FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cohen, LA Gutierrez, L Weiss, A Leichtmann-Bardoogo, Y Zhang, DL Crooks, DR Sougrat, R Morgenstern, A Galy, B Hentze, MW Lazaro, FJ Rouault, TA Meyron-Holtz, EG AF Cohen, Lyora A. Gutierrez, Lucia Weiss, Avital Leichtmann-Bardoogo, Yael Zhang, De-liang Crooks, Daniel R. Sougrat, Rachid Morgenstern, Avigail Galy, Bruno Hentze, Matthias W. Lazaro, Francisco J. Rouault, Tracey A. Meyron-Holtz, Esther G. TI Serum ferritin is derived primarily from macrophages through a nonclassical secretory pathway SO BLOOD LA English DT Article ID HUMAN ERYTHROID PRECURSORS; TRANSFERRIN IRON DELIVERY; ENDOPLASMIC-RETICULUM; REGULATORY PROTEIN-2; DIAGNOSTIC-VALUE; CONCANAVALIN-A; H-FERRITIN; METABOLISM; CELLS; RECEPTOR AB The serum ferritin concentration is a clinical parameter measured widely for the differential diagnosis of anemia. Its levels increase with elevations of tissue iron stores and with inflammation, but studies on cellular sources of serum ferritin as well as its subunit composition, degree of iron loading and glycosylation have given rise to conflicting results. To gain further understanding of serum ferritin, we have used traditional and modern methodologies to characterize mouse serum ferritin. We find that both splenic macrophages and proximal tubule cells of the kidney are possible cellular sources for serum ferritin and that serum ferritin is secreted by cells rather than being the product of a cytosolic leak from damaged cells. Mouse serum ferritin is composed mostly of L-subunits, whereas it contains few H-subunits and iron content is low. L-subunits of serum ferritin are frequently truncated at the C-terminus, giving rise to a characteristic 17-kD band that has been previously observed in lysosomal ferritin. Taken together with the fact that mouse serum ferritin is not detectably glycosylated, we propose that mouse serum ferritin is secreted through the nonclassical lysosomal secretory pathway. (Blood. 2010; 116(9):1574-1584) C1 [Cohen, Lyora A.; Weiss, Avital; Leichtmann-Bardoogo, Yael; Morgenstern, Avigail; Meyron-Holtz, Esther G.] Technion Israel Inst Technol, Fac Biotechnol & Food Engn, Lab Mol Nutr, IL-32000 Technion, Haifa, Israel. [Gutierrez, Lucia; Lazaro, Francisco J.] Univ Zaragoza, Dept Ciencia & Tecnol Mat & Fluidos, Zaragoza, Spain. [Zhang, De-liang; Crooks, Daniel R.; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD USA. [Sougrat, Rachid] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. [Galy, Bruno; Hentze, Matthias W.] European Mol Biol Lab, Heidelberg, Germany. RP Meyron-Holtz, EG (reprint author), Technion Israel Inst Technol, Fac Biotechnol & Food Engn, Lab Mol Nutr, IL-32000 Technion, Haifa, Israel. EM meyron@tx.technion.ac.il RI Gutierrez, Lucia/A-4305-2008; Meyron-Holtz, Esther/B-5991-2013; Lazaro, Francisco/K-5100-2014 OI Gutierrez, Lucia/0000-0003-2366-3598; Sougrat, Rachid/0000-0001-6476-1886; Zhang, Deliang/0000-0001-9478-5344; Hentze, Matthias/0000-0002-4023-7876; Lazaro, Francisco/0000-0003-3130-4237 FU US-Israel Binational Science Foundation [2007466]; Instituto de Salud Carlos III (Spain) [PI060549] FX This work was funded by the US-Israel Binational Science Foundation, Grant no. 2007466 (E.M.-H. and T.R.) and the Instituto de Salud Carlos III (Spain), project PI060549 (F.J.L.) NR 50 TC 111 Z9 117 U1 0 U2 7 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 SEP 2 PY 2010 VL 116 IS 9 BP 1574 EP 1584 DI 10.1182/blood-2009-11-253815 PG 11 WC Hematology SC Hematology GA 646VT UT WOS:000281572700026 PM 20472835 ER PT J AU Connolly, BM Choi, EY Gardsvoll, H Bey, AL Currie, BM Chavakis, T Liu, SH Molinolo, A Ploug, M Leppla, SH Bugge, TH AF Connolly, Brian M. Choi, Eun Young Gardsvoll, Henrik Bey, Alexandra L. Currie, Brooke M. Chavakis, Triantafyllos Liu, Shihui Molinolo, Alfredo Ploug, Michael Leppla, Stephen H. Bugge, Thomas H. TI Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation SO BLOOD LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; LIGNEOUS CONJUNCTIVITIS; DEFICIENT MICE; CELL RECRUITMENT; ANTHRAX TOXIN; RECEPTOR; GENE; FIBROSIS; BINDING; PROTEOLYSIS AB The urokinase plasminogen activator receptor (uPAR) has emerged as a potential regulator of cell adhesion, cell migration, proliferation, differentiation, and cell survival in multiple physiologic and pathologic contexts. The urokinase plasminogen activator (uPA) was the first identified ligand for uPAR, but elucidation of the specific functions of the uPA-uPAR interaction in vivo has been difficult because uPA has important physiologic functions that are independent of binding to uPAR and because uPAR engages multiple ligands. Here, we developed a new mouse strain (Plau(GFDhu/GFDhu)) in which the interaction between endogenous uPA and uPAR is selectively abrogated, whereas other functions of both the protease and its receptor are retained. Specifically, we introduced 4 amino acid substitutions into the growth factor domain (GFD) of uPA that abrogate uPAR binding while preserving the overall structure of the domain. Analysis of Plau(GFDhu/GFDhu) mice revealed an unanticipated role of the uPAuPAR interaction in suppressing inflammation secondary to fibrin deposition. In contrast, leukocyte recruitment and tissue regeneration were unaffected by the loss of uPA binding to uPAR. This study identifies a principal in vivo role of the uPA-uPAR interaction in cell-associated fibrinolysis critical for suppression of fibrin accumulation and fibrin-associated inflammation and provides a valuable model for further exploration of this multifunctional receptor. (Blood. 2010; 116(9):1593-1603) C1 [Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. [Choi, Eun Young; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Gardsvoll, Henrik; Ploug, Michael] Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. [Liu, Shihui; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Rm 211, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov FU National Institute of Dental and Craniofacial Research; National Institutes of Health; National Institute of Cancer Intramural Research; Danish National Research Foundation (Danish-Chinese Center for Proteases and Cancer); Lundbeck Foundation FX This study was supported by the National Institute of Dental and Craniofacial Research, National Institutes of Health, and National Institute of Cancer Intramural Research Programs, and grants from the Danish National Research Foundation (Danish-Chinese Center for Proteases and Cancer), and the Lundbeck Foundation. PlauGFDhu/GFDhu mice can be obtained by contacting Thomas Bugge (thomas.bugge@nih.gov). NR 50 TC 47 Z9 48 U1 0 U2 4 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 SEP 2 PY 2010 VL 116 IS 9 BP 1593 EP 1603 DI 10.1182/blood-2010-03-276642 PG 11 WC Hematology SC Hematology GA 646VT UT WOS:000281572700028 PM 20466854 ER PT J AU Dunn, JP Cowan, RL Volkow, ND Feurer, ID Li, R Williams, DB Kessler, RM Abumrad, NN AF Dunn, Julia P. Cowan, Ronald L. Volkow, Nora D. Feurer, Irene D. Li, Rui Williams, D. Brandon Kessler, Robert M. Abumrad, Naji N. TI Decreased dopamine type 2 receptor availability after bariatric surgery: Preliminary findings SO BRAIN RESEARCH LA English DT Article DE Dopamine; Obesity; Bariatric surgery; Receptor ID LAPAROSCOPIC SLEEVE GASTRECTOMY; POSITRON-EMISSION-TOMOGRAPHY; MORBIDLY OBESE SUBJECTS; GASTRIC BYPASS-SURGERY; EXTRASTRIATAL REGIONS; F-18 FALLYPRIDE; DORSAL STRIATUM; FOOD REWARD; WEIGHT-LOSS; PEPTIDE-YY AB Background: Diminished dopaminergic neurotransmission contributes to decreased reward and negative eating behaviors in obesity. Bariatric surgery is the most effective therapy for obesity and rapidly reduces hunger and improves satiety through unknown mechanisms. We hypothesized that dopaminergic neurotransmission would be enhanced after Roux-en-Y-Gastric Bypass (RYGB) and Vertical Sleeve Gastrectomy (VSG) surgery and that these changes would influence eating behaviors and contribute to the positive outcomes from bariatric surgery. Methods: Five females with obesity were studied preoperatively and at 7 weeks after RYGB or VSG surgery. Subjects underwent positron emission tomography (PET) imaging with a dopamine type 2 (DA D2) receptor radioligand whose binding is sensitive to competition with endogenous dopamine. Regions of interest (ROI) relevant to eating behaviors were delineated. Fasting enteroendocrine hormones were quantified at each time point. Results: Body weight decreased as expected after surgery. DA D2 receptor availability decreased after surgery. Regional decreases (mean +/- SEM) were caudate 10 +/- 3%, putamen 9 +/- 4%, ventral striatum 8 +/- 4%, hypothalamus 9 +/- 3%, substantia nigra 10 +/- 2%, medial thalamus 8 2%, and amygdala 9 3%. These were accompanied by significant decreases in plasma insulin (62%) and leptin (41%). Conclusion: The decreases in DA D2 receptor availability after RYGB and VSG most likely reflect increases in extracellular dopamine levels. Enhanced dopaminergic neurotransmission may contribute to improved eating behavior (e.g. reduced hunger and improved satiety) following these bariatric procedures. (C) 2010 Elsevier B.V. All rights reserved. C1 [Dunn, Julia P.] Vanderbilt Univ, Sch Med, Dept Med, Div Diabet Endocrinol & Metab, Nashville, TN 37232 USA. [Cowan, Ronald L.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37232 USA. [Feurer, Irene D.; Williams, D. Brandon; Abumrad, Naji N.] Vanderbilt Univ, Sch Med, Dept Surg, Nashville, TN 37232 USA. [Cowan, Ronald L.; Li, Rui; Kessler, Robert M.] Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37232 USA. [Feurer, Irene D.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37232 USA. [Volkow, Nora D.] Natl Inst Drug Abuse, Bethesda, MD USA. RP Dunn, JP (reprint author), Vanderbilt Univ, Sch Med, Dept Med, Div Diabet Endocrinol & Metab, 2213 Garland Ave,7465 MRBIV, Nashville, TN 37232 USA. EM julia.dunn@vanderbilt.edu FU Vanderbilt Environmental Health Science Scholars Program [NIEHS K12 ESO15855]; NIH [R01-DK070860]; NIDDK; NCRR/NIH [1 UL1 RR024975]; Vanderbilt Diabetes Research and Training Center [DK20593]; Vanderbilt Digestive Diseases Research Center [DK058404] FX We would like to thank Pamela Marks-Shulman, M.S., R.D. and Joan Kaiser, R.N. for their hard work in support of this study. J.P.D. received support from the Vanderbilt Environmental Health Science Scholars Program (NIEHS K12 ESO15855). This work was supported by NIH grants R01-DK070860, NIDDK to N.N.A. This work was also supported in part by Vanderbilt CTSA grant 1 UL1 RR024975 from NCRR/NIH, the Vanderbilt Diabetes Research and Training Center (DK20593), and the Vanderbilt Digestive Diseases Research Center (DK058404). NR 50 TC 64 Z9 65 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 2 PY 2010 VL 1350 SI SI BP 123 EP 130 DI 10.1016/j.brainres.2010.03.064 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 653EA UT WOS:000282069500014 PM 20362560 ER PT J AU Altshuler, DM Gibbs, RA Peltonen, L Dermitzakis, E Schaffner, SF Yu, FL Bonnen, PE de Bakker, PIW Deloukas, P Gabriel, SB Gwilliam, R Hunt, S Inouye, M Jia, XM Palotie, A Parkin, M Whittaker, P Chang, K Hawes, A Lewis, LR Ren, YR Wheeler, D Muzny, DM Barnes, C Darvishi, K Hurles, M Korn, JM Kristiansson, K Lee, C McCarroll, SA Nemesh, J Keinan, A Montgomery, SB Pollack, S Price, AL Soranzo, N Gonzaga-Jauregui, C Anttila, V Brodeur, W Daly, MJ Leslie, S McVean, G Moutsianas, L Nguyen, H Zhang, QR Ghori, MJR McGinnis, R McLaren, W Takeuchi, F Grossman, SR Shlyakhter, I Hostetter, EB Sabeti, PC Adebamowo, CA Foster, MW Gordon, DR Licinio, J Manca, MC Marshall, PA Matsuda, I Ngare, D Wang, VO Reddy, D Rotimi, CN Royal, CD Sharp, RR Zeng, CQ Brooks, LD McEwen, JE AF Altshuler, David M. Gibbs, Richard A. Peltonen, Leena Dermitzakis, Emmanouil Schaffner, Stephen F. Yu, Fuli Bonnen, Penelope E. de Bakker, Paul I. W. Deloukas, Panos Gabriel, Stacey B. Gwilliam, Rhian Hunt, Sarah Inouye, Michael Jia, Xiaoming Palotie, Aarno Parkin, Melissa Whittaker, Pamela Chang, Kyle Hawes, Alicia Lewis, Lora R. Ren, Yanru Wheeler, David Muzny, Donna Marie Barnes, Chris Darvishi, Katayoon Hurles, Matthew Korn, Joshua M. Kristiansson, Kati Lee, Charles McCarroll, Steven A. Nemesh, James Keinan, Alon Montgomery, Stephen B. Pollack, Samuela Price, Alkes L. Soranzo, Nicole Gonzaga-Jauregui, Claudia Anttila, Verneri Brodeur, Wendy Daly, Mark J. Leslie, Stephen McVean, Gil Moutsianas, Loukas Nguyen, Huy Zhang, Qingrun Ghori, Mohammed J. R. McGinnis, Ralph McLaren, William Takeuchi, Fumihiko Grossman, Sharon R. Shlyakhter, Ilya Hostetter, Elizabeth B. Sabeti, Pardis C. Adebamowo, Clement A. Foster, Morris W. Gordon, Deborah R. Licinio, Julio Manca, Maria Cristina Marshall, Patricia A. Matsuda, Ichiro Ngare, Duncan Wang, Vivian Ota Reddy, Deepa Rotimi, Charles N. Royal, Charmaine D. Sharp, Richard R. Zeng, Changqing Brooks, Lisa D. McEwen, Jean E. CA Int HapMap 3 Consortium TI Integrating common and rare genetic variation in diverse human populations SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; COPY NUMBER VARIATION; POSITIVE SELECTION; HAPLOTYPE MAP; VARIANTS; DISEASES; SIGNALS; REGIONS; SNPS AB Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of <= 5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation. C1 [Altshuler, David M.; Schaffner, Stephen F.; de Bakker, Paul I. W.; Gabriel, Stacey B.; Jia, Xiaoming; Parkin, Melissa; Korn, Joshua M.; McCarroll, Steven A.; Pollack, Samuela; Brodeur, Wendy; Nguyen, Huy; Shlyakhter, Ilya] Broad Inst, Cambridge, MA 02138 USA. [Gibbs, Richard A.; Yu, Fuli; Bonnen, Penelope E.; Chang, Kyle; Hawes, Alicia; Lewis, Lora R.; Ren, Yanru; Wheeler, David; Muzny, Donna Marie; Gonzaga-Jauregui, Claudia] Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. [Dermitzakis, Emmanouil; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, Fac Med, CH-1211 Geneva, Switzerland. [de Bakker, Paul I. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Genet, Boston, MA 02115 USA. [Deloukas, Panos; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Palotie, Aarno; Whittaker, Pamela; Barnes, Chris; Hurles, Matthew; Kristiansson, Kati; Soranzo, Nicole; Anttila, Verneri; Zhang, Qingrun; Ghori, Mohammed J. R.; McGinnis, Ralph; McLaren, William; Takeuchi, Fumihiko] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge CB10 1HH, England. [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Inst Mol Med Finland, FIN-00290 Helsinki, Finland. [Palotie, Aarno; Anttila, Verneri] Univ Helsinki, Dept Med Genet, FIN-00290 Helsinki, Finland. [Palotie, Aarno; Anttila, Verneri] Univ Cent Hosp, Helsinki 00290, Finland. [Darvishi, Katayoon; Lee, Charles] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Keinan, Alon] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Simches Res Ctr, Boston, MA 02114 USA. [Leslie, Stephen; McVean, Gil; Moutsianas, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Grossman, Sharon R.; Hostetter, Elizabeth B.; Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Ctr Syst Biol, Cambridge, MA 02215 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Preventat Med, Inst Human Virol N406, Baltimore, MD 21201 USA. [Foster, Morris W.] Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. [Gordon, Deborah R.] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA. [Licinio, Julio] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2603, Australia. [Manca, Maria Cristina] Inst Oncol Study & Prevent, I-50139 Florence, Italy. [Marshall, Patricia A.] Case Western Reserve Univ, Dept Bioeth, Sch Med TA200, Cleveland, OH 44106 USA. [Matsuda, Ichiro] Hlth Sci Univ Hokkaido, Tobetsu, Hokkaido 0610293, Japan. [Ngare, Duncan] Moi Univ, Dept Populat & Family Hlth, Eldoret 30100, Kenya. [Wang, Vivian Ota; Brooks, Lisa D.; McEwen, Jean E.] NHGRI, NIH, Bethesda, MD 20892 USA. [Reddy, Deepa] Univ Houston Clear Lake City, Dept Anthropol, Houston, TX 77058 USA. [Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Royal, Charmaine D.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. [Sharp, Richard R.] Cleveland Clin, Dept Bioeth, Cleveland, OH 44124 USA. [Zeng, Changqing] Chinese Acad Sci, Beijing Inst Genom, Beijing 101300, Peoples R China. RP Altshuler, DM (reprint author), Broad Inst, 7 Cambridge Ctr, Cambridge, MA 02138 USA. EM altshuler@molbio.mgh.harvard.edu; agibbs@bcm.edu RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; Licinio, Julio/L-4244-2013; de Bakker, Paul/B-8730-2009; OI Adebamowo, Clement/0000-0002-6571-2880; Altshuler, David/0000-0002-7250-4107; Deloukas, Panos/0000-0001-9251-070X; Hunt, Sarah/0000-0002-8350-1235; Barnes, Chris/0000-0002-9459-1395; Licinio, Julio/0000-0001-6905-5884; de Bakker, Paul/0000-0001-7735-7858; Anttila, Verneri/0000-0002-0073-4675; Soranzo, Nicole/0000-0003-1095-3852; Kristiansson, Kati/0000-0003-4688-107X; McLaren, William/0000-0001-6218-1116; Gonzaga-Jauregui, Claudia/0000-0002-4667-3679 FU USA National Institutes of Health; National Human Genome Research Institute; National Institute on Deafness and Other Communication Disorders; Wellcome Trust [068545/Z/02, 076113]; Louis-Jeantet Foundation; NCCR 'Frontiers in Genetics' (Swiss National Science Foundation); UK Medical Research Council [G0000934] FX We dedicate this work to Leena Peltonen for her vital leadership role in this study, and in memory of a valued friend and colleague. We thank E. Boerwinkle and R. Durbin for critical reading of the manuscript. We thank the USA National Institutes of Health, the National Human Genome Research Institute, the National Institute on Deafness and Other Communication Disorders and the Wellcome Trust for supporting the majority of this work. Funding was also provided by the Louis-Jeantet Foundation and the NCCR 'Frontiers in Genetics' (Swiss National Science Foundation). We thank the people from the following communities who were generous in donating their blood samples to be studied in this project: the Yoruba in Ibadan, Nigeria; the Maasai in Kinyawa, Kenya; the Luhya in Webuye, Kenya; the Han Chinese in Beijing, China; the Japanese in Tokyo, Japan; the Chinese in metropolitan Denver, Colorado; the Gujarati Indians in Houston, Texas; the Toscani in Italia; the community of African ancestry in the southwestern USA; and the community of Mexican ancestry in Los Angeles, California. We also thank the people in the Utah Centre d'Etude du Polymorphisme Humain community who allowed the samples they donated earlier to be used for the project. The authors acknowledge use of DNA from the 1958 British birth cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. The Illumina 550K genotype data for the 1958 British birth cohort samples were made available by the Sanger Institute. For the 1958 British birth cohort Affymetrix 500K genotype data, we thank the Wellcome Trust Case Control Consortium (http://www.wtccc.org.uk), which was funded by Wellcome Trust award 076113. NR 27 TC 1087 Z9 1100 U1 10 U2 105 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 2 PY 2010 VL 467 IS 7311 BP 52 EP 58 DI 10.1038/nature09298 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 645MB UT WOS:000281461200033 ER PT J AU Appel, LJ Wright, JT Greene, T Agodoa, LY Astor, BC Bakris, GL Cleveland, WH Charleston, J Contreras, G Faulkner, ML Gabbai, FB Gassman, JJ Hebert, LA Jamerson, KA Kopple, JD Kusek, JW Lash, JP Lea, JP Lewis, JB Lipkowitz, MS Massry, SG Miller, ER Norris, K Phillips, RA Pogue, VA Randall, OS Rostand, SG Smogorzewski, MJ Toto, RD Wang, XL AF Appel, Lawrence J. Wright, Jackson T., Jr. Greene, Tom Agodoa, Lawrence Y. Astor, Brad C. Bakris, George L. Cleveland, William H. Charleston, Jeanne Contreras, Gabriel Faulkner, Marquetta L. Gabbai, Francis B. Gassman, Jennifer J. Hebert, Lee A. Jamerson, Kenneth A. Kopple, Joel D. Kusek, John W. Lash, James P. Lea, Janice P. Lewis, Julia B. Lipkowitz, Michael S. Massry, Shaul G. Miller, Edgar R. Norris, Keith Phillips, Robert A. Pogue, Velvie A. Randall, Otelio S. Rostand, Stephen G. Smogorzewski, Miroslaw J. Toto, Robert D. Wang, Xuelei CA AASK Collaborative Res Grp TI Intensive Blood-Pressure Control in Hypertensive Chronic Kidney Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAGE RENAL-DISEASE; AFRICAN-AMERICAN; PROGRESSION; TRIAL; AASK; PROTEINURIA; OUTCOMES; DESIGN; DIET; RISK AB BACKGROUND In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. METHODS We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. RESULTS During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P = 0.27). However, the effects differed according to the baseline level of proteinuria (P = 0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P = 0.01). CONCLUSIONS In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. C1 [Appel, Lawrence J.] Johns Hopkins Univ, Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Wright, Jackson T., Jr.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. [Gassman, Jennifer J.; Wang, Xuelei] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Greene, Tom] Univ Utah, Sch Med, Div Clin Epidemiol, Salt Lake City, UT USA. [Agodoa, Lawrence Y.; Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Bakris, George L.] Univ Chicago, Pritzker Sch Med, Dept Med, Hypertens Dis Unit, Chicago, IL 60637 USA. [Lash, James P.] Univ Illinois, Dept Med, Chicago, IL USA. [Cleveland, William H.] Morehouse Sch Med, Multidisciplinary Res Ctr, Atlanta, GA 30310 USA. [Lea, Janice P.] Emory Univ, Sch Med, Emory Ctr Hypertens & Renal Dis Res, Atlanta, GA USA. [Contreras, Gabriel] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33136 USA. [Faulkner, Marquetta L.] Meharry Med Coll, Nashville, TN 37208 USA. [Lewis, Julia B.] Vanderbilt Univ, Sch Med, Div Nephrol, Nashville, TN 37212 USA. [Gabbai, Francis B.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Gabbai, Francis B.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Hebert, Lee A.] Ohio State Univ, Med Ctr, Div Nephrol, Columbus, OH 43210 USA. [Jamerson, Kenneth A.] Univ Michigan, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Kopple, Joel D.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Los Angeles, CA USA. [Kopple, Joel D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Massry, Shaul G.] Los Angeles Cty Univ So Calif, Med Ctr, Los Angeles, CA USA. [Smogorzewski, Miroslaw J.] Univ So Calif, Keck Sch Med, Div Nephrol, Los Angeles, CA 90033 USA. [Norris, Keith] Charles Drew Univ Med & Sci, Dept Internal Med, Los Angeles, CA USA. [Lipkowitz, Michael S.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Pogue, Velvie A.] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, Dept Med, New York, NY 10032 USA. [Pogue, Velvie A.] Columbia Univ, New York, NY USA. [Phillips, Robert A.] Univ Massachusetts, Sch Med, Cardiovasc Res Fdn, Worcester, MA USA. [Randall, Otelio S.] Howard Univ, Washington, DC 20059 USA. [Randall, Otelio S.] Howard Univ Hosp, Washington, DC USA. [Rostand, Stephen G.] Univ Alabama, Div Nephrol, Birmingham, AL USA. [Toto, Robert D.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA. RP Appel, LJ (reprint author), Johns Hopkins Univ, Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-618, Baltimore, MD 21205 USA. EM lappel@jhmi.edu FU National Institute of Diabetes and Digestive and Kidney Diseases; National Center on Minority Health and Health Disparities; National Institutes of Health [M01 RR-00080, M01 RR-00071, M0100032, P20-RR11145, M01 RR00827, M01 RR00052, 2P20 RR11104, RR029887, DK 2818-02]; King Pharmaceuticals FX Supported by grants to each clinical center and the coordinating center from the National Institute of Diabetes and Digestive and Kidney Diseases; by the Office of Research in Minority Health (now the National Center on Minority Health and Health Disparities); by institutional grants from the National Institutes of Health (M01 RR-00080, M01 RR-00071, M0100032, P20-RR11145, M01 RR00827, M01 RR00052, 2P20 RR11104, RR029887, and DK 2818-02); by King Pharmaceuticals, which provided monetary support and antihypertensive medications to each clinical center; and by Pfizer, AstraZeneca, GlaxoSmithKline, Forest Laboratories, Pharmacia, and Upjohn, which donated antihypertensive medications. NR 29 TC 267 Z9 281 U1 3 U2 28 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 SEP 2 PY 2010 VL 363 IS 10 BP 918 EP 929 DI 10.1056/NEJMoa0910975 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 645GW UT WOS:000281441500005 PM 20818902 ER PT J AU Probstfield, JL Cushman, WC Davis, BR Pressel, S Cutler, JA Einhorn, P Ford, C Oparil, S Whelton, P Wright, JT AF Probstfield, J. L. Cushman, W. C. Davis, B. R. Pressel, S. Cutler, J. A. Einhorn, P. Ford, C. Oparil, S. Whelton, P. Wright, J. T. TI Mortality and morbidity during and after the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN SP European Soc Cardiol C1 [Probstfield, J. L.] Univ Washington, Seattle, WA 98195 USA. [Cushman, W. C.] Memphis VAMC, Memphis, TN USA. [Davis, B. R.; Pressel, S.; Ford, C.] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. [Cutler, J. A.; Einhorn, P.] NHLBI, NIH, Bethesda, MD 20892 USA. [Oparil, S.] Univ Alabama Birmingham, Birmingham, AL USA. [Whelton, P.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Wright, J. T.] Univ Hosp Cleveland, Cleveland, OH USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 2010 VL 31 SU 1 BP 321 EP 321 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531902083 ER PT J AU Wang, KL Cheng, HM Chuang, SY Sung, SH Huang, CM Yu, WC Ting, CT Lakatta, EG Yin, FCP Chen, CH AF Wang, K. L. Cheng, H. M. Chuang, S. Y. Sung, S. H. Huang, C. M. Yu, W. C. Ting, C. T. Lakatta, E. G. Yin, F. C. P. Chen, C. H. TI Prehypertension or white-coat hypertension: which best relates to target-organs and future cardiovascular mortality? SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Wang, K. L.; Cheng, H. M.; Sung, S. H.; Huang, C. M.; Yu, W. C.; Chen, C. H.] Taipei Vet Gen Hosp, Taipei, Taiwan. [Chuang, S. Y.] Acad Sinica, Taipei 115, Taiwan. [Ting, C. T.] Taichung Vet Gen Hosp, Taichung, Taiwan. [Lakatta, E. G.] NIA, Baltimore, MD 21224 USA. [Yin, F. C. P.] Washington Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2010 VL 31 SU 1 BP 449 EP 449 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531903002 ER PT J AU Ugander, M Booker, OJ Hsu, LY Oki, AJ Aletras, AH Arai, AE AF Ugander, M. Booker, O. J. Hsu, L. Y. Oki, A. J. Aletras, A. H. Arai, A. E. TI Edematous peri-infarct myocardium has a greater extracellular volume fraction compared with normal myocardium - implications for late gadolinium enhancement SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Ugander, M.; Booker, O. J.; Hsu, L. Y.; Oki, A. J.; Aletras, A. H.; Arai, A. E.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2010 VL 31 SU 1 BP 585 EP 585 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531903540 ER PT J AU Briest, W Cooper, TK Tae, HJ Krawczyk, M Mcdonnell, NB Talan, MI AF Briest, W. Cooper, T. K. Tae, H. -J. Krawczyk, M. Mcdonnell, N. B. Talan, M. I. TI MMP-inhibition: a treatment for the vascular type of the Ehlers-Danlos syndrome? SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Briest, W.] Univ Leipzig, Ctr Heart, Dept Internal Med & Cardiol, Leipzig, Germany. [Cooper, T. K.] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Tae, H. -J.; Krawczyk, M.; Talan, M. I.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. [Mcdonnell, N. B.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2010 VL 31 SU 1 BP 701 EP 701 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531904432 ER PT J AU Roysland, R Omland, T Sabatine, MS Hsia, J Christophi, C Rice, MM Rouleau, JL Domanski, MJ Solomon, SD Braunwald, E AF Roysland, R. Omland, T. Sabatine, M. S. Hsia, J. Christophi, C. Rice, M. M. Rouleau, J. L. Domanski, M. J. Solomon, S. D. Braunwald, E. TI N-terminal pro-B-type natriuretic peptide is associated with the incidence of sudden cardiac death in patients with stable coronary artery disease and preserved left ventricular systolic function SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Roysland, R.; Omland, T.] Univ Oslo, Lorenskog, Norway. [Sabatine, M. S.; Solomon, S. D.; Braunwald, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Christophi, C.; Rice, M. M.] George Washington Univ, Rockville, MD USA. [Rouleau, J. L.] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Domanski, M. J.] NHLBI, NIH, Bethesda, MD 20892 USA. RI Solomon, Scott/I-5789-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2010 VL 31 SU 1 BP 840 EP 840 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531905407 ER PT J AU Briest, W Muller, GA Hansen, U Mcdonnell, NB Talan, MI AF Briest, W. Muller, G. A. Hansen, U. Mcdonnell, N. B. Talan, M. I. TI Selective suppression of the mutated form of collagen 3A1 by siRNA in fibroblasts from a patient with the vascular form of the Ehlers-Danlos syndrome SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Briest, W.] Univ Leipzig, Ctr Heart, Dept Internal Med & Cardiol, Leipzig, Germany. [Muller, G. A.] Univ Hosp Leipzig, Leipzig, Germany. [Hansen, U.] Univ Hosp Muenster, Inst Pathol Chem & Pathobiochem, Munster, Germany. [Mcdonnell, N. B.] NIA, Clin Invest Lab, Baltimore, MD 21224 USA. [Talan, M. I.] NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 2010 VL 31 SU 1 BP 908 EP 908 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531906125 ER PT J AU Borraccino, A Iannotti, RJ Lemma, P Cavallo, F AF Borraccino, A. Iannotti, R. J. Lemma, P. Cavallo, F. TI INFLUENCES OF PHYSICAL ACTIVITY AND SEDENTARY BEHAVIOR ON ADOLESCENT MEDICINE USE IN 17 COUNTRIES SO EPIDEMIOLOGIA & PREVENZIONE LA English DT Meeting Abstract C1 [Borraccino, A.; Lemma, P.; Cavallo, F.] Univ Turin, Dipartimento Sanita Pubbl & Microbiol, I-10124 Turin, Italy. [Iannotti, R. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RI Borraccino, Alberto/C-9013-2012 OI Borraccino, Alberto/0000-0001-8235-8775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFERENZE SCARL PI MILANO PA VIA RICCIARELLI N 29, MILANO, 20148, ITALY SN 1120-9763 J9 EPIDEMIOL PREV JI Epidemiol. Prev. PD SEP-DEC PY 2010 VL 34 IS 5-6 SU 1 BP 60 EP 60 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 701MF UT WOS:000285821300066 ER PT J AU Consonni, D De Matteis, S Pesatori, AC Lubin, JH Wacholder, S Tucker, M Caporaso, NE Bertazzi, PA Landi, MT AF Consonni, D. De Matteis, S. Pesatori, A. C. Lubin, J. H. Wacholder, S. Tucker, M. Caporaso, N. E. Bertazzi, P. A. Landi, M. T. TI LUNG CANCER AMONG CONSTRUCTION WORKERS IN A POPULATION-BASED CASE-CONTROL STUDY SO EPIDEMIOLOGIA & PREVENZIONE LA English DT Meeting Abstract C1 [Consonni, D.; Pesatori, A. C.; Bertazzi, P. A.] Univ Milan, Milan, Italy. [Consonni, D.; Pesatori, A. C.; Bertazzi, P. A.] Fdn IRCCS Ca Granda Osped Maggiore, Epidemiol Unit, Milan, Italy. [De Matteis, S.; Lubin, J. H.; Wacholder, S.; Tucker, M.; Caporaso, N. E.; Landi, M. T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU INFERENZE SCARL PI MILANO PA VIA RICCIARELLI N 29, MILANO, 20148, ITALY SN 1120-9763 J9 EPIDEMIOL PREV JI Epidemiol. Prev. PD SEP-DEC PY 2010 VL 34 IS 5-6 SU 1 BP 71 EP 71 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 701MF UT WOS:000285821300089 ER PT J AU Goedert, JJ Lauria, C Vitale, F Buscema, G Leggio, L Arena, G Graubard, IB Preiss, L Whitby, D Bonura, F Perna, A Viviano, E Gafa, L Messina, A Romano, N AF Goedert, J. J. Lauria, C. Vitale, F. Buscema, G. Leggio, L. Arena, G. Graubard, Barry, I Preiss, L. Whitby, D. Bonura, F. Perna, A. Viviano, E. Gafa, L. Messina, A. Romano, N. TI EXPOSURES TO PLANTS AND CLASSIC KAPOSI SARCOMA: A STUDY IN SICILY SO EPIDEMIOLOGIA & PREVENZIONE LA English DT Meeting Abstract C1 [Goedert, J. J.; Graubard, Barry, I] NIH, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lauria, C.; Buscema, G.; Leggio, L.; Arena, G.; Gafa, L.; Romano, N.] Sez Ragusa, Ragusa, Italy. [Vitale, F.; Bonura, F.; Perna, A.; Viviano, E.] Univ Palermo, Dip Igiene Microbiol G DAlessandro, I-90133 Palermo, Italy. [Preiss, L.] RTI Int, Res Triangle Pk, NC USA. [Whitby, D.] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. [Messina, A.] Univ Catania, Dip Sci Biomed, I-95124 Catania, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFERENZE SCARL PI MILANO PA VIA RICCIARELLI N 29, MILANO, 20148, ITALY SN 1120-9763 J9 EPIDEMIOL PREV JI Epidemiol. Prev. PD SEP-DEC PY 2010 VL 34 IS 5-6 SU 1 BP 134 EP 134 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 701MF UT WOS:000285821300228 ER PT J AU Ukegbu, UJ Onumah, BM Tambay, AV Ricks, M Miller, BV Tulloch-Reid, MK Sumner, AE AF Ukegbu, U. J. Onumah, B. M. Tambay, A. V. Ricks, M. Miller, B. V., III Tulloch-Reid, M. K. Sumner, A. E. TI RISK FOR KETOSIS-PRONE TYPE 2 DIABETES APPEARS TO BE GREATER IN BLACK-AFRICAN THAN AFRICAN-AMERICAN MEN SO ETHNICITY & DISEASE LA English DT Meeting Abstract C1 [Ukegbu, U. J.; Tambay, A. V.; Ricks, M.; Miller, B. V., III; Sumner, A. E.] NIH, Bethesda, MD 20892 USA. [Onumah, B. M.] Washington Hosp Ctr, Washington, DC 20010 USA. [Tulloch-Reid, M. K.] Univ W Indies, Kingston 7, Jamaica. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD FAL PY 2010 VL 20 IS 4 MA 022 BP S312 EP S312 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 702RK UT WOS:000285911600050 ER PT J AU Albert, PS Shih, JH AF Albert, Paul S. Shih, Joanna H. TI AN APPROACH FOR JOINTLY MODELING MULTIVARIATE LONGITUDINAL MEASUREMENTS AND DISCRETE TIME-TO-EVENT DATA SO ANNALS OF APPLIED STATISTICS LA English DT Article DE Joint models; shared random parameter models; informative dropout; regression calibration ID SURVIVAL-DATA; ERROR; BIOMARKERS; PROFILES AB In many medical studies, patients are followed longitudinally and interest is on assessing the relationship between longitudinal measurements and time to an event. Recently, various authors have proposed joint modeling approaches for longitudinal and time-to-event data for a single longitudinal variable. These joint modeling approaches become intractable with even a few longitudinal variables. In this paper we propose a regression calibration approach for jointly modeling multiple longitudinal measurements and discrete time-to-event data. Ideally, a two-stage modeling approach could be applied in which the multiple longitudinal measurements are modeled in the first stage and the longitudinal model is related to the time-to-event data in the second stage. Biased parameter estimation due to informative dropout makes this direct two-stage modeling approach problematic. We propose a regression calibration approach which appropriately accounts for informative dropout. We approximate the conditional distribution of the multiple longitudinal measurements given the event time by modeling all pairwise combinations of the longitudinal measurements using a bivariate linear mixed model which conditions on the event time. Complete data are then simulated based on estimates from these pairwise conditional models, and regression calibration is used to estimate the relationship between longitudinal data and time-to-event data using the complete data. We show that this approach performs well in estimating the relationship between multivariate longitudinal measurements and the time-to-event data and in estimating the parameters of the multiple longitudinal process subject to informative dropout. We illustrate this methodology with simulations and with an analysis of primary biliary cirrhosis (PBC) data. C1 [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by the Intramural Research Program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 25 TC 4 Z9 4 U1 1 U2 7 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 1932-6157 J9 ANN APPL STAT JI Ann. Appl. Stat. PD SEP PY 2010 VL 4 IS 3 BP 1517 EP 1532 DI 10.1214/10-AOAS339 PG 16 WC Statistics & Probability SC Mathematics GA 674YL UT WOS:000283787900018 PM 21938267 ER PT J AU Bhatia, PA Moaddel, R Wainer, IW AF Bhatia, Prateek A. Moaddel, Ruin Wainer, Irving W. TI Application of cellular membrane affinity chromatography in determining stereoselective interactions with ATP-binding cassette transporters SO CHIMICA OGGI-CHEMISTRY TODAY LA English DT Article ID MULTIDRUG-RESISTANCE; BREAST-CANCER; ABC TRANSPORTERS; P-GLYCOPROTEIN; PROTEIN; VERAPAMIL; PHASE; MRP1; LOCALIZATION; METABOLISM AB The ATP-binding cassette (ABC) efflux transporters plays a key role in drug absorption and excretion hence the determination of a compound's interaction with these transporters becomes a key element in drug discovery programs. ABC transporters also play a role in multiple drug resistance (MDR), a common obstacle in chemotherapeutic management of most neoplastic tumours as well as a number of other diseases such as malaria and tuberculosis. While there are a variety of approaches to the determination of drug interactions with ABC transporters, the direct measurement of stereoselective interactions remains a difficult task. In this review we address this issue and demonstrate that cellular membrane affinity chromatography (CMAC) utilizing columns containing immobilized ABC transporters can be used as a direct online method for the determination of stereoselective small molecule-drug transporter interactions. The CMAC columns discussed in this work contain the ABC transporter P-glycoprotein; the CMAC (Pgp) column, multiple drug resistant protein 1; the CMAC (MRP1) column, multiple drug resistance protein 2; the CMAC (MRP2) column and breast cancer resistant protein; the CMAC (BCRP) column. C1 [Bhatia, Prateek A.; Moaddel, Ruin; Wainer, Irving W.] NIA, NIH, Clin Invest Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Wainer, IW (reprint author), NIA, NIH, Clin Invest Lab, Biomed Res Ctr, 251 Bayview Blvd,Room 8B133, Baltimore, MD 21224 USA. FU National Institute on Aging FX This work was supported by funding from the National Institute on Aging Intramural Research Program. NR 27 TC 0 Z9 0 U1 1 U2 4 PU TEKNOSCIENZE PUBL PI MILANO PA VIALE BRIANZA 22, 20127 MILANO, ITALY SN 1973-8250 J9 CHIM OGGI JI Chim. Oggi-Chem. Today PD SEP-OCT PY 2010 VL 28 IS 5 BP 32 EP 36 PG 4 WC Biotechnology & Applied Microbiology; Chemistry, Multidisciplinary SC Biotechnology & Applied Microbiology; Chemistry GA 672KJ UT WOS:000283581600004 ER PT J AU Zhang, J Ng, KY Ho, PC AF Zhang, Jing Ng, Ka-Yun Ho, Paul C. TI Interaction of Oxazaphosphorines with Multidrug Resistance-Associated Protein 4 (MRP4) SO AAPS JOURNAL LA English DT Article DE cyclophosphamide; cytotoxicity; drug transporter; ifosfamide; multidrug resistance-associated protein 4 ID BREAST-CANCER; DRUG-RESISTANCE; SUBSTRATE-SPECIFICITY; REDUCED GLUTATHIONE; CONFERS RESISTANCE; HEPATIC MRP4; TRANSPORTERS; EXPRESSION; INDUCTION; RECEPTOR AB Multidrug resistance-associated protein 4 (MRP4) is an organic anion efflux pump capable of transporting nucleoside, nucleotide analogs, and cyclic nucleotide. MRP4 could have an influence on the resistance and transport of the two oxazaphosphorines, cyclophosphamide (CP) and ifosfamide (IF). V/HepG2 (HepG2, hepatoma cells stably transfected with an empty vehicle plasmid) and MRP4/HepG2 (HepG2 cells stably expressing MRP4) were exposed to CP and IF in the absence or presence of various MRP4 inhibitors. HepG2 and HEK293 human kidney cells were also used to investigate the inducing potency of oxazaphosphorines on the MRP4 expression. In this study, insertion of MRP4 gene in HepG2 cells was found to confer significant resistance to CP and IF in the 48-h drug-exposure assays. In the presence of various MRP4 inhibitors, the resistance to CP and IF was then partially reversed. These indicate that CP and IF are highly possible substrates of MRP4. In addition, CP and clofibrate (CFB), a reported MRP4 inducer, in vivo significantly increased the MRP4 expression at both protein level and mRNA level in HEK293 cells at higher concentrations, while IF significantly decreased the MRP4 expression at mRNA level at lower concentration and had no effect at higher concentrations. However, all tested compounds (CP, IF, and CFB) did not change the MRP4 protein expression in HepG2 cells. CP and CFB are cell-specific and concentration-dependent MRP4 inducers. The finding may have implications in the CP- r IF-based chemotherapy. C1 [Zhang, Jing; Ng, Ka-Yun; Ho, Paul C.] Natl Univ Singapore, Fac Sci, Dept Pharm, Singapore 117543, Singapore. [Ng, Ka-Yun] NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Ho, PC (reprint author), Natl Univ Singapore, Fac Sci, Dept Pharm, 18 Sci Dr 4, Singapore 117543, Singapore. EM phahocl@nus.edu.sg RI Ho, Paul/O-9652-2014 OI Ho, Paul/0000-0001-9213-7116 FU National University of Singapore [R148-000-066-112] FX We would like to thank Dr. Theresa Tan from the Department of Biochemistry, National University of Singapore for providing the MRP4 transfected HepG2 cells for this study. We would also like to acknowledge the scholarship for J. Zhang and the Academic Research Fund, R148-000-066-112, from the National University of Singapore. NR 35 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2010 VL 12 IS 3 BP 300 EP 308 DI 10.1208/s12248-010-9189-x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735NU UT WOS:000288425000006 PM 20405259 ER PT J AU Tian, J Atkinson, NL Portnoy, B Lowitt, NR AF Tian, Jing Atkinson, Nancy L. Portnoy, Barry Lowitt, Nancy R. TI The Development of a Theory-Based Instrument to Evaluate the Effectiveness of Continuing Medical Education SO ACADEMIC MEDICINE LA English DT Article ID HEALTH-CARE; PHYSICIAN BEHAVIOR; PLANNED BEHAVIOR; OUTCOMES AB Purpose To determine the psychometric properties of a theoretically based continuing medical education (CME) evaluation instrument examining attitudinal determinants of physicians' changes in medical practices after a CME intervention. The instrument's scales represented constructs from the theory of planned behavior. Method The authors based the template instrument on educational objectives of the CME intervention and adapted it to the clinical domain of preoperative breast cancer therapy. Development of the initial survey involved cognitive testing, pilot tests, and expert reviews. The authors asked 269 clinicians to complete the 35-item instrument before the CME intervention. Factor analysis and item analysis guided the development of the final six subscales: positive behavioral beliefs, negative behavioral beliefs, attitude toward the behavior, perceived behavior control (self-efficacy), subjective norms, and behavioral intention. Results Cognitive testing and pilot tests ensured the accuracy and clarity of the language and a reasonable survey length. Of the 269 clinicians, 168 (134 physicians) responded. Scales clustered according to the theoretical constructs. Items not loading in any subscales were eliminated. The final 25 items loaded on six subscales with loadings >0.54. Reliability for the subscales ranged from 0.73 to 0.93 (good for the scale development stage). The authors revised the instrument template and protocol after this initial study to increase the possibility of use in future CME evaluations. Conclusions The levels of content and construct validity and reliability of the CME evaluation instrument are acceptable for evaluation of CME activities targeting physicians. Instruments adapted from this template could potentially evaluate future CME activities. C1 [Tian, Jing] Univ Maryland, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21201 USA. [Atkinson, Nancy L.] Univ Maryland, Sch Publ Hlth, Dept Publ & Community Hlth, College Pk, MD 20742 USA. [Portnoy, Barry] NIH, Off Dis Prevent, Off Director, Bethesda, MD 20892 USA. [Lowitt, Nancy R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Tian, J (reprint author), Univ Maryland, Sch Med, Dept Med, Div Cardiol, 22 S Greene St N3W77, Baltimore, MD 21201 USA. EM tianjing@umd.edu FU National Institutes of Health/Office of Director Evaluation Express [07-1005 OD-ODP] FX This study was supported by National Institutes of Health/Office of Director Evaluation Express Award no. 07-1005 OD-ODP. NR 31 TC 10 Z9 10 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD SEP PY 2010 VL 85 IS 9 BP 1518 EP 1525 DI 10.1097/ACM.0b013e3181eac3fb PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 647IH UT WOS:000281611300026 PM 20736680 ER PT J AU Wlodawer, A Lubkowski, J Minor, W Jaskolski, M AF Wlodawer, Alexander Lubkowski, Jacek Minor, Wladek Jaskolski, Mariusz TI Is too 'creative' language acceptable in crystallography? SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Letter DE letters to the editor; crystallographic terminology AB While figures of speech are often useful and even educational, flashy titles combined with hyperbolae and imprecise language can mislead or deceive non-specialist readers and should therefore be avoided. The possibility of such confusion exists when poorly defined terms like `structure quality' or `super-resolution' are used to describe a protein structure. C1 [Wlodawer, Alexander; Lubkowski, Jacek] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. [Minor, Wladek] Univ Virginia, Charlottesville, VA USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ Poznan, Poznan, Poland. