GA 579KO UT WOS:000276369300029 PM 20372070 ER PT J AU Abdelmohsen, K Kim, MM Srikantan, S Mercken, EM Brennan, SE Wilson, GM de Cabo, R Gorospe, M AF Abdelmohsen, Kotb Kim, Mihee M. Srikantan, Subramanya Mercken, Evi M. Brennan, Sarah E. Wilson, Gerald M. de Cabo, Rafael Gorospe, Myriam TI miR-519 suppresses tumor growth by reducing HuR levels SO CELL CYCLE LA English DT Article DE RNA-binding protein; post-transcriptional gene regulation; tumor suppressor microRNA; translational control ID BINDING PROTEIN HUR; MESSENGER-RNAS; CANCER; EXPRESSION; MICRORNAS AB The RNA-binding protein huR is highly abundant in many cancers. huR expression was recently found to be repressed by microRNA miR-519, which potently lowered huR translation without influencing huR mRNA abundance. here, we examined the levels of huR and miR-519 in pairs of cancer and adjacent healthy tissues from ovary, lung and kidney. In the three sample collections, the cancer specimens showed dramatically higher huR levels, unchanged huR mRNA concentrations, and markedly reduced miR-519 levels, when compared with healthy tissues. As tested using human cervical carcinoma cells, miR-519 reduced tumorigenesis in athymic mice. Compared with the tumors arising from control cells, cells overexpressing miR-519 formed significantly smaller tumors, while cells expressing reduced miR-519 levels gave rise to substantially larger tumors. evidence that the miR-519-elicited reduction of huR was critical for its tumor suppressor influence was obtained by reducing huR, as huR-silenced cells formed markedly smaller tumors and were unable to form large tumors even after lowering miR-519 abundance. Together, our data reveal that miR-519 inhibits tumorigenesis in large part by repressing huR expression. C1 [Abdelmohsen, Kotb; Kim, Mihee M.; Srikantan, Subramanya; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. [Mercken, Evi M.; de Cabo, Rafael] NIA, Lab Expt Gerontol, IRP, NIH, Baltimore, MD 21224 USA. [Brennan, Sarah E.; Wilson, Gerald M.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Brennan, Sarah E.; Wilson, Gerald M.] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Abdelmohsen, K (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810; , rafael/0000-0003-2830-5693 FU American Cancer Society [RSG-07-293-01-GMC] FX This research was supported by the NIA-IRP, NIH. We thank N.K. Hooten, D. Boyer, and the NIA Animal Facility (NIA-IRP, NIH). S. E. B. and G. M. W. were funded by American Cancer Society grant RSG-07-293-01-GMC. NR 21 TC 55 Z9 57 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2010 VL 9 IS 7 BP 1354 EP 1359 PG 6 WC Cell Biology SC Cell Biology GA 579KO UT WOS:000276369300031 PM 20305372 ER PT J AU Ke, HN Parron, VI Reece, J Zhang, JY Akiyama, SK French, JE AF Ke, Hengning Parron, Vandy I. Reece, Jeff Zhang, Jennifer Y. Akiyama, Steven K. French, John E. TI BCL2 inhibits cell adhesion, spreading, and motility by enhancing actin polymerization SO CELL RESEARCH LA English DT Article DE BCL2; gelsolin; motility; actin polymerization ID MAMMARY EPITHELIAL-CELLS; TUMOR INVASION; BREAST-CANCER; GELSOLIN; MIGRATION; EXPRESSION; METASTASIS; INTEGRINS; CYTOSKELETON; ASSOCIATION AB BCL2 is best known as a multifunctional anti-apoptotic protein. However, little is known about its role in cell-adhesive and motility events. Here, we show that BCL2 may play a role in the regulation of cell adhesion, spreading, and motility. When BCL2 was overexpressed in cultured murine and human cell lines, cell spreading, adhesion, and motility were impaired. Consistent with these results, the loss of Bcl2 resulted in higher motility observed in Bcl2-null mouse embryonic fibroblast (MEF) cells compared to wild type. The mechanism of BCL2 regulation of cell adhesion and motility may involve formation of a complex containing BCL2, actin, and gelsolin, which appears to functionally decrease the severing activity of gelsolin. We have observed that the lysate from MCF-7 and NIH3T3 cells that overexpressed BCL2 enhanced actin polymerization in cell-free in vitro assays. Confocal immunofluorescent localization of BCL2 and F-actin during spreading consistently showed that increased expression of BCL2 resulted in increased F-actin polymerization. Thus, the formation of BCL2 and gelsolin complexes (which possibly contain other proteins) appears to play a critical role in the regulation of cell adhesion and migration. Given the established correlation of cell motility with cancer metastasis, this result may explain why the expression of BCL2 in some tumor cell types reduces the potential for metastasis and is associated with improved patient prognosis. Keywords: BCL2, gelsolin, motility, actin polymerization C1 [Ke, Hengning; Parron, Vandy I.; French, John E.] NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Reece, Jeff] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Akiyama, Steven K.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Zhang, Jennifer Y.] Duke Univ, Med Ctr, Dept Dermatol, Durham, NC 27710 USA. RP French, JE (reprint author), NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. EM hk71@notes.duke.edu; french@niehs.nih.gov OI Zhang, Jennifer/0000-0002-4485-1750 FU Division of Intramural Research of the NIEHS, NIH [Z01-ES02302511, Z01-ES2120714] FX We thank Dr Jau-shyong Hong (NIEHS), Dr Bob Petrovich (NIEHS), Ms Pamela D Arora (CIHR, Toronto), and Dr Yanhong Liao (Huazhong University) for materials, Dr Jeff Chou (NIEHS) for statistics, and Dr James Williams (NIEHS) for mass spectra analysis. We also thank Dr Azad Bonni (Harvard Medical School) for providing plasmid-expressing GST-bad. The Division of Intramural Research of the NIEHS, NIH supported this research through projects Z01-ES02302511 and Z01-ES2120714. NR 59 TC 22 Z9 23 U1 0 U2 4 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD APR PY 2010 VL 20 IS 4 BP 458 EP 469 DI 10.1038/cr.2010.21 PG 12 WC Cell Biology SC Cell Biology GA 585PG UT WOS:000276838100009 PM 20142842 ER PT J AU Bittins, CM Eichler, TW Hammer, JA Gerdes, HH AF Bittins, Claudia Margarethe Eichler, Tilo Wolf Hammer, John A., III Gerdes, Hans-Hermann TI Dominant-Negative Myosin Va Impairs Retrograde but Not Anterograde Axonal Transport of Large Dense Core Vesicles SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE Axonal transport; Hippocampal neurons; Large dense core vesicles; Myosin Va; Neuropeptide Y ID CULTURED HIPPOCAMPAL-NEURONS; SECRETORY GRANULE BIOGENESIS; SPLICED EXON-B; DEPENDENT TRANSPORT; NEUROTROPHIC FACTOR; SYNAPTIC SECRETION; CORTICAL-NEURONS; DENDRITIC SPINES; IN-VIVO; MOTOR AB Axonal transport of peptide and hormone-containing large dense core vesicles (LDCVs) is known to be a microtubule-dependent process. Here, we suggest a role for the actin-based motor protein myosin Va specifically in retrograde axonal transport of LDCVs. Using live-cell imaging of transfected hippocampal neurons grown in culture, we measured the speed, transport direction, and the number of LDCVs that were labeled with ectopically expressed neuropeptide Y fused to EGFP. Upon expression of a dominant-negative tail construct of myosin Va, a general reduction of movement in both dendrites and axons was observed. In axons, it was particularly interesting that the retrograde speed of LDCVs was significantly impaired, although anterograde transport remained unchanged. Moreover, particles labeled with the dominant-negative construct often moved in the retrograde direction but rarely in the anterograde direction. We suggest a model where myosin Va acts as an actin-dependent vesicle motor that facilitates retrograde axonal transport. C1 [Bittins, Claudia Margarethe; Eichler, Tilo Wolf; Gerdes, Hans-Hermann] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway. [Hammer, John A., III] NHLBI, Cell Biol Lab, Sect Mol Cell Biol, NIH, Bethesda, MD 20892 USA. RP Gerdes, HH (reprint author), Univ Bergen, Dept Biomed, Jonas Lies Vei 91, N-5009 Bergen, Norway. EM hans-hermann.gerdes@biomed.uib.no FU Meltzer Foundation FX The imaging was performed at the Molecular Imaging Center (FUGE, Norwegian Research Council), University of Bergen. The authors are grateful to W. Almers for providing NPY-EGFP and NPY-mRFP and to the University of Bergen for financial support including research fellowships. H.-H.G. acknowledges grants from the Meltzer Foundation. NR 54 TC 13 Z9 14 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD APR PY 2010 VL 30 IS 3 BP 369 EP 379 DI 10.1007/s10571-009-9459-2 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 580XQ UT WOS:000276484500006 PM 19787448 ER PT J AU Simmons, WK Reddish, M Bellgowan, PSF Martin, A AF Simmons, W. Kyle Reddish, Mark Bellgowan, Patrick S. F. Martin, Alex TI The Selectivity and Functional Connectivity of the Anterior Temporal Lobes SO CEREBRAL CORTEX LA English DT Article DE anterior temporal lobe; domain-general; functional connectivity; person knowledge; semantic hub ID AUDITORY SENTENCE COMPREHENSION; SEMANTIC MEMORY; LANGUAGE COMPREHENSION; NEURAL SYSTEMS; CORTICAL REPRESENTATION; MANIPULATABLE OBJECTS; CORTEX; BRAIN; FMRI; DEMENTIA AB One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by "resting-state" functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others. C1 [Simmons, W. Kyle; Reddish, Mark; Bellgowan, Patrick S. F.; Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Simmons, WK (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. EM simmonswkyle@mail.nih.gov RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU National Institute of Mental Health Intramural Research FX National Institute of Mental Health Intramural Research Program. NR 85 TC 101 Z9 101 U1 2 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2010 VL 20 IS 4 BP 813 EP 825 DI 10.1093/cercor/bhp149 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 568ZW UT WOS:000275566500006 PM 19620621 ER PT J AU Blasi, G Taurisano, P Papazacharias, A Caforio, G Romano, R Lobianco, L Fazio, L Di Giorgio, A Latorre, V Sambataro, F Popolizio, T Nardini, M Mattay, VS Weinberger, DR Bertolino, A AF Blasi, Giuseppe Taurisano, Paolo Papazacharias, Apostolos Caforio, Grazia Romano, Raffaella Lobianco, Luciana Fazio, Leonardo Di Giorgio, Annabella Latorre, Valeria Sambataro, Fabio Popolizio, Teresa Nardini, Marcello Mattay, Venkata S. Weinberger, Daniel R. Bertolino, Alessandro TI Nonlinear Response of the Anterior Cingulate and Prefrontal Cortex in Schizophrenia as a Function of Variable Attentional Control SO CEREBRAL CORTEX LA English DT Article DE attention; cognitive load; fMRI; parametric design ID EVENT-RELATED FMRI; WORKING-MEMORY; COGNITIVE CONTROL; VISUAL-ATTENTION; DYSFUNCTION; BRAIN; CONFLICT; ACTIVATION; PERFORMANCE; CAPACITY AB Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity. C1 [Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Nardini, Marcello; Bertolino, Alessandro] Univ Bari, Sect Mental Disorders, Psychiat Neurosci Grp, Dept Neurol & Psychiat Sci, I-70124 Bari, Italy. [Sambataro, Fabio; Mattay, Venkata S.; Weinberger, Daniel R.] Natl Inst Mental Hlth, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Popolizio, Teresa; Bertolino, Alessandro] Ist Ricovero & Cura Carattere Sci Casa Sollievo d, Dept Neuroradiol, I-71013 San Giovanni Rotondo, Italy. RP Bertolino, A (reprint author), Univ Bari, Sect Mental Disorders, Psychiat Neurosci Grp, Dept Neurol & Psychiat Sci, I-70124 Bari, Italy. EM a.bertolino@psichiat.uniba.it RI Sambataro, Fabio/E-3426-2010; Fazio, Leonardo/J-4570-2012; Bertolino, Alessandro/O-6352-2016; Di Giorgio, Annabella /D-7353-2017; OI Sambataro, Fabio/0000-0003-2102-416X; Fazio, Leonardo/0000-0003-4000-974X; Bertolino, Alessandro/0000-0002-1251-1380; Di Giorgio, Annabella /0000-0001-7876-3495; Papazacharias, Apostolos/0000-0001-5470-1601 FU NARSAD Young Investigator award FX 2007 NARSAD Young Investigator award to G. B. NR 43 TC 16 Z9 16 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD APR PY 2010 VL 20 IS 4 BP 837 EP 845 DI 10.1093/cercor/bhp146 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 568ZW UT WOS:000275566500008 PM 19633177 ER PT J AU Yang, QC Sun, LG Kong, DM Huang, T Wang, YH AF Yang QiChao Sun LiGuang Kong DeMing Huang Tao Wang YuHong TI Variation of Antarctic seal population in response to human activities in 20th century SO CHINESE SCIENCE BULLETIN LA English DT Article DE Antarctica; seal; population change; human activity; bio-element ID PENGUIN POPULATIONS; SOUTHERN-OCEAN; ICE; SEDIMENTS; RECORD; BAY AB A sediment core was collected from the Fildes Peninsula of Antarctica, which contained numerous seal hairs and was identified to be seal excrement deposition. By analyzing its total organic carbon (TOC) and concentrations of bio-elements, the seal population changes of the past century were reconstructed. The variation of seal population in the last century on the Fildes Peninsula is primarily controlled by human activities. The sealing industry in the early 20th century caused the dramatic decline of seal population. The protection of the Antarctic seals since the 1960s and the reduced seal's competition with whales for prey resources due to whaling lead to the recovery of seal population and make the high level of the seal population sustainable. C1 [Yang QiChao; Sun LiGuang; Kong DeMing; Huang Tao] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China. [Wang YuHong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Peoples R China. EM slg@ustc.edu.cn RI Huang, Tao/B-5915-2009 FU National Natural Science Foundation of China [40730107, 40676004]; National Key Technology RD Program [2006BAB 18B07] FX We are grateful to Resource-sharing Platform of Polar Samples & National Infrastructure of Nature for Science and Technology for providing samples (Grant No. 2005DKA21406-6). This work was supported by the National Natural Science Foundation of China (Grant Nos. 40730107 and 40676004) and National Key Technology R&D Program (Grant No. 2006BAB 18B07). NR 20 TC 6 Z9 10 U1 0 U2 3 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-6538 J9 CHINESE SCI BULL JI Chin. Sci. Bull. PD APR PY 2010 VL 55 IS 11 BP 1084 EP 1087 DI 10.1007/s11434-009-0581-9 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 586JL UT WOS:000276903400012 ER PT J AU Mondini, A Bronzoni, RVD Nunes, SHP Chiaravalloti-Neto, F Massad, E Alonso, WJ Zanotto, PMD Nogueira, ML AF Mondini, Adriano de Moraes Bronzoni, Roberta Vieira Pereira Nunes, Silvia Helena Chiaravalloti-Neto, Francisco Massad, Eduardo Alonso, Wladimir J. de Andrade Zanotto, Pablo Marinho Nogueira, Mauricio Lacerda TI Spatio-temporal tracking and phylodynamics of a DENV-3 outbreak in a city from Brazil SO CLADISTICS LA English DT Meeting Abstract CT 27th Annual Meeting of the Willi-Hennig-Society/8th Argentina Meeting of Cladistics and Biogeography CY OCT 28-31, 2008 CL San Javier, ARGENTINA SP Willi Hennig Soc C1 [Mondini, Adriano; de Moraes Bronzoni, Roberta Vieira; Pereira Nunes, Silvia Helena; Chiaravalloti-Neto, Francisco; Nogueira, Mauricio Lacerda] Fac Med Sao Jose Rio Preto FAMERP, Sao Jose Do Rio Preto, SP, Brazil. [Massad, Eduardo; de Andrade Zanotto, Pablo Marinho] Univ Sao Paulo, BR-05508 Sao Paulo, Brazil. [Alonso, Wladimir J.] Fogarty Int Ctr, Bethesda, MD USA. RI Massad, Eduardo/H-6143-2011; Nogueira, Mauricio/B-7599-2012; Chiaravalloti Neto, F*/F-8006-2012; Massad, Eduardo/B-1169-2012 OI Nogueira, Mauricio/0000-0003-1102-2419; Massad, Eduardo/0000-0002-7200-2916 NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0748-3007 J9 CLADISTICS JI Cladistics PD APR PY 2010 VL 26 IS 2 BP 218 EP 218 PG 1 WC Evolutionary Biology SC Evolutionary Biology GA 564LD UT WOS:000275214800071 ER PT J AU Glocker, EO Hennigs, A Nabavi, M Schaffer, AA Woellner, C Salzer, U Pfeifer, D Veelken, H Warnatz, K Tahami, F Jamal, S Manguiat, A Rezaei, N Amirzargar, AA Plebani, A Hannesschlager, N Gross, O Ruland, J Grimbacher, B AF Glocker, E-O Hennigs, A. Nabavi, M. Schaffer, A. A. Woellner, C. Salzer, U. Pfeifer, D. Veelken, H. Warnatz, K. Tahami, F. Jamal, S. Manguiat, A. Rezaei, N. Amirzargar, A. A. Plebani, A. Hannesschlager, N. Gross, O. Ruland, J. Grimbacher, B. TI Susceptibility to fungal infections due to a homozygous mutation in CARD9 SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT United Kingdom Primary Immunodeficiency Network Immunology Forum CY NOV 26-27, 2009 CL Bath, ENGLAND C1 [Glocker, E-O; Woellner, C.; Tahami, F.; Jamal, S.; Manguiat, A.; Grimbacher, B.] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Glocker, E-O; Woellner, C.; Tahami, F.; Jamal, S.; Manguiat, A.; Grimbacher, B.] UCL, London, England. [Hennigs, A.; Salzer, U.; Warnatz, K.] Univ Hosp Freiburg, Dept Rheumatol & Clin Immunol, Freiburg, Germany. [Nabavi, M.] Semnan Univ Med Sci, Semnan, Iran. [Schaffer, A. A.] NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. [Pfeifer, D.; Veelken, H.] Univ Hosp Freiburg, Dept Hematol & Oncol, Freiburg, Germany. [Rezaei, N.] Univ Tehran Med Sci, Growth & Dev Res Ctr, Ctr Excellence Pediat, Childrens Med Ctr, Tehran, Iran. [Amirzargar, A. A.] Univ Tehran Med Sci, Sch Med, Dept Immunol, Immunogenet Lab, Tehran, Iran. [Plebani, A.] Univ Brescia, Pediat Clin, Brescia, Italy. [Plebani, A.] Spedali Civil Brescia, Ist Med Mol Angelo Nocivelli, I-25125 Brescia, Italy. [Hannesschlager, N.; Gross, O.; Ruland, J.] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-8000 Munich, Germany. RI Plebani, Alessandro/C-8593-2011; Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012 OI Rezaei, Nima/0000-0002-3836-1827; NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 SU 1 BP 4 EP 5 PG 2 WC Immunology SC Immunology GA 585DZ UT WOS:000276805800011 ER PT J AU Woellner, C Gertz, ME Schaffer, AA Lagos, M Perro, M Glocker, EO Pietrogrande, MC Cossu, F Franco, JL Matamoros, N Pietrucha, B Heropolitanska-Pliszka, E Yeganch, M Moin, M Espanol, T Ehl, S Gennery, AR Abinun, M Breborowicz, A Niehues, T Kilic, SS Junker, A Turvey, SE Plebani, A Sanchez, B Garty, BZ Pignata, C Cancrini, C Litzman, J Sanal, O Batimann, U Bacchetta, R Hsu, AP Davis, JN Hammarstrom, L Davies, GE Eren, E Arkwright, PD Moilanen, JS Viemann, D Khan, S Marodi, L Cant, AJ Freeman, AF Puck, JM Holland, SM Grimbacher, B AF Woellner, C. Gertz, M. E. Schaffer, A. A. Lagos, M. Perro, M. Glocker, E.-O. Pietrogrande, M. C. Cossu, F. Franco, J. L. Matamoros, N. Pietrucha, B. Heropolitanska-Pliszka, E. Yeganch, M. Moin, M. Espanol, T. Ehl, S. Gennery, A. R. Abinun, M. Breborowicz, A. Niehues, T. Kilic, S. S. Junker, A. Turvey, S. E. Plebani, A. Sanchez, B. Garty, B-Z Pignata, C. Cancrini, C. Litzman, J. Sanal, O. Batimann, U. Bacchetta, R. Hsu, A. P. Davis, J. N. Hammarstrom, L. Davies, G. E. Eren, E. Arkwright, P. D. Moilanen, J. S. Viemann, D. Khan, S. Marodi, L. Cant, A. J. Freeman, A. F. Puck, J. M. Holland, S. M. Grimbacher, B. TI Mutations in the signal transducer and activator of transcription 3 (STAT3) and diagnostic guidelines for the Hyper-IgE Syndrome SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT United Kingdom Primary Immunodeficiency Network Immunology Forum CY NOV 26-27, 2009 CL Bath, ENGLAND SP UK Primary Immunodeficiency Network C1 [Woellner, C.; Perro, M.; Glocker, E.-O.; Grimbacher, B.] UCL, Dept Immunol & Mol Pathol, Royal Free Hosp, London WC1E 6BT, England. [Gertz, M. E.; Schaffer, A. A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lagos, M.] Univ Valparaiso, Catedra Inmunol, Escuela Med, Valparaiso, Chile. [Pietrogrande, M. C.] Univ Milan, Dept Pediat, Fdn Policlin IRCCS, I-20122 Milan, Italy. [Cossu, F.] Osped Microcitem, Bone Marrow Transplant Unit, Cagliari, Italy. [Franco, J. L.] Univ Antioqiua, Grp Primary Immunodeficiencies, Medellin, Colombia. [Matamoros, N.] Son Dureta Hosp, Serv Immunol, Palma de Mallorca, Spain. [Pietrucha, B.; Heropolitanska-Pliszka, E.] CMHI, Gastroenterol Hepatol & Immunol Clin, Warsaw, Poland. [Yeganch, M.; Moin, M.] Univ Tehran Med Sci, Children Med Ctr, Immunol Asthma & Allergy Res Inst, Tehran, Iran. [Espanol, T.] Hosp Valle De Hebron, Sch Med, Immunol Unit, Barcelona, Spain. [Ehl, S.] Univ Hosp Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany. [Gennery, A. R.; Abinun, M.; Cant, A. J.] Newcastle Univ, Childrens Bone Marrow Transplant Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Breborowicz, A.] Poznan Univ Med Sci, Dept Pediat Pulmonol Allergy & Clin Immunol, Dept Pediat 3, Poznan, Poland. [Niehues, T.] Univ Dusseldorf, HELIOS Klinikum Krefeld, Immunodeficiency & Pediat Rheumatol Ctr, D-4000 Dusseldorf, Germany. [Kilic, S. S.] Uludag Univ, Dept Pediat Immunol, Fac Med, Bursa, Turkey. [Junker, A.; Turvey, S. E.] British Columbia Childrens Hosp, Dept Pediat, Vancouver, BC V6H 3V4, Canada. [Junker, A.; Turvey, S. E.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Plebani, A.] Univ Brescia, Dept Pediat, I-25121 Brescia, Italy. [Plebani, A.] Univ Brescia, Inst Mol Med A Novicelli, I-25121 Brescia, Italy. [Sanchez, B.] Univ Hosp, Serv Immunol, Seville, Spain. [Garty, B-Z] Schneider Childrens Med Ctr, Dept Pediat, Petah Tiqwa, Israel. [Pignata, C.] Univ Naples Federico II, Dept Pediat, Naples, Italy. [Cancrini, C.] Univ Roma Tor Vergata, Div Infect Dis & Immunol, Bambino Gesu Childrens Hosp, Rome, Italy. [Litzman, J.] Masaryk Univ, St Annes Univ Hosp, Fac Med, Dept Clin Immunol & Allergol, Brno, Czech Republic. [Sanal, O.] Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey. [Batimann, U.] Hannover Med Sch, Dept Pediat Pulmonol & Neonatol, Hannover, Germany. [Bacchetta, R.] San Raffaele Telethon Inst Gene Therapy HSR TIGET, Milan, Italy. [Hsu, A. P.; Davis, J. N.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hammarstrom, L.] Karolinska Univ Hosp, Div Clin Immunol, Dept Lab Med, Karolinska Inst, Stockholm, Sweden. [Davies, G. E.] Great Ormond St Hosp Sick Children, Dept Immunol, London WC1N 3JH, England. [Eren, E.] Southampton Gen Hosp, Dept Immunol, Southampton SO9 4XY, Hants, England. [Arkwright, P. D.] Univ Manchester, Manchester M13 9PL, Lancs, England. [Moilanen, J. S.] Univ Oulu, Dept Clin Genet, Oulu, Finland. [Moilanen, J. S.] Univ Tampere, Fac Med, FIN-33101 Tampere, Finland. [Viemann, D.] Univ Munster, Inst Immunol, D-4400 Munster, Germany. [Viemann, D.] Univ Munster, Dept Pediat, D-4400 Munster, Germany. [Khan, S.] Scunthorpe Gen Hosp, Scunthorpe, England. [Marodi, L.] Univ Debrecen, Dept Infect & Pediat Immunol, Debrecen, Hungary. [Marodi, L.] Univ Debrecen, Hlth Sci Ctr, Debrecen, Hungary. [Freeman, A. F.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Puck, J. M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RI Moilanen, Jukka/G-2604-2012; Pignata, Claudio/O-2466-2013; Litzman, Jiri/E-2746-2012; Plebani, Alessandro/C-8593-2011; Schaffer, Alejandro/F-2902-2012 OI Moilanen, Jukka/0000-0002-8041-3205; Pignata, Claudio/0000-0003-1568-9843; NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9104 EI 1365-2249 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 SU 1 BP 4 EP 4 PG 1 WC Immunology SC Immunology GA 585DZ UT WOS:000276805800010 ER PT J AU Lopez-Herrera, G Martini, H Birmelin, J Workman, S Schaffer, AA Pfeifer, D Gertz, EM van der Meer, JWM Grimbacher, B AF Lopez-Herrera, G. Martini, H. Birmelin, J. Workman, S. Schaffer, A. A. Pfeifer, D. Gertz, E. M. van der Meer, J. W. M. Grimbacher, B. TI Further genetic linkage analysis in autosomal dominant common variable immunodeficiency SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT United Kingdom Primary Immunodeficiency Network Immunology Forum CY NOV 26-27, 2009 CL Bath, ENGLAND C1 [Lopez-Herrera, G.; Martini, H.; Birmelin, J.; Workman, S.; Grimbacher, B.] UCL, Royal Free Hosp, Dept Immunol & Mol Pathol, London, England. [Schaffer, A. A.; Gertz, E. M.] NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. [Pfeifer, D.] Univ Hosp Freiburg, Div Clin Immunol & Rheumatol, Sch Med, Freiburg, Germany. [van der Meer, J. W. M.] Radboud Univ Nijmegen Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. RI Schaffer, Alejandro/F-2902-2012; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 SU 1 BP 12 EP 12 PG 1 WC Immunology SC Immunology GA 585DZ UT WOS:000276805800025 ER PT J AU Glocker, EO Schaffer, AA Perro, M Allroth, A Sykora, KW Sauer, M Kreipe, H Nustede, R Woellner, C Baumann, U Salzer, U Segal, AW Klein, C Grimbacher, B AF Glocker, E-O Schaffer, A. A. Perro, M. Allroth, A. Sykora, K-W Sauer, M. Kreipe, H. Nustede, R. Woellner, C. Baumann, U. Salzer, U. Segal, W. A. Klein, C. Grimbacher, B. TI Severe early onset ileo-colitis can be caused by mutations in IL10RB and successfully treated by allogeneic hematopoietic stem cell transplantation SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Meeting Abstract CT United Kingdom Primary Immunodeficiency Network Immunology Forum CY NOV 26-27, 2009 CL Bath, ENGLAND C1 [Glocker, E-O; Perro, M.; Woellner, C.; Grimbacher, B.] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Schaffer, A. A.] NIH, Natl Ctr Biotechnol Informat, DHHS, Bethesda, MD 20892 USA. [Allroth, A.; Sykora, K-W; Sauer, M.; Klein, C.] Hannover Med Sch, Dept Pediat Hematol & Oncol, D-3000 Hannover, Germany. [Kreipe, H.] Hannover Med Sch, Inst Pathol, D-3000 Hannover, Germany. [Nustede, R.] Hannover Med Sch, Dept Pediat Surg, D-3000 Hannover, Germany. [Baumann, U.] Hannover Med Sch, Dept Pediat Pulmonol, D-3000 Hannover, Germany. [Salzer, U.] Univ Hosp Freiburg, Dept Rheumatol & Clin Immunol, Freiburg, Germany. [Segal, W. A.] UCL, Dept Med, London, England. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 SU 1 BP 14 EP 14 PG 1 WC Immunology SC Immunology GA 585DZ UT WOS:000276805800030 ER PT J AU Belkaid, Y Liesenfeld, O Maizels, RM AF Belkaid, Y. Liesenfeld, O. Maizels, R. M. TI 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Induction and control of regulatory T cells in the gastrointestinal tract: consequences for local and peripheral immune responses SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE Colitis; helminths; inflammatory bowel disease; microbiome; protozoa ID CONCURRENT NEMATODE INFECTION; BLOOD-STAGE MALARIA; HELMINTH INFECTION; DENDRITIC CELLS; RETINOIC ACID; INTESTINAL INFLAMMATION; AIRWAY INFLAMMATION; POLYGYRUS INFECTION; PARASITE INFECTION; TOXOPLASMA-GONDII AB P>Regulatory T cells play a crucial role in normal gut homeostasis, as well as during infection with microbial or parasitic pathogens. Prior to infection, interactions with the commensal microflora are essential to differentiation of a healthy steady-state level of immunoregulation, mediated through both Toll-like receptor-dependent and -independent pathways. The ingress of pathogenic organisms may, according to the context, promote or reverse the regulatory environment, with onward consequences for inflammation in both the intestinal and extra-intestinal settings. Appropriate regulation of gut immunity thus depends upon a complex three-way interplay between host cells, commensals and pathogens, and can exert a major impact on systemic responses including allergy and autoimmunity. C1 [Maizels, R. M.] Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. [Belkaid, Y.] NIAID, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. [Liesenfeld, O.] Inst Mikrobiol & Hyg, Charite, Berlin, Germany. RP Maizels, RM (reprint author), Univ Edinburgh, Inst Immunol & Infect Res, Edinburgh EH9 3JT, Midlothian, Scotland. EM r.maizels@ed.ac.uk NR 67 TC 7 Z9 9 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2010 VL 160 IS 1 BP 35 EP 41 DI 10.1111/j.1365-2249.2010.04131.x PG 7 WC Immunology SC Immunology GA 567JN UT WOS:000275443000006 PM 20415849 ER PT J AU Lopez, JE Schrumpf, ME Nagarajan, V Raffel, SJ McCoy, BN Schwan, TG AF Lopez, Job E. Schrumpf, Merry E. Nagarajan, Vijayaraj Raffel, Sandra J. McCoy, Brandi N. Schwan, Tom G. TI A Novel Surface Antigen of Relapsing Fever Spirochetes Can Discriminate between Relapsing Fever and Lyme Borreliosis SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED IMMUNOSORBENT ASSAYS; DISEASE SPIROCHETE; UNITED-STATES; B1B LYMPHOCYTES; SEROLOGICAL DISCRIMINATION; LINEAR PLASMIDS; NORTH-AMERICA; KANGAROO RATS; WOOD RATS; IN-VITRO AB In a previous immunoproteome analysis of Borrelia hermsii, candidate antigens that bound IgM antibodies from mice and patients infected with relapsing fever spirochetes were identified. One candidate that was identified is a hypothetical protein with a molecular mass of 57 kDa that we have designated Borrelia immunogenic protein A (BipA). This protein was further investigated as a potential diagnostic antigen for B. hermsii given that it is absent from the Borrelia burgdorferi genome. The bipA locus was amplified and sequenced from 39 isolates of B. hermsii that had been acquired from western North America. bipA was also expressed as a recombinant fusion protein. Serum samples from mice and patients infected with B. hermsii or B. burgdorferi were used to confirm the immunogenicity of the recombinant protein in patients infected with relapsing fever spirochetes. Lastly, in silico and experimental analysis indicated that BipA is a surface-exposed lipoprotein in B. hermsii. These findings enhance the capabilities of diagnosing infection with relapsing fever spirochetes. C1 [Lopez, Job E.; Schrumpf, Merry E.; Raffel, Sandra J.; McCoy, Brandi N.; Schwan, Tom G.] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. [Nagarajan, Vijayaraj] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Lopez, JE (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM lopezjob@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This research was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 60 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD APR PY 2010 VL 17 IS 4 BP 564 EP 571 DI 10.1128/CVI.00518-09 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 576TG UT WOS:000276170900012 PM 20147497 ER PT J AU Goldstein, DS AF Goldstein, David S. TI Cardiac ectopy in chronic autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Arrhythmia; Premature atrial contraction; Autonomic failure; Orthostatic hypotension; Parkinson disease; Multiple system atrophy; Pure autonomic failure; Baroreflex; Norepinephrine ID LEFT-VENTRICULAR HYPERTROPHY; SYMPATHETIC NEUROCIRCULATORY FAILURE; MULTIPLE SYSTEM ATROPHY; ORTHOSTATIC HYPOTENSION; PARKINSON-DISEASE; HYPERTENSION; CONTRACTION; ARRHYTHMIAS; CATECHOLS AB Chronic autonomic failure (CAF), as in Parkinson disease (PD), multiple system atrophy (MSA), and pure autonomic failure (PAF), typically entails baroreflex failure, neurogenic orthostatic hypotension (NOH), and supine hypertension. The combination might predispose to cardiac ectopy, which in turn might predispose to syncope and falls during manipulations decreasing venous return to the heart. This study assessed whether CAF is associated with an increased prevalence of cardiac ectopy. Recordings lasting a parts per thousand yen15 min of the electrocardiogram, beat-to-beat heart rate, and continuous blood pressure were reviewed from a total of 97 CAF patients (34 PD + NOH, 48 MSA, 15 PAF) and 82 control subjects (41 PD without NOH, 33 non-parkinsonian patients, 8 healthy volunteers). Cardiac ectopy was considered present if there were at least two premature beats or an arrhythmia. Atrial ectopy was found in 74% of patients with PD + NOH, 68% with MSA, and 63% with PAF, prevalences 2-3 times those in PD without NOH (28%, p < 0.0001) or other controls (24%, p < 0.0001). Atrial ectopy was related to subject age (p < 0.0001), supine systolic pressure (p < 0.0001), and the orthostatic fall in systolic pressure (p = 0.0007) and inversely with baroreflex-cardiovagal gain (p = 0.005) and the orthostatic increment in plasma norepinephrine (p = 0.0004). In two PD + NOH patients, atrial ectopy was associated with documented sustained hypotension after the Valsalva maneuver; and in an MSA patient, acute atrial flutter/fibrillation was associated with sudden loss of consciousness. CAF patients have a relatively high frequency of atrial ectopy, which might interact with baroreflex failure to increase morbidity from orthostatic hypotension. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10,Room 5N220, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU 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. Ms. Tereza Jenkins coordinated patient travel. LaToya Sewell, CRNP, and Sandra Pechnik, RN, assisted with clinical procedures and scheduling. Drs. Basil Eldadah, Richard Imrich, and Yehonatan Sharabi served as post-doctoral fellows when the work was done. The author thanks Dr. Douglas Rosing for reviewing and helpful comments about a draft of the manuscript. NR 21 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD APR PY 2010 VL 20 IS 2 BP 85 EP 92 DI 10.1007/s10286-009-0043-0 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 587SY UT WOS:000277014400006 PM 20012145 ER PT J AU Mitchell, JB Choudhuri, R Fabre, K Sowers, AL Citrin, D Zabludoff, SD Cook, JA AF Mitchell, James B. Choudhuri, Rajani Fabre, Kristin Sowers, Anastasia L. Citrin, Deborah Zabludoff, Sonya D. Cook, John A. TI In vitro and In vivo Radiation Sensitization of Human Tumor Cells by a Novel Checkpoint Kinase Inhibitor, AZD7762 SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA-DAMAGE; HISTONE H2AX; CANCER-CELLS; REPAIR; CAFFEINE; ARREST; TRIALS AB Purpose: Inhibition of checkpoint kinase 1 has been shown to enhance the cytotoxicity of DNA-damaging targeted chemotherapy through cell cycle checkpoint abrogation and impaired DNA damage repair. A novel checkpoint kinase 1/2 inhibitor, AZD7762, was evaluated for potential enhancement of radiosensitivity for human tumor cells in vitro and in vivo xenografts. Experimental Design: Survival of both p53 wild-type and mutant human cell lines was evaluated by clonogenic assay. Dose modification factors (DMF) were determined from survival curves (ratio of radiation doses for control versus drug treated at 10% survival). Flow cytometry, Western blot, and radiation-induced tumor regrowth delay assays were conducted. Results: AZD7762 treatment enhanced the radiosensitivity of p53-mutated tumor cell lines (DMFs ranging from 1.6-1.7) to a greater extent than for p53 wild-type tumor lines (DMFs ranging from 1.1-1.2). AZD7762 treatment alone exhibited little cytotoxicity to any of the cell lines and did not enhance the radiosensitivity of normal human fibroblasts (1522). AZD7762 treatment abrogated radiation-induced G(2) delay, inhibited radiation damage repair (assessed by gamma-H2AX), and suppressed radiation-induced cyclin B expression. HT29 xenografts exposed to five daily radiation fractions and to two daily AZD7762 doses exhibited significant radiation enhancement compared with radiation alone. Conclusions: AZD7762 effectively enhanced the radiosensitivity of mutated p53 tumor cell lines and HT29 xenografts and was without untoward toxicity when administered alone or in combination with radiation. The results of this study support combining AZD7762 with radiation in clinical trials. Clin Cancer Res; 16(7); 2076-84. (C)2010 AACR. C1 [Mitchell, James B.; Choudhuri, Rajani; Fabre, Kristin; Sowers, Anastasia L.; Cook, John A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Citrin, Deborah] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Zabludoff, Sonya D.] AstraZeneca R&D, Waltham, MA USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, Bldg 10,Room B3-B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 23 TC 78 Z9 78 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2010 VL 16 IS 7 BP 2076 EP 2084 DI 10.1158/1078-0432.CCR-09-3277 PG 9 WC Oncology SC Oncology GA 608OV UT WOS:000278595800011 PM 20233881 ER PT J AU Niu, G Sun, XL Cao, QZ Courter, D Koong, A Le, QT Gambhir, SS Chen, XY AF Niu, Gang Sun, Xilin Cao, Qizhen Courter, Donald Koong, Albert Le, Quynh-Thu Gambhir, Sanjiv Sam Chen, Xiaoyuan TI Cetuximab-Based Immunotherapy and Radioimmunotherapy of Head and Neck Squamous Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; METASTATIC COLORECTAL-CANCER; BINDING-SITE BARRIER; GENE COPY NUMBER; MONOCLONAL-ANTIBODIES; VEGF EXPRESSION; PLUS CETUXIMAB; MESSENGER-RNA; PHASE-II AB Purpose: To show the relationship between antibody delivery and therapeutic efficacy in head and neck cancers, in this study we evaluated the pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR)-targeted immunotherapy and radioimmunotherapy by quantitative positron emission tomography (PET) imaging. Experimental Design: EGFR expression on UM-SCC-22B and SCC1 human head and neck squamous cell cancer (HNSCC) cells were determined by flow cytometry and immunostaining. Tumor delivery and distribution of cetuximab in tumor-bearing nude mice were evaluated with small animal PET using (64)Cu-DOTA-cetuximab. The in vitro toxicity of cetuximab to HNSCC cells was evaluated by MTT assay. The tumor-bearing mice were then treated with four doses of cetuximab at 10 mg/kg per dose, and tumor growth was evaluated by caliper measurement. FDG PET was done after the third dose of antibody administration to evaluate tumor response. Apoptosis and tumor cell proliferation after cetuximab treatment were analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Ki-67 staining. Radioimmunotherapy was done with (90)Y-DOTA-cetuximab. Results: EGFR expression on UM-SCC-22B cells is lower than that on SCC1 cells. However, the UM-SCC-22B tumors showed much higher (64)Cu-DOTA-cetuximab accumulation than the SCC1 tumors. Cetuximab-induced apoptosis in SCC1 tumors and tumor growth was significantly inhibited, whereas an agonistic effect of cetuximab on UM-SCC-22B tumor growth was observed. After cetuximab treatment, the SCC1 tumors showed decreased FDG uptake, and the UM-SCC-22B tumors had increased FDG uptake. UM-SCC-22B tumors are more responsive to (90)Y-DOTA-cetuximab treatment than SCC1 tumors, partially due to the high tumor accumulation of the injected antibody. Conclusion: Cetuximab has an agonistic effect on the growth of UM-SCC-22B tumors, indicating that tumor response to cetuximab treatment is not necessarily related to EGFR expression and antibody delivery efficiency, as determined by PET imaging. Although PET imaging with antibodies as tracers has limited function in patient screening, it can provide guidance for targeted therapy using antibodies as delivery vehicles. Clin Cancer Res; 16(7); 2095-105. (C)2010 AACR. C1 [Niu, Gang; Sun, Xilin; Chen, Xiaoyuan] NIH, Lab Mol Imaging & Nanomed, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. [Niu, Gang] Ctr Clin, Imaging Sci Training Program, Bethesda, MD USA. [Sun, Xilin] Harbin Med Coll, Affiliated Hosp 4, Dept Med Imaging & Nucl Med, Harbin, Peoples R China. [Cao, Qizhen; Gambhir, Sanjiv Sam; Chen, Xiaoyuan] Stanford Univ, Sch Med, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA. [Courter, Donald; Koong, Albert; Le, Quynh-Thu] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. [Cao, Qizhen; Gambhir, Sanjiv Sam; Chen, Xiaoyuan] Stanford Univ, Sch Med, BioX Program, Stanford, CA 94305 USA. RP Chen, XY (reprint author), NIH, Lab Mol Imaging & Nanomed, Natl Inst Biomed Imaging & Bioengn, 31 Ctr Dr,31-1C22, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Cao, Qizhen/C-1172-2011 FU National Cancer Institute [R21 CA102123, P50 CA114747, U54 CA119367, R24 CA93862, R01 CA118582, P01 CA67166]; PHS [CA09302]; Department of Defense; Radiology and Imaging Sciences Department, NIH Clinical Center; National Institute of Biomedical Imaging and Bioengineering, NIH FX National Cancer Institute grants R21 CA102123 (X. Chen), P50 CA114747 (X. Chen), U54 CA119367 (X. Chen), R24 CA93862 (X. Chen), R01 CA118582 (Q.-T. Le), and P01 CA67166 (Q.-T. Le) and training grant PHS CA09302 (D. Courter) and Department of Defense Prostate Cancer Postdoctoral Training Award (G. Niu). Dr. G. Niu currently is an Imaging Sciences Training Fellowship jointly supported by Radiology and Imaging Sciences Department, NIH Clinical Center and Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, NIH. NR 43 TC 52 Z9 53 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2010 VL 16 IS 7 BP 2095 EP 2105 DI 10.1158/1078-0432.CCR-09-2495 PG 11 WC Oncology SC Oncology GA 608OV UT WOS:000278595800013 PM 20215534 ER PT J AU Verma, S VanRyzin, C Sinaii, N Kim, MS Nieman, LK Ravindran, S Calis, KA Arlt, W Ross, RJ Merke, DP AF Verma, Somya VanRyzin, Carol Sinaii, Ninet Kim, Mimi S. Nieman, Lynnette K. Ravindran, Shayna Calis, Karim A. Arlt, Wiebke Ross, Richard J. Merke, Deborah P. TI A pharmacokinetic and pharmacodynamic study of delayed- and extended-release hydrocortisone (ChronocortTM) vs. conventional hydrocortisone (CortefTM) in the treatment of congenital adrenal hyperplasia SO CLINICAL ENDOCRINOLOGY LA English DT Article ID 21-HYDROXYLASE DEFICIENCY; ADDISONS-DISEASE; ADULT MALES; CORTISOL; THERAPY; PREVALENCE; FERTILITY; CHILDREN; DENSITY; HEIGHT AB P>Objective Existing glucocorticoid treatment for congenital adrenal hyperplasia (CAH) is suboptimal and nonphysiological. We compared hormonal profiles during therapy with a new modified-release hydrocortisone (MR-HC), Chronocort (TM), to conventional hydrocortisone (HC), Cortef (TM), in patients with CAH. Design and patients We conducted a Phase 2, open-label, crossover pharmacokinetic and pharmacodynamic study in 14 patients (out of whom seven were male subjects, age ranging from 17 to 55) with classic 21-hydroxylase deficiency. One week of thrice daily HC (10, 5 and 15 mg) was followed by 1 month of once daily MR-HC (30 mg at 22:00 hours). Twenty four-hour sampling of cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione, and ACTH was performed at steady state. Measurements The primary outcome measures were 8- and 24-h area under the curve (AUC) hormones and 08:00 hours 17-OHP. Results Hydrocortisone therapy resulted in three cortisol peaks. A single cortisol peak occurred at approximately 06:00 hours on MR-HC. MR-HC resulted in significantly (P < 0 center dot 001) lower 24-h afternoon (12:00 to 20:00 hours), and night-time (20:00 to 04:00 hours) cortisol as compared with HC. From 04:00 to 12:00 hours, when physiological cortisol is highest, cortisol was higher on MR-HC than HC (P < 0 center dot 001). Patients on MR-HC had significantly (P < 0 center dot 05) higher afternoon (12:00 to 20:00 hours) 17-OHP, androstenedione and ACTH, but significantly (P = 0 center dot 025) lower 08:00 hours 17-OHP. No serious adverse events occurred. Conclusions Modified-release hydrocortisone represents a promising new treatment for CAH. Overnight adrenal androgens were well-controlled, but rose in the afternoon with once-daily dosing suggesting that a morning dose of glucocorticoid is needed. Further studies are needed to determine the optimal dosing regimen and long-term clinical outcome. C1 [VanRyzin, Carol; Sinaii, Ninet; Kim, Mimi S.; Ravindran, Shayna; Calis, Karim A.; Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Verma, Somya; Nieman, Lynnette K.; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD USA. [Arlt, Wiebke] Univ Birmingham, Sch Clin & Expt Med, Sect Endocrinol Diabet & Metab, Birmingham, W Midlands, England. [Ross, Richard J.] Univ Sheffield, Royal Hallamshire Hosp, Acad Unit Diabet, Endocrinol & Metab Sch Med, Sheffield S10 2JF, S Yorkshire, England. RP Merke, DP (reprint author), NIH, Ctr Clin, Bldg 10,Room 1-2740,10 Ctr Dr,MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov RI Ross, Richard/B-2672-2012; Arlt, Wiebke/B-6310-2009 OI Ross, Richard/0000-0001-9222-9678; Arlt, Wiebke/0000-0001-5106-9719 FU Phoqus Pharmaceuticals; Intramural Research Program of the National Institutes of Health; Phoqus Pharmaceuticals Ltd.; Congenital Adrenal Hyperplasia Research, Education and Support (CARES) Foundation; MRC Senior Clinical Fellow [G116/172]; Officers in the United States Public Health Service FX SV, CVR, NS, MSK, SR, KAC have nothing to declare. DPM and LKN received research funds from Phoqus Pharmaceuticals. WA received consultant fees from Phoqus Pharmaceuticals. RR has equity interests in and is employed as a consultant for Diurnal Ltd. RR holds the patent on Chronocort. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, (in part) by Phoqus Pharmaceuticals Ltd., and (in part) by the Congenital Adrenal Hyperplasia Research, Education and Support (CARES) Foundation. WA is a MRC Senior Clinical Fellow (G116/172). SV and DPM are Commissioned Officers in the United States Public Health Service. NR 34 TC 46 Z9 49 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2010 VL 72 IS 4 BP 441 EP 447 DI 10.1111/j.1365-2265.2009.03636.x PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563ZS UT WOS:000275180700003 PM 19486026 ER PT J AU Chowdhury, IN Sinaii, N Oldfield, EH Patronas, N Nieman, LK AF Chowdhury, Iffat N. Sinaii, Ninet Oldfield, Edward H. Patronas, Nicholas Nieman, Lynnette K. TI A change in pituitary magnetic resonance imaging protocol detects ACTH-secreting tumours in patients with previously negative results SO CLINICAL ENDOCRINOLOGY LA English DT Article ID CUSHINGS-DISEASE; MICROADENOMAS; ADENOMAS; 1.5-T; EXPERIENCE; GADOLINIUM; DIAGNOSIS; GLAND AB P>Objective While detection of pituitary tumours with magnetic resonance imaging (MRI) may reduce diagnostic costs and improve surgical outcomes for patients with Cushing's disease, the optimal T1-weighted spin-echo (SE) MRI protocol remains unknown. We hypothesized that specific MR scanning parameters influence detection of corticotropinomas. Design and patients Between December 1997 and November 2004, 21 of 84 consecutive patients with Cushing's disease had a falsely negative initial pituitary MRI study and a lesion identified subsequently at the National Institutes of Health Clinical Center. This study retrospectively reviewed and compared technical parameters used for the two pituitary T1-weighted SE MRIs in 18 patients with available scans. Measurements Repetition time (TR)/echo times (TE), field of view (FOV), matrix size, magnetic field strength, slice thickness, use of gadolinium contrast and the time interval between studies were recorded. Results The MRI interscan interval was 5 center dot 4 +/- 1 center dot 1 months. All scans used gadolinium, matrix sizes were similar and nearly all had 3-mm thick slices. Parameters that differed between the NIH- and externally performed scans were: TR (400 ms vs. 492 +/- 19 ms, P = 0 center dot 0002); TE (10 center dot 3 +/- 0 center dot 5 vs. 17 center dot 2 +/- 1 center dot 2 ms, P = 0 center dot 0003); FOV (12 x 12 cm vs.17 +/- 0 center dot 6 x 18 +/- 0 center dot 7 cm, P < 0 center dot 0001). Immunohistochemistry of tumours resected at transsphenoidal surgery confirmed all to be corticotropinomas. Conclusions Not all 'T1-weighted SE' scans are equally accurate. MRI technique, particularly FOV and TR/TE value, influences results. We recommend that endocrinologists consider pituitary MRI parameters when interpreting the results. C1 [Chowdhury, Iffat N.; Sinaii, Ninet; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD USA. [Oldfield, Edward H.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. [Patronas, Nicholas] NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), Bldg 10,CRC,1 East,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU National Institute of Child Health and Human Development; National Institute of Neurologic Disease and Stroke; Warren Grant Magnuson Clinical Center; National Institutes of Health FX This study was supported in part by the intramural programs of the National Institute of Child Health and Human Development, the National Institute of Neurologic Disease and Stroke, and the Warren Grant Magnuson Clinical Center, National Institutes of Health. NR 16 TC 9 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2010 VL 72 IS 4 BP 502 EP 506 DI 10.1111/j.1365-2265.2009.03646.x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563ZS UT WOS:000275180700012 PM 19500112 ER PT J AU Havekes, B King, K Lai, EW Romijn, JA Corssmit, EP Pacak, K AF Havekes, Bas King, Kathryn Lai, Edwin W. Romijn, Johannes A. Corssmit, Eleonora P. Pacak, Karel TI Response to Letter to the Editor by Dullaart et al. SO CLINICAL ENDOCRINOLOGY LA English DT Letter ID POSITRON-EMISSION-TOMOGRAPHY; SUPERIOR; TUMORS C1 [Havekes, Bas] Univ Hosp, Div Endocrinol, Dept Internal Med, Maastricht, Netherlands. [Havekes, Bas; King, Kathryn; Lai, Edwin W.; Pacak, Karel] NIH, Reprod & Adult Endocrinol Program, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Romijn, Johannes A.; Corssmit, Eleonora P.] Leiden Univ, Dept Endocrinol & Metab, Med Ctr, Leiden, Netherlands. RP Havekes, B (reprint author), Univ Hosp, Div Endocrinol, Dept Internal Med, Maastricht, Netherlands. EM karel@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD APR PY 2010 VL 72 IS 4 BP 569 EP 570 DI 10.1111/j.1365-2265.2009.03749.x PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 563ZS UT WOS:000275180700024 ER PT J AU Moslehi, R Signore, C Tamura, D Mills, JL DiGiovanna, JJ Tucker, MA Troendle, J Ueda, T Boyle, J Khan, SG Oh, KS Goldstein, AM Kraemer, KH AF Moslehi, R. Signore, C. Tamura, D. Mills, J. L. DiGiovanna, J. J. Tucker, M. A. Troendle, J. Ueda, T. Boyle, J. Khan, S. G. Oh, K-S Goldstein, A. M. Kraemer, K. H. TI Adverse effects of trichothiodystrophy DNA repair and transcription gene disorder on human fetal development SO CLINICAL GENETICS LA English DT Article DE development; DNA repair; human fetal; transcription; trichothiodystrophy genes ID ELEVATED LIVER-ENZYMES; C7ORF11 TTDN1 GENE; XERODERMA-PIGMENTOSUM; COCKAYNE-SYNDROME; REPAIR/TRANSCRIPTION GENE; XPD ERCC2; MUTATIONS; PREGNANCY; ABNORMALITIES; DISEASES AB The effects of DNA repair and transcription gene abnormalities in human pre-natal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10-6) recessive disorder caused by mutations in genes involved in nucleotide excision repair (NER) pathway and in transcription. Based on our novel clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (n = 24) with respect to abnormalities during their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (n = 18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Small for gestational age (SGA) < 10th percentile [Relative risk (RR ) = 9.3, 95% CI = 1.4-60.5, p = 0.02], SGA < 3rd percentile (RR = 7.2, 95% CI = 1.1-48.1, p = 0.04), and neonatal intensive care unit (NICU) hospitalization (RR = 6.4, 95% CI = 1.4-29.5, p = 0.02) occurred more frequently among TTD-affected neonates compared with their unaffected siblings. Compared with reference values from general obstetrical population, pregnancies that resulted in TTD-affected infants were significantly more likely to be complicated by hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (RR = 35.7, 95% CI = 7.6-92.5, p = 0.0002), elevated mid-trimester maternal serum human chorionic gonadotropin (hCG) levels (RR = 14.3, 95% CI = 7.0-16.6, p < 0.0001), SGA < 3rd percentile (RR = 13.9, 95% CI = 7.4-21.1, p < 0.0001), pre-term delivery (< 32 weeks) (RR = 12.0, 95% CI = 4.9-21.6, p < 0.0001), pre-eclampsia (RR = 4.0, 95% CI = 1.6-7.4, p = 0.006), and decreased fetal movement (RR = 3.3, 95% CI = 1.6-5.2, p = 0.0018). Abnormal placental development is an underlying mechanism that may explain the constellation of observed complications in our study. Thus, we hypothesize that TTD DNA repair and transcription genes play an important role in normal human placental development. C1 [Moslehi, R.] SUNY Albany, Canc Res Ctr, Rensselaer, NY 12144 USA. [Moslehi, R.] SUNY Albany, Dept Epidemiol & Biostat, Sch Publ Hlth, Rensselaer, NY 12144 USA. [Moslehi, R.] NCI, Biostat Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. [Signore, C.; Mills, J. L.] NICHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Eunice Kennedy Shriver,NIH,DHHS, Bethesda, MD USA. [Tamura, D.; DiGiovanna, J. J.; Ueda, T.; Boyle, J.; Khan, S. G.; Oh, K-S; Kraemer, K. H.] NCI, Basic Res Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. [DiGiovanna, J. J.] Brown Univ, Warren Alpert Med Sch, Div Dermatopharmocol, Providence, RI 02912 USA. [Tucker, M. A.; Goldstein, A. M.] NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20892 USA. [Troendle, J.] Eunice Kennedy Shriver NICHD, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD USA. RP Moslehi, R (reprint author), SUNY Albany, Canc Res Ctr, Room 310,1 Discovery Dr, Rensselaer, NY 12144 USA. EM rmoslehi@albany.edu RI Tucker, Margaret/B-4297-2015 FU DCEG; CCR; NCI; NIH; DHHS FX This study was supported by the Intramural Research Program of the DCEG and CCR, NCI, NIH and DHHS. NR 36 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2010 VL 77 IS 4 BP 365 EP 373 DI 10.1111/j.1399-0004.2009.01336.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 570KP UT WOS:000275674900011 PM 20002457 ER PT J AU Davis, BR Yan, Q Bui, JH Felix, K Moratto, D Muul, LM Prokopishyn, NL Blaese, RM Candotti, F AF Davis, Brian R. Yan, Qing Bui, Jacquelin H. Felix, Kumar Moratto, Daniele Muul, Linda M. Prokopishyn, Nicole L. Blaese, R. Michael Candotti, Fabio TI Somatic mosaicism in the Wiskott-Aldrich syndrome: Molecular and functional characterization of genotypic revertants SO CLINICAL IMMUNOLOGY LA English DT Article DE Somatic mosaicism; Somatic reversion; Immunodeficiency ID IN-VIVO REVERSION; SEVERE COMBINED IMMUNODEFICIENCY; WASP GENE-MUTATIONS; T-CELLS; 2ND-SITE MUTATIONS; LINKED THROMBOCYTOPENIA; EPIDERMOLYSIS-BULLOSA; INHERITED MUTATION; SYNAPSE FORMATION; PROTEIN GENE AB The reasons underlying the occurrence of multiple revertant genotypes in Wiskott-Aldrich syndrome (WAS) patients remain unclear. We have identified more than 30 revertant genotypes in a C995T WAS patient having 10-15% revertant, WAS protein (WASp)-expressing circulating lymphocytes [1]. Of 497 allospecific T-cell clones generated from the peripheral blood, 47.1% carried a revertant sequence. At( revertant T-cell clones exhibited restoration of WASp expression. However, anti-CD3-induced proliferative responses varied greatly amongst revertants. Several revertant T-cell clones expressed an internally deleted WASp mutant tacking much of the proline-rich region. This potentially accounts for the reduced anti-CD3 proliferative responses of these T-cell clones. We found no evidence for an increased DNA mutation rate in this patient. We conclude that the diversity of revertant genotypes in our patient does not result from an extraordinary mutation rate and that the amino acid sequence space explored by WASp in revertant T-cells is significantly smaller than might have been predicted from the diversity of revertant genotypes. (C) 2010 Elsevier Inc. All rights reserved. C1 [Davis, Brian R.; Yan, Qing; Bui, Jacquelin H.; Felix, Kumar] Univ Texas Hlth Sci Ctr, Brown Fdn, Ctr Stem Cell Res, Inst Mol Med, Houston, TX 77030 USA. [Prokopishyn, Nicole L.; Blaese, R. Michael] Inst Inherited Dis Res, Newtown, PA USA. [Moratto, Daniele; Muul, Linda M.; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. RP Davis, BR (reprint author), Univ Texas Hlth Sci Ctr, Brown Fdn, Ctr Stem Cell Res, Inst Mol Med, Houston, TX 77030 USA. EM brian.r.davis@uth.tmc.edu FU United States Immunodeficiency Network (USIDNET); National Institute for Allergy and Infectious Diseases [1R21AI082327]; National Foundation of Cancer Research (NFCR); Malcolm H. Wiener Foundation; NHGRI/NIH FX We thank patients WAS1 and WAS4 who generously participated in this study. We also thank Michael DiCola and Jonathan Rosenberg for providing valuable experimental assistance. This work was supported by grants to B.D. from the United States Immunodeficiency Network (USIDNET) and National Institute for Allergy and Infectious Diseases (1R21AI082327), to M.B. from National Foundation of Cancer Research (NFCR) and Malcolm H. Wiener Foundation, and to F.C. from the Intramural Research Program of NHGRI/NIH. NR 40 TC 12 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2010 VL 135 IS 1 BP 72 EP 83 DI 10.1016/j.clim.2009.12.011 PG 12 WC Immunology SC Immunology GA 571RJ UT WOS:000275772100008 PM 20123155 ER PT J AU Flexner, C Tierney, C Gross, R Andrade, A Lalama, C Eshleman, SH Aberg, J Sanne, I Parsons, T Kashuba, A Rosenkranz, SL Kmack, A Ferguson, E Dehlinger, M Mildvan, D AF Flexner, Charles Tierney, Camlin Gross, Robert Andrade, Adriana Lalama, Christina Eshleman, Susan H. Aberg, Judith Sanne, Ian Parsons, Teresa Kashuba, Angela Rosenkranz, Susan L. Kmack, Anne Ferguson, Elaine Dehlinger, Marjorie Mildvan, Donna CA ACTG A5073 Study Team TI Comparison of Once-Daily versus Twice-Daily Combination Antiretroviral Therapy in Treatment-Naive Patients: Results of AIDS Clinical Trials Group (ACTG) A5073, a 48-Week Randomized Controlled Trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LOPINAVIR/RITONAVIR-BASED REGIMEN; PROTEASE INHIBITORS; DOSING REGIMENS; ADHERENCE; NONINFERIOR; MEDICATION; OUTCOMES; PLASMA; TABLET; LESS AB Background. Dosing frequency is an important determinant of regimen effectiveness. Methods. To compare efficacy of once-daily (QD) versus twice-daily (BID) antiretroviral therapy, we randomized human immunodeficiency virus (HIV)-positive, treatment-naive patients to lopinavir-ritonavir (LPV/r) administered at a dosage of 400 mg of lopinavir and 100 mg of ritonavir BID (n = 160) or 800 mg of lopinavir and 200 mg of ritonavir QD (n = 161), plus either emtricitabine 200 mg QD and extended-release stavudine at a dosage of 100 mg QD or tenofovir at a dosage of 300 mg QD. Randomization was stratified by screening HIV RNA level < 100,000 copies/mL versus >= 100,000 copies/mL. The primary efficacy end point was sustained virologic response (SVR; defined as reaching and maintaining an HIV RNA level < 200 copies/mL) through week 48. Results. Subjects were 78% male, 33% Hispanic, and 34% black. A total of 82% of subjects completed the study, and 71% continued to receive the initially assigned dosage schedule. The probability of SVR did not differ significantly for the BID versus QD comparison, with an absolute proportional difference of 0.03 (95% confidence interval [CI], -0.07 to 0.12). The comparison depended on the screening RNA stratum (P = .038); in the higher RNA stratum, the probability of SVR was significantly better in the BID arm than in the QD arm: 0.89 (95% CI, 0.79-0.94) versus 0.76 (95% CI, 0.64-0.84), a difference of 0.13 (95% CI, 0.01-0.25). Lopinavir trough plasma concentrations were higher with BID dosing. Adherence to prescribed doses of LPV/r was 90.6% in the QD arm versus 79.9% in the BID arm (P < .001). Conclusions. Although subjects assigned to QD regimens had better adherence, overall treatment outcomes were similar in the QD and BID arms. Subjects with HIV RNA levels >= 100,000 copies/mL had better SVR with BID regimens at 48 weeks, which suggests a possible advantage in this setting for more frequent dosing. C1 [Flexner, Charles; Andrade, Adriana; Eshleman, Susan H.; Parsons, Teresa] Johns Hopkins Univ, Baltimore, MD 21287 USA. [Ferguson, Elaine; Dehlinger, Marjorie] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [Tierney, Camlin; Lalama, Christina; Rosenkranz, Susan L.