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. EM wlodawer@nih.gov RI Minor, Wladek/F-3096-2014; OI Minor, Wladek/0000-0001-7075-7090 NR 4 TC 2 Z9 2 U1 0 U2 9 PU WILEY-BLACKWELL 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 SEP PY 2010 VL 66 BP 1041 EP 1042 DI 10.1107/S090744491002799X PN 9 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 647RE UT WOS:000281635500011 PM 20823556 ER PT J AU Yang, JY Qi, J Han, WY Wang, F Wu, CF AF Yang, Jing-yu Qi, Jia Han, Wen-yan Wang, Fang Wu, Chun-fu TI Inhibitory role of oxytocin in psychostimulant-induced psychological dependence and its effects on dopaminergic and glutaminergic transmission SO ACTA PHARMACOLOGICA SINICA LA English DT Review DE psychostimulants; oxytocin; cocaine; methamphetamine; dopamine; glutamate ID CONDITIONED PLACE PREFERENCE; MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; EXTRACELLULAR LEVELS; CROSS-TOLERANCE; COCAINE; RATS; MICE; METHAMPHETAMINE; ADDICTION AB Psychostimulants are frequently abused as a result of their stimulatory effects on several neurotransmitter systems within the central nervous system. Both dopaminergic and glutaminergic neurotransmissions have been closely associated with psychostimulant dependence. In addition to its classical endocrine function in the periphery, oxytocin, an important neurohypophyseal neuropeptide in the central nervous system, has a wide range of behavioral effects, including regulating drug abuse. The present paper reviews the progress of research into the role of oxytocin in reducing psychostimulant-induced psychological dependence and the mechanisms by which oxytocin mediates its effects. C1 [Qi, Jia] NIDA, NIH, Baltimore, MD 21224 USA. [Yang, Jing-yu; Qi, Jia; Han, Wen-yan; Wang, Fang; Wu, Chun-fu] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. RP Wu, CF (reprint author), Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China. EM chunfuw@gmail.com RI QI, JIA/A-6337-2014 FU Key Laboratory for New Drug Screening and Key Laboratory for Pharmacodynamics of Liaoning Province; Outstanding Youth Fund of Liaoning province; National Key Scientific Project for New Drug Discovery and Development, China [2009ZX09301-012] FX This research was partially supported by the Project of Key Laboratory for New Drug Screening and Key Laboratory for Pharmacodynamics of Liaoning Province, the Outstanding Youth Fund of Liaoning province, and the National Key Scientific Project for New Drug Discovery and Development (2009ZX09301-012), 2009-2010, China. NR 46 TC 9 Z9 9 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD SEP PY 2010 VL 31 IS 9 BP 1071 EP 1074 DI 10.1038/aps.2010.140 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 646SK UT WOS:000281562900011 PM 20729875 ER PT J AU Bumb, A Brechbiel, MW Choyke, P AF Bumb, Ambika Brechbiel, Martin W. Choyke, Peter TI Macromolecular and dendrimer-based magnetic resonance contrast agents SO ACTA RADIOLOGICA LA English DT Review DE MRI; magnetic resonance imaging; molecular imaging; comparative studies ID NEPHROGENIC SYSTEMIC FIBROSIS; AFFINITY FOLATE RECEPTOR; WATER-PROTON RELAXATION; DTPA-LABELED DEXTRAN; HUMAN SERUM-ALBUMIN; BLOOD-POOL AGENT; GD-DTPA; POLYAMIDOAMINE DENDRIMER; MR-ANGIOGRAPHY; PHARMACOKINETIC PROPERTIES AB Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on poly-amidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed. C1 [Choyke, Peter] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Bumb, Ambika; Brechbiel, Martin W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Choyke, P (reprint author), NCI, Mol Imaging Program, NIH, Bldg 10,Room B3B69F,10 Ctr Dr, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov FU 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 98 TC 43 Z9 46 U1 2 U2 46 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0284-1851 EI 1600-0455 J9 ACTA RADIOL JI Acta Radiol. PD SEP PY 2010 VL 51 IS 7 BP 751 EP 767 DI 10.3109/02841851.2010.491091 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 649LM UT WOS:000281771500005 PM 20590365 ER PT J AU Dawson, DA Grant, BF AF Dawson, Deborah A. Grant, Bridget F. TI Should symptom frequency be factored into scalar measures of alcohol use disorder severity? SO ADDICTION LA English DT Article DE AUD severity; symptom frequency; validity ID DSM-IV ALCOHOL; IDENTIFICATION TEST AUDIT; NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE DISORDERS; SCREENING-TEST ASSIST; DEPENDENCE SCALE; CONSEQUENCES QUESTIONNAIRE; PREDICTIVE-VALIDITY; POPULATION-SAMPLE; AUDADIS-ADR AB Aims To evaluate whether weighting counts of alcohol use disorder (AUD) criteria or symptoms by their frequency of occurrence improves their association with correlates of AUD. Design and participants Data were collected in personal interviews with a representative sample of US adults interviewed in 1991-92. Analyses were conducted among past-year drinkers (12+ drinks, n = 18 352) and individuals with past-year DSM-IV AUD (n = 2770). Measurements Thirty-one symptom item indicators, whose frequency of occurrence was measured in eight categories, were used to create unweighted and frequency-weighted counts of DSM-IV past-year AUD symptoms and criteria. Correlates included density of familial alcoholism and past-year volume of ethanol intake, frequency of intoxication and utilization of alcohol treatment. Findings Although the AUD correlates were associated strongly and positively with the frequency of AUD symptom occurrence, weighting for symptom frequency did not strengthen their association consistently with AUD severity scores. Improved performance of the weighted scores was observed primarily among AUD correlates linked closely with the frequency of heavy drinking and among individuals with AUD. Criterion counts were correlated nearly as strongly as symptom counts with the AUD correlates. Conclusions Frequency weighting may add somewhat to the validity of AUD severity measures, especially those that are intended for use among individuals with AUD, e.g. in clinical settings. For studying the etiology and course of AUD in the general population, an equally effective and less time-consuming alternative to obtaining symptom frequency may be the use of unweighted criterion counts accompanied by independent measures of frequency of heavy drinking. C1 [Dawson, Deborah A.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3071, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov FU National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The study on which this paper is based, the National Longitudinal Alcohol Epidemiologic Survey, was sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, US Department of Health and Human Services. This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. The views and opinions expressed in this paper are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies or the US government. NR 56 TC 5 Z9 5 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD SEP PY 2010 VL 105 IS 9 BP 1568 EP 1579 DI 10.1111/j.1360-0443.2010.02994.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 635PK UT WOS:000280668200014 PM 20569231 ER PT J AU Nelson, DE Naimi, TS Brewer, RD Roeber, J AF Nelson, David E. Naimi, Timothy S. Brewer, Robert D. Roeber, James TI US state alcohol sales compared to survey data, 1993-2006 SO ADDICTION LA English DT Article DE Alcohol abuse; alcohol drinking; cross-sectional studies; drinking behaviors; health surveys; statistics ID LIVER-CIRRHOSIS MORTALITY; MEASURING QUANTITY; POPULATION-LEVEL; TELEPHONE SURVEY; CONSUMPTION; DRINKING; FREQUENCY; VALIDITY; PREVENTION; EXPERIENCE AB Aims Assess long-term trends of the correlation between alcohol sales data and survey data. Design Analyses of state alcohol consumption data from the US Alcohol Epidemiologic Data System based on sales, tax receipts or alcohol shipments. Cross-sectional, state annual estimates of alcohol-related measures for adults from the US Behavioral Risk Factor Surveillance System using telephone surveys. Setting United States. Participants State alcohol tax authorities, alcohol vendors, alcohol industry (sales data) and randomly selected adults aged >= 18 years 1993-2006 (survey data). Measurements State-level per capita annual alcohol consumption estimates from sales data. Self-reported alcohol consumption, current drinking, heavy drinking, binge drinking and alcohol-impaired driving from surveys. Correlation coefficients were calculated using linear regression models. Findings State survey estimates of consumption accounted for amedian of 22% to 32% of state sales data across years. Nevertheless, state consumption estimates from both sources were strongly correlated with annual r-values ranging from 0.55-0.71. State sales data had moderate-to-strong correlations with survey estimates of current drinking, heavy drinking and binge drinking (range of r-values across years: 0.57-0.65; 0.33-0.70 and 0.45-0.61, respectively), but a weaker correlation with alcoholimpaired driving (range of r-values: 0.24-0.56). There were no trends in the magnitude of correlation coefficients. Conclusions Although state surveys substantially underestimated alcohol consumption, the consistency of the strength of the association between sales consumption and survey data for most alcohol measures suggest both data sources continue to provide valuable information. These findings support and extend the distribution of consumption model and single distribution theory, suggesting that both sales and survey data are useful for monitoring population changes in alcohol use. C1 [Nelson, David E.] NCI, Canc Prevent Fellowship Program, Ctr Canc Training, Bethesda, MD 20892 USA. [Nelson, David E.; Naimi, Timothy S.; Brewer, Robert D.] Ctr Dis Control & Prevent, Alcohol Team, Emerging Invest & Analyt Methods Branch, Div Adult & Community Hlth,Natl Ctr Chron Dis Pre, Atlanta, GA USA. [Roeber, James] New Mexico Dept Hlth, Albuquerque, NM USA. RP Nelson, DE (reprint author), NCI, Canc Prevent Fellowship Program, Ctr Canc Training, 6120 Execut Blvd,Suite 150E,MSC 7105, Bethesda, MD 20892 USA. EM nelsonde@mail.nih.gov RI Stockwell, Tim/B-6662-2012 NR 50 TC 39 Z9 42 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0965-2140 J9 ADDICTION JI Addiction PD SEP PY 2010 VL 105 IS 9 BP 1589 EP 1596 DI 10.1111/j.1360-0443.2010.03007.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 635PK UT WOS:000280668200017 PM 20626370 ER PT J AU Schulze, S Huang, GS Krause, M Aubyn, D Quinones, VAB Schmidt, CK Mei, YF Schmidt, OG AF Schulze, Sabine Huang, Gaoshan Krause, Matthias Aubyn, Deborah Quinones, Vladimir A. Bolanos Schmidt, Christine K. Mei, Yongfeng Schmidt, Oliver G. TI Morphological Differentiation of Neurons on Microtopographic Substrates Fabricated by Rolled-Up Nanotechnology SO ADVANCED ENGINEERING MATERIALS LA English DT Article ID RAT HIPPOCAMPAL-NEURONS; CONTACT GUIDANCE; CELL-MIGRATION; CULTURE; GROWTH; SCAFFOLDS; SURFACES; ADHESION; CHANNELS; INVITRO AB Arrays of transparent rolled-up microtubes can easily be mass-produced using a combination of conventional photolithography, electron beam depositioning, and chemical etching techniques. Here, we culture primary mouse motor neurons and immortalised CAD cells, a cell line derived from the central nervous system, on various microtube substrates to investigate the influence of topographical surface features on the growth and differentiation behaviour of these cells. Our results indicate that the microtube chips not only support growth of both cell types but also provide a well-defined, geometrically confined 3D cell culture scaffold. Strikingly, our micropatterns act as a platform for axon guidance with protruding cell extensions aligning in the direction of the microtubes and forming complex square-shaped grid-like neurite networks. Our experiments open up a cost-efficient and bio-compatible way of analysing single cell behaviour in the context of advanced micro-/nanostructures with various biological applications ranging from neurite protection studies to cell sensor development. C1 [Schulze, Sabine; Huang, Gaoshan; Quinones, Vladimir A. Bolanos; Mei, Yongfeng; Schmidt, Oliver G.] IFW Dresden, Inst Integrat Nanosci, D-01069 Dresden, Germany. [Schmidt, Oliver G.] Tech Univ Chemnitz, D-09107 Chemnitz, Germany. [Schmidt, Christine K.] London Res Inst, Chromosome Segregat Lab, Canc Res UK, London WC2A 3PX, England. [Schmidt, Christine K.] NCI, Bethesda, MD 20892 USA. [Aubyn, Deborah] London Res Inst, Light Microscopy Lab, Canc Res UK, London WC2A 3PX, England. [Krause, Matthias] Kings Coll London, Randall Div Cell & Mol Biophys, London SE1 1UL, England. RP Schulze, S (reprint author), IFW Dresden, Inst Integrat Nanosci, Helmholtzstr 20, D-01069 Dresden, Germany. EM schmidtck@mail.nih.gov; mei@ifw-dresden.de RI Huang, GaoShan/C-3629-2008; Krause, Matthias/D-9814-2013; OI Krause, Matthias/0000-0002-3200-3199; Schmidt, Christine/0000-0002-8363-7933; Mei, Yongfeng/0000-0002-3314-6108 FU Volkswagen Foundation [I/84 072]; Germany/Hong Kong Joint Research Scheme [426/hk-PPP-cab]; Wellcome Trust [077429/Z/05/Z] FX We acknowledge Dr. Frank Uhlmann for hosting our biological experiments, Dr. Ina Weisswange for imaging advice, Emica Coric and Anne Weston for SEM measurements and Guillermo Menendez and Anna Wade for kindly providing us with primary mouse neurons. This work was financially supported by a grant from the Volkswagen Foundation (I/84 072) and partial support from the Germany/Hong Kong Joint Research Scheme (Grant No. 426/hk-PPP-cab). MK is supported by funds from a Wellcome Trust University Award (077429/Z/05/Z). NR 37 TC 29 Z9 30 U1 4 U2 28 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1438-1656 J9 ADV ENG MATER JI Adv. Eng. Mater. PD SEP PY 2010 VL 12 IS 9 SI SI BP B558 EP B564 DI 10.1002/adem.201080023 PG 7 WC Materials Science, Multidisciplinary SC Materials Science GA 677ML UT WOS:000283996400018 ER PT J AU Pinto, LA Sullivan, EL Rosenbaum, A Wyngarden, N Umhau, JC Miller, MW Taft, CT AF Pinto, Lavinia A. Sullivan, Eric L. Rosenbaum, Alan Wyngarden, Nicole Umhau, John C. Miller, Mark W. Taft, Casey T. TI Biological correlates of intimate partner violence perpetration SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE Intimate partner violence; Biological factors; Neuropsychology; Psychophysiology; Neurochemistry; Genetics ID MONOAMINE-OXIDASE-A; PHYSICAL HEALTH CONSEQUENCES; YOUNG-ADULT PRISONERS; HEART-RATE REACTIVITY; AL. 1995 TYPOLOGY; DOMESTIC VIOLENCE; AGGRESSIVE-BEHAVIOR; INTERGENERATIONAL TRANSMISSION; CONFLICT-TACTICS; FUNCTIONAL POLYMORPHISM AB An extensive literature documents biological correlates of general aggression, but there has been less focus on biological correlates of intimate partner violence (IPV). The purpose of this review is to summarize the research literature to date that has reported on biological factors in IPV perpetration. We review the existing literature on four domains of biological processes that have been examined with respect to IPV perpetration, including: head injury and neuropsychology; psychophysiology; neurochemistry, metabolism and endocrinology; and genetics. We critique the literature, discuss the clinical relevance of research findings, and provide some recommendations for future biologically-oriented IPV research. Published by Elsevier Ltd. C1 [Pinto, Lavinia A.; Miller, Mark W.; Taft, Casey T.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Sullivan, Eric L.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. [Rosenbaum, Alan; Wyngarden, Nicole] No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. [Umhau, John C.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. [Miller, Mark W.; Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA. EM Casey.Taft@va.gov FU NIMH NIH HHS [R01 MH079806] NR 111 TC 27 Z9 27 U1 11 U2 32 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD SEP-OCT PY 2010 VL 15 IS 5 BP 387 EP 398 DI 10.1016/j.avb.2010.07.001 PG 12 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 660VS UT WOS:000282675200008 PM 23393423 ER PT J AU Mittelman, M Alperson, SY Arcari, PM Donnelly, GF Ford, LC Koithan, M Kreitzer, MJ AF Mittelman, Michele Alperson, Sunny Yim Arcari, Patricia Martin Donnelly, Gloria Ferraro Ford, Loretta C. Koithan, Mary Kreitzer, Mary Jo TI NURSING AND INTEGRATIVE HEALTH CARE SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 [Alperson, Sunny Yim] NINR, Washington, DC USA. [Alperson, Sunny Yim] NIH, Ctr Clin, Washington, DC USA. [Arcari, Patricia Martin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Arcari, Patricia Martin] Benson Henry Inst Mind Body Med, Mind Body Program Mothers, Boston, MA USA. [Donnelly, Gloria Ferraro] Drexel Univ, Coll Nursing & Hlth Profess, Philadelphia, PA 19104 USA. [Ford, Loretta C.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Koithan, Mary] Univ Arizona, Coll Nursing, Tucson, AZ 85721 USA. [Kreitzer, Mary Jo] Univ Minnesota, Ctr Spiritual & Healing, Minneapolis, MN USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD SEP-OCT PY 2010 VL 16 IS 5 BP 74 EP 84 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V28TS UT WOS:000208703700014 PM 20882736 ER PT J AU Goldberger, JJ Bonow, RO Cuffe, M Dyer, A Rosenberg, Y O'Rourke, R Shah, PK Smith, SC AF Goldberger, Jeffrey J. Bonow, Robert O. Cuffe, Michael Dyer, Alan Rosenberg, Yves O'Rourke, Robert Shah, Prediman K. Smith, Sidney C., Jr. CA PACE-MI Investigators TI beta-Blocker use following myocardial infarction: Low prevalence of evidence-based dosing SO AMERICAN HEART JOURNAL LA English DT Article ID ASSOCIATION TASK-FORCE; CHRONIC HEART-FAILURE; DEVELOP PERFORMANCE-MEASURES; MEASURES WRITING COMMITTEE; RANDOMIZED-TRIAL; AMERICAN-COLLEGE; NORWEGIAN MULTICENTER; SECONDARY PREVENTION; PRACTICE GUIDELINES; HOSPITAL DISCHARGE AB Background Quality improvement programs have shown increased use of beta-blockers post-myocardial infarction (MI), but there are no data on whether appropriate doses are administered. Methods In a prospective registry that enrolled consecutive patients with MI, we evaluated beta-blocker dosing at discharge after MI and 3 weeks later and assessed clinical predictors for treatment with very low doses. We studied 1,971 patients (70.8% male) with a mean age of 63.9 +/- 13.7 years, of whom 48.2% had an ST-elevation MI. Results beta-Blocker utilization rates following MI were 93.2% at discharge: 20.1% received < 25% of target dose, 36.5% received < 25% of target dose, 26.4% received 26% to 50% of target dose, and 17.0% received >50% of target dose. Between discharge and 3 weeks, 76.4% had no change in beta-blocker dose, with 11.9% and 11.6% having their dose reduced and increased, respectively. Absence of hypertension, acute percutaneous coronary intervention, older age, and no angiotensin-converting enzyme inhibitor therapy were consistent predictors of treatment with very low beta-blocker doses. Conclusions Underdosing of beta-blockers is highly prevalent among patients post-MI. This represents an important opportunity in quality improvement for the care of patients who have suffered an MI. (Am Heart J 2010; 160:435-442.e1.) C1 [Goldberger, Jeffrey J.; Bonow, Robert O.; Dyer, Alan] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Cuffe, Michael] Duke Univ, Med Ctr, Durham, NC USA. [Rosenberg, Yves] NHLBI, NIH, Bethesda, MD 20892 USA. [O'Rourke, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shah, Prediman K.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Smith, Sidney C., Jr.] Univ N Carolina, Chapel Hill, NC USA. RP Goldberger, JJ (reprint author), Northwestern Univ, Feinberg Sch Med, 251 E Huron,Feinberg Pavil 8-503, Chicago, IL 60611 USA. EM j-goldberger@northwestern.edu OI Subacius, Haris/0000-0003-4061-1220 FU NHLBI NIH HHS [U01 HL080416, U01 HL080416-02] NR 40 TC 14 Z9 14 U1 0 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 SEP PY 2010 VL 160 IS 3 BP 435 EP U86 DI 10.1016/j.ahj.2010.06.023 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647YH UT WOS:000281656300009 PM 20826250 ER PT J AU Yan, RT Fernandes, V Yan, AT Cushman, M Redheuil, A Tracy, R Vogel-Claussen, J Bahrami, H Nasir, K Bluemke, DA Lima, JAC AF Yan, Raymond T. Fernandes, Veronica Yan, Andrew T. Cushman, Mary Redheuil, Alban Tracy, Russell Vogel-Claussen, Jens Bahrami, Hossein Nasir, Khurram Bluemke, David A. Lima, Joao A. C. TI Fibrinogen and left ventricular myocardial systolic function: The Multi-Ethnic Study of Atherosclerosis (MESA) SO AMERICAN HEART JOURNAL LA English DT Article ID INDIVIDUAL PARTICIPANT METAANALYSIS; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; RISK-FACTORS; ASYMPTOMATIC INDIVIDUALS; HARP MRI; ARTERY; INFLAMMATION AB Background Increasing evidence suggests that elevated plasma fibrinogen is associated with incident heart failure. However, the underlying pathophysiological mechanisms have not been well elucidated. Methods We examined the relationship between plasma fibrinogen level and peak systolic midwall circumferential strain (Ecc) at the base, mid cavity, and apex of the left ventricle measured by magnetic resonance imaging myocardial tagging in 1096 participants without clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Results After adjustment for demographics, established risk factors and body mass index, elevated fibrinogen was independently associated with reductions in absolute Ecc indicative of impaired systolic function in all regions (all P <= .015). The relationships were consistently significant upon further adjustment for measures of atherosclerosis (all P < .024) and were modestly attenuated with regional heterogeneity after additional adjustment for other inflammatory biomarker and N-terminal pro-brain natriuretic peptide. In this fully-adjusted model, every 1-SD (74 mg/dL) increment in plasma fibrinogen was independently associated with a reduction in left ventricular absolute Ecc of 0.29% (95% CI 0.03%-0.59%, P = .048) at the base, 0.22% (95% CI 0.006%-0.43%, P = .044) at mid cavity, 0.20% (95% CI = -0.035% to 0.43%, P = .097) at the apex, and 0.24% (95% CI = 0.05%-0.43%, P = .015) overall. Conclusions Among asymptomatic individuals without clinical cardiovascular disease, elevated fibrinogen is independently associated with impaired myocardial systolic function. These findings support roles of inflammation, procoagulation, and hyperviscosity underlying hyperfibrinogenemia in the pathogenesis of incipient myocardial dysfunction. (Am Heart J 2010;160:479-86.) C1 [Yan, Raymond T.; Redheuil, Alban; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. [Fernandes, Veronica] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Yan, Andrew T.] Univ Toronto, St Michaels Hosp, Div Cardiol, Toronto, ON M5B 1W8, Canada. [Cushman, Mary; Tracy, Russell] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [Vogel-Claussen, Jens] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [Bahrami, Hossein] Yale Univ, Dept Med, New Haven, CT 06520 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Bluemke, David A.] NIH, Bethesda, MD 20892 USA. RP Lima, JAC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA. EM jlima@jhmi.edu OI Bluemke, David/0000-0002-8323-8086 FU National Heart, Lung, and Blood Institute [RO1-HL66075-01]; Multi-Ethnic Study of Atherosclerosis study [NO1-HC-95162, NO1-HC-95168, NO1-HC-95169]; Canadian Institutes of Health Research; Royal College of Physicians and Surgeons of Canada FX This study was supported by the National Heart, Lung, and Blood Institute grant (RO1-HL66075-01) and the Multi-Ethnic Study of Atherosclerosis study contracts (NO1-HC-95162, NO1-HC-95168 and NO1-HC-95169). Dr Raymond Yan was supported by fellowship awards from the Canadian Institutes of Health Research and the Royal College of Physicians and Surgeons of Canada. NR 45 TC 12 Z9 14 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 SEP PY 2010 VL 160 IS 3 BP 479 EP 486 DI 10.1016/j.ahj.2010.06.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647YH UT WOS:000281656300015 PM 20826256 ER PT J AU Cheng, S Larson, MG Keyes, MJ McCabe, EL Newton-Cheh, C Levy, D Benjamin, EJ Vasan, RS Wang, TJ AF Cheng, Susan Larson, Martin G. Keyes, Michelle J. McCabe, Elizabeth L. Newton-Cheh, Christopher Levy, Daniel Benjamin, Emelia J. Vasan, Ramachandran S. Wang, Thomas J. TI Relation of QRS Width in Healthy Persons to Risk of Future Permanent Pacemaker Implantation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BUNDLE-BRANCH-BLOCK; COMPLETE ATRIOVENTRICULAR-BLOCK; MYOCARDIAL-INFARCTION; INTRAVENTRICULAR-CONDUCTION; ELDERLY PATIENTS; VALVE SURGERY; HEART-DISEASE; PATHOLOGY; DURATION; LOCATIONS AB In the setting of acute myocardial infarction, prolongation of the QRS interval on electrocardiography identifies patients at risk for needing permanent pacemaker implantation. However, the implications of prolonged QRS intervals in healthy subjects are unclear, especially given that the QRS prolongation encountered in this setting is typically mild. The aim of this study was to assess the relation between QRS duration and incident pacemaker implantation in a community-based cohort of 8,311 subjects (mean age 54 years, 55% women) who attended 17,731 routine examinations with resting 12-lead electrocardiography. QRS duration was analyzed as a continuous and a categorical variable (<100, 100 to <120, and >= 120 ms). During up to 35 years of follow-up, 157 participants (56 women) developed need for permanent pacemakers. In multivariable Cox regression models adjusting for cardiovascular risk factors and previous myocardial infarction or heart failure, mild QRS prolongation was associated with a threefold risk for pacemaker implantation (adjusted hazard ratio 2.90, 95% confidence interval 1.81 to 4.66, p < 0.0001), and bundle branch block was associated with a fourfold risk for pacemaker implantation (hazard ratio 4.43, 95% confidence interval 2.94 to 6.68, p < 0.0001). Each standard deviation increment in QRS duration (11 ms) was associated with an adjusted hazard ratio of 1.14 (95% confidence interval 1.11 to 1.18, p < 0.0001) for pacemaker placement. This association remained significant after excluding subjects with QRS durations >= 120 ms. In conclusion, subjects with prolonged QRS durations, even without bundle branch block, are at increased risk for future pacemaker implantation. Such individuals may warrant monitoring for progressive conduction disease. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 20102010;106:668-672) C1 [Cheng, Susan; Larson, Martin G.; Keyes, Michelle J.; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Cheng, Susan; McCabe, Elizabeth L.; Newton-Cheh, Christopher; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Larson, Martin G.; Newton-Cheh, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Cardiovasc Med, Boston, MA 02115 USA. [Keyes, Michelle J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Levy, Daniel; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Wang, TJ (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA USA. OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU Framingham Heart Study of the National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-25195] FX This work was supported by the Framingham Heart Study of the National Heart, Lung, and Blood Institute, Bethesda, Maryland (Contract Number N01-HC-25195) NR 22 TC 11 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2010 VL 106 IS 5 BP 668 EP 672 DI 10.1016/j.amjcard.2010.04.021 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647JW UT WOS:000281615800012 PM 20723643 ER PT J AU Grant, JE Potenza, MN Weinstein, A Gorelick, DA AF Grant, Jon E. Potenza, Marc N. Weinstein, Aviv Gorelick, David A. TI Introduction to Behavioral Addictions SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE behavioral addiction; classification; diagnosis; impulse control disorder; substance use disorder ID OBSESSIVE-COMPULSIVE DISORDER; IMPULSE CONTROL DISORDERS; GENDER-RELATED DIFFERENCES; PLACEBO-CONTROLLED TRIAL; PATHOLOGICAL GAMBLERS; CLINICAL-FEATURES; DOUBLE-BLIND; PSYCHIATRIC COMORBIDITY; PARKINSONS-DISEASE; ALCOHOL DEPENDENCE AB Background: Several behaviors, besides psychoactive substance ingestion, produce short-term reward that may engender persistent behavior, despite knowledge of adverse consequences, i.e., diminished control over the behavior. These disorders have historically been conceptualized in several ways. One view posits these disorders as lying along an impulsive-compulsive spectrum, with some classified as impulse control disorders. An alternate, but not mutually exclusive, conceptualization considers the disorders as non-substance or "behavioral" addictions. Objectives: Inform the discussion on the relationship between psychoactive substance and behavioral addictions. Methods: We review data illustrating similarities and differences between impulse control disorders or behavioral addictions and substance addictions. This topic is particularly relevant to the optimal classification of these disorders in the forthcoming fifth edition of the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders (DSMV). Results: Growing evidence suggests that behavioral addictions resemble substance addictions in many domains, including natural history, phenomenology, tolerance, comorbidity, overlapping genetic contribution, neurobiologicalmechanisms, and response to treatment, supporting the DSM-V Task Force proposed new category of Addiction and Related Disorders encompassing both substance use disorders and non-substance addictions. Current data suggest that this combined categorymay be appropriate for pathological gambling and a few other better studied behavioral addictions, e. g., Internet addiction. There is currently insufficient data to justify any classification of other proposed behavioral addictions. Conclusions and Scientific Significance: Proper categorization of behavioral addictions or impulse control disorders has substantial implications for the development of improved prevention and treatment strategies. C1 [Grant, Jon E.] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Potenza, Marc N.] Yale Univ, Sch Med, New Haven, CT USA. [Weinstein, Aviv] Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. [Gorelick, David A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP Gorelick, DA (reprint author), 251 Bayview Blvd, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS [ZIA DA000240-18]; NIDA NIH HHS [RC1 DA028279, ZIA DA000240-19, R01 DA019139] NR 102 TC 210 Z9 213 U1 12 U2 140 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD SEP PY 2010 VL 36 IS 5 BP 233 EP 241 DI 10.3109/00952990.2010.491884 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 663UY UT WOS:000282916900001 PM 20560821 ER PT J AU Khoury, MJ Gwinn, M Ioannidis, JPA AF Khoury, Muin J. Gwinn, Marta Ioannidis, John P. A. TI The Emergence of Translational Epidemiology: From Scientific Discovery to Population Health Impact SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE epidemiology; genomics; medicine; public health; translational research ID GENOME-WIDE ASSOCIATION; CLINICAL-RESEARCH; UNITED-STATES; PERSONALIZED MEDICINE; PUBLIC-HEALTH; DISEASE; RISK; CHALLENGES; PREVENTION; PROFILES AB Recent emphasis on translational research (TR) is highlighting the role of epidemiology in translating scientific discoveries into population health impact. The authors present applications of epidemiology in TR through 4 phases designated T1-T4, illustrated by examples from human genomics. In T1, epidemiology explores the role of a basic scientific discovery (e.g., a disease risk factor or biomarker) in developing a "candidate application" for use in practice (e.g., a test used to guide interventions). In T2, epidemiology can help to evaluate the efficacy of a candidate application by using observational studies and randomized controlled trials. In T3, epidemiology can help to assess facilitators and barriers for uptake and implementation of candidate applications in practice. In T4, epidemiology can help to assess the impact of using candidate applications on population health outcomes. Epidemiology also has a leading role in knowledge synthesis, especially using quantitative methods (e.g., meta-analysis). To explore the emergence of TR in epidemiology, the authors compared articles published in selected issues of the Journal in 1999 and 2009. The proportion of articles identified as translational doubled from 16% (11/69) in 1999 to 33% (22/66) in 2009 (P = 0.02). Epidemiology is increasingly recognized as an important component of TR. By quantifying and integrating knowledge across disciplines, epidemiology provides crucial methods and tools for TR. C1 [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Ioannidis, John P. A.] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA USA. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Ioannidis, John P. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@cdc.gov RI Ioannidis, John/G-9836-2011 NR 58 TC 108 Z9 117 U1 2 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2010 VL 172 IS 5 BP 517 EP 524 DI 10.1093/aje/kwq211 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643UF UT WOS:000281324100003 PM 20688899 ER PT J AU Khoury, MJ Gwinn, M Ioannidis, JPA AF Khoury, Muin J. Gwinn, Marta Ioannidis, John P. A. TI Khoury et al. Respond to "The Epicenter of Translational Science": Crossing All the T's SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID EPIDEMIOLOGY C1 [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA 30333 USA. [Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Biomed Res Inst, Ioannina, Greece. [Ioannidis, John P. A.] Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. [Ioannidis, John P. A.] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA USA. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Ioannidis, John P. A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Khoury, MJ (reprint author), Ctr Dis Control & Prevent, Off Publ Hlth Genom, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM muk1@cdc.gov RI Ioannidis, John/G-9836-2011 NR 8 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2010 VL 172 IS 5 BP 528 EP 529 DI 10.1093/aje/kwq214 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643UF UT WOS:000281324100005 ER PT J AU Alley, DE Metter, EJ Griswold, ME Harris, TB Simonsick, EM Longo, DL Ferrucci, L AF Alley, Dawn E. Metter, E. Jeffrey Griswold, Michael E. Harris, Tamara B. Simonsick, Eleanor M. Longo, Dan L. Ferrucci, Luigi TI Changes in Weight at the End of Life: Characterizing Weight Loss by Time to Death in a Cohort Study of Older Men SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aged; cachexia; cause of death; cohort studies; mortality; weight loss ID ALL-CAUSE MORTALITY; BODY-MASS INDEX; RISK-FACTOR; AGE; OVERWEIGHT; HEALTH; WOMEN AB The purpose of this analysis was to characterize the natural history of weight change in the years prior to death among older persons and to examine how this pattern varies according to longevity and cause of death. Weight trajectories were analyzed by using data from 800 male decedents from the Baltimore Longitudinal Study of Aging (Maryland, 1958-2005) observed beginning an average of 19 years before death. A model including 3 distinct periods of weight change (weight stability/gain, mild weight loss, and accelerated weight loss before death) provided the best fit for all age-at-death groups. Approximately 9 years before death, the rate of weight loss increased to an average of 0.39 kg/year (P < 0.001) for all-cause mortality. For cancer deaths, weight loss accelerated significantly 3 years before death, regardless of age group. For cardiovascular deaths, the best-fitting inflection point increased with age, from 5 years for participants aged 60-69 years to 9-10 years before death for those aged 80 years or older. Results suggest that weight loss in older persons may begin earlier than previously believed. The duration of weight loss for noncancer deaths suggests that even distal changes in energy balance may be linked to risk of death. C1 [Alley, Dawn E.