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Gross, Robert] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Aberg, Judith] NYU, Sch Med, New York, NY USA. [Mildvan, Donna] NYU, Beth Israel Med Ctr, New York, NY USA. [Kmack, Anne] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Kashuba, Angela] Univ N Carolina, Chapel Hill, NC USA. [Sanne, Ian] Univ Witwatersrand, Johannesburg, South Africa. RP Flexner, C (reprint author), Johns Hopkins Univ, Osler 503,600 N Wolfe St, Baltimore, MD 21287 USA. EM flex@jhmi.edu FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [U01 AI68636, AI068634] FX Financial support. National Institutes of Health and National Institute of Allergy and Infectious Diseases (grants U01 AI68636 and AI068634). Abbott Laboratories, Bristol-Myers Squibb, and Gilead Pharmaceuticals provided study medications. NR 22 TC 33 Z9 34 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2010 VL 50 IS 7 BP 1041 EP 1052 DI 10.1086/651118 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 563YO UT WOS:000275176900015 PM 20192725 ER PT J AU Hassim, S Shaw, PA Sangweni, P Malan, L Ntshani, E Mathibedi, MJ Stubbs, N Metcalf, JA Eckes, R Masur, H Komati, S AF Hassim, Shaheen Shaw, Pamela A. Sangweni, Phumelele Malan, Lizette Ntshani, Ella Mathibedi, Monkwe Jethro Stubbs, Nomso Metcalf, Julia A. Eckes, Risa Masur, Henry Komati, Stephanus CA Project Phidisa TI Detection of a Substantial Rate of Multidrug-Resistant Tuberculosis in an HIV-Infected Population in South Africa by Active Monitoring of Sputum Samples SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACID AMPLIFICATION TESTS; PULMONARY TUBERCULOSIS; DRUG-RESISTANCE; HIGH PREVALENCE; DIAGNOSIS; THERAPY AB Background. Tuberculosis (TB) coinfection with human immunodeficiency virus (HIV) is a substantial problem in South Africa. There has been a presumption that drug-resistant strains of TB are common in South Africa, but few studies have documented this impression. Methods. In Phidisa, a joint observational and randomized HIV treatment study for South African National Defence Force members and dependents, an initiative was launched to test subjects ( by use of microbiologic TB test) who appeared to be at high risk. We report results for HIV-infected subjects. Results. TB was identified by culture in 116 (19.9%) of 584 patients selected for sputum examination on the basis of suggestive symptoms. Smear was an insensitive technique for confirming the diagnosis: only 33% of culture-positive patients were identified by smear, with a 0.2% false-positive rate. Of the 107 culture-positive individuals with susceptibility testing, 22 (20.6%) were identified to be multidrug resistant (MDR), and 4 (3.7%) were identified to be extensively drug resistant. Culture-positive cases with a history of TB treatment had more than twice the rate of MDR than those without (27.1% vs 11.9%; P = .05). Conclusions. TB is common in this cohort of HIV-infected patients. Smear was not a sensitive technique for identifying culture-positive cases in this health system. Drug susceptibility testing is essential to proper patient management because MDR was present in 20.6% of culture-positive patients. Better management strategies are needed to reduce the development of MDR TB, because so many of these patients had received prior antituberculous therapy that was presumably not curative. C1 [Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Hassim, Shaheen; Sangweni, Phumelele; Malan, Lizette; Ntshani, Ella; Mathibedi, Monkwe Jethro; Stubbs, Nomso; Komati, Stephanus] S African Natl Def Force, Pretoria, South Africa. [Shaw, Pamela A.; Metcalf, Julia A.; Eckes, Risa; Masur, Henry] NIAID, Bethesda, MD 20892 USA. RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 9000 Rockville Pike,Bldg 10,Rm 2C145, Bethesda, MD 20892 USA. EM hmasur@nih.gov FU US Department of Health; National Institute of Allergy and Infectious Diseases; South African National Defence Force FX Financial support. US Department of Health, National Institute of Allergy and Infectious Diseases, and South African National Defence Force, under a collaborative agreement. NR 35 TC 15 Z9 15 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2010 VL 50 IS 7 BP 1053 EP 1059 DI 10.1086/651119 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 563YO UT WOS:000275176900016 PM 20196651 ER PT J AU Proschan, MA Brittain, EH Fay, MP AF Proschan, Michael A. Brittain, Erica H. Fay, Michael P. TI Does treatment effect depend on control event rate? Revisiting a meta-analysis of suicidality and antidepressant use in children SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; UNDERLYING RISK; ODDS RATIO; SPARSE; ESTIMATORS; VARIANCE; LOGIT; BIAS; ADD AB Background Weisberg et al. (Clin Trials 2009, 6: 109-18) illustrate that entry criteria in randomized trials can lead to results that are biased for the target population. Presenting data from a previously published meta-analysis of the effect of antidepressants in children on suicidality, they suggest a relationship between the control event rate and relative risk. Purpose Our purpose is threefold: (1) to show that natural methods of demonstrating a relationship between the control event rate and relative treatment benefit are fraught with danger, (2) to develop better methods, and (3) to assess whether there is evidence of such a relationship in the suicidality meta-analysis. Methods We propose an improved graphical method and an exact and approximate test of whether the treatment effect increases (or decreases) with the control event rate. Results The apparent relationship in the naive plot of relative risk against control rate is actually no stronger than what would be expected by chance. Results of our test do not support the conclusion that the odds ratio for suicidality varies with the control rate (one-sided p = 0.39). Limitations We are not able to apply the exact test to this data set. Simulation results indicate that the relationship would have to be very strong to detect it with these sample sizes and control event rates. Conclusions The difficulty in showing that the treatment effect in clinical trials differs by control rate is caused by 3 factors: (1) artificial correlation between a relative risk and control rate, (2) regression dilution bias because the independent variable - the control proportion - is subject to random variability, and (3) low power because we are trying to detect an interaction. Our graph and test are useful tools. Using them, we found no support for a relationship between the control event rate and treatment effect on suicidality. Clinical Trials 2010; 7: 109-117. http://ctj.sagepub.com. C1 [Proschan, Michael A.; Brittain, Erica H.; Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA. EM proscham@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 NR 20 TC 1 Z9 1 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2010 VL 7 IS 2 BP 109 EP 117 DI 10.1177/1740774510363310 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 580AQ UT WOS:000276419200001 PM 20338902 ER PT J AU Proshan, MA Brittain, EH Fay, MP AF Proshan, Michael A. Brittain, Erica H. Fay, Michael P. TI Apparent relationship between relative risk and control rate: statistical artifact or selection bias? Response SO CLINICAL TRIALS LA English DT Editorial Material C1 [Proshan, Michael A.; Brittain, Erica H.; Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Proshan, MA (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA. EM proscham@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2010 VL 7 IS 2 BP 120 EP 120 DI 10.1177/1740774510363517 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 580AQ UT WOS:000276419200003 ER PT J AU Friedman-Hill, SR Wagman, MR Gex, SE Pine, DS Leibenluft, E Ungerleider, LG AF Friedman-Hill, Stacia R. Wagman, Meryl R. Gex, Saskia E. Pine, Daniel S. Leibenluft, Ellen Ungerleider, Leslie G. TI What does distractibility in ADHD reveal about mechanisms for top-down attentional control? SO COGNITION LA English DT Article DE Selective attention; Distractor filtering; Children; ADHD ID DEFICIT-HYPERACTIVITY-DISORDER; VISUAL SELECTIVE ATTENTION; DEFICIT/HYPERACTIVITY DISORDER; RESPONSE VARIABILITY; INTRAINDIVIDUAL VARIABILITY; SUSTAINED ATTENTION; EXTRASTRIATE CORTEX; EXECUTIVE FUNCTIONS; DIRECTED ATTENTION; INHIBITORY CONTROL AB In this study, we attempted to clarify whether distractibility in ADHD might arise from increased sensory-driven interference or from inefficient top-down control. We employed an attentional filtering paradigm in which discrimination difficulty and distractor salience (amount of image "graying") were parametrically manipulated. Increased discrimination difficulty should add to the load of top-down processes, whereas increased distractor salience should produce stronger sensory interference. We found an unexpected interaction of discrimination difficulty and distractor salience. For difficult discriminations, ADHD children filtered distractors as efficiently as healthy children and adults; as expected, all three groups were slower to respond with high vs. low salience distractors. In contrast, for easy discriminations, robust between-group differences emerged: ADHD children were much slower and made more errors than either healthy children or adults. For easy discriminations, healthy children and adults filtered out high salience distractors as easily as low salience distractors, but ADHD children were slower to respond on trials with low salience distractors than they did on trials with high salience distractors. These initial results from a small sample of ADHD children have implications for models of attentional control, and ways in which it can malfunction. The fact that ADHD children exhibited efficient attentional filtering when task demands were high, but showed deficient and atypical distractor filtering under low task demands suggests that attention deficits in ADHD may stem from a failure to efficiently engage top-down control rather than an inability to implement filtering in sensory processing regions. Published by Elsevier B.V. C1 [Friedman-Hill, Stacia R.; Wagman, Meryl R.; Gex, Saskia E.; Ungerleider, Leslie G.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Pine, Daniel S.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Friedman-Hill, SR (reprint author), NIMH, Lab Brain & Cognit, NIH, Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM friedmans@mail.nih.gov FU Intramural NIH HHS [Z99 MH999999] NR 65 TC 21 Z9 21 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD APR PY 2010 VL 115 IS 1 BP 93 EP 103 DI 10.1016/j.cognition.2009.11.013 PG 11 WC Psychology, Experimental SC Psychology GA 576EF UT WOS:000276126400009 PM 20096409 ER PT J AU Sen, R Smale, ST AF Sen, Ranjan Smale, Stephen T. TI Selectivity of the NF-kappa B Response SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY LA English DT Article ID NUCLEAR EXPORT SIGNAL; C-REL; GENE-EXPRESSION; T-CELLS; TRANSCRIPTION FACTOR; DNA-BINDING; UBIQUITIN LIGASE; DENDRITIC CELLS; ACTIVATION; ALPHA AB NF-kappa B is activated by many stimuli and NF-kappa B binding sites have been identified in a wide variety of genes. Yet, NF-kappa B-dependent gene expression must be stimulus- and cell-type-specific. In others words, the cellular response to different NF-kappa B activating stimuli, such as TNF alpha, IL-1, and LPS, must be different; and the response of different cell types, such as lymphocytes, fibroblasts, or epithelial cells, to the same NF-kappa B-inducing stimulus must also be different. Finally, kinetics of gene expression must be accounted for, so that all NF-kappa B-dependent genes are not activated simultaneously even if cell type and stimulus are constant. Here, we explore the mechanistic framework in which such regulatory aspects of NF-kappa B-dependent gene expression have been analyzed because they are likely to form the basis for physiological responses. C1 [Sen, Ranjan] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21225 USA. [Smale, Stephen T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Sen, R (reprint author), NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21225 USA. EM ranjan.sen@nih.gov; smale@mednet.ucla.edu FU National Institute of Aging; NIH [R01 AI073868] FX Research in the NF-kappa B field performed in the authors' laboratories was supported by the Intramural Research Program of the National Institute of Aging (R.S.) and by NIH grant R01 AI073868 (S.T.S.). NR 57 TC 54 Z9 57 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1943-0264 J9 CSH PERSPECT BIOL JI Cold Spring Harbor Perspect. Biol. PD APR PY 2010 VL 2 IS 4 AR a000257 DI 10.1101/cshperspect.a000257 PG 15 WC Cell Biology SC Cell Biology GA 625GF UT WOS:000279882300001 PM 20452937 ER PT J AU Palmore, TN Henderson, DK AF Palmore, Tara N. Henderson, David K. TI Testing the tube: Assessing silver as a potential "silver bullet" for preventing ventilator-associated pneumonia SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE nosocomial infection; healthcare-associated; infection; pneumonia; ventilator-associated pneumonia; endotracheal tube ID COATED ENDOTRACHEAL-TUBES; RANDOMIZED-TRIAL C1 [Palmore, Tara N.; Henderson, David K.] NIH, Hosp Epidemiol Serv, Ctr Clin, Bethesda, MD 20892 USA. [Henderson, David K.] NIH, Off Director, Bethesda, MD 20892 USA. RP Palmore, TN (reprint author), NIH, Hosp Epidemiol Serv, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM dkh@nih.gov NR 12 TC 2 Z9 2 U1 0 U2 1 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 APR PY 2010 VL 38 IS 4 BP 1220 EP 1221 DI 10.1097/CCM.0b013e3181d1692a PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 581CW UT WOS:000276499700032 PM 20335705 ER PT J AU Luke, TC Casadevall, A Watowich, SJ Hoffman, SL Beigel, JH Burgess, TH AF Luke, Thomas C. Casadevall, Arturo Watowich, Stanley J. Hoffman, Stephen L. Beigel, John H. Burgess, Timothy H. TI Hark back: Passive immunotherapy for influenza and other serious infections SO CRITICAL CARE MEDICINE LA English DT Article DE influenza; passive; immunotherapy; convalescent; plasma; serum; immunoglobulin; antibody ID CONVALESCENT HUMAN SERUM; SARS PATIENTS; INTRAVENOUS IMMUNOGLOBULIN; COMPLICATING INFLUENZA; LIVER-TRANSPLANTATION; MATERNAL IMMUNIZATION; SERONEGATIVE PLASMA; HEMORRHAGIC-FEVER; ANTIBODY THERAPY; NEONATAL FERRETS AB The world is experiencing a pandemic of swine-origin influenza virus H1N1. A vaccine to prevent disease is now available, and millions have or will become ill before they can be vaccinated. The ability to use swine-origin influenza virus vaccines as a public health tool has been described as a "race against time." Oseltamivir and related drugs are being used in an effort to reduce morbidity and mortality, but their efficacy for treating severe influenza is suboptimal, and possible wide-spread emergence of oseltamivir-resistant mutants is a concern. Another approach for prevention and treatment of serious influenza is infusion of hyperimmune plasma. The United States has thousands of licensed blood product collection centers that produce millions of liters of plasma licensed by the Food and Drug Administration on an annual basis for the treatment of serious conditions. Immunotherapy using infusion of convalescent plasma (or hyperimmune intravenous immunoglobulin) has been reported to be an effective treatment for severe influenza and other virulent pathogens in animal models and humans. Plasma obtained from those that have recovered or were early recipients of vaccine offers a resource for production of an immediately available and potentially effective therapy at the local, state, and national level. Past, current, and future uses of immunotherapy and current advisory body recommendations for this approach are presented. (Crit Care Med 2010; 38[Suppl.]: e66-e73) C1 [Luke, Thomas C.] USN, Med Res Ctr, Henry Jackson Fdn, Silver Spring, MD USA. [Casadevall, Arturo] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Watowich, Stanley J.] Univ Texas Med Branch, Galveston, TX USA. [Hoffman, Stephen L.] Prot Potential LLC, Rockville, MD USA. [Beigel, John H.] NIAID, Bethesda, MD 20892 USA. RP Luke, TC (reprint author), USN, Med Res Ctr, Henry Jackson Fdn, Silver Spring, MD USA. EM thomas.luke@med.navy.mil NR 108 TC 30 Z9 32 U1 0 U2 4 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 APR PY 2010 VL 38 SU S BP E66 EP E73 DI 10.1097/CCM.0b013e3181d44c1e PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 745EC UT WOS:000289147300009 PM 20154602 ER PT J AU Morens, DM Taubenberger, JK Harvey, HA Memoli, MJ AF Morens, David M. Taubenberger, Jeffery K. Harvey, Hillery A. Memoli, Matthew J. TI The 1918 influenza pandemic: Lessons for 2009 and the future SO CRITICAL CARE MEDICINE LA English DT Article DE infectious diseases; influenza; influenza virus; pandemic; pathogenesis; pneumonia; viral diseases ID HANTAVIRUS PULMONARY SYNDROME; HONG-KONG INFLUENZA; UNITED-STATES; SEASONAL INFLUENZA; EXCESS MORTALITY; HOST IMMUNE; VIRUS; PNEUMONIA; PATHOGENESIS; PATHOLOGY AB The 1918 to 1919 H1N1 influenza pandemic is among the most deadly events in recorded human history, having killed an estimated 50 to 100 million persons. Recent H5N1 avian influenza epizootics associated with sporadic human fatalities have heightened concern that a new influenza pandemic, one at least as lethal as that of 1918, could be developing. In early 2009, a novel pandemic H1N1 influenza virus appeared, but it has not exhibited unusually high pathogenicity. Nevertheless, because this virus spreads globally, some scientists predict that mutations will increase its lethality. Therefore, to accurately predict, plan, and respond to current and future influenza pandemics, we must first better-understand the events and experiences of 1918. Although the entire genome of the 1918 influenza virus has been sequenced, many questions about the pandemic it caused remain unanswered. In this review, we discuss the origin of the 1918 pandemic influenza virus, the pandemic's unusual epidemiologic features and the causes and demographic patterns of fatality, and how this information should impact our response to the current 2009 H1N1 pandemic and future pandemics. After 92 yrs of research, fundamental questions about influenza pandemics remain unanswered. Thus, we must remain vigilant and use the knowledge we have gained from 1918 and other influenza pandemics to direct targeted research and pandemic influenza preparedness planning, emphasizing prevention, containment, and treatment. (Crit Care Med 2010; 38[Suppl.]: e10-e20) C1 [Morens, David M.; Taubenberger, Jeffery K.; Harvey, Hillery A.; Memoli, Matthew J.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dm270q@nih.gov NR 122 TC 39 Z9 40 U1 0 U2 18 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 APR PY 2010 VL 38 SU S BP E10 EP E20 DI 10.1097/CCM.0b013e3181ceb25b PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 745EC UT WOS:000289147300002 PM 20048675 ER PT J AU Grewal, SIS AF Grewal, Shiv I. S. TI RNAi-dependent formation of heterochromatin and its diverse functions SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; CENTROMERIC HETEROCHROMATIN; CHROMODOMAIN PROTEIN; HISTONE DEACETYLASE; CHP1 CHROMODOMAIN; UBIQUITIN LIGASE; DNA METHYLATION; FAMILY PROTEINS; POLYMERASE-II AB Expression profiling of eukaryotic genomes has revealed widespread transcription outside the confines of protein-coding genes, leading to production of antisense and non-coding RNAs (ncRNAs). Studies in Schizosaccharomyces pombe and multicellular organisms suggest that transcription and ncRNAs provide a framework for the assembly of heterochromatin, which has been linked to various chromosomal processes. In addition to gene regulation, heterochromatin is crucial for centromere function, cell fate determination as well as transcriptional and posttranscriptional silencing of repetitive DNA elements. Recently, heterochromatin factors have been shown to suppress antisense RNAs at euchromatic loci. These findings define conserved pathways that probably have major impact on the epigenetic regulation of eukaryotic genomes. C1 NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Grewal, SIS (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov FU National Institutes of Health, National Cancer Institute FX I thank F. Reyes-Turcu, NI. Zofall, N. Ashourian, N. Komissarova and H. Cam for helpful comments. Research in Grewal laboratory is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 80 TC 141 Z9 143 U1 2 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2010 VL 20 IS 2 BP 134 EP 141 DI 10.1016/j.gde.2010.02.003 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 601ON UT WOS:000278071700005 PM 20207534 ER PT J AU Stover, PJ Harlan, WR Hammond, JA Hendershot, T Hamilton, CM AF Stover, Patrick J. Harlan, William R. Hammond, Jane A. Hendershot, Tabitha Hamilton, Carol M. TI PhenX: a toolkit for interdisciplinary genetics research SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE cardiovascular disease; genome-wide association studies; metabolic syndrome; nutrition; PhenX (consensus measures for Phenotypes and eXposures) ID GENOME-WIDE ASSOCIATION; HUMAN-NUTRITION; FTO; EPIDEMIOLOGY; VARIANTS; GENOTYPE; DISEASE; DIET AB Purpose of review To highlight standard PhenX (consensus measures for Phenotypes and eXposures) measures for nutrition, dietary supplements, and cardiovascular disease research and to demonstrate how these and other PhenX measures can be used to further interdisciplinary genetics research. Recent findings PhenX addresses the need for standard measures in large-scale genomic research studies by providing investigators with high-priority, well established, low-burden measurement protocols in a web-based toolkit (https://www.phenxtoolkit.org). Cardiovascular and Nutrition and Dietary Supplements are just 2 of 21 research domains and accompanying measures included in the PhenX Toolkit. Summary Genome-wide association studies (GWAS) provide promise for the identification of genomic markers associated with different disease phenotypes, but require replication to validate results. Cross-study comparisons typically increase statistical power and are required to understand the roles of comorbid conditions and environmental factors in the progression of disease. However, the lack of comparable phenotypic, environmental, and risk factor data forces investigators to infer and to compare metadata rather than directly combining data from different studies. PhenX measures provide a common currency for collecting data, thereby greatly facilitating cross-study analysis and increasing statistical power for identification of associations between genotypes, phenotypes, and exposures. C1 [Hammond, Jane A.; Hendershot, Tabitha; Hamilton, Carol M.] RTI Int, Res Triangle Pk, NC 27709 USA. [Stover, Patrick J.] Cornell Univ, Ithaca, NY USA. [Harlan, William R.] Natl Lib Med, Chevy Chase, MD USA. RP Hamilton, CM (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM chamilton@rti.org FU NHGRI [U01 HG004597-01] FX The authors thank Dr Erin M. Ramos for the critical review of the manuscript and Jennifer Drolet for editorial review. This work was supported by NHGRI, Award No. U01 HG004597-01. NR 21 TC 29 Z9 30 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD APR PY 2010 VL 21 IS 2 BP 136 EP 140 DI 10.1097/MOL.0b013e3283377395 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 579LX UT WOS:000276373200006 PM 20154612 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Diversity of structure and function of response regulator output domains SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID MICROBIAL SIGNAL-TRANSDUCTION; GENERAL STRESS-RESPONSE; ESCHERICHIA-COLI K-12; DIGUANYLATE CYCLASE; TRANSCRIPTIONAL ACTIVATOR; DNA RECOGNITION; SYSTEMS; MECHANISM; DATABASE; METHYLESTERASE AB Response regulators (RRs) within two-component signal transduction systems control a variety of cellular processes. Most RRs contain DNA-binding output domains and serve as transcriptional regulators. Other RR types contain RNA-binding, ligand-binding, protein-binding or transporter output domains and exert regulation at the transcriptional, post-transcriptional or post-translational levels. In a significant fraction of RRs, output domains are enzymes that themselves participate in signal transduction: methylesterases, adenylate or diguanylate cyclases, c-di-GMP-specific phosphodiesterases, histidine kinases, serine/threonine protein kinases and protein phosphatases. In addition, there remain output domains whose functions are still unknown. Patterns of the distribution of various RR families are generally conserved within key microbial lineages and can be used to trace adaptations of various species to their unique ecological niches. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health FX I thank Armen Mulkidjanian and Sergei Mekhedov for helpful suggestions and many other colleagues for critical comments. This study was supported by the Intramural Research Program of the National Library of Medicine at the U.S. National Institutes of Health. NR 52 TC 144 Z9 150 U1 4 U2 28 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 EI 1879-0364 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2010 VL 13 IS 2 BP 150 EP 159 DI 10.1016/j.mib.2010.01.005 PG 10 WC Microbiology SC Microbiology GA 588KZ UT WOS:000277070100006 PM 20226724 ER PT J AU Murray, EA Wise, SP AF Murray, Elisabeth A. Wise, Steven P. TI Interactions between orbital prefrontal cortex and amygdala: advanced cognition, learned responses and instinctive behaviors SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID ANTERIOR CINGULATE CORTEX; FRONTAL-TEMPORAL DISCONNECTION; NUCLEUS-ACCUMBENS CORE; RHESUS-MONKEYS; ORBITOFRONTAL CORTEX; BASOLATERAL AMYGDALA; DOUBLE DISSOCIATION; DECISION-MAKING; STRATEGY IMPLEMENTATION; EMOTIONAL RESPONSES AB Recent research indicates that the orbital prefrontal cortex (PFo) represents stimulus valuations and that the amygdala updates these valuations. An exploration of how PFo and the amygdala interact could improve the understanding of both. PFo and the amygdala function cooperatively when monkeys choose objects associated with recently revalued foods. In other tasks, they function in opposition. PFo uses positive feedback to promote learning in object-reward reversal tasks, and PFo also promotes extinction learning. Amygdala function interferes with both kinds of learning. The amygdala underlies fearful responses to a rubber snake from the first exposure on, but PFo is necessary only after the initial exposure. The amygdala mediates an arousal response in anticipation of rewards, whereas PFo sometimes suppresses such arousal. A role for PFo in advanced cognition, for the amygdala in instinctive behavior, and for cortex-subcortex interactions in prioritizing behaviors provides one account for these findings. C1 [Murray, Elisabeth A.; Wise, Steven P.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, Bldg 49,Room 1B80,MSC 4415,49 Convent Dr, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 FU National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. We thank Dr Matthew Shapiro and Dr Peter Rudebeck for their comments on an earlier version of this manuscript. NR 61 TC 38 Z9 39 U1 3 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2010 VL 20 IS 2 BP 212 EP 220 DI 10.1016/j.conb.2010.02.001 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 604EA UT WOS:000278258900012 PM 20181474 ER PT J AU Goines, P Van de Water, J AF Goines, Paula Van de Water, Judy TI The immune system's role in the biology of autism SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE autism; autoantibodies; cytokines; immune system; immunoglobulin ID MIGRATION INHIBITORY FACTOR; SPECTRUM DISORDERS; UNAFFECTED SIBLINGS; FETAL-BRAIN; ANTIBRAIN ANTIBODIES; CYTOKINE PRODUCTION; CHILDREN; AUTOANTIBODIES; AUTOIMMUNITY; RESPONSES AB Purpose of review The following is a review of the most recent research concerning the potential role of immune system dysfunction in autism. This body of literature has expanded dramatically over the past few years as researchers continue to identify immune anomalies in individuals with autism. Recent findings The most exciting of these recent findings is the discovery of autoantibodies targeting brain proteins in both children with autism and their mothers. In particular, circulating maternal autoantibodies directed toward fetal brain proteins are highly specific for autism. This finding has great potential as a biomarker for disease risk and may provide an avenue for future therapeutics and prevention. Additionally, data concerning the cellular immune system in children with autism suggest there may be a defect in signaling pathways that are shared by the immune and central nervous systems. Although studies to explore this hypothesis are ongoing, there is great interest in the commonalities between the neural and immune systems and their extensive interactions. Summary In summary, the exciting research regarding the role of the immune system in autism spectrum disorders may have profound implications for diagnosis and treatment of this devastating disease. C1 [Goines, Paula; Van de Water, Judy] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA. [Goines, Paula; Van de Water, Judy] Univ Calif Davis, MIND Inst, Davis, CA 95616 USA. [Goines, Paula; Van de Water, Judy] Univ Calif Davis, NIEHS, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. RP Van de Water, J (reprint author), Div Rheumatol, 451 Hlth Sci Dr, Davis, CA 95616 USA. EM javandewater@ucdavis.edu FU NIEHS [1 P01 ES11269-01, 1 R01-ES015359]; U. S. Environmental Protection Agency (U. S. EPA) [R829388]; UC Davis M. I. N. D. Institute; Autism Speaks FX The author's studies cited herein were supported by grants NIEHS 1 P01 ES11269-01, the U. S. Environmental Protection Agency (U. S. EPA) through the Science to Achieve Results (STAR) program (grant R829388), NIEHS 1 R01-ES015359, the UC Davis M. I. N. D. Institute, and Autism Speaks. NR 73 TC 96 Z9 98 U1 5 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2010 VL 23 IS 2 BP 111 EP 117 DI 10.1097/WCO.0b013e3283373514 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 577BU UT WOS:000276196700004 PM 20160651 ER PT J AU Mattison, DR AF Mattison, Donald R. TI Environmental exposures and development SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE air pollution; birth defects; developmental disability; gene-environment; occupational exposure; water pollution ID AMBIENT AIR-POLLUTION; POLYCYCLIC AROMATIC-HYDROCARBONS; COLLABORATIVE PERINATAL PROJECT; NATIONAL BIRTH COHORT; FOR-GESTATIONAL-AGE; INTRAUTERINE GROWTH-RETARDATION; ADVERSE PREGNANCY OUTCOMES; CONGENITAL HEART-DEFECTS; NEURAL-TUBE DEFECTS; WORLD-TRADE-CENTER AB Purpose of review Summarize recent studies exploring the relationship between paternal and maternal environmental exposures to chemicals before, at the time of and after conception to adverse developmental outcomes including preterm birth, death, structural and functional abnormalities and growth restriction. Recent findings Recent studies have demonstrated that human pregnancy and development are vulnerable to environmental exposures of the father and mother to chemical, biological and physical agents. Exposures associated with adverse developmental outcomes include air and water pollution, chemicals in foods, occupational exposures, agricultural chemicals, metals, persistent and volatile organics. Developmental endpoints which are linked with these exposures include growth restriction, functional abnormalities, structural abnormalities, preterm delivery and death. Despite this general understanding we still have incomplete knowledge concerning most exposures and the biological interactions responsible for impaired development and preterm delivery. Summary Whereas single genes and individual chemical exposures are responsible for some instances of adverse pregnancy outcome or developmental disease, gene environment interactions are responsible for the majority. These gene-environment interactions may occur in the father, mother, placenta or fetus, suggesting that critical attention be given to maternal and paternal exposures and gene expression as they relate to the mode of action of the putative developmental toxicant both prior to and during pregnancy. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Mattison, DR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 31,Room 1B44, Bethesda, MD 20892 USA. EM mattisod@mail.nih.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health FX Funding for this work has been provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Health. NR 189 TC 30 Z9 34 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD APR PY 2010 VL 22 IS 2 BP 208 EP 218 DI 10.1097/MOP.0b013e32833779bf PG 11 WC Pediatrics SC Pediatrics GA 578XQ UT WOS:000276330900015 PM 20216314 ER PT J AU Chenoweth, JG Mckay, RDG Tesar, PJ AF Chenoweth, Josh G. McKay, Ronald D. G. Tesar, Paul J. TI Epiblast stem cells contribute new insight into pluripotency and gastrulation SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Review DE embryonic stem cells; epiblast; gastrulation; pluripotency ID HUMAN EMBRYONIC STEM; POSTIMPLANTATION MOUSE EMBRYOS; SELF-RENEWAL; GERM-LINE; CLONAL ANALYSIS; EGG-CYLINDERS; IN-VITRO; DIFFERENTIATION; EXPRESSION; CULTURE AB Gastrulation is the defining feature of metazoan development where it serves to apportion seemingly equivalent, pluripotent cells to specific fates. The three embryonic germ layers generated during gastrulation from the pluripotent epiblast including ectoderm, mesoderm, and definitive endoderm, contain the progenitors required to build all of the tissues of the developing organism. As a result, there is great interest in understanding the events that coordinate gastrulation. Because developing embryos in placental mammals are relatively inaccessible, stem cells are widely used for experimental and biochemical interrogation of these processes. Epiblast stem cells (EpiSCs) are grown from the post-implantation epiblast, which is the most proximal pluripotent tissue to the early somatic and germ cell precursors. Because EpiSCs can be propagated indefinitely in vitro as a stable state that recapitulates the properties of the post-implantation epiblast, they are uniquely positioned to provide novel insight into the developmental window where somatic and germ cell lineages are first established. Here we discuss the nature of EpiSCs and their significance in understanding gastrulation and cell specification in relationship to other pluripotent cell culture models. C1 [Tesar, Paul J.] Case Western Reserve Univ, Dept Genet, Ctr Stem Cell & Regenerat Med, Sch Med, Cleveland, OH 44106 USA. [Chenoweth, Josh G.; McKay, Ronald D. G.] NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tesar, PJ (reprint author), Case Western Reserve Univ, Dept Genet, Ctr Stem Cell & Regenerat Med, Sch Med, Cleveland, OH 44106 USA. EM paul.tesar@case.edu RI Tesar, Paul/C-9848-2014 OI Tesar, Paul/0000-0003-1532-3155 NR 67 TC 30 Z9 30 U1 4 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD APR PY 2010 VL 52 IS 3 BP 293 EP 301 DI 10.1111/j.1440-169X.2010.01171.x PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 576EG UT WOS:000276126500006 PM 20298258 ER PT J AU Reid, BS Sargent, TD Williams, T AF Reid, Bethany S. Sargent, Thomas D. Williams, Trevor TI Generation and Characterization of a Novel Neural Crest Marker Allele, Inka1-LacZ, Reveals a Role for Inka1 in Mouse Neural Tube Closure SO DEVELOPMENTAL DYNAMICS LA English DT Article DE neural crest; AP-2 alpha; Inka1; neural tube closure; PAK4 ID TRANSCRIPTION FACTOR AP-2; P21-ACTIVATED KINASES; HEAD MESENCHYME; DEFECTS; MORPHOGENESIS; AP-2-ALPHA; MICE; CELLS; TWIST AB Previous studies identified Inka1 as a gene regulated by AP-2 alpha in the neural crest required for craniofacial morphogenesis in fish and frog. Here, we extend the analysis of Inka1 function and regulation to the mouse by generating a LacZ knock-in allele. Inka1-LacZ allele expression occurs in the cephalic mesenchyme, heart, and paraxial mesoderm prior to E8.5. Subsequently, expression is observed in the migratory neural crest cells and their derivatives. Consistent with expression of Inka1 in tissues of the developing head during neurulation, a low percentage of Inka1(-/-) mice show exencephaly while the remainder are viable and fertile. Further studies indicate that AP-2 alpha is not required for Inka1 expression in the mouse, and suggest that there is no significant genetic interaction between these two factors during embryogenesis. Together, these data demonstrate that while the expression domain of Inka1 is conserved among vertebrates, its function and regulation are not. Developmental Dynamics 239:1188-1196, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Reid, Bethany S.; Williams, Trevor] Univ Colorado Denver, Dept Craniofacial Biol & Cell & Dev Biol, Aurora, CO 80045 USA. [Sargent, Thomas D.] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA. RP Williams, T (reprint author), Univ Colorado Denver, Dept Craniofacial Biol & Cell & Dev Biol, Mailstop 8120,12801 E 17th Ave,POB 6511, Aurora, CO 80045 USA. EM Trevor.Williams@ucdenver.edu FU NIDCR [DE12728] FX Grant sponsor: NIDCR: Grant number: DE12728. NR 29 TC 10 Z9 10 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 2010 VL 239 IS 4 BP 1188 EP 1196 DI 10.1002/dvdy.22248 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 581NR UT WOS:000276531200014 PM 20175189 ER PT J AU Xu, XZ Zhao, CX Wang, LY Tu, L Fang, XS Zheng, CL Edin, ML Zeldin, DC Wang, DW AF Xu, Xizhen Zhao, Chun Xia Wang, Luyun Tu, Ling Fang, Xiaosai Zheng, Changlong Edin, Matthew L. Zeldin, Darryl C. Wang, Dao Wen TI Increased CYP2J3 Expression Reduces Insulin Resistance in Fructose-Treated Rats and db/db Mice SO DIABETES LA English DT Article ID NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; DEPENDENT ENDOTHELIAL FUNCTION; HUMAN TISSUE KALLIKREIN; NECROSIS-FACTOR-ALPHA; SIGNALING PATHWAYS; METABOLIC SYNDROME; ARACHIDONIC-ACID; SKELETAL-MUSCLE; FUNCTIONAL-SIGNIFICANCE AB OBJECTIVE-Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. The anti-inflammatory, antihypertensive, and pro-proliferative effects of EETs suggest a possible beneficial role for EETs on insulin resistance and diabetes. RESEARCH DESIGN AND METHODS-This study investigated the effects of CYP2J3 epoxygenase gene therapy on insulin resistance and blood pressure in diabetic db/db mice and in a model of fructose-induced hypertension and insulin resistance in rats. RESULTS-CYP2J3 gene delivery in vivo increased EET generation, reduced blood pressure, and reversed insulin resistance as determined by plasma glucose levels, homeostasis model assessment insulin resistance index, and glucose tolerance test. Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPKs) in liver, muscle, heart, kidney, and aorta. Thus, overexpression of CYP2J3 protected against diabetes and insulin resistance in peripheral tissues through activation of insulin receptor and AMPK pathways. CONCLUSIONS-These results highlight the beneficial roles of the CYP epoxygenase-EET system in diabetes and insulin resistance. Diabetes 59:997-1005, 2010 C1 [Xu, Xizhen; Zhao, Chun Xia; Wang, Luyun; Tu, Ling; Fang, Xiaosai; Zheng, Changlong; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Internal Med, Tongji Hosp, Wuhan 430074, Peoples R China. [Xu, Xizhen; Zhao, Chun Xia; Wang, Luyun; Tu, Ling; Fang, Xiaosai; Zheng, Changlong; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Hypertens, Tongji Hosp, Wuhan 430074, Peoples R China. [Edin, Matthew L.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Internal Med, Tongji Hosp, Wuhan 430074, Peoples R China. EM dwwang@tjh.tjmu.edu.cn OI Edin, Matthew/0000-0002-7042-500X FU National Education Ministration project; Nature Science Foundation [30930039, 30700377]; Wuhan project [200870834407]; 973 program [2007CB512004]; National Institutes of Health, National Institute of Environmental Health Sciences FX This work was supported in part by funds from the National Education Ministration project, Nature Science Foundation Committee projects (Nos. 30930039 and 30700377), Wuhan project (200870834407), 973 program (2007CB512004), and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 43 TC 56 Z9 62 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2010 VL 59 IS 4 BP 997 EP 1005 DI 10.2337/db09-1241 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 582MH UT WOS:000276601200025 PM 20068141 ER PT J AU Calles-Escandon, J Lovato, LC Simons-Morton, DG Kendall, DM Pop-Busui, R Cohen, RM Bonds, DE Fonseca, VA Ismail-Beigi, F Banerji, MA Failor, A Hamilton, B AF Calles-Escandon, Jorge Lovato, Laura C. Simons-Morton, Denise G. Kendall, David M. Pop-Busui, Rodica Cohen, Robert M. Bonds, Denise E. Fonseca, Vivian A. Ismail-Beigi, Faramarz Banerji, Mary Ann Failor, Alan Hamilton, Bruce TI Effect of Intensive Compared With Standard Glycemia Treatment Strategies on Mortality by Baseline Subgroup Characteristics The Action to Control The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial SO DIABETES CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; PRIMARY PREVENTION; HEART-ASSOCIATION; GLUCOSE CONTROL; TYPE-2; DISEASE; EVENTS; TIME; COMPLICATIONS AB OBJECTIVE - To determine if baseline subgroups in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial can be identified for whom intensive compared with standard glycemia treatment had different effects on all-cause mortality. RESEARCH DESIGN AND METHODS - Exploratory post hoc intention-to-treat comparisons were made between intensive and standard glycemia groups on all-cause mortality by subgroups defined by baseline characteristics. RESULTS - There were few significant interactions between baseline characteristics and effects of intensive versus standard glycemia treatment on mortality: self-reported history of neuropathy (hazard ratio [HR] 1.95, 95% CI 1.41-2.69) versus no history of neuropathy (0.99, 0.79-1.26; P value for interaction 0.0008), higher A1C (A1C >8.5%: HR 1.64, 95% Cl 1.22- 2.22; A1C 7.5-8.4%: 1.00, 0.75-1.34; A1C <7.5%: 1.00, 0.67-1.50; P value for interaction 0.04), and aspirin use (HR 1.45, 95% CI 1.13-1.85, compared with 0.96, 0.72-1.27, in non-users; P value for interaction 0.03). CONCLUSIONS - We found a remarkable similarity of effect from intensive compared with standard glycemia treatment on mortality across most baseline subgroups. No differential effect was found in subgroups defined by variables anticipated to have an interaction: age, duration of diabetes, and previous history of cardiovascular disease. The three baseline characteristics that defined subgroups for which there was a differential effect on mortality may help identify patients with type 2 diabetes at higher risk of mortality from intensive regimens for glycemic control. Further research is warranted. C1 [Calles-Escandon, Jorge] Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC USA. [Lovato, Laura C.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Simons-Morton, Denise G.; Bonds, Denise E.] NHLBI, NIH, Bethesda, MD 20892 USA. [Kendall, David M.] Int Diabet Ctr, Minneapolis, MN USA. [Pop-Busui, Rodica] Univ Michigan, Sch Med, Dept Endocrinol Metab & Nutr, Ann Arbor, MI USA. [Cohen, Robert M.] Univ Cincinnati, Med Ctr, Div Endocrinol Diabet & Metab, Cincinnati, OH 45267 USA. [Fonseca, Vivian A.] Tulane Univ, Med Ctr, Endocrinol Sect, New Orleans, LA USA. [Ismail-Beigi, Faramarz] Univ Cleveland, Endocrinol Sect, VA Med Ctr, Cleveland, OH USA. [Banerji, Mary Ann] Suny Downstate Med Ctr, Endocrinol Sect, New York, NY USA. [Failor, Alan] Univ Washington, Div Endocrinol Nutr & Metab, Seattle, WA 98195 USA. [Hamilton, Bruce] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Hamilton, Bruce] VA Med Ctr, Baltimore, MD USA. RP Calles-Escandon, J (reprint author), Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC USA. EM jcalles@wfubmc.edu NR 25 TC 71 Z9 72 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 APR PY 2010 VL 33 IS 4 BP 721 EP 727 DI 10.2337/dc09-1471 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200005 PM 20103550 ER PT J AU Burbelo, PD Hirai, H Issa, AT Kingman, A Lernmark, A Ivarsson, SA Notkins, AL Iadarola, MJ AF Burbelo, Peter D. Hirai, Hiroki Issa, Alexandra T. Kingman, Albert Lernmark, Ake Ivarsson, Sten-A. Notkins, Abner L. Iadarola, Michael J. TI Comparison of Radioimmunoprecipitation With Luciferase Immunoprecipitation for Autoantibodies to GAD65 and IA-2 beta SO DIABETES CARE LA English DT Article ID AUTOANTIGENS; DISEASE AB OBJECTIVE - To compare the sensitivity and specificity of luciferase immunoprecipitation (LIPS) with radioimmunoprecipitation (RIP) for the measurement of autoantibodies to the type 1 diabetes autoantigens glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated protein (IA)-2 beta. RESEARCH DESIGN AND METHODS - Sera from 49 type 1 diabetic patients and 100 nondiabetic control subjects from Diabetes Antibody Standardization Program 2007 were used to screen for autoantibodies to GAD65. An additional 200 type 1 diabetic patients and 200 nondiabetic control subjects were used to validate the GAD65 results and screen for autoantibodies to IA-2 beta. RESULTS - LIPS showed equal sensitivity and specificity to RIP for detecting autoantibodies to GAD65 and IA-2 beta. Receiver-operating characteristic analysis revealed that the detection of autoantibodies to GAD65 and IA-2 beta by LIPS and RIP were not statistically different. CONCLUSIONS - The LIPS assay does not require the use of radioisotopes or in vitro transcription/translation and is a practical alternative at the clinical level for the RIP assay. C1 [Burbelo, Peter D.; Issa, Alexandra T.; Iadarola, Michael J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. [Hirai, Hiroki; Notkins, Abner L.] Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. [Lernmark, Ake; Ivarsson, Sten-A.] Malmo Univ Hosp, Dept Paediat, Malmo, Sweden. RP Iadarola, MJ (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, NIH, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov; miadarola@mail.nih.gov FU National Institute of Dental and Craniofacial Research, the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, the National Institutes of Health. NR 10 TC 14 Z9 19 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2010 VL 33 IS 4 BP 754 EP 756 DI 10.2337/dc09-1938 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200015 PM 20086252 ER PT J AU Bainbridge, KE Cheng, YJ Cowie, CC AF Bainbridge, Kathleen E. Cheng, Yiling J. Cowie, Catherine C. TI Potential Mediators of Diabetes-Related Hearing Impairment in the US Population National Health and Nutrition Examination Survey 1999-2004 SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR-DISEASE; RISK-FACTORS; MELLITUS; NEUROPATHIES; ASSOCIATION; PREVALENCE; ADULTS; EAR AB OBJECTIVE - We examined potential mediators of the reported association between diabetes and hearing impairment. RESEARCH DESIGN AND METHODS - Data come from 1,508 participants, aged 40-69 years, who completed audiometric testing during 1999-2004 in the National Health and Nutrition Examination Survey (NHANES). We defined hearing impairment as the pure-tone average >25 decibels hearing level of pure-tone thresholds at low/mid (500, 1,000, and 2,000 Hz) and high (3,000, 4,000, 6,000, and 8,000 Hz) frequencies. Using logistic regression, we examined whether controlling for vascular or neuropathic conditions, cardiovascular risk factors, glycemia, or inflammation diminished the association between diabetes and hearing impairment. RESULTS - Diabetes was associated with a 100% increased odds of low/mid-frequency hearing impairment (odds ratio 2.03 [95% CI 1.32-3.10]) and a 67% increased odds of high-frequency hearing impairment (1.67 [1.14-2.44]) in preliminary models after controlling for age, sex, race/ethnicity, education, smoking, and occupational noise exposure. Adjusting for peripheral neuropathy attenuated the association with low/mid-frequency hearing impairment (1.70 [1.02-2.82]). Adjusting for albuminuria and C-reactive protein attenuated the association with high-frequency hearing impairment (1.54 [1.02-2.32] and 1.50[1.01-2.23], respectively). Diabetes was not associated with high-frequency hearing impairment after controlling for A1C (1.09 [0.60-1.99]) but remained associated with low/mid-frequency impairment. We found no evidence suggesting that our observed relationship between diabetes and hearing impairment is due to hypertension or dyslipidemia. CONCLUSIONS - Mechanisms related to neuropathic or microvascular factors, inflammation, or hyperglycemia may be mediating the association of diabetes and hearing impairment. C1 [Bainbridge, Kathleen E.] Social & Sci Syst, Silver Spring, MD USA. [Cheng, Yiling J.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Cowie, Catherine C.] NIDDK, Bethesda, MD USA. RP Bainbridge, KE (reprint author), Social & Sci Syst, Silver Spring, MD USA. EM kbainbridge@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700001G] FX This work was financially supported by the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G). NR 24 TC 23 Z9 25 U1 1 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 APR PY 2010 VL 33 IS 4 BP 811 EP 816 DI 10.2337/dc09-1193 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200025 PM 20097782 ER PT J AU Curtis, JM Horton, ES Bahnson, J Gregg, EW Jakicic, JM Regensteiner, JG Ribisl, PM Soberman, JE Stewart, KJ Espeland, MA AF Curtis, Jeffrey M. Horton, Edward S. Bahnson, Judy Gregg, Edward W. Jakicic, John M. Regensteiner, Judith G. Ribisl, Paul M. Soberman, Judith E. Stewart, Kerry J. Espeland, Mark A. CA Look AHEAD Res Grp TI Prevalence and Predictors of Abnormal Cardiovascular Responses to Exercise Testing Among Individuals With Type 2 Diabetes The Look AHEAD (Action for Health in Diabetes) study SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; PULSE PRESSURE; RISK-FACTORS; TREADMILL EXERCISE; CLINICAL-TRIAL; MEN; MORTALITY; CAPACITY; PERFORMANCE AB OBJECTIVE - We examined maximal graded exercise test (GXT) results in 5,783 overweight/obese men and women, aged 45-76 years, with type 2 diabetes, who were entering the Look AHEAD (Action for Health in Diabetes) study, to determine the prevalence and correlates of exercise-induced cardiac abnormalities. RESEARCH DESIGN AND METHODS - Participants underwent symptom-limited maximal GXTs. Questionnaires and physical examinations were used to determine demographic, anthropometric, metabolic, and health status predictors of abnormal GXT results, which were defined as an ST segment depression >= 1.0 mm, ventricular arrhythmia, angina pectoris, poor postexercise heart rate recovery (<22 bpm reduction 2 min after exercise), or maximal exercise capacity less than 5.0 METs. Systolic blood pressure response to exercise was examined as a continuous variable, without a threshold to define abnormality. RESULTS - Exercise-induced abnormalities were present in 1,303 (22.5%) participants, of which 693 (12.0%) consisted of impaired exercise capacity. ST segment depression occurred in 440(7-6%), abnormal heart rate recovery in 206(5.0%), angina in 63 (1.1%), and arrhythmia in 41(0.7%). Of potential predictors, only greater age was associated with increased prevalence of all abnormalities. Other predictors were associated with some, but not all, abnormalities. Systolic blood pressure response decreased with greater age, duration of diabetes, and history of cardiovascular disease. CONCLUSIONS - We found a high rate of abnormal GXT results despite careful screening for cardiovascular disease symptoms. In this cohort of overweight and obese individuals with type 2 diabetes, greater age most consistently predicted abnormal GXT. Long-term follow-up of these participants will show whether these abnormalities are clinically significant. C1 [Curtis, Jeffrey M.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Horton, Edward S.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Bahnson, Judy; Espeland, Mark A.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Gregg, Edward W.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Jakicic, John M.] Univ Pittsburgh, Pittsburgh, PA USA. [Regensteiner, Judith G.