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Metter, E. Jeffrey; Simonsick, Eleanor M.; Longo, Dan L.; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Griswold, Michael E.] Univ Mississippi, Med Ctr, Ctr Biostat, Jackson, MS 39216 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Alley, DE (reprint author), 660 W Redwood St,221B, Baltimore, MD 21201 USA. EM dalley@epi.umaryland.edu FU National Institute on Aging Intramural Research Program; Robert Wood Johnson Foundation Health and Society Scholars Program; Organized Research Center on Aging at the University of Maryland, Baltimore FX This work was supported by the National Institute on Aging Intramural Research Program; the Robert Wood Johnson Foundation Health and Society Scholars Program; and the Organized Research Center on Aging at the University of Maryland, Baltimore. NR 26 TC 21 Z9 24 U1 3 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2010 VL 172 IS 5 BP 558 EP 565 DI 10.1093/aje/kwq168 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643UF UT WOS:000281324100010 PM 20682520 ER PT J AU Kristal, AR Arnold, KB Neuhouser, ML Goodman, P Platz, EA Albanes, D Thompson, IM AF Kristal, Alan R. Arnold, Kathryn B. Neuhouser, Marian L. Goodman, Phyllis Platz, Elizabeth A. Albanes, Demetrius Thompson, Ian M. TI Diet, Supplement Use, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; dietary supplements; food; micronutrients; prostatic neoplasms ID FOOD-FREQUENCY QUESTIONNAIRE; DAIRY-PRODUCTS; VITAMIN-E; SELENIUM SUPPLEMENTATION; ALCOHOL-CONSUMPTION; MULTIETHNIC COHORT; SCREENING TRIAL; CALCIUM INTAKE; BREAST-CANCER; FAT AB The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994-2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8-10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk. C1 [Kristal, Alan R.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Kristal, Alan R.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Platz, Elizabeth A.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Albanes, Demetrius] NCI, Bethesda, MD 20892 USA. [Thompson, Ian M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. RP Kristal, AR (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402,POB 19024, Seattle, WA 98109 USA. EM akristal@fhcrc.org RI Albanes, Demetrius/B-9749-2015; OI Kristal, Alan/0000-0002-7329-1617 FU National Cancer Institute [R01 CA63164, P01 CA37429, P01 CA108964] FX This work was supported by the following grants from the National Cancer Institute: R01 CA63164 (Prospective Cohort Study of Diet and Prostate Cancer), P01 CA37429 (Prostate Cancer Prevention Trial), and P01 CA108964 (Biology of the Prostate Cancer Prevention Trial). NR 56 TC 68 Z9 71 U1 4 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2010 VL 172 IS 5 BP 566 EP 577 DI 10.1093/aje/kwq148 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643UF UT WOS:000281324100011 PM 20693267 ER PT J AU Salinas, CA Kwon, EM FitzGerald, LM Feng, ZD Nelson, PS Ostrander, EA Peters, U Stanford, JL AF Salinas, Claudia A. Kwon, Erika M. FitzGerald, Liesel M. Feng, Ziding Nelson, Peter S. Ostrander, Elaine A. Peters, Ulrike Stanford, Janet L. TI Use of Aspirin and Other Nonsteroidal Antiinflammatory Medications in Relation to Prostate Cancer Risk SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE anti-inflammatory agents; non-steroidal; aspirin; odds ratio; polymorphism; genetic; prostaglandin-endoperoxide synthases; prostatic neoplasms ID INVERSE ASSOCIATION; GENETIC-VARIATION; LARGE COHORT; COX-2 GENE; DRUG-USE; CYCLOOXYGENASE-2; NSAIDS; EXPRESSION; PREVENTION; BREAST AB Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk. In a population-based case-control study designed to investigate the relation between these medications and prostate cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with prostate cancer between January 1, 2002, and December 31, 2005, and 942 age-matched controls from King County, Washington. A significant 21% reduction in the risk of prostate cancer was observed among current users of aspirin compared with nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (> 5 years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk. There was no evidence that the association with aspirin use varied by disease aggressiveness, but there was effect modification (P(interaction) = 0.02) with a genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763). Prostate cancer risk was not related to use of either nonaspirin NSAIDs or acetaminophen. These results contribute further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research. C1 [Salinas, Claudia A.; FitzGerald, Liesel M.; Feng, Ziding; Peters, Ulrike; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Salinas, Claudia A.; Peters, Ulrike; Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Feng, Ziding] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Nelson, Peter S.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Mailstop M4-B874,POB 19024, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [R01 CA092579, R03 CA121871, N01-PC-35142]; US Department of Defense [PC06445]; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute FX This work was supported by grants R01 CA092579 and R03 CA121871 and contract N01-PC-35142 from the National Cancer Institute, as well as by training grant PC06445 from the US Department of Defense (C. A. S.). Additional support was provided by the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute. NR 45 TC 42 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2010 VL 172 IS 5 BP 578 EP 590 DI 10.1093/aje/kwq175 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 643UF UT WOS:000281324100012 PM 20688905 ER PT J AU Patton, HM Yates, K Unalp-Arida, A Behling, CA Huang, TTK Rosenthal, P Sanyal, AJ Schwimmer, JB Lavine, JE AF Patton, Heather M. Yates, Katherine Unalp-Arida, Aynur Behling, Cynthia A. Huang, Terry T. -K. Rosenthal, Philip Sanyal, Arun J. Schwimmer, Jeffrey B. Lavine, Joel E. CA NASH CRN TI Association Between Metabolic Syndrome and Liver Histology Among Children With Nonalcoholic Fatty Liver Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID TRIGLYCERIDE TRANSFER PROTEIN; NUTRITION EXAMINATION SURVEY; CARDIOVASCULAR RISK-FACTORS; US ADOLESCENTS; ALANINE AMINOTRANSFERASE; INSULIN-RESISTANCE; NATIONAL-HEALTH; STEATOHEPATITIS; DEFINITION; PREVALENCE AB OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is considered the hepatic manifestation of metabolic syndrome (MetS) among adults. Emerging data suggest that MetS may be associated with nonalcoholic fatty liver disease (NAFLD) in children as well. We sought to determine whether MetS or its component features are associated with specific histological features or severity of NAFLD. METHODS: Children and adolescents aged 6-17 years enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) with clinical data obtained within 6 months of liver biopsy were included. MetS was defined as the presence of three or more of the following features as determined by application of age-adjusted normative values: central obesity, dyslipidemia, impaired fasting glucose, and elevated blood pressure. Liver biopsies were evaluated by the Pathology Committee of the NASH CRN. RESULTS: Two hundred fifty four children were included in the analysis, of whom 65 (26%) met specified criteria for MetS. Among children with MetS, there is a higher proportion of females who were on average older in age and pubertal. The risk of MetS was greatest among those with severe steatosis (odds ratio (OR)=2.58 for grade 3 vs. grade 1 steatosis, P=0.001). The presence of hepatocellular ballooning was also significantly associated with MetS (OR=2.10, P=0.03). Those with advanced fibrosis (stage 3/4) had an OR for MetS of 3.21 (P=0.04) vs. those without fibrosis (stage 0). Borderline zone 1 or definite NASH patterns compared with "not NASH" were strongly associated with MetS (OR=4.44, P=0.005 and OR=4.07, P=0.002, respectively). The mean NAFLD Activity Score (NAS) was greater among children with MetS vs. those without (4.8 +/- 1.4 vs. 4.3 +/- 1.4, P=0.01). Central obesity was significantly associated with steatosis, fibrosis, hepatocellular ballooning, and NAFLD pattern. Insulin resistance was significantly associated with steatosis, fibrosis, hepatocellular ballooning, NAS, and NAFLD pattern. CONCLUSIONS: MetS is common among children with NAFLD and is associated with severity of steatosis, hepatocellular ballooning, NAS, NAFLD pattern, and the presence of advanced fibrosis. Individual MetS features, particularly central obesity and insulin resistance, were also associated with severity of NAFLD. MetS features should be considered in children with NAFLD as individually and collectively they help identify children with more advanced disease. C1 [Patton, Heather M.; Schwimmer, Jeffrey B.; Lavine, Joel E.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Patton, Heather M.; Schwimmer, Jeffrey B.; Lavine, Joel E.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Yates, Katherine; Unalp-Arida, Aynur] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Behling, Cynthia A.] Pacific Rim Pathol Grp, San Diego, CA USA. [Huang, Terry T. -K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Rosenthal, Philip] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Med, Richmond, VA 23298 USA. RP Lavine, JE (reprint author), Morgan Stanley Childrens Hosp New York, 3959 Broadway,CHN7-702, New York, NY 10032 USA. EM jl3553@columbia.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713]; National Institute of Child Health and Human Development; General Clinical Research Centers [UL1RR024989, M01RR000750, M01RR00188, RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359]; National Institutes of Health, National Cancer Institute FX The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (Grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development. Several clinical centers use support from General Clinical Research Centers or Clinical and Translational Science Awards in the conduct of Nonalcoholic Steatohepatitis Clinical Research Network studies (Grants UL1RR024989, M01RR000750, M01RR00188, RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359). This study was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. NR 50 TC 65 Z9 70 U1 0 U2 4 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 SEP PY 2010 VL 105 IS 9 BP 2093 EP 2102 DI 10.1038/ajg.2010.152 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 646SM UT WOS:000281563100026 PM 20372110 ER PT J AU Shebl, FM El-Kamary, SS AF Shebl, Fatma M. El-Kamary, Samer S. TI Diabetes Mellitus, Obesity, and Hepatocellular Carcinoma: The Jury Is Still Out SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 [Shebl, Fatma M.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [El-Kamary, Samer S.] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Shebl, FM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7074, Rockville, MD 20852 USA. EM sheblf@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2010 VL 105 IS 9 BP 2116 EP 2117 DI 10.1038/ajg.2010.184 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 646SM UT WOS:000281563100039 PM 20818365 ER PT J AU Stevens, LA Schmid, CH Greene, T Zhang, YP Beck, GJ Froissart, M Hamm, LL Lewis, JB Mauer, M Navis, GJ Steffes, MW Eggers, PW Coresh, J Levey, AS AF Stevens, Lesley A. Schmid, Christopher H. Greene, Tom Zhang, Yaping (Lucy) Beck, Gerald J. Froissart, Marc Hamm, Lee L. Lewis, Julia B. Mauer, Michael Navis, Gerjan J. Steffes, Michael W. Eggers, Paul W. Coresh, Josef Levey, Andrew S. TI Comparative Performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study Equations for Estimating GFR Levels Above 60 mL/min/1.73 m(2) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Estimating equations; glomerular filtration rate; performance ID GLOMERULAR-FILTRATION-RATE; RENIN-ANGIOTENSIN SYSTEM; TYPE-1 DIABETIC-PATIENTS; SERUM CYSTATIN-C; COCKCROFT-GAULT; PREDICTIVE PERFORMANCE; AFRICAN-AMERICANS; KIDNEY-DISEASE; DUAL BLOCKADE; CREATININE AB Background: The Modification of Diet in Renal Disease (MDRD) Study equation underestimates measured glomerular filtration rate (GFR) at levels >60 mL/min/1.73 m(2), with variable accuracy among subgroups; consequently, estimated GFR (eGFR) >= 60 mL/min/1.73 m(2) is not reported by clinical laboratories. Here, performance of a more accurate GFR-estimating equation, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, is reported by level of GFR and clinical characteristics. Study Design: Test of diagnostic accuracy. Setting & Participants: Pooled data set of 3,896 people from 16 studies with measured GFR (not used for the development of either equation). Subgroups were defined by eGFR, age, sex, race, diabetes, prior solid-organ transplant, and body mass index. Index Tests: eGFR from the CKD-EPI and MDRD Study equations and standardized serum creatinine. Reference Test: Measured GFR using urinary or plasma clearance of exogenous filtration markers. Results: Mean measured GFR was 68 +/- 36 (SD) mL/min/1.73 m(2). For eGFR <30 mL/min/1.73 m(2), both equations have similar bias (median difference compared with measured GFR). For eGFR of 30-59 mL/min/1.73 m(2), bias was decreased from 4.9 to 2.1 mL/min/1.73 m(2) (57% improvement). For eGFR of 60-89 mL/min/1.73 m(2), bias was decreased from 11.9 to 4.2 mL/min/1.73 m(2) (61% improvement). For eGFR of 90-119 mL/min/1.73 m(2), bias was decreased from 10.0 to 1.9 mL/min/1.73 m(2) (75% improvement). Similar or improved performance was noted for most subgroups with eGFR <90 mL/min/1.73 m(2), other than body mass index <20 kg/m(2), with greater variation noted for some subgroups with eGFR >= 90 mL/min/1.73 m(2). Limitations: Limited number of elderly people and racial and ethnic minorities with measured GFR. Conclusions: The CKD-EPI equation is more accurate than the MDRD Study equation overall and across most subgroups. In contrast to the MDRD Study equation, eGFR >= 60 mL/min/1.73 m(2) can be reported using the CKD-EPI equation. Am J Kidney Dis 56: 486-495. (C) 2010 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved. C1 [Stevens, Lesley A.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Beck, Gerald J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Froissart, Marc] Paris Descartes Univ, Georges Pompidou European Hosp, Paris, France. [Hamm, Lee L.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA. [Lewis, Julia B.] Vanderbilt Univ, Nashville, TN USA. [Mauer, Michael; Steffes, Michael W.] Univ Minnesota, Minneapolis, MN USA. [Navis, Gerjan J.] Univ Groningen Hosp, Groningen, Netherlands. [Eggers, Paul W.] NIDDK, Bethesda, MD USA. [Coresh, Josef] Johns Hopkins Univ, Baltimore, MD USA. RP Stevens, LA (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM lstevens1@tuftsmedicalcenter.org OI Froissart, Marc/0000-0002-4010-3173 FU [UO1 DK 053869]; [UO1 DK 067651]; [UO1 DK 35073]; [K23-DK081017] FX This study was supported by grants UO1 DK 053869, UO1 DK 067651, UO1 DK 35073, and K23-DK081017. NR 48 TC 246 Z9 260 U1 1 U2 24 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 2010 VL 56 IS 3 BP 486 EP 495 DI 10.1053/j.ajkd.2010.03.026 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 642IH UT WOS:000281203200011 PM 20557989 ER PT J AU Solomon, BD Pineda-Alvarez, DE Raam, MS Bous, SM Keaton, AA Velez, JI Cummings, DAT AF Solomon, Benjamin D. Pineda-Alvarez, Daniel E. Raam, Manu S. Bous, Sophia M. Keaton, Amelia A. Velez, Jorge I. Cummings, Derek A. T. TI Analysis of Component Findings in 79 Patients Diagnosed With VACTERL Association SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE VACTERL; VACTERL association; VATER; VATER association ID RESPIRATORY-CHAIN DEFICIENCY; VATER-ASSOCIATION; CONGENITAL-ANOMALIES; ESOPHAGEAL ATRESIA; SONIC HEDGEHOG; SPECTRUM; MUTATION; DELINEATION; DEFINITION; FISTULA AB VACTERL association is a relatively common condition, though the causes remain poorly understood. We present data on 79 patients diagnosed with VACTERL association and perform statistical analysis on a selected subset of 60 patients with at least three component features, and who, after review, did not meet criteria for a likely alternate diagnosis. Considered individually, no two component features are significantly associated, but several multivariate statistical techniques suggest novel patterns of the co-occurrence of component features, and latent class cluster analysis demonstrates the presence of five major subgroups of patients. These findings have implications for both our understanding of VACTERL association and for the approach to research involving this condition. Published 2010 (C) Wiley-Liss, Inc. C1 [Solomon, Benjamin D.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Raam, Manu S.] NIH, Res Scholars Program, Howard Hughes Med Inst, Chevy Chase, MD USA. [Cummings, Derek A. T.] Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HG999999] NR 28 TC 25 Z9 29 U1 0 U2 0 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 SEP PY 2010 VL 152A IS 9 BP 2236 EP 2244 DI 10.1002/ajmg.a.33572 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 645XF UT WOS:000281498800013 PM 20683998 ER PT J AU Gyamfi, C Mele, L Wapner, RJ Spong, CY Peaceman, A Sorokin, Y Dudley, DJ Johnson, F Leveno, KJ Caritis, SN Mercer, BM Thorp, JM O'Sullivan, MJ Ramin, SM Carpenter, M Rouse, DJ Miodovnik, M Sibai, B AF Gyamfi, Cynthia Mele, Lisa Wapner, Ronald J. Spong, Catherine Y. Peaceman, Alan Sorokin, Yoram Dudley, Donald J. Johnson, Francee Leveno, Kenneth J. Caritis, Steve N. Mercer, Brian M. Thorp, John M., Jr. O'Sullivan, Mary J. Ramin, Susan M. Carpenter, Marshall Rouse, Dwight J. Miodovnik, Menachem Sibai, Baha TI The effect of plurality and obesity on betamethasone concentrations in women at risk for preterm delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 26-31, 2009 CL San Diego, CA SP Soc Maternal Fetal Med DE betamethasone concentration; obesity; twins ID PHARMACOKINETICS; CORTICOSTEROIDS AB OBJECTIVE: Antenatal corticosteroids (ACS) decrease respiratory distress syndrome in singleton gestations. Twin data are less clear. Obesity and body mass index (BMI) also affect medication distribution volume. We evaluated whether maternal or neonatal cord betamethasone concentrations differed in twin gestations or obese patients. STUDY DESIGN: Participants receiving betamethasone in a randomized controlled trial of weekly ACS were identified. We analyzed maternal delivery and cord serum betamethasone concentrations comparing singletons with twins and obese (BMI >= 30 kg/m(2)) with nonobese women. RESULTS: Fifty-five maternal and 45 cord blood samples were available. Unadjusted median maternal serum concentrations appeared paradoxically higher in both twin gestations and the obese. However, after controlling for confounders, there were no differences in betamethasone concentrations in maternal serum or cord blood between singletons and twins (P = .61 vs P = .14) or nonobese and obese women (P = .67 vs .12). CONCLUSION: Maternal and umbilical cord blood serum betamethasone concentrations are not different in twin gestations or obese women. C1 [Gyamfi, Cynthia] Columbia Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, New York, NY 10032 USA. [Wapner, Ronald J.] Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Peaceman, Alan] Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Sorokin, Yoram] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Dudley, Donald J.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Johnson, Francee] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Caritis, Steve N.] Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA. [Mercer, Brian M.] Case Western Reserve Univ, Dept Obstet & Gynecol, Cleveland, OH 44106 USA. [Thorp, John M., Jr.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. [O'Sullivan, Mary J.] Univ Miami, Miller Sch Med, Dept Obstet & Gynecol, Miami, FL 33136 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Houston, TX USA. [Carpenter, Marshall] Brown Univ, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Rouse, Dwight J.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Miodovnik, Menachem] Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. [Sibai, Baha] Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. [Mele, Lisa] George Washington Univ, Ctr Biostat, Dept Obstet & Gynecol, Washington, DC USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Obstet & Gynecol, Bethesda, MD USA. RP Gyamfi, C (reprint author), Columbia Univ, Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, 622 W 168th St,PH 16, New York, NY 10032 USA. EM cg2231@columbia.edu OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850; Berghella, Vincenzo/0000-0003-2854-0239 FU NCATS NIH HHS [UL1 TR000005]; NCRR NIH HHS [M01 RR000080, M01-RR-000080]; NICHD NIH HHS [HD21410, HD21414, HD27860, HD27861, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, R24 HD050924, U01 HD036801, U10 HD021410, U10 HD027860, U10 HD027869, U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122, U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10 HD040485-13, U10 HD040500, U10 HD040512, U10 HD040544, U10 HD040545, U10 HD040560, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560] NR 12 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2010 VL 203 IS 3 AR 219.e1 DI 10.1016/j.ajog.2010.04.047 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647FH UT WOS:000281602700013 PM 20579955 ER PT J AU Kominiarek, MA VanVeldhuisen, P Hibbard, J Landy, H Haberman, S Learman, L Wilkins, I Bailit, J Branch, W Burkman, R Gonzalez-Quintero, VH Gregory, K Hatjis, C Hoffman, M Ramirez, M Reddy, UM Troendle, J Zhang, J AF Kominiarek, Michelle A. VanVeldhuisen, Paul Hibbard, Judith Landy, Helain Haberman, Shoshana Learman, Lee Wilkins, Isabelle Bailit, Jennifer Branch, Ware Burkman, Ronald Gonzalez-Quintero, Victor Hugo Gregory, Kimberly Hatjis, Christos Hoffman, Matthew Ramirez, Mildred Reddy, Uma M. Troendle, James Zhang, Jun CA Consortium Safe Labor TI The maternal body mass index: a strong association with delivery route SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med, Univ Texas Med Branch, Dept Obstet & Gynecol DE body mass index; cesarean delivery; obesity ID PREVIOUS CESAREAN DELIVERY; WEIGHT-GAIN; NULLIPAROUS WOMEN; OBESE WOMEN; RISK-FACTOR; LABOR; POPULATION; MORBIDITY; SECTION; IMPACT AB OBJECTIVE: We sought to assess body mass index (BMI) effect on cesarean risk during labor. STUDY DESIGN: The Consortium on Safe Labor collected electronic data from 228,668 deliveries. Women with singletons >= 37 weeks and known BMI at labor admission were analyzed in this cohort study. Regression analysis generated relative risks for cesarean stratifying for parity and prior cesarean while controlling for covariates. RESULTS: Of the 124,389 women, 14.0% had cesareans. Cesareans increased with increasing BMI for nulliparas and multiparas with and without a prior cesarean. Repeat cesareans were performed in > 50% of laboring women with a BMI > 40 kg/m(2). The risk for cesarean increased as BMI increased for all subgroups, P < .001. The risk for cesarean increased by 5%, 2%, and 5% for nulliparas and multiparas with and without a prior cesarean, respectively, for each 1-kg/m(2) increase in BMI. CONCLUSION: Admission BMI is significantly associated with delivery route in term laboring women. Parity and prior cesarean are other important predictors. C1 [Kominiarek, Michelle A.; Learman, Lee] Indiana Univ Clarian Hlth, Indianapolis, IN USA. [VanVeldhuisen, Paul] EMMES Corp, Rockville, MD USA. [Hibbard, Judith; Wilkins, Isabelle] Univ Illinois, Chicago, IL USA. [Landy, Helain] Georgetown Univ Hosp, Washington, DC 20007 USA. [Haberman, Shoshana] Maimonides Hosp, Brooklyn, NY 11219 USA. [Bailit, Jennifer] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. [Branch, Ware] Univ Utah, Salt Lake City, UT USA. [Branch, Ware] Intermt Healthcare, Salt Lake City, UT USA. [Burkman, Ronald] Tufts Univ, Baystate Med Ctr, Springfield, MA USA. [Gonzalez-Quintero, Victor Hugo] Univ Miami, Miami, FL USA. [Gregory, Kimberly] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Hatjis, Christos] Akron City Hosp, Summa Hlth Syst, Akron, OH USA. [Hoffman, Matthew] Christiana Care Hlth Syst, Newark, DE USA. [Ramirez, Mildred] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. [Troendle, James; Zhang, Jun] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Kominiarek, MA (reprint author), Indiana Univ Clarian Hlth, Indianapolis, IN USA. FU Intramural NIH HHS; NICHD NIH HHS [HHSN267200603425C]; PHS HHS [HHSN267200603425C] NR 28 TC 15 Z9 15 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2010 VL 203 IS 3 AR 264.e1 DI 10.1016/j.ajog.2010.06.024 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647FH UT WOS:000281602700033 PM 20673867 ER PT J AU Oh, KJ Lee, KA Sohn, YK Park, CW Hong, JS Romero, R Yoon, BH AF Oh, Kyung Joon Lee, Kyung A. Sohn, Yoo-Kyung Park, Chan-Wook Hong, Joon-Seok Romero, Roberto Yoon, Bo Hyun TI Intraamniotic infection with genital mycoplasmas exhibits a more intense inflammatory response than intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE chorioamnionitis; CRP; interleukin-6; IL-6; intraamniotic inflammation; mycoplasmas; preterm birth; ureaplasma ID POLYMERASE-CHAIN-REACTION; BLOOD-CELL COUNT; UREAPLASMA-UREALYTICUM; AMNIOTIC-FLUID; CLINICAL-SIGNIFICANCE; MICROBIAL INVASION; CAVITY; FETAL; LABOR; CULTURES AB OBJECTIVE: The objective of the study was to compare the intensity of inflammatory responses between intraamniotic infection with genital mycoplasmas and intraamniotic infection with other microorganisms. STUDY DESIGN: We examined the intensity of intraamniotic and maternal inflammatory responses in 99 patients with preterm premature rupture of membranes and a positive amniotic fluid (AF) culture. AF was obtained by transabdominal amniocentesis or at the time of cesarean delivery. Patients were divided according to the recovered microorganisms: (1) genital mycoplasmas (n = 62); (2) other microorganisms (n = 31); or (3) mixed infection (n = 6). RESULTS: The median AF white blood cell (WBC) count, maternal blood WBC count, and plasma C-reactive protein concentrations were significantly higher in patients with intraamniotic infection with genital mycoplasmas than in those with intraamniotic infection with other microorganisms (P < .05 for each). CONCLUSION: Intraamniotic and maternal inflammatory responses are more intense in intraamniotic infection with genital mycoplasmas than in intraamniotic infection with other microorganisms in patients with preterm premature rupture of membranes. C1 [Oh, Kyung Joon; Lee, Kyung A.; Sohn, Yoo-Kyung; Park, Chan-Wook; Hong, Joon-Seok; Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Romero, Roberto] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. RP Yoon, BH (reprint author), Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110744, South Korea. EM yoonbh@snu.ac.kr RI Yoon, Bo Hyun/H-6344-2011; Park, Chan-Wook/J-5498-2012 FU Seoul National University; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This work was supported in part by Grant 03-2006-011-0 from the Seoul National University Hospital Research Fund and in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 36 TC 13 Z9 13 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2010 VL 203 IS 3 AR 211.e1 DI 10.1016/j.ajog.2010.03.035 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 647FH UT WOS:000281602700009 PM 20678747 ER PT J AU Graham, BB Mentink-Kane, MM I-Haddad, HE Purnell, S Zhang, L Zaiman, A Redente, EF Riches, DWH Hassoun, PM Bandeira, A Champion, HC Butrous, G Wynn, TA Tuder, RM AF Graham, Brian B. Mentink-Kane, Margaret M. I-Haddad, Hazim E. Purnell, Shawn Zhang, Li Zaiman, An Redente, Elizabeth F. Riches, David W. H. Hassoun, Paul M. Bandeira, Angela Champion, Hunter C. Butrous, Ghazwan Wynn, Thomas A. Tuder, Rubin M. TI Schistosomiasis-Induced Experimental Pulmonary Hypertension Role of Interleukin-13 Signaling SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; ARTERIAL-HYPERTENSION; CHRONIC HYPOXIA; MICE LACKING; TISSUE FIBROSIS; IMMUNE-RESPONSE; PROTEIN-KINASE; RECEPTOR; INHIBITION; IL-13 AB The mechanisms underlying schistosomiasis-induced pulmonary hypertension (PH), one of the most common causes of PH worldwide, remain unclear. We sought to determine whether Schistosoma mansoni causes experimental PH associated with pulmonary vascular remodeling in an interleukin (IL)-13-dependent manner. IL-13R alpha 1 is the canonical IL-13 signaling receptor, whereas IL-13R alpha 2 is a competitive non-signaling decoy receptor. Wild-type, IL-13R alpha 1(-/-), and IL-13R alpha 2(-/-) C57BL/6J mice were percutaneously infected with S. mansoni cercariae, followed by i.v. injection of eggs. We assessed PH with right ventricular catheterization, histological evaluation of pulmonary vascular remodeling, and detection of IL-13 and transforming growth factor-beta signaling. Infected mice developed pulmonary pen-egg granulomas and arterial remodeling involving predominantly the vascular media. In addition, gain-of-function IL-13Ra2-/- mice had exacerbated vascular remodeling and PH. Mice with loss of IL-13R alpha 1 function did not develop PH and had reduced pulmonary vascular remodeling. Moreover, the expression of resistin-like molecule-a, a target of IL-13 signaling, was increased in infected wild-type and IL-13R alpha 2(-/-) but not IL-13R alpha 1(-/-) mice. Phosphorylated Smad2/3, a target of transforming growth factor-beta signaling, was increased in both infected mice and humans with the disease. Our data indicate that experimental schistosomiasis causes PH and potentially relics on up-regulated IL-13 signaling. (Am J Pathol 2014 177:1549-1561: DO!: 10.2353/ajpath.2010.100063) C1 [Graham, Brian B.] Univ Colorado Denver, Program Translat Lung Research, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. NIAID, Colorado Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Cardiol, Baltimore, MD USA. Johns Hopkins Univ, Dept Pulmanary & Crit Care Med, Baltimore, MD USA. [Purnell, Shawn] Univ Calif Davis, Dept Pathol & Lab Med, Davis, CA 95616 USA. [Redente, Elizabeth F.] Natl Jewish Hlth, Program Cell Biol, Denver, CO USA. [Bandeira, Angela] Univ Fed Pernambuco, Dept Cardiol, Recife, PE, Brazil. [Champion, Hunter C.] Univ Pittsburgh, Dept Cardiol, Pittsburgh, PA USA. [Butrous, Ghazwan] Univ Kent, Pulm Vasc Res Inst, Canterbury CT2 7NZ, Kent, England. RP Graham, BB (reprint author), Univ Colorado Denver, Program Translat Lung Research, Div Pulm Sci & Crit Care Med, Res 2,9th Floor,Mail Stop C-272,12700 E 19th Ave, Aurora, CO 80045 USA. RI Wynn, Thomas/C-2797-2011 FU Cardiovascular Medical Research Fund; University of Colorado; National Institute of Allergy and Infectious Diseases; National Institutes of Health [F32HL095274, NIH R01HL068628] FX Supported by Cardiovascular Medical Research Fund, the Translational Lung Research Program at the University of Colorado, the Parker B Francis Fellowship Program, the Intramural Research Program of National Institute of Allergy and Infectious Diseases, National Institutes of Health, and National Institutes of Health grants F32HL095274 and NIH R01HL068628 NR 54 TC 33 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2010 VL 177 IS 3 BP 1549 EP 1561 DI 10.2353/ajpath.2010.100063 PG 13 WC Pathology SC Pathology GA 648TR UT WOS:000281717700047 PM 20671265 ER PT J AU Sorokin, Y Romero, R Mele, L Wapner, RJ Iams, JD Dudley, DJ Spong, CY Peaceman, AM Leveno, KJ Harper, M Caritis, SN Miodovnik, M Mercer, BM Thorp, JM O'Sullivan, MJ Ramin, SM Carpenter, MW Rouse, DJ Sibai, B AF Sorokin, Yoram Romero, Roberto Mele, Lisa Wapner, Ronald J. Iams, Jay D. Dudley, Donald J. Spong, Catherine Y. Peaceman, Alan M. Leveno, Kenneth J. Harper, Margaret Caritis, Steve N. Miodovnik, Menachem Mercer, Brian M. Thorp, John M. O'Sullivan, Mary Jo Ramin, Susan M. Carpenter, Marshall W. Rouse, Dwight J. Sibai, Baha TI Maternal Serum Interleukin-6, C-Reactive Protein, and Matrix Metalloproteinase-9 Concentrations as Risk Factors for Preterm Birth < 32 Weeks and Adverse Neonatal Outcomes SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Maternal serum; cytokines; preterm birth; neonatal morbidity ID UMBILICAL-CORD PLASMA; BLOOD-CELL COUNT; AMNIOTIC-FLUID INTERLEUKIN-6; NECROSIS-FACTOR-ALPHA; WHITE-MATTER LESIONS; PREMATURE RUPTURE; INTRAVENTRICULAR HEMORRHAGE; PERIVENTRICULAR LEUKOMALACIA; INFLAMMATORY RESPONSE; CEREBRAL-PALSY AB Elevated concentrations of interleukin-6 (IL-6), C-reactive protein (CRP), and matrix metalloproteinase-9 (MMP-9) in fetal and neonatal compartments have been associated with an increased risk for preterm birth (PTB) and/or neonatal morbidity. The purpose of this study was to determine if the maternal serum concentration of IL-6, CRP, and MMP-9 in women at risk for PTB, who are not in labor and have intact membranes, are associated with an increased risk for PTB < 32 weeks and/or neonatal morbidity. Maternal serum samples collected from 475 patients enrolled in a multicenter randomized controlled trial of single versus weekly corticosteroids for women at increased risk for preterm delivery were assayed. Serum was collected at randomization (24 to 32 weeks' gestation). Maternal serum concentrations of IL-6, CRP, and MMP-9 were subsequently determined using enzyme-linked immunoassays. Multivariate logistic regression analysis was performed to explore the relationship between maternal serum concentrations of IL-6, CRP, and MMP-9 and PTB <32 weeks, respiratory distress syndrome (RDS), chronic lung disease (CLD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and any sepsis. Maternal serum concentrations of IL-6 and CRP, but not MMP-9, above the 90th percentile at the time of randomization were associated with PTB <32 weeks. In contrast, there was no significant relationship between RDS and NEC and the maternal serum concentration of IL-6, CRP, or MMP-9 (univariate analysis). The development of CLD was associated with a high (above 90th percentile) IL-6 and CRP in maternal serum, even after adjustment for gestational age (GA) at randomization and treatment group. However, when GA at delivery was added to the model, this finding was nonsignificant. Neonatal sepsis was more frequent in neonates born to mothers with a high maternal serum concentration of CRP (>90th percentile). However, there was no significant association after adjustment for GA at randomization and treatment group. Logistic regression analysis for each analyte indicated that high maternal serum concentrations of IL-6 and CRP, but not MMP-9, were associated with an increased risk of IVH (odds ratio [OR] 4.60, 95% confidence interval [CI] 1.86 to 10.68; OR 4.07, 95% CI 1.63 to 9.50) after adjusting for GA at randomization and treatment group. Most babies (25/30) had grade I IVH. When GA at delivery was included, elevated IL-6 remained significantly associated with IVH (OR 2.77, 95% CI 1.02 to 7.09). An elevated maternal serum concentration of IL-6 and CRP are risk factors for PTB <32 weeks and subsequent development of neonatal IVH. An elevated maternal serum IL-6 appears to confer additional risk for IVH even after adjusting for GA at delivery. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Detroit, MI USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT USA. RP Sorokin, Y (reprint author), Hutzel Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3990 John R,Mailbox 163, Detroit, MI 48201 USA. EM ysorokin@med.wayne.edu OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD21414, HD27869, HD27917, HD27905, HD27860, HD27861, HD27915, HD34122, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD36801]; National Center for Research Resources [M01-RR-000080] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD21414, HD27869, HD27917, HD27905, HD27860, HD27861, HD27915, HD34122, HD34116, HD34208, HD34136, HD40500, HD40485, HD40544, HD40545, HD40560, HD40512, HD40485, HD36801) and M01-RR-000080 from the National Center for Research Resources. NR 39 TC 53 Z9 60 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD SEP PY 2010 VL 27 IS 8 BP 631 EP 639 DI 10.1055/s-0030-1249366 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 637GE UT WOS:000280804100007 PM 20195952 ER PT J AU Laroche, G Giguere, PM Roth, BL Trejo, J Siderovski, DP AF Laroche, Genevieve Giguere, Patrick M. Roth, Bryan L. Trejo, JoAnn Siderovski, David P. TI RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE calcium flux; muscarinic acetylcholine receptor; protease-activated receptor-1; regulators of G protein signaling; short interfering RNA duplexes ID 3RD INTRACELLULAR LOOP; COUPLED-RECEPTORS; ALPHA-SUBUNITS; STRUCTURAL DIVERSITY; M3 RECEPTOR; COMPLEX; CELLS; BINDING; FAMILY; DOMAIN AB Laroche G, Giguere PM, Roth BL, Trejo J, Siderovski DP. RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling. Am J Physiol Cell Physiol 299: C654-C664, 2010. First published June 23, 2010; doi: 10.1152/ajpcell.00441.2009.-Regulator of G protein signaling (RGS) proteins are considered key modulators of G protein-coupled receptor (GPCR)-mediated signal transduction. These proteins act directly on G alpha subunits in vitro to increase their intrinsic rate of GTP hydrolysis; this activity is central to the prevailing view of RGS proteins as negative regulators of agonist-initiated GPCR signaling. However, the specificities of action of particular RGS proteins toward specific GPCRs in an integrated cellular context remain unclear. Here, we developed a medium-throughput assay to address this question in a wholly endogenous context using RNA interference. We performed medium-throughput calcium mobilization assays of agonist-stimulated muscarinic acetylcholine and protease-activated receptors in human embryonic kidney 293 (HEK293) cells transfected with individual members of a "pooled duplex" short interfering RNA library targeting all conventional human RGS transcripts. Only knockdown of RGS11 increased both carbachol-mediated calcium mobilization and inositol phosphate accumulation. Surprisingly, we found that knockdown of RGS8 and RGS9, but not other conventional RGS proteins, significantly decreased carbachol-mediated calcium mobilization, whereas only RGS8 knockdown decreased protease-activated receptor-1 (PAR-1)-mediated calcium mobilization. Loss of responsiveness toward carbachol and PAR-1 agonist peptide upon RGS8 knockdown appears due, at least in part, to a loss in respective receptor cell surface expression, although this is not the case for RGS9 knockdown. Our data suggest a cellular role for RGS8 in the stable surface expression of M3 muscarinic acetylcholine receptor and PAR-1, as well as a specific and opposing set of functions for RGS9 and RGS11 in modulating carbachol responsiveness similar to that seen in Caenorhabditis elegans. C1 [Laroche, Genevieve; Giguere, Patrick M.; Roth, Bryan L.; Siderovski, David P.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Laroche, Genevieve; Giguere, Patrick M.; Roth, Bryan L.; Siderovski, David P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Laroche, Genevieve; Giguere, Patrick M.; Roth, Bryan L.; Siderovski, David P.] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. [Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Chapel Hill, NC 27599 USA. [Trejo, JoAnn] Univ Calif San Diego, Dept Pharmacol, San Diego, CA 92103 USA. RP Siderovski, DP (reprint author), Univ N Carolina, Dept Pharmacol, 4073 Genet Med Bldg,120 Mason Farm Rd,Suite 4010, Chapel Hill, NC 27599 USA. EM dsiderov@med.unc.edu RI Roth, Bryan/F-3928-2010; OI Siderovski, David/0000-0002-0688-8210 FU National Institute of General Medical Sciences [R01 GM062338]; Heart & Stroke Foundation of Canada FX This study was supported by National Institute of General Medical Sciences Grant R01 GM062338 (to D. P. Siderovski), postdoctoral fellowships from the Heart & Stroke Foundation of Canada (to G. Laroche and P. M. Giguere), and infrastructure support from the NIMH Psychoactive Drug Screening Program (to B. L. Roth). NR 44 TC 9 Z9 9 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 2010 VL 299 IS 3 BP C654 EP C664 DI 10.1152/ajpcell.00441.2009 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 644OR UT WOS:000281389100014 PM 20573995 ER PT J AU Varu, VN Ahanchi, SS Hogg, ME Bhikhapurwala, HA Chen, A Popowich, DA Vavra, AK Martinez, J Jiang, Q Saavedra, JE Hrabie, JA Keefer, LK Kibbe, MR AF Varu, Vinit N. Ahanchi, Sadie S. Hogg, Melissa E. Bhikhapurwala, Hussein A. Chen, Amy Popowich, Daniel A. Vavra, Ashley K. Martinez, Janet Jiang, Qun Saavedra, Joseph E. Hrabie, Joseph A. Keefer, Larry K. Kibbe, Melina R. TI Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE proliferation; arterial injury; vascular smooth muscle cells ID SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; INTIMAL HYPERPLASIA; ARTERIAL INJURY; IN-VIVO; GUANOSINE-MONOPHOSPHATE; PERIVASCULAR DELIVERY; METABOLIC SYNDROME; GENE-TRANSFER; HIGH GLUCOSE AB Varu VN, Ahanchi SS, Hogg ME, Bhikhapurwala HA, Chen A, Popowich DA, Vavra AK, Martinez J, Jiang Q, Saavedra JE, Hrabie JA, Keefer LK, Kibbe MR. Insulin enhances the effect of nitric oxide at inhibiting neointimal hyperplasia in a rat model of type 1 diabetes. Am J Physiol Heart Circ Physiol 299: H772-H779, 2010. First published June 18, 2010; doi:10.1152/ajpheart.01234.2009.-Diabetes confers greater restenosis from neointimal hyperplasia following vascular interventions. While localized administration of nitric oxide (NO) is known to inhibit neointimal hyperplasia, the effect of NO in type 1 diabetes is unknown. Thus the aim of this study was to determine the efficacy of NO following arterial injury, with and without exogenous insulin administration. Vascular smooth muscle cells (VSMC) from lean Zucker (LZ) rats were exposed to the NO donor, DETA/NO, following treatment with different glucose and/or insulin concentrations. DETA/NO inhibited VSMC proliferation in a concentration-dependent manner to a greater extent in VSMC exposed to normal-glucose vs. high-glucose environments, and even more effectively in normal-glucose/high-insulin and high-glucose/high-insulin environments. G(0)/G(1) cell cycle arrest and cell death were not responsible for the enhanced efficacy of NO in these environments. Next, type 1 diabetes was induced in LZ rats with streptozotocin. The rat carotid artery injury model was performed. Type 1 diabetic rats experienced no significant reduction in neointimal hyperplasia following arterial injury and treatment with the NO donor PROLI/NO. However, daily administration of insulin to type 1 diabetic rats restored the efficacy of NO at inhibiting neointimal hyperplasia (60% reduction, P < 0.05). In conclusion, these data demonstrate that NO is ineffective at inhibiting neointimal hyperplasia in an uncontrolled rat model of type 1 diabetes; however, insulin administration restores the efficacy of NO at inhibiting neointimal hyperplasia. Thus insulin may play a role in regulating the downstream beneficial effects of NO in the vasculature. C1 [Varu, Vinit N.; Ahanchi, Sadie S.; Hogg, Melissa E.; Bhikhapurwala, Hussein A.; Chen, Amy; Popowich, Daniel A.; Vavra, Ashley K.; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. [Varu, Vinit N.; Ahanchi, Sadie S.; Hogg, Melissa E.; Bhikhapurwala, Hussein A.; Chen, Amy; Popowich, Daniel A.; Vavra, Ashley K.; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA. [Varu, Vinit N.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Ahanchi, Sadie S.] Univ Illinois Mt Sinai, Dept Surg, Chicago, IL USA. [Saavedra, Joseph E.; Hrabie, Joseph A.] SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. [Keefer, Larry K.] Natl Canc Inst Frederick, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD USA. [Kibbe, Melina R.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA. RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, 676 N St Clair St 650, Chicago, IL 60611 USA. EM mkibbe@nmh.org RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Institutes of Health (NIH) [1 K08HL084203, 5 R0 1 EB003806-02]; Department of Veterans Affairs; Veterans Affairs Merit Review Grant; American Vascular Association; American Medical Association Foundation; Eleanor Prince Wood Grant; University of Illinois; Hilda Rosenbloom and Eleanor Baldwin; National Cancer Institute, NIH [N01-CO-2008-00001]; NIH, National Cancer Institute, Center for Cancer Research FX This work was supported, in part, by funding from the National Institutes of Health (NIH; 1 K08HL084203 and 5 R0 1 EB003806-02), the Department of Veterans Affairs, Veterans Affairs Merit Review Grant, the American Vascular Association, the American Medical Association Foundation 2007 Seed Grant, the Eleanor Prince Wood Grant, the Eleanor B. Pillsbury Grant-University of Illinois, and by the generosity of Hilda Rosenbloom and Eleanor Baldwin. In addition, part of this research was supported with federal funds from the National Cancer Institute, NIH, under contract N01-CO-2008-00001 with SAIC-Frederick, Inc. and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 46 TC 14 Z9 14 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2010 VL 299 IS 3 BP H772 EP H779 DI 10.1152/ajpheart.01234.2009 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 646JZ UT WOS:000281537400023 PM 20562340 ER PT J AU Hwang, S Gunaratne, R Rinschen, MM Yu, MJ Pisitkun, T Hoffert, JD Fenton, RA Knepper, MA Chou, CL AF Hwang, Shelly Gunaratne, Ruwan Rinschen, Markus M. Yu, Ming-Jiun Pisitkun, Trairak Hoffert, Jason D. Fenton, Robert A. Knepper, Mark A. Chou, Chung-Lin TI Vasopressin increases phosphorylation of Ser84 and Ser486 in Slc14a2 collecting duct urea transporters SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE phospho-specific antibody; confocal microscopy; immunofluorescence immunocytochemistry; immuno-electron microscopy ID LIGHT-CHAIN KINASE; SMOOTH-MUSCLE MYOSIN; RAT-KIDNEY; UT-A; MEMBRANE ACCUMULATION; GENOMIC ORGANIZATION; PLASMA-MEMBRANES; UT-A1; AQUAPORIN-2; EXPRESSION AB Hwang S, Gunaratne R, Rinschen MM, Yu M-J, Pisitkun T, Hoffert JD, Fenton RA, Knepper MA, Chou C-L. Vasopressin increases phosphorylation of Ser84 and Ser486 in Slc14a2 collecting duct urea transporters. Am J Physiol Renal Physiol 299: F559-F567, 2010. First published June 24, 2010; doi:10.1152/ajprenal. 00617.2009.-Vasopressin-regulated urea transport in the renal inner medullary collecting duct (IMCD) is mediated by two urea channel proteins, UT-A1 and UT-A3, derived from the same gene (Slc14a2) by alternative splicing. The NH2-terminal 459 amino acids are the same in both proteins. To study UT-A1/3 phosphorylation, we made phosphospecific antibodies to UT-A sequences targeting phospho-serines at positions 84 and 486, sites identified previously by protein mass spectrometry. Both antibodies proved specific, recognizing only the phosphorylated forms of UT-A1 and -A3. Immunoblotting of rat IMCD suspensions or whole inner medullas showed that the V2R-selective vasopressin analog 1-deamino-8-D-arginine vasopressin (dDAVP) increases phosphorylation at Ser84 (in UT-A1 and UT-A3) and Ser486 (in UT-A1) by about eightfold. Time course studies in rat IMCD suspensions showed maximum phosphorylation within 1 min of dDAVP exposure, consistent with the time course of vasopressin-stimulated phosphorylation of the vasopressin-sensitive water channel aquaporin-2 at Ser256. Confocal immunofluorescence in Brattleboro rat medullary tissue showed labeling limited to the IMCD, which increased markedly in response to dDAVP. Immuno-electron microscopy studies showed that both phosphorylated forms were present mainly in intracellular compartments in the presence of vasopressin. These studies demonstrate regulated phosphorylation of both UT-A1 and UT-A3 in response to vasopressin in a manner consistent with coordinate regulation of UT-A and aquaporin-2 in the renal IMCD. The findings add to prior evidence for vasopressin-induced phosphorylation of UT-A1, providing evidence that UT-A3 may be regulated by phosphorylation as well. C1 [Hwang, Shelly; Gunaratne, Ruwan; Rinschen, Markus M.; Yu, Ming-Jiun; Pisitkun, Trairak; Hoffert, Jason D.; Knepper, Mark A.; Chou, Chung-Lin] NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. [Fenton, Robert A.] Aarhus Univ, Dept Anat, Water & Salt Res Ctr, Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,MSC 1603,Bldg 10,Rm 6N260, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271; YU, MING-JIUN/0000-0003-0393-4696 FU Intramural Budget of the NHLBI [Z01-HL-001285]; American Physiological Society; Biomedical Exchange Program, Hannover; Braun Foundation, Melsungen; Danish Medical Research Council; Lundbeck Foundation; Novo Nordisk Foundation FX This study was supported by the Intramural Budget of the NHLBI (Project Z01-HL-001285). S. Hwang was supported by an American Physiological Society Undergraduate Summer Research Fellowship. M. M. Rinschen was supported by the Biomedical Exchange Program, Hannover and the Braun Foundation, Melsungen. R. A. Fenton is funded by the Danish Medical Research Council, The Lundbeck Foundation, and the Novo Nordisk Foundation. NR 44 TC 15 Z9 15 U1 0 U2 7 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 SEP PY 2010 VL 299 IS 3 BP F559 EP F567 DI 10.1152/ajprenal.00617.2009 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 646KC UT WOS:000281537700010 PM 20576681 ER PT J AU Parry, M AF Parry, Manon TI Betty Friedan: Feminist Icon and Founder of the National Organization for Women SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Parry, Manon] Univ Maryland, College Pk, MD 20742 USA. RP Parry, M (reprint author), Natl Lib Med, Exhibit Program, 8600 Rockville Pike,Bldg 38,Room 1E-21, Bethesda, MD 20894 USA. EM parrym@mail.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 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 SEP PY 2010 VL 100 IS 9 BP 1584 EP 1585 DI 10.2105/AJPH.2009.187534 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638AY UT WOS:000280863100012 PM 20634444 ER PT J AU Garofalo, ME Fee, E AF Garofalo, Mary E. Fee, Elizabeth TI Florence Nightingale (1820-1910): Feminism and Hospital Reform SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Garofalo, Mary E.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA. [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Garofalo, ME (reprint author), NIAID, Lab Host Defenses, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 1 U2 3 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 SEP PY 2010 VL 100 IS 9 BP 1588 EP 1588 DI 10.2105/AJPH.2009.188722 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638AY UT WOS:000280863100014 PM 20671260 ER PT J AU Theerman, P AF Theerman, Paul TI Julia Lathrop and the Children's Bureau SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 38,Room 1E-21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM paul_theerman@nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2010 VL 100 IS 9 BP 1589 EP 1590 DI 10.2105/APH.2009.188185 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638AY UT WOS:000280863100015 PM 20634442 ER PT J AU Fee, E Garofalo, ME AF Fee, Elizabeth Garofalo, Mary E. TI Florence Nightingale and the Crimean War SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. [Garofalo, Mary E.] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 6 Z9 7 U1 0 U2 1 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 SEP PY 2010 VL 100 IS 9 BP 1591 EP 1591 DI 10.2105/AJPH.2009.188607 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 638AY UT WOS:000280863100016 PM 20671261 ER PT J AU Mani, H Climent, F Colomo, L Pittaluga, S Raffeld, M Jaffe, ES AF Mani, Haresh Climent, Fina Colomo, Lluis Pittaluga, Stefania Raffeld, Mark Jaffe, Elaine S. TI Gall Bladder and Extrahepatic Bile Duct Lymphomas: Clinicopathological Observations and Biological Implications SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoma; gallbladder; bile duct; hepatic duct; cystic duct; cholecystitis; cholelithiasis; extranodal; intestinal follicular lymphoma; in situ mantle cell lymphoma; HHV-8/KSHV; plasmablastic lymphoma; primary effusion lymphoma; lymphomatous polyposis ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PRIMARY EFFUSION LYMPHOMA; OF-THE-LITERATURE; FOLLICULAR LYMPHOMA; MALIGNANT-LYMPHOMA; T-CELL; OBSTRUCTIVE-JAUNDICE; SOLID LYMPHOMAS AB Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare. We present the clinicopathological features of 19 cases from our files; 14 patients had primary lymphoma (13 involving gall bladder and 1 involving common hepatic duct), while 5 had systemic lymphoma on further workup. Most patients presented with symptoms mimicking cholecystitis. The most common primary lymphoma types were diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. Two cases had features of lymphomatous polyposis, one a case of follicular lymphoma and the second a case of mantle cell lymphoma, with disease limited to the mantle zones, so-called in situ mantle cell lymphoma. Other rare lymphoma subtypes not described earlier in this site included the extracavitary variant of primary effusion lymphoma and plasmablastic lymphoma. Patients with diffuse large B-cell lymphoma and extranodal marginal zone lymphoma were older (mean age 75.8 y) than those with other subtypes (mean age 47 y) and more likely to have gallstones (60% vs. 12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16 primary extrahepatic bile duct lymphomas. When compared with primary gall bladder lymphomas, those involving the extrahepatic bile ducts present at a younger age (47 y vs. 63 y) usually with obstructive jaundice, and are less often associated with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts show a broad spectrum of disease types, but in many respects mirror the spectrum of primary lymphomas of the gastrointestinal tract. C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Climent, Fina] Hosp Univ Bellvitge, Barcelona, Spain. [Colomo, Lluis] Hosp Clin Barcelona, Barcelona, Spain. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res,NIH, 10 Ctr Dr,Room 2B-40,MSC-1500, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov RI Colomo, Luis/A-2259-2016; OI Colomo, Luis/0000-0001-5236-5085; Jaffe, Elaine/0000-0003-4632-0301 FU Center for Clinical Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the Center for Clinical Research, National Cancer Institute, National Institutes of Health. NR 74 TC 14 Z9 15 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 SEP PY 2010 VL 34 IS 9 BP 1277 EP 1286 DI 10.1097/PAS.0b013e3181e9bb8b PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 646XW UT WOS:000281579800006 PM 20679881 ER PT J AU Lehmann, T Dao, A Yaro, AS Adamou, A Kassogue, Y Diallo, M Sekou, T Coscaron-Arias, C AF Lehmann, Tovi Dao, Adama Yaro, Alpha Seydou Adamou, Abdoulaye Kassogue, Yaya Diallo, Moussa Sekou, Traore Coscaron-Arias, Cecilia TI Aestivation of the African Malaria Mosquito, Anopheles gambiae in the Sahel SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID EFFECTIVE POPULATION-SIZE; DRY SEASON; CULEX-PIPIENS; SUDAN SAVANNA; COMPLEX MOSQUITOS; WESTERN KENYA; SURVIVAL; SENEGAL; MALI; TRANSMISSION AB The African malaria mosquito. Anopheles gambiae, inhabits diverse environments including dry savannas, where surface waters required for larval development are absent for 4-8 months per year Under such conditions, An gambiae virtually disappears Whether populations survive the long dry season by aestivation (a dormant state promoting extended longevity during the summer) or are reestablished by migrants from distant locations where larval sites persist has remained an enigma for over 60 years Resolving this question is important, because fragile dry season populations may be more susceptible to control. Here, we show unequivocally that An gambiae aestivates based on a demographic study and a mark release recapture experiment spanning the period from the end of one wet season to the beginning of the next. During the dry season. An. gambiae was barely detectable in Sahehan villages of Mali. Five days after the first rain. before a new generation of adults could be produced. mosquito abundance surged 10-fold, implying that most mosquitoes were concealed locally until the rain Four clays after the first rain, a marked female An gambiae s.s was recaptured Initially captured, marked, and released at the end of the previous wet season, she has survived the 7-month-long dry season These results provide evidence that An. gambiae persists throughout the dry season by aestivation and open new questions for mosquito and parasite research Improved malaria control by targeting aestivating mosquitoes using existing or novel strategies may be possible. C1 [Lehmann, Tovi; Coscaron-Arias, Cecilia] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Dao, Adama; Yaro, Alpha Seydou; Adamou, Abdoulaye; Kassogue, Yaya; Diallo, Moussa; Sekou, Traore] Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali. RP Lehmann, T (reprint author), NIAID, Lab Malaria & Vector Res, NIH, MS 8132,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This study was supported by the Intramural Research Program in National Institutes of Health, National Institute of Allergy and Infectious Diseases NR 37 TC 44 Z9 44 U1 1 U2 12 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 2010 VL 83 IS 3 BP 601 EP 606 DI 10.4269/ajtmh.2010.09-0779 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 645SZ UT WOS:000281487800028 PM 20810827 ER PT J AU Concheiro, M Gray, TR Shakleya, DM Huestis, MA AF Concheiro, Marta Gray, Teresa R. Shakleya, Diaa M. Huestis, Marilyn A. TI High-throughput simultaneous analysis of buprenorphine, methadone, cocaine, opiates, nicotine, and metabolites in oral fluid by liquid chromatography tandem mass spectrometry SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Oral fluid; Liquid chromatography tandem mass spectrometry; Buprenorphine; Bioanalytical methods; Forensics/toxicology ID SOLID-PHASE EXTRACTION; MULTIPLE ILLICIT DRUGS; QUANTITATIVE-ANALYSIS; HUMAN URINE; VALIDATION; BENZOYLECGONINE; AMPHETAMINES; COTININE; SALIVA; ABUSE AB A method for simultaneous determination of buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine (BE), ecgonine methyl ester (EME), anhydroecgonine methyl ester (AEME), morphine, codeine, 6-acetylmorphine (6AM), heroin, 6-acetylcodeine (6AC), nicotine, cotinine, and trans-3'-hydroxycotinine (OH-cotinine) by liquid chromatography tandem mass spectrometry in oral fluid (OF) was developed and extensively validated. Acetonitrile (800 mu L) and OF (250 mu L) were added to a 96-well Isolute-PPT+protein precipitation plate. Reverse-phase separation was achieved in 16 min and quantification was performed by multiple reaction monitoring. The assay was linear from 0.5 or 1 to 500 mu g/L. Intraday, interday, and total imprecision were less than 13% (n = 20), analytical recovery was 92-114% (n = 20), extraction efficiencies were more than 77% (n = 5), and process efficiencies were more than 45% (n = 5). Although ion suppression was detected for EME, cocaine, morphine, 6AC, and heroin (less than 56%) and enhancement was detected for BE and nicotine (less than 316%), deuterated internal standards compensated for these effects. The method was sensitive (limit of detection 0.2-0.8 mu g/L) and specific (no interferences) except that 3-hydroxy-4-methoxyamphetamine interfered with AEME. No carryover was detected, and all analytes were stable for 24 h at 22 A degrees C, for 72 h at 4 A degrees C, and after three freeze-thaw cycles, except cocaine, 6AC, and heroin (22-97% loss). The method was applied to 41 OF specimens collected throughout pregnancy with a SalivetteA (R) OF collection device from an opioid-dependent BUP-maintained pregnant woman. BUP ranged from 0 to 7,400 mu g/L, NBUP from 0 to 71 mu g/L, methadone from 0 to 3 mu g/L, nicotine from 32 to 5,020 mu g/L, cotinine from 125 to 508 mu g/L, OH-cotinine from 11 to 51 mu g/L, cocaine from 0 to 419 mu g/L, BE from 0 to 351 mu g/L, EME from 0 to 286 mu g/L, AEME from 0 to 7 mu g/L, morphine from 0 to 22 mu g/L, codeine from 0 to 1 mu g/L, 6AM from 0 to 4 mu g/L, and heroin from 0 to 2 mu g/L. All specimens tested negative for EDDP and 6AC. This method permits a fast and simultaneous quantification of 16 drugs and metabolites in OF, with good selectivity and sensitivity. C1 [Concheiro, Marta; Gray, Teresa R.; Shakleya, Diaa M.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, BRC, Baltimore, MD 21224 USA. [Concheiro, Marta] Univ Santiago de Compostela, Fac Med, Serv Toxicol Forense, Dpto Anat Patol & Ciencias Forenses, Santiago De Compostela 15782, A Coruna, Spain. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, BRC, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institutes of Health, National Institute on Drug Abuse FX This research was supported by the National Institutes of Health, Intramural Research Program, National Institute on Drug Abuse. NR 23 TC 28 Z9 29 U1 3 U2 27 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2010 VL 398 IS 2 BP 915 EP 924 DI 10.1007/s00216-010-3903-5 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 650IL UT WOS:000281842400029 PM 20652688 ER PT J AU Ryschkewitsch, CF Jensen, PN Monaco, MC Major, EO AF Ryschkewitsch, Caroline F. Jensen, Peter N. Monaco, Maria Chiara Major, Eugene O. TI JC Virus Persistence Following Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis Patients Treated with Natalizumab SO ANNALS OF NEUROLOGY LA English DT Article ID BK VIRUS; ANTIBODY AB JC virus (JCV) DNA in the cerebrospinal fluid (CSF) provides the laboratory confirmatory diagnosis of progressive multifocal leukoencephalopathy (PML) in patients whose clinical symptoms and magnetic resonance imaging findings are consistent with PML. The Laboratory of Molecular Medicine and Neuroscience (LMMN), National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), made the confirmatory laboratory diagnosis in 35 multiple sclerosis (MS) patients treated with natalizumab. Thirteen patients had 3 or more CSF samples taken from weeks to months following PML diagnosis. Seven of the 13 patients demonstrated persistence of JCV DNA in the CSF even though all patients experienced immune reconstitution inflammatory syndrome (IRIS), 11 patients had plasma exchange, and 2 had immunoabsorption. Specific anti-JCV antibody was measured in plasma/sera samples from 25 of the 35 patients. Most of the samples showed moderate to high or rising antibody levels from the time of PML diagnosis. However, plasma from 1 patient at or near the time of PML diagnosis had a titer considered seronegative and 2 other plasma samples from patients had titers considered at baseline for seropositivity. In several PML cases, viral persistence and neurological deficits have continued for several years, indicating that once initiated, JCV infection may not entirely clear, even with IRIS. ANN NEUROL 2010;68:384-391 C1 [Ryschkewitsch, Caroline F.; Jensen, Peter N.; Monaco, Maria Chiara; Major, Eugene O.] NINDS, LMMN, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINDS, LMMN, NIH, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov FU Division of Intramural Research, NINDS FX We thank all Laboratory of Molecular Medicine and Neuroscience (LMMN) members; K. Johnson, PhD, Senior Statistician, National Institute of Neurological Disorders and Stroke (NINDS) for data analysis in Fig 2; the staff at the Centers that provided the samples; and the cooperation of Biogen/Idec in their acquisition. LMMN, NINDS, receives support from the Division of Intramural Research, NINDS. There is no cost for the assays nor does the LMMN receive any form of compensation. All reports on sample tests go directly to the Centers and physicians who send the samples. NR 15 TC 54 Z9 54 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 2010 VL 68 IS 3 BP 384 EP 391 DI 10.1002/ana.22137 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 644ZX UT WOS:000281421800018 PM 20818792 ER PT J AU Cobb, BL Fei, Y Jonsson, R Bolstad, AI Brun, JG Rischmueller, M Lester, SE Witte, T Illei, G Brennan, M Bowman, S Moser, KL Harley, JB Sawalha, AH AF Cobb, Beth L. Fei, Yiping Jonsson, Roland Bolstad, Anne Isine Brun, Johan G. Rischmueller, Maureen Lester, Susan E. Witte, Torsten Illei, Gabor Brennan, Michael Bowman, Simon Moser, Kathy L. Harley, John B. Sawalha, Amr H. TI Genetic association between methyl-CpG binding protein 2 (MECP2) and primary Sjogren's syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; OVEREXPRESSION; EXPRESSION; VARIANTS C1 [Cobb, Beth L.; Fei, Yiping; Moser, Kathy L.; Harley, John B.; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. [Fei, Yiping; Harley, John B.; Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Jonsson, Roland; Bolstad, Anne Isine] Univ Bergen, Gade Inst, Broegelmann Res Lab, Bergen, Norway. [Bolstad, Anne Isine] Univ Bergen, Dept Clin Dent, Bergen, Norway. [Brun, Johan G.] Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway. [Brun, Johan G.] Univ Bergen, Rheumatol Sect, Bergen, Norway. [Rischmueller, Maureen] Queen Elizabeth Hosp, Dept Rheumatol, Adelaide, SA, Australia. [Lester, Susan E.] Hanson Inst, Arthritis Res Lab, Adelaide, SA, Australia. [Witte, Torsten] Hannover Med Sch, Clin Immunol & Rheumatol, D-3000 Hannover, Germany. [Illei, Gabor] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Gene Therapy & Therapeut Branch, Natl Inst Hlth, Bethesda, MD USA. [Brennan, Michael] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA. [Bowman, Simon] Univ Hosp Birmingham NHS Fdn Trust, Dept Rheumatol, Birmingham, W Midlands, England. [Harley, John B.; Sawalha, Amr H.] US Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu RI Witte, Torsten/B-5783-2016 FU Intramural NIH HHS; NCRR NIH HHS [P20 RR015577, P20 RR020143, P20 RR020143-06, P20 RR020143-07, P20-RR015577, P20-RR020143]; NIAID NIH HHS [R03 AI076729, R03 AI076729-01, R03 AI076729-02, R03AI076729, U19 AI082714]; NIAMS NIH HHS [P30 AR053483, P30-AR053483]; NIDCR NIH HHS [DE015223, R01 DE015223, R01 DE015223-05] NR 10 TC 15 Z9 16 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 2010 VL 69 IS 9 BP 1731 EP 1732 DI 10.1136/ard.2009.122903 PG 2 WC Rheumatology SC Rheumatology GA 636XB UT WOS:000280776700029 PM 20215141 ER PT J AU Mo, LJ Zhang, J Shi, JD Xuan, QA Yang, XL Qin, M Lee, C Klocker, H Li, QQ Mo, ZN AF Mo, Linjian Zhang, Ju Shi, Jiandang Xuan, Qiang Yang, Xiaoli Qin, Min Lee, Chung Klocker, Helmut Li, Qingdi Quentin Mo, Zengnan TI Human Kallikrein 7 Induces Epithelial-Mesenchymal Transition-like Changes in Prostate Carcinoma Cells: A Role in Prostate Cancer Invasion and Progression SO ANTICANCER RESEARCH LA English DT Article DE Human tissue kallikrein 7; morphological change; vimentin; prostate cancer; invasion; metastasis ID CORNEUM CHYMOTRYPTIC ENZYME; E-CADHERIN; STRATUM-CORNEUM; TGF-BETA; PROTEINASE; ACTIVATION; EXPRESSION; RECEPTORS; GROWTH; ASSAY AB Human tissue kallikrein 7 (hK7), a chymotrypsin-like secreted serine protease, catalyzes the degradation of intercellular adhesive structures in the cornified layer of the skin, leading to desquamation. Thus, hK7 is implicated in cancer invasion and metastasis. Although hK7 is highly expressed in prostate tissues, its biological role in prostate cancer progression is poorly understood. In the current study, we established an hK7-expressing cell model for prostate tumors by stably transfecting prostate carcinoma 22RV1 and DU145 cells with an expression vector encoding hK7. We found that there were no obvious differences in cell proliferation between cells overexpressing hK7 and cells transfected with empty vector (p>0.05). Intriguingly, a Matrigel invasion assay revealed that hK7 remarkably increased the migration and invasion of prostate cancer cells (p<0.01). Furthermore, hK7 induced epithelial mesenchymal transition-like changes in prostate carcinoma cells, as evidenced by scattered cellular growth, mesenchyma-like morphology, and up-regulated expression of vimentin, a mesenchymal marker. These novel findings suggest that hK7 plays an important role in mediating prostate cancer progression and that hK7 promotes invasion and metastasis, at least in part, through inducing the epithelial mesenchymal transition of prostatic carcinoma cells. C1 [Mo, Linjian; Xuan, Qiang; Yang, Xiaoli; Qin, Min; Mo, Zengnan] Guangxi Med Univ, Univ Hosp 1, Inst Urol, Nanning 530021, Peoples R China. [Zhang, Ju; Shi, Jiandang] Nankai Univ, Inst Mol Biol, Tianjin 300071, Peoples R China. [Lee, Chung] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Klocker, Helmut] Innsbruck Med Univ, Dept Urol, A-6010 Innsbruck, Austria. [Li, Qingdi Quentin] NIH, Bethesda, MD 20892 USA. RP Mo, ZN (reprint author), Guangxi Med Univ, Univ Hosp 1, Inst Urol, Nanning 530021, Peoples R China. EM liquenti@mail.nih.gov; mozengnan@gmail.com FU National Natural Science Foundation of China [30260110/C03030305]; First University Hospital of Guangxi Medical University FX This project was carried out at the Institute of Urology, First University Hospital of Guangxi Medical University and the Institute for Molecular Biology, Nankai University. This work was supported by grants from the National Natural Science Foundation of China (No. 30260110/C03030305) and the First University Hospital of Guangxi Medical University. NR 19 TC 16 Z9 16 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP PY 2010 VL 30 IS 9 BP 3413 EP 3420 PG 8 WC Oncology SC Oncology GA 665BI UT WOS:000283009400026 PM 20944116 ER PT J AU Chung, SM Wendeler, M Rausch, JW Beilhartz, G Gotte, M O'Keefe, BR Bermingham, A Beutler, JA Liu, SX Zhuang, XW Le Grice, SFJ AF Chung, Suhman Wendeler, Michaela Rausch, Jason W. Beilhartz, Greg Gotte, Matthias O'Keefe, Barry R. Bermingham, Alun Beutler, John A. Liu, Shixin Zhuang, Xiaowei Le Grice, Stuart F. J. TI Structure-Activity Analysis of Vinylogous Urea Inhibitors of Human Immunodeficiency Virus-Encoded Ribonuclease H SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; RNASE-H; SIGNIFICANT DISCREPANCIES; CALORIMETRIC ENTHALPIES; THUMB SUBDOMAIN; DNA-POLYMERASE; VANT-HOFF; TYPE-1; ACID; DERIVATIVES AB Vinylogous ureas 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b] thiophene-3-carboxamide and N-[3-(aminocarbonyl)- 4,5-dimethyl-2-thienyl]-2-furancarboxamide (compounds 1 and 2, respectively) were recently identified to be modestly potent inhibitors of the RNase H activity of HIV-1 and HIV-2 reverse transcriptase (RT). Both compounds shared a 3-CONH(2)-substituted thiophene ring but were otherwise structurally unrelated, which prevented a precise definition of the pharmacophore. We have therefore examined a larger series of vinylogous ureas carrying amide, amine, and cycloalkane modifications of the thiophene ring of compound 1. While cycloheptane-and cyclohexane-substituted derivatives retained potency, cyclopentane and cyclooctane substitutions eliminated activity. In the presence of a cycloheptane ring, modifying the 2-NH(2) or 3-CONH(2) functions decreased the potency. With respect to compound 2, vinylogous ureas whose dimethylthiophene ring contained modifications of the 2-NH(2) and 3-CONH(2) functions were investigated. 2-NH(2)-modified analogs displayed potency equivalent to or enhanced over that of compound 2, the most active of which, compound 16, reflected intramolecular cyclization of the 2-NH(2) and 3-CONH(2) groups. Molecular modeling was used to define an inhibitor binding site in the p51 thumb subdomain, suggesting that an interaction with the catalytically conserved His539 of the p66 RNase H domain could underlie inhibition of RNase H activity. Collectively, our data indicate that multiple functional groups of vinylogous ureas contribute to their potencies as RNase H inhibitors. Finally, single-molecule spectroscopy indicates that vinylogous ureas have the property of altering the reverse transcriptase orientation on a model RNA-DNA hybrid mimicking initiation plus-strand DNA synthesis. C1 [Chung, Suhman; Wendeler, Michaela; Rausch, Jason W.; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Beilhartz, Greg; Gotte, Matthias] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [O'Keefe, Barry R.; Bermingham, Alun; Beutler, John A.] NCI, Mol Targets Program, Frederick, MD 21702 USA. [Liu, Shixin; Zhuang, Xiaowei] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Zhuang, Xiaowei] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA. [Zhuang, Xiaowei] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, HIV Drug Resistance Program, Bldg 525,Room 312, Frederick, MD 21702 USA. EM legrices@mail.nih.gov RI Liu, Shixin/A-4560-2012; Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 FU National Cancer Institute, National Institutes of Health; Canadian Foundation for AIDS Research; NIH [GM 068518]; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX S.F.J.L.G. is supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health; M. G. is supported by a grant from the Canadian Foundation for AIDS Research; and X.Z. is supported by NIH grant GM 068518. X.Z. is a Howard Hughes Medical Institute investigator. This project was supported in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. NR 35 TC 29 Z9 30 U1 0 U2 9 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 SEP PY 2010 VL 54 IS 9 BP 3913 EP 3921 DI 10.1128/AAC.00434-10 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 639WC UT WOS:000281005900053 PM 20547794 ER PT J AU Shi, ZH Nie, GJ Duan, XL Rouault, T Wu, WS Ning, B Zhang, N Chang, YZ Zhao, BL AF Shi, Zhen-Hua Nie, Guangjun Duan, Xiang-Lin Rouault, Tracey Wu, Wen-Shuang Ning, Bo Zhang, Nan Chang, Yan-Zhong Zhao, Bao-Lu TI Neuroprotective Mechanism of Mitochondrial Ferritin on 6-Hydroxydopamine-Induced Dopaminergic Cell Damage: Implication for Neuroprotection in Parkinson's Disease SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID GREEN TEA POLYPHENOLS; ENDOPLASMIC-RETICULUM STRESS; NEUROBLASTOMA SH-SY5Y CELLS; CENTRAL-NERVOUS-SYSTEM; LABILE IRON POOL; ROS-NO PATHWAY; OXIDATIVE STRESS; COMPLEX-I; NEURODEGENERATIVE DISORDERS; INDUCED NEUROTOXICITY AB Neuronal iron homeostasis disruption and oxidative stress are closely related to the pathogenesis of Parkinson's disease (PD). Adult iron-regulatory protein 2 knockout (Ireb2(-/-)) mice develop iron accumulation in white matter tracts and nuclei in different brain area and display severe neurodegeneration in Purkinje cells of the cerebrum. Mitochondrial ferritin (MtFt), a newly discovered ferritin, specifically expresses in high energy-consuming cells, including neurons of brain and spinal cord. Interestingly, the decreased expression of MtFt in cerebrum, but not in striatum, matches the differential neurodegeneration pattern in these Ireb2(-/-) mice. To explore its effect on neurodegeneration, the effects of MtFt expression on 6-hydrodopamine (6-OHDA)-induced neuronal damage was examined. The overexpression of MtFt led to a cytosolic iron deficiency in the neuronal cells and significantly prevented the alteration of iron redistribution induced by 6-OHDA. Importantly, MtFt strongly inhibited mitochondrial damage, decreased production of the reactive oxygen species and lipid peroxidation, and dramatically rescued apoptosis by regulating Bcl-2, Bax and caspase-3 pathways. In conclusion, this study demonstrates that MtFt plays an important role in preventing neuronal damage in an 6-OHDA-induced parkinsonian phenotype by maintaining iron homeostasis. Regulation of MtFt expression in neuronal cells may provide a new neuroprotective strategy for PD. Antioxid. Redox Signal. 13, 783-796. C1 [Shi, Zhen-Hua; Duan, Xiang-Lin; Wu, Wen-Shuang; Zhang, Nan; Chang, Yan-Zhong] Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Hebei, Peoples R China. [Shi, Zhen-Hua; Zhao, Bao-Lu] Acad Sinica, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100080, Peoples R China. [Nie, Guangjun; Ning, Bo] Natl Ctr Nanosci & Technol China, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing, Peoples R China. [Rouault, Tracey] NICHHD, Program Mol Med, NIH, Bethesda, MD 20892 USA. RP Chang, YZ (reprint author), Hebei Normal Univ, Coll Life Sci, Lab Mol Iron Metab, Shijiazhuang 050016, Hebei, Peoples R China. EM frankyzchang@yahoo.com.hk; zhaobl@sun5.ibp.ac.cn RI Nie, Guangjun/A-9954-2011; OI nie, guangjun/0000-0001-5040-9793 FU National Natural Sciences Foundation of China [30871260, 10979011, 30900278]; Natural Science Foundation of Hebei Province [C2007000251]; High Technology Research and Development Project of China [2009AA03Z335]; State Key Development Program for Basic Research of China [2010CB933600]; Chinese Academy of Sciences FX This work was supported by grants from the National Natural Sciences Foundation of China (30871260; 10979011; 30900278), Natural Science Foundation of Hebei Province (C2007000251), High Technology Research and Development Project of China (2009AA03Z335) and the State Key Development Program for Basic Research of China (2010CB933600). GN gratefully acknowledges the support of Chinese Academy of Sciences, Hundred Talents Program. We also thank Dr. Manik Ghosh and Hayden Ollivierre-Wilson for preparation of the IRP-knockout mouse. Anti-MtFt antibody was a generous gift from Professor Sonia Levi and Dr. Paolo Santambrogio, Milan. NR 53 TC 30 Z9 34 U1 0 U2 19 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 SEP PY 2010 VL 13 IS 6 BP 783 EP 796 DI 10.1089/ars.2009.3018 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 628KY UT WOS:000280119800006 PM 20121342 ER PT J AU Sastalla, I Rosovitz, MJ Leppla, SH AF Sastalla, Inka Rosovitz, M. J. Leppla, Stephen H. TI Accidental Selection and Intentional Restoration of Sporulation-Deficient Bacillus anthracis Mutants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ILLEGITIMATE RECOMBINATION; SUBTILIS; GENE; BACTERIA; TRANSCRIPTION; EXPRESSION; PROMOTERS; REGULATOR; PROTEINS; MUTATION AB We demonstrate the frequent accidental enrichment of spontaneous sporulation-deficient mutants of Bacillus anthracis on solid medium and identify contributing factors. Mutations in spo0A, encoding the master regulator of sporulation initiation, were found in 38 of 53 mutants. Transductions using bacteriophage CP51 propagated on sporogenic bacteria allowed for the restoration of sporulation phenotypes. C1 [Sastalla, Inka; Rosovitz, M. J.; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Lab Bacterial Dis, NIH, Bldg 33, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU NIH, National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. NR 28 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2010 VL 76 IS 18 BP 6318 EP 6321 DI 10.1128/AEM.00950-10 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 648EV UT WOS:000281674100040 PM 20639373 ER PT J AU Zhang, HF Lountos, GT Ching, CB Jiang, RR AF Zhang, Hongfang Lountos, George T. Ching, Chi Bun Jiang, Rongrong TI Engineering of glycerol dehydrogenase for improved activity towards 1, 3-butanediol SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Glycerol dehydrogenase; Protein engineering; 1, 3-butanediol; 4-hydroxy-2-butanone ID SECONDARY ALCOHOL-DEHYDROGENASE; ESCHERICHIA-COLI; 4-HYDROXY-2-BUTANONE; OXIDATION; PURIFICATION; EXPRESSION; POLYMERS; CATALYST; CLONING AB The objective of this study was to use protein engineering techniques to enhance the catalytic activity of glycerol dehydrogenase (GlyDH) on racemic 1, 3-butanediol (1, 3-BDO) for the bioproduction of the important pharmaceutical intermediate 4-hydroxy-2-butanone. Three GlyDH genes (gldA) from Escherichia coli K-12, Salmonella enterica, and Klebsiella pneumoniae MGH78578 were shuffled to generate a random mutagenesis library. The nitroblue tetrazolium/phenazine methosulfate high throughput screening protocol was used to select four chimeric enzymes with up to a 2.6-fold improved activity towards 1, 3-BDO. A rational design method was also employed to further improve the enzyme activity after DNA shuffling. Based on the homology model of GlyDH (Escherichia coli), Asp121 was predicted to influence 1, 3-BDO binding and replaced with Ala by site-directed mutagenesis. Combination of the mutations from both DNA shuffling and rational design produced the best mutant with a V(max) value of 126.6 U/mg, a 26-fold activity increase compared with that of the wild type GlyDH from E. coli. C1 [Zhang, Hongfang; Ching, Chi Bun; Jiang, Rongrong] Nanyang Technol Univ, Sch Chem & Biomed Engn, Singapore 637459, Singapore. [Lountos, George T.] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Jiang, RR (reprint author), Nanyang Technol Univ, Sch Chem & Biomed Engn, 62 Nanyang Dr, Singapore 637459, Singapore. EM rrjiang@ntu.edu.sg RI Jiang , Rongrong/G-6217-2010; Lountos, George/B-3983-2015 NR 28 TC 19 Z9 21 U1 2 U2 30 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD SEP PY 2010 VL 88 IS 1 BP 117 EP 124 DI 10.1007/s00253-010-2735-8 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 638RZ UT WOS:000280914900013 PM 20585771 ER PT J AU Pati, HN Das, U Sakagami, H Kawase, M Chu, Q Wang, QT Stables, JP Dimmock, JR AF Pati, Hari N. Das, Umashankar Sakagami, Hiroshi Kawase, Masame Chu, Qing Wang, Qintao Stables, James P. Dimmock, Jonathan R. TI 1,3-Diaryl-2-propenones and 2-Benzylidene-1,3-indandiones: A Quest for Compounds Displaying Greater Toxicity to Neoplasms than Normal Cells SO ARCHIV DER PHARMAZIE LA English DT Article DE Apoptosis; Cytotoxicity; Neurotoxicity; Structure-activity relationships; Unsaturated ketones ID MULTIDRUG-RESISTANCE REVERSAL; ANTIMITOTIC CHALCONES; 2-ARYLIDENEBENZOCYCLOALKANONES; PHARMACOPHORE; CYTOTOXICITY; ANTICANCER; DRUGS AB A series of 1,3-diaryl-2-propenones 2a-j and analogous 2-benzylidene-1,3-indandiones 3a-j were evaluated against various neoplasms and normal cells. In general, greater cytotoxic potencies and selective toxicity to human malignant cells were observed by the compounds in series 2 rather than 3. In particular, 2i emerged as a lead molecule having an average CC(50) figure of 8.6 mu M and a selective index value of 18. Various physicochemical features of 2a-j were correlated with the cytotoxic potencies to neoplastic cell lines which provide guidelines for expansion of this series of compounds. The enone 2i induced internucleosomal DNA fragmentation and activated caspase-3 in HL-60 cells suggesting that one of the ways in which the cytotoxicity of the compounds in series 2 is mediated towards some of the cell lines used in this study is by apoptosis. Neurotoxicity in mice was generally lower in series 2 than 3a-j. C1 [Pati, Hari N.; Das, Umashankar; Dimmock, Jonathan R.] Univ Saskatchewan, Drug Design & Discovery Res Grp, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. [Sakagami, Hiroshi; Chu, Qing] Meikai Univ Sch Dent, Dept Diagnost & Therapeut Sci, Saitama, Japan. [Kawase, Masame] Matsuyama Univ, Fac Pharmaceut Sci, Matsuyama, Ehime, Japan. [Chu, Qing; Wang, Qintao] Fourth Mil Med Univ, Dept Periodontol & Oral Med, Sch Stomatol, Xian 710032, Peoples R China. [Stables, James P.] NINDS, Rockville, MD USA. RP Dimmock, JR (reprint author), Univ Saskatchewan, Drug Design & Discovery Res Grp, Coll Pharm & Nutr, Saskatoon, SK S7N 5C9, Canada. EM jr.dimmock@usask.ca FU Canadian Institutes of Health Research; Ministry of Education, Science, Sports and Culture of Japan [19592156] FX The authors thank the Canadian Institutes of Health Research for a grant to J. R. Dimmock and the Ministry of Education, Science, Sports and Culture of Japan for a Grant-in-Aid (No. 19592156) to H. Sakagami. The National Institute of Neurological Disorders and Stroke, USA kindly undertook the in-vivo experimentation with mice and rats. Erin Watson is thanked for assisting with some of the literature retrieval. NR 28 TC 3 Z9 3 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0365-6233 J9 ARCH PHARM JI Arch. Pharm. PD SEP PY 2010 VL 343 IS 9 BP 535 EP 541 DI 10.1002/ardp.200900308 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 662FS UT WOS:000282793400006 PM 20806272 ER PT J AU Bigos, KL Mattay, VS Callicott, JH Straub, RE Vakkalanka, R Kolachana, B Hyde, TM Lipska, BK Kleinman, JE Weinberger, DR AF Bigos, Kristin L. Mattay, Venkata S. Callicott, Joseph H. Straub, Richard E. Vakkalanka, Radhakrishna Kolachana, Bhaskar Hyde, Thomas M. Lipska, Barbara K. Kleinman, Joel E. Weinberger, Daniel R. TI Genetic Variation in CACNA1C Affects Brain Circuitries Related to Mental Illness SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GENOME-WIDE ASSOCIATION; BIPOLAR-DISORDER; NEURAL MECHANISMS; AMYGDALA ACTIVITY; SCHIZOPHRENIA; RISK; MEMORY; VARIANTS; SIBLINGS; AUTISM AB Context: The CACNA1C gene (alpha-1C subunit of the L-type voltage-gated calcium channel) has been identified as a risk gene for bipolar disorder and schizophrenia, but the mechanism of association has not been explored. Objective: To identify the neural system mechanism that explains the genetic association between the CACNA1C gene and psychiatric illness using neuroimaging and human brain expression. Design: We used blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure brain activation in circuitries related to bipolar disorder and schizophrenia by comparing CACNA1C genotype groups among healthy subjects. We tested the effect of genotype on messenger RNA (mRNA) levels of CACNA1C in postmortem human brain. A case-control analysis was used to determine the association of CACNA1C genotype with schizophrenia. Setting: National Institutes of Health Clinical Center. Patients: Healthy men and women of white race/ethnicity participated in the fMRI study. Postmortem samples from normal human brains were used for the brain expression study. Patients with schizophrenia and healthy subjects were used in the case-control analysis. Main Outcome Measures: BOLD fMRI, mRNA levels in postmortem brain samples, and genetic association with schizophrenia. Results: The risk-associated single-nucleotide polymorphism (SNP rs1006737) in CACNA1C predicted increased hippocampal activity during emotional processing (P=.001 uncorrected, P((false recovery rate [FDR]))=.05, z=3.20) and increased prefrontal activity during executive cognition (P=2.8e-05 uncorrected, P(FDR)=.01, z=4.03). The risk-associated SNP also predicted increased expression of CACNA1C mRNA in human brain (P=.002). CACNA1C was associated with schizophrenia in our case-control sample (odds ratio, 1.77; P=.03). Conclusions: The risk-associated SNP in CACNA1C maps to circuitries implicated in genetic risk for bipolar disorder and schizophrenia. Its effects in human brain expression implicate a molecular and neural system mechanism for the clinical genetic association. C1 [Bigos, Kristin L.; Mattay, Venkata S.; Straub, Richard E.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Mattay, Venkata S.; Callicott, Joseph H.; Straub, Richard E.; Vakkalanka, Radhakrishna; Kolachana, Bhaskar; Hyde, Thomas M.; Lipska, Barbara K.; Kleinman, Joel E.] NIMH, Clin Brain Disorders Branch, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Div Intramural Res Program, NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Lipska, Barbara/E-4569-2017; OI Callicott, Joseph/0000-0003-1298-3334 FU National Institute of Mental Health, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 41 TC 128 Z9 133 U1 1 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2010 VL 67 IS 9 BP 939 EP 945 PG 7 WC Psychiatry SC Psychiatry GA 649JD UT WOS:000281764000009 PM 20819988 ER PT J AU Khoury, SJ Healy, BC Kivisakk, P Viglietta, V Egorova, S Guttmann, CRG Wedgwood, JF Hafler, DA Weiner, HL Buckle, G Cook, S Reddy, S AF Khoury, Samia J. Healy, Brian C. Kivisakk, Pia Viglietta, Vissia Egorova, Svetlana Guttmann, Charles R. G. Wedgwood, Josiah F. Hafler, David A. Weiner, Howard L. Buckle, Guy Cook, Sandra Reddy, Susheel TI A Randomized Controlled Double-Masked Trial of Albuterol Add-on Therapy in Patients With Multiple Sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; GLATIRAMER ACETATE; T-CELLS; NEUROTROPHIC FACTOR; LONGITUDINAL DATA; BRAIN; INTERLEUKIN-12; DISEASE; MECHANISMS; RESPONSES AB Background:Interleukin 12 (IL-12), a cytokine that promotes generation of helper T cells subtype 1, is increased in multiple sclerosis. Albuterol sulfate, a beta 2-adrenergic agonist, reduces IL-12 expression, so we tested the effect of albuterol as an add-on treatment to glatiramer acetate therapy. Objectives: To investigate the clinical and immunologic effects of albuterol treatment as an add-on therapy in patients starting glatiramer acetate treatment. Design: Single-center double-masked clinical trial. Setting: Academic research. Patients: Subjects with relapsing-remitting multiple sclerosis. Main Outcome Measures: In this single-center double-masked clinical trial, subjects with relapsing-remitting multiple sclerosis were randomized to receive a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of placebo daily for 2 years or a subcutaneous injection of glatiramer acetate (20 mg) plus an oral dose of albuterol daily for 2 years. The primary clinical efficacy measurement was the change in Multiple Sclerosis Functional Composite at 2 years, and the primary immunologic end point was the change in expression of IL-13 and interferon gamma at each study time point. The clas-sification level of evidence from this trial is C for each question, as this is the first class II clinical trial addressing the efficacy of glatiramer acetate plus albuterol. Results: Forty-four subjects were randomized to receive glatiramer acetate plus albuterol or glatiramer acetate plus placebo, and 39 subjects contributed to the analysis. Improvement in the Multiple Sclerosis Functional Composite was observed in the glatiramer acetate plus albuterol group at the 6-month (P=.005) and 12-month (P=.04) time points but not at the 24-month time point. A delay in the time to first relapse was also observed in the glatiramer acetate plus albuterol group (P=.03). Immunologically, IL-13 and interferon-gamma production decreased in both treatment groups, and a treatment effect on IL-13 production was observed at the 12-month time point (P<.05). Adverse events were generally mild, and only 3 moderate or severe events were considered related to the treatment. Conclusion: Treatment with glatiramer acetate plus albuterol is well tolerated and improves clinical outcomes in patients with multiple sclerosis. C1 [Khoury, Samia J.; Kivisakk, Pia; Viglietta, Vissia; Hafler, David A.; Weiner, Howard L.; Buckle, Guy; Cook, Sandra] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. [Egorova, Svetlana; Guttmann, Charles R. G.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Ctr Neurol Imaging, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Wedgwood, Josiah F.] NIAID, NIH, Bethesda, MD 20892 USA. [Reddy, Susheel] Rho Inc, Chapel Hill, NC USA. RP Khoury, SJ (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Room 710,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM skhoury@rics.bwh.harvard.edu OI khoury, samia/0000-0003-3198-6063 FU National Institute of Allergy and Infectious Diseases [U19A1046130]; EpiVax; LifeCycle Pharmaceutical; PDL; BioPharma; Repligen; Wyeth Pharmaceuticals; Allozyne, Inc; EISAI Research Institute; Xceed Molecular Corporation; Actelion; AutoImmune; Biogen Idec; EMD Serono; Enzo; Gen-. entech; Teva Neuroscience; Vascular Biogenics; Millennium Pharmaceuticals; Bayer; Pfizer FX This study was supported in part by Autoimmunity Center of Excellence Study grant U19A1046130 from the National Institute of Allergy and Infectious Diseases (Dr Khoury).; Dr Khoury has received consulting or lecture fees from EpiVax, LifeCycle Pharmaceutical, PDL, BioPharma, Repligen, and Wyeth Pharmaceuticals. Dr Hafler has received consulting or lecture fees from Allozyne, Inc, EISAI Research Institute, Xceed Molecular Corporation, and Actelion. Dr Weiner has received consulting or lecture fees from AutoImmune, Biogen Idec, EMD Serono, Enzo, Gen-. entech, Teva Neuroscience, and Vascular Biogenics and has received grant support from Millennium Pharmaceuticals. Dr Buckle has received consulting or lecture fees from Bayer, Biogen Idec, EMD Serono, Pfizer, and Teva Neuroscience. NR 32 TC 20 Z9 21 U1 0 U2 1 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 SEP PY 2010 VL 67 IS 9 BP 1055 EP 1061 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 653OW UT WOS:000282102800002 PM 20837847 ER PT J AU Tobian, AAR Gray, RH Quinn, TC AF Tobian, Aaron A. R. Gray, Ronald H. Quinn, Thomas C. TI When Is a Review Article Not a Review Article? Reply SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; MALE CIRCUMCISION; HUMAN-PAPILLOMAVIRUS; HPV INFECTIONS; HIV PREVENTION; YOUNG MEN; METAANALYSIS; HSV-2; RISK C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Gray, Ronald H.] Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Quinn, Thomas C.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21205 USA. [Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Quinn, TC (reprint author), Johns Hopkins Univ, Dept Med, Sch Med, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA. EM tquinn@jhmi.edu NR 15 TC 0 Z9 0 U1 1 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 SEP PY 2010 VL 164 IS 9 BP 884 EP 884 PG 1 WC Pediatrics SC Pediatrics GA 646SX UT WOS:000281564200018 ER PT J AU Lieb, W Gona, P Larson, MG Massaro, JM Lipinska, I Keaney, JF Rong, JA Corey, D Hoffmann, U Fox, CS Vasan, RS Benjamin, EJ O'Donnell, CJ Kathiresan, S AF Lieb, Wolfgang Gona, Philimon Larson, Martin G. Massaro, Joseph M. Lipinska, Izabella Keaney, John F., Jr. Rong, Jian Corey, Diane Hoffmann, Udo Fox, Caroline S. Vasan, Ramachandran S. Benjamin, Emelia J. O'Donnell, Christopher J. Kathiresan, Sekar TI Biomarkers of the Osteoprotegerin Pathway Clinical Correlates, Subclinical Disease, Incident Cardiovascular Disease, and Mortality SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE coronary heart disease; vascular biology; osteoprotegerin; receptor activator of nuclear factor-kappa B ligand ID SERUM OSTEOPROTEGERIN; CORONARY-ARTERY; VASCULAR CALCIFICATION; RECEPTOR ACTIVATOR; DEFICIENT MICE; BONE-DENSITY; RANKL; LIGAND; RISK; OSTEOPOROSIS AB Objective-Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappa B (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD). Methods and Results-Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61 +/- 9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality. Conclusion-Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community. (Arterioscler Thromb Vasc Biol. 2010; 30: 1849-1854.) C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Lieb, Wolfgang; Gona, Philimon; Larson, Martin G.; Massaro, Joseph M.; Rong, Jian; Corey, Diane; Fox, Caroline S.; Vasan, Ramachandran S.; Benjamin, Emelia J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. [O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Gona, Philimon; Larson, Martin G.; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA. [Lipinska, Izabella; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan@partners.org RI Lieb, Wolfgang/C-1990-2012; OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; Doris Duke Charitable Foundation; [R01-HL076784]; [1R01-AG028321]; [R01-HL064753] FX This work was supported by the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract no. N01-HC-25195) and by R01-HL076784, 1R01-AG028321, and R01-HL064753 (to E.J.B.). Dr Kathiresan was funded by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation and by a Mentored Patient-Oriented Research Career Development Award from the National Heart, Lung, and Blood Institute. NR 27 TC 70 Z9 76 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1849 EP U386 DI 10.1161/ATVBAHA.109.199661 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900025 PM 20448212 ER PT J AU Dhingra, R Gona, P Wang, TJ Fox, CS D'Agostino, RB Vasan, RS AF Dhingra, Ravi Gona, Philimon Wang, Thomas J. Fox, Caroline S. D'Agostino, Ralph B., Sr. Vasan, Ramachandran S. TI Serum gamma-Glutamyl Transferase and Risk of Heart Failure in the Community SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE epidemiology; heart failure; risk factors; oxidative stress; gamma-glutamyl transferase ID CORONARY MICROVASCULAR FUNCTION; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; METABOLIC SYNDROME; OXIDATIVE STRESS; PROGNOSTIC VALUE; BLOOD-PRESSURE; TRANSPEPTIDASE AB Objective-To examine the association of serum gamma-glutamyltransferase (GGT) with incident heart failure. Methods and Results-We related serum GGT to the incidence of heart failure in 3544 (mean age, 44.5 years; 1833 women and 1711 men) Framingham Study participants who were free of heart failure and myocardial infarction. On follow-up (mean, 23.6 years), 188 participants (77 women) developed new-onset heart failure. In multivariable Cox proportional hazards regression models adjusting for standard risk factors and alcohol consumption as time-varying covariates (updated every 4 years), each SD increase in log-GGT was associated with a 1.39-fold risk of heart failure (95% CI, 1.20 to 1.62). The linearity of the association was confirmed by multivariable-adjusted splines, and the relations remained robust on additional adjustment for hepatic aminotransferases and C-reactive protein. Participants with a serum GGT level at the median or greater had a 1.71-fold risk of heart failure (95% CI, 1.21 to 2.41) compared with individuals with GGT concentrations less than the median. GGT marginally increased the model C-statistic from 0.85 to 0.86 but improved the risk reclassification modestly (net reclassification index, 5.7%; P = 0.01). Conclusion-In this prospective study of a large community-based sample, higher serum GGT concentrations within the "normal" range were associated with greater risk of heart failure and incrementally improved prediction of heart failure risk. (Arterioscler Thromb Vasc Biol. 2010;30:1855-1860.) C1 [Dhingra, Ravi; Wang, Thomas J.; Fox, Caroline S.; D'Agostino, Ralph B., Sr.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Dhingra, Ravi] Dartmouth Hitchcock Med Ctr, Div Cardiol, Lebanon, NH 03766 USA. [Dhingra, Ravi] Harvard Univ, Sch Publ Hlth, Masters Publ Hlth Program, Boston, MA 02115 USA. [Gona, Philimon; D'Agostino, Ralph B., Sr.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Fox, Caroline S.] NHLBI, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Max, Mad/E-5238-2010; OI Max, Mad/0000-0001-6966-6829; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [N01-HC-25195, N01HV28178, R01HL71039, R01HL67288] FX This study was supported by contracts N01-HC-25195, N01HV28178 (Dr Vasan), R01HL71039 (Dr Vasan), and R01HL67288 (Dr Vasan) from the National Heart, Lung, and Blood Institute's Framingham Heart Study. NR 40 TC 30 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 2010 VL 30 IS 9 BP 1855 EP 1860 DI 10.1161/ATVBAHA.110.207340 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 641NX UT WOS:000281135900026 PM 20539015 ER PT J AU Rider, LG Miller, FW AF Rider, Lisa G. Miller, Frederick W. TI Mast Cells and Type I Interferon Responses in the Skin of Patients With Juvenile Dermatomyositis: Are Current Therapies Just Scratching the Surface? SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID PERIPHERAL-BLOOD; DISEASE-ACTIVITY; GENE-EXPRESSION; POLYMYOSITIS; AUTOANTIBODIES; ASSOCIATION; INVOLVEMENT; ARTHRITIS; MUSCLE C1 [Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Rider, LG (reprint author), CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [ZIA ES101081-08] NR 29 TC 3 Z9 3 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 SEP PY 2010 VL 62 IS 9 BP 2619 EP 2622 DI 10.1002/art.27525 PG 4 WC Rheumatology SC Rheumatology GA 665TT UT WOS:000283059100008 PM 20506242 ER PT J AU Ertem, G Steudel, A Emmerich, K Lagaly, G Schuhmann, R AF Ertem, Goezen Steudel, Annett Emmerich, Katja Lagaly, Gerhard Schuhmann, Rainer TI Correlation Between the Extent of Catalytic Activity and Charge Density of Montmorillonites SO ASTROBIOLOGY LA English DT Article DE Mars; Origin of life; Montmorillonite; Mineral catalysis; Layer charge density; X-ray diffractometry ID ALKYLAMMONIUM LAYER-SILICATES; PARAFFIN-LIKE STRUCTURES; PHOENIX LANDING SITE; CLAY-MINERALS; OLIGOMERIZATION REACTIONS; CATIONIC TENSIDES; MARTIAN SOIL; MARS; SURFACES; ARRANGEMENT AB The clay mineral montmorillonite is a member of the phyllosilicate group of minerals, which has been detected on martian soil. Montmorillonite catalyzes the condensation of activated monomers to form RNA-like oligomers. Extent of catalysis, that is, the yield of oligomers, and the length of the longest oligomer formed in these reactions widely varies with the source of montmorillonite (i.e., the locality where the mineral is mined). This study was undertaken to establish whether there exists a correlation between the extent of catalytic property and the charge density of montmorillonites. Charge density was determined by saturating the montmorillonites with alkyl ammonium cations that contained increasing lengths of alkyl chains, [CH(3)-(CH(2))(n)-NH(3)](+), where n = 3-16 and 18, and then measuring d((001)), interlayer spacing of the resulting montmorillonite-alkyl ammonium-montmorillonite complex by X-ray diffractometry (XRD). Results demonstrate that catalytic activity of montmorillonites with lower charge density is superior to that of higher charge density montmorillonite. They produce longer oligomers that contain 9 to 10 monomer units, while montmorillonite with high charge density catalyzes the formation of oligomers that contain only 4 monomer units. The charge density of montmorillonites can also be calculated from the chemical composition if elemental analysis data of the pure mineral are available. In the next mission to Mars, CheMin (Chemistry and Mineralogy), a combined X-ray diffraction/X-ray fluorescence instrument, will provide information on the mineralogical and elemental analysis of the samples. Possible significance of these results for planning the future missions to Mars for the search of organic compounds and extinct or extant life is discussed. C1 [Ertem, Goezen] NIH, Bethesda, MD 20892 USA. [Ertem, Goezen] Carl Sagan Ctr, SETI Inst, Mountain View, CA USA. [Steudel, Annett; Emmerich, Katja; Schuhmann, Rainer] Karlsruhe Inst Technol, Competence Ctr Mat Moisture, Karlsruhe, Germany. [Steudel, Annett; Emmerich, Katja; Schuhmann, Rainer] Karlsruhe Inst Technol, Inst Funct Interfaces, Karlsruhe, Germany. [Lagaly, Gerhard] Univ Kiel, Inst Organ Chem, D-2300 Kiel, Germany. RP Ertem, G (reprint author), NIH, 10 Ctr Dr 3N322, Bethesda, MD 20892 USA. EM ertemg@mail.nih.gov NR 41 TC 3 Z9 3 U1 4 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1531-1074 J9 ASTROBIOLOGY JI Astrobiology PD SEP PY 2010 VL 10 IS 7 BP 743 EP 749 DI 10.1089/ast.2009.0436 PG 7 WC Astronomy & Astrophysics; Biology; Geosciences, Multidisciplinary SC Astronomy & Astrophysics; Life Sciences & Biomedicine - Other Topics; Geology GA 671EM UT WOS:000283483100007 PM 20854214 ER PT J AU Gogtay, N AF Gogtay, Nitin TI PROGRESSIVE GM ABNORMALITIES IN CHILDHOOD-ONSET SCHIZOPHRENIA (COS): INSIGHTS FROM GENETIC AND IMAGING STUDIES SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2010 VL 44 SU 1 BP A8 EP A8 PG 1 WC Psychiatry SC Psychiatry GA 664IX UT WOS:000282954700015 ER PT J AU Lenroot, RK Giedd, JN AF Lenroot, Rhoshel K. Giedd, Jay N. TI THE STRUCTURAL AND FUNCTIONAL DEVELOPMENTAL TRAJECTORY OF THE FRONTAL CORTEX SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Meeting Abstract C1 [Lenroot, Rhoshel K.] Univ New S Wales, Sydney, NSW, Australia. [Lenroot, Rhoshel K.] Neurosci Res Australia, Sydney, NSW, Australia. [Lenroot, Rhoshel K.; Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. 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 NR 6 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD SEP PY 2010 VL 44 SU 1 BP A7 EP A7 PG 1 WC Psychiatry SC Psychiatry GA 664IX UT WOS:000282954700012 ER PT J AU Subbiah, M Xiao, S Khattar, SK Dias, FM Collins, PL Samal, SK AF Subbiah, Madhuri Xiao, Sa Khattar, Sunil K. Dias, Flavia Militino Collins, Peter L. Samal, Siba K. TI Pathogenesis of Two Strains of Avian Paramyxovirus Serotype 2, Yucaipa and Bangor, in Chickens and Turkeys SO AVIAN DISEASES LA English DT Article DE avian paramyxovirus serotype 2; APMV-2 strain Yucaipa; APMV-2 strain Bangor; pathogenesis; chickens and turkeys; immunohistochemistry ID NEWCASTLE-DISEASE VIRUS; COMPLETE NUCLEOTIDE-SEQUENCE; RESPIRATORY-DISEASE; GENOME SEQUENCE; WILD BIRDS; SEROLOGICAL SURVEY; MALLARD DUCK; PROTEIN; POULTRY; ISRAEL AB Nine serologic types of avian paramyxovirus (APMV) have been recognized. Newcastle disease virus (APMV-1) is the most extensively characterized virus, while relatively little information is available for the other APMV serotypes. In the present study, we examined the pathogenicity of two strains of APMV-2, Yucaipa and Bangor, in 9-day-old embryonated chicken eggs, 1-day-old specific-pathogen-free (SPF) chicks, and 4-wk-old SPF chickens and turkeys. The mean death time in 9-day-old embryonated chicken eggs was more than 168 hr for both strains, and their intracerebral pathogenicity index (ICPI) was zero, indicating that these viruses are nonpathogenic in chickens. When inoculated intracerebrally in 1-day-old chicks, neither strain caused disease or replicated detectably in the brain. This suggests that the zero ICPI value of APMV-2 reflects the inability of the virus to grow in neural cells. Groups of twelve 4-wk-old SPF chickens and turkeys were inoculated oculonasally with either strain, and three birds per group were euthanatized on days 2, 4, 6, and 14 postinoculation for analysis. There were no overt clinical signs of illnesses, although all birds seroconverted by day 6. The viruses were isolated predominantly from the respiratory and alimentary tracts. Immunohistochemistry studies also showed the presence of a large amount of viral antigens in epithelial linings of respiratory and alimentary tracts. There also was evidence of systemic spread even though the cleavage site of the viral fusion glycoprotein does not contain the canonical furin protease cleavage site. C1 [Subbiah, Madhuri; Xiao, Sa; Khattar, Sunil K.; Dias, Flavia Militino; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, 8075 Greenmead Dr, College Pk, MD 20742 USA. EM ssamal@umd.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [N01A060009] FX We thank Daniel Rockemann and all our laboratory members for their excellent technical assistance; LaShae Green, Shin-Hee Kim, Arthur Samuel, and Anandan Paldurai for critical reading of this manuscript. This research was supported in part by National Institute of Allergy and Infectious Diseases (NIAID) contract no. N01A060009 (85% support) and the NIAID, National Institute of Health Intramural Research Program (15% support). NR 57 TC 6 Z9 6 U1 1 U2 4 PU AMER ASSOC AVIAN PATHOLOGISTS PI ATHENS PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD SEP PY 2010 VL 54 IS 3 BP 1050 EP 1057 DI 10.1637/9380-041910-Reg.1 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 658XS UT WOS:000282528600012 PM 20945787 ER PT J AU Grave, GD Huang, TTK Maddox, YT AF Grave, Gilman D. Huang, Terry T-K. Maddox, Yvonne T. TI Working Together to Reduce Pediatric Obesity SO BARIATRIC NURSING AND SURGICAL PATIENT CARE LA English DT Editorial Material ID CHILDHOOD OBESITY; UNITED-STATES; FATTY LIVER; ADOLESCENTS; CHILDREN; EPIDEMIC C1 [Grave, Gilman D.; Maddox, Yvonne T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Huang, Terry T-K.] Univ Nebraska Med Ctr, Omaha, NE USA. RP Grave, GD (reprint author), NICHD, Ctr Res Mothers & Children, 6100 Execut Blvd,Room 4B-05, Bethesda, MD 20892 USA. EM gg37v@nih.gov NR 18 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 1557-1459 J9 BARIAT NURS SURG PAT JI Bariatr. Nurs. Surg. Patient Care PD SEP PY 2010 VL 5 IS 3 BP 197 EP 202 DI 10.1089/bar.2010.9902 PG 6 WC Nursing SC Nursing GA 646BT UT WOS:000281510600002 ER PT J AU Klaiber, M Kruse, M Volker, K Schroter, J Feil, R Freichel, M Gerling, A Feil, S Dietrich, A Londono, JEC Baba, HA Abramowitz, J Birnbaumer, L Penninger, JM Pongs, O Kuhn, M AF Klaiber, Michael Kruse, Martin Voelker, Katharina Schroeter, Juliane Feil, Robert Freichel, Marc Gerling, Andrea Feil, Susanne Dietrich, Alexander Londono, Juan Eduardo Camacho Baba, Hideo A. Abramowitz, Joel Birnbaumer, Lutz Penninger, Josef M. Pongs, Olaf Kuhn, Michaela TI Novel insights into the mechanisms mediating the local antihypertrophic effects of cardiac atrial natriuretic peptide: role of cGMP-dependent protein kinase and RGS2 SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE ANP; Angiotensin II; cGMP-dependent protein kinase; RGS2; Cardiac hypertrophy ID GUANYLYL CYCLASE-A; DEFICIENT MICE; BLOOD-PRESSURE; TRPC3 CHANNELS; HYPERTROPHY; RECEPTOR; HEART; HYPERTENSION; MYOCYTES; SYSTEM AB Cardiac atrial natriuretic peptide (ANP) locally counteracts cardiac hypertrophy via the guanylyl cyclase-A (GC-A) receptor and cGMP production, but the downstream signalling pathways are unknown. Here, we examined the influence of ANP on beta-adrenergic versus Angiotensin II (Ang II)-dependent (G(s) vs. G(alpha q) mediated) modulation of Ca(2+) (i)-handling in cardiomyocytes and of hypertrophy in intact hearts. L-type Ca(2+) currents and Ca(2+) (i) transients in adult isolated murine ventricular myocytes were studied by voltage-clamp recordings and fluorescence microscopy. ANP suppressed Ang II-stimulated Ca(2+) currents and transients, but had no effect on isoproterenol stimulation. Ang II suppression by ANP was abolished in cardiomyocytes of mice deficient in GC-A, in cyclic GMP-dependent protein kinase I (PKG I) or in the regulator of G protein signalling (RGS) 2, a target of PKG I. Cardiac hypertrophy in response to exogenous Ang II was significantly exacerbated in mice with conditional, cardiomyocyte-restricted GC-A deletion (CM GC-A KO). This was concomitant to increased activation of the Ca(2+)/calmodulin-dependent prohypertrophic signal transducer CaMKII. In contrast, beta-adrenoreceptor-induced hypertrophy was not enhanced in CM GC-A KO mice. Lastly, while the stimulatory effects of Ang II on Ca(2+)-handling were absent in myocytes of mice deficient in TRPC3/TRPC6, the effects of isoproterenol were unchanged. Our data demonstrate a direct myocardial role for ANP/GC-A/cGMP to antagonize the Ca(2+) (i)-dependent hypertrophic growth response to Ang II, but not to beta-adrenergic stimulation. The selectivity of this interaction is determined by PKG I and RGS2-dependent modulation of Ang II/AT(1) signalling. Furthermore, they strengthen published observations in neonatal cardiomyocytes showing that TRPC3/TRPC6 channels are essential for Ang II, but not for beta-adrenergic Ca(2+) (i)-stimulation in adult myocytes. C1 [Klaiber, Michael; Voelker, Katharina; Schroeter, Juliane; Kuhn, Michaela] Univ Wurzburg, Inst Physiol, D-97070 Wurzburg, Germany. [Kruse, Martin; Pongs, Olaf] Univ Hamburg, Inst Neurale Signalverarbeitung, Zentrum Mol Neurobiol, Hamburg, Germany. [Feil, Robert; Gerling, Andrea; Feil, Susanne] Univ Tubingen, Interfak Inst Biochem, Tubingen, Germany. [Freichel, Marc; Londono, Juan Eduardo Camacho] Univ Saarland, Homburg, Germany. [Dietrich, Alexander] Univ Marburg, Inst Pharmakol & Toxikol, D-3550 Marburg, Germany. [Baba, Hideo A.] Univ Duisburg Essen, Univ Hosp Essen, Inst Pathol, Essen, Germany. [Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Res Triangle Pk, NC USA. [Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1010 Vienna, Austria. RP Kuhn, M (reprint author), Univ Wurzburg, Inst Physiol, Rontgenring 9, D-97070 Wurzburg, Germany. EM michaela.kuhn@mail.uni-wuerzburg.de RI Dietrich, Alexander/G-8619-2013; Penninger, Josef/I-6860-2013; Feil, Robert/B-8918-2014; Abramowitz, Joel/A-2620-2015; OI Penninger, Josef/0000-0002-8194-3777; Feil, Robert/0000-0002-7335-4841; Dietrich, Alexander/0000-0002-1168-8707 FU Deutsche Forschungsgemeinschaft [SFB 487]; NIH [Z01-ES101684] FX This study was supported by the Deutsche Forschungsgemeinschaft (SFB 487 to Michaela Kuhn). HEK293 cells stably expressing rat GC-A were generously provided by Dr. RueyBing Yang, Academia Sinica, Taipei, Taiwan. The plasmids for expression of human RGS2 and PKG I alpha were kindly provided by Dr. Thomas Wieland (Institute of Pharmacology, University of Mannheim-Heidelberg, Germany) and Dr. Stepan Gambaryan (Department of Clinical Biochemistry, University of Wurzburg, Germany), respectively.; Michael Klaiber performed and evaluated the fluorometric calcium measurements, western blotting, and heart morphometry. Martin Kruse performed and evaluated the electrophysiological calcium measurements. Katharina Volker performed the isolation of myocytes and in vivo studies. Juliane Schroter provided some technical help with the western blot analyses. Drs. Robert, Susanne Feil and Gerling generated and provided the PKG I deficient ("rescue") mice and anti-PKG I antibody. Drs. Freichel, Dietrich, Camacho Londono, Joel Abramowitz, and Lutz Birnbaumer generated or provided the TRPC3/C6 knockout mice. The generation of these mice was supported by the Intramural Research Program of the NIH (Z01-ES101684 to JA and LB). Dr. Baba prepared the cardiac tissues for histology. Dr. Penninger provided RGS2 knockout mice. Michaela Kuhn conceived of and directed the study, analyzed the data, and wrote the manuscript, having helpful discussions with Dr. Pongs. NR 51 TC 40 Z9 40 U1 1 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD SEP PY 2010 VL 105 IS 5 BP 583 EP 595 DI 10.1007/s00395-010-0098-z PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 635HZ UT WOS:000280647500003 PM 20352235 ER PT J AU Lipska, BK AF Lipska, Barbara K. TI ANTIPSYCHOTICS AND ADULT NEUROGENESIS SO BEHAVIOURAL PHARMACOLOGY LA English DT Meeting Abstract CT Meeting on Drugs, Psychiatric Disorders and Neurogenesis CY SEP 03-05, 2010 CL Tours, FRANCE C1 [Lipska, Barbara K.] NIMH, NIH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD SEP PY 2010 VL 21 IS 5-6 BP 582 EP 582 PG 1 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 641IS UT WOS:000281119000033 ER PT J AU Turanov, AA Kehr, S Marino, SM Yoo, MH Carlson, BA Hatfield, DL Gladyshev, VN AF Turanov, Anton A. Kehr, Sebastian Marino, Stefano M. Yoo, Min-Hyuk Carlson, Bradley A. Hatfield, Dolph L. Gladyshev, Vadim N. TI Mammalian thioredoxin reductase 1: roles in redox homoeostasis and characterization of cellular targets SO BIOCHEMICAL JOURNAL LA English DT Article DE cellular target; redox control; thioredoxin; thioredoxin reductase 1 ID EARLY EMBRYONIC LETHALITY; MITOCHONDRIAL THIOREDOXIN; SELENOCYSTEINE; LIVER; GENE; SELENOPROTEINS; APOPTOSIS; SYSTEM AB The classical Trx (thioredoxin) system, composed of TR (Trx reductase), Trx and NADPH, defines a major pathway of cellular thiol-based redox regulation. Three TRs have been identified in mammals: (i) cytosolic TR1, (ii) mitochondrial TR3 and (iii) testes-specific TGR (Trx-glutathione reductase). All three are selenocysteine-containing enzymes with broad substrate specificity in in vitro assays, but which protein substrates are targeted by TRs in vivo is not well understood. In the present study, we used a mechanism-based approach to characterize the molecular targets of TR1 Cytosolic Trx1 was the major target identified in rat and mouse liver, as well as in rat brain and mouse serum. The results suggest that the main function of TR1 is to reduce Trx1. We also found that TR1-based affinity resins provide a convenient tool for specific isolation of Trxs from a variety of biological samples. To better assess the role of TRs in redox homoeostasis, we comparatively analysed TR1- and TR3-knockdown cells. Although cells deficient in TR1were particularly sensitive to diamide, TR3-knockdown cells were more sensitive to hydrogen peroxide. To further examine the TR1-Trx1 redox pair, we used mice with a liver-specific knockout of selenocysteine tRNA. In this model, selenocysteine insertion into TR1 was blocked, but the truncated form of this protein was not detected. Instead, TR I and TR3 levels were decreased in the knockout samples. Diminished hepatic TR I function was associated with elevated Trx1 levels, but this protein was mostly in the oxidized state. Overall, this study provides evidence for the key role of the TR1-Trx1 pair in redox homoeostasis. C1 [Turanov, Anton A.; Kehr, Sebastian; Marino, Stefano M.; Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. [Turanov, Anton A.; Kehr, Sebastian; Marino, Stefano M.; Gladyshev, Vadim N.] Univ Nebraska, Redox Biol Ctr, Lincoln, NE 68588 USA. [Turanov, Anton A.; Marino, Stefano M.; Gladyshev, Vadim N.] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Turanov, Anton A.; Marino, Stefano M.; Gladyshev, Vadim N.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yoo, Min-Hyuk; Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev@rics.bwh.harvard.edu RI Gladyshev, Vadim/A-9894-2013 FU National Institutes of Health [GM065204]; Center for Cancer Research, NCI, NIH FX This work was supported by the National Institutes of Health [grant number GM065204 (to V.N.G.)] and the Intramural Program of the Center for Cancer Research, NCI, NIH (to D.L.H.). NR 23 TC 34 Z9 37 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 2010 VL 430 BP 285 EP 293 DI 10.1042/BJ20091378 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645TX UT WOS:000281490200012 PM 20536427 ER PT J AU Kolli, N Mikolajczyk, J Drag, M Mukhopadhyay, D Moffatt, N Dasso, M Salvesen, G Wilkinson, KD AF Kolli, Nagamalleswari Mikolajczyk, Jowita Drag, Marcin Mukhopadhyay, Debaditya Moffatt, Nela Dasso, Mary Salvesen, Guy Wilkinson, Keith D. TI Distribution and paralogue specificity of mammalian deSUMOylating enzymes SO BIOCHEMICAL JOURNAL LA English DT Article DE deSUMOylating enzyme; small ubiquitin-related modifier (SUMO); substrate specificity; SUMO-specific processing protease (SENP) ID SUMO-SPECIFIC PROTEASE; UBIQUITIN-LIKE PROTEINS; OXIDATIVE STRESS; STRUCTURAL BASIS; NUCLEAR-PORE; C-TERMINUS; HEAT-SHOCK; SENP1; NUCLEOLAR; COMPLEX AB The covalent attachment of SUMO (small ubiquitin-like protein modifier) to target proteins results in modifications in their activity, binding interactions, localization or half-life. The reversal of this modification is catalysed by SENPs (SUMO-specific processing proteases). Mammals contain four SUMO paralogues and six SENP enzymes. In the present paper, we describe a systematic analysis of human SENPs, integrating estimates of relative selectivity for SUMO 1 and SUMO2, and kinetic measurements of recombinant C-terminal cSENPs (SENP catalytic domains). We first characterized the reaction of each endogenous SENP and cSENPs with HA SUMO-VS [HA (haemagglutinin)-tagged SUMO-vinyl sulfones], active-site-directed irreversible inhibitors of SENPs. We found that all cSENPs and endogenous SENP I react with both SUMO paralogues, whereas all other endogeneous SENPs in mammalian cells and tissues display high selectivity for SUMO2-VS. To obtain more quantitative data, the kinetic properties of purified cSENPs were determined using SUMO1- or SUMO2-AMC (7-amino-4-methylcoumarin) as substrate. All enzymes bind their respective substrates with high affinity. cSENP1 and cSENP2 process either SUMO substrate with similar affinity and catalytic efficiency; cSENP5 and cSENP6 show marked catalytic specificity for SUMO2 as measured by K(m) and k(cat) whereas cSENP7 works only on SUMO2. Compared with cSENPs, recombinant full-length SENP1 and SENP2 show differences in SUMO selectivity, indicating that paralogue specificity is influenced by the presence of the variable N-terminal domain of each SENP. Our data suggest that SUMO2 metabolism is more dynamic than that of SUMO1 since most SENPs display a marked preference for SUMO2. C1 [Kolli, Nagamalleswari; Moffatt, Nela; Wilkinson, Keith D.] Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. [Mikolajczyk, Jowita; Drag, Marcin; Salvesen, Guy] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Mukhopadhyay, Debaditya; Dasso, Mary] NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Wilkinson, KD (reprint author), Emory Univ, Dept Biochem, Atlanta, GA 30322 USA. EM keith.wilkinson@emory.edu OI Dasso, Mary/0000-0002-5410-1371 FU National Institutes of Health [5RO1GM066355] FX This work was supported by the National Institutes of Health [grant number 5RO1GM066355]. NR 58 TC 49 Z9 49 U1 1 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 2010 VL 430 BP 335 EP 344 DI 10.1042/BJ20100504 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645TX UT WOS:000281490200017 PM 20590526 ER PT J AU Camilli, TC Weeraratna, AT AF Camilli, Tura C. Weeraratna, Ashani T. TI Striking the target in Wnt-y conditions: Intervening in Wnt signaling during cancer progression SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE Wnt; Wnt5A; Calcium; PCP; beta-Catenin; Cancer ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3-BETA; RECEPTOR TYROSINE KINASE; HUMAN COLORECTAL-CANCER; FAMILIAL ADENOMATOUS POLYPOSIS; CONVERGENT EXTENSION MOVEMENTS; ACUTE LYMPHOBLASTIC-LEUKEMIA; BETA-CATENIN MUTATIONS; PLANAR CELL POLARITY; CHRONIC MYELOID-LEUKEMIA AB Wnt signaling can be divided into three pathways, namely the canonical Wnt/beta-catenin pathway, and the non-canonical (or heretical) Wnt/Ca(2+) and planar cell polarity (PCP) pathways. Although the canonical Wnt/beta-catenin pathway is the best described in cancer, increasing data points to the importance of the heretical Wnt pathways in several aspects of tumor progression. The recent advances in understanding the players and mechanisms by which these Wnt pathways contribute to cancer progression have led to the identification of numerous molecules that are already, or could be considered, targets for cancer therapy. Published by Elsevier Inc. C1 [Weeraratna, Ashani T.] NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, 251 Bayview Blvd,Suite 100,Rm08C226, Baltimore, MD 21224 USA. EM weerarat@mail.nih.gov FU National Institute on Aging FX TCC and ATVV are supported by the Intramural Research Program of the National Institute on Aging. We regret that we were unable to cite all of the work of many great scientists in the Wnt signaling field due to space constraints. NR 218 TC 28 Z9 30 U1 0 U2 3 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 SEP 1 PY 2010 VL 80 IS 5 SI SI BP 702 EP 711 DI 10.1016/j.bcp.2010.03.002 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 627FL UT WOS:000280024800018 PM 20211149 ER PT J AU Lisk, G Pain, M Sellers, M Gurnev, PA Pillai, AD Bezrukov, SM Desai, SA AF Lisk, Godfrey Pain, Margaret Sellers, Morgan Gurnev, Philip A. Pillai, Ajay D. Bezrukov, Sergey M. Desai, Sanjay A. TI Altered plasmodial surface anion channel activity and in vitro resistance to permeating antimalarial compounds SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE Ion channel mutants; Gating; Selectivity; Noise analysis; Plasmodium falciparum; PSAC ID FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; MALARIA PARASITE; BLASTICIDIN-S; PROTEIN-SYNTHESIS; MAMMALIAN-CELLS; TRANSPORT; INHIBITORS; PERMEABILITY; METABOLITES AB Erythrocytes infected with malaria parasites have increased permeability to various solutes. These changes may be mediated by an unusual small conductance ion channel known as the plasmodial surface anion channel (PSAC). While channel activity benefits the parasite by permitting nutrient acquisition, it can also be detrimental because water-soluble antimalarials may more readily access their parasite targets via this channel. Recently, two such toxins, blasticidin S and leupeptin, were used to select mutant parasites with altered PSAC activities, suggesting acquired resistance via reduced channel-mediated toxin uptake. Surprisingly, although these toxins have similar structures and charge, we now show that reduced permeability of one does not protect the intracellular parasite from the other. Leupeptin accumulation in the blasticidin S-resistant mutant was relatively preserved, consistent with retained in vitro susceptibility to leupeptin. Subsequent in vitro selection with both toxins generated a double mutant parasite having additional changes in PSAC, implicating an antimalarial resistance mechanism for water-soluble drugs requiring channel-mediated uptake at the erythrocyte membrane. Characterization of these mutants revealed a single conserved channel on each mutant, albeit with distinct gating properties. These findings are consistent with a shared channel that mediates uptake of ions, nutrients and toxins. This channel's gating and selectivity properties can be modified in response to in vitro selective pressure. Published by Elsevier B.V. C1 [Lisk, Godfrey; Pain, Margaret; Sellers, Morgan; Pillai, Ajay D.; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Gurnev, Philip A.; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov FU National Institutes of Health; NIAID; NICHD; Medicines for Malaria Venture (MMV) FX We thank Ian Bathurst, the Medicines for Malaria Venture Project Director for these studies, and Michael Fay for help with statistical analysis. This research was funded by the Intramural Research Programs of the National Institutes of Health, NIAID and NICHD, and by the Medicines for Malaria Venture (MMV). NR 55 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD SEP PY 2010 VL 1798 IS 9 BP 1679 EP 1688 DI 10.1016/j.bbamem.2010.04.013 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 636PY UT WOS:000280752100005 PM 20451492 ER PT J AU Kumar, A Shukla, S Mandal, A Shukla, S Ambudkar, SV Prasad, R AF Kumar, Antresh Shukla, Suneet Mandal, Ajeet Shukla, Sudhanshu Ambudkar, Suresh V. Prasad, Rajendra TI Divergent signature motifs of nucleotide binding domains of ABC multidrug transporter, CaCdr1p of pathogenic Candida albicans, are functionally asymmetric and noninterchangeable SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE ABC transporter; Nucleotide binding domain; Signature motif; Drug resistance; Drug transport; ATPase activity ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CFTR CHLORIDE CHANNELS; ATP-BINDING; DRUG TRANSPORTER; P-GLYCOPROTEIN; SACCHAROMYCES-CEREVISIAE; WALKER-B; RESISTANCE; CDR1P; HYDROLYSIS AB Nucleotide binding domains (NBDs) of the multidrug transporter of Candida albicans, CaCdr1p, possess unique divergent amino acids in their conserved motifs. For example, NBD1 (N-terminal-NBD) possesses conserved signature motifs, while the same motif is divergent in NBD2 (C-terminal-NBD). In this study, we have evaluated the contribution of these conserved and divergent signature motifs of CaCdr1p in ATP catalysis and drug transport. By employing site-directed mutagenesis, we made three categories of mutant variants. These included mutants where all the signature motif residues were replaced with either alanines or mutants with exchanged equipositional residues to mimic the conservancy and degeneracy in opposite domain. In addition, a set of mutants where signature motifs were swapped to have variants with either both the conserved or degenerated entire signature motif. We observed that conserved and equipositional residues of NBD1 and NBD2 and swapped signature motif mutants showed high susceptibility to all the tested drugs with simultaneous abrogation in ATPase and R6G efflux activities. However, some of the mutants displayed a selective increase in susceptibility to the drugs. Notably, none of the mutant variants and WT-CaCdr1p showed any difference in drug and nucleotide binding. Our mutational analyses show not only that certain conserved residues of NBD1 signature sequence (S304, G306, and E307) are important in ATP hydrolysis and R6G efflux but also that a few divergent residues (N1002 and E1004) of NBD2 signature motif have evolved to be functionally relevant and are not interchangeable. Taken together, our data suggest that the signature motifs of CaCdr1p, whether it is divergent or conserved, are nonexchangeable and are functionally critical for ATP hydrolysis. (C) 2010 Elsevier By. All rights reserved. C1 [Kumar, Antresh; Mandal, Ajeet; Prasad, Rajendra] Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shukla, Sudhanshu] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Prasad, R (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, Membrane Biol Lab, New Delhi 110067, India. EM rp47jnu@gmail.com RI shukla, suneet/B-4626-2012; OI Shukla, Sudhanshu/0000-0002-7091-7215 FU University Grants Commission, India; Department of Biotechnology [BT/PR9100/Med/29/03/2007, BT/PR9563/BRB/10/567/2007, BT/PR11158/BRB/10/640/2008]; National Institutes of Health, National Cancer Institute, Centre for Cancer Research FX We thank R.D. Cannon for the gifts of the plasmid. We thank Ranbaxy Laboratories Ltd., New Delhi, India, for providing fluconazole. AK acknowledges the University Grants Commission, India for the support in the form of Senior Research Fellowship.; The work presented in this paper has been supported in part by grants to R.P. from the Department of Biotechnology (BT/PR9100/Med/29/03/2007, BT/PR9563/BRB/10/567/2007, and BT/PR11158/BRB/10/640/2008). SS and SVA were supported by the intramural research program from the National Institutes of Health, National Cancer Institute, Centre for Cancer Research. NR 55 TC 7 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD SEP PY 2010 VL 1798 IS 9 BP 1757 EP 1766 DI 10.1016/j.bbamem.2010.05.017 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 636PY UT WOS:000280752100014 PM 20546701 ER PT J AU Galan, C Woodard, GE Dionisio, N Salido, GM Rosado, JA AF Galan, Carmen Woodard, Geoffrey E. Dionisio, Natalia Salido, Gines M. Rosado, Juan A. TI Lipid rafts modulate the activation but not the maintenance of store-operated Ca2+ entry SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE Orai1; TRPC1; TRPC6; STIM1; Lipid rafts; Lanthanum ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; HUMAN PLATELETS; CALCIUM-ENTRY; ACTIN CYTOSKELETON; CHANNEL FUNCTION; PLASMA-MEMBRANE; TRPC CHANNELS; CRAC CHANNEL; KEY ROLE; STIM1 AB Different studies have reported that proteins involved in Ca2+ entry are localized in discrete plasma membrane domains known as lipid rafts, which have been suggested to support store-operated Ca2+ entry by facilitating STIM1 clustering in endoplasmic reticulum-plasma membrane junctions as well as the interaction of STIM1 with TRPC1. Here we report that treatment of HEK293 cells with thapsigargin (TG) results in the activation of Ca2+ entry with two components, an early, La3+-sensitive, component and a late component that shows both La3+-sensitive and -insensitive constituents. Preincubation with methyl-beta-cyclodextrin (M beta CD) prevented TG-induced activation of Ca2+ entry but, in contrast, enhanced this process after its activation. Addition of M beta CD after store depletion did not modify the La3+-sensitive store-operated divalent cation entry but increased La3+-insensitive non-capacitative Ca2+ entry. Cell stimulation with TG results in a transient increase in Orai1 co-immunoprecipitation with STIM1, TRPC1 and TRPC6. TG-induced association of these proteins was significantly attenuated by preincubation for 30 min with m beta CD, without altering surface expression of Orai1 or TRPCs. In contrast, the association of Orai1 with STIM1 or TRPC1 was unaffected when M beta CD was added after store depletion with TG. Addition of M beta CD to TG-treated cells promoted dissociation between Orai1 and TRPC6, as well as non-capacitative Ca2+ entry. TRPC6 expression silencing indicates that M beta CD-enhanced non-capacitative Ca2+ entry was mediated by TRPC6. In conclusion, lipid raft domains are necessary for the activation but not the maintenance of SOCE probably due to the support of the formation of Ca2+ signalling complexes involving Orai1. TRPCs and STIM1. (C) 2010 Elsevier B.V. All rights reserved. C1 [Galan, Carmen; Dionisio, Natalia; Salido, Gines M.; Rosado, Juan A.] Univ Extremadura, Dept Physiol, Cell Physiol Res Grp, Caceres 10071, Spain. [Woodard, Geoffrey E.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Rosado, JA (reprint author), Univ Extremadura, Dept Physiol, Cell Physiol Res Grp, Caceres 10071, Spain. EM jarosado@unex.es RI Woodard, Geoffrey/A-8608-2009; Salido, Gines/A-4292-2009; rosado, juan/H-3488-2015 OI Salido, Gines/0000-0002-8687-2445; rosado, juan/0000-0002-9749-2325 FU MEC [BFU2007-60104]; Junta de Extremadura-FEDER [GRU090]; Spanish Ministry of Science and Innovation [PTA2008-0870-P]; Junta de Extremadura [PRE09020] FX Supported by MEC grant BFU2007-60104. G.E.W. hold a visit grant from Junta de Extremadura-FEDER (GRU090). C.G. and N.D. are supported by Spanish Ministry of Science and Innovation (PTA2008-0870-P) and Junta de Extremadura (PRE09020), respectively. We are grateful to Dr. Indu Ambudkar for generously providing plasmids. NR 54 TC 24 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD SEP PY 2010 VL 1803 IS 9 BP 1083 EP 1093 DI 10.1016/j.bbamcr.2010.06.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 638VM UT WOS:000280925600012 PM 20600358 ER PT J AU Petrucci, R Saso, L Kumar, V Prasad, AK Malhotra, SV Parmar, VS Marrosu, G AF Petrucci, Rita Saso, Luciano Kumar, Vineet Prasad, Ashok K. Malhotra, Sanjay V. Parmar, Virinder S. Marrosu, Giancarlo TI A spectroelectrochemical and chemical study on oxidation of 7,8-dihydroxy-4-methylcoumarin (DHMC) and some related compounds in aprotic medium SO BIOCHIMIE LA English DT Article DE Antioxidants; Polyphenols oxidation; Radical anions; Semiquinones; Spectroelectrochemistry ID LOW-DENSITY-LIPOPROTEIN; NITROGEN-CENTERED RADICALS; SUBSTITUTED 4-METHYLBENZOPYRAN-2-ONES; ANTIOXIDANT ACTIVITY; LIPID-PEROXIDATION; BIOCHEMICAL-ACTION; IN-VITRO; HYDROXYCINNAMIC ACIDS; PROTEIN FRAGMENTATION; PHENOLIC-COMPOUNDS AB Electrochemical and chemical oxidation of 7,8-hydroxy-4-methylcoumarin (DHMC 1) and 7,8-diacetoxy-4-methylcoumarin (DAMC 4) were studied to investigate the mechanisms occurring in their antioxidant activities in acetonitrile, under electron transfer and H-atom transfer conditions. Electrolysis and chemical reactions were followed on-line by monitoring the UV spectral changes with time. The anodic oxidation of DHMC, studied by cyclic voltammetry and controlled potential electrolysis, occurs via a reversible one-step two-electrons process, yielding the corresponding stable phenoxonium cation. Moreover, the chemical oxidation with an H-atom acceptor also follows a similar path, yielding the stable neutral quinonic product. Intermediates were never evidenced in both cases. Only in the presence of a strong base, an anodic oxidation product mono-electronic was evidenced, likely the DHMC radical anion. However, the anodic oxidation of the acetoxy derivative DAMC occurs at very high potential values, ruling out the possibility that the antioxidant activity observed in vivo might occur via an electron transfer mechanism; no reactions were evidenced with an H-atom acceptor. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Petrucci, Rita; Marrosu, Giancarlo] Univ Roma La Sapienza, Dipartimento Ingn Chim Mat Ambiente, I-00161 Rome, Italy. [Saso, Luciano] Univ Roma La Sapienza, Dipartimento Fisiol & Farmacol Vittorio Erspamer, I-00185 Rome, Italy. [Kumar, Vineet; Prasad, Ashok K.; Parmar, Virinder S.] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India. [Kumar, Vineet; Malhotra, Sanjay V.] Natl Canc Inst Frederick, Lab Synthet Chem, Dev Therapeut Program Support, SAIC Frederick, Frederick, MD 21702 USA. RP Petrucci, R (reprint author), Univ Roma La Sapienza, Dipartimento Ingn Chim Mat Ambiente, Via Castro Laurenziano 7, I-00161 Rome, Italy. EM rita.petrucci@uniroma1.it RI saso, luciano/F-6306-2012; OI saso, luciano/0000-0003-4530-8706; MARROSU, Giancarlo/0000-0002-0462-3809 FU Ministero dell'Universita e dellaRicerca Scientifica e Tecnologica (MURST) FX We thank the Ministero dell'Universita e dellaRicerca Scientifica e Tecnologica (MURST) for financial support. NR 52 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD SEP PY 2010 VL 92 IS 9 BP 1123 EP 1129 DI 10.1016/j.biochi.2010.06.008 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652GM UT WOS:000281991400006 PM 20600572 ER PT J AU Kumar, V Parmar, VS Malhotra, SV AF Kumar, Vineet Parmar, Virinder S. Malhotra, Sanjay V. TI Structural modifications of nucleosides in ionic liquids SO BIOCHIMIE LA English DT Review DE Nucleosides; Ionic liquids; Solubility; Anti-viral drugs ID PYRIMIDINE NUCLEOSIDES; EFFICIENT METHOD; ANTIVIRAL DRUGS; SELECTIVE BENZOYLATION; ENZYMATIC RESOLUTION; BETA-ELIMINATION; CATALYSIS; ANALOGS; OLIGONUCLEOTIDES; CHEMISTRY AB Nucleoside chemistry represents an important research area for drug discovery, as many nucleoside analogs are prominent drugs and have been widely applied for cancer and viral chemotherapy. However, the synthesis of modified nucleosides presents a major challenge, which is further aggravated by poor solubility of these compounds in common organic solvents. Most of the currently available methods for nucleoside modification employ toxic high boiling solvents; require long reaction time and tedious workup methods. As such, there is constant effort to develop process chemistry in alternative medium to limit the use of organic solvents that are hazardous to the environment and can be deleterious to human health. One such approach is to use ionic liquids, which are 'designer materials' with unique and tunable physico-chemical properties. Studies have shown that methodologies using ionic liquids are highly efficient and convenient for the synthesis of nucleoside analogs, as demonstrated by the preparation of pharmaceutically important anti-viral drugs. This article summarizes recent efforts on nucleoside modification using ionic liquids. (C) 2010 Elsevier Masson SAS. All rights reserved. C1 [Kumar, Vineet; Malhotra, Sanjay V.] NCI, Lab Synthet Chem, SAIC Frederick Inc, Frederick, MD 21702 USA. [Parmar, Virinder S.] Univ Delhi, Dept Chem, Delhi 110007, India. RP Malhotra, SV (reprint author), NCI, Lab Synthet Chem, SAIC Frederick Inc, 1050 Boyles St, Frederick, MD 21702 USA. EM malhotrasa@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The authors acknowledge financial support from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 48 TC 10 Z9 10 U1 0 U2 8 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD SEP PY 2010 VL 92 IS 9 BP 1260 EP 1265 DI 10.1016/j.biochi.2010.02.019 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 652GM UT WOS:000281991400023 PM 20178825 ER PT J AU Volkow, ND Wang, GJ Fowler, JS Tomasi, D Telang, F Baler, R AF Volkow, Nora D. Wang, Gene-Jack Fowler, Joanna S. Tomasi, Dardo Telang, Frank Baler, Ruben TI Addiction: Decreased reward sensitivity and increased expectation sensitivity conspire to overwhelm the brain's control circuit SO BIOESSAYS LA English DT Review DE addiction; brain disease; dopamine; reward circuit ID STRIATAL DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; COCAINE ABUSERS; DRUG-ADDICTION; METHYLPHENIDATE; HUMANS; RECEPTORS; OCCUPANCY; SYSTEMS; RATS AB Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co-opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction. C1 [Volkow, Nora D.; Baler, Ruben] Natl Inst Drug Abuse, NIH, Bethesda, MD USA. [Wang, Gene-Jack; Fowler, Joanna S.; Tomasi, Dardo; Telang, Frank] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 FU Intramural NIH HHS [ZIA AA000550-06] NR 54 TC 127 Z9 131 U1 3 U2 27 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD SEP PY 2010 VL 32 IS 9 BP 748 EP 755 DI 10.1002/bies.201000042 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 647NK UT WOS:000281625000005 PM 20730946 ER PT J AU Pruim, RJ Welch, RP Sanna, S Teslovich, TM Chines, PS Gliedt, TP Boehnke, M Abecasis, GR Willer, CJ AF Pruim, Randall J. Welch, Ryan P. Sanna, Serena Teslovich, Tanya M. Chines, Peter S. Gliedt, Terry P. Boehnke, Michael Abecasis, Goncalo R. Willer, Cristen J. TI LocusZoom: regional visualization of genome-wide association scan results SO BIOINFORMATICS LA English DT Article ID COMMON VARIANTS; IDENTIFICATION; SNPS; TOOL AB Genome-wide association studies (GWAS) have revealed hundreds of loci associated with common human genetic diseases and traits. We have developed a web-based plotting tool that provides fast visual display of GWAS results in a publication-ready format. LocusZoom visually displays regional information such as the strength and extent of the association signal relative to genomic position, local linkage disequilibrium (LD) and recombination patterns and the positions of genes in the region. C1 [Welch, Ryan P.; Teslovich, Tanya M.; Gliedt, Terry P.; Boehnke, Michael; Abecasis, Goncalo R.; Willer, Cristen J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Welch, Ryan P.; Teslovich, Tanya M.; Gliedt, Terry P.; Boehnke, Michael; Abecasis, Goncalo R.; Willer, Cristen J.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Pruim, Randall J.] Calvin Coll, Dept Math & Stat, Grand Rapids, MI 49546 USA. [Welch, Ryan P.] Univ Michigan, Sch Med, Bioinformat Grad Program, Ann Arbor, MI 48109 USA. [Sanna, Serena] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. [Chines, Peter S.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Willer, CJ (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. EM cristen@umich.edu RI Abecasis, Goncalo/B-7840-2010; OI Willer, Cristen/0000-0001-5645-4966; sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825 FU Calvin College; National Institue of Diabetes and Digestive and Kidney Diseases [DK062370]; National Human Genome Research Institute [HG000376, HG000040, HG002651, HG005214]; National Institute of Mental Health [MH084698]; National Heart, Lung and Blood Institute [K99HL094535] FX R.J.P. is supported by a Research Fellowship from Calvin College. M. B. and T. M. T. are supported by grants from the National Institue of Diabetes and Digestive and Kidney Diseases (DK062370, PI M. B.). M. B., T.N.T. and G. R. A. are supported by the National Human Genome Research Institute (HG000376, PI M. B.; for T. M. T. HG000040, PI M. B.; HG002651, PI G. R. A. and HG005214, PI G. R. A.). G. R. A. is additionally funded by the National Institute of Mental Health (MH084698). C.J.W. is funded by a Pathway to Independence Award from the National Heart, Lung and Blood Institute (K99HL094535, PI C.J.W.). NR 8 TC 667 Z9 673 U1 2 U2 19 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD SEP PY 2010 VL 26 IS 18 BP 2336 EP 2337 DI 10.1093/bioinformatics/btq419 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 648SK UT WOS:000281714100054 PM 20634204 ER PT J AU Thomason, ME Henry, ML Hamilton, JP Joormann, J Pine, DS Ernst, M Goldman, D Mogg, K Bradley, BP Britton, JC Lindstrom, KM Monk, CS Sankin, LS Louro, HMC Gotlib, IH AF Thomason, Moriah E. Henry, Melissa L. Hamilton, J. Paul Joormann, Jutta Pine, Daniel S. Ernst, Monique Goldman, David Mogg, Karin Bradley, Brendan P. Britton, Jennifer C. Lindstrom, Kara M. Monk, Christopher S. Sankin, Lindsey S. Louro, Hugo M. C. Gotlib, Ian H. TI Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Attention; Emotion; Children; Serotonin; Gene; fMRI; 5-HTTLPR; Adolescence ID STRESSFUL LIFE EVENTS; PREFRONTAL CORTEX ACTIVATION; GENERALIZED ANXIETY DISORDER; PROMOTER POLYMORPHISM; MAJOR DEPRESSION; ATTENTIONAL BIAS; ANGRY FACES; 5-HTTLPR POLYMORPHISM; FACIAL EXPRESSIONS; TRAIT ANXIETY AB Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material. (C) 2010 Elsevier B.V. All rights reserved. C1 [Thomason, Moriah E.; Henry, Melissa L.; Hamilton, J. Paul; Louro, Hugo M. C.; Gotlib, Ian H.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. [Joormann, Jutta] Univ Miami, Dept Psychol, Miami, FL USA. [Pine, Daniel S.; Ernst, Monique; Goldman, David; Britton, Jennifer C.; Lindstrom, Kara M.; Sankin, Lindsey S.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD USA. [Mogg, Karin; Bradley, Brendan P.] Univ Southampton, Dept Psychol, Southampton SO9 5NH, Hants, England. [Monk, Christopher S.] Univ Michigan, Dept Psychol, Ann Arbor, MI USA. RP Thomason, ME (reprint author), Stanford Univ, Dept Psychol, Jordan Hall,Bldg 420, Stanford, CA 94305 USA. EM moriah@stanford.edu RI Mogg, Karin/C-1181-2008; Bradley, Brendan/B-9724-2008; Britton, Jennifer/J-4501-2013; Monk, Christopher/J-1805-2014; Goldman, David/F-9772-2010; OI Mogg, Karin/0000-0002-2738-7378; Goldman, David/0000-0002-1724-5405; Bradley, Brendan/0000-0003-2801-4271 FU National Institute of Mental Health [MH081583, MH074849]; NARSAD Young Investigator Award FX This project was supported by awards from the National Institute of Mental Health [MH081583 to MET, and MH074849 to IHG], and by a NARSAD Young Investigator Award to MET, and by funding from the NIMH-Intramural Research Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank Melissa Henry, Sarah Victor, Emily Dennis, Rebecca Johnson, Meggy Wang, and Hannah Kang for their assistance in acquiring the scan data, and Yamanda Wright, Kirsten Gilbert, and Lindsey Sherdell for their assistance in participant recruitment, screening, and conducting structured behavioral interviews. NR 57 TC 39 Z9 40 U1 7 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD SEP PY 2010 VL 85 IS 1 BP 38 EP 44 DI 10.1016/j.biopsycho.2010.04.009 PG 7 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 642DB UT WOS:000281182600005 PM 20493234 ER PT J AU Kroger, N Bacher, U Bader, P Bottcher, S Borowitz, MJ Dreger, P Khouri, I Macapintac, H Olavarria, E Radich, J Stock, W Vose, JM Weisdorf, D Willasch, A Giralt, S Bishop, MR Wayne, AS AF Kroeger, Nicolaus Bacher, Ulrike Bader, Peter Boettcher, Sebastian Borowitz, Michael J. Dreger, Peter Khouri, Issa Macapintac, Homer Olavarria, Eduardo Radich, Jerald Stock, Wendy Vose, Julie M. Weisdorf, Daniel Willasch, Andre Giralt, Sergio Bishop, Michael R. Wayne, Alan S. TI NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Disease-Specific Methods and Strategies for Monitoring Relapse following Allogeneic Stem Cell Transplantation. Part I: Methods, Acute Leukemias, and Myelodysplastic Syndromes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic stem cell transplantation; Minimal residual disease; Chimerism; Acute leukemia; Myelodysplastic syndrome ID MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; POLYMERASE-CHAIN-REACTION; WT1 GENE-EXPRESSION; TIME QUANTITATIVE PCR; MULTIPARAMETER FLOW-CYTOMETRY; SINGLE-NUCLEOTIDE POLYMORPHISMS; CHRONIC MYELOGENOUS LEUKEMIA AB Relapse has become the major cause of treatment failure after allogeneic stem cell transplantation. Outcome of patients with clinical relapse after transplantation generally remains poor, but intervention prior to florid relapse improves outcome for certain hematologic malignancies. To detect early relapse or minimal residual disease, sensitive methods such as molecular genetics, tumor-specific molecular primers, fluorescein in situ hybridization, and multiparameter flow cytometry (MFC) are commonly used after allogeneic stem cell transplantation to monitor patients, but not all of them are included in the commonly employed disease-specific response criteria. The highest sensitivity and specificity can be achieved by molecular monitoring of tumor- or patient-specific markers measured by polymerase chain reaction-based techniques, but not all diseases have such targets for monitoring. Similar high sensitivity can be achieved by determination of donor chimerism, but its specificity regarding detection of relapse is low and differs substantially among diseases. Here, we summarize the current knowledge about the utilization of such sensitive monitoring techniques based on tumor-specific markers and donor cell chimerism and how these methods might augment the standard definitions of posttransplant remission, persistence, progression, relapse, and the prediction of relapse. Critically important is the need for standardization of the different residual disease techniques and to assess the clinical relevance of minimal residual disease and chimerism surveillance in individual diseases, which in turn, must be followed by studies to assess the potential impact of specific interventional strategies. Biol Blood Marrow Transplant 16: 1187-1211(2010) (C) 2010 American Society for Blood and Marrow Transplantation C1 [Kroeger, Nicolaus] Univ Hamburg Hosp, Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, D-20246 Hamburg, Germany. [Bader, Peter; Willasch, Andre] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany. [Boettcher, Sebastian] Univ Hosp Schleswig Holstein, Dept Med 2, Kiel, Germany. [Borowitz, Michael J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Dreger, Peter] Univ Heidelberg, Dept Med 5, D-6900 Heidelberg, Germany. [Khouri, Issa; Giralt, Sergio] Univ Texas MD Anderson Canc Ctr, Div Hematol, Houston, TX 77030 USA. [Macapintac, Homer] Univ Texas MD Anderson Canc Ctr, Div Nucl Med, Houston, TX 77030 USA. [Olavarria, Eduardo] Hosp Navarra, Serv Hematol, Pamplona, Spain. [Radich, Jerald] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Vose, Julie M.] Univ Nebraska, Med Ctr, Omaha, NE USA. [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN USA. [Bishop, Michael R.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kroger, N (reprint author), Univ Hamburg Hosp, Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Martinstr 52, D-20246 Hamburg, Germany. EM nkroeger@uke.de; waynea@mail.nih.gov NR 250 TC 43 Z9 43 U1 1 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 SEP PY 2010 VL 16 IS 9 BP 1187 EP 1211 DI 10.1016/j.bbmt.2010.06.008 PG 25 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 643NS UT WOS:000281304000001 PM 20558311 ER PT J AU Stringaris, K Adams, S Uribe, M Eniafe, R Wu, CO Savani, BN Barrett, AJ AF Stringaris, Kate Adams, Sharon Uribe, Marcelo Eniafe, Rhoda Wu, Colin O. Savani, Bipin N. Barrett, A. John TI Donor KIR Genes 2DL5A, 2DSI and 3DSI Are Associated with a Reduced Rate of Leukemia Relapse After HLA-Identical Sibling Stem Cell Transplantation for Acute Myeloid Leukemia but Not Other Hematologic Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE NK cells; Stem cell transplantation; Activatory KIR; Relapse; Acute myelogenous leukemia ID ACUTE LYMPHOBLASTIC-LEUKEMIA; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ABSOLUTE LYMPHOCYTE COUNT; NATURAL-KILLER-CELLS; FREE SURVIVAL; NK CELLS; RECOVERY; ALLOREACTIVITY AB Stem cell transplantation (SCT) from a healthy donor can be curative for patients with hematologic malignancies resistant to other treatments. Elimination of malignant cells through a graft-versus-leukemia (GVL) effect involves donor T and natural killer (NK) cells, but their relative contribution to this process is poorly defined. NK cell alloreactivity and GVL effects are controlled by the nature of the interaction of NK activation receptors and killer-immunoglobulin-like-receptors (KIR) with major histocompatibility locus class I antigens on the target cell. We performed KIR-genotyping of HLA-identical sibling donors in 246 T cell-depleted SCTs to identify genetic factors affecting transplant outcome (treatment-related mortality [TRM], leukemic relapse, and survival). Univariate and multivariate analysis of transplant-related risk factors and KIR genotyping was performed to identify independent variables predictive of outcome for different forms of leukemia. Further to confirming known predictive factors for TRM and survival (CD34 cell dose, patient age, disease stage), statistical analysis revealed that 3 donor B haplotype KIR genes, 2DL5A, 2DSI, and 3DSI, were associated with significantly less relapse in patients with acute myelogenous leukemia (AML) (13% versus 57%) but not in patients with other myelogenous or lymphoid malignancies. AML patients receiving SCT from donors with these KIR genes relapsed 4 times less frequently than patients transplanted from donors with other KIR genotypes. These findings suggest specific, genetically determined, interactions between NK cells and AML cells that facilitate the GVL effect, and have implications for donor selection for AML patients. Biol Blood Marrow Transplant 16: 1257-1264 (2010) Published by Elsevier Inc. C1 [Stringaris, Kate; Eniafe, Rhoda; Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Adams, Sharon; Uribe, Marcelo] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Div Hematol Oncol,Dept Med, Nashville, TN USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC-3-5330, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov FU Intramural NIH HHS [ZIA HL006105-02] NR 22 TC 43 Z9 48 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 SEP PY 2010 VL 16 IS 9 BP 1257 EP 1264 DI 10.1016/j.bbmt.2010.03.004 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 643NS UT WOS:000281304000007 PM 20302958 ER PT J AU Jeong, JW Kwak, I Lee, KY Kim, TH Large, MJ Stewart, CL Kaestner, KH Lydon, JP DeMayo, FJ AF Jeong, Jae-Wook Kwak, Inseok Lee, Kevin Y. Kim, Tae Hoon Large, Michael J. Stewart, Colin L. Kaestner, Klaus H. Lydon, John P. DeMayo, Francesco J. TI Foxa2 Is Essential for Mouse Endometrial Gland Development and Fertility SO BIOLOGY OF REPRODUCTION LA English DT Article DE decidua; female reproductive tract; Foxa2; gland development; implantation; uterus ID LEUKEMIA INHIBITORY FACTOR; FEMALE REPRODUCTIVE-TRACT; FORKHEAD BOX A1; TRANSCRIPTION FACTORS; BETA-CATENIN; PROGESTERONE-RECEPTOR; BLASTOCYST IMPLANTATION; EMBRYO IMPLANTATION; LUNG MORPHOGENESIS; UTERINE GLANDS AB During embryonic development, Foxa2 is required for the formation of the node and notochord, and ablation of this gene results in defects in gastrulation, neural tube patterning, and gut morphogenesis. Foxa2 has been shown to be expressed specifically in the glandular epithelium of the murine uterus. To study the uterine function of Foxa2, this gene was conditionally ablated in the mouse uterus by crossing mice with floxed Foxa2 alleles, Foxa2(IoxP/IoxP), with the Pgr(cre) mouse model. Pgr(cre/+) Foxa2(IoxP/IoxP) mice showed significantly reduced fertility. Analysis of the uterus on Day 5.5 of pregnancy showed disrupted blastocyst implantation. Pgr(cre/+) Foxa2(IoxP/IoxP) mice also showed a severe impairment of the uterus to respond to the artificial induction of the decidual response. Morphological examination of the uteri of these mice showed a severe reduction in the number of endometrial glands. The loss of endometrial glands resulted in the reduction of leukemia inhibitory factor (Lif) expression. The lack of a decidual response could be partially rescued by an intrauterine injection of LIF before the initiation of the decidual response. This analysis demonstrates that Foxa2 regulates endometrial gland development and that mice with a loss of endometrial glands cannot support implantation in part due to the loss of LIF, which is a requisite for fertility in the mouse. C1 [Jeong, Jae-Wook; Lee, Kevin Y.; Kim, Tae Hoon; Large, Michael J.; Lydon, John P.; DeMayo, Francesco J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Kwak, Inseok] Silla Univ, Dept Biol Sci, Pusan, South Korea. [Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. [Kaestner, Klaus H.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. RP DeMayo, FJ (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM fdemayo@bcm.tmc.edu FU NIH [R01HD057873, R01CA77530, R01HD042311, U54HD0077495] FX Supported by NIH grant R01HD057873 (to J.W.J.), NIH grant R01CA77530 (to J.P.L.), and NIH grants R01HD042311 and U54HD0077495 (to F.J.D.). NR 52 TC 62 Z9 63 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD SEP PY 2010 VL 83 IS 3 BP 396 EP 403 DI 10.1095/biolreprod.109.083154 PG 8 WC Reproductive Biology SC Reproductive Biology GA 641TY UT WOS:000281153800011 PM 20484741 ER PT J AU Kang-Sickel, JCC Stober, VP French, JE Nylander-French, LA AF Kang-Sickel, Juei-Chuan C. Stober, Vandy P. French, John E. Nylander-French, Leena A. TI Exposure to naphthalene induces naphthyl-keratin adducts in human epidermis in vitro and in vivo SO BIOMARKERS LA English DT Article DE Biomarkers; dermal exposure; jet fuel; keratin adducts; naphthalene (CAS 91-20-3) ID POLYCYCLIC AROMATIC-HYDROCARBONS; XENOBIOTIC-METABOLIZING ENZYMES; JP-8 JET FUEL; HUMAN SKIN; DERMAL EXPOSURE; TERMINAL DIFFERENTIATION; GENETIC POLYMORPHISMS; MAINTENANCE WORKERS; URINARY NAPHTHOLS; CYTOCHROMES P450 AB We observed naphthyl-keratin adducts and dose-related metabolic enzyme induction at the mRNA level in reconstructed human epidermis in vitro after exposure to naphthalene. Immunofluorescence detection of 2-naphthyl-keratin-1 adducts confirmed the metabolism of naphthalene and adduction of keratin. We also observed naphthyl-keratin adducts in dermal tape-strip samples collected from naphthalene-exposed workers at levels ranging from 0.004 to 6.104 pmol adduct mu g(-1) keratin. We have demonstrated the ability of the human skin to metabolize naphthalene and to form naphthyl-keratin adducts both in vitro and in vivo. The results indicate the potential use of keratin adducts as biomarkers of dermal exposure. C1 [Kang-Sickel, Juei-Chuan C.; Stober, Vandy P.; Nylander-French, Leena A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [French, John E.] Natl Inst Environm Hlth Sci, Host Susceptibil Branch, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Nylander-French, LA (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Environm Sci & Engn, CB 7431,Rosenau Hall, Chapel Hill, NC 27599 USA. EM leena_french@unc.edu FU US Air Force (Texas Tech University) [1331/0489-01]; National Institute of Environmental Health Sciences [P42ES05948, ES021134]; National Institute for Occupational Safety and Health [T42/CCT422952, T42/008673] FX The authors declare they have no competing financial interests. This work was supported by US Air Force (Texas Tech University subcontract 1331/0489-01), National Institute of Environmental Health Sciences (grant number P42ES05948 and the Division of Intramural Research ES021134) and National Institute for Occupational Safety and Health (grant numbers T42/CCT422952, T42/008673). The authors report no conflicts of interest. NR 50 TC 8 Z9 8 U1 2 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD SEP PY 2010 VL 15 IS 6 BP 488 EP 497 DI 10.3109/1354750X.2010.485700 PG 10 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 639LJ UT WOS:000280976000002 PM 20500019 ER PT J AU Mukherjee, B Ahn, J Gruber, SB Ghosh, M Chatterjee, N AF Mukherjee, Bhramar Ahn, Jaeil Gruber, Stephen B. Ghosh, Malay Chatterjee, Nilanjan TI Case-Control Studies of Gene-Environment Interaction: Bayesian Design and Analysis SO BIOMETRICS LA English DT Article DE Case-only design; Gene-environment independence; Highest posterior density interval; Molecular epidemiology of colorectal cancer; Multinomial-Dirichlet; Posterior odds ID SAMPLE-SIZE DETERMINATION; MATCHED CASE-CONTROL; CASE-ONLY DESIGNS; CONTINGENCY-TABLES; REQUIREMENTS; INDEPENDENCE; POWER; EXPOSURE; MODELS; ERRORS AB P>With increasing frequency, epidemiologic studies are addressing hypotheses regarding gene-environment interaction. In many well-studied candidate genes and for standard dietary and behavioral epidemiologic exposures, there is often substantial prior information available that may be used to analyze current data as well as for designing a new study. In this article, first, we propose a proper full Bayesian approach for analyzing studies of gene-environment interaction. The Bayesian approach provides a natural way to incorporate uncertainties around the assumption of gene-environment independence, often used in such an analysis. We then consider Bayesian sample size determination criteria for both estimation and hypothesis testing regarding the multiplicative gene-environment interaction parameter. We illustrate our proposed methods using data from a large ongoing case-control study of colorectal cancer investigating the interaction of N-acetyl transferase type 2 (NAT2) with smoking and red meat consumption. We use the existing data to elicit a design prior and show how to use this information in allocating cases and controls in planning a future study that investigates the same interaction parameters. The Bayesian design and analysis strategies are compared with their corresponding frequentist counterparts. C1 [Mukherjee, Bhramar; Ahn, Jaeil] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Gruber, Stephen B.] Univ Michigan, Dept Epidemiol Human Genet & Internal Med, Ann Arbor, MI 48109 USA. [Ghosh, Malay] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. [Chatterjee, Nilanjan] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Mukherjee, B (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. EM bhramar@umich.edu FU NSF [DMS 07-06935, SES-063426]; NIH [R03 CA130045-01, R01 CA81488]; National Heart Lung and Blood Institute [R01 HL091172-01]; National Cancer Institute FX The research of Bhramar Mukherjee was partially supported by NSF DMS 07-06935 and NIH grant R03 CA130045-01. The Molecular Epidemiology of Colorectal Cancer Study is supported via NIH grant R01 CA81488. The research of Nilanjan Chatterjee was supported by a Gene-Environment Initiative (GEI) grant from the National Heart Lung and Blood Institute (R01 HL091172-01) and by the Intramural research program of the National Cancer Institute. Malay Ghosh's research was supported in part by NSF grant SES-063426. NR 49 TC 7 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 934 EP 948 DI 10.1111/j.1541-0420.2009.01357.x PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000029 PM 19930190 ER PT J AU Nason, M Follmann, D AF Nason, Martha Follmann, Dean TI Design and Analysis of Crossover Trials for Absorbing Binary Endpoints SO BIOMETRICS LA English DT Article DE Mantel-Haenszel; Mixture model; Time-varying covariates ID PREVENTION; DISEASE AB P>The crossover is a popular and efficient trial design used in the context of patient heterogeneity to assess the effect of treatments that act relatively quickly and whose benefit disappears with discontinuation. Each patient can serve as her own control as within-individual treatment and placebo responses are compared. Conventional wisdom is that these designs are not appropriate for absorbing binary endpoints, such as death or HIV infection. We explore the use of crossover designs in the context of these absorbing binary endpoints and show that they can be more efficient than the standard parallel group design when there is heterogeneity in individuals' risks. We also introduce a new two-period design where first period "survivors" are rerandomized for the second period. This design combines the crossover design with the parallel design and achieves some of the efficiency advantages of the crossover design while ensuring that the second period groups are comparable by randomization. We discuss the validity of the new designs and evaluate both a mixture model and a modified Mantel-Haenszel test for inference. The mixture model assumes no carryover or period effects while the Mantel-Haenszel approach conditions out period effects. Simulations are used to compare the different designs and an example is provided to explore practical issues in implementation. C1 [Nason, Martha; Follmann, Dean] NIAID, Biostat Res Branch, Div Clin Res, Bethesda, MD 20892 USA. RP Nason, M (reprint author), NIAID, Biostat Res Branch, Div Clin Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mnason@niaid.nih.gov; dfollmann@niaid.nih.gov NR 12 TC 13 Z9 13 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 958 EP 965 DI 10.1111/j.1541-0420.2009.01358.