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Soberman, Judith E.] Univ Tennessee, Memphis, TN USA. [Stewart, Kerry J.] Johns Hopkins Univ, Baltimore, MD USA. RP Curtis, JM (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. EM jfcurtis@mail.nih.gov FU NCATS NIH HHS [UL1 TR000005] NR 24 TC 13 Z9 13 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 APR PY 2010 VL 33 IS 4 BP 901 EP 907 DI 10.2337/dc09-1787 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 584ZI UT WOS:000276793200042 PM 20056948 ER PT J AU Yeung, EH Hu, FB Solomon, CG Chen, L Louis, GM Schisterman, E Willett, WC Zhang, C AF Yeung, E. H. Hu, F. B. Solomon, C. G. Chen, L. Louis, G. M. Schisterman, E. Willett, W. C. Zhang, C. TI Life-course weight characteristics and the risk of gestational diabetes SO DIABETOLOGIA LA English DT Article DE Birthweight; Body mass index; Gestational diabetes mellitus; Life-course weight; Waist ID IMPAIRED GLUCOSE-TOLERANCE; GROWTH-FACTOR-I; BIRTH-WEIGHT; METABOLIC SYNDROME; CHILDHOOD; MELLITUS; SIZE; DETERMINANTS; SENSITIVITY; SECRETION AB We prospectively determined the risk of gestational diabetes mellitus in association with life-course weight characteristics and adult abdominal adiposity. We investigated the joint and independent impact of birthweight, childhood size by somatotypes, adolescent and adult BMI, and abdominal adiposity on gestational diabetes mellitus risk among the 21,647 women in the Nurses' Health Study II who reported a singleton pregnancy between 1989 and 2001. A total of 1,386 incident cases of gestational diabetes mellitus were reported. Relative risk was estimated by pooled logistic regression adjusting for age, prematurity, race, smoking status, parental history of diabetes, age of first birth, parity and physical activity. Birthweight was inversely associated with gestational diabetes mellitus risk (p = 0.02 for trend). Childhood somatotypes at ages 5 and 10 years were not associated with risk. U-shaped associations were found for BMI at age 18 years and somatotype at age 20 years. Weight gain between adolescence and adulthood, pre-gravid BMI and abdominal adiposity were positively associated with risk (p < 0.01 for all trends). Multivariate adjusted RRs for gestational diabetes from lowest to highest quintile of WHR were 1.00, 1.50, 1.51, 2.03, 2.12 (p = 0.0003 for trend). Lower birthweight (< 7 lb) without adulthood overweight (BMI > 25 kg/m(2)) was associated with a 20% increased risk (95% CI 1.02-1.41). However, adulthood overweight alone was related to a 2.36 times greater risk (95% CI 2.12-3.77). Although lower birthweight is an independent risk factor for gestational diabetes mellitus, weight gain since early adulthood, and overall and central obesity in adulthood were more strongly associated with elevated risk of the condition independently of other known risk factors. C1 [Yeung, E. H.; Louis, G. M.; Schisterman, E.; Zhang, C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, Bethesda, MD 20892 USA. [Hu, F. B.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hu, F. B.; Willett, W. C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hu, F. B.; Willett, W. C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Hu, F. B.; Willett, W. C.] Harvard Univ, Sch Med, Boston, MA USA. [Solomon, C. G.] Brigham & Womens Hosp, Div Gen Med, Dept Med, Boston, MA 02115 USA. [Solomon, C. G.] Brigham & Womens Hosp, Div Womens Hlth, Dept Med, Boston, MA 02115 USA. [Chen, L.] Louisiana State Univ, Hlth Sci Ctr, Program Epidemiol, Sch Publ Hlth, New Orleans, LA USA. RP Yeung, EH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, 6100 Execut Blvd,7B03, Bethesda, MD 20892 USA. EM yeungedw@mail.nih.gov; zhangcu@mail.nih.gov RI Sriwisit, Sukhumaphorn/G-1405-2011; Yeung, Edwina/F-5992-2015; OI Yeung, Edwina/0000-0002-3851-2613; Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 FU National Institutes of Health [CA50385, DK58845]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This study was funded by research grants CA50385 and DK58845 from the National Institutes of Health. E. H. Yeung, G. M. Louis, E. Schisterman and C. Zhang were supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 29 TC 17 Z9 18 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2010 VL 53 IS 4 BP 668 EP 678 DI 10.1007/s00125-009-1634-y PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 562WU UT WOS:000275087100011 PM 20043144 ER PT J AU Prokunina-Olsson, L Hall, JL AF Prokunina-Olsson, L. Hall, J. L. TI Evidence for neuroendocrine function of a unique splicing form of TCF7L2 in human brain, islets and gut SO DIABETOLOGIA LA English DT Article DE Brain-gut-islets axis; CART; Gene expression; Neuroendocrine regulation; TCF7L2; Type 2 diabetes ID GLUCOSE; NEURONS AB Variants in the TCF7L2 gene remain the strongest genetic associations with increased risk of type 2 diabetes. Recently, we identified a unique splicing form of TCF7L2 expressed in pancreatic islets, pancreas and colon and detected by assay 'ex13-13b'. The expression of ex13-13b strongly correlated with proinsulin in glucose-stimulated pancreatic islets, suggesting a potential role for this form in the development of type 2 diabetes. The goal of this study was to further characterise this unique TCF7L2 splicing form in human tissues. We used a panel of 34 human tissues and 80 human cell lines to measure the expression of assay ex13-13b with use of quantitative RT-PCR. The highest expression of assay ex13-13b was detected in several areas of the brain (hypothalamus/thalamus, occipital lobe) and in neuronal cell line SHS5Y5. Low expression was confirmed in pancreatic islets, small intestine, pancreas and colon, while no expression was detected in other human tissues and cell lines. The expression of assay ex13-13b correlated with the gene for cocaine- and amphetamine-regulated transcript (CART, also known as CARTPT) in a panel of human tissues (n = 12, r = 0.85, p = 0.00046), pancreatic islets (n = 23, r = 0.62, p = 0.0016) and colon (n = 98, r = 0.54, p < 0.0001). The significant correlation between expression of a unique splicing form of TCF7L2, named here TCF7L2-NE, and CART, the gene for an anorexigenic neurohormone expressed in the central and peripheral nervous system, suggests that these transcripts may share neuroendocrine functions important for brain, gut and pancreatic islets. C1 [Prokunina-Olsson, L.] NCI, Lab Translat Genom, NIH, Bethesda, MD 20892 USA. [Hall, J. L.] Univ Minnesota, Dept Med, Lillehei Heart Inst, Ctr Dev Biol, Minneapolis, MN 55455 USA. RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Genom, NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM prokuninal@mail.nih.gov OI Prokunina-Olsson, Ludmila/0000-0002-9622-2091 FU NCI/NIH; NIH [1R21DK078029-01] FX We are grateful to the Molecular Targets Team, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis (DCTD), National Cancer Institute (NCI)/National Institutes of Health (NIH) for providing RNA samples from NCI-60 cell lines, to the Islet Cell Resource Centers and the National Disease Research Interchange Network for human islets, to F. S. Collins and M. R. Erdos (National Human Genome Research Institute [NHGRI]/NIH) for sharing samples of pancreatic islets and helpful comments, and to S. Bowell for help with procurement of tissues from the University ofMinnesota Tissue Procurement Facility. We would also like to thank M. Carlson and C. Welch for their help in preparing samples for analysis. The study was supported by the intramural research program of NCI/NIH and by the NIH grant 1R21DK078029-01 (J. L. Hall). NR 11 TC 11 Z9 12 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2010 VL 53 IS 4 BP 712 EP 716 DI 10.1007/s00125-009-1640-0 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 562WU UT WOS:000275087100015 PM 20033802 ER PT J AU Stevenson, LG Fedorko, DP Zelazny, AM AF Stevenson, Lindsay G. Fedorko, Daniel P. Zelazny, Adrian M. TI An enhanced method for the identification of Leishmania spp. using real-time polymerase chain reaction and sequence analysis of the 7SL RNA gene region SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Leishmania; Identification; PCR; Sequencing ID CUTANEOUS LEISHMANIASIS; DONOVANI COMPLEX; KETOCONAZOLE; DIAGNOSIS AB The accurate identification of Leishmania spp. is important for the treatment of infected patients. Molecular methods offer an alternative to time-consuming traditional laboratory techniques for species determination. We redesigned a 7SL RNA gene-based polymerase chain reaction and sequence assay for increased species identification. DNA extracted from 17 reference strains and 10 cultured clinical isolates was examined. Sequence comparison was used successfully to identify organisms to the complex level with intercomplex similarity ranging from 77.5% to 98.4%. Many species within each complex were discriminated accurately by this method including Leishmania major, Leishmania tropica, Leishmania aethiopica, Leishmania guyanensis, and the previously indistinguishable Leishmania braziliensis and Leishmania panamensis. The Leishmania donovani complex members remain indistinguishable by this method, as are the representatives of Leishmania amazonensis/Leishmania garnhami and Leishmania mexicana/Leishmania pifanoi. Published by Elsevier Inc. C1 [Stevenson, Lindsay G.; Fedorko, Daniel P.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Zelazny, AM (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM azelazny@mail.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 15 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD APR PY 2010 VL 66 IS 4 BP 432 EP 435 DI 10.1016/j.diagmicrobio.2009.11.005 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 574FD UT WOS:000275973200013 PM 20226334 ER PT J AU Kurkjian, C Kummar, S AF Kurkjian, Carla Kummar, Shivaani TI Advances in the Treatment of Metastatic Colorectal Cancer SO DM DISEASE-A-MONTH LA English DT Article ID GROWTH-FACTOR RECEPTOR; FLUOROURACIL PLUS LEUCOVORIN; III COLON-CANCER; MULTICENTER RANDOMIZED-TRIAL; HIGH-DOSE LEUCOVORIN; GENE COPY NUMBER; PHASE-III; CONTINUOUS-INFUSION; 1ST-LINE TREATMENT; ORAL CAPECITABINE AB The treatment of metastatic colorectal cancer has undergone major advances yielding significant improvements in survival over the past decade. These advances have evolved due to the benefits of combination chemotherapy and the incorporation of biologic therapy. However, as we struggle to provide optimum care while sparing patients ineffective therapy and undue cost, the importance of tailored therapy to maximize benefit will become increasingly important. This article reviews the major advances in the treatment of patients with metastatic colorectal cancer and the burgeoning developments in individualized therapy. C1 [Kurkjian, Carla] Univ Oklahoma, Dept Hematol Oncol, Oklahoma City, OK 73190 USA. [Kummar, Shivaani] NCI, Med Oncol Branch, Clin Res Ctr, Bethesda, MD 20892 USA. RP Kurkjian, C (reprint author), Univ Oklahoma, Dept Hematol Oncol, Oklahoma City, OK 73190 USA. NR 68 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 0011-5029 EI 1557-8194 J9 DM-DIS MON JI DM-Dis.-a-Mon. PD APR PY 2010 VL 56 IS 4 BP 187 EP 203 DI 10.1016/j.disamonth.2009.12.005 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 581NU UT WOS:000276531500001 PM 20350652 ER PT J AU Saha, TD Compton, WM Pulay, AJ Stinson, FS Ruan, WJ Smith, SM Grant, BF AF Saha, Tulshi D. Compton, Wilson M. Pulay, Attila J. Stinson, Frederick S. Ruan, W. June Smith, Sharon M. Grant, Bridget F. TI Dimensionality of DSM-IV nicotine dependence in a national sample: An item response theory application SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Nicotine dependence; Item response theory; Nicotine use criterion; Psychiatric assessment; DSM-V revision ID ALCOHOL-USE DISORDER; MARGINAL MAXIMUM-LIKELIHOOD; GENERAL-POPULATION SAMPLE; HEAVY SOCIAL DRINKERS; EPIDEMIOLOGIC SURVEY; PSYCHIATRIC-DISORDERS; SYMPTOM EXPRESSION; SUBSTANCE USE; EM ALGORITHM; RASCH MODEL AB Background: Research focusing on the development of a dimensional representation of DSM-IV nicotine dependence is scarce and prior research has not assessed the role of nicotine use criteria in that a dimensional representation, nor the invariance of the DSM-IV nicotine dependence criteria across important population subgroups. Methods: Using a large, representative sample of the U.S. population, this study utilized item response theory (IRT) analyses to explore the dimensionality of DSM-IV nicotine dependence criteria and several candidate criteria for cigarette use among past-year cigarette smokers (n = 10,163). Results: Factor analyses demonstrated the unidimensionality of nicotine dependence criteria and IRT analyses demonstrated good fit of the observed responses and the underlying, unobserved latent trait of dependence severity. The model containing all seven DSM-IV dependence criteria, along with the consumption criterion of smoking at least a quarter of a pack of cigarettes in a day in the past year, was identified as the best-fitting model. No differential criterion functioning was shown across sex, race-ethnicity, and age subgroups. Discussion: Major implications of this study are discussed in terms of the addition of a dimensional representation of nicotine dependence to pre-existing categorical representations of the disorder in the DSM-V, and the need for a nicotine consumption criterion to improve representations of nicotine dependence severity. (C) 2009 Published by Elsevier Ireland Ltd. C1 [Saha, Tulshi D.; Pulay, Attila J.; Stinson, Frederick S.; Ruan, W. June; Smith, Sharon M.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. [Compton, Wilson M.] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,5635 Fishers Lane,MS 9304, Rockville, MD 20852 USA. EM bgrant@willco.niaaa.nih.gov RI Pulay, Attila/B-6155-2011 FU National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The NESARC was supported by the National Institute on Alcohol Abuse and Alcoholism, with supplemental support from the National Institute on Drug Abuse. This survey was also supported by the intramural program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. NR 43 TC 22 Z9 22 U1 6 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2010 VL 108 IS 1-2 BP 21 EP 28 DI 10.1016/j.drugalcdep.2009.11.012 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 579NB UT WOS:000276376600004 PM 20045597 ER PT J AU Strat, Y Grant, BF Ramoz, N Gorwood, P AF Le Strat, Yann Grant, Bridget F. Ramoz, Nicolas Gorwood, Philip TI A new definition of early age at onset in alcohol dependence SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE NESARC; Alcohol dependence; Admixture test; DSM-V; Age at onset ID SUBSTANCE-USE DISORDERS; ADMIXTURE ANALYSIS; ENVIRONMENTAL CONTRIBUTIONS; LINKAGE ANALYSIS; MALE TWINS; NICOTINE; PSYCHOPATHOLOGY; ABUSE; ASSOCIATIONS; ADOLESCENCE AB Objective: The accurate cut-off of an early onset of alcohol dependence is unknown. The objectives of this analysis are (1) to confirm that ages at onset variability in alcohol dependence is best described as a two subgroups entity, (2) to define the most appropriate cut-off, and (3) to test the relevancy of such distinction. Method: Data were drawn the Epidemiologic Survey on Alcohol and Related Conditions (NESARC). This study focused on the 4782 adults with lifetime alcohol dependence. Results: The best-fit model distinguished two subgroups of age at onset of alcohol dependence, with a cut-off point at 22 years. Subjects with an earlier onset of alcohol dependence (<= 22 years old) reported higher lifetime rates of specific phobia, antisocial behaviors and nearly all addictive disorders. Conclusions: The early onset of alcohol dependence is best defined as beginning before the age of 22 years. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Le Strat, Yann; Ramoz, Nicolas; Gorwood, Philip] INSERM, Ctr Psychiat & Neurosci, U894, U675, F-75014 Paris, France. [Grant, Bridget F.] NIAAA, Washington, DC USA. [Gorwood, Philip] St Anna Hosp Paris 6, AP HP, Paris, France. RP Strat, Y (reprint author), INSERM, Ctr Psychiat & Neurosci, U894, U675, 2 Ter Rue Alesia, F-75014 Paris, France. EM yann.lestrat@inserm.fr RI ramoz, nicolas/K-3316-2015; OI GORWOOD, Philip/0000-0003-1845-3676 FU National Institute on Alcohol Abuse and Alcoholism; NIAAA, National Institutes of Health; Societe Francaise de Tabacologie FX The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the National Institute on Alcohol Abuse and Alcoholism and funded, in part, by the Intermural Program, NIAAA, National Institutes of Health. YLS is funded by an unrestricted grant from the Societe Francaise de Tabacologie. The funding sources had no 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. NR 40 TC 2 Z9 2 U1 4 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2010 VL 108 IS 1-2 BP 43 EP 48 DI 10.1016/j.drugalcdep.2009.11.011 PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 579NB UT WOS:000276376600007 ER PT J AU Pulay, AJ Stinson, FS Ruan, WJ Smith, SM Pickering, RP Dawson, DA Grant, BF AF Pulay, Attila J. Stinson, Frederick S. Ruan, W. June Smith, Sharon M. Pickering, Roger P. Dawson, Deborah A. Grant, Bridget F. TI The relationship of DSM-IV personality disorders to nicotine dependence-results from a national survey SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Personality disorders; Nicotine dependence; Epidemiology; Neurobiology; Smoking exposure; Self-medication hypothesis ID PSYCHIATRIC DIAGNOSTIC MODULES; GENERAL-POPULATION SAMPLE; ALCOHOL-USE-DISORDER; DRUG-USE DISORDERS; EPIDEMIOLOGIC SURVEY; UNITED-STATES; ANXIETY DISORDERS; 5-FACTOR MODEL; SMOKING STATUS; CO-MORBIDITY AB This study examined the prevalence of nicotine dependence (ND) and its associations with DSM-IV personality disorders (PDs) among current smokers (n = 7078), controlling for sociodemographic characteristics and comorbid Axis I and II disorders. Data were derived from a nationally representative sample of the U.S. population. Although all PDs were significantly associated with ND when sociodemographic factors were controlled, only schizotypal, borderline, narcissistic and obsessive-compulsive PDs were associated with ND after adding controls for Axis I and other Axis II disorders. These associations remained significant after controlling for degree of smoking exposure. The results suggest that both shared and PD-specific pathogenetic factors underlie these PD-ND associations. Implications are also discussed in terms of the relationship between personality features of schizotypal, borderline, narcissistic and obsessive-compulsive PDs and the self-medication hypothesis and the role of neurotransmission. Published by Elsevier Ireland Ltd. C1 [Pulay, Attila J.; Stinson, Frederick S.; Ruan, W. June; Smith, Sharon M.; Pickering, Roger P.; Dawson, Deborah A.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Pulay, AJ (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3080,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM pulaya@mail.nih.gov RI Pulay, Attila/B-6155-2011 FU National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), is sponsored by the National Institute on Alcohol Abuse and Alcoholism, with supplemental support from the ,. This work was supported, in part, by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. None of the sources of funding had any influence on the design, results or interpretation of this analysis, the writing of this report, or the decision to submit the paper for publication. NR 36 TC 25 Z9 25 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2010 VL 108 IS 1-2 BP 141 EP 145 DI 10.1016/j.drugalcdep.2009.12.004 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 579NB UT WOS:000276376600021 PM 20079976 ER PT J AU Swanson, HI Njar, VCO Yu, Z Castro, DJ Gonzalez, FJ Williams, DE Huang, Y Kong, ANT Doloff, JC Ma, J Waxman, DJ Scott, EE AF Swanson, Hollie I. Njar, Vincent C. O. Yu, Zhen Castro, David J. Gonzalez, Frank J. Williams, David E. Huang, Ying Kong, Ah-Ng T. Doloff, Joshua C. Ma, Jie Waxman, David J. Scott, Emily E. TI Targeting Drug-Metabolizing Enzymes for Effective Chemoprevention and Chemotherapy SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RESISTANT PROSTATE-CANCER; ANTITUMOR-ACTIVITY; TRANSPLACENTAL CARCINOGENESIS; CYTOCHROME-P450 ENZYMES; RECEPTOR; PHARMACOKINETICS; CYCLOPHOSPHAMIDE; HYDROCARBON; MECHANISMS; PREVENTION AB The primary focus of chemoprevention research is the prevention of cancer using pharmacological, biological, and nutritional interventions. Chemotherapeutic approaches that have been used successfully for both the prevention and treatment of a number of human malignancies have arisen from the identification of specific agents and appropriate molecular targets. Although drug-metabolizing enzymes have historically been targeted in attempts to block the initial, genotoxic events associated with the carcinogenic process, emerging evidence supports the idea that manipulating drug-metabolizing enzymes may also be an effective strategy to be used for treating tumor progression, invasion, and, perhaps, metastasis. This report summarizes a symposium that presents some recent progress in this area. One area of emphasis is the development of a CYP17 inhibitor for treatment of prostate cancer that may also have androgen-independent anticancer activity at higher concentrations. A second focus is the use of a mouse model to investigate the effects of aryl hydrocarbon receptor and Cyp1b1 status and chemopreventative agents on transplacental cancer. A third area of focus is the phytochemical manipulation of not only cytochrome P450 (P450) enzymes but also phase II inflammatory and antioxidant enzymes via the nuclear factor-erythroid 2-related factor 2 pathway to block tumor progression. A final highlight is the use of prodrugs activated by P450 enzymes to halt tumor growth and considerations of dosing schedule and targeted delivery of the P450 transgene to tumor tissue. In addition to highlighting recent successes in these areas, limitations and areas that should be targeted for further investigation are discussed. C1 [Scott, Emily E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Swanson, Hollie I.] Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY USA. [Njar, Vincent C. O.] Thomas Jefferson Univ, Dept Pharmaceut Sci, Jefferson Sch Pharm, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. [Yu, Zhen; Castro, David J.; Williams, David E.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. [Huang, Ying; Kong, Ah-Ng T.] Rutgers State Univ, Sch Pharm, Dept Pharmaceut, Piscataway, NJ USA. [Doloff, Joshua C.; Ma, Jie; Waxman, David J.] Boston Univ, Dept Biol, Div Cell & Mol Biol, Boston, MA 02215 USA. RP Scott, EE (reprint author), Univ Kansas, Dept Med Chem, 4067 Malott Hall, Lawrence, KS 66045 USA. EM eescott@ku.edu OI Waxman, David/0000-0001-7982-9206 FU National Institutes of Health National Cancer Institute [CA11799101, CA02744028, CA90890, CA073674, CA094828, CA118947, CA49248]; National Institutes of Health National Institute of Environmental Health Sciences [ES00726316A1, ES07060, ES00210]; Linus Pauling Institute at Oregon State University FX This work was supported in part by the National Institutes of Health National Cancer Institute [Grants CA11799101, CA02744028, CA90890, CA073674, CA094828, CA118947, CA49248] (to V.C.O.N., D. E. W., A.N.K., and D.J.W., respectively); the National Institutes of Health National Institute of Environmental Health Sciences [Grants ES00726316A1, ES07060, ES00210] (to V.C.O.N., D. E. W.); and The Linus Pauling Institute at Oregon State University (to D. E. W.). NR 24 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2010 VL 38 IS 4 BP 539 EP 544 DI 10.1124/dmd.109.031351 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 570JJ UT WOS:000275670000001 PM 20233842 ER PT J AU Rana, R Chen, YP Ferguson, SS Kissling, GE Surapureddi, S Goldstein, JA AF Rana, Ritu Chen, Yuping Ferguson, Stephen S. Kissling, Grace E. Surapureddi, Sailesh Goldstein, Joyce A. TI Hepatocyte Nuclear Factor 4 alpha Regulates Rifampicin-Mediated Induction of CYP2C Genes in Primary Cultures of Human Hepatocytes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; GLUCOCORTICOID-RECEPTOR; GAMMA COACTIVATOR-1-ALPHA; TRANSCRIPTION FACTORS; CYTOCHROMES P450; HUMAN LIVER; CROSS-TALK; EXPRESSION; FACTOR-4-ALPHA AB CYP2C enzymes are expressed constitutively and comprise similar to 20% of the total cytochrome P450 in human liver. However, the factors influencing the transcriptional regulation of the CYP2C subfamily have only been addressed recently. In the present study, we used primary cultures of human hepatocytes to investigate the role of HNF4 alpha in the pregnane X receptor (PXR)/rifampicin-mediated upregulation of CYP2C8, CYP2C9, and CYP2C19 gene expression. We first identified new proximal cis-acting HNF4 alpha sites in the proximal CYP2C8 promoter [at -181 base pairs (bp) from the translation start site] and the CYP2C9 promoter (at -211 bp). Both sites bound HNF4 alpha in gel shift assays. Thus, these and recent studies identified a total of three HNF4 alpha sites in the CYP2C9 promoter and two in the CYP2C8 promoter. Mutational studies showed that the HNF4 alpha sites are needed for up-regulation of the CYP2C8 and CYP2C9 promoters by rifampicin. Furthermore, silencing of HNF4 alpha abolished transactivation of the CYP2C8 and CYP2C9 promoters by rifampicin. Constitutive promoter activity was also decreased. Quantitative polymerase chain reaction analysis demonstrated that silencing HNF4 alpha reduced the constitutive expression of CYP2C8 (53%), CYP2C9 (55%), and CYP2C19 (43%) mRNAs and significantly decreased the magnitude of the rifampicin-mediated induction of CYP2C8 (6.6-versus 2.7-fold), CYP2C9 (3-versus 1.5-fold), and CYP2C19 (1.8-versus 1.1-fold). These results provide clear evidence that HNF4 alpha contributes to the constitutive expression of the human CYP2C genes and is also important for upregulation by the PXR agonist rifampicin. C1 [Rana, Ritu; Chen, Yuping; Surapureddi, Sailesh; Goldstein, Joyce A.] NIEHS, Human Metab Sect, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. [Ferguson, Stephen S.] Invitrogen Corp CellzDirect, Durham, NC USA. RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Pharmacol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Rana, Ritu/F-2591-2011; Goldstein, Joyce/A-6681-2012 FU National Institutes of Health National Institute of Environmental Health Sciences [ZO1-ES02124] FX This study was supported by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences [Intramural Project ZO1-ES02124]. NR 38 TC 24 Z9 25 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2010 VL 38 IS 4 BP 591 EP 599 DI 10.1124/dmd.109.030387 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 570JJ UT WOS:000275670000007 PM 20086032 ER PT J AU Cheng, SY Leonard, JL Davis, PJ AF Cheng, Sheue-Yann Leonard, Jack L. Davis, Paul J. TI Molecular Aspects of Thyroid Hormone Actions SO ENDOCRINE REVIEWS LA English DT Review ID NUCLEAR RECEPTOR-COREPRESSOR; ACTIVATED PROTEIN-KINASE; TUMOR-TRANSFORMING GENE; RAT CEREBROCORTICAL SYNAPTOSOMES; II IODOTHYRONINE 5'-DEIODINASE; DOMINANT-NEGATIVE ACTIVITY; SECRETING PITUITARY-TUMOR; ALVEOLAR EPITHELIAL-CELLS; BASAL PROTON CONDUCTANCE; FIBROBLAST-GROWTH-FACTOR AB Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T-3 via transcriptional regulation. Two TR genes, alpha and beta, encode four T-3-binding receptor isoforms (alpha 1, beta 1, beta 2, and beta 3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T-3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T-3 target genes, by the developmental-and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T-3-dependent manner. In the absence of T-3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T-3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of the TR beta gene cause resistance to thyroid hormones to exhibit an array of symptoms due to decreasing the sensitivity of target tissues to T-3. Genetically engineered knockin mouse models also reveal that mutations of the TRs could lead to other abnormalities beyond resistance to thyroid hormones, including thyroid cancer, pituitary tumors, dwarfism, and metabolic abnormalities. Thus, the deleterious effects of mutations of TRs are more severe than previously envisioned. These genetic-engineered mouse models provide valuable tools to ascertain further the molecular actions of unliganded TRs in vivo that could underlie the pathogenesis of hypothyroidism. Actions of thyroid hormone that are not initiated by liganding of the hormone to intranuclear TR are termednongenomic. They may begin at the plasma membrane or in cytoplasm. Plasma membrane-initiated actions begin at a receptor on integrin alpha v beta 3 that activates ERK1/2 and culminate in local membrane actions on ion transport systems, such as the Na+/H+ exchanger, or complex cellular events such as cell proliferation. Concentration of the integrin on cells of the vasculature and on tumor cells explains recently described proangiogenic effects of iodothyronines and proliferative actions of thyroid hormone on certain cancer cells, including gliomas. Thus, hormonal events that begin nongenomically result in effects in DNA-dependent effects. L-T-4 is an agonist at the plasma membrane without conversion to T-3. Tetraiodothyroacetic acid is a T-4 analog that inhibits the actions of T-4 and T-3 at the integrin, including angiogenesis and tumor cell proliferation. T-3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin alpha v beta 3. Downstream consequences of phosphatidylinositol 3-kinase activation by T-3 include specific gene transcription and insertion of Na, K-ATPase in the plasma membrane and modulation of the activity of the ATPase. Thyroid hormone, chiefly T-3 and diiodothyronine, has important effects on mitochondrial energetics and on the cytoskeleton. Modulation by the hormone of the basal proton leak in mitochondria accounts for heat production caused by iodothyronines and a substantial component of cellular oxygen consumption. Thyroid hormone also acts on the mitochondrial genome via imported isoforms of nuclear TRs to affect several mitochondrial transcription factors. Regulation of actin polymerization by T-4 and rT(3), but not T-3, is critical to cell migration. This effect has been prominently demonstrated in neurons and glial cells and is important to brain development. The actin-related effects in neurons include fostering neurite outgrowth. A truncated TR alpha 1 isoform that resides in the extranuclear compartment mediates the action of thyroid hormone on the cytoskeleton. (Endocrine Reviews 31: 139-170, 2010) C1 [Davis, Paul J.] Ordway Res Inst Inc, Albany Med Coll, Signal Transduct Lab, Albany, NY 12208 USA. [Cheng, Sheue-Yann] NCI, Mol Biol Lab, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. [Leonard, Jack L.] Univ Massachusetts, Sch Med, Dept Cellular & Mol Physiol, Worcester, MA 01655 USA. RP Davis, PJ (reprint author), Ordway Res Inst Inc, Albany Med Coll, Signal Transduct Lab, 150 New Scotland Ave, Albany, NY 12208 USA. EM pdavis@ordwayresearch.org FU Beltrone Foundation; Charitable Leadership Foundation FX The authors regret omissions of references dictated by manuscript length limitations. We appreciate the contributions from colleagues and collaborators who participated in the studies conducted by the authors that are described in this review. P.J.D. acknowledges the generous research laboratory endowment established at Ordway by M. Frank and Margaret C. Rudy and the support from the Beltrone Foundation, Candace K. Weir, and Charitable Leadership Foundation Medical Technology Acceleration Program. The authors are grateful for discussions of the manuscript with colleagues, including Faith B. Davis, Alan P. Farwell, Deborah M. Leonard, and H.-Y. Lin. Margaret Wood expertly assisted in the preparation of the manuscript. NR 297 TC 412 Z9 439 U1 10 U2 99 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD APR PY 2010 VL 31 IS 2 BP 139 EP 170 DI 10.1210/er.2009-0007 PG 32 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578UB UT WOS:000276320300001 PM 20051527 ER PT J AU Lee, EK Gorospe, M AF Lee, Eun Kyung Gorospe, Myriam TI Minireview: Posttranscriptional Regulation of the Insulin and Insulin-Like Growth Factor Systems SO ENDOCRINOLOGY LA English DT Review ID RECEPTOR MESSENGER-RNA; TRACT-BINDING PROTEIN; FACTOR-I; GENE-EXPRESSION; 5'-UNTRANSLATED REGION; 3'-UNTRANSLATED REGION; TRANSLATIONAL CONTROL; GLUCOSE-HOMEOSTASIS; CELLS; HUR AB Insulin and IGFs share structural similarities and regulate metabolic processes including glucose homeostasis. Acute alterations in glucose levels trigger rapid changes in insulin concentration and insulin signaling. These processes are tightly regulated by posttranscriptional mechanisms that alter the stability and translation of mRNAs encoding insulin and the insulin receptor. Long-term glucose homeostasis is also modulated by IGFs and IGF receptors, whose expression is likewise subject to changes in the stability and translation of the encoding mRNAs. The control of mRNA half-life and translation is governed by RNA-binding proteins and microRNAs that interact with target transcripts at the 3' and 5' untranslated regions. In this review, we describe the RNA-binding proteins and microRNAs that target the mRNAs encoding insulin, IGFs, and their receptors. We discuss how these mRNA-binding factors help to elicit timely, versatile, and tissue-specific changes in insulin and IGF function, thereby effecting critical control of energy metabolism. (Endocrinology 151: 1403-1408, 2010) C1 [Lee, Eun Kyung; Gorospe, Myriam] NIA, Intramural Res Program, NIH, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Intramural Res Program, NIH, Cellular & Mol Biol Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU National Institutes of Health FX Address all correspondence and requests for reprints to: Myriam Gorospe, National Institute on Aging-Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, Maryland 21224. E-mail: myriam-gorospe@nih.gov.; This work was supported by the National Institute on Aging-Intramural Research Program, National Institutes of Health ( to E. K. L. and M. G.).; Disclosure Summary: The authors have nothing to disclose. NR 50 TC 38 Z9 39 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2010 VL 151 IS 4 BP 1403 EP 1408 DI 10.1210/en.2009-1123 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 572YL UT WOS:000275874000006 PM 20032049 ER PT J AU Liu, XX Arnold, JT Blackman, MR AF Liu, Xunxian Arnold, Julia T. Blackman, Marc R. TI Dehydroepiandrosterone Administration or G alpha q Overexpression Induces beta-Catenin/T-Cell Factor Signaling and Growth via Increasing Association of Estrogen Receptor-beta/Dishevelled2 in Androgen-Independent Prostate Cancer Cells SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; WNT/BETA-CATENIN; STROMAL CELLS; NUCLEAR TRANSLOCATION; GENE-EXPRESSION; IGF-I; WNT; PATHWAY; TRANSCRIPTION; TCF AB beta-Catenin/T-cell factor signaling (beta-CTS) plays multiple critical roles in carcinogenesis and is blocked by androgens in androgen receptor (AR)-responsive prostate cancer (PrCa) cells, primarily via AR sequestration of beta-catenin from T-cell factor. Dehydroepiandrosterone (DHEA), often used as an over-the-counter nutritional supplement, is metabolized to androgens and estrogens in humans. The efficacy and safety of unregulated use of DHEA are unclear. We now report that DHEA induces beta-CTS via increasing association of estrogen receptor (ER)-beta with Dishevelled2 (Dvl2) in AR nonresponsive human PrCa DU145 cells, a line of androgen-independent PrCa (AiPC) cells. The induction is temporal, as assessed by measuring kinetics of the association of ER beta/Dvl2, protein expression of the beta-CTS targeted genes, c-Mycandcyclin D1, and cell growth. However, in PC-3 cells, another human AiPC cell line, DHEA exerts no detectible effects, partly due to their lower expression of G alpha-subunits and DHEA down-regulation of ER beta/Dvl2 association. When G alpha q is over-expressed in PC-3 cells, beta-CTS is constitutively induced, including increasing c-Myc and cyclin D1 protein expression. This effect involved increasing associations of G alpha q/Dvl2 and ER alpha/Dvl2 and promoted cell growth. These activities require ER beta in DU-145 and PC-3 cells because they are blocked by ICI 182-780 treatment inactivating ER beta, small interfering RNA administration depleting ER beta, or AR overexpression arresting ER beta. These data suggest that novel pathways activating beta-CTS play roles in the progression of AiPC. Although DHEA may enhance PrCa cell growth via androgenic or estrogenic pathways, the effects of DHEA administration on clinical prostate function remain to be determined. (Endocrinology 151: 1428-1440, 2010) C1 [Liu, Xunxian; Arnold, Julia T.; Blackman, Marc R.] NIH, Endocrine Sect, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Liu, XX (reprint author), NIH, Endocrine Sect, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. EM xunxian1@mail.nih.gov FU National Institutes of Health (Bethesda, MD) FX We thank Dr. Ranganath Muniyappa and Dr. Ashani T. Weeraratna for their thoughtful reviews of this manuscript.; Address all correspondence and requests for reprints to: Xunxian Liu, Endocrine Section, Laboratory of Clinical Investigation, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Maryland 20892. E-mail: xunxianl@mail.nih.gov.; This work was supported by the Intramural Research Program of the National Center for Complementary and Alternative Medicine, National Institutes of Health (Bethesda, MD). Current address for M. R. B.: Veterans Affairs Medical Center, Research Service (151), 50 Irving Street, Washington, DC 20422.; Disclosure Summary: The authors have nothing to disclose. NR 49 TC 7 Z9 7 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2010 VL 151 IS 4 BP 1428 EP 1440 DI 10.1210/en.2009-0885 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 572YL UT WOS:000275874000009 PM 20176724 ER PT J AU Lu, CX Zhao, L Ying, H Willingham, MC Cheng, SY AF Lu, Changxue Zhao, Li Ying, Hao Willingham, Mark C. Cheng, Sheue-yann TI Growth Activation Alone Is Not Sufficient to Cause Metastatic Thyroid Cancer in a Mouse Model of Follicular Thyroid Carcinoma SO ENDOCRINOLOGY LA English DT Article ID FOCAL-ADHESION KINASE; HORMONE RECEPTOR MUTATIONS; BETA-RECEPTOR; ALPHA-V-BETA-3 INTEGRIN; ACTIN DYNAMICS; CELL-LINES; SRC; EXPRESSION; MICE; TSH AB TSH is the major stimulator of thyrocyte proliferation, but its role in thyroid carcinogenesis remains unclear. To address this question, we used a mouse model of follicular thyroid carcinoma (FTC) (TR beta(PV/PV) mice). These mice, harboring a dominantly negative mutation (PV) of the thyroid hormone-beta receptor (TR beta), exhibit increased serum thyroid hormone and elevated TSH. To eliminate TSH growth-stimulating effect, TR beta(PV/PV) mice were crossed with TSH receptor gene knockout (TSHR(-/-)) mice. Wild-type siblings of TR beta(PV/PV) mice were treated with an antithyroid agent, propylthiouracil, to elevate serum TSH for evaluating long-term TSH effect (WT-PTU mice). Thyroids from TR beta(PV/PV)TSHR(-/-) showed impaired growth with no occurrence of FTC. Both WT-PTU and TR beta(PV/PV) mice displayed enlarged thyroids, but only TR beta(PV/PV) mice developed metastatic FTC. Molecular analyses indicate that PV acted, via multiple mechanisms, to activate the integrins-Src-focal adhesion kinase-p38 MAPK pathway and affect cytoskeletal restructuring to increase tumor cell migration and invasion. Thus, growth stimulated by TSH is a prerequisite but not sufficient for metastatic cancer to occur. Additional genetic alterations ( such as PV), destined to alter focal adhesion and migration capacities, are required to empower hyperplastic follicular cells to invade and metastasize. These in vivo findings provide new insights in understanding carcinogenesis of the human thyroid. ( Endocrinology 151: 1929-1939, 2010) C1 [Lu, Changxue; Zhao, Li; Ying, Hao; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Intramural Research Program of National Institutes of Health; National Cancer Institute; Center for Cancer Research FX Address all correspondence and requests for reprints to: Sheue-yann Cheng, Ph. D., Laboratory of Molecular Biology, National Cancer Institute, 37 Convent Drive, Room 5128, Bethesda, Maryland 20892-4264. E-mail: chengs@mail.nih.gov.; This work was supported by the Intramural Research Program of National Institutes of Health, National Cancer Institute, and Center for Cancer Research.; Disclosure Summary: The authors have nothing to disclose. NR 43 TC 31 Z9 31 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2010 VL 151 IS 4 BP 1929 EP 1939 DI 10.1210/en.2009-1017 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 572YL UT WOS:000275874000060 PM 20133453 ER PT J AU Zhang, YM Bergman, JJGHM Weusten, B Dawsey, SM Fleischer, DE Lu, N He, S Wang, GQ AF Zhang, Y. M. Bergman, J. J. G. H. M. Weusten, B. Dawsey, S. M. Fleischer, D. E. Lu, N. He, S. Wang, G. Q. TI Radiofrequency ablation for early esophageal squamous cell neoplasia SO ENDOSCOPY LA English DT Editorial Material ID HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; FOLLOW-UP; CARCINOMA; LINXIAN; CHINA; RISK C1 [Zhang, Y. M.; He, S.; Wang, G. Q.] Chinese Acad Med Sci, Dept Endoscopy, Canc Inst & Hosp, Beijing 100021, Peoples R China. [Bergman, J. J. G. H. M.; Weusten, B.] Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol & Hepatol, NL-1105 AZ Amsterdam, Netherlands. [Weusten, B.] St Antonius Hosp, Dept Gastroenterol & Hepatol, Nieuwegein, Netherlands. [Dawsey, S. M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Fleischer, D. E.] Mayo Clin, Dept Gastroenterol & Hepatol, Scottsdale, AZ USA. [Lu, N.] Chinese Acad Med Sci, Dept Pathol, Canc Inst & Hosp, Beijing 100021, Peoples R China. RP Wang, GQ (reprint author), Chinese Acad Med Sci, Dept Endoscopy, Canc Inst & Hosp, 17 Panjiayuan, Beijing 100021, Peoples R China. EM wangguiq@126.com FU Intramural NIH HHS [Z99 CA999999, ZIA CP000185-05] NR 15 TC 10 Z9 11 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD APR PY 2010 VL 42 IS 4 BP 327 EP 333 DI 10.1055/s-0029-1244017 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 575WQ UT WOS:000276101100012 PM 20235007 ER PT J AU Zhang, LP Freeman, LEB Nakamura, J Hecht, SS Vandenberg, JJ Smith, MT Sonawane, BR AF Zhang, Luoping Freeman, Laura E. Beane Nakamura, Jun Hecht, Stephen S. Vandenberg, John J. Smith, Martyn T. Sonawane, Babasaheb R. TI Formaldehyde and Leukemia: Epidemiology, Potential Mechanisms, and implications for Risk Assessment SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE formaldehyde; epidemiology; myeloid leukemia; DNA damage; DNA adducts; risk assessment ID PROTEIN CROSS-LINKS; HEMATOPOIETIC STEM-CELLS; PERIPHERAL LYMPHOCYTES; OCCUPATIONAL-EXPOSURE; INHALED FORMALDEHYDE; FUNERAL DIRECTORS; MEXICO-CITY; DNA-DAMAGE; IN-VITRO; MORTALITY AB Formaldehyde is widely used in the United States and other countries. Occupational and environmental exposures to formaldehyde may be associated with an increased risk of leukemia in exposed individuals. However, risk assessment of formaldehyde and leukemia has been challenging due to inconsistencies in human and animal studies and the lack of a known mechanism for leukemia induction. Here, we provide a summary of the symposium at the Environmental Mutagen Society Meeting in 2008, which focused on the epidemiology of formaldehyde and leukemia, potential mechanisms, and implication for risk assessment, with emphasis on future directions in multidisciplinary formaldehyde research. Updated results of two of the three largest industrial cohort studies of formaldehyde-exposed workers have shown positive associations with leukemia, particularly myeloid leukemia, and a recent meta-analysis of studies to date supports this association. Recent mechanistic studies have shown the formation of formaldehyde-induced DNA adducts and characterized the essential DNA repair pathways that mitigate formaldehyde toxicity. The implications of the updated findings for the design of future studies to more effectively assess the risk of leukemia arising from formaldehyde exposure were discussed and specific recommendations were made. A toxicogenomic approach in experimental models and human exposure studies, together with the measurement of biomarkers of internal exposure, such as formaldehyde-DNA and protein adducts, should prove fruitful. It was recognized that increased communication among scientists who perform epidemiology, toxicology, biology, and risk assessment could enhance the design of future studies, which could ultimately reduce uncertainty in the risk assessment of formaldehyde and leukemia. Environ. Mol. Mutagen. 51:181-191, 2010. Published 2009 Wiley-Liss, Inc. C1 [Zhang, Luoping; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Freeman, Laura E. Beane] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Nakamura, Jun] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Hecht, Stephen S.] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA. [Vandenberg, John J.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Sonawane, Babasaheb R.] US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 50 Univ Hall, Berkeley, CA 94720 USA. EM luoping@berkeley.edu RI Beane Freeman, Laura/C-4468-2015; OI Beane Freeman, Laura/0000-0003-1294-4124; Hecht, Stephen/0000-0001-7228-1356; Vandenberg, John/0000-0003-2619-9460 FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES017452, R01 ES017452-01] NR 77 TC 38 Z9 43 U1 4 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR PY 2010 VL 51 IS 3 BP 181 EP 191 DI 10.1002/em.20534 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 579NV UT WOS:000276379300001 PM 19790261 ER PT J AU Vlaanderen, J Portengen, L Rothman, N Lan, Q Kromhout, H Vermeulen, R AF Vlaanderen, Jelle Portengen, Lutzen Rothman, Nathaniel Lan, Qing Kromhout, Hans Vermeulen, Roe TI Flexible Meta-Regression to Assess the Shape of the Benzene-Leukemia Exposure-Response Curve SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE benzene; epidemiology; leukemia; meta-regression; quantitative risk assessment ID EPIDEMIOLOGIC RISK ASSESSMENT; DISTRIBUTION WORKERS; TREND ESTIMATION; ALBUMIN ADDUCTS; LUNG-CANCER; METAANALYSIS; MORTALITY; METABOLISM; COHORT; BIOMARKERS AB BACKGROUND: Previous evaluations of the shape of the benzene leukemia exposure response curve (ERC) were based on a single set or on small sets of human occupational studies. Integrating evidence from all available studies that are of sufficient quality combined with flexible meta-regression models is likely to provide better insight into the functional relation between benzene exposure and risk of leukemia. OBJECTIVES: We used natural splines in a flexible meta-regression method to assess the shape of the benzene leukemia ERG. METHODS: We fitted meta-regression models to 30 aggregated risk estimates extracted from nine human observational studies and performed sensitivity analyses to assess the impact of a priori assessed study characteristics on the predicted ERG. RESULTS: The natural spline showed a supralinear shape at cumulative exposures less than 100 ppm-years, although this model fitted the data only marginally better than a linear model (p = 0.06). Stratification based on study design and jackknifing indicated that the cohort studies had a considerable impact on the shape of the ERG at high exposure levels (> 100 ppm-years) but that predicted risks for the low exposure range (< 50 ppm-years) were robust. CONCLUSIONS: Although limited by the small number of studies and the large heterogeneity between studies, the inclusion of all studies of sufficient quality combined with a flexible meta-regression method provides the most comprehensive evaluation of the benzene leukemia ERG to date. The natural spline based on all data indicates a significantly increased risk of leukemia [relative risk (RR) = 1.14; 95% confidence interval (CI), 1.04-1.26] at an exposure level as low as 10 ppm-years. C1 [Vlaanderen, Jelle] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, NL-3584 CK Utrecht, Netherlands. [Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Vlaanderen, J (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands. EM J.J.Vlaanderen@uu.nl RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU European Union [FOOD-CT-2005-513943] FX This work was performed as part of the work package "integrated risk assessment" of the Environmental Cancer Risk, Nutrition and Individual Susceptibility Network of Excellence, operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (FOOD-CT-2005-513943). NR 53 TC 20 Z9 20 U1 1 U2 10 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2010 VL 118 IS 4 BP 526 EP 532 DI 10.1289/ehp.0901127 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 580NA UT WOS:000276454800026 PM 20064779 ER PT J AU Birnbaum, LS AF Birnbaum, Linda S. TI Applying Research to Public Health Questions: Biologically Relevant Exposures SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Birnbaum, LS (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 5 TC 8 Z9 8 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2010 VL 118 IS 4 BP A152 EP A153 DI 10.1289/ehp.1002015 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 580NA UT WOS:000276454800001 PM 20368121 ER PT J AU Quinn, TC Samet, JM AF Quinn, Thomas C. Samet, Jonathan M. TI Epidemiologic Approaches to Global Health SO EPIDEMIOLOGIC REVIEWS LA English DT Article DE acquired immunodeficiency syndrome; communicable diseases; environmental health; epidemiologic methods; HIV; maternal welfare; population surveillance; world health AB In this introduction to volume 32 of Epidemiologic Reviews, the authors highlight the diversity and complexity of global health concerns, and they frame the 12 articles included in this issue within the diverse topics of research in this emerging and ever-expanding field. The authors emphasize the need for ongoing research related to the methods used in global health and for comprehensive surveillance, and they offer suggestions for future directions in global health research. C1 [Quinn, Thomas C.] Johns Hopkins Univ, Ctr Global Hlth, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, Bethesda, MD 20892 USA. [Samet, Jonathan M.] Univ So Calif, Dept Prevent Med, USC Inst Global Hlth, Los Angeles, CA 90089 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Ctr Global Hlth, Rangos Bldg,855 N Wolfe St,Suite 530, Baltimore, MD 21205 USA. EM tquinm2@jhmi.edu FU Intramural NIH HHS [ZIA AI000361-28]; NICHD NIH HHS [R24 HD042854] NR 20 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PD APR PY 2010 VL 32 IS 1 BP 1 EP 4 DI 10.1093/epirev/mxq007 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 630JV UT WOS:000280270100001 PM 20581220 ER PT J AU Marcus, FI McKenna, WJ Sherrill, D Basso, C Bauce, B Bluemke, DA Calkins, H Corrado, D Cox, MGPJ Daubert, JP Fontaine, G Gear, K Hauer, R Nava, A Picard, MH Protonotarios, N Saffitz, JE Sanborn, DMY Steinberg, JS Tandri, H Thiene, G Towbin, JA Tsatsopoulou, A Wichter, T Zareba, W AF Marcus, Frank I. McKenna, William J. Sherrill, Duane Basso, Cristina Bauce, Barbara Bluemke, David A. Calkins, Hugh Corrado, Domenico Cox, Moniek G. P. J. Daubert, James P. Fontaine, Guy Gear, Kathleen Hauer, Richard Nava, Andrea Picard, Michael H. Protonotarios, Nikos Saffitz, Jeffrey E. Sanborn, Danita M. Yoerger Steinberg, Jonathan S. Tandri, Harikrishna Thiene, Gaetano Towbin, Jeffrey A. Tsatsopoulou, Adalena Wichter, Thomas Zareba, Wojciech TI Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia SO EUROPEAN HEART JOURNAL LA English DT Article DE Arrhythmias, cardiac; Arrhythmogenic right ventricular cardiomyopathy/dysplasia; Death, sudden, cardiac; Diagnosis; Echocardiography; Electrocardiography; Magnetic resonance imaging ID GENOTYPE-PHENOTYPE ASSESSMENT; TASK-FORCE CRITERIA; MAGNETIC-RESONANCE; NAXOS-DISEASE; WOOLLY HAIR; PALMOPLANTAR KERATODERMA; QUANTITATIVE ASSESSMENT; DILATED CARDIOMYOPATHY; ENDOMYOCARDIAL BIOPSY; WALL-MOTION AB Background In 1994, an International Task Force proposed criteria for the clinical diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) that facilitated recognition and interpretation of the frequently nonspecific clinical features of ARVC/D. This enabled confirmatory clinical diagnosis in index cases through exclusion of phenocopies and provided a standard on which clinical research and genetic studies could be based. Structural, histological, electrocardiographic, arrhythmic, and familial features of the disease were incorporated into the criteria, subdivided into major and minor categories according to the specificity of their association with ARVC/D. At that time, clinical experience with ARVC/D was dominated by symptomatic index cases and sudden cardiac death victims the overt or severe end of the disease spectrum. Consequently, the 1994 criteria were highly specific but lacked sensitivity for early and familial disease. Methods and Results Revision of the diagnostic criteria provides guidance on the role of emerging diagnostic modalities and advances in the genetics of ARVC/D. The criteria have been modified to incorporate new knowledge and technology to improve diagnostic sensitivity, but with the important requisite of maintaining diagnostic specificity. The approach of classifying structural, histological, electrocardiographic, arrhythmic, and genetic features of the disease as major and minor criteria has been maintained. In this modification of the Task Force criteria, quantitative criteria are proposed and abnormalities are defined on the basis of comparison with normal subject data. Conclusions The present modifications of the Task Force Criteria represent a working framework to improve the diagnosis and management of this condition. C1 [Marcus, Frank I.; Sherrill, Duane; Gear, Kathleen] Univ Arizona, Tucson, AZ USA. [McKenna, William J.] Heart Hosp, London, England. [Basso, Cristina; Bauce, Barbara; Corrado, Domenico; Nava, Andrea; Thiene, Gaetano] Univ Padua, Sch Med, Padua, Italy. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Calkins, Hugh; Tandri, Harikrishna] Johns Hopkins Univ Hosp, Baltimore, MD USA. [Cox, Moniek G. P. J.; Hauer, Richard] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Daubert, James P.] Univ Rochester, Strong Mem Hosp, Rochester, NY 14642 USA. [Zareba, Wojciech] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Steinberg, Jonathan S.] St Lukes Roosevelt Hosp, New York, NY USA. [Fontaine, Guy] Hop La Pitie Salpetriere, Paris, France. [Picard, Michael H.; Sanborn, Danita M. Yoerger] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Saffitz, Jeffrey E.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Protonotarios, Nikos; Tsatsopoulou, Adalena] Yannis Protonotarios Med Ctr, Hora Naxos, Greece. [Towbin, Jeffrey A.] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Wichter, Thomas] Marien Hosp, Osnabruck, Germany. RP Marcus, FI (reprint author), Sarver Heart Ctr, 1501 N Campbell,Rm 5153,Box 245037, Tucson, AZ USA. EM fmarcus@u.arizona.edu RI McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Picard, Michael/0000-0002-9264-3243; Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung & Blood Institute [R13 HL086825]; Office of Rare Disorders [R13 HL086825]; National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD [U01-HL65594, U01-HL65652, U01-HL65691, K23-HL093350]; European Commission, Brussels, Belgium [QLG1-CT-2000-01091]; International Society for Holter and Noninvasive Electrocardiography; Peter French Memorial Foundation, United Desert Charities; Podolsky Family Foundation FX This project was supported by National Institutes of Health research grant R13 HL086825, funded by the National Heart, Lung & Blood Institute and the Office of Rare Disorders, and was supported in part by research grants U01-HL65594, U01-HL65652, U01-HL65691, and K23-HL093350 from the National Heart, Lung and Blood Institute of the National Institutes of Health, Bethesda, MD, and by research grant QLG1-CT-2000-01091 5th Framework Programme from the European Commission, Brussels, Belgium. Additional funding was obtained from the International Society for Holter and Noninvasive Electrocardiography and donations from the Peter French Memorial Foundation, United Desert Charities, the Podolsky Family Foundation, and private donors Mr and Mrs L. Becker, Mr and Mrs H. Danz, Mr K. Dorn, Mr T. Livolsi, Mr and Mrs L. Long, and Mr and Mrs H. Wilmerding. NR 59 TC 327 Z9 347 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2010 VL 31 IS 7 BP 806 EP 814 DI 10.1093/eurheartj/ehq025 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 586FZ UT WOS:000276892800012 PM 20172912 ER PT J AU Chen, X Subleski, JJ Hamano, R Howard, OMZ Wiltrout, RH Oppenheim, JJ AF Chen, Xin Subleski, Jeffrey J. Hamano, Ryoko Howard, O. M. Zack Wiltrout, Robert H. Oppenheim, Joost J. TI Co-expression of TNFR2 and CD25 identifies more of the functional CD4(+)FOXP3(+) regulatory T cells in human peripheral blood SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD25; Human regulatory T cells; Peripheral blood; TNFR2 ID IN-VITRO; EXPRESSION; TOLERANCE; CTLA-4; P75; COSTIMULATOR; MAINTENANCE; SUPPRESSION; ACTIVATION; INDUCTION AB Previously, we found that co-expression of CD25 and TNFR2 identified the most suppressive subset of mouse Treg. In this study, we report that human peripheral blood (PB) FOXP3(+) cells present in CD25(high), CD25(low) and even CD25(-) subsets of CD4(+) cells expressed high levels of TNFR2. Consequently, TNFR2-expressing CD4(+)CD25(+) Treg included all of the FOXP3(+) cells present in the CD4(+)CD25(high) subset as well as a substantial proportion of the FOXP3(+) cells present in the CD4(+)CD25(low) subset. Flow cytometric analysis of PB identified five-fold more Treg, determined by FOXP3 expression, in the CD4(+)CD25(+)TNFR2(+) subset than in the CD4(+)CD25(high) subset. In addition, similar levels of FOXP3(+) cells were identified in both the CD4(+)CD25(+)TNFR2(+) and CD4(+)CD25(+) CD127(low/-) subsets. Furthermore, the CD4(+)CD25(+)TNFR2(+) subset expressed high levels of CTLA-4, CD45RO, CCR4 and low levels of CD45RA and CD127, a phenotype characteristic of Treg. Upon TCR stimulation, human PB CD4(+)CD25(+)TNFR2(+) cells were anergic and markedly inhibited the proliferation and cytokine production of co-cultured T-responder cells. In contrast, CD4(+)CD25(+)TNFR2(-) and CD4(+)CD25(-)TNFR2(+) T cells did not show inhibitory activity. As some non-Treg express TNFR2, the combination of CD25 and TNFR2 must be used to identify a larger population of human Treg, a population that may prove to be of diagnostic and therapeutic benefit in cancer and autoimmune diseases. C1 [Chen, Xin] NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, Frederick, MD 21702 USA. [Subleski, Jeffrey J.; Wiltrout, Robert H.] NCI Frederick, Expt Immunol Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Hamano, Ryoko; Howard, O. M. Zack; Oppenheim, Joost J.] NCI Frederick, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI Frederick, BSP, SAIC Frederick Inc, Mol Immunoregulat Lab,CIP, POB 8,Bldg 560,Room 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU National Cancer Institute, National Institutes of Health, Center for Cancer Research [HHSN261200800001E] 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 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 US Government. NR 32 TC 59 Z9 62 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2010 VL 40 IS 4 BP 1099 EP 1106 DI 10.1002/eji.200940022 PG 8 WC Immunology SC Immunology GA 590FS UT WOS:000277210800020 PM 20127680 ER PT J AU Loomis, K Smith, B Feng, Y Garg, H Yavlovich, A Campbell-Massa, R Dimitrov, DS Blumenthal, R Xiao, XD Puri, A AF Loomis, Kristin Smith, Brandon Feng, Yang Garg, Himanshu Yavlovich, Amichai Campbell-Massa, Ryan Dimitrov, Dimiter S. Blumenthal, Robert Xiao, Xiaodong Puri, Anu TI Specific targeting to B cells by lipid-based nanoparticles conjugated with a novel CD22-ScFv SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE Liposomes; Targeting; B-cell Lymphoma; Anti-CD22 ScEv; Drug delivery ID NON-HODGKINS-LYMPHOMA; HUMANIZED ANTI-CD22 ANTIBODY; PRECLINICAL MANUFACTURE; LIPOSOMAL DOXORUBICIN; MONOCLONAL-ANTIBODIES; ANTICANCER DRUGS; ANTIGEN RECEPTOR; ANIMAL TOXICITY; MURINE MODEL; CD22 AB The CD22 antigen is a viable target for therapeutic intervention for B-cell lymphomas. Several therapeutic anti-CD22 antibodies as well as an anti-CD22-based immunotoxin (HA22) are currently under investigation in clinical settings. Coupling of anti-CD22 reagents with a nano-drug delivery vehicle is projected to significantly improve treatment efficacies. Therefore, we generated a mutant of the targeting segment of HA22 (a CD22 scFv) to increase its soluble expression (mut-HA22), and conjugated it to the surface of sonicated liposomes to generate immunoliposomes (mut-HA22-liposomes). We examined liposome binding and uptake by CD22(+) B-lymphocytes (BJAB) by using calcein and/or rhodamine PE-labeled liposomes. We also tested the effect of targeting on cellular toxicity with doxorubicin-loaded liposomes. We report that: (i) Binding of mut-HA22-liposomes to BJAB cells was significantly greater than liposomes not conjugated with mut-HA22 (control liposomes), and mut-HA22-liposomes bind to and are taken in by BJAB cells in a dose and temperature-dependent manner, respectively; (ii) This binding occurred via the interaction with the cellular CD22 as pre-incubation of the cells with mut-HA22 blocked subsequent liposome binding; (iii) Intracellular localization of mut-HA22-liposomes at 37 degrees C but not at 4 degrees C indicated that our targeted liposomes were taken up through an energy dependent process via receptor-mediated endocytosis; and (iv) Mut-HA22-liposomes loaded with doxorubicin exhibited at least 2-3 fold more accumulation of doxorubicin in BJAB cells as compared to control liposomes. Moreover, these liposomes showed at least a 2-4 fold enhanced killing of BJAB or Raji cells (CD22(+)), but not SUP-T1 cells (CD22(-)). Taken together these data suggest that these 2nd-generation liposomes may serve as promising carriers for targeted drug delivery to treat patients suffering from B-cell lymphoma. Published by Elsevier Inc. C1 [Loomis, Kristin; Smith, Brandon; Feng, Yang; Garg, Himanshu; Yavlovich, Amichai; Campbell-Massa, Ryan; Dimitrov, Dimiter S.; Blumenthal, Robert; Xiao, Xiaodong; Puri, Anu] NCI, CCR Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Puri, A (reprint author), NCI, CCR Nanobiol Program, NIH, Bldg 469 Rm 216A,POB B,Miller Dr, Frederick, MD 21702 USA. EM XiaoX@MedImmune.com; apuri@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX We wish to thank Ira Pastan and Mitchel Ho, Laboratory of Molecular Biology, NCI, NIH for providing reagents. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank Dr. Prabhakar Gudla and Ms. Kim Peifley (Image Analysis Laboratory, ATP, SAIC-Frederick) for help with the confocal microscopy. We thank Julie Belanger and Eli Heldman for critical reading of the manuscript. NR 52 TC 22 Z9 23 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD APR PY 2010 VL 88 IS 2 BP 238 EP 249 DI 10.1016/j.yexmp.2010.01.006 PG 12 WC Pathology SC Pathology GA 584HB UT WOS:000276741000004 PM 20122924 ER PT J AU Poston, B Christou, EA Enoka, JA Enoka, RM AF Poston, Brach Christou, Evangelos A. Enoka, Joel A. Enoka, Roger M. TI Timing variability and not force variability predicts the endpoint accuracy of fast and slow isometric contractions SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Hand; First dorsal interosseus; Force control; Neural noise ID SIGNAL-DEPENDENT NOISE; MOTOR-OUTPUT VARIABILITY; OLD ADULTS; TACTILE AFFERENTS; MOVEMENT ACCURACY; CORTICAL CONTROL; ARM MOVEMENTS; INDEX FINGER; MUSCLE; YOUNG AB The purpose of the study was to determine the contributions of endpoint variance and trajectory variability to the endpoint accuracy of goal-directed isometric contractions when the target force and contraction speed were varied. Thirteen young adults (25 +/- A 6 years) performed blocks of 15 trials at each of 2 contraction speeds and 4 target forces. Subjects were instructed to match the peak of a parabolic force trajectory to a target force by controlling the abduction force exerted by the index finger. The time to peak force was either 150 ms (fast) or 1 s (slow). The target forces were 20, 40, 60, and 80% of the maximal force that could be achieved in 150 ms during an MVC. The same absolute forces were required for both contraction speeds. Endpoint accuracy and variability in force and time along with intramuscular EMG activity of the agonist (first dorsal interosseus) and antagonist (second palmar interosseus) muscles were quantified for each block of trials. The principal dependent variables were endpoint error (shortest distance between the coordinates of the target and the peak force), endpoint variance (sum of the variance in peak force and time to peak force), trial-to-trial variability (SD of peak force and time to peak force), SD of the force trajectory (SD of the detrended force from force onset to peak force), normalized peak EMG amplitude, and the SD of normalized peak EMG amplitude. Stepwise multiple linear regression models were used to determine the EMG activity parameters that could explain the differences observed in endpoint error and endpoint variance. Endpoint error increased with target force for the fast contractions, but not for the slow contractions. In contrast, endpoint variance was greatest at the lowest force and was not associated with endpoint error at either contraction speed. Furthermore, force trajectory SD was not associated with endpoint error or endpoint variance for either contraction speed. Only the trial-to-trial variability of the timing predicted endpoint accuracy for fast and slow contractions. These findings indicate that endpoint error in tasks that require force and timing accuracy is minimized by controlling timing variability but not force variability, and that endpoint error is not related to the amplitude of the activation signal. C1 [Poston, Brach] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Poston, Brach] Arizona State Univ, Dept Kinesiol, Tempe, AZ USA. [Christou, Evangelos A.] Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA. [Enoka, Joel A.; Enoka, Roger M.] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA. RP Poston, B (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM brach.poston@nih.gov FU National Institute on Aging (NIA [AG024662, AG031769, AG09000]; NIA Predoctoral Training Fellowship [T32 AG00279-05] FX This work was supported by National Institute on Aging (NIA) awards AG024662 and AG031769 (EAC) and AG09000 (RME). B. Poston was supported by NIA Predoctoral Training Fellowship T32 AG00279-05 (PI Robert Schwartz). NR 54 TC 8 Z9 9 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2010 VL 202 IS 1 BP 189 EP 202 DI 10.1007/s00221-009-2126-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 575EM UT WOS:000276049600017 PM 20033680 ER PT J AU Carvalho, WA Maruyama, SR Franzin, AM Abatepaulo, ARR Anderson, JM Ferreira, BR Ribeiro, JMC More, DD Maia, AAM Valenzuela, JG Garcia, GR Santos, IKFD AF Carvalho, Wanessa Araujo Maruyama, Sandra Regina Franzin, Alessandra Mara Rodrigues Abatepaulo, Antonio Roberto Anderson, Jennifer M. Ferreira, Beatriz Rossetti Chaves Ribeiro, Jose Marcos More, Daniela Dantas Mendes Maia, Antonio Augusto Valenzuela, Jesus G. Garcia, Gustavo Rocha de Miranda Santos, Isabel K. Ferreira TI Rhipicephalus (Boophilus) microplus: Clotting time in tick-infested skin varies according to local inflammation and gene expression patterns in tick salivary glands SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Rhipicephalus (Boophilus) microplus; Haemostasis; Clotting time; Ticks; Bos taurus taurus; Bos taurus indicus; Saliva; Haematophagy; Transcriptome ID ORNITHODOROS-SAVIGNYI ACARI; BLOOD-COAGULATION; BOS-TAURUS; THROMBIN INHIBITOR; INTRAVASCULAR COAGULATION; IXODES-SCAPULARIS; HAEMAPHYSALIS-LONGICORNIS; PROTEINASE-INHIBITOR; TISSUE FACTOR; CATTLE TICK AB Ticks deposit saliva at the site of their attachment to a host in order to inhibit haemostasis, inflammation and innate and adaptive immune responses. The anti-haemostatic properties of tick saliva have been described by many studies, but few show that tick infestations or its anti-haemostatic components exert systemic effects in vivo. In the present study, we extended these observations and show that, compared with normal skin, bovine hosts that are genetically susceptible to tick infestations present an increase in the clotting time of blood collected from the immediate vicinity of haemorrhagic feeding pools in skin infested with different developmental stages of Rhipicepahlus microplus; conversely, we determined that clotting time of tick-infested skin from genetically resistant bovines was shorter than that of normal skin. Coagulation and inflammation have many components in common and we determined that in resistant bovines, eosinophils and basophils, which are known to contain tissue factor, are recruited in greater numbers to the inflammatory site of tick bites than in susceptible hosts. Finally, we correlated the observed differences in clotting times with the expression profiles of transcripts for putative anti-haemostatic proteins in different developmental stages of R. microplus fed on genetically susceptible and resistant hosts: we determined that transcripts coding for proteins similar to these molecules are overrepresented in salivary glands from nymphs and males fed on susceptible bovines. Our data indicate that ticks are able to modulate their host's local haemostatic reactions. In the resistant phenotype, larger amounts of inflammatory cells are recruited and expression of anti-coagulant molecules is decreased tick salivary glands, features that can hamper the tick's blood meal. (C) 2010 Elsevier Inc. All rights reserved. C1 [Carvalho, Wanessa Araujo; Maruyama, Sandra Regina; Franzin, Alessandra Mara; Rodrigues Abatepaulo, Antonio Roberto; More, Daniela Dantas; Garcia, Gustavo Rocha; de Miranda Santos, Isabel K. Ferreira] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. [Anderson, Jennifer M.; Chaves Ribeiro, Jose Marcos; Valenzuela, Jesus G.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Ferreira, Beatriz Rossetti] Univ Sao Paulo, Ribeirao Preto Sch Nursing, Dept Maternal & Child & Publ Hlth Nursing, BR-14049900 Ribeirao Preto, SP, Brazil. [Mendes Maia, Antonio Augusto] Univ Sao Paulo, Sch Anim Sci & Food Technol, Dept Basic Sci, BR-13635900 Pirassununga, SP, Brazil. [de Miranda Santos, Isabel K. Ferreira] Embrapa Recursos Genet & Biotecnol, BR-70770900 Brasilia, DF, Brazil. RP Santos, IKFD (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Depto Bioquim & Imunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM imsantos@fmrp.usp.br RI Ferreira, Beatriz/C-2003-2012; Maruyama, Sandra/G-1171-2012; de Miranda Santos, Isabel/B-7597-2012; Garcia, Gustavo/E-5182-2013; Franzin, Alessandra/D-4545-2013; de Miranda Santos, Isabel/D-5261-2016; OI Ferreira, Beatriz/0000-0002-6781-2236; de Miranda Santos, Isabel/0000-0002-0438-4430; Maruyama, Sandra/0000-0001-6807-1452; Ribeiro, Jose/0000-0002-9107-0818 FU Fundaco de Amparo A Pesquisa do Estado de SAO Paulo - FAPESP; Conselho Nacional de Pesquisa e Desenvolvimento Cientifico e Tecnologico - CNPq; National Institute of Allergy and Infectious Diseases FX This work received financial support from Fundaco de Amparo A Pesquisa do Estado de SAO Paulo - FAPESP and Conselho Nacional de Pesquisa e Desenvolvimento Cientifico e Tecnologico - CNPq, and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. The authors thank Dr. Ivo M. Francischetti for reading the manuscript and his comments for its improvement and Dr. Joao S. Silva for generous and continuing support of this work performed in his laboratory. W.A.C., S.R.C.M., G.R-G. and D.D.M. received scholarships from FAPESP and ARRA and A.M.F. received scholarships from Coordenaao de Aperfeiqoamento de Pessoal de Nivel Superior - CAPES. NR 54 TC 15 Z9 17 U1 1 U2 7 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 APR PY 2010 VL 124 IS 4 BP 428 EP 435 DI 10.1016/j.exppara.2009.12.013 PG 8 WC Parasitology SC Parasitology GA 565PQ UT WOS:000275306800010 PM 20045690 ER PT J AU Jackson, WM Nesti, LJ Tuan, RS AF Jackson, Wesley M. Nesti, Leon J. Tuan, Rocky S. TI Potential therapeutic applications of muscle-derived mesenchymal stem and progenitor cells SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE MPCs; MSCs; regenerative medicine; skeletal muscle stem cells; tissue engineering ID HUMAN SKELETAL-MUSCLE; HUMAN TRABECULAR BONE; VIVO GENE-THERAPY; MYOGENIC ENDOTHELIAL-CELLS; MORPHOGENETIC PROTEIN 4; REGENERATIVE MEDICINE; IMMUNOLOGICAL-PROPERTIES; TECHNOLOGY INSIGHT; CARTILAGE REPAIR; DENTAL-TISSUES AB Importance of the field: Mesenchymal adult stem cells have properties that make them attractive for use in tissue engineering and regenerative medicine. They are inherently plastic, enabling them to differentiate along different lineages, and promote wound healing and regeneration of surrounding tissues by modulating immune and inflammatory responses, promoting angiogenesis and secreting other trophic factors. Unlike embryonic stem cells, clinical uses of mesenchymal stem cells are not encumbered by ethical considerations or legal restrictions. Areas covered in this review: We discuss skeletal muscle as a source of mesenchyma I stem and progenitor cells by reviewing their biology and current applications in tissue engineering and regenerative medicine. This paper covers literature from the last 5 - 10 years. What the reader will gain: Skeletal muscle is a plentiful source of mesenchymal stem and progenitor cells. This tissue may be obtained via routine biopsy or collection after surgical debridement. We describe the biology of these cells and provide an overview of therapeutic applications currently being developed to take advantage of their regenerative properties. Take home message: There is potential for stem and progenitor cells derived from skeletal muscle to be incorporated in clinical interventions, either as a cellular therapy to modify the natural history of disease or as a component of engineered tissue constructs that can replace diseased or damaged tissues. C1 [Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, Pittsburgh, PA 15232 USA. [Jackson, Wesley M.; Nesti, Leon J.; Tuan, Rocky S.] NIAMSD, NIH, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Jackson, Wesley M.; Nesti, Leon J.] NIAMSD, NIH, Dept Hlth & Human Serv, Clin & Expt Orthopaed Lab, Bethesda, MD 20892 USA. [Nesti, Leon J.] Walter Reed Army Med Ctr, Dept Orthopaed & Rehabil, Washington, DC 20307 USA. RP Tuan, RS (reprint author), Univ Pittsburgh, Sch Med, Ctr Cellular & Mol Engn, Dept Orthopaed Surg, 450 Technol Dr,Room 221, Pittsburgh, PA 15232 USA. EM rst13@pitt.edu FU Military Amputee Research Program [P05-A011]; Comprehensive Neurosciences Program [CNP-2008-CR01]; NIH [Z01 AR41131] FX LJ Nesti has received funding from the Military Amputee Research Program #P05-A011 and Comprehensive Neurosciences Program #CNP-2008-CR01. RS Tuan received NIH intramural Support (Z01 AR41131). NR 117 TC 41 Z9 48 U1 4 U2 20 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD APR PY 2010 VL 10 IS 4 BP 505 EP 517 DI 10.1517/14712591003610606 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 582CQ UT WOS:000276573500003 PM 20218920 ER PT J AU Franco, R Canela, EI Casado, V Ferre, S AF Franco, Rafael Canela, Enric I. Casado, Vicent Ferre, Sergi TI Platforms for the identification of GPCR targets, and of orthosteric and allosteric modulators SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE binding; drug discovery; GPCR dimer; heteromer; label-free ID PROTEIN-COUPLED RECEPTORS; CELL-SURFACE RECEPTORS; FREE OPTICAL BIOSENSOR; HIGHER-ORDER OLIGOMERS; ENERGY-TRANSFER BRET; DRUG DISCOVERY; LIVING CELLS; ADENOSINE RECEPTOR; CRYSTAL-STRUCTURE; OPIOID RECEPTORS AB Areas covered in this review: The review provides a summary of old and new approaches for GPCR target identification and for the screening of molecules acting on GPCR targets. The new findings in the field are presented as well as an opinion about how these developments may help GPCR drug discovery. Importance in the field: GPCRs have been the most useful family of proteins in terms of targets for drug discovery. The expectations for GPCR target identification and discovery of new drugs acting on 'old' or 'new' GPCR targets are very high. Given the fact that the pace at which new 'GPCR drugs' appear in the market is decreasing and since the new developments in the field are not being translated into drug discovery there is a need to review the field from a critical perspective. Take home message: To overcome the limitation of the old approaches used in GPCR target identification and drugs discovery new approaches are required. In particular successful approaches in GPCR drug discovery should take into account that the real GPCR targets for a given disease are not GPCR monomers but GPCR heteromers. What the reader will gain: The reader will gain an overview of the strategies currently used and their pros and cons. The reader will also understand that new strategies may help in accelerating the access of GPCR into the market, and also notice that successful strategies should take advantage of the new findings in the field of GPCRs. C1 [Franco, Rafael] Univ Navarra, CIMA, E-31080 Pamplona, Spain. [Franco, Rafael; Canela, Enric I.; Casado, Vicent] Univ Barcelona, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. [Ferre, Sergi] Natl Inst Drug Abuse, Dept Hlth & Human Serv, NIH, Intramural Res Program, Baltimore, MD 21224 USA. RP Franco, R (reprint author), Univ Navarra, CIMA, E-31080 Pamplona, Spain. EM rfranco@unav.es RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 FU Spanish `Ministerio de Ciencia, Innovacion y Tecnologia' [SAF2008- 00146, SAF2008- 03229-E, SAF2009- 07276]; Fundacio La Marato de TV3 [060110]; National Institute on Drug Abuse FX This research was supported by grant SAF2008- 00146, SAF2008- 03229-E and SAF2009- 07276 from the Spanish `Ministerio de Ciencia, Innovacion y Tecnologia', grant 060110 from Fundacio La Marato de TV3 and from the Intramural Funds of the National Institute on Drug Abuse. NR 90 TC 5 Z9 5 U1 0 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD APR PY 2010 VL 5 IS 4 BP 391 EP 403 DI 10.1517/17460441003653163 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 591DM UT WOS:000277279200007 PM 22823089 ER PT J AU Weiss, BM Kuehl, WM AF Weiss, Brendan M. Kuehl, W. Michael TI Advances in understanding monoclonal gammopathy of undetermined significance as a precursor of multiple myeloma SO EXPERT REVIEW OF HEMATOLOGY LA English DT Review DE MGUS; monoclonal gammopathy of undetermined significance; multiple myeloma; pathogenesis ID LIGHT-CHAIN RATIO; INDEPENDENT RISK-FACTOR; PLASMA-CELL DISORDERS; SIGNIFICANCE MGUS; NATURAL-HISTORY; WORKING GROUP; 1ST-DEGREE RELATIVES; MARROW ANGIOGENESIS; PRIMARY AMYLOIDOSIS; PESTICIDE EXPOSURE AB Monoclonal gammopathy of undetermined significance (MGUS) affects at least 3% of the population above the age of 50 and is the precursor to multiple myeloma (MM), an incurable malignancy of plasma cells. Recent advances in MGUS include: an improved understanding of the pathogenesis of MGUS and its progression to MM, involving molecular events intrinsic to the malignant plasma cell as well as the microenvironment; novel techniques to assess risk for progression to MM using serum-free light-chain analysis and immunophenotyping; and a renewed interest in chemoprevention of MM. In the future, continued improvement in our understanding of MGUS will lead to the development of better biomarkers for prognosis and therapies for chemoprevention of MM. C1 [Weiss, Brendan M.] Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. [Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Weiss, BM (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, 6900 Georgia Ave NW, Washington, DC 20307 USA. EM brendan.weiss@us.army.mil FU NIH, National Cancer Institute, Center for Cancer Research; Binding Site, Inc., Birmingham, UK FX The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Army, nor the US Government. W Michael Kuehl is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Other research support was provided by The Binding Site, Inc., Birmingham, UK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 75 TC 3 Z9 3 U1 1 U2 5 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4086 J9 EXPERT REV HEMATOL JI Expert Rev. Hematol. PD APR PY 2010 VL 3 IS 2 BP 165 EP 174 DI 10.1586/EHM.10.13 PG 10 WC Hematology SC Hematology GA 687TT UT WOS:000284801500010 PM 20473362 ER PT J AU Matsuda, KM Chung, JY Hewitt, SM AF Matsuda, Kant M. Chung, Joon-Yong Hewitt, Stephen M. TI Histo-proteomic profiling of formalin-fixed, paraffin-embedded tissue SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE formalin-fixed; paraffin-embedded tissue; high throughput; multiplex protein analysis; protein array; protein extraction; proteomic profiling; radiographic-histopathologic correlation; tissue immunoblotting; tissue microarray ID PHASE PROTEIN MICROARRAYS; IMAGING MASS-SPECTROMETRY; WATER DIFFUSION; GENE-EXPRESSION; GROWTH-FACTOR; QUANTUM DOTS; COLON-CANCER; LUNG-CANCER; IN-VIVO; THERAPY AB In the functional proteome era, the proteomic profiling of clinicopathologic-annotated tissues is an essential step for mining and evaluating candidate biomarkers for disease. For many diseases, but especially cancer, the development of predictive biomarkers requires performing assays directly on the diseased tissue. The last decade has seen the explosion of both prognostic and predictive biomarkers in the research setting but few of these biomarkers have entered widespread clinical use. Previously, application of routine proteomic methodologies to clinical formalin-fixed and paraffin-embedded tissue specimens has provided unsatisfactory results. In this paper, we will discuss recent advancements in proteomic profiling technology for clinical applications. These approaches focus on the retention of histomorphologic information as an element of the proteomic analysis. C1 [Matsuda, Kant M.; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Ctr Canc Res, NIH,MSC Adv Technol Ctr 4605, Bethesda, MD 20892 USA. [Chung, Joon-Yong] NCI, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Ctr Canc Res, NIH,MSC Adv Technol Ctr 4605, Bethesda, MD 20892 USA. EM genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 78 TC 15 Z9 15 U1 2 U2 4 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD APR PY 2010 VL 7 IS 2 BP 227 EP 237 DI 10.1586/EPR.09.106 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 590FV UT WOS:000277211100014 PM 20377389 ER PT J AU Tate, JE Patel, MM Steele, AD Gentsch, JR Payne, DC Cortese, MM Nakagomi, O Cunliffe, NA Jiang, BM Neuzil, KM de Oliveira, LH Glass, RI Parashar, UD AF Tate, Jacqueline E. Patel, Manish M. Steele, A. Duncan Gentsch, Jon R. Payne, Daniel C. Cortese, Margaret M. Nakagomi, Osamu Cunliffe, Nigel A. Jiang, Baoming Neuzil, Kathleen M. de Oliveira, Lucia H. Glass, Roger I. Parashar, Umesh D. TI Global impact of rotavirus vaccines SO EXPERT REVIEW OF VACCINES LA English DT Review DE diarrhea; rotavirus; rotavirus vaccination; vaccine effectiveness ID ORAL POLIOVIRUS VACCINE; PLACEBO-CONTROLLED TRIAL; 1ST 2 YEARS; UNITED-STATES; YOUNG-CHILDREN; DOUBLE-BLIND; DEVELOPING-COUNTRIES; PROTECTIVE IMMUNITY; CHILDHOOD DIARRHEA; RHESUS-HUMAN AB The WHO has recently recommended the inclusion of rotavirus vaccine in the national immunization programs of all countries. In countries in the Americas, Europe and Australia that have adopted routine childhood immunization against rotavirus, significant reductions in the burden of severe childhood diarrhea have been observed. Besides protecting vaccinated children, disease rates also appear to be reduced in unvaccinated children, suggesting indirect benefits from vaccination (i.e., herd protection). Early clinical trial data from Africa and Asia are promising, and further efforts are needed to optimize the benefits of vaccination in developing countries where vaccines are likely to have their greatest impact. C1 [Tate, Jacqueline E.; Patel, Manish M.; Gentsch, Jon R.; Payne, Daniel C.; Cortese, Margaret M.; Jiang, Baoming; Parashar, Umesh D.] US CDC, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Steele, A. Duncan; Neuzil, Kathleen M.] PATH, Rotavirus Vaccine Program, Seattle, WA USA. [Nakagomi, Osamu] Nagasaki Univ, Dept Mol Microbiol & Immunol, Grad Sch Biomed Sci, Nagasaki 852, Japan. [Cunliffe, Nigel A.] Univ Liverpool, Dept Med Microbiol & Genitourinary, Liverpool L69 3BX, Merseyside, England. [de Oliveira, Lucia H.] Pan Amer Hlth Org, Immunizat Unit, Family & Community Hlth, Washington, DC 20037 USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Tate, JE (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd NE,MS A47, Atlanta, GA 30333 USA. EM jqt8@cdc.gov RI Inada, Mami/G-4783-2011; OI Cunliffe, Nigel/0000-0002-5449-4988 FU GSK Biologicals; SPMSD; GlaxoSmithKline; Banyu Pharmatheuticals FX Nigel A Cunliffe has received research grant support and lecture fees from GSK Biologicals and SPMSD. Osamu Nakagomi has received research grants from GlaxoSmithKline and Banyu Pharmatheuticals. Jacqueline E Tate, Manish M Patel, A Duncan Steele, Jon R Gentsch, Daniel C Payne, Margaret M Cortese, Baoming Jiang, Roger I Glass and Umesh D Parashar do not have any relevant disclosures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 128 TC 55 Z9 58 U1 0 U2 11 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2010 VL 9 IS 4 BP 395 EP 407 DI 10.1586/ERV.10.17 PG 13 WC Immunology SC Immunology GA 590GV UT WOS:000277214200013 PM 20370550 ER PT J AU Djalilian, AR Kim, JY Saeed, HN Holland, EJ Chan, CC AF Djalilian, A. R. Kim, J. Y. Saeed, H. N. Holland, E. J. Chan, C-C TI Histopathology and treatment of corneal disease in keratitis, ichthyosis, and deafness (KID) syndrome SO EYE LA English DT Letter C1 [Djalilian, A. R.] Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Kim, J. Y.] Emory Univ, Emory Eye Ctr, Atlanta, GA 30322 USA. [Saeed, H. N.] Loyola Univ Hlth Syst, Stritch Sch Med, Maywood, IL USA. [Holland, E. J.] Univ Cincinnati, Cincinnati Eye Inst, Cincinnati, OH USA. [Chan, C-C] NEI, NIH, Bethesda, MD 20892 USA. RP Djalilian, AR (reprint author), Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. EM adjalili@uic.edu FU Intramural NIH HHS [ZIA EY000222-24] NR 5 TC 3 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD APR PY 2010 VL 24 IS 4 BP 738 EP 740 DI 10.1038/eye.2009.178 PG 5 WC Ophthalmology SC Ophthalmology GA 583SY UT WOS:000276701300040 PM 19590522 ER PT J AU Abdala, APL Liu, BHH Rybak, IA Smith, JC Paton, JFR AF Abdala, Ana Paula Lima Liu, Beihui H. Rybak, Ilya A. Smith, Jeffrey C. Paton, Julian F. R. TI New lentiviral vector to selectively target glycinergic neurons in the brainstem SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Abdala, Ana Paula Lima; Liu, Beihui H.; Paton, Julian F. R.] Univ Bristol, Bristol Heart Inst, Bristol, Avon, England. [Rybak, Ilya A.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501610 ER PT J AU Abdala, APL Liu, BH Rybak, IA Smith, JC Paton, JFR AF Abdala, Ana Paula Lima Liu, Beihui H. Rybak, Ilya A. Smith, Jeffrey C. Paton, Julian F. R. TI Role of GlyT(2) expressing neurons in the Botzinger Complex for respiratory rhythm and pattern generation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Abdala, Ana Paula Lima; Liu, Beihui H.; Paton, Julian F. R.] Univ Bristol, Bristol Heart Inst, Bristol, Avon, England. [Rybak, Ilya A.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500428 ER PT J AU Advani, T Hensler, JG Cheng, K Rice, KC Koek, W AF Advani, Tushar Hensler, Julie G. Cheng, Kejun Rice, Kenner C. Koek, Wouter TI Stimulation of [S-35]GTP gamma S binding by GABA(B) receptor agonists and positive modulators in different mouse brain regions SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Advani, Tushar; Hensler, Julie G.; Koek, Wouter] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500878 ER PT J AU Alkhalil, A Strand, S Mucker, E Huggins, JW Jahrling, PB Ibrahim, SM AF Alkhalil, Abdulnaser Strand, Sarah Mucker, Eric Huggins, John W. Jahrling, Peter B. Ibrahim, Sofi M. TI Inhibition of Monkeypox virus replication by RNAi SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Alkhalil, Abdulnaser; Strand, Sarah; Mucker, Eric; Huggins, John W.; Ibrahim, Sofi M.] USAMRIID, Frederick, MD USA. [Jahrling, Peter B.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503133 ER PT J AU Andrews, K Roseland, J Middleton, A Feinberg, M Zhao, CW Holden, J Dwyer, J Picciano, MF Saldanha, L Sempos, C Bailey, R Douglass, L AF Andrews, Karen Roseland, Janet Middleton, Angela Feinberg, Matthew Zhao, Cuiwei Holden, Joanne Dwyer, Johanna Picciano, Mary Frances Saldanha, Leila Sempos, Christopher Bailey, Regan Douglass, Larry TI The Dietary Supplement Ingredient Database: Comparison of adult and children's multivitamin/mineral (MVM) products SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Andrews, Karen; Roseland, Janet; Middleton, Angela; Feinberg, Matthew; Zhao, Cuiwei; Holden, Joanne] ARS, USDA, BHNRC NDL, Beltsville, MD USA. [Dwyer, Johanna; Picciano, Mary Frances; Saldanha, Leila; Sempos, Christopher; Bailey, Regan] NIH ODS, DHHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502759 ER PT J AU Apopa, PL Vesci, J Boutaud, O Jadhav, A Simeonov, A Rai, G Maloney, DJ Holman, T Kenyon, V Holinstat, M AF Apopa, Patrick Leo Vesci, Joanne Boutaud, Olivier Jadhav, Ajit Simeonov, Anton Rai, Ganesha Maloney, David J. Holman, Ted Kenyon, Victor Holinstat, Michael TI 12-Lipoxygenase plays a significant role in regulation of human platelets activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Apopa, Patrick Leo; Vesci, Joanne; Holinstat, Michael] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Boutaud, Olivier] Vanderbilt Univ, Nashville, TN USA. [Jadhav, Ajit; Simeonov, Anton; Rai, Ganesha; Maloney, David J.] NHGRI, Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Holman, Ted; Kenyon, Victor] UCSC, Santa Cruz, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504370 ER PT J AU Bagattin, A Hugendubler, L Mueller, E AF Bagattin, Alessia Hugendubler, Lynne Mueller, Elisabetta TI Characterization of a novel transcriptional feedback loop regulating lipid metabolism SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bagattin, Alessia; Hugendubler, Lynne; Mueller, Elisabetta] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507068 ER PT J AU Bailey, R Carriquiry, A Gahche, J Dodd, K Joseph, M Dwyer, J Yetley, E Sempos, C Picciano, MF AF Bailey, Regan Carriquiry, Alicia Gahche, Jaime Dodd, Kevin Joseph, Maria Dwyer, Johanna Yetley, Elizabeth Sempos, Chris Picciano, Mary Frances TI Adjusting Serum Biomarkers of Folate Status for Within-person Variation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bailey, Regan; Dwyer, Johanna; Yetley, Elizabeth; Sempos, Chris; Picciano, Mary Frances] NIH, Bethesda, MD 20892 USA. [Carriquiry, Alicia; Joseph, Maria] Iowa State Univ, Ames, IA USA. [Gahche, Jaime] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Dodd, Kevin] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505093 ER PT J AU Bailey, R Gahche, J Mills, J Dodd, K Dwyer, J Yetley, E Sempos, C Carriquiry, A Joseph, M Picciano, MF AF Bailey, Regan Gahche, Jaime Mills, James Dodd, Kevin Dwyer, Johanna Yetley, Elizabeth Sempos, Chris Carriquiry, Alicia Joseph, Maria Picciano, Mary Frances TI Unmetabolized Serum Folic Acid in Older Adults in the United States SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bailey, Regan; Dwyer, Johanna; Yetley, Elizabeth; Sempos, Chris; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Gahche, Jaime] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Mills, James] NICHHD, NIH, Bethesda, MD 20892 USA. [Dodd, Kevin] NCI, NIH, Bethesda, MD 20892 USA. [Carriquiry, Alicia; Joseph, Maria] Iowa State Univ, Ames, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504898 ER PT J AU Balasubramanian, R De Castro, S Maruoka, H Jacobson, KA AF Balasubramanian, Ramachandran De Castro, Sonia Maruoka, Hirsohi Jacobson, Kenneth A. TI Attenuation of beta-cell death by P2Y(6) receptor agonist: A novel drug target for diabetes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Balasubramanian, Ramachandran; De Castro, Sonia; Maruoka, Hirsohi; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501886 ER PT J AU Bazzano, LAL Gu, DF Chen, CS Huang, JF Chen, J Rao, D Jaquish, C James, H Duan, XF Chen, JC Kelly, T Rice, T Hamm, LL Whelton, P He, J AF Bazzano, Lydia Angela Louise Gu, Dongfeng Chen, Chung-Shiuan Huang, Jian-feng Chen, Jing Rao, Dabeeru Jaquish, Cashell James, Hixson Duan, Xiufang Chen, Ji-chun Kelly, Tanika Rice, Treva Hamm, L. Lee Whelton, Paul He, Jiang TI Effect of Dietary Sodium and Potassium Intervention on Blood Glucose SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bazzano, Lydia Angela Louise; Chen, Chung-Shiuan; Chen, Jing; Kelly, Tanika; He, Jiang] Tulane Univ, Sch Publ Hlth, New Orleans, LA 70118 USA. [Gu, Dongfeng; Huang, Jian-feng; Duan, Xiufang; Chen, Ji-chun] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China. [Gu, Dongfeng; Huang, Jian-feng; Duan, Xiufang; Chen, Ji-chun] Chinese Acad Med Sci, Fu Wai Hosp, Beijing 100730, Peoples R China. [Rao, Dabeeru; Rice, Treva] Washington Univ, Sch Med, St Louis, MO USA. [Jaquish, Cashell] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [James, Hixson] Univ Texas Sch Publ Hlth, Human Genet Ctr, Houston, TX USA. [Hamm, L. Lee] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Whelton, Paul] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502784 ER PT J AU Beydoun, MA Fanelli-Kuczmarski, MT Beydoun, HA Shroff, MR Mason, M Evans, MK Zonderman, AB AF Beydoun, May A. Fanelli-Kuczmarski, Marie T. Beydoun, Hind A. Shroff, Monal R. Mason, Marc Evans, Michele K. Zonderman, Alan B. TI Plasma folate's association with depressive symptoms among US adults: the role of dietary intake and diet quality SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Beydoun, May A.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, IRP, Baltimore, MD 21224 USA. [Fanelli-Kuczmarski, Marie T.] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Shroff, Monal R.] Michigan State Univ, E Lansing, MI 48824 USA. [Mason, Marc] MedStar Res Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506403 ER PT J AU Bhattacharyya, N Wiench, M Andreopoulou, P Connolly, B Bugge, T Gafni, RI Collins, MT AF Bhattacharyya, Nisan Wiench, Malgorzata Andreopoulou, Panagiota Connolly, Brian Bugge, Thomas Gafni, Rachel I. Collins, Michael T. TI cAMP-mediated processing of FGF23: involvement of O-glycosylation and furin SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bhattacharyya, Nisan; Andreopoulou, Panagiota; Gafni, Rachel I.; Collins, Michael T.] NIDCR, CSDB, NIH, Bethesda, MD USA. [Connolly, Brian; Bugge, Thomas] NIDCR, NIH, Bethesda, MD USA. [Wiench, Malgorzata] NCI, LRBGE, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506791 ER PT J AU Blatch, S AF Blatch, Sydella TI Mentoring Students from Undergrad Through Tenure SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Blatch, Sydella] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504156 ER PT J AU Blaty, DE Arias, HR Rosenberg, A Targowska-Duda, KM Feuerbach, D Jozwiak, K Moaddel, R Wainer, IW AF Blaty, Doug E. Arias, Hugo R. Rosenberg, Avraham Targowska-Duda, Katarzyna M. Feuerbach, Dominik Jozwiak, Krzysztof Moaddel, Ruin Wainer, Irving W. TI Interaction of tricyclic antidepressants with the human (h)alpha 4 beta 2 nicotinic receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Blaty, Doug E.] Midwestern Univ, Arizona Coll Osteopath Med, Glendale, AZ USA. [Arias, Hugo R.] Midwestern Univ, Glendale, AZ USA. [Rosenberg, Avraham; Moaddel, Ruin; Wainer, Irving W.] NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Targowska-Duda, Katarzyna M.; Jozwiak, Krzysztof] Med Univ Lublin, Dept Chem, Lublin, Poland. [Feuerbach, Dominik] Novartis Inst Biomed Res, Basel, Switzerland. RI Targowska-Duda, Katarzyna/I-3434-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502109 ER PT J AU Bobe, G Murphy, G Albert, PS Sansbury, LB Schatzkin, A Lanza, E Colburn, NH Cross, AJ AF Bobe, Gerd Murphy, Gwen Albert, Paul S. Sansbury, Leah B. Schatzkin, Arthur Lanza, Elaine Colburn, Nancy H. Cross, Amanda J. TI Association between Serum Cytokine Concentrations, Flavonol Intake and Colorectal Adenoma Recurrence in the Polyp Prevention Trial (PPT) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bobe, Gerd] Oregon State Univ, Dept Anim Sci, Linus Pauling Inst, Corvallis, OR 97331 USA. [Bobe, Gerd; Lanza, Elaine; Colburn, Nancy H.] NCI, Lab Canc Prevent, CCR, Frederick, MD 21701 USA. [Murphy, Gwen] NCI, Infect & Immunoepidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Sansbury, Leah B.] NCI, DCCPS, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. [Schatzkin, Arthur; Cross, Amanda J.] NCI, DCEG, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. [Albert, Paul S.] NICHHD, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501280 ER PT J AU Bonzo, JA Patterson, AD Krausz, KW Gonzalez, FJ AF Bonzo, Jessica A. Patterson, Andrew D. Krausz, Kristopher W. Gonzalez, Frank J. TI Metabolomic analysis of the Hepatocyte Nuclear Factor 1 Alpha knockout mouse SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bonzo, Jessica A.; Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Bethesda, MD 20892 USA. [Bonzo, Jessica A.] NIGMS, NIH, Bethesda, MD USA. RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505162 ER PT J AU Brosh, RM Sommers, J Suhasini, A Leonard, T Deakyne, J Mazin, A Shin-Ya, K Kitao, H Wu, YL AF Brosh, Robert Michael Sommers, Joshua Suhasini, Avvaru Leonard, Thomas Deakyne, Julianna Mazin, Alexander Shin-ya, Kazuo Kitao, Hiroyuki Wu, Yuliang TI Fanconi Anemia Group J Mutation Abolishes its DNA Repair Function by Uncoupling DNA Translocation from Helicase Activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Brosh, Robert Michael; Sommers, Joshua; Suhasini, Avvaru; Wu, Yuliang] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. [Leonard, Thomas] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Deakyne, Julianna; Mazin, Alexander] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19104 USA. [Shin-ya, Kazuo] Natl Inst Adv Ind Sci & Technol, Tokyo, Japan. [Kitao, Hiroyuki] Kyoto Univ, Ctr Radiat Biol, Dept Late Effect Studies, Lab DNA Damage Signaling, Kyoto 606, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507528 ER PT J AU Cao, XF Tuo, JS Shen, DF Liu, M Chan, CC AF Cao, Xiaoguang Tuo, Jingsheng Shen, Defen Liu, Melissa Chan, Chi-Chao TI The Effect of Quercetin in Cultured Human RPE Cells under Oxidative Stress and in Ccl2/Cx3cr1 Double Deficient Mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Cao, Xiaoguang; Tuo, Jingsheng; Shen, Defen; Liu, Melissa; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cao, Xiaoguang] Peking Univ, Peoples Hosp, Beijing 100871, Peoples R China. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500417 ER PT J AU Carmona-Rivera, C Bonifacino, JS Gahl, WA Cadilla, CL AF Carmona-Rivera, Carmelo Bonifacino, Juan S. Gahl, William A. Cadilla, Carmen L. TI Divalent interaction between HPS1 and HPS4 to form the Biogenesis of related Organelles 3 (BLOC-3) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Carmona-Rivera, Carmelo; Gahl, William A.] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. [Bonifacino, Juan S.] NICHHD, NIH, Bethesda, MD 20892 USA. [Cadilla, Carmen L.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501053 ER PT J AU Caulfield, LE Zavaleta, N Chen, P Putnick, D Bornstein, MH DiPietro, J AF Caulfield, Laura Elizabeth Zavaleta, Nelly Chen, Ping Putnick, Diane Bornstein, Marc H. DiPietro, Janet TI 1. Maternal zinc supplementation during pregnancy: effects on offspring autonomic function at 4 1/2 years of age SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Caulfield, Laura Elizabeth; Chen, Ping] Johns Hopkins BSPH, IH Nutr, Baltimore, MD USA. [DiPietro, Janet] Johns Hopkins BSPH, Pop Fam Repro, Baltimore, MD USA. [Zavaleta, Nelly] IIN, Lima, Peru. [Putnick, Diane; Bornstein, Marc H.] NICHD, CFR, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506557 ER PT J AU Chatterjee, R Rishi, V Rozenberg, J Bhattacharya, P Glass, K Zhao, JF Vinson, C AF Chatterjee, Raghunath Rishi, Vikas Rozenberg, Julian Bhattacharya, Paramita Glass, Kimberly Zhao, Jianfei Vinson, Charles TI A new function for methyl CpG: Creating a C/EBP alpha binding site & mediating tissue-specific gene expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chatterjee, Raghunath; Rishi, Vikas; Rozenberg, Julian; Bhattacharya, Paramita; Zhao, Jianfei; Vinson, Charles] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Glass, Kimberly] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507014 ER PT J AU Chou, CL Kassai, EM Knepper, MA AF Chou, C-L Kassai, E. M. Knepper, M. A. TI Vasopressin Triggers Phosphorylation of Na-K-2Cl Cotransporter (NKCC1) in Rat Inner Medullary Collecting Duct (IMCD) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chou, C-L; Kassai, E. M.; Knepper, M. A.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500399 ER PT J AU Chuang, AI Yang, MD Dalvi, P Gonzalez, FJ Harper, PA Ito, S AF Chuang, Andrew I. Yang, Mingdong Dalvi, Pooja Gonzalez, Frank J. Harper, Patricia A. Ito, Shinya TI Human CYP3A Expression under Hypertonic Stimuli In Vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Chuang, Andrew I.; Yang, Mingdong; Dalvi, Pooja; Harper, Patricia A.; Ito, Shinya] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505022 ER PT J AU Copeland, WC AF Copeland, William C. TI Defects in mitochondrial DNA replication and human disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Copeland, William C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500055 ER PT J AU Cui, YH Xiao, L Rao, JN Zou, TT Liu, L Gorospe, M Wang, JY AF Cui, Yuhong Xiao, Lan Rao, Jaladanki N. Zou, Tongtong Liu, Lan Gorospe, Myriam Wang, Jian-Ying TI Translational Regulation of CUG-BP1 by Polyamines through the RNA-binding Protein HuR SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Cui, Yuhong; Xiao, Lan; Rao, Jaladanki N.; Zou, Tongtong; Liu, Lan; Wang, Jian-Ying] Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. [Gorospe, Myriam] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500607 ER PT J AU Davis, GR Wang, PY Hwang, PM AF Davis, Greggory Ryan Wang, Pingyun Hwang, Paul M. TI Effect of mouse strain on mitochondrial biogenesis and exercise SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Davis, Greggory Ryan] Louisiana State Univ, Baton Rouge, LA 70803 USA. [Wang, Pingyun; Hwang, Paul M.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500077 ER PT J AU Dever, TE Saini, P Eyler, DE Green, R AF Dever, Thomas E. Saini, Preeti Eyler, Daniel E. Green, Rachel TI Hypusine-containing Protein eIF5A Promotes Translation Elongation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Dever, Thomas E.; Saini, Preeti] NICHD, NIH, Bethesda, MD USA. [Eyler, Daniel E.; Green, Rachel] Johns Hopkins Univ, Sch Med, HHMI, Dept Mol Biol & Genet, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500235 ER PT J AU Dmitrieva, NI Malide, D Burg, MB AF Dmitrieva, Natalia I. Malide, Daniela Burg, Maurice B. TI Mre11 expression in mitochondria of renal cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Dmitrieva, Natalia I.; Malide, Daniela; Burg, Maurice B.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500625 ER PT J AU Edwards, SK Burg, MB Dmitrieva, NI AF Edwards, Sarah K. Burg, Maurice B. Dmitrieva, Natalia I. TI Effects of high NaCl on cellular glutathione and glutathionylation of proteins in HeLa cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Edwards, Sarah K.; Burg, Maurice B.; Dmitrieva, Natalia I.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501249 ER PT J AU Erinosho, T Thompson, O Moser, R Nebeling, L Thompson, F Yaroch, A AF Erinosho, Temitope Thompson, Olivia Moser, Richard Nebeling, Linda Thompson, Frances Yaroch, Amy TI Attitudes and knowledge of fruit and vegetable recommendations among adults using the National Cancer Institute (NCI) Food Attitudes and Behaviors (FAB) survey SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Erinosho, Temitope; Moser, Richard; Nebeling, Linda; Thompson, Frances] NCI, Rockville, MD USA. [Thompson, Olivia; Yaroch, Amy] Ctr Human Nutr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501619 ER PT J AU Feric, M Hoffert, JD Pisitkun, T Knepper, MA AF Feric, Marina Hoffert, J. D. Pisitkun, T. Knepper, M. A. TI Large-scale identification of phosphorylation sites in renal cortical transporters SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Feric, Marina; Hoffert, J. D.; Pisitkun, T.; Knepper, M. A.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500383 ER PT J AU Fischer, RS Gardel, M Ma, XF Adelstein, RS Waterman, CM AF Fischer, Robert S. Gardel, Margaret Ma, Xufei Adelstein, Robert S. Waterman, Clare M. TI Actomyosin contraction and adhesion control angiogenic sprouting and guidance SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Fischer, Robert S.; Ma, Xufei; Adelstein, Robert S.; Waterman, Clare M.] NHLBI, Bethesda, MD 20892 USA. [Gardel, Margaret] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500302 ER PT J AU Fleshman, MK Cope, KA Novotny, JA Riedl, K Schwartz, SJ Jones, PJ Baer, DJ Harrison, EH AF Fleshman, Matthew Kintz Cope, Keary A. Novotny, Janet A. Riedl, Ken Schwartz, Steven J. Jones, Peter J. Baer, David J. Harrison, Earl H. TI Efficiency of intestinal absorption of beta-carotene (BC) is not correlated with cholesterol (CHL) absorption in humans SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Fleshman, Matthew Kintz; Riedl, Ken; Schwartz, Steven J.; Harrison, Earl H.] Ohio State Univ, Columbus, OH 43210 USA. [Cope, Keary A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Novotny, Janet A.; Baer, David J.] ARS, BHNRC, USDA, Beltsville, MD USA. [Jones, Peter J.] Univ Manitoba, Winnipeg, MB, Canada. RI Riedl, Ken/G-8621-2014 OI Riedl, Ken/0000-0002-9020-3471 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502875 ER PT J AU Flood, A Renehan, A Adams, K Leitzmann, M Hollenbeck, AR Schatzkin, A AF Flood, Andrew Renehan, Andrew Adams, Kenneth Leitzmann, Michael Hollenbeck, Albert R. Schatzkin, Arthur TI Trajectories of weight change from late adolescence to late middle age for lean and obese individuals SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Flood, Andrew] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Renehan, Andrew] Univ Manchester, Manchester, Lancs, England. [Adams, Kenneth] Hlth Partners Res Fdn, Minneapolis, MN USA. [Leitzmann, Michael] Univ Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Renehan, Andrew/K-5992-2015 OI Renehan, Andrew/0000-0003-4309-4396 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502850 ER PT J AU Fowler, JS Wang, GJ Volkow, ND AF Fowler, Joanna S. Wang, Gene-Jack Volkow, Nora D. TI Imaging Brain Chemistry in Diseases of Addiction SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Fowler, Joanna S.; Wang, Gene-Jack] Brookhaven Natl Lab, Upton, NY 11973 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500198 ER PT J AU Free, RB Namkung, Y Hazelwood, LA Sibley, DR AF Free, R. Benjamin Namkung, Yoon Hazelwood, Lisa A. Sibley, David R. TI Sorting nexin-25 interacts with D-1 and D-2 dopamine receptors to regulate receptor expression and signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Free, R. Benjamin; Namkung, Yoon; Hazelwood, Lisa A.; Sibley, David R.] NINDS, MNS, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501686 ER PT J AU Fufa, TD Wakano, C Byun, JS Haggerty, CM Elenitoba-Johnson, K Thirman, MJ Raffeld, M Hewitt, S Gardner, K AF Fufa, Temesgen D. Wakano, Clay Byun, Jung S. Haggerty, Cynthia M. Elenitoba-Johnson, Kojo Thirman, Michael J. Raffeld, Mark Hewitt, Stephen Gardner, Kevin TI The Eleven-nineteen Lysine-rich Leukemia Gene (ELL) Couples Transcription Elongation with Epigenetic Signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Fufa, Temesgen D.] Howard Univ, Coll Med, Washington, DC USA. [Fufa, Temesgen D.; Wakano, Clay; Byun, Jung S.; Haggerty, Cynthia M.; Raffeld, Mark; Hewitt, Stephen; Gardner, Kevin] NCI, Bethesda, MD 20892 USA. [Elenitoba-Johnson, Kojo] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Thirman, Michael J.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503514 ER PT J AU Gahche, JJ Bailey, R Mirel, L Dwyer, J Russell, R Sempos, C Picciano, MF AF Gahche, Jaime Jacqueline Bailey, Regan Mirel, Lisa Dwyer, Johanna Russell, Robert Sempos, Christopher Picciano, Mary Frances TI Iodine intake from dietary supplements among pregnant females in the US: National Health and Nutrition Examination Survey 1999-2006 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gahche, Jaime Jacqueline; Mirel, Lisa] Natl Ctr Hlth Stat, CDC, Hyattsville, MD 20782 USA. [Bailey, Regan; Dwyer, Johanna; Russell, Robert; Sempos, Christopher; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504726 ER PT J AU Gallazzini, M Heussler, GE Williams, CK Burg, MB Ferraris, JD AF Gallazzini, Morgan Heussler, Gary E. Williams, Chester K. Burg, Maurice B. Ferraris, Joan D. TI Phosphorylation of TonEBP/OREBP by cyclin dependent kinase 5 (CDK5) mediates its NaCl-induced nuclear translocation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gallazzini, Morgan; Heussler, Gary E.; Williams, Chester K.; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502014 ER PT J AU Gao, ZG Ding, Y Jacobson, KA AF Gao, Zhan-Guo Ding, Yi Jacobson, Kenneth A. TI UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gao, Zhan-Guo] NIDDK, LBC, NIH, Bethesda, MD USA. [Ding, Yi] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Jacobson, Kenneth A.] NIDDK, LBC, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500529 ER PT J AU Gebauer, SK Courville, AB Rozgony, NR Baer, DJ AF Gebauer, Sarah K. Courville, Amber B. Rozgony, Nancy R. Baer, David J. TI Effect of a controlled-diet supplemented with whey protein, soy protein, or carbohydrate on inflammation-related CVD risk factors SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gebauer, Sarah K.; Rozgony, Nancy R.; Baer, David J.] ARS, USDA, Beltsville, MD USA. [Courville, Amber B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505054 ER PT J AU Gee, KW Johnstone, T Hogenkamp, DJ Yoshimura, R Whittemore, ER Gu, ZL Yakel, J AF Gee, Kelvin W. Johnstone, Timothy Hogenkamp, Derk J. Yoshimura, Ryan Whittemore, Edward R. Gu, Zhenglin Yakel, Jerrel TI Dual Allosteric Modulators of Neuronal Nicotinic-Acetylcholine and GABA-A Receptors SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gee, Kelvin W.; Johnstone, Timothy; Hogenkamp, Derk J.; Yoshimura, Ryan; Whittemore, Edward R.] Univ Calif Irvine, Irvine, CA USA. [Gu, Zhenglin; Yakel, Jerrel] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501256 ER PT J AU Gibbs, JD Bian, T Menendez, D Resnick, MA Imani, F AF Gibbs, John D. Bian, Tao Menendez, Daniel Resnick, Michael A. Imani, Farhad TI Respiratory syncytial virus hijacks the tumor-suppressor p53 to enhance its replication in lung epithelial cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gibbs, John D.; Bian, Tao; Imani, Farhad] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Menendez, Daniel; Resnick, Michael A.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RI Bian, Tao/I-7604-2013 NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501883 ER PT J AU Goldstein, DS Sewell, L Holmes, CS AF Goldstein, David S. Sewell, LaToya Holmes, Courtney S. TI Cardiorenal Sympathetic Denervation and Baroreflex Failure in Parkinson Disease with Orthostatic Hypotension SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Goldstein, David S.; Sewell, LaToya; Holmes, Courtney S.] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504128 ER PT J AU Grabow, W Severcan, I Chworos, A Shapiro, B Luc, J AF Grabow, Wade Severcan, Isil Chworos, Arkadiusz Shapiro, Bruce Luc, Jaeger TI The design and characterization of an RNA nanoring for use in RNA interference drug delivery SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Grabow, Wade; Severcan, Isil; Chworos, Arkadiusz; Luc, Jaeger] USCB, Santa Barbara, CA USA. [Shapiro, Bruce] NCI, Ctr Canc Res, Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506540 ER PT J AU Gunaratne, R Pisitkun, T Braucht, DWW Xie, L Rinschen, MM Hoffert, JD Chou, CL Knepper, MA AF Gunaratne, Ruwan Pisitkun, T. Braucht, D. W. W. Xie, L. Rinschen, M. M. Hoffert, J. D. Chou, C-L Knepper, M. A. TI Phospho-specific antibodies to Ser126 and Ser874 of the apical Na-K-2Cl cotransporter (NKCC2) demonstrate vasopressin-regulated phosphorylation in the renal thick ascending limb (TAL) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Gunaratne, Ruwan; Pisitkun, T.; Braucht, D. W. W.; Xie, L.; Rinschen, M. M.; Hoffert, J. D.; Chou, C-L; Knepper, M. A.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500482 ER PT J AU Hazelwood, LA Romanelli, RJ Free, RB Roof, RA Javitch, JA Neve, KA Sibley, DR AF Hazelwood, Lisa A. Romanelli, Robert J. Free, R. Benjamin Roof, Rebecca A. Javitch, Jonathan A. Neve, Kim A. Sibley, David R. TI Lipid rafts and membrane cholesterol are involved in regulating D2 dopamine receptor signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hazelwood, Lisa A.; Free, R. Benjamin; Roof, Rebecca A.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Rockville, MD USA. [Romanelli, Robert J.; Neve, Kim A.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Javitch, Jonathan A.] Columbia Univ, Dept Psychiat, New York, NY USA. [Javitch, Jonathan A.] Columbia Univ, Dept Pharmacol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501706 ER PT J AU Hiranita, T Kopajtic, T Cao, JJ Newman, AH AF Hiranita, Takato Kopajtic, Theresa Cao, Jianjing Newman, Amy H. TI Evaluation of N-Substituted Benztropine (BZT) Analogs for Cocaine Antagonist Effects in Rats Trained to Self-Administer Cocaine SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hiranita, Takato; Kopajtic, Theresa; Cao, Jianjing; Newman, Amy H.] NIDA, Medicat Discovery Res Branch, IRP, NIH,DHHS, Baltimore, MD USA. [Hiranita, Takato] NIH, JSPS Res Fellowship Japanese Biomed & Behav Res, Baltimore, MD USA. RI Hiranita, Takato/G-6567-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503790 ER PT J AU Hoadley, KA Xu, DY Xue, YT Wang, WD Keck, JL AF Hoadley, Kelly A. Xu, Dongyi Xue, Yutong Wang, Weidong Keck, James L. TI The structure of the RMI core complex resembles the RPA interface SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hoadley, Kelly A.; Keck, James L.] Univ Wisconsin, Dept Biomol Chem, Madison, WI USA. [Xu, Dongyi; Xue, Yutong; Wang, Weidong] NIA, Genet Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507100 ER PT J AU Holmes, CS Goldstein, DS AF Holmes, Courtney S. Goldstein, David S. TI Contamination of the Norepinephrine Pro-Drug Droxidopa by Dihydroxyphenylacetaldehyde SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Holmes, Courtney S.; Goldstein, David S.] NINDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503839 ER PT J AU Houston, DK Tooze, J Neiberg, R Shea, K Hausman, D Johnson, MA Cauley, J Bauer, D Tylavsky, F Visser, M Simonsick, E Harris, T Kritchevsky, SB AF Houston, Denise K. Tooze, Janet Neiberg, Rebecca Shea, Kyla Hausman, Dorothy Johnson, Mary Ann Cauley, Jane Bauer, Doug Tylavsky, Frances Visser, Marjolein Simonsick, Eleanor Harris, Tamara Kritchevsky, Stephen B. TI Vitamin D status and lower extremity function: the Health ABC Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Houston, Denise K.; Tooze, Janet; Neiberg, Rebecca; Shea, Kyla; Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Hausman, Dorothy; Johnson, Mary Ann] Univ Georgia, Athens, GA 30602 USA. [Cauley, Jane] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, Doug] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tylavsky, Frances] Univ Tennessee, Memphis, TN USA. [Visser, Marjolein] Vrije Univ Amsterdam, Amsterdam, Netherlands. [Simonsick, Eleanor; Harris, Tamara] NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504261 ER PT J AU Hromi-Fiedler, A Bermudez-Millan, A Chapman, D Segura-Perez, S Damio, G Melgar-Quinonez, H Perez-Escamilla, R AF Hromi-Fiedler, Amber Bermudez-Millan, Angela Chapman, Donna Segura-Perez, Sofia Damio, Grace Melgar-Quinonez, Hugo Perez-Escamilla, Rafael TI Food insecurity is a risk factor for elevated levels of depression symptoms among low-income pregnant Latinas SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hromi-Fiedler, Amber; Chapman, Donna] Univ Connecticut, Storrs, CT USA. [Hromi-Fiedler, Amber; Bermudez-Millan, Angela; Chapman, Donna; Segura-Perez, Sofia; Damio, Grace; Perez-Escamilla, Rafael] Connecticut NIH EXPORT Ctr Eliminating Hlth Dispa, Storrs, CT USA. [Bermudez-Millan, Angela; Segura-Perez, Sofia; Damio, Grace] Hispan Hlth Council, Hartford, CT USA. [Melgar-Quinonez, Hugo] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. [Perez-Escamilla, Rafael] Yale Univ, Sch Publ Hlth, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502321 ER PT J AU Hromi-Fiedler, A Bermudez-Millan, A Chapman, D Segura-Perez, S Damio, G Perez-Escamilla, R AF Hromi-Fiedler, Amber Bermudez-Millan, Angela Chapman, Donna Segura-Perez, Sofia Damio, Grace Perez-Escamilla, Rafael TI Gestational weight gain knowledge among low-income pregnant Latinas SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hromi-Fiedler, Amber; Chapman, Donna] Univ Connecticut, Storrs, CT USA. [Hromi-Fiedler, Amber; Bermudez-Millan, Angela; Chapman, Donna; Segura-Perez, Sofia; Damio, Grace; Perez-Escamilla, Rafael] Connecticut NIH EXPORT Ctr Eliminating Hlth Dispa, Storrs, CT USA. [Bermudez-Millan, Angela; Segura-Perez, Sofia; Damio, Grace] Hispan Hlth Council, Hartford, CT USA. [Perez-Escamilla, Rafael] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502383 ER PT J AU Hruby, A Jacques, PF Rumawas, ME Fox, CS Meigs, JB Troy, LM AF Hruby, Adela Jacques, Paul F. Rumawas, Marcella E. Fox, Caroline S. Meigs, James B. Troy, Lisa M. TI Mediterranean-Style Dietary Pattern and Incident Diabetes in the Framingham Heart Study Offspring SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hruby, Adela; Jacques, Paul F.; Rumawas, Marcella E.; Troy, Lisa M.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Hruby, Adela; Jacques, Paul F.; Troy, Lisa M.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA. [Fox, Caroline S.; Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502308 ER PT J AU Hu, JX Wang, Y Zhang, XH Lloyd, JR Li, JH Karpiak, J Costanzi, S Wess, J AF Hu, Jianxin Wang, Yan Zhang, Xiaohong Lloyd, John R. Li, Jianhua Karpiak, Joel Costanzi, Stefano Wess, Jurgen TI Crosslinking Analysis of the M3 Muscarinic Acetylcholine Receptor/G alpha q Interface in Both the Inactive and Active States SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hu, Jianxin; Wang, Yan; Zhang, Xiaohong; Lloyd, John R.; Li, Jianhua; Karpiak, Joel; Costanzi, Stefano; Wess, Jurgen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506857 ER PT J AU Huang, KP Huang, FL AF Huang, Kuo-Ping Huang, Freesia L. TI Long-term potentiation (LTP) induces co-localization of calmodulin and neurogranin in the dendritic spines of mouse hippocampal CA1 pyramidal neurons SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Huang, Kuo-Ping; Huang, Freesia L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506419 ER PT J AU Huertas, A Das, SR Emin, M Inamdar, NM Rifkind, JM Bhattacharya, S Bhattacharya, J AF Huertas, Alice Das, Shonit R. Emin, Memet Inamdar, Nilufar M. Rifkind, Joseph M. Bhattacharya, Sunita Bhattacharya, Jahar TI Hypoxia activates NF kappa B and HIF1 alpha in an erythrocyte-dependent manner in lung endothelium SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Huertas, Alice; Das, Shonit R.; Emin, Memet; Inamdar, Nilufar M.; Bhattacharya, Sunita; Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Med, Lung Biol Lab, New York, NY 10032 USA. [Huertas, Alice; Das, Shonit R.; Emin, Memet; Inamdar, Nilufar M.; Bhattacharya, Sunita; Bhattacharya, Jahar] Columbia Univ Coll Phys & Surg, Dept Pediat, Lung Biol Lab, New York, NY 10032 USA. [Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505379 ER PT J AU Hwang, S Chou, CL Yu, MJ Rinschen, M Gunaratne, R Pisitkun, T Hoffert, JD Knepper, MA AF Hwang, Shelly Chou, C-L Yu, M-J Rinschen, M. Gunaratne, R. Pisitkun, T. Hoffert, J. D. Knepper, M. A. TI Vasopressin-Regulated Phosphorylation of Urea Transporter Proteins, UT-A1 and UT-A3, in Rat Inner Medullary Collecting Duct (IMCD) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Hwang, Shelly; Chou, C-L; Yu, M-J; Rinschen, M.; Gunaratne, R.; Pisitkun, T.; Hoffert, J. D.; Knepper, M. A.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500341 ER PT J AU Iwamoto, T Nakamura, T Yamada, A Yamada, Y Fukumoto, S AF Iwamoto, Tsutomu Nakamura, Takashi Yamada, Aya Yamada, Yoshihiko Fukumoto, Satoshi TI Pannexin 3, a gap junction protein, Regulates Odontoblasts Differentiation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Iwamoto, Tsutomu; Nakamura, Takashi; Yamada, Aya; Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Div Pediat Dent, Sendai, Miyagi 980, Japan. [Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503776 ER PT J AU Izumi, Y Gallazzini, M Ferraris, JD Burg, MB AF Izumi, Yuiricho Gallazzini, Morgan Ferraris, Joan D. Burg, Maurice B. TI Lowering NaCl accelerates degradation of TonEBP/OREBP mRNA SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Izumi, Yuiricho; Gallazzini, Morgan; Ferraris, Joan D.; Burg, Maurice B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502771 ER PT J AU Jardin, I Woodard, GE Lopez, JJ Salido, GM Rosado, JA AF Jardin, Isaac Woodard, Geoffrey E. Lopez, Jose J. Salido, Gines M. Rosado, Juan A. TI Agonist-induced Ca2+ mobilization is regulated by a complex involving Orai1, hTRPC3 and the type I inositol 1,4,5-trisphosphate receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Jardin, Isaac; Lopez, Jose J.; Salido, Gines M.; Rosado, Juan A.] Univ Extremadura, Dept Physiol, Caceres, Spain. [Woodard, Geoffrey E.] NIDDKD, NIH, Bethesda, MD 20892 USA. RI Salido, Gines/A-4292-2009; rosado, juan/H-3488-2015; Jardin, Isaac/E-8310-2016 OI Salido, Gines/0000-0002-8687-2445; rosado, juan/0000-0002-9749-2325; Jardin, Isaac/0000-0003-4575-8264 NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504529 ER PT J AU Jie, C Shah, YM Ma, XC Pang, XY Krausz, KW Gonzalez, FJ AF Jie Cheng Shah, Yatrik M. Ma, Xiaochao Pang, Xiaoyan Krausz, Kristopher W. Gonzalez, Frank J. TI Rifaximin Protection of DSS-Induced Inflammatory Bowel Disease by Inhibition of Nuclear Factor Kappa B through Activation of Human Pregnane X Receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Jie Cheng; Pang, Xiaoyan; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shah, Yatrik M.] Univ Michigan, Sch Med, Dept Internal Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA. [Ma, Xiaochao] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Krausz, Kristopher W.] NIH, Lab Metab, Ctr Canc Res, Inst Canc, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501578 ER PT J AU Kaludercic, N Takimoto, E Nagayama, T Lai, E Chen, K Shih, JC Pacak, K Kass, DA Di Lisa, F Paolocci, N AF Kaludercic, Nina Takimoto, Eiki Nagayama, Takahiro Lai, Edwin Chen, Kevin Shih, Jean C. Pacak, Karel Kass, David A. Di Lisa, Fabio Paolocci, Nazareno TI Monoamine oxidase B gene deletion prevents cardiac pump dysfunction in mice with pressure overload SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kaludercic, Nina; Takimoto, Eiki; Nagayama, Takahiro; Kass, David A.; Paolocci, Nazareno] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Kaludercic, Nina; Di Lisa, Fabio] Univ Padua, Padua, Italy. [Lai, Edwin; Pacak, Karel] NICHD, NIH, Bethesda, MD USA. [Chen, Kevin; Shih, Jean C.] Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506435 ER PT J AU Kang, JH Tsai-Morris, CH Dufau, ML AF Kang, Jung-Hoon Tsai-Morris, Chon-Hwa Dufau, Maria L. TI Estradiol (E2) Regulation And ER alpha, C/EBP beta And SP1 Interactions Are Essential For Human Prolactin Receptor (hPRLR) Gene Transcription In a Live Cell-Based System SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kang, Jung-Hoon; Tsai-Morris, Chon-Hwa; Dufau, Maria L.] NICHD, Sect Mol Endocrinol, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505264 ER PT J AU Kimura, AK Kim, HY AF Kimura, Atsuko Kakio Kim, Hee-Yong TI Role of PS Product Inhibition in Accumulation of Phosphatidylserine (PS) in Neuronal Membranes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kimura, Atsuko Kakio; Kim, Hee-Yong] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507202 ER PT J AU Kinyamu, HK Yang, J Archer, T AF Kinyamu, Harriet Karimi Yang, Jun Archer, Trevor TI Inhibiting the 26S Proteasome Expands Glucocorticoid Receptor Transcriptional Networks via Chromatin Modifications SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kinyamu, Harriet Karimi; Yang, Jun; Archer, Trevor] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504447 ER PT J AU Kirby, TW Beard, WA Wilson, SH London, RE AF Kirby, Thomas W. Beard, William A. Wilson, Samuel H. London, Robert E. TI NMR study of the effect of Zn on conformational activation of rat DNA polymerase beta SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kirby, Thomas W.; Beard, William A.; Wilson, Samuel H.; London, Robert E.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503128 ER PT J AU Kohut, SJ DeCicco-Skinner, KL Riley, AL AF Kohut, Stephen J. DeCicco-Skinner, Kathleen L. Riley, Anthony L. TI Modulation of the cocaine cue by predictable and unpredictable stress in rats: relation to monoamine transporter levels SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kohut, Stephen J.] NIDA, Medicat Discovery Res Branch, IRP, NIH,DHHS, Baltimore, MD USA. [Kohut, Stephen J.; DeCicco-Skinner, Kathleen L.; Riley, Anthony L.] American Univ, Washington, DC 20016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505071 ER PT J AU Kramer, KL AF Kramer, Kenneth L. TI Coordination of dorsoventral axis formation by multiple heparan sulfate proteoglycans SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kramer, Kenneth L.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500101 ER PT J AU Kumar, A Greggio, E Beilina, A Kaganovich, A Chan, D Wolozin, B Cookson, M AF Kumar, Azad Greggio, Elisa Beilina, Alexandra Kaganovich, Alice Chan, Diane Wolozin, Ben Cookson, Mark TI The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kumar, Azad; Kaganovich, Alice; Cookson, Mark] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Greggio, Elisa; Beilina, Alexandra] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Chan, Diane; Wolozin, Ben] Boston Univ, Sch Med, Dept Pharmacol & Neurol, Boston, MA 02118 USA. RI Greggio, Elisa/H-6119-2013 OI Greggio, Elisa/0000-0002-8172-3598 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503805 ER PT J AU Kunduri, SS Nayeem, M Falck, J Schnermann, J Mustafa, SJ AF Kunduri, Swati Sarada Nayeem, Mohammad Falck, John Schnermann, Jurgen Mustafa, S. Jamal TI Exaggerated vasoconstriction depends on omega-hydroxyylase through adenosine A(1)receptor (AR) in A(1) WT compared to A(1) KO mouse aorta SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kunduri, Swati Sarada; Nayeem, Mohammad; Mustafa, S. Jamal] W Virginia Univ, Morgantown, WV 26506 USA. [Falck, John] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504418 ER PT J AU Kunkel, TA AF Kunkel, Thomas A. TI Eukaryotic DNA Replication Fidelity SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kunkel, Thomas A.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500129 ER PT J AU Kuzmiak, S Glancy, B Sweazea, K Willis, W AF Kuzmiak, Sarah Glancy, Brian Sweazea, Karen Willis, Wayne TI Mitochondrial function in sparrow pectoralis muscle SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kuzmiak, Sarah; Glancy, Brian; Sweazea, Karen; Willis, Wayne] Arizona State Univ, Tempe, AZ USA. [Glancy, Brian] NIH, Bethesda, MD 20892 USA. RI Glancy, Brian/P-3163-2016 OI Glancy, Brian/0000-0002-8571-244X NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505739 ER PT J AU Leung, PK Hu, L Feng, H Krsmanovic, LZ Catt, KJ AF Leung, Po Ki Hu, Lian Feng, Hao Krsmanovic, Lazar Z. Catt, Kevin J. TI Cellular Distribution, Homo-oligomerization and Functional Characterization of GnRH Receptors in Immortalized GnRH Neurons SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Leung, Po Ki; Hu, Lian; Feng, Hao; Krsmanovic, Lazar Z.; Catt, Kevin J.] NIH, Sect Hormonal Regulat, PDEGEN, HICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506448 ER PT J AU Li, LL Eisner, C Huang, YN Choi, DS Schnermann, J AF Li, Lingli Eisner, Christoph Huang, Yuning Choi, Doo-Sup Schnermann, Jurgen TI Locomotor activity and blood pressure in conscious mice with targeted deletion of the equilibrative nucleoside transporter 1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Li, Lingli; Eisner, Christoph; Huang, Yuning; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. [Choi, Doo-Sup] Mayo Clinc, Mol Pharmacol Exp Therapeut, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504861 ER PT J AU Li, XL Guo, XM Williams, J Bienstock, R AF Li, Xiaoling Guo, Xiumei Williams, Jason Bienstock, Rachelle TI Phosphorylation of Thr522 activates SIRT1 and is required for DYRK-mediated cell survival in response to DNA damage SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Li, Xiaoling; Guo, Xiumei] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. [Williams, Jason] NIEHS, Lab Struct Biol, NIH, Res Triangle Pk, NC 27709 USA. [Bienstock, Rachelle] NIEHS, Sci Comp Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504007 ER PT J AU Liao, JY Prater, C Thakur, S Imani, F AF Liao, Jie-Ying Prater, Chrissy Thakur, Sheetal Imani, Farhad TI Conversion of Adenines to Inosines in RNA During Virus Infections Activates Innate Immune Responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Liao, Jie-Ying; Prater, Chrissy; Thakur, Sheetal; Imani, Farhad] NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504083 ER PT J AU Liao, MJ Zhang, Y Dufau, M AF Liao, Mingjuan Zhang, Ying Dufau, Maria TI PC4 is a coactivator for basal and TSA-induced Luteinizing Hormone Receptor (LHR) transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Liao, Mingjuan; Zhang, Ying; Dufau, Maria] NICHD, Mol Endocrinol Sect, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505595 ER PT J AU Lin, YH Hibbeln, JR Zhou, WY Loewke, J Brown, JA Lands, WEM Wells, EM Goldman, LR Salem, N AF Lin, Yuhong Hibbeln, Joseph R. Zhou, Weiyin Loewke, James Brown, James A. Lands, William E. M. Wells, Ellen M. Goldman, Lynn R. Salem, Norman, Jr. TI Robotic high throughput fatty acid analysis of umbilical cord serum SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Lin, Yuhong; Hibbeln, Joseph R.; Zhou, Weiyin; Loewke, James; Brown, James A.; Lands, William E. M.; Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. [Wells, Ellen M.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Goldman, Lynn R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500462 ER PT J AU Liou, AP Lu, XP Zhao, XL Pechhold, S Raybould, H Wank, S AF Liou, Alice Peiyu Lu, Xinping Zhao, Xilin Pechhold, Susanne Raybould, Helen Wank, Steve TI The G-protein coupled receptor GPR40 mediates long chain fatty acid induced cholecystokinin secretion SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Liou, Alice Peiyu; Raybould, Helen] Univ Calif Davis, Sch Vet Med Anat Physiol & Cell Biol, Davis, CA 95616 USA. [Lu, Xinping; Zhao, Xilin; Pechhold, Susanne; Wank, Steve] NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502710 ER PT J AU Luginbuhl, K Pisitkun, T Rinschen, M Hoffert, J Knepper, MA AF Luginbuhl, Kelli Pisitkun, Trairak Rinschen, Markus Hoffert, Jason Knepper, Mark A. TI Toward comprehensive quantitative proteomics using subcellular fractionation and LC-MS/MS SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Luginbuhl, Kelli; Pisitkun, Trairak; Rinschen, Markus; Hoffert, Jason; Knepper, Mark A.] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503356 ER PT J AU Mahabir, S Baer, D Pfeiffer, R Taylor, PR AF Mahabir, Somdat Baer, David Pfeiffer, Ruth Taylor, Philip R. TI Effects of alcohol and alcohol-metabolizing SNPs on serum vitamin D levels in postmenopausal women in a controlled feeding study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mahabir, Somdat] NCI, Modifiable Risk Factors Branch, EGRP DCCPS, NIH, Beltsville, MD USA. [Pfeiffer, Ruth] NCI, Biostat Branch, NIH, Beltsville, MD USA. [Taylor, Philip R.] NCI, Genet Epidemiol Branch, DCEG, NIH, Beltsville, MD USA. [Baer, David] ARS, USDA, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503087 ER PT J AU McDowell, KA Quiroz, C Ferre, S Yarowsky, P AF McDowell, Kimberly Anne Quiroz, Cesar Ferre, Sergi Yarowsky, Paul TI The role of orexin and dopamine in sleep alterations from the progressive, neurotoxin-induced model of parkinsonism SO FASEB JOURNAL LA English DT Meeting Abstract C1 [McDowell, Kimberly Anne; Yarowsky, Paul] Univ MD, Program Neurosci, Baltimore, MD USA. [McDowell, Kimberly Anne; Yarowsky, Paul] Univ MD, Baltimore, MD USA. [Quiroz, Cesar; Ferre, Sergi] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502266 ER PT J AU Miller, DS Wang, XQ AF Miller, David S. Wang, Xueqian TI The aryl hydrocarbon receptor (AhR) upregulates P-glycoprotein (P-gp) at the blood-brain barrier (BBB) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Miller, David S.; Wang, Xueqian] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502250 ER PT J AU Mizzen, CA Zheng, YP Pesavento, J Schultz-Norton, J John, S Nardulli, A Kelleher, N Hager, G AF Mizzen, Craig Andrew Zheng, Yupeng Pesavento, James Schultz-Norton, Jennifer John, Sam Nardulli, Ann Kelleher, Neil Hager, Gordon TI Phosphorylation of histone H1 at specific sites during gene transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mizzen, Craig Andrew; Zheng, Yupeng; Pesavento, James; Schultz-Norton, Jennifer; Nardulli, Ann; Kelleher, Neil] Univ Illinois, Urbana, IL 61801 USA. [John, Sam; Hager, Gordon] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503537 ER PT J AU Mutoh, S Osabe, M Moore, R Vinal, K Sueyoshi, T Negishi, M AF Mutoh, Shingo Osabe, Makoto Moore, Rickie Vinal, Kellie Sueyoshi, Tatsuya Negishi, Masahiko TI RACK1 regulates PP2A-mediated de-phosphorylation of threonine 38 of the human nuclear xenobiotic receptor CAR SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mutoh, Shingo; Osabe, Makoto; Moore, Rickie; Vinal, Kellie; Sueyoshi, Tatsuya; Negishi, Masahiko] NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500768 ER PT J AU Nagineni, CN Kommineni, VK William, A Hooks, JJ Detrick, B AF Nagineni, Chandra N. Kommineni, Vijay K. William, Abitha Hooks, John J. Detrick, Barbara TI Regulation of VEGFs expression in human retinal cells by cytokines: implications for the role of inflammation in age-related macular degeneration SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Nagineni, Chandra N.; Kommineni, Vijay K.; William, Abitha; Hooks, John J.] NEI, NIH, Bethesda, MD 20892 USA. [Detrick, Barbara] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505243 ER PT J AU Nakamura, T Yuasa, K Jimenez, L Unda, F Koyama, E Fukumoto, S Yamada, Y AF Nakamura, Takashi Yuasa, Kenji Jimenez, Lucia Unda, Fernando Koyama, Eiki Fukumoto, Satoshi Yamada, Yoshihiko TI Essential roles of zinc finger factor epiprofin in tooth development SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Nakamura, Takashi; Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Dept Oral Hlth & Dev Sci, Sendai, Miyagi 980, Japan. [Nakamura, Takashi; Yuasa, Kenji; Yamada, Yoshihiko] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Jimenez, Lucia; Unda, Fernando] Univ Basque Country, Dept Cell Biol & Histol, Vizcaya, Spain. [Koyama, Eiki] Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503460 ER PT J AU Nayeem, MA Zeldin, DC Boegehold, MA Falck, JR AF Nayeem, Mohammed A. Zeldin, Darryl C. Boegehold, Mathew A. Falck, John R. TI Salt modulates vascular response in eNOS-null mice through adenosine A2A receptor: role of CYP450 epoxygenase and soluble epoxide hydrolase SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Nayeem, Mohammed A.; Boegehold, Mathew A.] W Virginia Univ, Ctr Cardiovasc & Resp Sci, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Falck, John R.] Univ Texas Dallas, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507444 ER PT J AU Nayeem, MA Zeldin, DC Boegehold, MA Ponnoth, DS Roush, KP Falck, JR AF Nayeem, Mohammed A. Zeldin, Darryl C. Boegehold, Mathew A. Ponnoth, Dovenia S. Roush, Kevin P. Falck, John R. TI Salt induced vascular response through adenosine A(2A) receptor: role of CYP epoxygenase and soluble epoxide hydrolase SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Nayeem, Mohammed A.; Boegehold, Mathew A.; Ponnoth, Dovenia S.; Roush, Kevin P.] W Virginia Univ, Ctr Cardiovasc & Resp Sci, Morgantown, WV 26506 USA. [Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Falck, John R.] Univ Texas Dallas, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504363 ER PT J AU Negus, SS Morrissey, EM Rosenberg, MB Altarifi, A Cheng, K Rice, KC AF Negus, S. Stevens Morrissey, Ember M. Rosenberg, Marisa B. Altarifi, Ahmad Cheng, K. Rice, Kenner C. TI Pain-related depression of intracranial self-stimulation in rats: effects of the kappa opioid agonist U69,593 and the kappa opioid antagonist norbinaltorphimine SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Negus, S. Stevens; Morrissey, Ember M.; Rosenberg, Marisa B.; Altarifi, Ahmad] Virginia Commonwealth Univ, Richmond, VA USA. [Cheng, K.; Rice, Kenner C.] NIAAA, Chem Biol Res Branch, NIDA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503125 ER PT J AU Oaks, B Dodd, KW Meinhold, CL Jiao, L Church, TR Stolzenberg-Solomon, RZ AF Oaks, Brietta Dodd, Kevin W. Meinhold, Cari L. Jiao, Li Church, Timothy R. Stolzenberg-Solomon, Rachael Z. TI Folate intake post-folic acid grain fortification and pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Oaks, Brietta] Univ Calif Davis, Davis, CA USA. [Dodd, Kevin W.] NCI, Biometry Res Grp, Canc Prevent Div, NIH, Rockville, MD USA. [Meinhold, Cari L.; Jiao, Li; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Church, Timothy R.] Univ Minnesota, Sch Publ Hlth, Dept Environm Hlth Sci, Minneapolis, MN USA. RI Kitahara, Cari/R-8267-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502478 ER PT J AU Oubrahim, H Wilson, B Chock, PB AF Oubrahim, Hammou Wilson, Brenda Chock, P. Boon TI Pasteurella multocida toxin activates mTORC1 and induces cell spreading in Swiss 3T3 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Oubrahim, Hammou; Chock, P. Boon] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Wilson, Brenda] Univ Illinois, Dept Microbiol, Urbana, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500871 ER PT J AU Petersen, SS Donaldson, JG AF Petersen, Shariska S. Donaldson, Julie G. TI Characterization of clathrin-independent endocytosis in epithelial cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Petersen, Shariska S.; Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501887 ER PT J AU Pittman, YR Dever, TE AF Pittman, Yvette Renee Dever, Thomas E. TI Analysis of flanking nucleotide contributions to translation start codon selection in yeast SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Pittman, Yvette Renee; Dever, Thomas E.] NIH, Lab Gene Regulat & Dev, Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502395 ER PT J AU Preusch, PC Basavappa, R Chin, J Edmonds, C Flicker, P Lewis, C Smith, W Wehrle, J Berg, J AF Preusch, Peter C. Basavappa, Ravi Chin, Jean Edmonds, Charles Flicker, Paula Lewis, Catherine Smith, Ward Wehrle, Janna Berg, Jeremy TI NIGMS PSI:Biology Initiative - Enabling High-Throughput Structural Biology and Structural Genomics SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Preusch, Peter C.; Basavappa, Ravi; Chin, Jean; Edmonds, Charles; Flicker, Paula; Lewis, Catherine; Smith, Ward; Wehrle, Janna; Berg, Jeremy] NIGMS, Div Cell Biol & Biophys, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507143 ER PT J AU Rankin, ML Sibley, DR AF Rankin, Michele Lynn Sibley, David R. TI Constitutive PKC phosphorylation of the D1 dopamine receptor inhibits receptor signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rankin, Michele Lynn; Sibley, David R.] NINDS, MNS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501101 ER PT J AU Reardon, BJ Kritchevsky, SB Harris, T Houston, DK Bauer, D Koster, A Newman, A Cassano, PA AF Reardon, Brian J. Kritchevsky, Stephen B. Harris, Tamara Houston, Denise K. Bauer, Doug Koster, Annemarie Newman, Anne Cassano, Patricia A. TI Association of 25-hydroxyvitamin D (25-OH-D) with Lung Function in the Health, Aging and Body Composition (Health ABC) Study SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Reardon, Brian J.; Cassano, Patricia A.] Cornell Univ, Ithaca, NY USA. [Kritchevsky, Stephen B.; Houston, Denise K.] Wake Forest Univ, Med Ctr, Sticht Ctr Aging, Winston Salem, NC USA. [Harris, Tamara; Koster, Annemarie] NIA, Bethesda, MD 20892 USA. [Bauer, Doug] UCSF, San Francisco, CA USA. [Newman, Anne] Univ Pittsburgh, Pittsburgh, PA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500380 ER PT J AU Rieger, S Contreras, JE AF Rieger, Sandra Contreras, Jorge E. TI Regulation of heart rate in zebrafish embryos SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rieger, Sandra] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. [Contreras, Jorge E.] NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500531 ER PT J AU Rosenberg, MB Folk, JE Rice, KC Negus, SS AF Rosenberg, Marisa Brooke Folk, John E. Rice, Kenner C. Negus, Sidney Stevens TI Pain-related depression of intracranial self-stimulation in rats: effects of the delta opioid agonist SNC80 and the psychomotor stimulant cocaine SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Rosenberg, Marisa Brooke; Negus, Sidney Stevens] Virginia Commonwealth Univ, Richmond, VA USA. [Folk, John E.; Rice, Kenner C.] NIAAA, Chem Biol Res Branch, NIDA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502789 ER PT J AU Saha, A Munasinghe, J Zhang, ZJ Heffer, A Mukherjee, AB AF Saha, Arjun Munasinghe, Jeeva Zhang, Zhongjian Heffer, Alison Mukherjee, Anil B. TI How blood brain barrier is breached in a mouse model of INCL SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Saha, Arjun; Zhang, Zhongjian; Heffer, Alison; Mukherjee, Anil B.] NICHD, Sect Dev Genet, NIH, Bethesda, MD USA. [Munasinghe, Jeeva] NINDS, IN VIVO NMR Ctr HNQ2 3, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505646 ER PT J AU Saldanha, LG Sempos, CT Costello, RB AF Saldanha, Leila G. Sempos, Christopher T. Costello, Rebecca B. TI Quality of reporting dietary supplement research in scientific publications and other observations SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Saldanha, Leila G.; Sempos, Christopher T.; Costello, Rebecca B.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505895 ER PT J AU Seidel, S Roeschel, T Kahl, T Schnermann, J Bachmann, S Paliege, A AF Seidel, Saskia Roeschel, Tom Kahl, Thomas Schnermann, Jurgen Bachmann, Sebastian Paliege, Alexander TI Annexin A1 mediates the effects of dexamethasone on macula densa cyclooxygenase-2 expression SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Seidel, Saskia; Roeschel, Tom; Kahl, Thomas; Bachmann, Sebastian; Paliege, Alexander] Charite, Berlin, Germany. [Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506332 ER PT J AU Sempos, C Carriquirry, A Bailey, R Joseph, M Durazo, R Yetley, B Dawson-Hughes, B Dwyer, J Picciano, MF AF Sempos, Christopher Carriquirry, Alicia Bailey, Regan Joseph, Maria Durazo, Ramon Yetley, Beth Dawson-Hughes, Bess Dwyer, Johanna Picciano, Mary Frances TI Adjusting Serum Biomarker of Vitamin D Status for Within-person Variation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sempos, Christopher; Bailey, Regan; Yetley, Beth; Dwyer, Johanna; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Carriquirry, Alicia; Joseph, Maria] Iowa State Univ, Ames, IA USA. [Durazo, Ramon] Loyola Univ, Maywood, IL 60153 USA. [Dawson-Hughes, Bess] Tufts Univ, Boston, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505213 ER PT J AU Shi, YB AF Shi, Yun-Bo TI Molecular and genetic studies of histone-modifying complexes in thyroid hormone action during Xenopus development. SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shi, Yun-Bo] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675500104 ER PT J AU Sikdar, N Myung, K AF Sikdar, Nilabja Myung, Kyungjae TI Elg1 (Enhanced level of genome instability 1) has an essential role in early development and suppressing tumorigenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sikdar, Nilabja; Myung, Kyungjae] NHGRI, Genome Instabil Sect, GMBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506458 ER PT J AU Smit, E Sempos, CT Rehm, J Huguet, N Crespo, CJ AF Smit, Ellen Sempos, Christopher T. Rehm, Jurgen Huguet, Nathalie Crespo, Carlos J. TI The relationship between alcohol intake and mortality in Whites, Blacks and Hispanics using the NHIS Mortality Linked Data Set SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Smit, Ellen] Oregon State Univ, Corvallis, OR 97331 USA. [Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Rehm, Jurgen] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Huguet, Nathalie; Crespo, Carlos J.] Portland State Univ, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675505309 ER PT J AU Song, P Kim, JH Suh, PG Ryu, S AF Song, Parkyong Kim, Jong Hyun Suh, Phann-ghill Ryu, Sungho TI Anti-cancer drug F-59 regulates glucose metabolism through AMPK SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Song, Parkyong; Suh, Phann-ghill; Ryu, Sungho] Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang, South Korea. [Kim, Jong Hyun] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507145 ER PT J AU Su, LJ Arab, L Steck, S Schroeder, JC Fontham, ETH Bensen, JT Mohler, JL AF Su, L. Joseph Arab, Lenore Steck, Susan Schroeder, Jane C. Fontham, Elizabeth T. H. Bensen, Jeannette T. Mohler, James L. TI Obesity and Prostate Cancer Aggressiveness among African and Caucasian American SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Su, L. Joseph] NCI, Bethesda, MD 20892 USA. [Arab, Lenore] Univ Calif Los Angeles, Los Angeles, CA USA. [Steck, Susan] Univ S Carolina, Columbia, SC 29208 USA. [Schroeder, Jane C.] Natl Inst Environm Hlth Sci, Durham, NC USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Bensen, Jeannette T.] Univ N Carolina, Chapel Hill, NC USA. [Mohler, James L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502594 ER PT J AU Tabung, F Steck, SE Su, LJ Arab, L Fontham, ETH Bensen, J Hebert, JR Zhang, HM Mohler, JL AF Tabung, Fredoline Steck, Susan E. Su, L. Joseph Arab, Lenore Fontham, Elizabeth T. H. Bensen, Jeannette Hebert, James R. Zhang, Hongmei Mohler, James L. TI Whole grain and dietary fiber intake and prostate cancer aggressiveness by race SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tabung, Fredoline; Steck, Susan E.; Hebert, James R.; Zhang, Hongmei] Univ S Carolina, Columbia, SC 29208 USA. [Su, L. Joseph] NCI, NIH, Rockville, MD USA. [Arab, Lenore] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Fontham, Elizabeth T. H.] Louisiana State Univ, Sch Publ Hlth, Hlth Sci Ctr, New Orleans, LA USA. [Bensen, Jeannette] Univ N Carolina, Chapel Hill, NC USA. [Mohler, James L.] Roswell Pk Canc Inst, Dept Urol, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504238 ER PT J AU Tasevska, N Park, Y Subar, AF Schatzkin, A Potischman, N AF Tasevska, Natasa Park, Yikyung Subar, Amy F. Schatzkin, Arthur Potischman, Nancy TI Added sugars in diet and risk of total and cause-specific mortality in a large US cohort SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tasevska, Natasa; Subar, Amy F.; Potischman, Nancy] NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507484 ER PT J AU Tauseef, M Knezevic, N Kini, V Vogel, S Birnbaumer, L Malik, A Mehta, D AF Tauseef, Mohammad Knezevic, Nebojsa Kini, Vidisha Vogel, Stephen Birnbaumer, Lutz Malik, Asrar Mehta, Dolly TI TRPC6 and TRPC1 functionally interact to mediate Ca2+entry in endothelial cells to induce lung vascular permeability SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tauseef, Mohammad; Knezevic, Nebojsa; Kini, Vidisha; Vogel, Stephen; Malik, Asrar; Mehta, Dolly] Univ Illinois, Chicago, IL USA. [Birnbaumer, Lutz] NIEHS, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504745 ER PT J AU Thakur, SA Zalinger, Z Johnson, TR Minor, RAC Graham, BS Imani, F AF Thakur, Sheetal A. Zalinger, Zachary Johnson, Teresa R. Minor, Radiah A. Corn Graham, Barney S. Imani, Farhad TI PKR Regulates Immunoglobulin Class Switching during RSV infection In Vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Thakur, Sheetal A.; Zalinger, Zachary; Imani, Farhad] NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Johnson, Teresa R.; Graham, Barney S.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Minor, Radiah A. Corn] N Carolina Agr & Tech State Univ, Greensboro, NC 27411 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504228 ER PT J AU Topanurak, S Gallazzini, M Ferraris, JD Burg, MB AF Topanurak, Supachai Gallazzini, Morgan Ferraris, Joan D. Burg, Maurice B. TI High NaCl or urea inhibits glycerophosphocholine (GPC) phosphodiesterase (GDPD5) activity and reduces phosphorylation of GDPD5-T587 SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Topanurak, Supachai; Gallazzini, Morgan; Ferraris, Joan D.; Burg, Maurice B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503217 ER PT J AU Tsai, SYA Hayashi, T Harvey, BK Wang, Y Wu, WW Shen, RF Zhang, YQ Becker, KG Hoffer, BJ Su, TP AF Tsai, Shang-Yi Anne Hayashi, Teruo Harvey, Brandon K. Wang, Yun Wu, Well W. Shen, Rong-Feng Zhang, Yongqing Becker, Kevin G. Hoffer, Barry J. Su, Tsung-Ping TI Sigma-1 receptors regulate hippocampal dendritic spine formation via a free radical-sensitive mechanism involving Rac1 center dot GTP pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tsai, Shang-Yi Anne; Hayashi, Teruo; Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, CNRB, NIH, Baltimore, MD USA. [Harvey, Brandon K.; Wang, Yun] NIDA, Neural Protect & Regenerat Sect, MNB, NIH, Baltimore, MD USA. [Hoffer, Barry J.] NIDA, Cellular Neurophysiol Sect, CNRB, NIH, Baltimore, MD USA. [Wu, Well W.; Shen, Rong-Feng] NIA, Prote & Analyt Biochem Unit, NIH, Baltimore, MD 21224 USA. [Zhang, Yongqing; Becker, Kevin G.] NIA, Gene Express & Genom Unit, RRB, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675507094 ER PT J AU Tsuji, P Irons, R Carlson, B Yoo, MH Xu, XM Formenko, D Gladyshev, V Hatfield, D Davis, C AF Tsuji, Petra Irons, Robert Carlson, Bradley Yoo, Min-Hyuk Xu, Xue-Ming Formenko, Dmitri Gladyshev, Vadim Hatfield, Dolph Davis, Cindy TI Role of the 15kDa selenoprotein (Sep15) in colon cancer prevention SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tsuji, Petra] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Carlson, Bradley; Yoo, Min-Hyuk; Xu, Xue-Ming; Hatfield, Dolph] NCI, Lab Canc Prevent, Bethesda, MD 20892 USA. [Tsuji, Petra; Davis, Cindy] NCI, Nutr Sci Res Grp, Rockville, MD USA. [Irons, Robert] VE Irons Inc, Kansas City, MO USA. [Formenko, Dmitri] Univ Nebraska, Lincoln, NE USA. [Gladyshev, Vadim] Brigham & Womens Hosp, Harvard Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503259 ER PT J AU Tuo, JS Pang, JJ Cao, XG Shen, DF Zhang, J Scaria, A Wadsworth, SC Pechan, P Hauswirth, WW Chan, CC AF Tuo, Jingsheng Pang, Ji-Jing Cao, XiaoGuang Shen, Defen Zhang, Jun Scaria, Abraham Wadsworth, Samuel C. Pechan, Peter Hauswirth, William W. Chan, Chi-Chao TI AAV-mediated sFLT-1 gene therapy ameliorates retinal lesions in Ccl2/Cx3cr1 deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Tuo, Jingsheng; Cao, XiaoGuang; Shen, Defen; Zhang, Jun; Chan, Chi-Chao] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Pang, Ji-Jing; Hauswirth, William W.] Univ Florida, Dept Ophthalmol, Gainesville, FL USA. [Scaria, Abraham; Wadsworth, Samuel C.; Pechan, Peter] Genzyme Corp, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502025 ER PT J AU Villar, J Tsai-Morris, CH Dufau, ML AF Villar, Joaquin Tsai-Morris, Chon-Hwa Dufau, Maria L. TI An Androgen Response-Like Element Half-Site Is Essential For Androgen Regulation Of Gonadotropin Regulated Testicular RNA Helicase (GRTH/DDX25) Transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Villar, Joaquin; Tsai-Morris, Chon-Hwa; Dufau, Maria L.] NICHD, Sect Mol Endocrinol, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506475 ER PT J AU Wan, FY Weaver, A Lenardo, MJ AF Wan, Fengyi Weaver, Amanda Lenardo, Michael J. TI Sam68 directs NF-kB for IL2RA gene transcription SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wan, Fengyi; Weaver, Amanda; Lenardo, Michael J.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675503503 ER PT J AU Wang, PM Martin, WJ AF Wang, Ping Ming Martin, William J., II TI Morphometric analysis of bleomycin-induced alveolar epithelium type 2 cell injury and cell shape changes during repair in murine lungs SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Ping Ming] NIEHS, Lab Resp Biol, Res Triangle Pk, NC USA. [Martin, William J., II] NIEHS, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675504397 ER PT J AU Wang, YF Beydoun, M Li, J Liu, YH Moreno, LA AF Wang, Youfa Beydoun, May Li, Ji Liu, Yinghui Moreno, Luis A. TI Do children and their parents eat a similar diet? Association between child and parental dietary intakes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Youfa; Li, Ji; Liu, Yinghui] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Beydoun, May] NIA, NIH, Baltimore, MD 21224 USA. [Moreno, Luis A.] Univ Zaragoza, Dept Pediat, Zaragoza, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506555 ER PT J AU Wang, YF Beydoun, M Caballero, B AF Wang, Youfa Beydoun, May Caballero, Benjamin TI Has the obesity epidemic leveled off in US children? What do recent data tell us? SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Youfa; Caballero, Benjamin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Beydoun, May] NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675506526 ER PT J AU Yoon, GA Cho, YS Yeum, KJ Chen, CY Tang, G Blumberg, JB Russell, RM Yoon, S Lee-Kim, YC AF Yoon, G-A Cho, Y-S Yeum, K-J Chen, C-Yo Tang, G. Blumberg, J. B. Russell, R. M. Yoon, S. Lee-Kim, Y. C. TI Common plant foods consumed in Korea are rich source of phytochemicals SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Yoon, G-A; Yeum, K-J; Chen, C-Yo; Tang, G.; Blumberg, J. B.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Yoon, G-A] Dong Ewi Univ, Pusan, South Korea. [Cho, Y-S] Florida Coastal Sch Law, Jacksonville, FL USA. [Russell, R. M.] NIH, Off Director, Bethesda, MD 20892 USA. [Yoon, S.; Lee-Kim, Y. C.] Yonsei Univ, Seoul 120749, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501119 ER PT J AU Zhang, ZY Lanza, E Mitchell, D Mentor-Marcel, R Colburn, N Hartman, T AF Zhang, Zhiying Lanza, Elaine Mitchell, Diane Mentor-Marcel, Roycelynn Colburn, Nancy Hartman, Terryl TI A legume enriched diet facilitates weight loss and improves biomarkers of insulin resistance and inflammation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Zhang, Zhiying; Mitchell, Diane; Hartman, Terryl] Penn State Univ, University Pk, PA 16802 USA. [Lanza, Elaine; Mentor-Marcel, Roycelynn; Colburn, Nancy] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675502465 ER PT J AU Zhou, XM Gallazzini, M Burg, MB Ferraris, JD AF Zhou, Xiaoming Gallazzini, Morgan Burg, Maurice B. Ferraris, Joan D. TI Contribution of SHP-1 protein tyrosine phosphatase to osmotic regulation of the transcription factor TonEBP/OREBP SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Zhou, Xiaoming] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Gallazzini, Morgan; Burg, Maurice B.; Ferraris, Joan D.] NIH, LKEM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2010 VL 24 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V28IW UT WOS:000208675501785 ER PT J AU Imudia, AN Kumar, S Diamond, MP DeCherney, AH Armant, DR AF Imudia, Anthony N. Kumar, Sanjeev Diamond, Michael P. DeCherney, Alan H. Armant, D. Randall TI Transcervical retrieval of fetal cells in the practice of modern medicine: a review of the current literature and future direction SO FERTILITY AND STERILITY LA English DT Review DE Cervical mucus; ectopic pregnancy; fetal cells; genetic analysis; immunological markers; intrauterine lavage; prenatal diagnosis; transcervical cell collection; trophoblast ID NONINVASIVE PRENATAL-DIAGNOSIS; IN-SITU HYBRIDIZATION; 1ST TRIMESTER; TROPHOBLAST CELLS; HLA-G; MATERNAL PLASMA; UTERINE LAVAGE; CERVICAL-MUCUS; DOWN-SYNDROME; QF-PCR AB Objective: To review published methods for transcervical collection of fetal cells and to assess the potential of this approach for application in prenatal diagnosis. Main Outcome Measure(s): Retrospective analysis of efforts at prenatal diagnosis with trophoblast cells shed into the lower uterine pole that accumulate within the cervical mucus at the level of the internal os. Result(s): Minimally invasive techniques that include cervical mucus aspiration, cervical swabbing, and cervical or intrauterine lavage can be used to retrieve trophoblast cells during the first trimester for diagnostic purposes, including for prenatal genetic analysis. Fetal cells have been identified in these specimens with success rates that vary from 40% to 90%. The disparity in reported success rates can be a function of gestational age, collection method, operator variability, detection sensitivity, or pregnancy status. Molecular approaches have been devised to determine fetal sex and identify aneuploidies. Antibody markers have proven useful to select trophoblast cells for genetic analysis and to demonstrate that the abundance of recoverable fetal cells diminishes in abnormal gestations, such as in ectopic pregnancy or blighted ovum. Conclusion(s): Transcervical collection of fetal cells offers several avenues for prenatal diagnosis that with further refinement could one day provide valuable information for the management of ongoing pregnancies. (Fertil Steril(R) 2010;93:1725-30. (C) 2010 by American Society for Reproductive Medicine.) C1 [Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, Detroit, MI 48201 USA. [DeCherney, Alan H.; Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, CS Mott Ctr, 275 E Hancock Ave, Detroit, MI 48201 USA. EM darmant@med.wayne.edu OI Diamond, Michael/0000-0001-6353-4489; Armant, D. Randall/0000-0001-5904-9325 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services 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, U.S. Department of Health and Human Services. NR 47 TC 9 Z9 9 U1 3 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2010 VL 93 IS 6 BP 1725 EP 1730 DI 10.1016/j.fertnstert.2009.11.022 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 583LS UT WOS:000276678100001 PM 20056202 ER PT J AU Stratton, P Levens, ED Hartog, B Piquion, J Wei, QX Merino, M Nieman, LK AF Stratton, Pamela Levens, Eric D. Hartog, Beth Piquion, Johann Wei, Qingxiang Merino, Maria Nieman, Lynnette K. TI Endometrial effects of a single early luteal dose of the selective progesterone receptor modulator CDB-2914 SO FERTILITY AND STERILITY LA English DT Article DE CDB-2914; endometrium; luteal phase; single dose; selective progesterone receptor modulators ID EMERGENCY POSTCOITAL CONTRACEPTION; NORMALLY CYCLING WOMEN; MENSTRUAL-CYCLE; MIFEPRISTONE RU-486; PHASE; ANTIPROGESTIN; RADIOIMMUNOASSAY; EXPRESSION; MATURATION; RU486 AB Objective: To test potential contraceptive mechanisms of the selective P receptor modulator CDB-2914 in the early luteal phase. Design: Prospective randomized clinical trial. Setting: Clinical research center. Patient(s): Fifty-six women with regular cycles. Intervention(s): Women received a single dose of CDB-2914 (10,50, or 100 mg) or placebo given after ovulation and within 2 days of the LH surge. Four to 6 days later, a transvaginal ultrasound scan measured endometrial thickness, and an endometrial biopsy specimen was obtained. Main Outcome Measure(s): The endometrium was evaluated by thickness and by immunohistochemical analysis for P-dependent markers; safety laboratory tests were performed, and E, and P levels were obtained. Result(s): CDB-2914 caused a significant dose-dependent decrease in endometrial thickness, an increase in glandular P receptors, and a decrease in peripheral node addressins. Estradiol and P levels and menstrual cycle timing were not altered. No adverse effects were observed. Conclusion(s): The alteration in endometrial thickness and P-dependent markers of implantation in the absence of changes in hormone levels and cycle length suggests that CDB-2914 may have contraceptive properties. (Fertil Steril (R) 2010;93:2035-41. (C)2010 by American Society for Reproductive Medicine.) C1 [Stratton, Pamela; Levens, Eric D.; Piquion, Johann; Wei, Qingxiang; Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Hartog, Beth] George Washington Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Washington, DC 20037 USA. [Merino, Maria] NCI, Lab Surg Pathol, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), CRC, Bldg 10,1 East,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM NiemanL@mail.nih.gov FU National Institute of Child Health and Human Development; National Cancer Institute FX Supported by the intramural National Institutes of Health program of the National Institute of Child Health and Human Development and the National Cancer Institute. NR 29 TC 36 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2010 VL 93 IS 6 BP 2035 EP 2041 DI 10.1016/j.fertnstert.2008.12.057 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 583LS UT WOS:000276678100047 PM 19200989 ER PT J AU Yin, XB Chen, LA Sun, LG Wang, M Luo, HH Ruan, DY Wang, YH Wang, ZM AF Yin, Xuebin Chen, Liang Sun, Liguang Wang, Ming Luo, Honghao Ruan, Diyun Wang, Yuhong Wang, Zhangmin TI WHY DO PENGUINS NOT DEVELOP SKELETAL FLUOROSIS? SO FLUORIDE LA English DT Article DE Adelie penguins; Chitin; Organic fluoride; Penguin bones; Skeletal fluorosis ID ENDEMIC FLUOROSIS; GUIZHOU PROVINCE; FLUORIDE CONTENT; BONE; CHINA; EXPOSURE; ABSORPTION; RATS AB Despite having an exceptionally high fluorine (F) concentration in their bones (up to 9000 mu g/g in the present study), radiographs of mature Adelie penguins (Pygoscelis adeliae) do not show any symptoms of skeletal fluorosis. In this research, a series of chemical fractionation and speciation analyses for F gave a tentative explanation for this seemingly abnormal fact. The results showed that the inorganic fraction of F in penguin bones represented only about one-third of the total F with the rest bound organically, mostly in the form of fluorinated chitin or its derivatives. A laboratory experiment with rats on a high F intake indicated that chitin might prevent skeletal fluorosis by effectively combining with F and inhibiting abnormal mineralization, thereby decreasing the expected increase in bone mineral density. C1 [Yin, Xuebin; Chen, Liang; Sun, Liguang; Wang, Ming; Luo, Honghao; Ruan, Diyun; Wang, Zhangmin] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Yin, Xuebin; Wang, Zhangmin] USTC CityU Joint Adv Res Ctr, ALERT, Jiangsu 215123, Peoples R China. [Chen, Liang; Wang, Ming; Ruan, Diyun] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn FU National Natural Science Foundation of China [40476001, 40231002] FX Financial support from the National Natural Science Foundation of China (No. 40476001 and 40231002) is greatly acknowledged. NR 29 TC 4 Z9 9 U1 1 U2 5 PU INT SOC FLUORIDE RESEARCH PI OCEAN VIEW PA 727 BRIGHTON RD,, OCEAN VIEW 9035, DUNEDIN, NEW ZEALAND SN 0015-4725 J9 FLUORIDE JI Fluoride PD APR-JUN PY 2010 VL 43 IS 2 BP 108 EP 118 PG 11 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 651GR UT WOS:000281916100004 ER PT J AU Gilbert, JR Gotts, SJ Carver, FW Martin, A AF Gilbert, Jessica R. Gotts, Stephen J. Carver, Frederick W. Martin, Alex TI Object repetition leads to local increases in the temporal coordination of neural responses SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE repetition priming; repetition suppression; synchrony; evoked power; MEG; theta; alpha; beta ID EVENT-RELATED POTENTIALS; MONKEY INFEROTEMPORAL CORTEX; OSCILLATORY BRAIN ACTIVITY; TOP-DOWN; NEURONAL OSCILLATIONS; CORTICAL ACTIVITY; VISUAL-ATTENTION; AMNESIC PATIENTS; WORD REPETITION; FACE PERCEPTION AB Experience with visual objects leads to later improvements in identification speed and accuracy ("repetition priming"), but generally leads to reductions in neural activity in single-cell recording studies in animals and fMRI studies in humans. Here we use event-related, source-localized MEG (ER-SAM) to evaluate the possibility that neural activity changes related to priming in occipital, temporal, and prefrontal cortex correspond to more temporally coordinated and synchronized activity, reflected in local increases in the amplitude of low-frequency activity fluctuations (i.e. evoked power) that are time-locked to stimulus onset. Subjects (N = 17) identified pictures of objects that were either novel or repeated during the session. Tests in two separate low-frequency bands (theta/alpha: 5-15 Hz; beta: 15-35 Hz) revealed increases in evoked power (5-15 Hz) for repeated stimuli in the right fusiform gyrus, with the earliest significant increases observed 100-200 ms after stimulus onset. Increases with stimulus repetition were also observed in striate/extrastriate cortex (15-35 Hz) by 200-300 ms post-stimulus, along with a trend for a similar pattern in right lateral prefrontal cortex (5-15 Hz). Our results suggest that experience-dependent reductions in neural activity may affect improved behavioral identification through more coordinated, synchronized activity at low frequencies, constituting a mechanism for more efficient neural processing with experience. C1 [Gilbert, Jessica R.; Gotts, Stephen J.; Martin, Alex] NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Carver, Frederick W.] NIMH, MEG Core Facil, NIH, Bethesda, MD 20892 USA. RP Gotts, SJ (reprint author), NIMH, Sect Cognit Neuropsychol, Lab Brain & Cognit, NIH, Bldg 10,Rm 4C-104,10 Ctr Dr,MSC 1366, Bethesda, MD 20892 USA. EM gottss@mail.nih.gov RI martin, alex/B-6176-2009; Gotts, Stephen/J-4842-2012 FU National Institute of Mental Health FX This work was supported by the National Institute of Mental Health Intramural Research Program. We'd like to thank Tom Holroyd, Richard Coppola, and Avniel Ghuman for technical advice and helpful discussions. NR 86 TC 17 Z9 17 U1 3 U2 3 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD APR PY 2010 VL 4 AR 30 DI 10.3389/fnhum.2010.00030 PG 12 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 600IE UT WOS:000277978200004 PM 20463867 ER PT J AU Goutelle, S Walsh, TJ Jelliffe, RW Golden, JA Little, E Devoe, C Mickiene, D Hayes, M Conte, JE AF Goutelle, S. Walsh, T. J. Jelliffe, R. W. Golden, J. A. Little, E. Devoe, C. Mickiene, D. Hayes, M. Conte, J. E. TI Population analysis and simulation of micafungin intrapulmonary pharmacokinetics in adult lung transplant patients SO FUNDAMENTAL & CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Goutelle, S.] Hop Pierre Garraud, Hosp Civils Lyon, Serv Pharmaceut ADCAPT, Lyon, France. [Goutelle, S.] Univ Lyon 1, CNRS, UMR Biometrie & Biol Evolut 5558, F-69622 Villeurbanne, France. [Walsh, T. J.; Mickiene, D.] NCI, Bethesda, MD 20892 USA. [Jelliffe, R. W.] Univ So Calif, Lab Appl Pharmacokinet, Los Angeles, CA USA. [Golden, J. A.; Little, E.; Hayes, M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Little, E.; Devoe, C.; Conte, J. E.] Amer Hlth Sci, San Francisco, CA USA. [Conte, J. E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0767-3981 J9 FUND CLIN PHARMACOL JI Fundam. Clin. Pharmacol. PD APR PY 2010 VL 24 SU 1 MA 243 BP 50 EP 50 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 576PH UT WOS:000276156800244 ER PT J AU Trimble, EL Abrams, JS Ansher, SS Smith, MA Zwiebel, JA Tomaszewski, JE AF Trimble, Edward L. Abrams, Jeffrey S. Ansher, Sherry S. Smith, Malcolm A. Zwiebel, James A. Tomaszewski, Joseph E. TI Developing and evaluating new drugs for cancer treatment: perspectives from the US National Cancer Institute SO FUTURE MEDICINAL CHEMISTRY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA C1 [Trimble, Edward L.; Abrams, Jeffrey S.; Ansher, Sherry S.; Smith, Malcolm A.; Zwiebel, James A.; Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diag, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Div Canc Treatment & Diag, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM tt6m@nih.gov NR 17 TC 1 Z9 1 U1 0 U2 1 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 J9 FUTURE MED CHEM JI Future Med. Chem. PD APR PY 2010 VL 2 IS 4 BP 555 EP 559 DI 10.4155/FMC.10.11 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 587UH UT WOS:000277018600009 PM 21426005 ER PT J AU Prosser, LA Lauer, RT VanSant, AF Barbe, MF Lee, SCK AF Prosser, Laura A. Lauer, Richard T. VanSant, Ann F. Barbe, Mary F. Lee, Samuel C. K. TI Variability and symmetry of gait in early walkers with and without bilateral cerebral palsy SO GAIT & POSTURE LA English DT Article DE Cerebral palsy; Gait; Variability; Symmetry; Early walking ID ELECTRONIC WALKWAY; DOWN-SYNDROME; CHILDREN; WALKING; RELIABILITY; PARAMETERS; INTERVENTIONS; ADULTS AB Purpose: Investigating gait characteristics during the early stages of walking in CP may contribute to the understanding of the development of impaired gait. The objective of this study was to investigate differences in the variability and symmetry of spatiotemporal gait characteristics during the early years of walking in children with bilateral spastic CP compared to children with similar amounts of walking experience and typical development (TD). Methods: The spatiotemporal gait parameters of 31 children (15 with spastic CP, 16 with TD) who had an average of 28.5 (18.1 SD) months of walking experience were collected using an instrumented walkway. Results: All primary spatiotemporal parameters were reduced in the CP group, who also demonstrated greater stride-to-stride variability, compared to the TD group. There were no statistically significant differences in side-to-side symmetry between groups. Implications: Clinical trials investigating gait interventions during the early years of walking in children with CP should be conducted to determine if treatment can reduce the functional limitations that are present during the emergence of walking skills. Further investigation should examine variability and symmetry in the kinematics, kinetics, and muscle activity patterns of early walkers with CP, and the effect of treatment on the variability and symmetry of walking characteristics. Published by Elsevier B.V. C1 [Prosser, Laura A.] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. [Lauer, Richard T.; VanSant, Ann F.; Barbe, Mary F.] Temple Univ, Dept Phys Therapy, Philadelphia, PA 19122 USA. [Lauer, Richard T.] Temple Univ, Dept Elect & Comp Engn, Philadelphia, PA 19122 USA. [Barbe, Mary F.] Temple Univ, Dept Anat & Cell Biol, Philadelphia, PA 19122 USA. [Lee, Samuel C. K.] Univ Delaware, Phys Therapy Dept, Newark, DE USA. [Lee, Samuel C. K.] Shriners Hosp Children, Philadelphia, PA USA. RP Prosser, LA (reprint author), NIH, Dept Rehabil Med, Bldg 10-CRC,1-1469,10 Ctr Dr, Bethesda, MD 20892 USA. EM laura.prosser@nih.gov RI Prosser, Laura/C-1242-2009; Van Mulders, Benjamin/P-1241-2014 FU Section on Pediatrics, American Physical Therapy Association; NINDS [R03NS048875]; NICHD [R01HD043859]; NIH, Clinical Center FX The authors thank Steve Capella and Jenny Lee for their assistance with data collection, and Diana Deshefy, Samuel Pierce, and Erin Sheeder for assistance with recruitment. The equipment, supplies, and travel to data collection sites for this study were funded by a Clinical Research Grant to Dr. Prosser from the Section on Pediatrics, American Physical Therapy Association. NINDS R03NS048875 to Dr. Lauer provided support for the principal investigator and a co-investigator, and NICHD R01HD043859 to Dr. Lee provided support for a co-investigator and research aides. This research was also supported in part by the Intramural Research Program of the NIH, Clinical Center. This work was completed in partial fulfillment of Dr. Prosser's Ph.D. in Physical Therapy from Temple University, Philadelphia, PA. NR 26 TC 13 Z9 14 U1 0 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD APR PY 2010 VL 31 IS 4 BP 522 EP 526 DI 10.1016/j.gaitpost.2010.03.001 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 603AY UT WOS:000278181500021 PM 20338763 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, Constance E. Everhart, James E. TI Trunk Fat Is Associated With Increased Serum Levels of Alanine Aminotransferase in the United States SO GASTROENTEROLOGY LA English DT Article DE Alanine aminotransferase; Body composition; Dual-energy x-ray absorptiometry; National Health and Nutrition Examination Survey ID VISCERAL ADIPOSE-TISSUE; INSULIN-RESISTANCE SYNDROME; BODY-MASS INDEX; LIVER-DISEASE; METABOLIC SYNDROME; HEPATIC STEATOSIS; LEG FAT; OPPOSITE ASSOCIATIONS; WAIST CIRCUMFERENCE; ARTERIAL STIFFNESS AB BACKGROUND & AIMS: Liver injury is associated with obesity and related measures, such as body mass index (BMI) and waist circumference. The relationship between liver injury and body composition has not been evaluated in a population-based study. METHODS: Using data from a US population-based survey, we examined the contributions of body composition, measured by dual-energy x-ray absorptiometry (DXA), to increased serum alanine aminotransferase (ALT) activity among 11,821 adults without viral hepatitis. Trunk fat, extremity fat, trunk lean, and extremity lean mass were divided by height squared and used to categorize subjects into quintiles; logistic regression odds ratios (OR) were calculated for increased ALT. RESULTS: Increased ALT was associated with higher measures of fat and lean mass (P < .001) after adjustment for alcohol consumption and other liver injury risk factors in separate models for each DXA measure. Trunk fat was associated with increased ALT (P < .001) in models also including any 1 of the other 3 measures. Extremity fat was independently inversely associated among women (P < .001). Trunk and extremity lean mass were not independently related to increased ALT. In models that contained all 4 DXA measures, the OR (95% confidence interval [CI]) for increased ALT for the highest, relative to lowest, quintile of trunk fat/height squared was 13.8 (95% CI: 5.4-35.3) for men and 7.8 (95% CI: 3.9-15.8) for women. When BMI, waist circumference, and trunk fat were considered together, only trunk fat remained independently associated with increased ALT. CONCLUSIONS: Trunk fat is a major body composition determinant of increased ALT, supporting the hypothesis that liver injury can be induced by metabolically active intraabdominal fat. C1 [Ruhl, Constance E.] Social & Sci Syst Inc, Silver Spring, MD 20910 USA. [Everhart, James E.] NIDDKD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU National Institute of Diabetes and Digestive and Kidney Diseases [HHSN267200700001G] FX This work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN267200700001G). NR 54 TC 22 Z9 22 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2010 VL 138 IS 4 BP 1346 EP U187 DI 10.1053/j.gastro.2009.12.053 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 575TP UT WOS:000276091800024 PM 20060831 ER PT J AU Kang, TH Chung, JY Monie, A Pai, SI Hung, CF Wu, TC AF Kang, T. H. Chung, J-Y Monie, A. Pai, S. I. Hung, C-F Wu, T-C TI Enhancing DNA vaccine potency by co-administration of xenogenic MHC class-I DNA SO GENE THERAPY LA English DT Article DE DNA vaccine; xenogenic MHC class-I; electroporation ID ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; ELECTRIC PULSES; TUMOR-ANTIGEN; GENE-TRANSFER; OPTIMIZATION; IMMUNITY; ENHANCEMENT; COMBINATION; STRATEGIES AB Intramuscular administration of DNA vaccines can lead to the generation of antigen-specific immune responses through cross-priming mechanisms. We propose a strategy that is capable of leading to local inflammation and enhancing cross-priming, thus resulting in improved antigen-specific immune responses. Therefore, in this study, we evaluated the immunological responses elicited through electroporation-mediated intramuscular administration of a DNA vaccine encoding calreticulin (CRT) linked to human papillomavirus type 16 E7 (CRT-E7) in combination with DNA expressing HLA-A2 as compared with CRT-E7 DNA vaccination alone. We found that the co-administration of a DNA vaccine in conjunction with a DNA encoding a xenogenic major histocompatibility complex (MHC) molecule could significantly enhance the E7-specific CD8+ T-cell immune responses and antitumor effects against an E7-expressing tumor, TC-1, in C57BL/6 tumor-bearing mice. Furthermore, a similar enhancement in E7-specific immune responses was observed by the co-administration of CRT-E7 DNA with DNA encoding other types of xenogenic MHC class-I molecules. This strategy was also applicable to another antigenic system, ovalbumin. Further characterization of the injection site revealed that the co-administration of HLA-A2 DNA led to a significant increase in the number of infiltrating CD8+ T lymphocytes and CD11b/c+ antigen-presenting cells. Furthermore, the E7-specific immune responses generated by intramuscular co-administration of CRT-E7 with HLA-A2 DNA were reduced in HLA-A2 transgenic mice. Thus, our data suggest that intramuscular co-administration of DNA encoding xenogenic MHC class-I can further improve the antigen-specific immune responses, as well as antitumor effects generated by DNA vaccines through enhancement of cross-priming mechanisms. Gene Therapy (2010) 17, 531-540; doi: 10.1038/gt.2009.152; published online 26 November 2009 C1 [Kang, T. H.; Monie, A.; Hung, C-F; Wu, T-C] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Chung, J-Y] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Pai, S. I.] Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. [Hung, C-F; Wu, T-C] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. [Wu, T-C] Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Wu, T-C] Johns Hopkins Med Inst, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Wu, TC (reprint author), Johns Hopkins Univ, Dept Pathol, Sch Med, CRBII Room 309,1550 Orleans St, Baltimore, MD 21231 USA. EM wutc@jhmi.edu OI Chung, Joon-Yong/0000-0001-5041-5982 FU American Cancer Society; National Cancer Institute SPORE in Cervical Cancer [P50 CA098252]; [1 RO1 CA114425-01] FX This work was supported by the American Cancer Society (CF Hung) and National Cancer Institute SPORE in Cervical Cancer P50 CA098252 and the 1 RO1 CA114425-01 (T-C Wu). NR 31 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2010 VL 17 IS 4 BP 531 EP 540 DI 10.1038/gt.2009.152 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 580CZ UT WOS:000276425800011 PM 19940864 ER PT J AU Ziauddin, MF Guo, ZS O'Malley, ME Austin, F Popovic, PJ Kavanagh, MA Li, J Sathaiah, M Thirunavukarasu, P Fang, B Lee, YJ Bartlett, DL AF Ziauddin, M. F. Guo, Z. S. O'Malley, M. E. Austin, F. Popovic, P. J. Kavanagh, M. A. Li, J. Sathaiah, M. Thirunavukarasu, P. Fang, B. Lee, Y. J. Bartlett, D. L. TI TRAIL gene-armed oncolytic poxvirus and oxaliplatin can work synergistically against colorectal cancer SO GENE THERAPY LA English DT Article DE virotherapy; vaccinia; gene therapy; chemotherapy; colorectal cancer ID VACCINIA VIRUS; PERITONEAL CARCINOMATOSIS; COLON-CANCER; INDUCED APOPTOSIS; THYMIDINE KINASE; LIGAND TRAIL; THERAPY; CHEMOTHERAPY; RESISTANCE; COMBINATION AB We have explored a unique combination therapy for metastatic colorectal cancer. This strategy combines a potent and new oncolytic poxvirus expressing a membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or TNFSF10) and oxaliplatin (Ox) chemotherapy. We hypothesized that TRAIL expression would increase the efficacy of the oncolytic poxvirus, and that the therapeutic efficacy would be further enhanced by combination with chemotherapy. The cytotoxicity to cancer cells by Ox, oncolytic vaccinia virus (VV) and trail gene-armed VV alone or in combination was tested in vitro. The trail gene armed oncolytic VV-expressed high levels of TRAIL in infected cancer cells and had greater potency as a cytotoxic agent compared with the parent VV. Ox alone exerted concentration-dependent cytotoxicity. In vitro, the combination of the two agents applied at suboptimal concentrations for individual therapy displayed synergy in inducing cancer cells into enhanced levels of apoptosis/necrosis. Western blot analyses were consistent with the notion that TRAIL induced cancer cell death mainly through apoptosis, whereas Ox and vJS6 induced cell death more through non-apoptotic death pathways. In two aggressive colorectal carcinomatosis models derived from human HCT116 and murine MC38 cells, the combination therapy displayed synergistic or additive antitumor activity and prolonged the survival of the tumor-bearing mice compared with either Ox chemotherapy or vvTRAIL-mediated oncolytic gene therapy alone. This combination strategy may provide a new avenue to treating peritoneal carcinomatosis and other types of metastases of colorectal cancer. Gene Therapy (2010) 17, 550-559; doi: 10.1038/gt.2010.5; published online 25 February 2010 C1 [Bartlett, D. L.] Univ Pittsburgh, Dept Surg, Div Surg Oncol, Sch Med, Pittsburgh, PA 15213 USA. [Ziauddin, M. F.; Guo, Z. S.; O'Malley, M. E.; Austin, F.; Popovic, P. J.; Li, J.; Sathaiah, M.; Thirunavukarasu, P.; Lee, Y. J.; Bartlett, D. L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. [Kavanagh, M. A.; Bartlett, D. L.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Fang, B.] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA. RP Bartlett, DL (reprint author), Univ Pittsburgh, Dept Surg, Div Surg Oncol, Sch Med, UPCI Res Pavil,Suite 1-46,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM bartlettdl@upmc.edu FU NIH [CA100415]; David C Koch Regional Therapy Cancer Center FX We thank Ms Hui Xu for technical assistance and Ms Eve Blasko for excellent administrative assistance. This work was supported in part by the NIH R01 grant CA100415, the Intramural Research Program of the NIH and by David C Koch Regional Therapy Cancer Center. NR 52 TC 13 Z9 15 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2010 VL 17 IS 4 BP 550 EP 559 DI 10.1038/gt.2010.5 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 580CZ UT WOS:000276425800013 PM 20182517 ER PT J AU Ordaz, SJ Lenroot, RK Wallace, GL Clasen, LS Blumenthal, JD Schmitt, JE Giedd, JN AF Ordaz, S. J. Lenroot, R. K. Wallace, G. L. Clasen, L. S. Blumenthal, J. D. Schmitt, J. E. Giedd, J. N. TI Are there differences in brain morphometry between twins and unrelated singletons? A pediatric MRI study SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Adolescent; brain; child; singleton; twin ID BIRTH-WEIGHT; COGNITIVE-ABILITIES; DEVELOPING-CHILDREN; ADOLESCENCE; GROWTH; VARIABILITY; CHILDHOOD; PRETERM; INTELLIGENCE; MULTIVARIATE AB Twins provide a unique capacity to explore relative genetic and environmental contributions to brain development, but results are applicable to non-twin populations only to the extent that twin and singleton brains are alike. A reason to suspect differences is that as a group twins are more likely than singletons to experience adverse prenatal and perinatal events that may affect brain development. We sought to assess whether this increased risk leads to differences in child or adolescent brain anatomy in twins who do not experience behavioral or neurological sequelae during the perinatal period. Brain MRI scans of 185 healthy pediatric twins (mean age = 11.0, SD = 3.6) were compared to scans of 167 age- and sex-matched unrelated singletons on brain structures measured, which included gray and white matter lobar volumes, ventricular volume, and area of the corpus callosum. There were no significant differences between groups for any structure, despite sufficient power for low type II (i.e. false negative) error. The implications of these results are twofold: (1) within this age range and for these measures, it is appropriate to include healthy twins in studies of typical brain development, and (2) findings regarding heritability of brain structures obtained from twin studies can be generalized to non-twin populations. C1 [Ordaz, S. J.; Lenroot, R. K.; Wallace, G. L.; Clasen, L. S.; Blumenthal, J. D.; Giedd, J. N.] NIMH, Child Psychiat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Ordaz, S. J.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Lenroot, R. K.] Univ New S Wales, Sydney, NSW, Australia. [Lenroot, R. K.] Prince Wales Med Res Inst, Sydney, NSW, Australia. [Schmitt, J. E.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Schmitt, J. E.] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. [Schmitt, J. E.] Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 4C110,10 Ctr Dr, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Wallace, Gregory/0000-0003-0329-5054 FU National Institute of Mental Health (NIH) [MH-20030, MH-65322] FX This work was supported by the Intramural Research Program of the NIH and by National Institute of Mental Health (NIH grants MH-20030 and MH-65322). The authors would like to thank the participants and their families for their time, and also Elizabeth Molloy, Michael Rosenthal, Blythe Rose and Kristin Taylor for their assistance with data collection. NR 53 TC 12 Z9 12 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD APR PY 2010 VL 9 IS 3 BP 288 EP 295 DI 10.1111/j.1601-183X.2009.00558.x PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 582NN UT WOS:000276604800004 PM 20100212 ER PT J AU Shriner, D Adeyemo, A Chen, GJ Rotimi, CN AF Shriner, Daniel Adeyemo, Adebowale Chen, Guanjie Rotimi, Charles N. TI Practical Considerations for Imputation of Untyped Markers in Admixed Populations SO GENETIC EPIDEMIOLOGY LA English DT Article DE admixture; African American; coverage; reference panel ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; GENOTYPE DATA; LINKAGE-DISEQUILIBRIUM; MISSING GENOTYPES; INFERENCE; ADMIXTURE; PHASE; SNPS; INDIVIDUALS AB Imputation of genotypes for markers untyped in a study sample has become a standard approach to increase genome coverage in genome-wide association studies at practically zero cost. Most methods for imputing missing genotypes extend previously described algorithms for inferring haplotype phase. These algorithms generally fall into three classes based on the underlying model for estimating the conditional distribution of haplotype frequencies: a cluster-based model, a multinomial model, or a population genetics-based model. We compared BEAGLE, PLINK, and MACH, representing the three classes of models, respectively, with specific attention to measures of imputation success and selection of the reference panel for an admixed study sample of African Americans. Based on analysis of chromosome 22 and after calibration to a fixed level of 90% concordance between experimentally determined and imputed genotypes, MACH yielded the largest absolute number of successfully imputed markers and the largest gain in coverage of the variation captured by Hap Map reference panels. Following the common practice of performing imputation once, the Yoruba in Ibadan, Nigeria (YRI) reference panel outperformed other Hap Map reference panels, including (1) African ancestry from Southwest USA (ASW) data, (2) an unweighted combination of the Northern and Western Europe (CEU) and YRI data into a single reference panel, and (3) a combination of the CEU and YRI data into a single reference panel with weights matching estimates of admixture proportions. For our admixed study sample, the optimal strategy involved imputing twice with the Hap Map CEU and YRI reference panels separately and then merging the data sets. Genet. Epidemiol. 34:258-265, 2010. Published 2009 Wiley-Liss, Inc. C1 [Shriner, Daniel; Adeyemo, Adebowale; Chen, Guanjie; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. RP Shriner, D (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA. EM shrinerda@mail.nih.gov OI Adeyemo, Adebowale/0000-0002-3105-3231 FU National Institutes of Health [S06GM008016-32010, S06GM008016-380111]; Coriell Institute for Medical Research FX The Howard University Family Study was supported by National Institutes of Health grants S06GM008016-320107 to C. N. R and S06GM008016-380111 to A. A. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of the National Institutes of Health. Genotyping support was provided by the Coriell Institute for Medical Research. NR 35 TC 19 Z9 21 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD APR PY 2010 VL 34 IS 3 BP 258 EP 265 DI 10.1002/gepi.20457 PG 8 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 580KW UT WOS:000276448100008 PM 19918757 ER PT J AU Basavaraju, U Shebl, F Palmer, AJ Hold, GL Rabkin, CS El-Omar, EM AF Basavaraju, U. Shebl, F. Palmer, A. J. Hold, G. L. Rabkin, C. S. El-Omar, E. M. TI CYTOKINE GENE POLYMORPHISMS, CYTOKINE LEVELS AND RISK OF COLORECTAL NEOPLASIA IN THE SCREENED POPULATION OF NORTHEAST SCOTLAND SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY MAR 22-25, 2010 CL Liverpool, ENGLAND SP British Soc Gastroenterol C1 [Basavaraju, U.; Palmer, A. J.; Hold, G. L.; El-Omar, E. M.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Shebl, F.; Rabkin, C. S.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2010 VL 59 SU 1 BP A44 EP A45 DI 10.1136/gut.2009.209015d PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577ZT UT WOS:000276263700108 ER PT J AU Hold, G El-Omar, E Chow, W Risch, H Gammon, M Vaughan, T Lissowska, J Lochhead, P Rabkin, C Ng, M AF Hold, G. El-Omar, E. Chow, W. Risch, H. Gammon, M. Vaughan, T. Lissowska, J. Lochhead, P. Rabkin, C. Ng, M. TI ASSESSMENT OF NOVEL GENETIC POLYMORPHISMS AND RISK OF UPPER GASTROINTESTINAL CARCINOMA SO GUT LA English DT Meeting Abstract CT Annual General Meeting of the British-Society-of-Gastroenterology CY MAR 22-25, 2010 CL Liverpool, ENGLAND SP British Soc Gastroenterol C1 [Hold, G.] Gastrointestinal Res Grp, Aberdeen, Scotland. [El-Omar, E.] Inst Med Sci, Div Med & Dent, Aberdeen, Scotland. [Chow, W.; Rabkin, C.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Risch, H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Gammon, M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Vaughan, T.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Publ Hlth, Program Epidemiol, Seattle, WA 98195 USA. [Lissowska, J.] Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. [Lissowska, J.] M Sklodowska Curie Inst Oncol, Warsaw, Poland. [Lochhead, P.] Univ Aberdeen, Div Med & Dent, Aberdeen, Scotland. [Ng, M.] Yale Univ, Sch Med, Div Med & Dent, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD APR PY 2010 VL 59 SU 1 BP A21 EP A22 DI 10.1136/gut.2009.208959z PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 577ZT UT WOS:000276263700053 ER PT J AU Massad, LS Evans, CT Wilson, TE Goderre, JL Hessol, NA Henry, D Colie, C Strickler, HD Levine, AM Watts, DH Weber, KM AF Massad, L. Stewart Evans, Charlesnika T. Wilson, Tracey E. Goderre, Johanna L. Hessol, Nancy A. Henry, Donna Colie, Christine Strickler, Howard D. Levine, Alexandra M. Watts, D. Heather Weber, Kathleen M. TI Knowledge of cervical cancer prevention and human papillomavirus among women with HIV SO GYNECOLOGIC ONCOLOGY LA English DT Article DE HPV; Cervical cancer prevention; Pap test; Health education; HIV in women ID HUMAN-IMMUNODEFICIENCY-VIRUS; PAPANICOLAOU SMEARS; INTERAGENCY HIV; FOLLOW-UP; HPV; INFECTION; COLPOSCOPY; ADHERENCE; ABNORMALITIES; INFORMATION AB Objective. To assess knowledge of and attitudes towards human papillomavirus (HPV), Pap testing, and the HPV vaccine. Methods. In a multicenter U.S. cohort study, women with the human immunodeficiency virus (HIV) and at-risk comparison women completed 44-item standardized self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results were correlated with demographic variables, measures of education and attention, and medical factors. Data were clustered using principal component analysis. Significant associations were assessed in multivariable models. Results. Among 1588 women, HIV seropositive women better understood facts about cervical cancer prevention and HPV than seronegative women, but both had substantial knowledge deficits. Almost all women considered Pap testing important, although 53% of HIV seropositive and 48% of seronegative women considered cervical cancer not preventable (P = 0.21). Only 44% of HIV seropositive women knew Paps assess the cervix, versus 42% of HIV seronegative women (P = 0.57). Both groups understood that HPV causes genital warts and cervical cancer (67% of HIV seropositive vs. 55% of seronegative women, P = 0.002). About half of both groups considered HPV vaccination extremely important for cervical cancer prevention. HIV seronegative women were more likely to report learning of HPV vaccination through advertising than from clinicians (81% vs. 64%, P<0.0001). Conclusion. High risk women need effective education about cervical cancer prevention, HPV, and HPV vaccination. (C) 2010 Elsevier Inc. All rights reserved. C1 [Massad, L. Stewart] Washington Univ, Sch Med, St Louis, MO USA. [Evans, Charlesnika T.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Evans, Charlesnika T.] Hines VA Med Ctr, Dept Vet Affairs, Chicago, IL USA. [Wilson, Tracey E.] Downstate Med Ctr, Brooklyn, NY USA. [Goderre, Johanna L.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Hessol, Nancy A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Henry, Donna] Montefiore Med Ctr, Bronx, NY 10467 USA. [Colie, Christine] Georgetown Univ, Sch Med, Washington, DC USA. [Strickler, Howard D.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Levine, Alexandra M.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Levine, Alexandra M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Weber, Kathleen M.] CORE Ctr John Stroger Hosp Cook Cty, Chicago, IL USA. RP Massad, LS (reprint author), Div Gynecol Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA. EM massadl@wudosis.wustl.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute [R01 CA85178-01]; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Data in this manuscript were collected by the Women's Interagency HIV Study (WIHS) Collaborative Study Group with centers (Principal Investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff); Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (Alexandra Levine); Chicago Consortium (Mardge Cohen); Data Coordinating Center (Stephen Gange). The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). H.D. Strickler was supported by NCI R01 CA85178-01. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 34 TC 15 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2010 VL 117 IS 1 BP 70 EP 76 DI 10.1016/j.ygyno.2009.12.030 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 582JV UT WOS:000276594200014 PM 20106513 ER PT J AU Byron, SA Gartside, MG Wellens, CL Goodfellow, PJ Birrer, MJ Campbell, IG Pollock, PM AF Byron, Sara A. Gartside, Michael G. Wellens, Candice L. Goodfellow, Paul J. Birrer, Michael J. Campbell, Ian G. Pollock, Pamela M. TI FGFR2 mutations are rare across histologic subtypes of ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian carcinoma; FGFR2; Mutation ID BETA-CATENIN MUTATION; TUMOR-CELL LINES; APERT-SYNDROME; ENDOMETRIAL CARCINOMA; SURFACE EPITHELIUM; STRUCTURAL BASIS; STAGE-III; EXPRESSION; ACTIVATION; DYSPLASIA AB Objective. Ovarian cancer is the leading cause of death from gynecologic malignancies in the Western world. Fibroblast growth factor receptor (FGFR) signaling has been implicated to play a role in ovarian tumorigenesis. Mutational activation of one member of this receptor family, FGFR2, is a frequent event in endometrioid endometrial cancer. Given the similarities in the histologic and molecular genetics of ovarian and endometrial cancers, we hypothesized that activating FGFR2 mutations may occur in a subset of endometrioid ovarian tumors, and possibly other histotypes. Methods. Six FGFR2 exons were sequenced in 120 primary ovarian tumors representing the major histologic subtypes. Results. FGFR2 mutation was detected at low frequency in endometrioid (1/46, 2.2%) and serous (1/41, 2.4%) ovarian cancer. No mutations were detected in clear cell, mucinous, or mixed histology tumors or in the ovarian cancer cell lines tested. Functional characterization of the FGFR2 mutations confirmed that the mutations detected in ovarian cancer result in receptor activation. Conclusions. Despite the low incidence of FGFR2 mutations in ovarian cancer, the two FGFR2 mutations identified in ovarian tumors (S252W, Y376C) overlap with the oncogenic mutations previously identified in endometrial tumors, suggesting activated FGFR2 may contribute to ovarian cancer pathogenesis in a small subset of ovarian tumors. (C) 2009 Elsevier Inc. All rights reserved. C1 [Byron, Sara A.; Gartside, Michael G.; Wellens, Candice L.; Pollock, Pamela M.] Translat Genom Res Inst, Canc & Cell Biol Div, Phoenix, AZ 85004 USA. [Goodfellow, Paul J.] Washington Univ, Sch Med, Siteman Canc Ctr, Barnes Jewish Hosp, St Louis, MO 63110 USA. [Birrer, Michael J.] NCI, Cell & Canc Biol Dept, Ctr Canc Res, Bethesda, MD 20892 USA. [Campbell, Ian G.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [Campbell, Ian G.] Peter MacCallum Canc Ctr, Victorian Breast Canc Res Consortium, Canc Genet Lab, Melbourne, Vic, Australia. RP Pollock, PM (reprint author), Translat Genom Res Inst, Canc & Cell Biol Div, 445 N 5th St, Phoenix, AZ 85004 USA. EM ppollock@tgen.org RI campbell, Ian/F-6006-2011 FU Department of Defense [W81XWH-08-1-0244]; National Health and Medical Research Council (Australia); Victorian Breast Cancer Research Consortium (Australia); American Cancer Society [PF-07-215-01-TBE] FX We would like to thank the TGen Sequencing Core for their excellent work and Dr. John Carpten (Translational Genomics Research Institute) for providing ovarian cancer cell line DNAs. We gratefully acknowledge funding from the Department of Defense CDMRP Ovarian Cancer Research Program (W81XWH-08-1-0244, PMP), the National Health and Medical Research Council (Australia) (IGC), the Victorian Breast Cancer Research Consortium (Australia) (IGC), and the American Cancer Society (PF-07-215-01-TBE, SAB). NR 39 TC 18 Z9 21 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2010 VL 117 IS 1 BP 125 EP 129 DI 10.1016/j.ygyno.2009.12.002 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 582JV UT WOS:000276594200022 PM 20106510 ER PT J AU Lakatta, EG AF Lakatta, Edward G. TI A paradigm shift for the heart's pacemaker SO HEART RHYTHM LA English DT Editorial Material DE Ca(2+)/calmodulin-dependent protein kinase II (CaMKII); Cardiac sinoatrial node; Ion channel; Local calcium release; Pacemaker cell; Phospholamban; Protein kinase A; Ryanodine receptor; Sarcoplasmic reticulum ID SINOATRIAL NODAL CELLS; DIASTOLIC DEPOLARIZATION; RYANODINE RECEPTOR; CA2+ RELEASES; BASAL; STIMULATION C1 NIA Intramural Res Program, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA Intramural Res Program, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000863-02] NR 17 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD APR PY 2010 VL 7 IS 4 BP 559 EP 564 DI 10.1016/j.hrthm.2009.12.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 576ZV UT WOS:000276190000022 PM 20156611 ER PT J AU Sloand, EM Barrett, AJ AF Sloand, Elaine M. Barrett, A. J. TI Immunosuppression for Myelodysplastic Syndrome: How Bench to Bedside to Bench Research Led to Success SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Immunosuppression; Myelodysplastic syndrome; Tumor necrosis factor; IFN gamma ID NECROSIS-FACTOR-ALPHA; BONE-MARROW-CELLS; RESIDUAL DISEASE DETECTION; CYCLOSPORINE-A THERAPY; ANTITHYMOCYTE GLOBULIN; IN-VITRO; APLASTIC-ANEMIA; FUSION PROTEIN; MDS PATIENTS; WILMS-TUMOR AB Laboratory evidence and clinical evidence suggest that some patients with myelodysplastic syndrome (MDS) have immunologically mediated disease. This article describes the laboratory evidence supporting a role for the immune system in the marrow failure of MDS and clinical trials using IST in these patients. C1 [Sloand, Elaine M.; Barrett, A. J.] NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, Div Intramural Res, Bldg 10 CRC,4-5230,10 Ctr Dr, Bethesda, MD 20892 USA. EM sloande@nhlbi.nih.gov FU Intramural NIH HHS [ZIA HL006106-02] NR 66 TC 13 Z9 14 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 331 EP + DI 10.1016/j.hoc.2010.02.009 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300005 PM 20359629 ER PT J AU Beachy, SH Aplan, PD AF Beachy, Sarah H. Aplan, Peter D. TI Mouse Models of Myelodysplastic Syndromes SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Myelodysplastic syndrome; Mouse model; Xenotransplant; Genetically engineered mice; Hoxa ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MITOCHONDRIAL-DNA MUTATIONS; EMBRYONIC STEM-CELLS; TRANSGENIC MICE; SCID MICE; HEMATOPOIETIC PRECURSORS; ANTITHYMOCYTE GLOBULIN; NOD/SCID MICE; BONE-MARROW AB Three general approaches have been used to model myelodysplastic syndrome (MDS) in mice, including treatment with mutagens or carcinogens, xenotransplantation of human MDS cells, and genetic engineering of mouse hematopoietic cells. This article discusses the phenotypes observed in available mouse models for MDS with a concentration on a model that leads to aberrant expression of conserved homeobox genes that are important regulators of normal hematopoiesis. Using these models of MDS should allow a more complete understanding of the disease process and provide a platform for preclinical testing of therapeutic approaches. C1 [Beachy, Sarah H.; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, 8901 Wisconsin Ave,Navy 8 Room 5101, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Aplan, Peter/K-9064-2016 FU National Institutes of Health, National Cancer Institute FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 71 TC 10 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 2010 VL 24 IS 2 BP 361 EP + DI 10.1016/j.hoc.2010.02.002 PG 16 WC Oncology; Hematology SC Oncology; Hematology GA 588BE UT WOS:000277040300007 PM 20359631 ER PT J AU Wang, H Park, O Lafdil, F Shen, KZ Horiguchi, N Yin, S Fu, XY Kunos, G Gao, B AF Wang, Hua Park, Ogyi Lafdil, Fouad Shen, Kezhen Horiguchi, Norio Yin, Shi Fu, Xin-Yuan Kunos, George Gao, Bin TI Interplay of Hepatic and Myeloid Signal Transducer and Activator of Transcription 3 in Facilitating Liver Regeneration via Tempering Innate Immunity SO HEPATOLOGY LA English DT Article ID PARTIAL-HEPATECTOMY; RAT-LIVER; MICE; STAT3; CONTRIBUTES; NEUTROPHILS; ENDOTOXIN; SURVIVAL; FAILURE; INJURY AB Liver regeneration triggered by two-thirds partial hepatectomy is accompanied by elevated hepatic levels of endotoxin, which contributes to the regenerative process, but liver inflammation and apoptosis remain paradoxically limited. Here, we show that signal transducer and activator of transcription 3 (STAT3), an important anti-inflammatory signal, is activated in myeloid cells after partial hepatectomy and its conditional deletion results in an enhanced inflammatory response. Surprisingly, this is accompanied by an improved rather than impaired regenerative response with increased hepatic STAT3 activation, which may contribute to the enhanced liver regeneration. Indeed, conditional deletion of STAT3 in both hepatocytes and myeloid cells results in elevated activation of STAT1 and apoptosis of hepatocytes, and a dramatic reduction in survival after partial hepatectomy, whereas additional global deletion of STAT1 protects against these effects. Conclusion: An interplay of myeloid and hepatic STAT3 signaling is essential to prevent liver failure during liver regeneration through tempering a strong innate inflammatory response mediated by STAT1 signaling. (HEPATOLOGY 2010;51:1354-1362.) C1 [Wang, Hua; Park, Ogyi; Lafdil, Fouad; Shen, Kezhen; Horiguchi, Norio; Yin, Shi; Gao, Bin] NIAAA, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. [Kunos, George] NIAAA, Sect Neuroendocrinol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Fu, Xin-Yuan] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU NIAAA; NIH FX This work was supported by the intramural program of NIAAA, NIH. NR 32 TC 18 Z9 19 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2010 VL 51 IS 4 BP 1354 EP 1362 DI 10.1002/hep.23430 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 581QC UT WOS:000276538100033 PM 20041412 ER PT J AU Andersen, JB Loi, R Perra, A Factor, VM Ledda-Columbano, GM Columbano, A Thorgeirsson, SS AF Andersen, Jesper B. Loi, Roberto Perra, Andrea Factor, Valentina M. Ledda-Columbano, Giovanna M. Columbano, Amedeo Thorgeirsson, Snorri S. TI Progenitor-Derived Hepatocellular Carcinoma Model in the Rat SO HEPATOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; CELL ORIGIN; FUNCTIONAL GENOMICS; OXIDATIVE STRESS; UNITED-STATES; STEM-CELLS; EXPRESSION; CANCER; GENE; LIVER AB Human hepatocellular carcinoma (HCC) is a heterogeneous disease of distinct clinical subgroups. A principal source of tumor heterogeneity may be cell type of origin, which in liver includes hepatocyte or adult stem/progenitor cells. To address this issue, we investigated the molecular mechanisms underlying the fate of the enzyme-altered preneoplastic lesions in the resistant hepatocyte (RH) model. Sixty samples classified as focal lesions, adenoma, and early and advanced HCCs were microdissected after morphological and immunohistochemical evaluation and subjected to global gene expression profiling. The analysis of progression of the persistent glutathione S-transferase (GSTP)(+) focal lesions to fully developed HCC showed that approximately 50% of persistent nodules and all HCCs expressed cytokeratin 19 (CK19), whereas 14% of remodeling nodules were CK19(+). Unsupervised hierarchical clustering of the expression profiles also grouped the samples according to CK19 expression. Furthermore, supervised analysis using the differentially expressed genes in each cluster combined with gene connectivity tools identified 1308 unique genes and a predominance of the AP-1/JUN network in the CK19+ lesions. In contrast, the CK19-negative cluster exhibited only limited molecular changes (156 differentially expressed genes versus normal liver) consistent with remodeling toward differentiated phenotype. Finally, comparative functional genomics showed a stringent clustering of CK19+ early lesions and advanced HCCs with human HCCs characterized by poor prognosis. Furthermore, the CK19-associated gene expression signature accurately predicted patient survival (P < 0.009) and tumor recurrence (P < 0.006). Conclusion: Our data establish CK19 as a prognostic marker of early neoplastic lesions and strongly suggest the progenitor derivation of HCC in the rat RH model. The capacity of CK19-associated gene signatures to stratify HCC patients according to clinical prognosis indicates the usefulness of the RH model for studies of stem/progenitor-derived HCC. (HEPATOLOGY 2010;51:1401-1409.) C1 [Andersen, Jesper B.; Factor, Valentina M.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Loi, Roberto; Perra, Andrea; Ledda-Columbano, Giovanna M.; Columbano, Amedeo] Univ Cagliari, Dept Toxicol, Oncol & Mol Pathol Unit, Cagliari, Italy. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bldg 37,Room 4146A,37 Convent Dr, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov OI Loi, Roberto/0000-0003-2371-3874; Andersen , Jesper B/0000-0003-1760-5244; Columbano, Amedeo/0000-0002-6956-9030 FU NIH, National Cancer Institute, Center for Cancer Research; Associazione Italiana Ricerca sul Cancro (AIRC), Italy FX Supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and by funds from Associazione Italiana Ricerca sul Cancro (AIRC), Italy. NR 46 TC 63 Z9 64 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2010 VL 51 IS 4 BP 1401 EP 1409 DI 10.1002/hep.23488 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 581QC UT WOS:000276538100038 PM 20054870 ER PT J AU Aweeka, FT Stek, A Best, BM Hu, C Holland, D Hermes, A Burchett, SK Read, J Mirochnick, M Capparelli, EV AF Aweeka, F. T. Stek, A. Best, B. M. Hu, C. Holland, D. Hermes, A. Burchett, S. K. Read, J. Mirochnick, M. Capparelli, E. V. CA Int Maternal Pediat Adolescent TI Lopinavir protein binding in HIV-1-infected pregnant women SO HIV MEDICINE LA English DT Article DE lopinavir; pharmacokinetics; plasma proteins; pregnancy; protein binding ID PLASMA; GLYCOPROTEIN; PHARMACOKINETICS; EXPOSURE; DRUGS AB Background Pregnancy may alter protein binding (PB) of highly bound protease inhibitors due to changes in plasma concentrations of albumin and alpha-1 acid glycoprotein (AAG). Small changes in PB can greatly impact the fraction of drug unbound (FU) exerting pharmacological effect. We report lopinavir (LPV) PB during third trimester (antepartum, AP) compared to >= 1.7 weeks postpartum (PP) to determine if FU changes compensate for reduced total concentrations reported previously. Methods P1026s enrolled women receiving LPV/ritonavir, soft gel capsules 400/100 mg or 533/133 mg twice daily. LPV FU, albumin and AAG were determined AP and PP. Results AP/PP samples were available from 29/25 women respectively with all but one woman receiving the same dose AP/PP. LPV FU was increased 18% AP vs. PP (mean 0.96 +/- 0.16% AP vs. 0.82 +/- 0.21% PP, P=0.001). Mean protein concentrations were reduced AP (AAG=477 mg/L; albumin=3.28 mg/dL) vs. PP (AAG=1007 mg/L; albumin=3.85 mg/dL) (P < 0.0001 for each comparison). AAG concentration correlated with LPV binding. Total LPV concentration did not correlate with LPV FU AP or PP. However, higher LPV concentration PP was associated with reduced PB and higher FU after adjustment for AAG. Conclusions LPV FU was higher and AAG lower AP vs. PP. The 18% increase in LPV FU AP is smaller than the reduction in total LPV concentration reported previously and is not of sufficient magnitude to eliminate the need for an increased dose during pregnancy. C1 [Aweeka, F. T.] Univ Calif San Francisco, Drug Res Unit, San Francisco, CA 94143 USA. [Stek, A.] Univ So Calif, Los Angeles, CA USA. [Best, B. M.; Holland, D.; Capparelli, E. V.] Univ Calif San Diego, San Diego, CA 92103 USA. [Hu, C.] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Hermes, A.] Abbott Labs, Abbott Pk, IL 60064 USA. [Burchett, S. K.] Childrens Hosp, Boston, MA 02115 USA. [Read, J.] NICHD, Bethesda, MD USA. [Mirochnick, M.] BU Sch Med, Boston, MA USA. RP Aweeka, FT (reprint author), Univ Calif San Francisco, Drug Res Unit, 521 Parnassus Ave, San Francisco, CA 94143 USA. EM faweeka@sfghsom.ucsf.edu RI Hu, Chengcheng/A-8391-2017 FU National Institute of Allergy and Infectious Diseases (NIAID) [U01AI068632, 1 U01 AI068616]; National Center for Research Resources [M01 RR00533, 5 M01 RR01271]; National Institute of Child Health and Human Development [N01-HD-3-3365, U01-HD-031318-11] FX The project described was supported by Grant Number U01AI068632 and 1 U01 AI068616 from the National Institute of Allergy and Infectious Diseases (NIAID). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.; This study was also supported by the General Clinical Research Center Units funded by the National Center for Research Resources (Grant M01 RR00533, 5 M01 RR01271), the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development (Contract N01-HD-3-3365), and the Pediatric Pharmacology Research Unit Network of the National Institute for Child Health and Human Development (Grant U01-HD-031318-11). NR 16 TC 31 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD APR PY 2010 VL 11 IS 4 BP 232 EP 238 DI 10.1111/j.1468-1293.2009.00767.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 563AM UT WOS:000275097600002 PM 20002783 ER PT J AU Zhai, W Xu, C Ling, Y Liu, S Deng, J Qi, Y Londos, C Xu, G AF Zhai, W. Xu, C. Ling, Y. Liu, S. Deng, J. Qi, Y. Londos, C. Xu, G. TI Increased Lipolysis in Adipose Tissues is Associated with Elevation of Systemic Free Fatty Acids and Insulin Resistance in Perilipin Null Mice SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE perilipin; lipolysis; free fatty acids; lipase; insulin resistance ID HORMONE-SENSITIVE LIPASE; PRIMARY RAT ADIPOCYTES; DIFFERENTIATION-RELATED PROTEIN; NECROSIS-FACTOR-ALPHA; TRIGLYCERIDE LIPASE; LIPID DROPLETS; FOOD-DEPRIVATION; STIMULATION; DIET; METABOLISM AB Elevated plasma levels of free fatty acids (FFAs) are thought to restrict glucose utilization and induce insulin resistance. Plasma FFA concentrations are primarily governed by lipolysis in adipocytes. Perilipin surrounds the lipid droplet in adipocytes and has a dual role in lipolysis regulation. Perilipin null mice studied by two independent laboratories exhibited similar phenotypes of reduced adipose mass and resistance to diet-induced obesity, but have inconsistent metabolic parameters such as plasma levels of FFA, glucose, and insulin. This discrepancy may be due to differences in genetic background, generation, and nutritional status of the animals examined. In this study, we examined the major metabolic parameters in 129/SvEv perilipin null mice fasted for 4 h and observed increased plasma concentrations of FFA, glycerol, glucose, and insulin. An increase in the score for the homeostasis model assessment of insulin resistance index confirmed the insulin resistance in perilipin null mice, which may be attributed to the plasma FFA elevation. Basal lipolysis was increased in adipose tissues or primary adipocytes isolated from perilipin null mice with increased mass and activity of hormone-sensitive lipase and adipose triglyceride lipase. The increased lipolytic action may accelerate FFA efflux from the adipose tissues to the bloodstream, thereby accounting for systemic FFA elevation and, hence, insulin resistance in perilipin null mice. C1 [Zhai, W.; Ling, Y.; Qi, Y.] Zhengzhou Univ, Dept Biol, Zhengzhou 450001, Peoples R China. [Zhai, W.; Xu, C.; Liu, S.; Deng, J.; Xu, G.] Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China. [Londos, C.] NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ling, Y (reprint author), Zhengzhou Univ, Dept Biol, Zhengzhou 450001, Peoples R China. EM lingye508@yahoo.com; xug@bjmu.edu.cn FU National Basic Research Program of China [2009CB941603]; National Natural Science Foundation of China [30890042, 30770803, 30670779]; Natural Science Foundation of Beijing Province of China [5072030] FX This work was supported by the National Basic Research Program of China (2009CB941603), the National Natural Science Foundation of China (30890042, 30770803, and 30670779), and the Natural Science Foundation of Beijing Province of China (5072030). Dr. G. Xu dedicates this paper to the memory of his mentor, Dr. Constantine Londos, at NIDDK, the U. S. National Institutes of Health. Dr. Londos was a scientist who firstly identified the lipid roplet-associated protein perilipins and they function to regulate lipolysis of fats stored in adipocytes. Dr. Londos passed away, 6 December 2009, while this paper was being printed. NR 45 TC 18 Z9 22 U1 1 U2 10 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD APR PY 2010 VL 42 IS 4 BP 247 EP 253 DI 10.1055/s-0029-1243599 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 575WR UT WOS:000276101200005 PM 20091459 ER PT J AU Nicodemus, KK Callicott, JH Higier, RG Luna, A Nixon, DC Lipska, BK Vakkalanka, R Giegling, I Rujescu, D St Clair, D Muglia, P Shugart, YY Weinberger, DR AF Nicodemus, Kristin K. Callicott, Joseph H. Higier, Rachel G. Luna, Augustin Nixon, Devon C. Lipska, Barbara K. Vakkalanka, Radhakrishna Giegling, Ina Rujescu, Dan St Clair, David Muglia, Pierandrea Shugart, Yin Yao Weinberger, Daniel R. TI Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging SO HUMAN GENETICS LA English DT Article ID SINGLE NUCLEOTIDE POLYMORPHISM; BIPOLAR DISORDER; JAPANESE POPULATION; NEURITE OUTGROWTH; ASSOCIATION ANALYSIS; GENETIC ASSOCIATION; SCOTTISH POPULATION; POWER CALCULATIONS; WORKING-MEMORY; NO ASSOCIATION AB The etiology of schizophrenia likely involves genetic interactions. DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis. We tested for epistasis between these genes in a schizophrenia case-control study using machine learning algorithms (MLAs: random forest, generalized boosted regression and Monte Carlo logic regression). Convergence of MLAs revealed a subset of seven SNPs that were subjected to 2-SNP interaction modeling using likelihood ratio tests for nested unconditional logistic regression models. Of the (7)C(2) = 21 interactions, four were significant at the alpha = 0.05 level: DISC1 rs1411771-CIT rs10744743 OR = 3.07 (1.37, 6.98) p = 0.007; CIT rs3847960-CIT rs203332 OR = 2.90 (1.45, 5.79) p = 0.003; CIT rs3847960-CIT rs440299 OR = 2.16 (1.04, 4.46) p = 0.038; one survived Bonferroni correction (NDEL1 rs4791707-CIT rs10744743 OR = 4.44 (2.22, 8.88) p = 0.00013). Three of four interactions were validated via functional magnetic resonance imaging (fMRI) in an independent sample of healthy controls; risk associated alleles at both SNPs predicted prefrontal cortical inefficiency during the N-back task, a schizophrenia-linked intermediate biological phenotype: rs3847960-rs440299; rs1411771-rs10744743, rs4791707-rs10744743 (SPM5 p < 0.05, corrected), although we were unable to statistically replicate the interactions in other clinical samples. Interestingly, the CIT SNPs are proximal to exons that encode the DISC1 interaction domain. In addition, the 3' UTR DISC1 rs1411771 is predicted to be an exonic splicing enhancer and the NDEL1 SNP is similar to 3,000 bp from the exon encoding the region of NDEL1 that interacts with the DISC1 protein, giving a plausible biological basis for epistasis signals validated by fMRI. C1 [Nicodemus, Kristin K.; Callicott, Joseph H.; Higier, Rachel G.; Luna, Augustin; Nixon, Devon C.; Lipska, Barbara K.; Vakkalanka, Radhakrishna; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Nicodemus, Kristin K.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [Nicodemus, Kristin K.] Univ Oxford, Dept Clin Pharmacol, Oxford OX3 7DQ, England. [Giegling, Ina; Rujescu, Dan] Univ Munich, Sect Mol & Clin Neurobiol, Dept Psychiat, D-80336 Munich, Germany. [St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen AB25 2ZD, Scotland. [Muglia, Pierandrea] GlaxoSmithKline Inc, I-37135 Verona, Italy. [Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci Ctr, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM kristin.nicodemus@well.ox.ac.uk; weinberd@mail.nih.gov OI Callicott, Joseph/0000-0003-1298-3334 NR 73 TC 41 Z9 42 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2010 VL 127 IS 4 BP 441 EP 452 DI 10.1007/s00439-009-0782-y PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 570DD UT WOS:000275650900007 PM 20084519 ER PT J AU Sergeev, YV Caruso, RC Meltzer, MR Smaoui, N MacDonald, IM Sieving, PA AF Sergeev, Y. V. Caruso, R. C. Meltzer, M. R. Smaoui, N. MacDonald, I. M. Sieving, P. A. TI Molecular modeling of retinoschisin with functional analysis of pathogenic mutations from human X-linked retinoschisis SO HUMAN MOLECULAR GENETICS LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; JUVENILE RETINOSCHISIS; XLRS1 GENE; B-WAVE; ELECTRORETINOGRAPHIC FINDINGS; ENDOPLASMIC-RETICULUM; CLINICAL PHENOTYPE; A-WAVE; PREDICTION; CHAPERONE AB Gene mutations that encode retinoschisin (RS1) cause X-linked retinoschisis (XLRS), a form of juvenile macular and retinal degeneration that affects males. RS1 is an adhesive protein which is proposed to preserve the structural and functional integrity of the retina, but there is very little evidence of the mechanism by which protein changes are related to XLRS disease. Here, we report molecular modeling of the RS1 protein and consider perturbations caused by mutations found in human XLRS subjects. In 60 XLRS patients who share 27 missense mutations, we then evaluated possible correlations of the molecular modeling with retinal function as determined by the electroretinogram (ERG) a- and b-waves. The b/a-wave ratio reflects visual-signal transfer in retina. We sorted the ERG b/a-ratios by patient age and by the mutation impact on protein structure. The majority of RS1 mutations caused minimal structure perturbation and targeted the protein surface. These patients' b/a-ratios were similar across younger and older subjects. Maximum structural perturbations from either the removal or insertion of cysteine residues or changes in the hydrophobic core were associated with greater difference in the b/a-ratio with age, with a significantly smaller ratio at younger ages, analogous to the ERG changes with age observed in mice with no RS1-protein expression due to a recombinant RS1-knockout gene. The molecular modeling suggests an association between the predicted structural alteration and/or damage to retinoschisin and the severity of XLRS as measured by the ERG analogous to the RS1-knockout mouse. C1 [Sergeev, Y. V.; Meltzer, M. R.; Sieving, P. A.] NEI, OGVFB, NIH, Bethesda, MD 20892 USA. [Caruso, R. C.