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000031 PM 19930189 ER PT J AU Albert, PS Shih, JH AF Albert, Paul S. Shih, Joanna H. TI On Estimating the Relationship between Longitudinal Measurements and Time-to-Event Data Using a Simple Two-Stage Procedure SO BIOMETRICS LA English DT Article DE Informative dropout; Joint model; Regression calibration; Two-stage models ID LIKELIHOOD APPROACH; MODELS AB Ye, Lin, and Taylor (2008, Biometrics 64, 1238-1246) proposed a joint model for longitudinal measurements and time-to-event data in which the longitudinal measurements are modeled with a semiparametric mixed model to allow for the complex patterns in longitudinal biomarker data. They proposed a two-stage regression calibration approach that is simpler to implement than a joint modeling approach. In the first stage of their approach, the mixed model is fit without regard to the time-to-event data. In the second stage, the posterior expectation of an individual's random effects from the mixed-model are included as covariates in a Cox model. Although Ye et al. (2008) acknowledged that their regression calibration approach may cause a bias due to the problem of informative dropout and measurement error, they argued that the bias is small relative to alternative methods. In this article, we show that this bias may be substantial. We show how to alleviate much of this bias with an alternative regression calibration approach that can be applied for both discrete and continuous time-to-event data. Through simulations, the proposed approach is shown to have substantially less bias than the regression calibration approach proposed by Ye et al. (2008). In agreement with the methodology proposed by Ye et al. (2008), an advantage of our proposed approach over joint modeling is that it can be implemented with standard statistical software and does not require complex estimation techniques. C1 [Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Albert, PS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM albertp@mail.nih.gov FU NCI NIH HHS [CA110518] NR 11 TC 8 Z9 8 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD SEP PY 2010 VL 66 IS 3 BP 983 EP 987 DI 10.1111/j.1541-0420.2009.01324.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 651TM UT WOS:000281950000034 PM 20849547 ER PT J AU Chatterjee, N Sinha, S Diver, WR Feigelson, HS AF Chatterjee, Nilanjan Sinha, Samiran Diver, W. Ryan Feigelson, Heather Spencer TI Analysis of cohort studies with multivariate and partially observed disease classification data SO BIOMETRIKA LA English DT Article DE Competing-risk; Etiologic heterogeneity; Influence function; Missing cause of failure; Partial likelihood; Proportional hazard regression; Two-stage model ID COMPETING RISKS MODEL; MISSING CAUSE; FAILURE AB Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort. C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Sinha, Samiran] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Diver, W. Ryan; Feigelson, Heather Spencer] Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. EM chattern@mail.nih.gov; sinha@stat.tamu.edu FU National Cancer Institute, National Institutes of Health, USA FX The research of Dr. Chatterjee, and partially that of Dr. Sinha, was supported by the intramural program of the National Cancer Institute, National Institutes of Health, USA. NR 9 TC 12 Z9 12 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD SEP PY 2010 VL 97 IS 3 BP 683 EP 698 DI 10.1093/biomet/asq036 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 638OK UT WOS:000280904000011 ER PT J AU Ghosh, AK Dawson, ZL Moon, DK Bai, RL Hamel, E AF Ghosh, Arun K. Dawson, Zachary L. Moon, Deuk Kyu Bai, Ruoli Hamel, Ernest TI Synthesis and biological evaluation of new jasplakinolide (jaspamide) analogs SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Jasplakinolide; Actin filament; Natural product; Synthesis; Antitumor activity ID ENANTIOSELECTIVE TOTAL-SYNTHESIS; MARINE SPONGE; F-ACTIN; (+)-JASPLAKINOLIDE JASPAMIDE; NATURAL-PRODUCT; CYCLODEPSIPEPTIDE; POLYMERIZATION; PHALLOIDIN; (-)-DOLICULIDE; CELLS AB Synthesis and biological evaluation of jasplakinolide analogs are described. The synthesis of analogs utilized a diastereoselective syn-aldol reaction and an orthoester Claisen rearrangement as key steps. All synthetic analogs were evaluated for their ability to disrupt the actin cytoskeleton. Compounds 2, 3, and 4 essentially displayed similar activity to jasplakinolide. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Ghosh, Arun K.; Dawson, Zachary L.; Moon, Deuk Kyu] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Dawson, Zachary L.; Moon, Deuk Kyu] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu FU National Institutes of Health FX This research was supported in part by the National Institutes of Health. NR 38 TC 8 Z9 8 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 1 PY 2010 VL 20 IS 17 BP 5104 EP 5107 DI 10.1016/j.bmcl.2010.07.023 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 642UT UT WOS:000281247000026 PM 20678932 ER PT J AU Hu, KN Tycko, R AF Hu, Kan-Nian Tycko, Robert TI What can solid state NMR contribute to our understanding of protein folding? SO BIOPHYSICAL CHEMISTRY LA English DT Review DE Protein folding; Freeze-trapping; Chemical denaturation; Conformational ensembles; Solid state NMR; Villin; HP35 ID ANGLE-SPINNING NMR; NUCLEAR-MAGNETIC-RESONANCE; VILLIN HEADPIECE SUBDOMAIN; X-RAY-SCATTERING; RESIDUAL DIPOLAR COUPLINGS; POLYPROLINE-II HELIX; MOLECULAR TORSIONAL ANGLE; 3-HELIX BUNDLE PROTEINS; BETA-AMYLOID PEPTIDE; PROTON-ENHANCED NMR AB Complete understanding of the folding process that connects a structurally disordered state of a protein to an ordered, biochemically functional state requires detailed characterization of intermediate structural states with high resolution and site specificity. While the intrinsically inhomogeneous and dynamic nature of unfolded and partially folded states limits the efficacy of traditional X-ray diffraction and solution NMR in structural studies, solid state NMR methods applied to frozen solutions can circumvent the complications due to molecular motions and conformational exchange encountered in unfolded and partially folded states. Moreover, solid state NMR methods can provide both qualitative and quantitative structural information at the site-specific level, even in the presence of structural inhomogeneity. This article reviews relevant solid state NMR methods and their initial applications to protein folding studies. Using either chemical denaturation to prepare unfolded states at equilibrium or a rapid freezing apparatus to trap non-equilibrium, transient structural states on a sub-millisecond time scale, recent results demonstrate that solid state NMR can contribute essential information about folding processes that is not available from more familiar biophysical methods. Published by Elsevier B.V. C1 [Hu, Kan-Nian; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov FU Intramural NIH HHS [ZIA DK029063-03] NR 128 TC 14 Z9 14 U1 4 U2 43 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD SEP PY 2010 VL 151 IS 1-2 BP 10 EP 21 DI 10.1016/j.bpc.2010.05.009 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 633NO UT WOS:000280510000002 PM 20542371 ER PT J AU Herring, AH Reddy, UM AF Herring, A. H. Reddy, U. M. TI Recurrence risk of stillbirth in the second pregnancy SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Editorial Material ID SUBSEQUENT C1 [Herring, A. H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Herring, A. H.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA. [Reddy, U. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA. RP Herring, AH (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. EM amy_herring@unc.edu FU NICHD NIH HHS [R24 HD050924] NR 6 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD SEP PY 2010 VL 117 IS 10 BP 1173 EP 1174 DI 10.1111/j.1471-0528.2010.02655.x PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 639QJ UT WOS:000280989000001 PM 20722642 ER PT J AU Zhang, X Mumford, SL Cnattingius, S Schisterman, EF Kramer, MS AF Zhang, X. Mumford, S. L. Cnattingius, S. Schisterman, E. F. Kramer, M. S. TI Reduced birthweight in short or primiparous mothers: physiological or pathological? SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article DE Birthweight; directed acyclic graph; effect decomposition; gestational age; maternal height; parity perinatal mortality ID MARGINAL STRUCTURAL MODELS; FETAL-GROWTH; STANDARDS; PREGNANCIES; DEATH; EPIDEMIOLOGY; DETERMINANTS; RETARDATION; ASSOCIATION; MORTALITY AB Objective Customisation of birthweight-for-gestational-age standards for maternal characteristics assumes that variation in birth weight as a result of those characteristics is physiological, rather than pathological. Maternal height and parity are among the characteristics widely assumed to be physiological. Our objective was to test that assumption by using an association with perinatal mortality as evidence of a pathological effect. Design Population-based cohort study. Setting Sweden. Population A total of 952 630 singletons born at 28 weeks of gestation in the period 1992-2001. Methods We compared perinatal mortality among mothers of short stature (< 160 cm) versus those of normal height (160 cm), and primiparous versus multiparous mothers, using an internal reference of estimated fetal weight for gestational age. The total effects of maternal height and parity were estimated, as well as the effects of height and parity independent of birthweight (controlled direct effects). All analyses were based on fetuses at risk, using marginal structural Cox models for the estimation of total and controlled direct effects. Main outcome measures Perinatal mortality, stillbirth, and early neonatal mortality. Results The estimated total effect (HR; 95% CI) of short stature on perinatal death among short mothers was 1.2 (95% CI 1.1-1.3) compared with women of normal height; the effect of short stature independent of birthweight (controlled direct effect) was 0.8 (95% CI 0.6-1.0) among small-for-gestational-age (SGA) births, but 1.1 (95% CI 1.0-1.3) among non-SGA births. Similar results were observed for primiparous mothers. Conclusions The effect of maternal short stature or primiparity on perinatal mortality is partly mediated through SGA birth. Thus, birthweight differences resulting from these maternal characteristics appear not only to be physiological, but also to have an important pathological component. C1 [Zhang, X.; Kramer, M. S.] McGill Univ, Dept Pediat, Fac Med, Montreal, PQ H3A 2T5, Canada. [Mumford, S. L.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. [Cnattingius, S.] Karolinska Inst, Clin Epidemiol Unit, Dept Med, Stockholm, Sweden. [Kramer, M. S.] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. RP Kramer, MS (reprint author), Montreal Childrens Hosp, 2300 Tupper St Les Tourelles, Montreal, PQ H3H 1P3, Canada. EM michael.kramer@mcgill.ca OI Schisterman, Enrique/0000-0003-3757-641X FU Canadian Institutes of Health Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Supported by a grant from the Canadian Institutes of Health Research. EFS and SLM are supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 40 TC 14 Z9 14 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD SEP PY 2010 VL 117 IS 10 BP 1248 EP 1254 DI 10.1111/j.1471-0528.2010.02642.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 639QJ UT WOS:000280989000011 PM 20618317 ER PT J AU Pulanic, D Cowen, EW Baird, K Bishop, MR Pavletic, SZ AF Pulanic, D. Cowen, E. W. Baird, K. Bishop, M. R. Pavletic, S. Z. TI Development of severe sclerotic chronic GVHD during treatment with dasatinib SO BONE MARROW TRANSPLANTATION LA English DT Letter ID VERSUS-HOST-DISEASE; IMATINIB MESYLATE; EFFICACY; FIBROSIS C1 [Pulanic, D.; Bishop, M. R.; Pavletic, S. Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cowen, E. W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Baird, K.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pulanic, D (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pulanicd@mail.nih.gov FU Intramural NIH HHS NR 10 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2010 VL 45 IS 9 BP 1469 EP 1470 DI 10.1038/bmt.2009.368 PG 2 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 648CS UT WOS:000281668600014 PM 20062096 ER PT J AU Costigan, M Belfer, I Griffin, RS Dai, F Barrett, LB Coppola, G Wu, TX Kiselycznyk, C Poddar, M Lu, Y Diatchenko, L Smith, S Cobos, EJ Zaykin, D Allchorne, A Shen, PH Nikolajsen, L Karppinen, J Mannikko, M Kelempisioti, A Goldman, D Maixner, W Geschwind, DH Max, MB Seltzer, Z Woolf, CJ AF Costigan, Michael Belfer, Inna Griffin, Robert S. Dai, Feng Barrett, Lee B. Coppola, Giovanni Wu, Tianxia Kiselycznyk, Carly Poddar, Minakshi Lu, Yan Diatchenko, Luda Smith, Shad Cobos, Enrique J. Zaykin, Dmitri Allchorne, Andrew Shen, Pei-Hong Nikolajsen, Lone Karppinen, Jaro Mannikko, Minna Kelempisioti, Anthi Goldman, David Maixner, William Geschwind, Daniel H. max, Mitchell B. Seltzer, Ze'ev woolf, Clifford J. TI Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1 SO BRAIN LA English DT Article DE neuropathic pain; phenotype; molecular genetics; axonal injury; gene expression ID DORSAL-ROOT GANGLION; MAINE LUMBAR SPINE; GATED POTASSIUM CHANNELS; PERIPHERAL-NERVE INJURY; NONSURGICAL MANAGEMENT; NEUROPATHIC PAIN; SCIATICA SECONDARY; DISC HERNIATION; ALPHA-SUBUNITS; SODIUM-CHANNEL AB Not all patients with nerve injury develop neuropathic pain. The extent of nerve damage and age at the time of injury are two of the few risk factors identified to date. In addition, preclinical studies show that neuropathic pain variance is heritable. To define such factors further, we performed a large-scale gene profiling experiment which plotted global expression changes in the rat dorsal root ganglion in three peripheral neuropathic pain models. This resulted in the discovery that the potassium channel alpha subunit KCNS1, involved in neuronal excitability, is constitutively expressed in sensory neurons and markedly downregulated following nerve injury. KCNS1 was then characterized by an unbiased network analysis as a putative pain gene, a result confirmed by single nucleotide polymorphism association studies in humans. A common amino acid changing allele, the 'valine risk allele', was significantly associated with higher pain scores in five of six independent patient cohorts assayed (total of 1359 subjects). Risk allele prevalence is high, with 18-22% of the population homozygous, and an additional 50% heterozygous. At lower levels of nerve damage (lumbar back pain with disc herniation) association with greater pain outcome in homozygote patients is P = 0.003, increasing to P = 0.0001 for higher levels of nerve injury (limb amputation). The combined P-value for pain association in all six cohorts tested is 1.14 E-08. The risk profile of this marker is additive: two copies confer the most, one intermediate and none the least risk. Relative degrees of enhanced risk vary between cohorts, but for patients with lumbar back pain, they range between 2- and 3-fold. Although work still remains to define the potential role of this protein in the pathogenic process, here we present the KCNS1 allele rs734784 as one of the first prognostic indicators of chronic pain risk. Screening for this allele could help define those individuals prone to a transition to persistent pain, and thus requiring therapeutic strategies or lifestyle changes that minimize nerve injury. C1 [Belfer, Inna; Dai, Feng; Poddar, Minakshi; max, Mitchell B.] Univ Pittsburgh, Dept Anesthesiol, Mol Epidemiol Pain Program, Pittsburgh, PA 15261 USA. [Costigan, Michael; Griffin, Robert S.; Barrett, Lee B.; Cobos, Enrique J.; Allchorne, Andrew; woolf, Clifford J.] Childrens Hosp, FM Kirby Neurobiol Ctr, Boston, MA 02115 USA. [Costigan, Michael; Griffin, Robert S.; Barrett, Lee B.; Cobos, Enrique J.; Allchorne, Andrew; woolf, Clifford J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Coppola, Giovanni; Geschwind, Daniel H.] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Wu, Tianxia] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. [Kiselycznyk, Carly; Shen, Pei-Hong; Goldman, David] NIAAA, Neurogenet Lab, NIH, Rockville, MD 20892 USA. [Lu, Yan; Seltzer, Ze'ev] Univ Toronto, Comparat Pain Phen & Genom Lab, Ctr Study Pain, Fac Dent, Toronto, ON M5G 1G6, Canada. [Lu, Yan; Seltzer, Ze'ev] Univ Toronto, Comparat Pain Phen & Genom Lab, Ctr Study Pain, Fac Med, Toronto, ON M5G 1G6, Canada. [Diatchenko, Luda; Smith, Shad; Maixner, William] Univ N Carolina, Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA. [Zaykin, Dmitri] NIEHS, Durham, NC 27709 USA. [Nikolajsen, Lone] Aarhus Univ Hosp, Danish Pain Res Ctr, DK-8000 Aarhus, Denmark. [Karppinen, Jaro; Mannikko, Minna; Kelempisioti, Anthi] Univ Oulu, Dept Med Biochem & Mol Biol, Oulu 90014, Finland. RP Belfer, I (reprint author), Univ Pittsburgh, Dept Anesthesiol, Mol Epidemiol Pain Program, 3550 Terrace St,Scaife Hall A-1310, Pittsburgh, PA 15261 USA. EM belferi@upmc.edu RI Cobos, Enrique/E-9077-2016; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU National Institutes of Health (NIH), National Institute of Environmental Health Sciences; Spanish Ministry for Science and Innovation; NIH [R01 NS038253, NS058870]; Canada Research Chair Programme FX Intramural Research Programme of the National Institutes of Health (NIH), National Institute of Environmental Health Sciences to D.Z.; Spanish Ministry for Science and Innovation/Fulbright programme to E.J.C.; NIH support R01 NS038253 and NS058870 (C.J.W.); Canada Research Chair Programme to Z.S. NR 43 TC 113 Z9 114 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD SEP PY 2010 VL 133 BP 2519 EP 2527 DI 10.1093/brain/awq195 PN 9 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 646HE UT WOS:000281529000005 PM 20724292 ER PT J AU Singh, A Mishra, A Hewitt, S Sharma, KC Saxena, S AF Singh, A. Mishra, A. Hewitt, S. Sharma, Chand K. Saxena, Sunita TI Identification of immunohistochemical markers that differentiate fibroblastic meningioma from schwannoma: a tissue microarray based approach SO BRAIN PATHOLOGY LA English DT Meeting Abstract CT 17th International Congress of Neuropathology (ICN 2010) CY SEP 11-15, 2010 CL Salzburg, AUSTRIA C1 [Singh, A.; Mishra, A.; Saxena, Sunita] Inst Pathol ICMR, New Delhi, India. [Hewitt, S.] NCI, NIH, Bethesda, MD 20892 USA. [Sharma, Chand K.] VMMC, Dept Neurosurg, New Delhi, India. [Sharma, Chand K.] Safdarjang Hosp, New Delhi, India. 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 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2010 VL 20 SU 1 BP 67 EP 67 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 649TZ UT WOS:000281798100238 ER PT J AU Ruiz-Narvaez, EA Rosenberg, L Rotimi, CN Cupples, LA Boggs, DA Adeyemo, A Cozier, YC Adams-Campbell, LL Palmer, JR AF Ruiz-Narvaez, Edward A. Rosenberg, Lynn Rotimi, Charles N. Cupples, L. Adrienne Boggs, Deborah A. Adeyemo, Adebowale Cozier, Yvette C. Adams-Campbell, Lucile L. Palmer, Julie R. TI Genetic variants on chromosome 5p12 are associated with risk of breast cancer in African American women: the Black Women's Health Study SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Chromosome 5p12; African Americans; SNP ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON VARIANTS; POPULATIONS; ADMIXTURE; ALLELES; LINKAGE AB Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case-control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women's Health Study. We used the Cochran-Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant. C1 [Ruiz-Narvaez, Edward A.; Rosenberg, Lynn; Boggs, Deborah A.; Cozier, Yvette C.; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Ruiz-Narvaez, Edward A.; Rosenberg, Lynn; Cozier, Yvette C.; Palmer, Julie R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Rotimi, Charles N.; Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD USA. [Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Adams-Campbell, Lucile L.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Palmer, JR (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM jpalmer@bu.edu OI Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X; Cupples, L. Adrienne/0000-0003-0273-7965; Cozier, Yvette/0000-0003-0625-7256; Adeyemo, Adebowale/0000-0002-3105-3231 FU National Cancer Institute, Division of Cancer Control and Population Science [R01CA058420, R01CA098663]; National Center for Research Resources [U54 RR020278] FX We thank the Black Women's Health Study participants for their continuing participation in this research effort. This work was supported by grants R01CA058420 and R01CA098663 from the National Cancer Institute, Division of Cancer Control and Population Science (http://www.cancercontrol.cancer.gov). The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources (http://www.broadinstitute.org/sections/science/projects/broad/ncrr-cent er-genotyping-analysis). NR 21 TC 22 Z9 22 U1 0 U2 2 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 SEP PY 2010 VL 123 IS 2 BP 525 EP 530 DI 10.1007/s10549-010-0775-5 PG 6 WC Oncology SC Oncology GA 637HK UT WOS:000280807900022 PM 20140701 ER PT J AU Maurex, L Lekander, M Nilsonne, A Andersson, EE Asberg, M Ohman, A AF Maurex, Liselotte Lekander, Mats Nilsonne, Asa Andersson, Eva E. Asberg, Marie Ohman, Arne TI Social problem solving, autobiographical memory, trauma, and depression in women with borderline personality disorder and a history of suicide attempts SO BRITISH JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID PSYCHOPATHOLOGICAL RATING-SCALE; DELIBERATE SELF-HARM; DSM-III-R; MAJOR DEPRESSION; NONDEPRESSED PATIENTS; DECISION-MAKING; SPECIFICITY; RUMINATION; MOOD; PARASUICIDE AB Objectives. The primary aim of this study was to compare the retrieval of autobiographical memory and the social problem-solving performance of individuals with borderline personality disorder (BPD) and a history of suicide attempts, with and without concurrent diagnoses of depression and/or post-traumatic stress disorder (PTSD), to that of controls. Additionally, the relationships between autobiographical memory, social problem-solving skills, and various clinical characteristics were examined in the BPD group. Design. Individuals with BPD who had made at least two suicide attempts were compared to controls with regard to specificity of autobiographical memory and social problem-solving skills. Autobiographical memory specificity and social problem-solving skills were further studied in the BPD group by comparing depressed participants to non-depressed participants; and autobiographical memory specificity was also studied by comparing participants with and without PTSD. Method. A total of 47 women with a diagnosis of BPD and 30 controls completed the Autobiographical Memory Test, assessing memory specificity, and the means-end problem solving-procedure, measuring social problem-solving skills. The prevalence of suicidal/self-injurious behaviour, and the exposure to violence, was also assessed in the BPD group. Results. Compared to controls, participants with BPD showed reduced specificity of autobiographical memory, irrespective of either concurrent depression, previous depression, or concurrent PTSD. The depressed BPD group displayed poor problem-solving skills. Further, an association between unspecific memory and poor problem-solving was displayed in the BPD group. Conclusion. Our results confirmed that reduced specificity of autobiographical memory is an important characteristic of BPD individuals with a history of suicide attempt, independent of depression, or PTSD. Reduced specificity of autobiographical memory was further related to poor social problem-solving capacity in the BPD group. C1 [Maurex, Liselotte; Lekander, Mats; Nilsonne, Asa; Ohman, Arne] Karolinska Inst, Psychol Sect, Dept Clin Neurosci, S-17177 Stockholm, Sweden. [Lekander, Mats] Karolinska Inst, Osher Ctr Integrat Med, S-17177 Stockholm, Sweden. [Andersson, Eva E.] Karolinska Inst, Sect Psychiat, Dept Clin Neurosci, S-17177 Stockholm, Sweden. [Asberg, Marie] Karolinska Inst, Dept Clin Sci, S-17177 Stockholm, Sweden. [Ohman, Arne] Stockholm Brain Inst, Stockholm, Sweden. [Ohman, Arne] Univ Florida, NIMH Ctr Res Emot & Attent, Gainesville, FL USA. RP Maurex, L (reprint author), Karolinska Inst, Psychol Sect, Dept Clin Neurosci, S-17177 Stockholm, Sweden. EM Liselotte.Maurex@ki.se NR 50 TC 19 Z9 19 U1 2 U2 18 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER LE1 7DR, LEICS, ENGLAND SN 0144-6657 J9 BRIT J CLIN PSYCHOL JI Br. J. Clin. Psychol. PD SEP PY 2010 VL 49 BP 327 EP 342 DI 10.1348/014466509X454831 PN 3 PG 16 WC Psychology, Clinical SC Psychology GA 651XI UT WOS:000281960500004 PM 19555523 ER PT J AU Li, Y Seifert, MF Lim, SY Salem, N Watkins, BA AF Li, Yong Seifert, Mark F. Lim, Sun-Young Salem, Norman, Jr. Watkins, Bruce A. TI Bone mineral content is positively correlated to n-3 fatty acids in the femur of growing rats SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE n-3 Fatty acids; DHA; Docosapentaenoic acid n-6; Rat femur ID CONJUGATED LINOLEIC-ACID; DOCOSAHEXAENOIC ACID; TOOTH MOVEMENT; DIETARY RATIO; DENSITY; CALCIUM; ALTERS; SUPPLEMENTATION; PHOSPHOLIPIDS; METABOLISM C1 [Li, Yong; Watkins, Bruce A.] Purdue Univ, Lipid Chem & Mol Biol Lab, W Lafayette, IN 47907 USA. [Seifert, Mark F.; Watkins, Bruce A.] Indiana Univ Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. [Lim, Sun-Young] Korea Maritime Univ, Div Marine Environm & Biosci, Pusan 606791, South Korea. [Salem, Norman, Jr.] NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. RP Watkins, BA (reprint author), Purdue Univ, Lipid Chem & Mol Biol Lab, 745 Agr Mall Dr, W Lafayette, IN 47907 USA. EM baw@purdue.edu FU National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The present study was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. NR 30 TC 32 Z9 32 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD SEP PY 2010 VL 104 IS 5 BP 674 EP 685 DI 10.1017/S0007114510001133 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 650XP UT WOS:000281887900008 PM 20420751 ER PT J AU Song, XY Sun, LQ Mu, XY Dinse, GE AF Song, Xinyuan Sun, Liuquan Mu, Xiaoyun Dinse, Gregg E. TI Additive hazards regression with censoring indicators missing at random SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Additive hazards model; censoring; kernel smoother; missing at random; weighted estimating equation ID PRODUCT-LIMIT ESTIMATORS; COMPETING RISKS MODEL; EFFICIENT ESTIMATION; SURVIVAL FUNCTION; FAILURE; COEFFICIENTS; INFORMATION; KERNELS AB In this article, the authors consider a semiparametric additive hazards regression model for right-censored data that allows some censoring indicators to be missing at random. They develop a class of estimating equations and use an inverse probability weighted approach to estimate the regression parameters. Nonparametric smoothing techniques are employed to estimate the probability of non-missingness and the conditional probability of an uncensored observation. The asymptotic properties of the resulting estimators are derived. Simulation studies show that the proposed estimators perform well. They motivate and illustrate their methods with data from a brain cancer clinical trial. The Canadian Journal of Statistics 38: 333 351; 2010 (C) 2010 Statistical Society of Canada C1 [Song, Xinyuan] Dept Stat, Shatin, Hong Kong, Peoples R China. [Sun, Liuquan; Mu, Xiaoyun] Chinese Acad Sci, Acad Math & Syst Sci, Inst Appl Math, Beijing 100190, Peoples R China. [Dinse, Gregg E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Song, XY (reprint author), Dept Stat, Shatin, Hong Kong, Peoples R China. EM xysong@sta.cuhk.edu.hk FU Research Grant Council of the Hong Kong Special Administration Region; National Natural Science Foundation of China; National Basic Research Program of China (973 Program); Key Laboratory of RCSDS, CAS; NIH, National Institute of Environmental Health Sciences FX The authors would like to thank the Editor (Paul Gustafson), the Associate Editor, two reviewers and Shyamal Peddada for their constructive and insightful comments and suggestions that greatly improved the article. Xinyuan Song's research was fully supported by two grants from the Research Grant Council of the Hong Kong Special Administration Region. Liuquan Sun's research was fully supported by the National Natural Science Foundation of China Grants, the National Basic Research Program of China (973 Program) and Key Laboratory of RCSDS, CAS. Gregg Dinse's research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 29 TC 6 Z9 7 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 2010 VL 38 IS 3 BP 333 EP 351 PG 19 WC Statistics & Probability SC Mathematics GA 642BW UT WOS:000281179300002 PM 21197117 ER PT J AU Schlom, J AF Schlom, Jeffrey TI The MUC1-C oncoprotein as a target in hematologic malignancies SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE MUC1; CML; Bcr-Abl; myeloid blasts; differentiation; self-renewal; targeted therapies; peptide drugs ID THERAPY C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 12 TC 2 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD SEP 1 PY 2010 VL 10 IS 5 DI 10.4161/cbt.10.5.13150 PG 3 WC Oncology SC Oncology GA 651EZ UT WOS:000281909400012 PM 20716962 ER PT J AU Ruder, EH Hartman, TJ Rovine, MJ Dorgan, JF AF Ruder, Elizabeth H. Hartman, Terryl J. Rovine, Michael J. Dorgan, Joanne F. TI Birth characteristics and age at menarche: results from the dietary intervention study in children (DISC) SO CANCER CAUSES & CONTROL LA English DT Article DE Menarche; Birth weight; Birth length; Gestational age; Puberty; Breast cancer ID BREAST-CANCER RISK; UNITED-STATES; BODY-SIZE; OPPOSING INFLUENCES; PREGNANCY ESTRIOL; POSTNATAL-GROWTH; CHILDHOOD GROWTH; HORMONE-LEVELS; EARLY PUBERTY; GIRLS AB Objective To examine whether birth weight, birth length, and gestational age are individually associated with age at menarche. Methods Analyses were conducted using data from n = 278 female participants in the Dietary Intervention Study in Children (DISC). Age at menarche was prospectively collected as part of the original DISC investigation. DISC participants self-reported birth weight, birth length, and gestational age with assistance from their mothers and other records as part of the DISC06 Follow-up Study at ages 25-29. Linear regression was used to estimate the association of birth characteristics and age at menarche. Results Birth weight was positively associated with age at menarche (p <= 0.01) in multiple regression analyses after controlling for BMI-for-age percentile, race and DISC treatment group. No statistically significant relationships were detected between either length or gestational age and age at menarche. Conclusions Higher birth weight may be associated with a modest delay in age at menarche. C1 [Ruder, Elizabeth H.] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Rovine, Michael J.] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. [Dorgan, Joanne F.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Ruder, EH (reprint author), NCI, Canc Prevent Fellowship Program, NIH, 6120 Execut Blvd,Suite 320,MSC 7236, Bethesda, MD 20892 USA. EM rudereh@mail.nih.gov FU National Cancer Institute [R01CA104670] FX The work described was supported by Grant Number R01CA104670 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 48 TC 7 Z9 7 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2010 VL 21 IS 9 BP 1379 EP 1386 DI 10.1007/s10552-010-9565-y PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 638NQ UT WOS:000280902000003 PM 20495859 ER PT J AU Carsin, AE Drummond, FJ Black, A van Leeuwen, PJ Sharp, L Murray, LJ Connolly, D Egevad, L Boniol, M Autier, P Comber, H Gavin, A AF Carsin, A-E. Drummond, F. J. Black, A. van Leeuwen, P. J. Sharp, L. Murray, L. J. Connolly, D. Egevad, L. Boniol, M. Autier, P. Comber, H. Gavin, A. TI Impact of PSA testing and prostatic biopsy on cancer incidence and mortality: comparative study between the Republic of Ireland and Northern Ireland SO CANCER CAUSES & CONTROL LA English DT Article DE Prostate cancer; Trends; PSA tests; Incidence; Mortality ID INTERPRETING TRENDS; SURVEILLANCE SERIES; UNITED-STATES; THERAPY; RATES; RISK; MEN; GUIDELINES; CARCINOMA; COUNTRIES AB Objectives To investigate the impact of different PSA testing policies and health-care systems on prostate cancer incidence and mortality in two countries with similar populations, the Republic of Ireland (RoI) and Northern Ireland (NI). Methods Population-level data on PSA tests, prostate biopsies and prostate cancer cases 1993-2005 and prostate cancer deaths 1979-2006 were compiled. Annual percentage change (APC) was estimated by join-point regression. Results Prostate cancer rates were similar in both areas in 1994 but increased rapidly in RoI compared to NI. The PSA testing rate increased sharply in RoI (APC = +23.3%), and to a lesser degree in NI (APC = +9.7%) to reach 412 and 177 tests per 1,000 men in 2004, respectively. Prostatic biopsy rates rose in both countries, but were twofold higher in RoI. Cancer incidence rates rose significantly, mirroring biopsy trends, in both countries reaching 440 per 100,000 men in RoI in 2004 compared to 294 in NI. Median age at diagnosis was lower in RoI (71 years) compared to NI (73 years) (p < 0.01) and decreased significantly over time in both countries. Mortality rates declined from 1995 in both countries (APC = -1.5% in RoI, -1.3% in NI) at a time when PSA testing was not widespread. Conclusions Prostatic biopsy rates, rather than PSA testing per se, were the main driver of prostate cancer incidence. Because mortality decreases started before screening became widespread in RoI, and mortality remained low in NI, PSA testing is unlikely to be the explanation for declining mortality. C1 [Carsin, A-E.; Drummond, F. J.; Sharp, L.; Comber, H.] Natl Canc Registry Ireland, Cork, Ireland. [Black, A.] NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [van Leeuwen, P. J.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands. [Murray, L. J.] Queens Univ Belfast, Canc Epidemiol & Prevent Res Grp, Belfast, Antrim, North Ireland. [Connolly, D.] Belfast City Hosp, Dept Urol, Belfast BT9 7AD, Antrim, North Ireland. [Egevad, L.; Boniol, M.; Autier, P.] Int Agcy Res Canc, F-69372 Lyon, France. [Gavin, A.] Queens Univ Belfast, No Ireland Canc Registry, Belfast, Antrim, North Ireland. RP Carsin, AE (reprint author), Natl Canc Registry Ireland, Bldg 6800,Cork Airport Business Pk,Kinsale Rd, Cork, Ireland. EM acarsin@creal.cat RI Boniol, Mathieu/F-9623-2011; Autier, Philippe/A-4402-2014 OI Boniol, Mathieu/0000-0003-1052-5604; Autier, Philippe/0000-0003-1538-5321 FU Public Health Agency Northern Ireland; Department of Health and Children (Republic of Ireland); Northern Ireland Research & Development Office and the Health Research Board (Dublin) [NS/2004/20] FX The Northern Ireland Cancer Registry is funded by the Public Health Agency Northern Ireland, and the National Cancer Registry of Ireland is funded by the Department of Health and Children (Republic of Ireland). Some aspects of the data collection for this study were funded by a grant from the Northern Ireland Research & Development Office and the Health Research Board (Dublin) [grant number NS/2004/20]. The study funders had no role in the study design, the collection, analysis and interpretation of the data. All authors were independent from the funding source. NR 38 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 2010 VL 21 IS 9 BP 1523 EP 1531 DI 10.1007/s10552-010-9581-y PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 638NQ UT WOS:000280902000019 PM 20514514 ER PT J AU Fox, E Maris, JM Cohn, SL Goodspeed, W Goodwin, A Kromplewski, M Medina, D Xiong, H Krivoshik, A Widemann, B Adamson, PC Balis, FM AF Fox, Elizabeth Maris, John M. Cohn, Susan L. Goodspeed, Wendy Goodwin, Anne Kromplewski, Marie Medina, Diane Xiong, Hao Krivoshik, Andrew Widemann, Brigitte Adamson, Peter C. Balis, Frank M. TI Pharmacokinetics of orally administered ABT-751 in children with neuroblastoma and other solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Pharmacokinetics; Tubulin binding agent; Neuroblastoma ID BIOAVAILABLE TUBULIN INHIBITOR; PEDIATRIC-PATIENTS; CELL-LINES; PHASE-1; BINDING; AGENT; E7010 AB To describe the pharmacokinetics of orally administered ABT-751 and its conjugated metabolites in children with neuroblastoma and other solid tumors and to relate pharmacokinetic parameters to toxicity and therapeutic outcomes. Patients (median age, 11 years) with neuroblastoma (n = 37) or other solid tumors (n = 25) had pharmacokinetic sampling after the first dose of ABT-751 (75-250 mg/m(2)/day) on a 7-day or 21-day schedule. ABT-751 and its glucuronide and sulfate metabolites were quantified with an HPLC/MS/MS assay. Pharmacokinetic parameters were derived with non-compartmental methods. The relative bioavailability of more water soluble capsule and suspension formulations was assessed. ABT-751 peaked in plasma at 2 h and declined monoexponentially with a t (1/2) of 5.1 h. The apparent clearance was 33 ml/min/m(2) and was age-independent. The AUC(0-a) increased in proportion to the dose, and at 200 mg/m(2) the median AUC(0-a) was 91 mcg h/ml and the C (ave) was 3.9 mcg/ml. Inter-and intra-patient variability was low. The metabolites were detected in plasma 30 min post-dose and peaked 3-5 h after the dose. The glucuronide:sulfate molar AUC(0-a) ratio was 0.57. Less than 1% of the dose was excreted in urine as parent drug; 13% of the dose was excreted as sulfate metabolite and 10% as glucuronide metabolite. The relative bioavailability of the water soluble capsule and suspension formulations was 105 and 93%, respectively. AUC(0-a) was higher in patients experiencing dose-limiting toxicity. Oral ABT-751 pharmacokinetics was dose-proportional and age-independent with minimal intra- and inter-patient variability in children. C1 [Fox, Elizabeth; Goodspeed, Wendy; Goodwin, Anne; Widemann, Brigitte; Balis, Frank M.