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Smaoui, N.] GeneDx, Gaithersburg, MD USA. [MacDonald, I. M.] Univ Alberta, Royal Alexandra Hosp, Edmonton, AB, Canada. RP Sergeev, YV (reprint author), NEI, OGVFB, NIH, Bldg 10,Rm 10B10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sergeevy@nei.nih.gov OI MacDonald, Ian/0000-0001-7472-8385 FU National Institutes of Health [Z01-EY000476-01, Z01-DC000065-08] FX This work was supported by National Institutes of Health (Z01-EY000476-01 to Y.V.S., and Z01-DC000065-08 to P.A.S.). NR 64 TC 17 Z9 18 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 2010 VL 19 IS 7 BP 1302 EP 1313 DI 10.1093/hmg/ddq006 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 572HK UT WOS:000275818500013 PM 20061330 ER PT J AU Jiang, XS Wassif, CA Backlund, PS Song, L Holtzclaw, LA Li, Z Yergey, AL Porter, FD AF Jiang, Xiao-Sheng Wassif, Christopher A. Backlund, Peter S. Song, Li Holtzclaw, Lynne A. Li, Zheng Yergey, Alfred L. Porter, Forbes D. TI Activation of Rho GTPases in Smith-Lemli-Opitz syndrome: pathophysiological and clinical implications SO HUMAN MOLECULAR GENETICS LA English DT Article ID LINKED MENTAL-RETARDATION; NUCLEOTIDE EXCHANGE FACTOR; MOUSE MODEL; CHOLESTEROL-DEFICIENCY; CEREBELLAR HYPOPLASIA; STATISTICAL-MODEL; MASS-SPECTROMETRY; REDUCTASE GENE; LIM KINASES; IN-VIVO AB Smith-Lemli-Opitz syndrome (SLOS) is a malformation syndrome with neurocognitive deficits due to mutations of DHCR7 that impair the reduction of 7-dehydrocholesterol to cholesterol. To investigate the pathological processes underlying the neurocognitive deficits, we compared protein expression in Dhcr7(+/+) and Dhcr7(Delta 3-5/Delta 3-5) brain tissue. One of the proteins identified was cofilin-1, an actin depolymerizing factor which regulates neuronal dendrite and axon formation. Differential expression of cofilin-1 was due to increased phosphorylation. Phosphorylation of cofilin-1 is regulated by Rho GTPases through Rho-Rock-Limk-Cofilin-1 and Rac/Cdc42-Pak-Limk-Cofilin-1 pathways. Pull-down assays were used to demonstrate increased activation of RhoA, Rac1 and Cdc42 in Dhcr7(Delta 3-5/Delta 3-5) brains. Consistent with increased activation of these Rho GTPases, we observed increased phosphorylation of both Limk and Pak in mutant brain tissue. Altered Rho/Rac signaling impairs normal dendritic and axonal formation, and mutations in genes encoding regulators and effectors of the Rho GTPases underlie other human mental retardation syndromes. Thus, we hypothesized that aberrant activation of Rho/Rac could have functional consequences for dendrite and axonal growth. In vitro analysis of Dhcr7(Delta 3-5/Delta 3-5) hippocampal neurons demonstrated both axonal and dendritic abnormalities. Developmental abnormalities of neuronal process formation may contribute to the neurocognitive deficits found in SLOS and may represent a potential target for therapeutic intervention. C1 [Jiang, Xiao-Sheng; Wassif, Christopher A.; Song, Li; Porter, Forbes D.] Eunice Kennedy Shriver Natl Inst Child Hlth, Sect Mol Dysmorphol, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Backlund, Peter S.; Yergey, Alfred L.] Eunice Kennedy Shriver Natl Inst Child Hlth, Sect Mass Spectrometry & Metab, Off Sci Director, Bethesda, MD 20892 USA. [Holtzclaw, Lynne A.] Eunice Kennedy Shriver Natl Inst Child Hlth, Sect Cell Biol & Signal Transduct, Program Dev Neurosci, Bethesda, MD 20892 USA. [Li, Zheng] NIMH, Unit Synapse Dev & Plast, Gene Cognit & Psychosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHD, Sect Mol Dysmorphol, PDGEN, NIH,DHHS, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov RI Li, Zheng/I-8016-2014; OI Li, Zheng/0000-0002-2978-2531; Wassif, Christopher/0000-0002-2524-1420 FU Eunice Kennedy Shriver National Institute of Child Health, National Institutes of Health; National Institute of Mental Health, National Institutes of Health FX This work was supported by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health, National Institutes of Health; and the intramural research program of the National Institute of Mental Health, National Institutes of Health. Microscopy imaging was performed at the Microscopy & Imaging Core (National Institute of Child Health and Human Development, NIH) with the assistance of Dr Vincent Schram, Chip Dye and Dr James T. Russell. NR 52 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 2010 VL 19 IS 7 BP 1347 EP 1357 DI 10.1093/hmg/ddq011 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 572HK UT WOS:000275818500017 PM 20067919 ER PT J AU Horvath, A Bertherat, J Groussin, L Guillaud-Bataille, M Tsang, K Cazabat, L Libe, R Remmers, E Rene-Corail, F Faucz, FR Clauser, E Calender, A Bertagna, X Carney, JA Stratakis, CA AF Horvath, Anelia Bertherat, Jerome Groussin, Lionel Guillaud-Bataille, Marine Tsang, Kitman Cazabat, Laure Libe, Rosella Remmers, Elaine Rene-Corail, Fernande Faucz, Fabio Rueda Clauser, Eric Calender, Alain Bertagna, Xavier Carney, J. Aidan Stratakis, Constantine A. TI Mutations and Polymorphisms in the Gene Encoding Regulatory Subunit Type 1-Alpha of Protein Kinase A (PRKAR1A): An Update SO HUMAN MUTATION LA English DT Article DE PRKAR1A; PKA; mutations; polymorphisms; Carney complex; CNC ID NODULAR ADRENOCORTICAL DISEASE; CARNEY-COMPLEX; ENDOCRINE OVERACTIVITY; ADRENAL-HYPERPLASIA; SPOTTY PIGMENTATION; ANCHORING PROTEIN; CARDIAC MYXOMA; I-ALPHA; CAMP; DELETION AB PRKAR1A encodes the regulatory subunit type 1-alpha (RI alpha) of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Inactivating PRKAR1A mutations are known to be responsible for the multiple neoplasia and lentiginosis syndrome Carney complex (CNC). To date, at least 117 pathogenic variants in PRKAR1A have been identified (online database: http://prkar1a.nichd.nih.gov). The majority are subject to nonsense mediated mRNA decay (NMD), leading to RI alpha haploinsufficiency and, as a result, activated cAMP signaling. Recently, it became apparent that CNC may be caused not only by RI alpha haploinsufficiency, but also by the expression of altered Rh protein, as proven by analysis of expressed mutations in the gene, consisting of aminoacid substitutions and in-frame genetic alterations. In addition, a new subgroup of mutations that potentially escape NMD and result in CNC through altered (rather than missing) protein has been analyzed these are frame-shifts in the 3' end of the coding sequence that shift the stop codon downstream of the normal one. The mutation detection rate in CNC patients is recently estimated at above 60%; PRKAR1A mutation-negative CNC patients are characterized by significant phenotypic heterogeneity. In this report, we present a comprehensive analysis of all presently known PRKAR1A sequence variations and discuss their molecular context and clinical phenotype. Hum Mutat 31:369-379, 2010. Published 2010 Wiley-Liss, Inc. C1 [Horvath, Anelia; Tsang, Kitman; Faucz, Fabio Rueda; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Bertherat, Jerome; Groussin, Lionel; Guillaud-Bataille, Marine; Cazabat, Laure; Libe, Rosella; Rene-Corail, Fernande; Clauser, Eric; Bertagna, Xavier] Inst Cochin, Endocrinol Metab & Canc Dept, CNRS, INSERM,U567,UMR8104, Paris, France. [Bertherat, Jerome; Groussin, Lionel; Libe, Rosella; Rene-Corail, Fernande; Bertagna, Xavier] Univ Paris 05, Paris, France. [Bertherat, Jerome; Groussin, Lionel; Bertagna, Xavier] Hop Cochin, AP HP, Dept Endocrinol, F-75674 Paris, France. [Guillaud-Bataille, Marine; Clauser, Eric] Hop Cochin, AP HP, Dept Biostat, F-75674 Paris, France. [Remmers, Elaine] NIAMS, Genet & Genom Branch, Bethesda, MD USA. [Faucz, Fabio Rueda] Pontificia Univ Catolica Parana, Mol Genet Lab, Curitiba, Parana, Brazil. [Calender, Alain] Univ Lyon 1, CNRS, UMR 5201, Unit Genet & Endocrine Tumors, F-69365 Lyon, France. [Calender, Alain] CHU Lyon, Lyon, France. Ohio State Univ, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, PDEGEN, NIH,CRC, Bldg 10,Room I-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Faucz, Fabio/C-1607-2009 FU National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH) [Z01-HD-000642-04] FX We thank the patients and their families who participated in our research studies and donated their time for this investigation. This work was supported, in part, by the National Institute of Child Health and Human Development (NICHD), intramural National Institutes of Health (NIH) project Z01-HD-000642-04 to Dr. C. Stratakis, and, in part, by the NIH Clinical Center. NR 52 TC 74 Z9 77 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2010 VL 31 IS 4 BP 369 EP 379 DI 10.1002/humu.21178 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 585FS UT WOS:000276810600001 PM 20358582 ER PT J AU Zhu, JL Obel, C Basso, O Olsen, J AF Zhu, Jin Liang Obel, Carsten Basso, Olga Olsen, Jorn TI Parental infertility and developmental coordination disorder in children SO HUMAN REPRODUCTION LA English DT Article DE assisted reproduction technologies; developmental coordination disorder; infertility ID INTRACYTOPLASMIC SPERM INJECTION; IN-VITRO FERTILIZATION; NATIONAL BIRTH COHORT; ASSISTED CONCEPTION; ICSI CHILDREN; BORN; SINGLETONS; IVF; AGE; VALIDITY AB It has previously been reported that children born after infertility treatment had a slight delay in early motor milestones. In this study, we examined whether children of infertile couples with or without infertility treatment had a higher risk of developmental coordination disorder (DCD). We used data on parental infertility and DCD among 23 167 singletons from the Danish National Birth Cohort (1996-2002). Data on time to pregnancy (TTP) and infertility treatment were collected early in pregnancy. Data on DCD in children were collected using the Developmental Coordination Disorder Questionnaire, filled in by the mothers during follow-up when the children were 7 years old. We used the recommended cut-off for the age group to classify children. Compared with children born of fertile couples, children conceived after a waiting TTP of longer than 12 months had a slightly higher risk of DCD [odds ratio (OR) 1.35, 95% confidence interval (CI) 1.03-1.77], but the estimated OR was not significant in children born after infertility treatment (OR 1.19, 95% CI 0.86-1.66). None of the individual treatment procedures was significantly associated with a higher risk of DCD. Children of parents who had not planned their pregnancy showed no elevated risk. Our findings are overall reassuring, although it is possible that low fecundity may be associated with a modestly increased risk of DCD. C1 [Zhu, Jin Liang; Obel, Carsten; Olsen, Jorn] Univ Aarhus, Sch Publ Hlth, Dept Epidemiol, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. [Obel, Carsten] Aarhus Univ Hosp, Dept Obstet, Perinatal Epidemiol Res Unit, DK-8200 Aarhus, Denmark. [Obel, Carsten] Aarhus Univ Hosp, Dept Paediat, Perinatal Epidemiol Res Unit, DK-8200 Aarhus N, Denmark. [Basso, Olga] NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. [Olsen, Jorn] Univ Calif Los Angeles, Dept Epidemiol, Sch Publ Hlth, Los Angeles, CA 90095 USA. RP Zhu, JL (reprint author), Univ Aarhus, Sch Publ Hlth, Dept Epidemiol, Danish Epidemiol Sci Ctr, Bartholins Alle 2, DK-8000 Aarhus C, Denmark. EM zjl@soci.au.dk RI Basso, Olga/E-5384-2010; Olsen, Jorn/F-8801-2015 OI Basso, Olga/0000-0001-9298-4921; Olsen, Jorn/0000-0001-7462-5140 FU Danish Medical Research Council [271-07-0402]; NIH, National Institute of Environmental Health Sciences [Z01 ES044003]; Danish National Research Foundation; Pharmacy Foundation; Egmont Foundation; March of Dimes Birth Defects Foundation; Augustinus Foundation; Health Foundation FX This work was supported by a grant from the Danish Medical Research Council (No. 271-07-0402) and, in part, by the Intramural program of the NIH, National Institute of Environmental Health Sciences (Z01 ES044003). The Danish National Research Foundation has established the Danish Epidemiology Science Centre that initiated and created the Danish National Birth Cohort. The cohort is furthermore a result of a major grant from this Foundation. Additional support for the Danish National Birth Cohort is obtained from the Pharmacy Foundation, the Egmont Foundation, the March of Dimes Birth Defects Foundation, the Augustinus Foundation and the Health Foundation. NR 32 TC 9 Z9 9 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2010 VL 25 IS 4 BP 908 EP 913 DI 10.1093/humrep/deq010 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 572HH UT WOS:000275818200013 PM 20139428 ER PT J AU Matsusaka, T Asano, T Niimura, F Kinomura, M Shimizu, A Shintani, A Pastan, I Fogo, AB Ichikawa, I AF Matsusaka, Taiji Asano, Takako Niimura, Fumio Kinomura, Masaru Shimizu, Akihiro Shintani, Ayumi Pastan, Ira Fogo, Agnes B. Ichikawa, Iekuni TI Angiotensin Receptor Blocker Protection Against Podocyte-Induced Sclerosis Is Podocyte Angiotensin II Type 1 Receptor-Independent SO HYPERTENSION LA English DT Article DE podocyte; glomerulosclerosis; chronic renal failure; AT(1) antagonist; knockout mice; proteinuria ID GLOMERULAR CAPILLARY WALL; MOUSE MODEL; DIABETIC-NEPHROPATHY; INTACT GLOMERULUS; IN-VIVO; GLOMERULOSCLEROSIS; INHIBITION; INJURY; MICE; RATS AB In the present study, we tested the hypothesis that the renoprotective effect of an angiotensin receptor blocker depends on the angiotensin II type 1 (AT(1)) receptor on podocytes. For this purpose, we generated podocyte-specific knockout mice for the AT(1) gene (Agtr1a) and crossed with NEP25, in which selective podocyte injury can be induced by immunotoxin, anti-Tac(Fv)-PE38. Four weeks after the addition of anti-Tac(Fv)-PE38, urinary albumin: creatinine ratio was not attenuated in Agtr1a knockout/NEP25 mice (n = 18) compared with that in control NEP25 mice (n = 13; 8.08 +/- 2.41 in knockout versus 4.84 +/- 0.73 in control). Both strains of mice showed similar degrees of sclerosis (0.66 +/- 0.17 versus 0.82 +/- 0.27 on a 0 to 4 scale) and downregulation of nephrin (5.78 +/- 0.45 versus 5.65 +/- 0.58 on a 0 to 8 scale). In contrast, AT(1) antagonist or an angiotensin I-converting enzyme inhibitor, but not hydralazine, remarkably attenuated proteinuria and sclerosis in NEP25 mice. Moreover, continuous angiotensin II infusion induced microalbuminuria similarly in both Agtr1a knockout and wild-type mice. Thus, angiotensin inhibition can protect podocytes and prevent the development of glomerulosclerosis independent of podocyte AT(1). Possible mechanisms include inhibitory effects on AT(1) of other cells or through mechanisms independent of AT(1). Our study further demonstrates that measures that directly affect only nonpodocyte cells can have beneficial effects even when sclerosis is triggered by podocyte-specific injury. (Hypertension. 2010;55:967-973.) C1 [Matsusaka, Taiji; Kinomura, Masaru] Tokai Univ, Sch Med, Dept Internal Med, Kanagawa 2591193, Japan. [Matsusaka, Taiji; Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA. [Fogo, Agnes B.] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. [Fogo, Agnes B.; Ichikawa, Iekuni] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. [Shintani, Ayumi] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA. [Matsusaka, Taiji] Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591193, Japan. [Niimura, Fumio] Tokai Univ, Sch Med, Dept Pediat, Kanagawa 2591193, Japan. [Ichikawa, Iekuni] Tokai Univ, Sch Med, Dept Bioeth, Kanagawa 2591193, Japan. [Pastan, Ira] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Asano, Takako] Natl Def Med Coll, Dept Pediat, Tokorozawa, Saitama 359, Japan. [Shimizu, Akihiro] Jikei Univ, Sch Med, Dept Internal Med, Div Kidney & Hypertens, Tokyo, Japan. RP Matsusaka, T (reprint author), Tokai Univ, Sch Med, Dept Internal Med, 143 Shimokasuya, Kanagawa 2591193, Japan. EM taijim@is.icc.u-tokai.ac.jp FU Japan Society for the Promotion of Science [16109005, 18209030]; MEXT Japan; National Institute of Diabetes and Digestive and Kidney Disease [DK037868, DK044757]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; Daiichi Sankyo Co, Ltd FX This study was supported by a Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (16109005 and 18209030), the High-Tech Research Center Project of MEXT Japan, and the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease (National Institutes of Health grants DK037868 and DK044757), as well as in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.; I. I. has received research funds from Daiichi Sankyo Co, Ltd. NR 36 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 2010 VL 55 IS 4 BP 967 EP U288 DI 10.1161/HYPERTENSIONAHA.109.141994 PG 16 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 570TS UT WOS:000275701600027 PM 20142565 ER PT J AU Hiby, SE Ashrafian-Bonab, M Farrell, L Single, RM Balloux, F Carrington, M Moffett, A Ebrahimi, Z AF Hiby, Susan E. Ashrafian-Bonab, Maziar Farrell, Lydia Single, Richard M. Balloux, Francois Carrington, Mary Moffett, Ashley Ebrahimi, Zahra TI Erratum to: Distribution of killer cell immunoglobulin-like receptors(KIR) and their HLA-C ligands in two Iranian populations (vol 62, pg 65, 2010) SO IMMUNOGENETICS LA English DT Correction C1 [Hiby, Susan E.; Farrell, Lydia; Moffett, Ashley] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. [Ashrafian-Bonab, Maziar] Univ Portsmouth, Dept Biol Sci, Portsmouth, Hants, England. [Single, Richard M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA. [Balloux, Francois] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Infect Dis Epidemiol, MRC Ctr Outbreak Anal & Modelling, London W2 1PG, England. [Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Ebrahimi, Zahra] Iranian Acad Ctr Educ Culture & Res, Infertil Treatment Highly Specialized Ctr, Qom, Iran. RP Hiby, SE (reprint author), Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England. EM seh1002@cam.ac.uk; am485@cam.ac.uk NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD APR PY 2010 VL 62 IS 4 BP 261 EP 261 DI 10.1007/s00251-010-0436-1 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 573HJ UT WOS:000275899600007 ER PT J AU Andrews, PW Benvenisty, N Knowles, BB McKay, RDG Oh, SKW Pera, MF Rossant, J Stacey, GN AF Andrews, Peter W. Benvenisty, Nissim Knowles, Barbara B. McKay, Ronald D. G. Oh, Steve K. W. Pera, Martin F. Rossant, Janet Stacey, Glyn N. TI Human ES cell lines-introduction SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Editorial Material C1 [Andrews, Peter W.] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. [Benvenisty, Nissim] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Knowles, Barbara B.] Inst Med Biol, Singapore 138648, Singapore. [McKay, Ronald D. G.] NINDS, Mol Biol Lab, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. [Oh, Steve K. W.] ASTAR, Bioproc Technol Inst, Singapore 138668, Singapore. [Pera, Martin F.] Univ So Calif, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, USC Keck Sch Med, Los Angeles, CA 90033 USA. [Rossant, Janet] Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1L7, Canada. [Stacey, Glyn N.] Natl Inst Biol Stand & Control Hlth Protect Agcy, UK Stem Cell Bank, Div Cell Biol & Imaging, S Mimms EN6 3QG, Herts, England. RP Andrews, PW (reprint author), Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. EM p.w.andrews@sheffield.ac.uk RI PERA, MARTIN/A-9812-2012 OI PERA, MARTIN/0000-0001-6239-0428 NR 5 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 2010 VL 46 IS 3-4 SI SI BP 167 EP 168 DI 10.1007/s11626-010-9306-2 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 584QZ UT WOS:000276768700001 ER PT J AU Akopian, V Andrews, PW Beil, S Benvenisty, N Brehm, J Christie, M Ford, A Fox, V Gokhale, PJ Healy, L Holm, F Hovatta, O Knowles, BB Ludwig, TE McKay, RDG Miyazaki, T Nakatsuji, N Oh, SKW Pera, MF Rossant, J Stacey, GN Suemori, H AF Akopian, Veronika Andrews, Peter W. Beil, Stephen Benvenisty, Nissim Brehm, Jennifer Christie, Megan Ford, Angela Fox, Victoria Gokhale, Paul J. Healy, Lyn Holm, Frida Hovatta, Outi Knowles, Barbara B. Ludwig, Tenneille E. McKay, Ronald D. G. Miyazaki, Takamichi Nakatsuji, Norio Oh, Steve K. W. Pera, Martin F. Rossant, Janet Stacey, Glyn N. Suemori, Hirofumi CA Int Stem Cell Initiative Consortiu TI Comparison of defined culture systems for feeder cell free propagation of human embryonic stem cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE Human embryonic stem cell; Cell culture; Defined cell culture media; Comparative study ID FIBROBLAST-GROWTH-FACTOR; SERUM-FREE MEDIUM; SELF-RENEWAL; MAINTAINS PLURIPOTENCY; HUMAN BLASTOCYSTS; HUMAN ESCS; DIFFERENTIATION; LINES; MOUSE; MAINTENANCE AB There are many reports of defined culture systems for the propagation of human embryonic stem cells in the absence of feeder cell support, but no previous study has undertaken a multi-laboratory comparison of these diverse methodologies. In this study, five separate laboratories, each with experience in human embryonic stem cell culture, used a panel of ten embryonic stem cell lines (including WA09 as an index cell line common to all laboratories) to assess eight cell culture methods, with propagation in the presence of Knockout Serum Replacer, FGF-2, and mouse embryonic fibroblast feeder cell layers serving as a positive control. The cultures were assessed for up to ten passages for attachment, death, and differentiated morphology by phase contrast microscopy, for growth by serial cell counts, and for maintenance of stem cell surface marker expression by flow cytometry. Of the eight culture systems, only the control and those based on two commercial media, mTeSR1 and STEMPRO, supported maintenance of most cell lines for ten passages. Cultures grown in the remaining media failed before this point due to lack of attachment, cell death, or overt cell differentiation. Possible explanations for relative success of the commercial formulations in this study, and the lack of success with other formulations from academic groups compared to previously published results, include: the complex combination of growth factors present in the commercial preparations; improved development, manufacture, and quality control in the commercial products; differences in epigenetic adaptation to culture in vitro between different ES cell lines grown in different laboratories. C1 [Andrews, Peter W.; Ford, Angela; Gokhale, Paul J.] Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. [Akopian, Veronika; Beil, Stephen; Fox, Victoria; Pera, Martin F.] Univ So Calif, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Keck Sch Med, Los Angeles, CA 90033 USA. [Benvenisty, Nissim] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. [Brehm, Jennifer; Ludwig, Tenneille E.] WiCell Res Inst, Madison, WI 53707 USA. [Christie, Megan; Healy, Lyn; Stacey, Glyn N.] Natl Inst Biol Stand & Control Hlth Protect Agcy, UK Stem Cell Bank, Div Cell Biol & Imaging, S Mimms EN6 3QG, Herts, England. [Holm, Frida; Hovatta, Outi] Karolinska Univ Hosp, Karolinska Inst, Dept Clin Sci Technol & Intervent, SE-14186 Stockholm, Sweden. [Knowles, Barbara B.] Inst Med Biol 8A Biomed Grove, Singapore 138648, Singapore. [McKay, Ronald D. G.] NIH, Stem Cell Unit, Bethesda, MD 20892 USA. [Miyazaki, Takamichi; Nakatsuji, Norio; Suemori, Hirofumi] Kyoto Univ, Inst Frontier Med Sci, Kyoto 6068507, Japan. [Oh, Steve K. W.] ASTAR, Bioproc Technol Inst, Singapore 138668, Singapore. [Rossant, Janet] Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1L7, Canada. RP Andrews, PW (reprint author), Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. EM p.w.andrews@sheffield.ac.uk; p.j.gokhale@sheffield.ac.uk RI PERA, MARTIN/A-9812-2012; OI PERA, MARTIN/0000-0001-6239-0428; Gokhale, Paul/0000-0001-7225-4403 FU International Stem Cell Forum; ESTOOLS; European Union; National Center for Research Resources; National Institutes of Health; Department of Health and Human Services [HHSN309200582085C] FX This study was supported by funding from the International Stem Cell Forum (www.stemcellforum.org). In addition, further support for the Test Laboratory at the Karolinska Institute (Hovatta and Holm) by ESTOOLS, a Six Framework Integrated Project funded by the European Union. In addition, at the Test Laboratory at WiCell (Ludwig and Brehm) this project was funded in whole or in part with Federal funds from the National Center for Research Resources, National Institutes of Health, Department of Health and Human Services, under Contract no. HHSN309200582085C. The content of this publication does not necessarily reflect the views or policies of the U.S. Department of Health and Human Services nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We thank all member laboratories of the International Stem Cell Initiative for their input into the design of the study. The media mTeSR1 and hESF9 were supplied free of charge by StemCell Technologies Inc., Canada, and Cell Science & Technology Institute, Inc., Japan (CSTI), respectively. WiCell, USA provided cultures of WA09 hESC. The study design was initiated and discussed at international meetings of the ISCI held at The Jackson Laboratory, Bar Harbor, ME, USA. NR 29 TC 81 Z9 82 U1 0 U2 22 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 2010 VL 46 IS 3-4 SI SI BP 247 EP 258 DI 10.1007/s11626-010-9297-z PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 584QZ UT WOS:000276768700014 ER PT J AU Dreher-Lesnick, SM Ceraul, SM Lesnick, SC Gillespie, JJ Anderson, JM Jochim, RC Valenzuela, JG Azad, AF AF Dreher-Lesnick, S. M. Ceraul, S. M. Lesnick, S. C. Gillespie, J. J. Anderson, J. M. Jochim, R. C. Valenzuela, J. G. Azad, A. F. TI Analysis of Rickettsia typhi-infected and uninfected cat flea (Ctenocephalides felis) midgut cDNA libraries: deciphering molecular pathways involved in host response to R-typhi infection SO INSECT MOLECULAR BIOLOGY LA English DT Article DE flea; rickettsia; midgut; R; typhi ID INSECT STOMOXYS-CALCITRANS; TICK DERMACENTOR-VARIABILIS; INNATE IMMUNE-RESPONSES; LISTERIA-MONOCYTOGENES; PHLEBOTOMUS-PAPATASI; SERINE PROTEASES; PLASMODIUM-YOELII; GENE-EXPRESSION; AEDES-AEGYPTI; MOSQUITO AB Murine typhus is a flea-borne febrile illness that is caused by the obligate intracellular bacterium, Rickettsia typhi. The cat flea, Ctenocephalides felis, acquires R. typhi by imbibing a bloodmeal from a rickettsemic vertebrate host. To explore which transcripts are expressed in the midgut in response to challenge with R. typhi, cDNA libraries of R. typhi-infected and uninfected midguts of C. felis were constructed. In this study, we examined midgut transcript levels for select C. felis serine proteases, GTPases and defence response genes, all thought to be involved in the fleas response to feeding or infection. An increase in gene expression was observed for the serine protease inhibitors and vesicular trafficking proteins in response to feeding. In addition, R. typhi infection resulted in an increase in gene expression for the chymotrypsin and rab5 that we studied. Interestingly, R. typhi infection had little effect on expression of any of the defence response genes that we studied. We are unsure as to the physiological significance of these gene expression profiles and are currently investigating their potential roles as it pertains to R. typhi infection. To our knowledge, this is the first report of differential expression of flea transcripts in response to infection with R. typhi. C1 [Dreher-Lesnick, S. M.; Ceraul, S. M.; Gillespie, J. J.; Azad, A. F.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Lesnick, S. C.] Univ Maryland, Dept Biol, College Pk, MD 20742 USA. [Gillespie, J. J.] Virginia Tech, Bioinformat Facil, Virginia Bioinformat Inst, Blacksburg, VA USA. [Anderson, J. M.; Jochim, R. C.; Valenzuela, J. G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA. RP Ceraul, SM (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 685 W Baltimore St,Room HSFI,Suite 380, Baltimore, MD 21201 USA. EM scera001@umaryland.edu RI Jochim, Ryan/C-6756-2013; OI Gillespie, Joseph/0000-0002-5447-7264 FU NIAID [AI017828, AI59118, AI043006, HHSN266200400035C]; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We would like to thank Jose Ribero for providing the bioinformatics analyses software and for review of the manuscript. AFA acknowledges support from NIAID grants, AI017828, AI59118 and AI043006. JJG acknowledges support from NIAID contract HHSN266200400035C awarded to Bruno W. Sobral (Virginia Bioinformatics Institute at Virginia Tech). Because RCJ, JMA and JGV are government employees and part of this is a government work, the work is in the public domain in the United States. This work was supported in part by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the National Institutes of Health. NR 56 TC 5 Z9 5 U1 1 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD APR PY 2010 VL 19 IS 2 BP 229 EP 241 DI 10.1111/j.1365-2583.2009.00978.x PG 13 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 564AM UT WOS:000275182900009 PM 20017753 ER PT J AU Christian, MD Joynt, GM Hick, JL Colvin, J Danis, M Sprung, CL AF Christian, Michael D. Joynt, Gavin M. Hick, John L. Colvin, John Danis, Marion Sprung, Charles L. TI Critical care triage SO INTENSIVE CARE MEDICINE LA English DT Article DE Critical care triage; Triage; Staff protection; Recommendations; Standard operating procedures; Intensive care unit; Hospital; H1N1; Influenza epidemic; Pandemic; Infection control; Disaster ID MASS CRITICAL-CARE; 2009 INFLUENZA A(H1N1); JANUARY 26-27; ILL PATIENTS; TASK-FORCE; MECHANICAL VENTILATION; DEFINITIVE CARE; ALLOCATION; MEDICINE; DISASTER AB Purpose: To provide recommendations and standard operating procedures for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on critical care triage. Methods: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including critical care triage. Results: Key recommendations include: (1) establish an Incident Management System with Emergency Executive Control Groups at facility, local, regional/state or national levels to exercise authority and direction over resources; (2) developing fair and equitable policies may require restricting ICU services to patients most likely to benefit; (3) usual treatments and standards of practice may be impossible to deliver; (4) ICU care and treatments may have to be withheld from patients likely to die even with ICU care and withdrawn after a trial in patients who do not improve or deteriorate; (5) triage criteria should be objective, ethical, transparent, applied equitably and be publically disclosed; (6) trigger triage protocols for pandemic influenza only when critical care resources across a broad geographic area are or will be overwhelmed despite all reasonable efforts to extend resources or obtain additional resources; (7) triage of patients for ICU should be based on those who are likely to benefit most or a 'first come, first served' basis; (8) a triage officer should apply inclusion and exclusion criteria to determine patient qualification for ICU admission. Conclusions: Judicious planning and adoption of protocols for critical care triage are necessary to optimize outcomes during a pandemic. C1 [Sprung, Charles L.] Hadassah Hebrew Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. [Christian, Michael D.] Univ Toronto, Div Infect Dis & Crit Care, Dept Natl Def, Canadian Forces & Dept Med,Mt Sinai Sch, Toronto, ON, Canada. [Joynt, Gavin M.] Chinese Univ Hong Kong, Dept Anesthesia & Intens Care, Prince Wales Hosp, Sha Tin, Hong Kong, Peoples R China. [Colvin, John] Ninewells Hosp, Dept Anaesthesiol, Dundee DD1 9SY, Scotland. [Hick, John L.] Hennepin Cty Med Ctr, Dept Emergency Med, Minneapolis, MN 55415 USA. [Danis, Marion] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Sprung, CL (reprint author), Hadassah Hebrew Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. EM charles.sprung@ekmd.huji.ac.il RI Joynt, Gavin/C-7606-2009; Montgomery, Hugh/C-2592-2008 OI Joynt, Gavin/0000-0002-5823-3435; Montgomery, Hugh/0000-0001-8797-5019 FU Intramural NIH HHS [Z99 CL999999] NR 30 TC 16 Z9 17 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2010 VL 36 SU 1 BP S55 EP S64 DI 10.1007/s00134-010-1765-0 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 653QO UT WOS:000282112000007 PM 20213422 ER PT J AU Joynt, GM Loo, S Taylor, BL Margalit, G Christian, MD Sandrock, C Danis, M Leoniv, Y Sprung, CL AF Joynt, Gavin M. Loo, Shi Taylor, Bruce L. Margalit, Gila Christian, Michael D. Sandrock, Christian Danis, Marion Leoniv, Yuval Sprung, Charles L. TI Coordination and collaboration with interface units SO INTENSIVE CARE MEDICINE LA English DT Article DE Coordination and collaboration; Recommendations; Standard operating procedures; Intensive care unit; Hospital; H1N1; Influenza epidemic; Pandemic; Disaster ID CRITICALLY-ILL; CRITICAL-CARE; DISASTER; TRIAGE AB Purpose: To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on enhancing coordination and collaboration between the ICU and other key stakeholders. Methods: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including coordination and collaboration. Results: Key recommendations include: (1) establish an Incident Management System with Emergency Executive Control Groups at facility, local, regional/state or national levels to exercise authority and direction over resource use and communications; (2) develop a system of communication, coordination and collaboration between the ICU and key interface departments within the hospital; (3) identify key functions or processes requiring coordination and collaboration, the most important of these being manpower and resources utilization (surge capacity) and re-allocation of personnel, equipment and physical space; (4) develop processes to allow smooth inter-departmental patient transfers; (5) creating systems and guidelines is not sufficient, it is important to: (a) identify the roles and responsibilities of key individuals necessary for the implementation of the guidelines; (b) ensure that these individuals are adequately trained and prepared to perform their roles; (c) ensure adequate equipment to allow key coordination and collaboration activities; (d) ensure an adequate physical environment to allow staff to properly implement guidelines; (6) trigger events for determining a crisis should be defined. Conclusions: Judicious planning and adoption of protocols for coordination and collaboration with interface units are necessary to optimize outcomes during a pandemic. C1 [Sprung, Charles L.] Hadassah Hebrew Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. [Joynt, Gavin M.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anesthesia & Intens Care, Sha Tin, Hong Kong, Peoples R China. [Loo, Shi] Tan Tock Seng Hosp, Dept Anaesthesiol, Singapore, Singapore. [Taylor, Bruce L.] Portsmouth Hosp NHS Trust, Dept Crit Care, Portsmouth, Hants, England. [Margalit, Gila] Chaim Sheba Med Ctr, Dept Emergency Serv, IL-52621 Tel Hashomer, Israel. [Christian, Michael D.] Mt Sinai Hosp, Dept Med Infect Dis & Crit Care, Toronto, ON M5G 1X5, Canada. [Christian, Michael D.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Sandrock, Christian] UC Davis Sch Med, Intens Care Unit, Div Pulm & Crit Care Med & Infect Dis, Sacramento, CA USA. [Danis, Marion] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. [Leoniv, Yuval] Chaim Sheba Med Ctr, Dept Anesthesiol & Crit Care Med, IL-52621 Tel Hashomer, Israel. RP Sprung, CL (reprint author), Hadassah Hebrew Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. EM charles.sprung@ekmd.huji.ac.il RI Joynt, Gavin/C-7606-2009; Montgomery, Hugh/C-2592-2008 OI Joynt, Gavin/0000-0002-5823-3435; Montgomery, Hugh/0000-0001-8797-5019 FU Intramural NIH HHS [Z99 CL999999] NR 12 TC 8 Z9 8 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD APR PY 2010 VL 36 SU 1 BP S21 EP S31 DI 10.1007/s00134-010-1762-3 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 653QO UT WOS:000282112000003 PM 20213418 ER PT J AU Titus-Ernstoff, L Troisi, R Hatch, EE Palmer, JR Hyer, M Kaufman, R Adam, E Noller, K Hoover, RN AF Titus-Ernstoff, L. Troisi, R. Hatch, E. E. Palmer, J. R. Hyer, M. Kaufman, R. Adam, E. Noller, K. Hoover, R. N. TI Birth defects in the sons and daughters of women who were exposed in utero to diethylstilbestrol (DES) SO INTERNATIONAL JOURNAL OF ANDROLOGY LA English DT Article; Proceedings Paper CT 5th Copenhagen Workshop on Endocrine Disruptgers - Ubiquitous Endocrine Disrupters and Possible Human Health Effects CY MAY 20-22, 2009 CL Copenhagen, DENMARK DE birth defects; diethylstilbestrol; epigenetic alterations; maternal exposure; prenatal exposure ID PRENATAL EXPOSURE; SEX-HORMONES; FOLLOW-UP; PREGNANCY; TUMORS; RISK; MEN; DESCENDANTS; FERTILITY; CANCER AB P>Prenatal exposure to diethylstilbestrol (DES) is associated with adverse health outcomes, including anatomic anomalies of the reproductive tract in women and of the genitourinary tract in men. The mouse model, which replicates many DES-related effects seen in humans, suggests that prenatal DES exposure causes alterations that may affect the next generation of offspring. We asked women participating in a large, multi-centre study of prenatal DES exposure to report birth defects occurring among 4029 sons and 3808 daughters (i.e., the third generation). A subcohort of 793 third generation daughters was also queried for birth defects. We used logistic regression models to generate odds ratio and 95% confidence intervals for the association between prenatal DES exposure in the mother and birth defects in the offspring. Based on the mothers' reports, overall birth defects were elevated in the sons (OR = 1.53; 95% CI = 1.04, 2.23) and in the daughters (OR = 2.35; 95% CI = 1.44, 3.82). Most estimates of association were imprecise, but daughters appeared to have an excess of heart conditions (OR = 4.56; 95% CI = 1.27, 16.34). Our data suggest a possible association between the mother's prenatal DES exposure and birth defects in their offspring, particularly in daughters. We cannot, however, rule-out the possible influence of reporting bias. In particular, the exposed daughters' elevated risk of cardiac defects may be as a result of the underreporting of these conditions by unexposed mothers. C1 [Titus-Ernstoff, L.] Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH 03756 USA. [Titus-Ernstoff, L.] Dartmouth Med Sch, Dept Pediat, Lebanon, NH 03756 USA. [Titus-Ernstoff, L.] Hood Ctr Children & Families, Lebanon, NH 03756 USA. [Troisi, R.; Hoover, R. N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hatch, E. E.] Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. [Palmer, J. R.] Boston Univ, Slone Epidemiol Unit, Sch Publ Hlth, Brookline, MA USA. [Hyer, M.] Informat Management Serv Inc, Rockville, MD USA. [Kaufman, R.] Methodist Hosp, Dept Obstet & Gynecol, Houston, TX 77030 USA. [Adam, E.] Bayer Coll Med, Dept Virol & Epidemiol, Houston, TX USA. [Noller, K.] Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Med Sch, Dept Community & Family Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM linda.titus-ernstoff@dartmouth.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [CP 51010, N01 CP001012, CP 01012, N01 CP051019, N01 CP055507, N01 CP055508, N01 CP055509, N01 CP055510, N01 CP055511] NR 38 TC 28 Z9 28 U1 0 U2 9 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-6263 J9 INT J ANDROL JI Int. J. Androl. PD APR PY 2010 VL 33 IS 2 BP 377 EP 383 DI 10.1111/j.1365-2605.2009.01010.x PG 7 WC Andrology SC Endocrinology & Metabolism GA 569XO UT WOS:000275636400025 PM 20002218 ER PT J AU Takaku, S Terabe, M Ambrosino, E Peng, J Lonning, S McPherson, JM Berzofsky, JA AF Takaku, Shun Terabe, Masaki Ambrosino, Elena Peng, Judy Lonning, Scott McPherson, John M. Berzofsky, Jay A. TI Blockade of TGF-beta enhances tumor vaccine efficacy mediated by CD8(+) T cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE TGF-beta; vaccine; prophylactic ID GROWTH-FACTOR-BETA; REGULATORY CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; IMMUNE-RESPONSES; COLON-CANCER; MICE CAUSES; IMMUNOSURVEILLANCE; METASTASIS; TGF-BETA-1; ANTIBODIES AB Though TGF-beta inhibition enhances antitumor immunity mediated by CD8(+) T cells in several tumor models, it is not always sufficient for rejection of tumors. In this study, to maximize the antitumor effect of TGF-beta blockade, we tested the effect of anti-TGF-beta combined with an irradiated tumor vaccine in a subcutaneous CT26 colon carcinoma tumor model. The irradiated tumor cell vaccine alone in prophylactic setting significantly delayed tumor growth, whereas anti-TGF-beta antibodies alone did not show any antitumor effect. However, tumor growth was inhibited significantly more in vaccinated mice treated with anti-TGF-beta antibodies compared to vaccinated mice without anti-TGF-beta, suggesting that anti-TGF-beta synergistically enhanced irradiated tumor vaccine efficacy. CD8+ T-cell depletion completely abrogated the vaccine efficacy, and so protection required CD8(+) T cells. Depletion of CD25(+) T regulatory cells led to the almost complete rejection of tumors without the vaccine, whereas anti-TGF-beta did not change the number of CD25(+) T regulatory cells in unvaccinated and vaccinated mice. Though the abrogation of CD1d-restricted NKT cells, which have been reported to induce TGF-beta production by MDSC through an IL-13-IL-4R-STAT6 pathway, partially enhanced antitumor immunity regardless of vaccination, abrogation of the NKT cell-IL-13-IL-4R-STAT-6 immunoregulatory pathway did not enhance vaccine efficacy. Taken together, these data indicated that anti-TGF-beta enhances efficacy of a prophylactic vaccine in normal individuals despite their not having the elevated TGF-beta levels found in patients with cancer and that the effect is not dependent on TGF-beta solely from CD4(+)CD25(+) T regulatory cells or the NKT cell-IL-13-IL-4R-STAT-6 immunoregulatory pathway. C1 [Takaku, Shun; Terabe, Masaki; Ambrosino, Elena; Peng, Judy; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Lonning, Scott; McPherson, John M.] Genzyme Corp, Framingham, MA 01701 USA. RP Terabe, M (reprint author), NCI, Vaccine Branch, NIH, Bldg 10 Room 6B12,9000 Rockville Pike, Bethesda, MD 20892 USA. EM terabe@mail.nih.gov FU Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research FX Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research NR 48 TC 34 Z9 36 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2010 VL 126 IS 7 BP 1666 EP 1674 DI 10.1002/ijc.24961 PG 9 WC Oncology SC Oncology GA 560YA UT WOS:000274940200013 PM 19830696 ER PT J AU Lanoy, E Costagliola, D Engels, EA AF Lanoy, Emilie Costagliola, Dominique Engels, Eric A. TI Skin cancers associated with HIV infection and solid-organ transplantation among elderly adults SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE skin neoplasm; immunosuppression; aged; HIV; AIDS; transplant ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MUIR-TORRE-SYNDROME; CELL-CARCINOMA; UNITED-STATES; SEBACEOUS CARCINOMA; RECIPIENTS; RISK; AIDS; PATIENT; HIV/AIDS AB Immunosuppression may be etiologic for some skin cancers. We investigated the impact of human immunodeficiency virus (HIV) infection and solid-organ transplantation on skin cancer risk. We conducted a population-based case-control study among elderly U.S. adults (non-Hispanic whites, age 67 years or older), using Surveillance, Epidemiology and End Results Medicare linked data. The study comprised 29,926 skin cancer cases (excluding basal cell and squamous cell carcinomas) and 119,704 controls, frequency-matched by gender, age and calendar year (1987-2002). Medicare claims identified solid-organ transplantation or HIV infection before cancer diagnosis/control selection. As negative controls, we evaluated other medical conditions (e.g., hypertension and depression) and cancers (breast, colon and prostate) not linked to immunosuppression. Odds ratios (ORs) compared prevalence in cases and controls, adjusted for matching factors and number of prior physician claims. Risks of Kaposi sarcoma (N = 602) and cutaneous non-Hodgkin lymphoma (N = 1,836) were increased with solid-organ transplantation (OR [95%CI]: 11.06 [5.27-23.23] and 2.27 [1.00-5.15], respectively) and HIV infection (21.58 [11.94-38.99] and 2.41 [1.05-5.52], respectively). Solid-organ transplantation was also associated with increased risks of Merkel cell carcinoma (N = 1,286; OR [95%CI] 4.95 [2.62-9.34]) and other cutaneous sarcomas (N = 972; 4.19 [1.83-9.56]). Solid-organ transplantation was non significantly associated with melanoma (N = 23,974); (OR 1.36 [95%CI 0.98-1.88]). Null or weak associations were observed for negative control medical conditions and cancers. Solid-organ transplantation and HIV infection were followed by increased risk for some skin cancer subtypes among elderly adults. These results highlight the potential role of immunity in development of skin cancers. C1 [Lanoy, Emilie; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Lanoy, Emilie; Costagliola, Dominique] INSERM, U943, Paris, France. [Lanoy, Emilie; Costagliola, Dominique] Univ Paris 06, UMR S943, Paris, France. [Costagliola, Dominique] Grp Hosp Pitie Salpetriere, AP HP, Serv Malad Infect & Trop, Paris, France. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7076, Rockville, MD 20892 USA. EM engelse@exchange.nih.gov RI Lanoy, Emilie/A-8541-2011; Costagliola, Dominique/H-5849-2011 OI Lanoy, Emilie/0000-0002-4789-7770; Costagliola, Dominique/0000-0003-0765-0869 FU Intramural NIH HHS [Z01 CP010150-08] NR 35 TC 35 Z9 35 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2010 VL 126 IS 7 BP 1724 EP 1731 DI 10.1002/ijc.24931 PG 8 WC Oncology SC Oncology GA 560YA UT WOS:000274940200019 PM 19810102 ER PT J AU Mbulaiteye, SM Anderson, WF Bhatia, K Rosenberg, PS Linet, MS Devesa, SS AF Mbulaiteye, Sam M. Anderson, William F. Bhatia, Kishor Rosenberg, Philip S. Linet, Martha S. Devesa, Susan S. TI Trimodal age-specific incidence patterns for Burkitt lymphoma in the United States, 1973-2005 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE non-Hodgkin lymphoma; epidemiology; multistage cancer models; tri/bimodal cancer; Epstein-Barr virus ID TEMPORAL VARIATION; COHORT MODELS; CANCER RATES; PERIOD; DISEASE; RISK; TRENDS; TUMOR; AIDS AB Burkitt lymphoma (BL) is a unique B-cell non-Hodgkin lymphoma with 3 established clinical-epidemiological variants: endemic, sporadic and AIDS-related BL. BL variants show characteristic dysregulation of MYC gene, but the causes of MYC dysregulation or BL arising at different ages are poorly understood. Therefore, we examined population-based BL incidence patterns in the United States to determine age-related risk. BL case and population data were obtained from the NCI's Surveillance, Epidemiology and End Results Databases (1973-2005). Standard cross-sectional age-standardized and age-specific incidence rates were stratified by sex and race and supplemented with age-period-cohort models. We analyzed 3,058 BL cases diagnosed during 1,160,300,297 person-years of observation. Age-standardized incidence rates rose 6.8% per year (95% CI 4.5-9.1) for males and 7.1% (95% CI 3.2-11.1) for females during the study period. The rate among males was 3.2 times that among females, and among Whites 1.3 times that among Blacks. Male-to-female incidence rate ratios did not differ by race, but were 4.2 for pediatric (0-19 years), 4.1 for adult (20-59 years) and 2.0 for geriatric (>60 years) BL. Cross-sectional age-specific rates showed 2 separate peaks among males and females, near ages 10 and 75 years, and a 3rd peak near age 40 years among males. The tri/bimodal incidence pattern was present in sensitivity analyses excluding registries with many HIV/AIDS cases and in period-specific, cohort-specific analyses. To our knowledge, tri/bimodal incidence patterns have not previously been reported for BL. Trimodal/bimodal BL suggests heterogeneity in etiology or biology of BL diagnosed at different ages in males and females. C1 [Mbulaiteye, Sam M.; Bhatia, Kishor] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet DCEG, Bethesda, MD 20892 USA. [Anderson, William F.; Rosenberg, Philip S.; Devesa, Susan S.] NCI, Biostat Branch, DCEG, Bethesda, MD 20892 USA. [Linet, Martha S.] NCI, Radiat Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. RP Mbulaiteye, SM (reprint author), 6120 Execut Blvd,Execut Plaza S,Rm 7080,MSC 7248, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health, Department of Health and Human Services FX Grant sponsor: Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services NR 38 TC 20 Z9 21 U1 2 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2010 VL 126 IS 7 BP 1732 EP 1739 DI 10.1002/ijc.24934 PG 8 WC Oncology SC Oncology GA 560YA UT WOS:000274940200020 PM 19810101 ER PT J AU Koh, KK Quon, MJ Han, SH Lee, Y Kim, SJ Koh, Y Shin, EK AF Koh, Kwang Kon Quon, Michael J. Han, Seung Hwan Lee, Yonghee Kim, Soo Jin Koh, Yesl Shin, Eak Kyun TI Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE Anti-hypertensive drugs; Endothelial function; Adipocytokines; Hypertension; Insulin resistance ID PLASMA ADIPONECTIN LEVELS; ARM ASCOT-BPLA; ANGIOTENSIN-II; HYPERTENSIVE PATIENTS; INSULIN SENSITIVITY; ENDOTHELIAL FUNCTION; THERAPEUTIC INTERVENTIONS; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; BLOOD-PRESSURE AB Background: ASCOT-BPLA study demonstrates that in hypertensive subjects, atenolol+bendroflumethiazide therapy is associated with higher incidence of adverse cardiovascular outcomes and developing diabetes than an amlodipine+perindopril regimen. This is not explained by changes in blood pressure alone. We hypothesized that distinct vascular and metabolic effects of anti-hypertensive drugs may explain these differential effects. Methods: Either placebo or one class of anti-hypertensive drug (atenolol 100 mg, amlodipine 10 mg, hydrochlorothiazide 50 mg, ramipril 10 mg, or candesartan 16 mg) was given daily during 8 weeks to 31 patients in each of 6 arms of a randomized, single-blind, placebo-controlled, parallel study. Results: Atenolol, amlodipine, and candesartan therapies significantly reduced systolic blood pressure when compared with ramipril (P<0.05 by ANOVA). Atenolol and thiazide therapies increased triglycerides levels greater than ramipril or candesartan (P=0.005 by ANOVA). Amlodipine significantly increased HDL cholesterol levels greater than atenolol (P=0.011 by ANOVA). Ramipril and candesartan therapies improved FMD and increased adiponectin levels and insulin sensitivity to a greater extent than atenolol or thiazide therapies (P<0.001 and P<0.015 by ANOVA). Amlodipine therapy increased adiponectin levels greater than atenolol therapy (P<0.05 by ANOVA). Ramipril, candesartan, and amlodipine therapies significantly decreased leptin levels to a greater extent when compared with atenolol or thiazide therapies (P<0.001 by ANOVA). Amlodipine therapies significantly decreased resistin levels greater than ramipril or candesartan therapies (P=0.001 by ANOVA). Conclusions: We observed differential effects of anti-hypertensive drugs on endothelial dysfunction and plasma adipocytokines. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Koh, Kwang Kon] Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. [Quon, Michael J.] NIH, Diabet Unit, NCCAM, Bethesda, MD 20892 USA. [Koh, Yesl] Northwestern Univ, Weinberg Coll Arts & Sci, Evanston, IL USA. [Lee, Yonghee] Univ Seoul, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Univ, Gil Med Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@gilhospital.com OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Gil Medical Center, Gachon University [2005-1, 2006-1]; Korean Society of Hypertension [KSH-2004, KSH-2005] FX This study was partly supported by grants from established investigator award (2005-1, 2006-1), Gil Medical Center, Gachon University and Korean Society of Hypertension (KSH-2004, 2005). NR 55 TC 42 Z9 44 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD APR 1 PY 2010 VL 140 IS 1 BP 73 EP 81 DI 10.1016/j.ijcard.2008.11.017 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 572GU UT WOS:000275816600011 PM 19059660 ER PT J AU Brumback, LC Kronmal, R Heckbert, SR Ni, HY Hundley, WG Lima, JA Bluemke, DA AF Brumback, Lyndia C. Kronmal, Richard Heckbert, Susan R. Ni, Hanyu Hundley, W. Gregory Lima, Joao A. Bluemke, David A. TI Body size adjustments for left ventricular mass by cardiovascular magnetic resonance and their impact on left ventricular hypertrophy classification SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE Cardiovascular risk; Hypertension; Hypertrophy; LV mass index; Magnetic resonance imaging; Obesity ID CONGESTIVE-HEART-FAILURE; POPULATION-ATTRIBUTABLE RISK; END-POINT REDUCTION; LOSARTAN INTERVENTION; GENDER-DIFFERENCES; DIABETES-MELLITUS; SYSTOLIC FUNCTION; CORONARY EVENTS; HYPERTENSION; PREDICTION AB Methods to index left ventricular (LV) mass, measured by cardiovascular magnetic resonance (CMR), for body size have not been investigated. The purposes of this study were to develop allometric indices for LV mass measured by CMR and compare estimates of the prevalence and predictive value of LV hypertrophy defined by a new allometric height-weight index, LV mass/body surface area (BSA), height indices (a new allometric height index; and previously derived indices from echocardiographic measurements: LV mass/height(2), LV mass/height(2.7)), and non-indexed LV mass. 5,004 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with CMR measurements of LV mass and no clinical cardiovascular disease at baseline were followed for a median of 4.1 years. The new indices and limits for hypertrophy (95th percentile) were derived from 822 normal-weight, normotensive, non-diabetic MESA participants. 107 events (coronary heart disease or stroke) were observed. The estimated prevalence of hypertrophy at baseline and hazard ratio for event associated with hypertrophy were 8% and 2.4 with the new allometric height-weight index, 11% and 2.2 with LV mass/BSA, 23-24% and 2.0-2.1 with height indices, and 20% and 1.7 with non-indexed LV mass. A statistically significant difference was detected between the hazard ratios based on the new height-weight index and non-indexed LV mass. The prevalence of hypertrophy is higher for indices that do not account for weight. The predictive value of hypertrophy is significantly better with the new allometric height-weight index than with non-indexed LV mass and may be better than indices without weight. C1 [Brumback, Lyndia C.; Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Ni, Hanyu] NHLBI, Bethesda, MD 20892 USA. [Hundley, W. Gregory] Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. [Hundley, W. Gregory] Wake Forest Univ, Dept Radiol, Winston Salem, NC 27109 USA. [Lima, Joao A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Lima, Joao A.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Bluemke, David A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Brumback, LC (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM lynb@u.washington.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95168] FX This research was supported by contracts N01-HC-95159 and N01-HC-95168 from the National Heart, Lung, and Blood Institute. NR 48 TC 31 Z9 31 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD APR PY 2010 VL 26 IS 4 BP 459 EP 468 DI 10.1007/s10554-010-9584-5 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 581ME UT WOS:000276526600012 PM 20107905 ER PT J AU Allison, KC Lundgren, JD O'Reardon, JP Geliebter, A Gluck, ME Vinai, P Mitchell, JE Schenck, CH Howell, MJ Crow, SJ Engel, S Latzer, Y Tzischinsky, O Mahowald, MW Stunkard, AJ AF Allison, Kelly C. Lundgren, Jennifer D. O'Reardon, John P. Geliebter, Allan Gluck, Marci E. Vinai, Piergiuseppe Mitchell, James E. Schenck, Carlos H. Howell, Michael J. Crow, Scott J. Engel, Scott Latzer, Yael Tzischinsky, Orna Mahowald, Mark W. Stunkard, Albert J. TI Proposed Diagnostic Criteria for Night Eating Syndrome SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID BARIATRIC SURGERY; BULIMIA-NERVOSA; OBESE-PATIENTS; FOOD-INTAKE; DISORDER; PREVALENCE; SERTRALINE; PATTERNS; FEATURES AB Objective: To propose criteria for diagnosis of the night eating syndrome (NES). Method: An international research meeting was held in April 2008, and consensus criteria for NES diagnosis were determined. Results: The core criterion is an abnormally increased food intake in the evening and nighttime, manifested by (1) consumption of at least 25% of intake after the evening meal, and/or (2) nocturnal awakenings with ingestions at least twice per week. Awareness of the eating episodes is required, as is distress or impairment in functioning. Three of five modifiers must also be endorsed. These criteria must be met for a minimum duration of 3 months. Discussion: These criteria help standardize the definition of NES. Additional aspects of the nosology of NES yet to be fully elaborated include its relationship to other eating and sleep disorders. Assessment and analytic tools are needed to assess these new criteria more accurately. (C) 2009 by Wiley Periodicals, Inc. C1 [Allison, Kelly C.; O'Reardon, John P.; Stunkard, Albert J.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Lundgren, Jennifer D.] Univ Missouri, Dept Psychol, Kansas City, MO 64110 USA. [Geliebter, Allan] Columbia Univ, Med Ctr, Dept Psychiat, New York, NY USA. [Geliebter, Allan] NY Obes Res Ctr, New York, NY USA. [Geliebter, Allan] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Geliebter, Allan] Touro Grad Sch, New York, NY USA. [Gluck, Marci E.] NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ USA. [Vinai, Piergiuseppe] Studi Cognit Res Grp, GNOSIS Res Grp Cuneo, Milan, Italy. [Mitchell, James E.; Engel, Scott] Neuropsychiat Res Inst, Fargo, ND USA. [Mitchell, James E.; Engel, Scott] Univ N Dakota, Sch Med & Hlth Sci, Grand Forks, ND 58201 USA. [Schenck, Carlos H.; Mahowald, Mark W.] Hennepin Cty Med Ctr, Minnesota Reg Sleep Disorders Ctr, Minneapolis, MN 55415 USA. [Schenck, Carlos H.; Howell, Michael J.; Mahowald, Mark W.] Univ Minnesota, Sch Med, Dept Neurol, Minneapolis, MN 55455 USA. [Crow, Scott J.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Latzer, Yael] Univ Haifa, IL-31999 Haifa, Israel. [Tzischinsky, Orna] Emek Yezreel Coll, Dept Psychol, Emek Yezreel, Israel. RP Allison, KC (reprint author), 3535 Market St,Suite 3021, Philadelphia, PA 19104 USA. EM kca@mail.med.upenn.edu FU Intramural NIH HHS [Z99 DK999999]; NIDDK NIH HHS [R01 DK074046-03, R01 DK074046, R01 DK074046-01A1, R01 DK074046-01A1S1, R01 DK074046-02, R01 DK074046-02S1, R01 DK074046-02S2, R01 DK074046-04, R01 DK074046-05] NR 43 TC 99 Z9 100 U1 2 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD APR PY 2010 VL 43 IS 3 BP 241 EP 247 DI 10.1002/eat.20693 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 572PB UT WOS:000275844000006 PM 19378289 ER PT J AU Cole, SR Platt, RW Schisterman, EF Chu, HT Westreich, D Richardson, D Poole, C AF Cole, Stephen R. Platt, Robert W. Schisterman, Enrique F. Chu, Haitao Westreich, Daniel Richardson, David Poole, Charles TI Illustrating bias due to conditioning on a collider SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Bias; selection; methods; epidemiologic ID CAUSAL DIAGRAMS; EPIDEMIOLOGY; KNOWLEDGE; INFERENCE; DESIGN; MODELS AB That conditioning on a common effect of exposure and outcome may cause selection, or collider-stratification, bias is not intuitive. We provide two hypothetical examples to convey concepts underlying bias due to conditioning on a collider. In the first example, fever is a common effect of influenza and consumption of a tainted egg-salad sandwich. In the second example, case-status is a common effect of a genotype and an environmental factor. In both examples, conditioning on the common effect imparts an association between two otherwise independent variables; we call this selection bias. C1 [Cole, Stephen R.; Westreich, Daniel; Richardson, David; Poole, Charles] UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Platt, Robert W.] McGill Univ, Dept Biostat, Montreal, PQ, Canada. [Schisterman, Enrique F.] Eunice Kennedy Shriver NICHD, Epidemiol Branch, NIH, Bethesda, MD USA. [Chu, Haitao] UNC Gillings Sch Global Publ Hlth, Dept Biostat, Chapel Hill, NC USA. RP Cole, SR (reprint author), UNC Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. EM cole@unc.edu RI Platt, Robert/G-5847-2012; OI Chu, Haitao/0000-0003-0932-598X; Platt, Robert/0000-0002-5981-8443; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA16086]; NIAAA NIH HHS [R01-AA-01759]; NIAID NIH HHS [R03-AI-071763, P30-AI-50410, R03 AI071763, T32 AI007001]; NIEHS NIH HHS [P30-ES-10126] NR 17 TC 158 Z9 158 U1 7 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2010 VL 39 IS 2 BP 417 EP 420 DI 10.1093/ije/dyp334 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 578OT UT WOS:000276303800019 PM 19926667 ER PT J AU Coleman, CM Scheremeta, BH Boyce, A Mauck, RL Tuan, RS AF Coleman, C. M. Scheremeta, B. H. Boyce, A. Mauck, R. L. Tuan, R. S. TI Fracture healing in GDF-5 deficient mice SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Meeting Abstract CT 2nd Joint Meeting of the Bone-Research-Society/British-Society-for-Matrix-Biology CY JUN 14-16, 2009 CL Univ Coll London, London, ENGLAND SP Bone Res Soc, British Soc Matrix Biol HO Univ Coll London C1 [Coleman, C. M.] Natl Univ Ireland Galway, Regenerat Med Inst, Galway 00000, Ireland. [Scheremeta, B. H.] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Boyce, A.] NIH, Div Musculoskeletal Dis, Bethesda, MD 20891 USA. [Mauck, R. L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Tuan, R. S.] NIAMSD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD APR PY 2010 VL 91 IS 2 BP A18 EP A18 PG 1 WC Pathology SC Pathology GA 564IE UT WOS:000275205700009 ER PT J AU Irlbeck, T Massaro, JM Bamberg, F O'Donnell, CJ Hoffmann, U Fox, CS AF Irlbeck, T. Massaro, J. M. Bamberg, F. O'Donnell, C. J. Hoffmann, U. Fox, C. S. TI Association between single-slice measurements of visceral and abdominal subcutaneous adipose tissue with volumetric measurements: the Framingham Heart Study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE abdominal adiposity; adipose tissue quantification; single-slice measurement; computed tomography; cardiovascular risk factors ID COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; METABOLIC SYNDROME; RISK-FACTORS; COMMUNITY; FAT AB Objective: Volumetric visceral abdominal adipose tissue (VAT) and subcutaneous abdominal adipose tissue (SAT) as measured by computed tomography (CT) are associated with metabolic risk factors. We sought to identify the correlations of VAT and SAT between area-based measures at different anatomic locations with volumetric measurements to identify the optimal anatomic site, and to relate measurements at this site with metabolic risk factors. Methods: We measured SAT and VAT volumes across the total imaging volume, whereas we measured SAT and VAT area at seven predefined anatomic landmarks in 200 participants from the Framingham Heart Study (mean age 54 years, 50% women) who underwent abdominal multi-detector CT. Correlation coefficients were used to assess the association between area measurements and volumes as well as metabolic risk factors stratified by gender. Results: Area-based measurements of SAT and VAT obtained at all anatomic landmarks were strongly associated with SAT and VAT volumes (all r>0.93, P<0.0001 and r>0.87, P<0.0001, for women and men; respectively). Consistently, area-based measurements of SAT and VAT obtained at L(3/4) were most strongly associated with volumetric measured VAT and SAT independent of age (both r=0.99 in men, r=0.96 for SAT and r=0.99 for VAT in women, all P-value <0.0001) and were similarly correlated with risk factors compared with SAT and VAT volumes (all P<0.05 for fasting plasma glucose, triglycerides, high-density lipoprotein, systolic blood pressure). Conclusion: Among area-based measurements of SAT and VAT, those obtained at the level of L(3/4) were strongly associated with SAT and VAT volumes and cardio-metabolic risk factors in both men and women. International Journal of Obesity (2010) 34, 781-787; doi: 10.1038/ijo.2009.279; published online 12 January 2010 C1 [O'Donnell, C. J.; Fox, C. S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Irlbeck, T.; Bamberg, F.; Hoffmann, U.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Massaro, J. M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, C. J.] Harvard Univ, Sch Med, Dept Med, Cardiol Div,Massachusetts Gen Hosp, Boston, MA USA. [Fox, C. S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM foxca@nlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195] FX This study was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195). NR 18 TC 38 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2010 VL 34 IS 4 BP 781 EP 787 DI 10.1038/ijo.2009.279 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 580WQ UT WOS:000276481700023 PM 20065971 ER PT J AU Zhou, XL Yang, XY Popescu, NC AF Zhou, Xiaoling Yang, Xu-Yu Popescu, Nicholas C. TI Synergistic antineoplastic effect of DLC1 tumor suppressor protein and histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), on prostate and liver cancer cells: Perspectives for therapeutics SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE DLC1; tumor suppressor gene; SAHA; apoptosis; cell proliferation; tumorigenicity; prostate cancer cells; liver cancer cells ID HUMAN BREAST-CANCER; PROMOTER HYPERMETHYLATION; HEPATOCELLULAR-CARCINOMA; MULTIPLE-MYELOMA; IN-VIVO; GENE; THERAPY; TUMORIGENICITY; EXPRESSION; GROWTH AB Inactivation of tumor suppressor genes is a major contributing alteration in the initiation or progression of cancer. The human tumor suppressor gene DLC1 (deleted in liver cancer 1) is frequently downregulated or silenced in multiple cancers, predominantly by epigenetic mechanisms. With the Current considerable interest and progress in epigenetic therapy, a number of promising antineoplastic agents, particularly histone deacetylase (HDAC) inhibitors, have been developed and Used Successfully in clinical trials. Both DLC1 and HDAC inhibitors exert antineoplastic functions, and their combined action Could be exploited for a more effective cancer therapy. To evaluate the potential benefits of this approach, we examined the antineoplastic effects of adenoviral (Ad)-DLC1-mediated transduction and exposure to suberoylanilide hydroxamic acid (SAHA), a powerful HDAC inhibitor, in two human cancer cell lines that lack intrinsic DLC1 expression, 22Rv1 prostate cancer cells and 7703K human hepatocellular carcinoma cells. Consistent with the oncosuppressive function of DLC1 in several cancers. including prostate and liver cancer. transduction of 22Rv1 and 7703K cells with all Ad-DLC1 expression vector resulted in alterations of cell morphology, induction of apoptosis, and inhibition of cell proliferation, migration, and anchorage-independent growth. A low concentration of SAHA (5 IN) efficiently restored the expression of DLC1 in 22Rv1 cells that lack DLC1 expression due to historic deacetylation but had a minimal effect in 7703K cells in which silencing of the DLC1 gene is due mainly to promoter hypermethylation. Regardless of the epigenetic mechanism of DLC1 inactivation, SAHA treatment of DLC1-transduced cells had a synergistic inhibitory effect on tumor, cell proliferation and tumorigenesis in both cell lines. In 22Rv1 cells, this combination regimen nearly abolished the formation of colonies in semisolid media as a measure of tumorigenicity in vitro. Current in vitro results validate this protocol as a potentially new therapeutic option in certain cancers. C1 [Zhou, Xiaoling; Yang, Xu-Yu; Popescu, Nicholas C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI yang, xuyu/D-1414-2012 FU National Cancer Institute, NIH FX This work was Supported by the Intramural Research Program of the National Cancer Institute, NIH. We Would like to thank Drs Yung-Jue Bang and Tai Young Kim for providing the DLC1 promotor-luciferase construct and Dr Victoria Richon for helpful suggestions. NR 39 TC 8 Z9 9 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 2010 VL 36 IS 4 BP 999 EP 1005 DI 10.3892/ijo_00000580 PG 7 WC Oncology SC Oncology GA 571ZD UT WOS:000275794300031 PM 20198346 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Profile Likelihood and Incomplete Data SO INTERNATIONAL STATISTICAL REVIEW LA English DT Article DE Censoring; evidential analysis; law of likelihood; likelihood paradigm; missing data; partial identification ID PARTIALLY IDENTIFIED PARAMETERS; STATISTICAL EVIDENCE; CONFIDENCE-INTERVALS; COMPETING RISKS; TRIALS; MODELS AB According to the law of likelihood, statistical evidence is represented by likelihood functions and its strength measured by likelihood ratios. This point of view has led to a likelihood paradigm for interpreting statistical evidence, which carefully distinguishes evidence about a parameter from error probabilities and personal belief. Like other paradigms of statistics, the likelihood paradigm faces challenges when data are observed incompletely, due to non-response or censoring, for instance. Standard methods to generate likelihood functions in such circumstances generally require assumptions about the mechanism that governs the incomplete observation of data, assumptions that usually rely on external information and cannot be validated with the observed data. Without reliable external information, the use of untestable assumptions driven by convenience could potentially compromise the interpretability of the resulting likelihood as an objective representation of the observed evidence. This paper proposes a profile likelihood approach for representing and interpreting statistical evidence with incomplete data without imposing untestable assumptions. The proposed approach is based on partial identification and is illustrated with several statistical problems involving missing data or censored data. Numerical examples based on real data are presented to demonstrate the feasibility of the approach. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA. RP Zhang, ZW (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA. EM Zhiwei.Zhang@nih.gov FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported in part by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development. The author would like to thank two anonymous referees whose comments have improved the manuscript greatly. NR 23 TC 4 Z9 5 U1 0 U2 1 PU INT STATISTICAL INST PI VOORBURG PA 428 PRINSES BEATRIXLAAN, 2270 AZ VOORBURG, NETHERLANDS SN 0306-7734 J9 INT STAT REV JI Int. Stat. Rev. PD APR PY 2010 VL 78 IS 1 BP 102 EP 116 DI 10.1111/j.1751-5823.2010.00107.x PG 15 WC Statistics & Probability SC Mathematics GA 577TI UT WOS:000276246500007 PM 21278854 ER PT J AU Hackler, L Wan, J Swaroop, A Qian, J Zack, DJ AF Hackler, Laszlo, Jr. Wan, Jun Swaroop, Anand Qian, Jiang Zack, Donald J. TI MicroRNA Profile of the Developing Mouse Retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID POSTTRANSCRIPTIONAL REGULATION; EXPRESSION; TARGETS; IDENTIFICATION; SPECIFICATION; DEGENERATION; DROSOPHILA; DISEASE; TISSUES; GENES AB PURPOSE. MicroRNAs (miRNAs) are short, noncoding transcripts that negatively regulate gene expression. They are implicated in diverse cellular processes. The purpose of this study was to obtain a global expression profile of miRNAs in the developing retina and identify differences in miRNA expression between adult rod and cone photoreceptors. METHODS. Locked nucleic acid (LNA) microarrays were used to investigate the miRNA transcriptome of the developing mouse retina and brain. Real-time PCR was used to validate the array findings. Laser capture microdissection was used to determine the miRNA spatial pattern of expression. RESULTS. One hundred thirty-eight miRNAs were expressed at at least one of the investigated time points. Several miRNAs showed significant changes in expression between embryonic day 15 and adult age in both retina and brain. Cluster analysis identified subgroups of miRNAs showing defined expression profiles. Globally, correlation of expression was higher, with increasing sequence similarity of the mature miRNAs. The miRNAs with identical seed sequences exhibited highly correlated expression profiles. The co-expression of selected host gene and intronic miRNA pairs was confirmed in adult retina. In some cases, expression profiles of miRNAs showed weak correlation with those of their host transcripts, suggesting posttranscriptional regulation of miRNAs during development. In addition, the miRNA transcriptome of rod-and cone-dominant retinas showed only minor differences, and no miRNAs specific for either cell-type were identified. CONCLUSIONS. Global expression profiling revealed dozens of miRNAs with significant expression changes in the developing retina. Precise patterns of expression of miRNAs suggest their specific roles in development. (Invest Ophthalmol Vis Sci. 2010; 51:1823-1831) DOI: 10.1167/iovs.09-4657 C1 [Hackler, Laszlo, Jr.; Wan, Jun; Qian, Jiang; Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. [Zack, Donald J.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA. [Zack, Donald J.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. [Swaroop, Anand] NEI, NNRL, NIH, Bethesda, MD 20892 USA. [Swaroop, Anand] Univ Michigan, Dept Ophthalmol, Ann Arbor, MI USA. [Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Zack, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Smith Bldg 400 N Broadway, Baltimore, MD 21287 USA. EM jqian2@jhmi.edu; dzack@jhmi.edu RI Wan, Jun/H-7132-2013; Wan, Jun/A-2177-2014; OI Wan, Jun/0000-0001-9286-6562; Wan, Jun/0000-0001-9286-6562; Zack, Don/0000-0002-7966-1973; Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute; National Institutes of Health; Foundation Fighting Blindness; Research to Prevent Blindness, Inc.; Guerrieri Family Foundation FX Supported in part by research grants from the National Eye Institute, National Institutes of Health, and the Foundation Fighting Blindness, unrestricted funds from Research to Prevent Blindness, Inc., and generous gifts from Robert and Clarice Smith and The Guerrieri Family Foundation. NR 29 TC 39 Z9 39 U1 0 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2010 VL 51 IS 4 BP 1823 EP 1831 DI 10.1167/iovs.09-4657 PG 9 WC Ophthalmology SC Ophthalmology GA 574ND UT WOS:000275995800005 PM 19933188 ER PT J AU Johnson, TV Bull, ND Hunt, DP Marina, N Tomarev, SI Martin, KR AF Johnson, Thomas V. Bull, Natalie D. Hunt, David P. Marina, Nephtali Tomarev, Stanislav I. Martin, Keith R. TI Neuroprotective Effects of Intravitreal Mesenchymal Stem Cell Transplantation in Experimental Glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL GANGLION-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RETROGRADE AXONAL-TRANSPORT; HUMAN NEURAL PROGENITORS; A-INDUCED AUTOIMMUNITY; SPINAL-CORD-INJURY; RAT MODEL; STROMAL CELLS; OPTIC-NERVE; NEUROTROPHIC FACTOR AB PURPOSE. Retrograde neurotrophic factor transport blockade has been implicated in the pathophysiology of glaucoma. Stem cell transplantation appears to ameliorate some neurodegenerative conditions in the brain and spinal cord, in part by neurotrophic factor secretion. The present study was conducted to determine whether local or systemic bone marrow-derived mesenchymal stem cell (MSC) transplantation can confer neuroprotection in a rat model of laser-induced ocular hypertensive glaucoma. METHODS. MSCs were isolated from the bone marrow of adult wild-type and transgenic rats that ubiquitously express green fluorescent protein. MSCs were transplanted intravitreally 1 week before, or intravenously on the day of, ocular hypertension induction by laser photocoagulation of the trabecular meshwork. Ocular MSC localization and integration were determined by immunohistochemistry. Optic nerve damage was quantified by counting axons within optic nerve cross-sections 4 weeks after laser treatment. RESULTS. After intravitreal transplantation, MSCs survived for at least 5 weeks. Cells were found mainly in the vitreous cavity, though a small proportion of discrete cells migrated into the host retina. Intravitreal MSC transplantation resulted in a statistically significant increase in overall RGC axon survival and a significant decrease in the rate of RGC axon loss normalized to cumulative intraocular pressure exposure. After intravenous transplantation, MSCs did not migrate to the injured eye. Intravenous transplantation had no effect on optic nerve damage. CONCLUSIONS. Local, but not systemic, transplantation of MSCs was neuroprotective in a rat glaucoma model. Autologous intravitreal transplantation of MSCs should be investigated further as a potential neuroprotective therapy for glaucoma. (Invest Ophthalmol Vis Sci. 2010; 51: 2051-2059) DOI:10.1167/iovs.09-4509 C1 [Johnson, Thomas V.; Bull, Natalie D.; Hunt, David P.; Marina, Nephtali; Martin, Keith R.] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 0PY, England. [Johnson, Thomas V.; Tomarev, Stanislav I.] NEI, Mol Mech Glaucoma Sect, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, KR (reprint author), Univ Cambridge, Ctr Brain Repair, Forvie Site,Robinson Way, Cambridge CB2 0PY, England. EM krgm2@cam.ac.uk RI Johnson, Thomas/C-9351-2011 OI Johnson, Thomas/0000-0002-5372-5457 FU GSK Clinician Scientist Fellowship; Fight for Sight (UK); National Institutes of Health; Gates-Cambridge Trust; Cambridge University Hospitals NHS Foundation Trust; Richard Norden Glaucoma Research Fund; Fight for Sight; National Eye Institute FX Supported by a GSK Clinician Scientist Fellowship (KRM); a Fight for Sight (UK) research grant (NDB); a National Institutes of Health OxCam Scholarship (TVJ); the Gates-Cambridge Trust (TVJ); Cambridge University Hospitals NHS Foundation Trust; the Richard Norden Glaucoma Research Fund; Fight for Sight (UK); and the National Eye Institute Intramural Research Program. NR 60 TC 109 Z9 121 U1 1 U2 16 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2010 VL 51 IS 4 BP 2051 EP 2059 DI 10.1167/iovs.09-4509 PG 9 WC Ophthalmology SC Ophthalmology GA 574ND UT WOS:000275995800034 PM 19933193 ER PT J AU Hendrickson, SL Jabs, DA Van Natta, M Lewis, RA Wallace, DC O'Brien, SJ AF Hendrickson, Sher L. Jabs, Douglas A. Van Natta, Mark Lewis, Richard Alan Wallace, Douglas C. O'Brien, Stephen J. TI Mitochondrial Haplogroups Are Associated With Risk of Neuroretinal Disorder in HIV-Positive Patients SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE AIDS; mitochondrial DNA; neuroretinal disorder ID HEREDITARY OPTIC NEUROPATHY; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; VISUAL-ACUITY LOSS; OCULAR COMPLICATIONS; CYTOMEGALOVIRUS RETINITIS; INFECTED INDIVIDUALS; AIDS; DNA; LIPOATROPHY AB Although highly active antiretroviral therapy has improved survivorship dramatically and decreased the incidence of cytomegalovirus retinitis among patients with AIDS, other ophthalmic complications continue to occur. One complication observed in similar to 12% of HIV-infected patients is a presumed neuroretinal disorder (NRD), manifested as decreased contrast sensitivity and associated with vague subjective complaints of hazy vision. Pathologically, patients with AIDS even without ocular opportunistic infections have loss of optic nerve axons, suggestive of mitochondrial dysfunction. We explored whether variation in mitochondrial DNA was associated with time to NRD in HIV-infected patients in the Longitudinal Study of Ocular Complications of AIDS cohort. Within the Western European, or "N", mitochondrial DNA macrohaplogroup, haplogroup J, was associated with 80% decrease in the risk of progression to NRD during the study (hazard ratio = 0.20, P = 0.039) and suggested an independent association with protection against NRD in a cross-section of all patients taken at enrollment (1.5% vs. 8.9% in patients with vs. without haplogroup J, respectively, P = 0.05). These data suggest that mitochondrial genotype may influence propensity to develop HIV-associated NRD in patients with AIDS. C1 [Hendrickson, Sher L.; O'Brien, Stephen J.] Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Jabs, Douglas A.; Van Natta, Mark] Johns Hopkins Univ, Dept Epidemiol, Ctr Clin Trials, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Ophthalmol, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lewis, Richard Alan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Ecol & Evolutionary Biol, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Biol Chem, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. [Wallace, Douglas C.] Univ Calif Irvine, Dept Pediat, Ctr Mol & Mitochondrial Med & Genet, Irvine, CA 92717 USA. RP Hendrickson, SL (reprint author), Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. EM hendricksons@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; National Eye Institute [U10 EY 08052]; Johns Hopkins University Bloomberg School of Public Health [U10 EY 08057]; University of Wisconsin, Madison School of Medicine [U10 EY 08067] FX This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. Longitudinal Studies of the Ocular Complications of AIDS is supported by cooperative agreements from the National Eye Institute to The Mount Sinai School of Medicine (U10 EY 08052), The Johns Hopkins University Bloomberg School of Public Health (U10 EY 08057), and the University of Wisconsin, Madison School of Medicine (U10 EY 08067). NR 30 TC 14 Z9 14 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2010 VL 53 IS 4 BP 451 EP 455 DI 10.1097/QAI.0b013e3181cb8319 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 567YW UT WOS:000275486600003 PM 20098332 ER PT J AU Shaffer, DN Ngetich, IK Bautista, CT Sawe, FK Renzullo, PO Scott, PT Kibaya, RM Imbuki, KO Michael, NL Birx, DL Wasunna, MK Robb, ML AF Shaffer, Douglas N. Ngetich, Ignatius K. Bautista, Christian T. Sawe, Frederick K. Renzullo, Philip O. Scott, Paul T. Kibaya, Rukia M. Imbuki, Kennedy O. Michael, Nelson L. Birx, Deborah L. Wasunna, Monique K. Robb, Merlin L. TI HIV-1 Incidence Rates and Risk Factors in Agricultural Workers and Dependents in Rural Kenya: 36-Month Follow-Up of the Kericho HIV Cohort Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; incidence; cohort; Kericho; Kenya ID REPRODUCTIVE AGE; KAGERA REGION; INFECTION; UGANDA; POPULATION; PREVALENCE; TRENDS; MALAWI; PROSTITUTES; TANZANIA AB Background: Incidence data from prospective cohort studies using rigorous laboratory methods are important in designing and evaluating HIV vaccine and therapeutic clinical trials and health care programs. We report 36-month HIV-1 incidence rates and demographic and psychosocial risks from the Kericho cohort in rural Kenya's southern Rift Valley Province. Methods: Thirty-six month, prospective, closed, observational cohort study of adult plantation workers and dependents followed biannually. HIV-1 incidence rates per 100 person-years (py) were calculated, and Cox regression analyses were used to estimate hazards ratios (HR) associated with seroconversion. Results: Two thousand four hundred volunteers (mean age +/- SD = 30.1 +/- 8.5 years; 36.5% women) participated. Twenty-nine new HIV cases were identified in year 1 of follow-up, which increased to cumulative totals of 49 and 63 cases in years 2 and 3, respectively. The corresponding 1-, 2-, and 3-year incidence rates were 1.41 [95% confidence interval (CI) = 0.95-2.02], 1.16 (95% CI = 0.86-1.54), and 1.00 (95% CI = 0.77-1.28) per 100 py. Risk factors associated with HIV seroconversion included the following: of the Luo tribe (HR = 3.31; 95% CI = 1.65-6.63), marriage more than once (HR = 2.83; 95% CI = 1.20-6.69), self-reported male circumcision (HR = 0.32; 95% CI = 0.17-0.60), history of sexually transmitted infection (HR = 2.40; 95% CI = 1.09-5.26), history of substance abuse during sex (HR = 2.44; 95% CI = 1.16-5.13), and history of transactional sex (HR = 3.30; 95% CI = 1.79-6.09). Conclusions: HIV-1 incidence rates were relatively low in adult plantation workers and dependents in rural Kenya. Cohorts including higher risk populations (eg, commercial sex workers) warrant consideration for regional HIV preventive vaccine trials. Even low incidence, well-described cohorts generate valuable epidemiological clinical trial data. C1 [Shaffer, Douglas N.; Ngetich, Ignatius K.; Bautista, Christian T.; Sawe, Frederick K.; Scott, Paul T.; Kibaya, Rukia M.; Imbuki, Kennedy O.; Michael, Nelson L.; Birx, Deborah L.; Robb, Merlin L.] US Mil HIV Res Program, Rockville, MD USA. [Shaffer, Douglas N.] Kenya Walter Reed Project HIV Program, US Army Med Res Unit, Kericho, Kenya. [Shaffer, Douglas N.; Scott, Paul T.; Michael, Nelson L.; Birx, Deborah L.] Walter Reed Army Inst Res, Rockville, MD USA. [Ngetich, Ignatius K.; Sawe, Frederick K.; Kibaya, Rukia M.; Imbuki, Kennedy O.; Wasunna, Monique K.] Kenya Govt Med Res Ctr, Kericho, Kenya. [Ngetich, Ignatius K.; Sawe, Frederick K.; Kibaya, Rukia M.; Imbuki, Kennedy O.; Wasunna, Monique K.] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Bautista, Christian T.] Adv Mil Med Inc, Henry M Jackson Fdn, Rockville, MD USA. [Renzullo, Philip O.; Robb, Merlin L.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Shaffer, DN (reprint author), Kenya Walter Reed Project HIV Program, US Army Med Res Unit, Kericho, Kenya. EM dshaffer@wrp-kch.org RI Bautista, Christian/B-2812-2011 FU Walter Reed Army Institute of Research Institutional Research Board [RV142]; HIV and Malaria Cohort Study Among Plantation Workers and Adult Dependents in Kericho, Kenya, is funded through the United States Military HIV Research Program FX Supported by The Walter Reed Army Institute of Research Institutional Research Board human use protocol #855 (RV142); "HIV and Malaria Cohort Study Among Plantation Workers and Adult Dependents in Kericho, Kenya," is funded through the United States Military HIV Research Program (the Walter Reed Army Institute of Research and the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc). NR 24 TC 5 Z9 5 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2010 VL 53 IS 4 BP 514 EP 521 DI 10.1097/QAI.0b013e3181bcdae0 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 567YW UT WOS:000275486600013 PM 19855286 ER PT J AU Chaturvedi, AK AF Chaturvedi, Anil K. TI Beyond Cervical Cancer: Burden of Other HPV-Related Cancers Among Men and Women SO JOURNAL OF ADOLESCENT HEALTH LA English DT Review DE Human papillomavirus; Vaccination ID SQUAMOUS-CELL CARCINOMA; PAPILLOMAVIRUS-ASSOCIATED CANCERS; RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; INCIDENCE TRENDS; UNITED-STATES; NECK CANCERS; OROPHARYNGEAL CANCERS; QUADRIVALENT VACCINE; YOUNG-WOMEN AB Human papillomavirus (HPV) infection is a necessary cause of cervical cancer, and is etiologically associated with a subset of cancers of the anus, oropharynx, penis, vagina, and vulva. Current data indicate that HPV infection is potentially associated with 90%-93% of anal cancers, 12%-63% of oropharyngeal cancers, 36%-40% of penile cancers, 40%-64% of vaginal cancers, and 40%-51% of vulvar cancers. HPV infection accounts for up to 492,800 cervical cancers and 97,215 cases of noncervical HPV-related cancers worldwide during 2002, including up to 50,780 cancers among men (13,485 anal cancers, 26,775 oropharyngeal cancers, and 10,520 penile cancers) and up to 46,435 cancers among women (14,787 anal cancers, 6,048 oropharyngeal cancers, and 25,600 vaginal/vulvar cancers). In the United States annually (1998-2003), up to 10,846 cervical cancers, 4,753 noncervical cancers among men, and 4,128 noncervical cancers among women are potentially attributable to HPV infection. Incidence rates for cervical cancer have declined significantly during the past 30 years in the United States, consistent with the success of Pap smear screening. However, incidence rates for anal, oropharyngeal, and vulvar cancers have increased substantially in recent years. The high proportion of cervical and noncervical cancers caused by HPV types 16 and 18, that is, 70%-76% for cervical cancers and 63%-95% for noncervical cancers, underscores the potential for prevention of a majority of cervical as well as noncervical HPV-related cancers through prophylactic HPV vaccination. (C) 2010 Society for Adolescent Medicine. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, Rockville, MD 20852 USA. RP Chaturvedi, AK (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, NIH, 6120 Execut Blvd,EPS 7072, Rockville, MD 20852 USA. EM chaturva@mail.nih.gov RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Merck Co., Inc FX This article appears in a supplement to the Journal of Adolescent Health sponsored by SciMed LLC and supported by an educational grant from Merck & Co., Inc. Dr. Chaturvedi has no relevant conflicts to report and was not compensated for his work on this article. NR 58 TC 114 Z9 119 U1 3 U2 49 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 2010 VL 46 IS 4 SU 1 BP S20 EP S26 DI 10.1016/j.jadohealth.2010.01.016 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 571VP UT WOS:000275784300004 PM 20307840 ER PT J AU Mueller, GA Edwards, LL Aloor, JJ Fessler, MB Glesner, J Pomes, A Chapman, MD London, RE Pedersen, LC AF Mueller, Geoffrey A. Edwards, Lori L. Aloor, Jim J. Fessler, Michael B. Glesner, Jill Pomes, Anna Chapman, Martin D. London, Robert E. Pedersen, Lars C. TI The structure of the dust mite allergen Der p 7 reveals similarities to innate immune proteins SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; allergens; dust mites; Der p 7; LPS-binding protein; Toll-like receptor 4; lipopeptide; innate immunity ID T-CELL RESPONSES; BET V 1; BINDING-PROTEIN; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; CROSS-REACTIVITY; MAJOR ALLERGEN; ASTHMA; FOLD; IGE AB Background: Sensitization to house dust mite allergens is strongly correlated with asthma. Der p 7 elicits strong IgE antibody and T-cell responses in patients with mite allergy. However, the structure and biological function of this important allergen are unknown. Allergen function might contribute to allergenicity, as shown for the protease activity of group I mite allergens and the interaction with the innate immune system by group 2 mite allergens. Objective: We sought to determine the crystal structure of Der p 7 and to investigate its biological function. Methods: X-ray crystallography was used to determine the Der p 7 structure. Nuclear magnetic resonance analysis and biochemical assays were used to examine the binding of Der p 7 to predicted ligands. Results: Der p 7 has an elongated structure, with two 4-stranded antiparallel beta-sheets that wrap around a long C-terminal helix. The fold of Der p 7 is similar to that of LPS-binding protein (LBP), which interacts with Toll-like receptors after binding LPS and other bacterially derived lipid ligands. Nuclear magnetic resonance and biochemical assays indicate that Der p 7 does not bind I,PS but binds with weak affinity to the bacterial lipopeptide polymyxin B in the predicted binding site of Der p 7. Conclusions: Der p 7 binds a bacterially derived lipid product, a common feature of some allergens. The finding that the group 7, as well as the group 2, mite allergens are structurally similar to different proteins in the Toll-like receptor pathway further strengthens the connections between dust mites, innate immunity, and allergy. (J Allergy Clin Immunol 2010;125:909-17.) C1 [Mueller, Geoffrey A.; Edwards, Lori L.; London, Robert E.; Pedersen, Lars C.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Edwards, Lori L.] Natl Inst Environm Hlth Sci, Prot Express Core Facil, Res Triangle Pk, NC 27709 USA. [Aloor, Jim J.; Fessler, Michael B.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Glesner, Jill; Pomes, Anna; Chapman, Martin D.] INDOOR Biotechnol Inc, Charlottesville, VA USA. RP Mueller, GA (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, 111 TW Alexander Dr MD-MR01, Res Triangle Pk, NC 27709 USA. EM mueller3@niehs.nih.gov OI Pomes, Anna/0000-0002-8729-1829 FU National Institutes of Health (NIH) [AI077653]; National Institute of Environmental Health Sciences; National Institute for Allergy and Infectious Diseases; National Institute for Environmental Health Sciences FX Supported in part by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences, and by NIH grant AI077653 (A.P. and M.D.C.) from the National Institute for Allergy and Infectious Diseases.; Disclosure of potential conflict of interest: M. D. Chapman is an owner of Indoor Biotechnologies, Inc, and Indoor Biotechnologies Ltd and has received research support front the National Institute for Environmental Health Sciences. The rest of the authors have declare that they have no conflict of interest. NR 57 TC 55 Z9 55 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2010 VL 125 IS 4 BP 909 EP 917 DI 10.1016/j.jaci.2009.12.016 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 584XP UT WOS:000276787900018 PM 20226507 ER PT J AU Caminha, I Fleisher, TA Hornung, RL Dale, JK Niemela, JE Price, S Davis, J Perkins, K Dowdell, KC Brown, MR Rao, VK Oliveira, JB AF Caminha, Iusta Fleisher, Thomas A. Hornung, Ronald L. Dale, Janet K. Niemela, Julie E. Price, Susan Davis, Joie Perkins, Katie Dowdell, Kennichi C. Brown, Margaret R. Rao, V. Koneti Oliveira, Joao Bosco TI Using biomarkers to predict the presence of FAS mutations in patients with features of the autoimmune lymphoproliferative syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID DISEASE C1 [Caminha, Iusta; Fleisher, Thomas A.; Niemela, Julie E.; Brown, Margaret R.; Oliveira, Joao Bosco] NIAID, Dept Lab Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Dale, Janet K.] NIAID, Off Clin Res, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Price, Susan; Davis, Joie; Rao, V. Koneti] NIAID, ALPS Unit, NIH, Bethesda, MD 20892 USA. [Dowdell, Kennichi C.] NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hornung, Ronald L.] NCI, Clin Serv Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Perkins, Katie] NCI, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Caminha, I (reprint author), NIAID, Dept Lab Med, Ctr Clin, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM oliveirajb@cc.nih.gov OI Oliveira, Joao/0000-0001-9388-8173; Niemela, Julie/0000-0003-4197-3792 FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z01 CL010287-11, Z01 CL010287-12]; NCI NIH HHS [HHSN261200800001E] NR 7 TC 33 Z9 34 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2010 VL 125 IS 4 BP 946 EP 949 DI 10.1016/j.jaci.2009.12.983 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 584XP UT WOS:000276787900026 PM 20227752 ER PT J AU Cohen, SG Mazzullo, JC AF Cohen, Sheldon G. Mazzullo, Joy C. TI Slow reactive substance of anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Cohen, Sheldon G.; Mazzullo, Joy C.] NIAID, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2010 VL 125 IS 4 BP 950 EP 951 DI 10.1016/j.jaci.2009.12.940 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 584XP UT WOS:000276787900027 PM 20226503 ER PT J AU Kendall, PC Compton, SN Walkup, JT Birmaher, B Albano, AM Sherrill, J Ginsburg, G Rynn, M McCracken, J Gosch, E Keeton, C Bergman, L Sakolsky, D Suveg, C Iyengar, S March, J Piacentini, J AF Kendall, Philip C. Compton, Scott N. Walkup, John T. Birmaher, Boris Albano, Anne Marie Sherrill, Joel Ginsburg, Golda Rynn, Moira McCracken, James Gosch, Elizabeth Keeton, Courtney Bergman, Lindsey Sakolsky, Dara Suveg, Cindy Iyengar, Satish March, John Piacentini, John TI Clinical characteristics of anxiety disordered youth SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Anxiety; Anxiety in children and adolescence; Comorbidities ID SELF-STATEMENT QUESTIONNAIRE; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; GLOBAL ASSESSMENT SCALE; CHILDHOOD ANXIETY; INTERVIEW SCHEDULE; PSYCHOMETRIC PROPERTIES; SOCIAL PHOBIA; NEGATIVE AFFECTIVITY; PARENT VERSION AB Reports the characteristics of a large, representative sample of treatment-seeking anxious youth (N = 488). Participants, aged 7-17 years (mean 10.7 years), had a principal DSM-IV diagnosis of separation anxiety disorder (SAD), generalized anxiety disorder (GAD), or social phobia (SP). Although youth with a co-primary diagnosis for which a different disorder-specific treatment would be indicated (e.g., major depressive disorder, substance abuse) were not included, there were few other exclusion criteria. Participants and their parent/guardian underwent an extensive baseline assessment using a broad array of measures capturing diagnostic status, anxiety symptoms and severity, and areas of functional impairment. Means and standard deviations of the measures of psychopathology and data on diagnostic status are provided. The sample had moderate to severe anxiety disorder and was highly comorbid, with 55.3% of participants meeting criteria for at least one non-targeted DSM-IV disorder. Anxiety disorders in youth often do not present as a single/focused disorder: such disorders in youth overlap in symptoms and are highly comorbid among themselves. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Kendall, Philip C.] Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, Philadelphia, PA 19122 USA. [Compton, Scott N.; March, John] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Walkup, John T.; Ginsburg, Golda; Keeton, Courtney] Johns Hopkins Univ Hosp, Div Child & Adolescent Psychiat, Baltimore, MD 21287 USA. [Birmaher, Boris; Sakolsky, Dara] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Albano, Anne Marie; Rynn, Moira] Columbia Univ, Med Ctr, New York State Psychiat Inst, New York, NY 10032 USA. [Sherrill, Joel] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [McCracken, James; Bergman, Lindsey; Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Gosch, Elizabeth] Philadelphia Coll Osteopath Med, Dept Psychol, Philadelphia, PA 19131 USA. [Suveg, Cindy] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Iyengar, Satish] Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. RP Kendall, PC (reprint author), Temple Univ, Dept Psychol, Child & Adolescent Anxiety Disorders Clin, 1701 N 13th St, Philadelphia, PA 19122 USA. EM pkendall@temple.edu RI Piacentini, John/C-4645-2011 FU NIMH NIH HHS [K23 MH075843, L40 MH072315, L40 MH072315-02, U01 MH063747, U01 MH063747-01A1, U01 MH063747-02, U01 MH063747-03, U01 MH063747-04, U01 MH063747-05, U01 MH063747-06] NR 67 TC 110 Z9 113 U1 5 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2010 VL 24 IS 3 BP 360 EP 365 DI 10.1016/j.janxdis.2010.01.009 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 575GJ UT WOS:000276054700010 PM 20206470 ER PT J AU Kenworthy, L Case, L Harms, MB Martin, A Wallace, GL AF Kenworthy, Lauren Case, Laura Harms, Madeline B. Martin, Alex Wallace, Gregory L. TI Adaptive Behavior Ratings Correlate With Symptomatology and IQ Among Individuals With High-Functioning Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Adaptive behavior; Social skills; IQ; Symptomatology; Asperger's syndrome ID DIAGNOSTIC INTERVIEW; DEVELOPMENTAL DISORDERS; CHILDREN; VINELAND; PREDICTORS; SCALES; RELIABILITY; DEFICITS; DOMAINS; AGE AB Caregiver report on the Adaptive Behavior Assessment System-II (ABAS) for 40 high-functioning individuals with Autism Spectrum Disorders (ASD) and 30 typically developing (TD) individuals matched for age, IQ, and sex ratio revealed global adaptive behavior deficits in ASD, with social skills impairments particularly prominent. Within the ASD group, adaptive communication skills were positively related to IQ while global adaptive functioning was negatively associated with autism symptomatology. Autistic behavior ratings related negatively to ABAS scores in the TD but not the ASD group. This investigation demonstrates: the utility of an adaptive functioning checklist for capturing impairments, even in high-functioning individuals with ASD; and that a relationship between social abilities and autism exists independently of intelligence. C1 [Kenworthy, Lauren; Case, Laura; Harms, Madeline B.; Martin, Alex; Wallace, Gregory L.] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA. [Kenworthy, Lauren] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Kenworthy, L (reprint author), Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, 15245 Shady Grove Rd,South Bldg,Suite 350, Rockville, MD 20850 USA. EM lkenwort@cnmc.org RI martin, alex/B-6176-2009; OI Case, Laura/0000-0003-3730-2451; Wallace, Gregory/0000-0003-0329-5054 FU Intramural NIH HHS [Z99 MH999999] NR 26 TC 29 Z9 29 U1 5 U2 22 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 2010 VL 40 IS 4 BP 416 EP 423 DI 10.1007/s10803-009-0911-4 PG 8 WC Psychology, Developmental SC Psychology GA 568UZ UT WOS:000275550200002 PM 19949846 ER PT J AU Gorlick, R Khanna, C AF Gorlick, Richard Khanna, Chand TI Osteosarcoma SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GROWTH-FACTOR-I; METASTATIC BEHAVIOR; PEDIATRIC OSTEOSARCOMA; OSTEOGENIC-SARCOMA; CANCER METASTASIS; MET/HGF RECEPTOR; BONE METASTASIS; BREAST-CANCER; STEM-CELLS; EXPRESSION AB It has been difficult to identify the molecular features central to the pathogenesis of osteosarcoma owing to a lack of understanding of the cell or origin, the absence of identifiable precursor lesions, and its marked genetic complexity at the time of presentation Interestingly, several human genetic disorders and familial cancer syndromes, such as Li-Fraumeni syndrome, are linked to an increased risk of osteosarcoma Association of these same genetic alterations and osteosarcoma risk have been confirmed in murine models Osteosarcoma is associated with a variety of genetic abnormalities that are among the most commonly observed in human cancer, it remains unclear, however, what events initiate and are necessary to form osteosarcoma The availability of new resources for studying osteosarcoma and newer research methodologies offer an opportunity and promise to answer these currently unanswered questions Even in the absence of a more fundamental understanding of osteosarcoma, association studies and preclinical drug testing may yield clinically relevant information (C) 2010 American Society for Bone and Mineral Research. C1 [Gorlick, Richard] Yeshiva Univ, Dept Pediat & Mol Pharmacol, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, Clin Res Ctr, Washington, DC USA. RP Gorlick, R (reprint author), Yeshiva Univ, Dept Pediat, Albert Einstein Coll Med, Childrens Hosp Montefiore, 3415 Bainbridge Ave,3rd Floor, Bronx, NY 10467 USA. NR 83 TC 49 Z9 49 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 2010 VL 25 IS 4 BP 683 EP 691 DI 10.1002/jbmr.77 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589YF UT WOS:000277189400001 PM 20205169 ER PT J AU Cesare, S Nantel, A Marshall, JC Fernandes, BF Antecka, E Orellana, ME Abourbih, D Saornil, AM Burnier, MN AF Di Cesare, Sebastian Nantel, Andre Marshall, Jean-Claude Fernandes, Bruno F. Antecka, Emilia Orellana, Maria E. Abourbih, Daniel Saornil, Antonia M. Burnier, Miguel N., Jr. TI Expression profiling of formalin-fixed paraffin embedded primary human uveal melanomas using DASL matrices SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE Uveal melanoma; FFPE; DASL; Expression profiling; Histopathology; Clinical parameters ID CHROMOSOME-3; SURVIVAL; HER3; AMPLIFICATION; METASTASIS; DELETION; REVEALS; SAMPLES; CANCER; TUMORS AB Fresh biopsied ocular tumor tissues are difficult to obtain for the purpose of performing microarray experiments on extracted nucleic acids. Present technology allows for extraction of total RNA from formalin-fixed paraffin embedded (FFPE) tissue analyzed by the cDNA mediated Annealing Sectioning and Ligation (DASL) method. We aimed to correlate gene transcript differences between two uveal melanoma (UM) clinical-histopathological parameters (metastasis, cell type). A total of 43 FFPE UM were used. The expression of RPL13a, a ribosomal protein gene, for each sample was used to evaluate the quality of RNA extracted from FFPE tissue. Gene expression values generated from the array were analyzed using the GeneSpring GX software (Agilent). Immunohistochemistry was used in order to validate transcriptional findings at the protein level. A total of 106 genes were identified with (P < 0.05, Welch ANOVA test) a difference in transcript abundance for the metastasis clinical parameter. Furthermore, we identified 64 genes with a statistically significant (P < 0.05) difference in transcript abundance between the spindle and epithelioid cell types. Each individual sample for both groups (metastasis, cell type) exhibited distinct transcriptional profiles that were separated on a PCA. Positive nuclear immunostaining for LIG4-metastasis, ErbB3-cell type was found to be associated with better patient prognosis and outcome. To the best of our knowledge, this is the first time that a successful retrospective analysis has been done with UM FFPE RNA. This data may lead to future customized therapeutic targets, which may improve the now unchanged mortality rate of this particular malignancy. C1 [Di Cesare, Sebastian; Marshall, Jean-Claude; Fernandes, Bruno F.; Antecka, Emilia; Orellana, Maria E.; Abourbih, Daniel; Burnier, Miguel N., Jr.] McGill Univ, Ctr Hlth, Henry C Witelson Ophthalm Pathol Lab, Montreal, PQ H3A 2B4, Canada. [Di Cesare, Sebastian; Marshall, Jean-Claude; Fernandes, Bruno F.; Antecka, Emilia; Orellana, Maria E.; Saornil, Antonia M.; Burnier, Miguel N., Jr.] McGill Univ, Ctr Hlth, Henry C Witelson Ophthalm Pathol Registry, Montreal, PQ H3A 2B4, Canada. [Nantel, Andre] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. [Marshall, Jean-Claude] NCI, NIH, Bethesda, MD 20892 USA. [Fernandes, Bruno F.; Burnier, Miguel N., Jr.] Univ Fed Sao Paulo, UNIFESP EPM, Dept Ophthalmol, Sao Paulo, Brazil. [Saornil, Antonia M.] Univ Valladolid, Dept Ophthalmol, Ocular Pathol Lab, Valladolid, Spain. RP Cesare, S (reprint author), McGill Univ, Ctr Hlth, Henry C Witelson Ophthalm Pathol Lab, 3775 Univ St,Lyman Duff Bldg,Room 216, Montreal, PQ H3A 2B4, Canada. EM sebastian.dicesare@mail.mcgill.ca FU Cedars Cancer Institute; Hellen Keller Foundation FX This work was funded entirely by grants received from the Cedars Cancer Institute, and The Hellen Keller Foundation. We would like to take this opportunity to thank Dr. Nicholas Bertos and all other members of the McGill Molecular Oncology Group for technical support regarding microarray technology and optimization. NR 30 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-5216 EI 1432-1335 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD APR PY 2010 VL 136 IS 4 BP 577 EP 586 DI 10.1007/s00432-009-0692-3 PG 10 WC Oncology SC Oncology GA 557RC UT WOS:000274686800012 ER PT J AU Soetandyo, N Wang, QY Ye, YH Li, LY AF Soetandyo, Nia Wang, Qiuyan Ye, Yihong Li, Lianyun TI Role of intramembrane charged residues in the quality control of unassembled T-cell receptor alpha-chains at the endoplasmic reticulum SO JOURNAL OF CELL SCIENCE LA English DT Article DE ER-associated degradation (ERAD)/retrotranslocation/dislocation; Oligomerization; Intramembrane charge; Degradation signal/degron; TCR alpha ID PROTEIN DISULFIDE-ISOMERASE; ER-ASSOCIATED DEGRADATION; ANTIGEN RECEPTOR; MOLECULAR CHAPERONES; MISFOLDED PROTEINS; RETROTRANSLOCATION; CYTOSOL; COMPLEX; RECOGNITION; ASSOCIATION AB Endoplasmic reticulum (ER)-associated degradation (ERAD) of unassembled T-cell receptor alpha-chain (TCR alpha) is reliant on the presence of two basic residues in the transmembrane (TM) segment of TCR alpha. The precise role of these residues in ER quality control is unclear. Here, we show that a TCR alpha mutant lacking these intramembrane charged residues has a tendency to form homooligomers through an interchain disulfide bond that involves a specific pair of cysteine residues. Covalent oligomerization of TCR alpha appears to stabilize it at the ER membrane. The presence of a single lysine residue at specific positions within the TCR alpha TM domain abolishes its oligomerization and causes its rapid degradation. Conversely, when TCR alpha oligomerization is induced by a bivalent compound, the degradation of TCR alpha is inhibited. Together, these results suggest that the intramembrane charged residues in TCR alpha do not function as a signal for substrate recognition in ERAD. Instead, their primary role is to reduce TCR alpha oligomerization, maintaining it in a retrotranslocation-competent state. Our results also suggest that the ERAD machinery is inefficient when coping with oligomerized substrates, indicating a requirement for chaperone-mediated protein disassembly in the ER lumen prior to retrotranslocation. C1 [Soetandyo, Nia; Wang, Qiuyan; Ye, Yihong] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Li, Lianyun] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China. RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov; lilianyun@whu.edu.cn FU National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Ron Kopito (Stanford University, CA, USA) for reagents, Darrell Hurt (NIAID, MD, USA) for computer modeling and Juan Bonifacino (NICHD, MD, USA) for critical reading of the manuscript. The research is supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. Deposited in PMC for release after 12 months. NR 46 TC 16 Z9 16 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 2010 VL 123 IS 7 BP 1031 EP 1038 DI 10.1242/jcs.059758 PG 8 WC Cell Biology SC Cell Biology GA 573GI UT WOS:000275896200005 PM 20332119 ER PT J AU Liu, W Singh, SR Hou, SX AF Liu, Wei Singh, Shree Ram Hou, Steven X. TI JAK-STAT Is Restrained by Notch to Control Cell Proliferation of the Drosophila Intestinal Stem Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE JAK-STAT; STEM CELL; DROSOPHILA; INTESTINE ID BACTERIAL-INFECTION; MIDGUT; ACTIVATION; ENCODES; PATHWAY; KINASE; FAMILY; DETECT; TESTIS; GENES AB The Drosophila midgut epithelium undergoes continuous regeneration that is sustained by multipotent intestinal stem cells (ISCs) underneath. Notch signaling has dual functions to control ISC behavior: it slows down the ISC proliferation and drives the activated ISCs into different differentiation pathways at a dose-dependent manner. Here we identified a molecular mechanism to unite these two contradictory functions. We found JAK-STAT signaling controls ISC proliferation and this ability is negatively regulated by Notch at least through a transcriptional control of the JAK-STAT signaling ligand, unpaired (upd). This study provides insight into how stem cells, under steady conditions, balance the processes of proliferation and differentiation to maintain the stable cellular composition of a healthy tissue. J. Cell. Biochem. 109: 992999, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Liu, Wei; Singh, Shree Ram; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Liu, W (reprint author), NCI, Mouse Canc Genet Program, NIH, Bldg 560,Room 12-70, Frederick, MD 21702 USA. EM weiliu@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU NIH; National Cancer Institute FX Grant sponsor: Intramural Research Program of NIH; Grant sponsor: National Cancer Institute. NR 22 TC 58 Z9 67 U1 2 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 1 PY 2010 VL 109 IS 5 BP 992 EP 999 DI 10.1002/jcb.22482 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 580AN UT WOS:000276418900019 PM 20082318 ER PT J AU Henning, EC Warach, S Spatz, M AF Henning, Erica C. Warach, Steven Spatz, Maria TI Hypertension-induced vascular remodeling contributes to reduced cerebral perfusion and the development of spontaneous stroke in aged SHRSP rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ASL; hypertension; MRI; perfusion; SHRSP; stroke ID BLOOD-FLOW; PRONE RATS; GLUCOSE-UTILIZATION; BRAIN-DAMAGE; ISCHEMIA; REPERFUSION; COLLATERALS; PROTEOMICS; MATRIX; EDEMA AB Stroke in spontaneously-hypertensive, stroke-prone (SHRSP) rats is of particular interest because the pathogenesis is believed to be similar to that in the clinical setting. In this study, we employed multi-modal MRI-ASL, DWI, T(2), GRE, T(1) (pre/post contrast)-to investigate the natural history of spontaneous cerebral infarction and the specific role of cerebral perfusion in disease development. Twelve female SHRSP rats (age: similar to 1 year) were imaged within 1 to 3 days of symptom onset. The distribution of ischemic lesions was the following: 28.1% visual, 21.9% striatal, 18.8% motorsensory, 12.5% thalamic, 12.5% auditory, 3.1% frontal/prelimbic, and 3.1% multiple areas. Ischemic lesions had significantly reduced blood flow in comparison with healthy tissue. Ischemic lesions were characterized by hyperplastic, thrombosed, and compressed vessels. These findings suggest that ischemic lesion development is related to hypertension-induced vascular remodeling and persistent hypoperfusion. This model should be useful for studying the relationship between chronic hypertension and subsequent stroke, both in terms of primary and secondary prevention. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 827-836; doi:10.1038/jcbfm.2009.246; published online 2 December 2009 C1 [Henning, Erica C.] Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Spatz, Maria] Naval Med Res Ctr, Silver Spring, MD USA. RP Henning, EC (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bldg 10,Room B1D733,10 Ctr Dr,MSC 1063, Bethesda, MD 20892 USA. EM henninge@ninds.nih.gov RI Henning, Erica/E-8542-2010 FU Division of Intramural Research of the National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Division of Intramural Research of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. We thank Afonso C Silva, PhD, and Fernando P Paiva, PhD, for assistance in ASL optimization and setup. We also thank Christl A Ruetzler, BA, for advice on histological analysis and Ashleigh R Martin, BA, for assistance in MRI analysis. NR 40 TC 21 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2010 VL 30 IS 4 BP 827 EP 836 DI 10.1038/jcbfm.2009.246 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 577BZ UT WOS:000276197200017 PM 19953101 ER EF