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Maris, John M.; Kromplewski, Marie; Adamson, Peter C.; Balis, Frank M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA. [Maris, John M.; Kromplewski, Marie; Adamson, Peter C.; Balis, Frank M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Cohn, Susan L.] Univ Chicago, Chicago, IL 60637 USA. [Medina, Diane; Xiong, Hao; Krivoshik, Andrew] Abbott Labs, Abbott Pk, IL 60064 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10,Rm 1-5750, Bethesda, MD 20892 USA. EM foxb@mail.nih.gov OI Cohn, Susan/0000-0001-5749-7650 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research.; Abbott Laboratories FX This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. Additional funding to Children's Hospital of Philadelphia and Children's Memorial Hospital was provided by Abbott Laboratories. NR 10 TC 13 Z9 13 U1 1 U2 2 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 SEP PY 2010 VL 66 IS 4 BP 737 EP 743 DI 10.1007/s00280-009-1218-z PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 627TP UT WOS:000280066100013 PM 20044751 ER PT J AU Fletcher, O Johnson, N Silva, ID Orr, N Ashworth, A Nevanlinna, H Heikkinen, T Aittomaki, K Blomqvist, C Burwinkel, B Bartram, CR Meindl, A Schmutzler, RK Cox, A Brock, I Elliott, G Reed, MWR Southey, MC Smith, L Spurdle, AB Hopper, JL Couch, FJ Olson, JE Wang, XS Fredericksen, Z Schurmann, P Waltes, R Bremer, M Dork, T Devilee, P van Asperen, CJ Tollenaar, RAEM Seynaeve, C Hall, P Czene, K Humphreys, K Liu, JJ Ahmed, S Dunning, AM Maranian, M Pharoah, PDP Chenevix-Trench, G Beesley, J Bogdanova, NV Antonenkova, NN Zalutsky, IV Anton-Culver, H Ziogas, A Brauch, H Ko, YD Hamann, U Fasching, PA Strick, R Ekici, AB Beckmann, MW Giles, GG Severi, G Baglietto, L English, DR Milne, RL Benitez, J Arias, JI Pita, G Nordestgaard, BG Bojesen, SE Flyger, H Kang, D Yoo, KY Noh, DY Mannermaa, A Kataja, V Kosma, VM Garcia-Closas, M Chanock, S Lissowska, J Brinton, LA Chang-Claude, J Wang-Gohrke, S Broeks, A Schmidt, MK van Leeuwen, FE Van't Veer, LJ Margolin, S Lindblom, A Humphreys, MK Morrison, J Platte, R Easton, DF Peto, J AF Fletcher, Olivia Johnson, Nichola Silva, Isabel dos Santos Orr, Nick Ashworth, Alan Nevanlinna, Heli Heikkinen, Tuomas Aittomaki, Kristiina Blomqvist, Carl Burwinkel, Barbara Bartram, Claus R. Meindl, Alfons Schmutzler, Rita K. Cox, Angela Brock, Ian Elliott, Graeme Reed, Malcolm W. R. Southey, Melissa C. Smith, Letitia Spurdle, Amanda B. Hopper, John L. Couch, Fergus J. Olson, Janet E. Wang, Xianshu Fredericksen, Zachary Schuermann, Peter Waltes, Regina Bremer, Michael Doerk, Thilo Devilee, Peter van Asperen, Christie J. Tollenaar, Rob A. E. M. Seynaeve, Caroline Hall, Per Czene, Kamila Humphreys, Keith Liu, Jianjun Ahmed, Shahana Dunning, Alison M. Maranian, Melanie Pharoah, Paul D. P. Chenevix-Trench, Georgia Beesley, Jonathan Bogdanova, Natalia V. Antonenkova, Natalia N. Zalutsky, Iosif V. Anton-Culver, Hoda Ziogas, Argyrios Brauch, Hiltrud Ko, Yon-Dschun Hamann, Ute Fasching, Peter A. Strick, Reiner Ekici, Arif B. Beckmann, Matthias W. Giles, Graham G. Severi, Gianluca Baglietto, Laura English, Dallas R. Milne, Roger L. Benitez, Javier Ignacio Arias, Jose Pita, Guillermo Nordestgaard, Borge G. Bojesen, Stig E. Flyger, Henrik Kang, Daehee Yoo, Keun-Young Noh, Dong Young Mannermaa, Arto Kataja, Vesa Kosma, Veli-Matti Garcia-Closas, Montserrat Chanock, Stephen Lissowska, Jolanta Brinton, Louise A. Chang-Claude, Jenny Wang-Gohrke, Shan Broeks, Annegien Schmidt, Marjanka K. van Leeuwen, Flora E. Van't Veer, Laura J. Margolin, Sara Lindblom, Annika Humphreys, Manjeet K. Morrison, Jonathan Platte, Radka Easton, Douglas F. Peto, Julian CA KConFab Investigators AOCS Grp GENICA Consortium Breast Canc Assoc Consortium TI Missense Variants in ATM in 26,101 Breast Cancer Cases and 29,842 Controls SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; ATAXIA-TELANGIECTASIA; SUSCEPTIBILITY ALLELES; CONFER SUSCEPTIBILITY; TRUNCATING MUTATIONS; COMMON VARIANTS; RISK; GENE; SPECTRUM; PROTEIN AB Background: Truncating mutations in ATM have been shown to increase the risk of breast cancer but the effect of missense variants remains contentious. Methods: We have genotyped five polymorphic (minor allele frequency, 0.9-2.6%) missense single nucleotide polymorphisms (SNP) in ATM (S49C, S707P, F858L, P1054R, and L1420F) in 26,101 breast cancer cases and 29,842 controls from 23 studies in the Breast Cancer Association Consortium. Results: Combining the data from all five SNPs, the odds ratio (OR) was 1.05 for being a heterozygote for any of the SNPs and 1.51 for being a rare homozygote for any of the SNPs with an overall trend OR of 1.06 (P(trend) = 0.04). The trend OR among bilateral and familial cases was 1.12 (95% confidence interval, 1.02-1.23; P(trend) = 0.02). Conclusions: In this large combined analysis, these five missense ATM SNPs were associated with a small increased risk of breast cancer, explaining an estimated 0.03% of the excess familial risk of breast cancer. Impact: Testing the combined effects of rare missense variants in known breast cancer genes in large collaborative studies should clarify their overall contribution to breast cancer susceptibility. Cancer Epidemiol Biomarkers Prev; 19(9); 2143-51. (C) 2010 AACR. C1 [Fletcher, Olivia; Johnson, Nichola; Orr, Nick; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, BBCS, London SW3 6JB, England. [Fletcher, Olivia; Silva, Isabel dos Santos; Peto, Julian] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. [Peto, Julian] Inst Canc Res, Surrey, England. [Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki Breast Canc Study HEBCS, FIN-00290 Helsinki, Finland. [Aittomaki, Kristiina] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki Breast Canc Study HEBCS, Helsinki, Finland. [Blomqvist, Carl] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki Breast Canc Study HEBCS, Helsinki, Finland. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, GC HBOC, Heidelberg, Germany. [Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany. [Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany. [Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Ctr Clin, Cologne, Germany. [Reed, Malcolm W. R.] Univ Sheffield, Sch Med, Acad Unit Surg Oncol, SBCS, Sheffield, S Yorkshire, England. [Cox, Angela; Brock, Ian; Elliott, Graeme] Univ Sheffield, Sch Med, Inst Canc Studies, SBCS, Sheffield, S Yorkshire, England. [Southey, Melissa C.; Smith, Letitia; Hopper, John L.; Bojesen, Stig E.; Flyger, Henrik] Univ Melbourne, ABCFS, Melbourne, Vic 3010, Australia. [Spurdle, Amanda B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Couch, Fergus J.; Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Schuermann, Peter; Doerk, Thilo] Hannover Med Sch, Dept Obstet & Gynaecol, Hannover Breast Canc Study HABCS, D-3000 Hannover, Germany. [Waltes, Regina; Bremer, Michael] Hannover Med Sch, Dept Radiat Oncol, Hannover Breast Canc Study HABCS, D-3000 Hannover, Germany. [Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, Breast Canc Study ORIGO, NL-2300 RA Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Breast Canc Study ORIGO, Leiden, Netherlands. [van Asperen, Christie J.] Leiden Univ, Dept Clin Genet, Med Ctr, Breast Canc Study ORIGO, Leiden, Netherlands. [Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Breast Canc Study ORIGO, Leiden, Netherlands. [Seynaeve, Caroline] Erasmus MC Daniel Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Hall, Per; Czene, Kamila; Humphreys, Keith] Karolinska Inst, Dept Med Epidemiol & Biostat, Singapore & Swedish Breast Canc Study SASBAC, Stockholm, Sweden. [Liu, Jianjun] Genome Inst Singapore, Human Genet Lab, Singapore, Singapore. [Ahmed, Shahana; Dunning, Alison M.; Maranian, Melanie; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Studies Epidemiol & Risk Factors Canc Hered SEARC, Cambridge, England. [Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Studies Epidemiol & Risk Factors Canc Hered SEARC, Cambridge, England. [Chenevix-Trench, Georgia; Beesley, Jonathan] Queensland Inst Med Res, Kathleen Cuningham Fdn Consortium Res Familial Br, Brisbane, Qld 4006, Australia. [Chenevix-Trench, Georgia; Beesley, Jonathan] Peter MacCallum Canc Ctr, Australian Ovarian Canc Study AOCS, Melbourne, Vic, Australia. [Bogdanova, Natalia V.] Hannover Med Sch, HMBCS, Dept Obstet & Gynaecol, D-3000 Hannover, Germany. [Bogdanova, Natalia V.] Hannover Med Sch, HMBCS, Dept Radiat Oncol, D-3000 Hannover, Germany. [Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Breast Canc Study, Irvine, CA USA. [Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Gene Environm Interact & Breast Canc Germany GENI, D-7000 Stuttgart, Germany. [Hamann, Ute] Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. [Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany. [Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany. Univ Bochum, Inst Ruhr, BGFA Res Inst Occupat Med,German Social Accid Ins, Bochum, Germany. [Fasching, Peter A.; Strick, Reiner; Beckmann, Matthias W.] Univ Hosp Erlangen, Bavarian Breast Canc Cases & Controls BBCC, Univ Breast Ctr, Erlangen, Germany. [Ekici, Arif B.] Univ Hosp Erlangen, Bavarian Breast Canc Cases & Controls BBCC, Inst Human Genet, Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gynecol & Obstet, Los Angeles, CA 90095 USA. [Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Melbourne Collaborat Cohort Study MCCS, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Milne, Roger L.; Benitez, Javier; Pita, Guillermo] Spanish Natl Canc Ctr, Breast Canc Study CNIO BCS Study, Madrid, Spain. [Benitez, Javier] CIBERER, Valencia, Spain. [Ignacio Arias, Jose] Monte Naranco Hosp, Oviedo, Spain. [Nordestgaard, Borge G.] Univ Copenhagen, Herlev Univ Hosp, Copenhagen Breast Canc Study, Dept Clin Biochem, Copenhagen, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Herlev Univ Hosp, Copenhagen Breast Canc Study, Dept Breast Surg, Copenhagen, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Herlev Univ Hosp, CGPS, Dept Breast Surg, Copenhagen, Denmark. [Nordestgaard, Borge G.] Univ Copenhagen, Herlev Univ Hosp, CGPS, Dept Clin Biochem, Copenhagen, Denmark. [Kang, Daehee; Yoo, Keun-Young; Noh, Dong Young] Seoul Natl Univ, Coll Med, Seoul Breast Canc Study SEBCS, Seoul, South Korea. [Mannermaa, Arto; Kosma, Veli-Matti] Univ Kuopio, KBCP, Inst Clin Med Pathol & Forens Med, FIN-70211 Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland. [Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti] Bioctr Kuopio, Kuopio, Finland. [Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland. [Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland. [Garcia-Closas, Montserrat; Chanock, Stephen; Brinton, Louise A.] NCI, PBCS, Div Canc Epidemiol & Genet, Rockville, MD USA. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Dept Epidemiol & Canc Prevent, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Chang-Claude, Jenny] German Canc Res Ctr DFKZ, Genet Epidemiol Study Breast Canc Age 50, Heidelberg, Germany. [Wang-Gohrke, Shan] Ulm Med Sch, Dept Gynecol & Obstet, Ulm, Germany. [Broeks, Annegien; Schmidt, Marjanka K.; van Leeuwen, Flora E.; Van't Veer, Laura J.] Netherlands Canc Inst, ABCS, Amsterdam, Netherlands. [Margolin, Sara; Lindblom, Annika] Karolinska Inst, Dept Pathol & Oncol, Dept Mol Med & Surg, Karloinska Breast Canc Study KARBAC, Stockholm, Sweden. [Humphreys, Manjeet K.; Morrison, Jonathan; Platte, Radka; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Canc Res UK Genet Epidemiol Unit, BCAC, Cambridge, England. [Burwinkel, Barbara] Univ Heidelberg, Dept Obstet & Gynecol, GC HBOC, Heidelberg, Germany. RP Fletcher, O (reprint author), Inst Canc Res, Breakthrough Breast Canc Res Ctr, BBCS, 237 Fulham Rd, London SW3 6JB, England. EM olivia.fletcher@icr.ac.uk RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Ekici, Arif/C-3971-2013; Smith, Letitia /J-9035-2014; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Spurdle, Amanda/A-4978-2011; OI Dunning, Alison Margaret/0000-0001-6651-7166; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Giles, Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188; Czene, Kamila/0000-0002-3233-5695; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Spurdle, Amanda/0000-0003-1337-7897; Lissowska, Jolanta/0000-0003-2695-5799 FU Breakthrough Breast Cancer; NHS; National Cancer Research Network; Helsinki University Central Hospital; Academy of Finland [110663]; Finnish Cancer Society; Sigrid Juselius Foundation; Deutsche Krebshilfe [107054]; Center of Molecular Medicine; Cologne; Helmholtz Society; Dietmar-Hopp Foundation; Yorkshire Cancer Research and the Breast Cancer Campaign; National Health and Medical Research Council of Australia (NHMRC) [145604, 145684, 288704, 454508, 199600, 209057, 251533, 396414]; NIH [CA102740-01A2, CA122340, CA128978, CA116201]; National Cancer Institute, NIH [CA-95-011, CA-58860]; Cancer Care Ontario [CA69467]; Columbia University [CA69398]; Fox Chase Cancer Center [CA69631]; Huntsman Cancer Institute [CA69446]; Northern California Cancer Center [CA69417]; University of Melbourn [CA69638]; New South Wales Cancer Council; Victorian Health Promotion Foundation; Prostate Cancer Foundation of Australia; Susan G. Komen Breast Cancer Foundation; Hannover Medical School; German Research Foundation (DFG) [Do761/2-1]; German Academic Exchange Program; Dutch Cancer Society [NKI 2001-2423, 2007-3839]; Agency for Science, Technology and Research of Singapore (A*STAR); National Breast Cancer Foundation; Chief Physician Johan Boserup and Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Council of Tasmania; Cancer Council of South Australia; Cancer Foundation of Western Australia; U.S. Army [DAMD17-01-1-0729]; Lon V Smith Foundation [LVS-18840]; German Human Genome Project; German Federal Ministry of Education and Research (BMBF) [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation of Medical Research, Stuttgart, Germany; Deutsches Krebsforschungszentrum, Heidelberg, Germany; University Hospital of Erlangen; VicHealth; Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra Cancer; Fondo de Investigacion Sanitario [PI081120, PI081583]; Lise Boserup Fund; Danish Medical Research Council; Copenhagen University Hospital; Herlev Hospital; National Research and Development (R&D) Program for Cancer Control [0620410-1]; Ministry of Health and Welfare, Republic of Korea [AO30001]; Kuopio University Hospital; Finnish Cancer Foundation; National Cancer Institute, Department of Health and Human Services; Deutsche Krebshilfe e.V. [70492]; Dutch National Genomics Initiative; Swedish Cancer Society; Gustav V Julilee Foundation; European Union [BM0606]; Cancer Research UK (CR-UK) [C490/A11021, C8197/A10865, C1287/A10118, C1287/A7497] FX The BBCS is funded by Cancer Research UK (CR-UK) and Breakthrough Breast Cancer and acknowledges NHS funding to the NIHR Biomedical Research Centre and the National Cancer Research Network. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland grant 110663, the Finnish Cancer Society, and the Sigrid Juselius Foundation. The GC-HBOC study was supported by Deutsche Krebshilfe grant 107054, the Center of Molecular Medicine, Cologne, the Helmholtz Society, and the Dietmar-Hopp Foundation. The SBCS was supported by Yorkshire Cancer Research and the Breast Cancer Campaign. The ABCFS was supported by National Health and Medical Research Council of Australia (NHMRC) grant 145604, NIH grant CA102740-01A2, and National Cancer Institute, NIH grant CA-95-011 through cooperative agreements with members of the Breast Cancer Family Registry and principal investigators, Cancer Care Ontario grant CA69467, Columbia University grant CA69398, Fox Chase Cancer Center grant CA69631, Huntsman Cancer Institute grant CA69446, Northern California Cancer Center grant CA69417, and University of Melbourne grant CA69638. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of collaborating centers in the Breast CFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the Breast CFR. The ABCFS was initially supported by the NHMRC, the New South Wales Cancer Council, and the Victorian Health Promotion Foundation. J.L. Hopper is an Australia Fellow of the NHMRC and Victorian Breast Cancer Research Consortium Group Leader. M. C. Southey and A. B. Spurdle are Senior Research Fellows of the NHMRC. Genotyping was in part supported by the Prostate Cancer Foundation of Australia. The MCBCS was supported by NIH grants CA122340 and CA128978, an NIH Breast Cancer Specialized Program of Research Excellence award to the Mayo Clinic (CA116201), and a Susan G. Komen Breast Cancer Foundation award. The HABCS was supported by an intramural grant from Hannover Medical School and German Research Foundation (DFG) grant Do761/2-1. The HMBCS was supported by short-term fellowships from the German Academic Exchange Program (N. Bogdanova) and the Friends of Hannover Medical School (N. Bogdanova). The ORIGO study was supported by the Dutch Cancer Society. The SASBAC study was supported by the Agency for Science, Technology and Research of Singapore (A*STAR), the NIH, and the Susan G. Komen Breast Cancer Foundation. SEARCH is funded by CR-UK programme grant C490/A11021. A. M. Dunning is supported by CR-UK grant C8197/A10865 and P. D. P. Pharoah is a Senior Clinical Research Fellow of CR-UK. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow-Up Study was funded by NHMRC grants 145684, 288704, and 454508. Financial support for the AOCS was provided by U.S. Army Medical Research and Materiel Command grant DAMD17-01-1-0729, the Cancer Council of Tasmania, Cancer Foundation of Western Australia, and NHMRC grant 199600. G. Chenevix-Trench is supported by the NHMRC. The UCIBCS is supported by NIH, National Cancer Institute grant CA-58860 and Lon V Smith Foundation grant LVS-18840.; The GENICA study was supported by the German Human Genome Project and German Federal Ministry of Educaton and Research (BMBF) grants 01KW9975/5, 01KW9976/8, 01KW9977/0, and 01KW0114. Genotyping analysis was supported by the Robert Bosch Foundation of Medical Research, Stuttgart, Germany, and the Deutsches Krebsforschungszentrum, Heidelberg, Germany. The work of the BBCC was partly funded by ELAN-Fond of the University Hospital of Erlangen. Infrastructure support for the MCCS recruitment and follow-up is provided by The Cancer Council Victoria, whereas cohort recruitment was partly funded by VicHealth. This work using the MCCS was supported by NHMRC grants 209057, 251533, and 396414 and genotyping was in part supported by the Prostate Cancer Foundation of Australia. The CNIO-BCS was supported by the Genome Spain Foundation, the Red Tematica de Investigacion Cooperativa en Cancer, the Asociacion Espanola Contra Cancer, and Fondo de Investigacion Sanitario grants PI081120 (J. Beesley) and PI081583 (R.L. Milne.). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Copenhagen University Hospital, Herlev Hospital. The SEBCS was supported National Research and Development (R&D) Program for Cancer Control grant 0620410-1 and Korea Health 21 R&D Project grant AO30001, Ministry of Health and Welfare, Republic of Korea. The KBCP is supported by the EVO funds of Kuopio University Hospital and the Finnish Cancer Foundation. The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services. The GESBC was supported by Deutsche Krebshilfe e.V. grant 70492. Funding for the ABCS was provided by Dutch Cancer Society grants NKI 2001-2423 and 2007-3839 and the Dutch National Genomics Initiative. KARBAC acknowledges funding from the Swedish Cancer Society and the Gustav V Julilee Foundation. The BCAC is funded by CR-UK grants C1287/A10118 and C1287/A7497. Meetings of the BCAC have been funded by the European Union COST Programme (BM0606). D. F. Easton is a Principal Research Fellow of CR-UK. NR 36 TC 16 Z9 16 U1 1 U2 10 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 SEP PY 2010 VL 19 IS 9 BP 2143 EP 2151 DI 10.1158/1055-9965.EPI-10-0374 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800004 PM 20826828 ER PT J AU George, SM Neuhouser, ML Mayne, ST Irwin, ML Albanes, D Gail, MH Alfano, CM Bernstein, L McTiernan, A Reedy, J Smith, AW Ulrich, CM Ballard-Barbash, R AF George, Stephanie M. Neuhouser, Marian L. Mayne, Susan T. Irwin, Melinda L. Albanes, Demetrius Gail, Mitchell H. Alfano, Catherine M. Bernstein, Leslie McTiernan, Anne Reedy, Jill Smith, Ashley W. Ulrich, Cornelia M. Ballard-Barbash, Rachel TI Postdiagnosis Diet Quality Is Inversely Related to a Biomarker of Inflammation among Breast Cancer Survivors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; OBESE POSTMENOPAUSAL WOMEN; HEALTHY EATING INDEX-2005; PHYSICAL-ACTIVITY; SOLEUS MUSCLE; WEIGHT-LOSS; ADIPONECTIN; ADIPOKINES; PATTERNS; QUESTIONNAIRE AB Background: Inflammation and immune response have potential prognostic implications for breast cancer survivors. We examined how postdiagnosis diet quality is cross-sectionally related to biomarkers of inflammation and adipose-derived hormones among breast cancer survivors and determined whether physical activity or body size modified any observed associations. Methods: Participants included 746 women diagnosed with stage 0 to IIIA breast cancer. Thirty months after diagnosis, the women completed food frequency questionnaires. We scored diet quality with the Healthy Eating Index (HEI)-2005. Serum concentrations of C-reactive protein (CRP), serum amyloid A, leptin, and adiponectin were measured in fasting 30 mL blood samples. Log biomarker values were regressed on quartiles of HEI-2005 scores in multivariate models, and beta scores were exponentiated and expressed as geometric means within quartiles of HEI-2005 scores. Results: Women with better versus poor quality postdiagnosis diets, as defined by higher HEI-2005 scores (Q4 versus Q1), had lower concentrations of CRP (1.6 mg/L versus 2.5 mg/L), but no significant difference in concentrations of serum amyloid A, leptin, or adiponectin. Among women not engaging in recreational physical activity after diagnosis, better diet quality was associated with lower CRP concentrations (2.5 mg/L versus 5.0 mg/L), but no association was observed among women engaging in any recreational physical activity (1.4 mg/L versus 1.6 mg/L; P heterogeneity = 0.03). Conclusions: Among breast cancer survivors, a better-quality diet seems to be associated with lower levels of chronic inflammation. Impact: Lower levels of chronic inflammation have been associated with improved survival after breast cancer. Cancer Epidemiol Biomarkers Prev; 19(9); 2220-8. (C) 2010 AACR. C1 [George, Stephanie M.; Mayne, Susan T.; Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [George, Stephanie M.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Rockville, MD USA. [Reedy, Jill; Smith, Ashley W.; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA. [Neuhouser, Marian L.; McTiernan, Anne; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA USA. [Ulrich, Cornelia M.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Heidelberg, Germany. RP George, SM (reprint author), NCI, 6120 Execut Blvd,Suite 320,MSC 7232, Bethesda, MD 20892 USA. EM materess@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Cancer Institute [N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, T32 CA09661, T32 CA105666]; National Institutes of Health [M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX National Cancer Institute Grants N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, T32 CA09661 and T32 CA105666. A portion of this work was conducted through the Clinical Research Center at the University of Washington and supported by the National Institutes of Health Grant M01-RR-00037 and the University of New Mexico Grant NCRR M01-RR-0997. Data collection for the Women's Contraceptive and Reproductive Experiences Study at the University of Southern California was supported by Contract No. N01-HD-3-3175 from the National Institute of Child Health and Human Development, and patient identification was supported in part by Contract 050Q-8709-S1528 from the California Department of Health Services. NR 40 TC 27 Z9 28 U1 2 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 SEP PY 2010 VL 19 IS 9 BP 2220 EP 2228 DI 10.1158/1055-9965.EPI-10-0464 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800011 PM 20716617 ER PT J AU Douglas, JB Silverman, DT Pollak, MN Tao, YZ Soliman, AS Stolzenberg-Solomon, RZ AF Douglas, Jason B. Silverman, Debra T. Pollak, Michael N. Tao, Yuzhen Soliman, Amr S. Stolzenberg-Solomon, Rachael Z. TI Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 Molar Ratio and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GROWTH-FACTOR-I; BINDING-PROTEINS; FACTOR SYSTEM; INSULIN; AUTOCRINE; RECEPTOR; TUMORIGENESIS; EXPRESSION; HEALTH; CELLS AB Background: Experimental evidence suggests that an overexpression of insulin-like growth factor (IGF)-I is implicated in human pancreatic tumors. Increased IGF-II and decreased IGF binding protein (IGFBP)-3 serum concentrations have been linked to a number of other cancers. Methods: We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up of up to 11.7 years). Two controls (n = 374), who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex, and date of blood draw. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with the use of conditional logistic regression, adjusting for smoking. Results: IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly associated with pancreatic cancer (highest compared with lowest quartile: OR, 1.58; 95% CI, 0.91-2.76; and P-trend = 0.25; OR, 0.86; 95% CI, 0.49-1.50; and P-trend = 0.31; and OR, 0.88; 95% CI, 0.51-1.51; and P-trend = 0.47, respectively). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels (highest compared with lowest quartile: OR, 1.54; 95% CI, 0.89-2.66; P-trend = 0.04). Conclusion: A higher IGF-I/IGFBP-3 molar ratio represents increased free IGF-I, which may be a risk factor for pancreatic cancer. Impact: Our results highlight the importance of this biomarker for further investigation in large prospective cohort studies and pooled analysis with other prospective cohorts. Cancer Epidemiol Biomarkers Prev; 19(9); 2298-306. (C) 2010 AACR. C1 [Douglas, Jason B.; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. [Silverman, Debra T.] NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. [Douglas, Jason B.; Soliman, Amr S.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Pollak, Michael N.; Tao, Yuzhen] McGill Univ, Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael N.; Tao, Yuzhen] McGill Univ, Montreal, PQ, Canada. RP Stolzenberg-Solomon, RZ (reprint author), Suite 320,6120 Execut Blvd, Rockville, MD 20852 USA. EM rs221z@nih.gov RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NIH, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services FX NIH Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services. NR 32 TC 37 Z9 38 U1 1 U2 5 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 SEP PY 2010 VL 19 IS 9 BP 2298 EP 2306 DI 10.1158/1055-9965.EPI-10-0400 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800020 PM 20699371 ER PT J AU Bradford, PT Anderson, WF Purdue, MP Goldstein, AM Tucker, MA AF Bradford, Porcia T. Anderson, William F. Purdue, Mark P. Goldstein, Alisa M. Tucker, Margaret A. TI Rising Melanoma Incidence Rates of the Trunk among Younger Women in the United States SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; PERIOD-COHORT MODELS; SUN EXPOSURE; AGE-PERIOD; SITE DISTRIBUTION; ANATOMIC SITE; TRENDS; ASSOCIATION; SEX AB Background: Melanoma rates are rising among young women, possibly due to increasing UV radiation to previously protected body sites. Therefore, we examined melanoma incidence trends by age, gender, and body site. Descriptive methods were complemented with the age-period-cohort parameters net drift and longitudinal age trend. Methods: Case and population data were obtained from the Surveillance, Epidemiology, and End Results (SEER) 9 Registries Database (1975-2006). Net drift summarized the average annual percentage change in log-linear rates per year of calendar-time (or year of diagnosis). Longitudinal age trend summarized the average annual percentage change by attained age at diagnosis. Early-and late-onset melanomas have low and high longitudinal age trends, respectively. Results: There were 105,829 melanomas diagnosed in the SEER 9 Registries. The overall age-adjusted incidence rate (IR) for melanoma was 17.7/100,000 person-years. Age-specific IRs were greater among women than men prior to age 40 years. Among women, IRs decreased for all anatomic sites relative to the trunk. The highest net drift occurred in truncal lesions among women (net drift, 3.8%/year of calendar time; 95% confidence interval, 3.5-4.0%). The lowest longitudinal age trends also were observed for truncal lesions among women (longitudinal age trend, 5.4%/year of attained age; 95% confidence interval, 5.1-5.7). Conclusions: Although melanoma IRs overall have risen for decades, the combination of high net drift and low longitudinal age trend show that melanomas are rising preferentially on the trunk among young women. Impact: Future surveillance and analytic studies should consider melanoma effect modification by age, gender, and body site. Cancer Epidemiol Biomarkers Prev; 19(9); 2401-6. (C) 2010 AACR. C1 [Bradford, Porcia T.; Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Anderson, William F.; Purdue, Mark P.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bradford, PT (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS,Room 7005, Rockville, MD 20852 USA. EM bradfordp@mail.nih.gov RI Tucker, Margaret/B-4297-2015; Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU National Institutes of Health; National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Grant Support; Intramural Research Program of the National Institutes of Health and the National Cancer Institute, Division of Cancer Epidemiology and Genetics. The SEER Program is operated by the National Cancer Institute Surveillance Research Program. NR 25 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 SEP PY 2010 VL 19 IS 9 BP 2401 EP 2406 DI 10.1158/1055-9965.EPI-10-0503 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800031 PM 20826837 ER PT J AU Amaral, AFS Cantor, KP Silverman, DT Malats, N AF Amaral, Andre F. S. Cantor, Kenneth P. Silverman, Debra T. Malats, Nuria TI Selenium and Bladder Cancer Risk: a Meta-analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROSTATE-CANCER; TOENAIL SELENIUM; SELENIFEROUS AREA; SERUM SELENIUM; PREVENTION; SUPPLEMENTATION; TRIAL; HETEROGENEITY; MECHANISMS; BIOMARKERS AB Background: Selenium is considered to be an antioxidant, and its high levels have been inversely associated with cancer risk of several sites. This meta-analysis examined the relationship between levels of selenium measured in serum and toenails, and the risk of bladder cancer. Methods: A meta-analysis using data from seven published epidemiologic studies (three case-control, three nested case-control, one case-cohort) published before March 2010 was done to examine the association between levels of selenium and bladder cancer. Fixed and random effects analyses were done to calculate meta-odds ratio (mOR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the I(2) statistic. Results: Overall, the risk of bladder cancer was inversely associated with elevated levels of selenium according to a random-effects model (mOR = 0.61; 95% CI, 0.42-0.87). The mORs were 0.95 (95% CI, 0.69-1.27) and 0.55 (95% CI, 0.32-0.95) among men and women, respectively. Sex, type of sample specimen, smoking status, and study design were found to be potential sources of heterogeneity. Conclusions: A significant protective effect of selenium, observed mainly among women, may result from gender-specific differences in its accumulation and excretion. The heterogeneity found among studies was mainly linked to the different biological sample specimens used to measure the selenium concentrations and the small size of the studies. Although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support these preliminary evidence. Impact: The present results suggest a beneficial effect of high selenium intake for bladder cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2407-15. (C) 2010 AACR. C1 [Amaral, Andre F. S.; Malats, Nuria] Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid 28029, Spain. [Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Malats, N (reprint author), Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, C Melchor Fernandez Almagro 3, Madrid 28029, Spain. EM nmalats@cnio.es RI Malats, Nuria/H-7041-2015; Amaral, Andre/A-7662-2008 OI Malats, Nuria/0000-0003-2538-3784; Amaral, Andre/0000-0002-0369-9449 FU Red Tematica de Investigacion Cooperativa en Cancer; Instituto de Salud Carlos III; Spanish Ministry of Science and Innovation; Association for International Cancer Research [AICR09-0780] FX Grant Support; Red Tematica de Investigacion Cooperativa en Cancer, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and by the Association for International Cancer Research (AICR09-0780). NR 40 TC 49 Z9 52 U1 0 U2 13 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 SEP PY 2010 VL 19 IS 9 BP 2407 EP 2415 DI 10.1158/1055-9965.EPI-10-0544 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 648HS UT WOS:000281683800032 PM 20807831 ER PT J AU Memmott, RM Mercado, JR Maier, CR Kawabata, S Fox, SD Dennis, PA AF Memmott, Regan M. Mercado, Jose R. Maier, Colleen R. Kawabata, Shigeru Fox, Stephen D. Dennis, Phillip A. TI Metformin Prevents Tobacco Carcinogen-Induced Lung Tumorigenesis SO CANCER PREVENTION RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; A/J MICE; DIABETES-MELLITUS; DEFICIENT MICE; BREAST-CANCER; T-CELLS; IN-VIVO; DIET; GROWTH; MECHANISM AB Activation of the mammalian target of rapamycin (mTOR) pathway is an important and early event in tobacco carcinogen-induced lung tumorigenesis, and therapies that target mTOR could be effective in the prevention or treatment of lung cancer. The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMP-activated protein kinase (AMPK), which can inhibit the mTOR pathway. To test this, A/J mice were treated with oral metformin after exposure to the tobacco carcinogen 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK). Metformin reduced lung tumor burden by up to 53% at steady-state plasma concentrations that are achievable in humans. mTOR was inhibited in lung tumors but only modestly. To test whether intraperitoneal administration of metformin might improve mTOR inhibition, we injected mice and assessed biomarkers in liver and lung tissues. Plasma levels of metformin were significantly higher after injection than oral administration. In liver tissue, metformin activated AMPK and inhibited mTOR. In lung tissue, metformin did not activate AMPK but inhibited phosphorylation of insulin-like growth factor-I receptor/insulin receptor (IGF-1R/IR), Akt, extracellular signal-regulated kinase (ERK), and mTOR. This suggested that metformin indirectly inhibited mTOR in lung tissue by decreasing activation of insulin-like growth factor-I receptor/insulin receptor and Akt upstream of mTOR. Based on these data, we repeated the NNK-induced lung tumorigenesis study using intraperitoneal administration of metformin. Metformin decreased tumor burden by 72%, which correlated with decreased cellular proliferation and marked inhibition of mTOR in tumors. These studies show that metformin prevents tobacco carcinogen-induced lung tumorigenesis and support clinical testing of metformin as a chemopreventive agent. Cancer Prev Res; 3(9); 1066-76. (C) 2010 AACR. C1 [Memmott, Regan M.; Mercado, Jose R.; Maier, Colleen R.; Kawabata, Shigeru; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Fox, Stephen D.] Sci Applicat Int Corp Frederick Inc, Lab Prote & Analyt Technol, Frederick, MD USA. RP Dennis, PA (reprint author), Natl Canc Inst Navy Med Oncol, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 40 TC 193 Z9 201 U1 2 U2 23 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 SEP PY 2010 VL 3 IS 9 BP 1066 EP 1076 DI 10.1158/1940-6207.CAPR-10-0055 PG 11 WC Oncology SC Oncology GA 646KH UT WOS:000281538400005 PM 20810672 ER PT J AU Tichelaar, JW Yan, Y Tan, Q Wang, YA Estensen, RD Young, MR Colburn, NH Yin, HL Goodin, C Anderson, MW You, M AF Tichelaar, Jay W. Yan, Ying Tan, Qing Wang, Yian Estensen, Richard D. Young, Matthew R. Colburn, Nancy H. Yin, Hulian Goodin, Colleen Anderson, Marshall W. You, Ming TI A Dominant-Negative c-jun Mutant Inhibits Lung Carcinogenesis in Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR; AP-1 ACTIVITY; CANCER CELLS; PULMONARY CARCINOGENESIS; AEROSOLIZED BUDESONIDE; CHEMOPREVENTIVE AGENTS; INDUCED TRANSFORMATION; GENE-EXPRESSION; TRANSGENIC MICE; TARGET GENES AB Lung cancer is the leading cause of cancer mortality in the United States and worldwide. The identification of key regulatory and molecular mechanisms involved in lung tumorigenesis is therefore critical to increase our understanding of this disease and could ultimately lead to targeted therapies to improve prevention and treatment. Induction of members of the activator protein-1 (AP-1) transcription factor family has been described in human non-small cell lung carcinoma. Activation of AP-1 can either stimulate or repress transcription of multiple gene targets, ultimately leading to increased cell proliferation and inhibition of apoptosis. In the present study, we show induction of AP-1 in carcinogen-induced mouse lung tumors compared with surrounding normal lung tissue. We then used a transgenic mouse model directing conditional expression of the dominant-negative c-jun mutant TAM67 in lung epithelial cells to determine the effect of AP-1 inhibition on mouse lung tumorigenesis. Consistent with low AP-1 activity in normal lung tissue, TAM67 expression had no observed effects in adult mouse lung. TAM67 decreased tumor number and overall lung tumor burden in chemically induced mouse lung tumor models. The most significant inhibitory effect was observed on carcinoma burden compared with lower-grade lesions. Our results support the concept that AP-1 is a key regulator of mouse lung tumorigenesis, and identify AP-1-dependent transcription as a potential target to prevent lung tumor progression. Cancer Prev Res; 3(9); 1148-56. (C) 2010 AACR. C1 [Tichelaar, Jay W.; Yan, Ying; Tan, Qing; Wang, Yian; You, Ming] Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, Sch Med, St Louis, MO 63110 USA. [Estensen, Richard D.] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Young, Matthew R.; Colburn, Nancy H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA. [Yin, Hulian] Cincinnati Childrens Hosp Med Ctr, Dept Anesthesia, Cincinnati, OH USA. [Goodin, Colleen; Anderson, Marshall W.] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH USA. RP Tichelaar, JW (reprint author), Washington Univ, Dept Surg, Alvin J Siteman Canc Ctr, Sch Med, 660 S Euclid Ave, St Louis, MO 63110 USA. EM tichelaarj@wustl.edu RI Tichelaar, Jay/B-9148-2011 FU NIH [P01CA096964, R03CA137819, R01CA139959] FX NIH grants P01CA096964, R03CA137819, and R01CA139959. NR 55 TC 6 Z9 6 U1 0 U2 0 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 SEP PY 2010 VL 3 IS 9 BP 1148 EP 1156 DI 10.1158/1940-6207.CAPR-10-0023 PG 9 WC Oncology SC Oncology GA 646KH UT WOS:000281538400014 PM 20716630 ER PT J AU Chow, HHS Garland, LL Hsu, CH Vining, DR Chew, WM Miller, JA Perloff, M Crowell, JA Alberts, DS AF Chow, H-H. Sherry Garland, Linda L. Hsu, Chiu-Hsieh Vining, Donna R. Chew, Wade M. Miller, Jessica A. Perloff, Marjorie Crowell, James A. Alberts, David S. TI Resveratrol Modulates Drug- and Carcinogen-Metabolizing Enzymes in a Healthy Volunteer Study SO CANCER PREVENTION RESEARCH LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ARYL-HYDROCARBON RECEPTOR; OXIDATIVE DNA-DAMAGE; HUMAN PLASMA; CHEMOPREVENTIVE AGENT; TRANS-RESVERATROL; CANCER PREVENTION; EPITHELIAL-CELLS; RED WINE; PHASE-I AB Resveratrol has been shown to exhibit cancer-preventive activities in preclinical studies. We conducted a clinical study to determine the effect of pharmacologic doses of resveratrol on drug-and carcinogen-metabolizing enzymes. Forty-two healthy volunteers underwent baseline assessment of cytochrome P450 (CYP) and phase II detoxification enzymes. CYP1A2, CYP2D6, CYP2C9, and CYP3A4 enzyme activities were measured by the metabolism of caffeine, dextromethorphan, losartan, and buspirone, respectively. Blood lymphocyte glutathione S-transferase (GST) activity and GST-pi level and serum total and direct bilirubin, a surrogate for UDP-glucuronosyl transferase (UGT) 1A1 activity, were measured to assess phase II enzymes. After the baseline evaluation, study participants took 1 g of resveratrol once daily for 4 weeks. Enzyme assessment was repeated upon intervention completion. Resveratrol intervention was found to inhibit the phenotypic indices of CYP3A4, CYP2D6, and CYP2C9 and to induce the phenotypic index of 1A2. Overall, GST and UGT1A1 activities were minimally affected by the intervention, although an induction of GST-pi level and UGT1A1 activity was observed in individuals with low baseline enzyme level/activity. We conclude that resveratrol can modulate enzyme systems involved in carcinogen activation and detoxification, which may be one mechanism by which resveratrol inhibits carcinogenesis. However, pharmacologic doses of resveratrol could potentially lead to increased adverse drug reactions or altered drug efficacy due to inhibition or induction of certain CYPs. Further clinical development of resveratrol for cancer prevention should consider evaluation of lower doses of resveratrol to minimize adverse metabolic drug interactions. Cancer Prev Res; 3(9); 1168-75. (C) 2010 AACR. C1 [Chow, H-H. Sherry; Garland, Linda L.; Hsu, Chiu-Hsieh; Vining, Donna R.; Chew, Wade M.; Miller, Jessica A.; Alberts, David S.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Perloff, Marjorie] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Crowell, James A.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Chow, HHS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. EM schow@azcc.arizona.edu FU National Cancer Institute [N01-CN-35158] FX National Cancer Institute contract N01-CN-35158. NR 34 TC 96 Z9 98 U1 0 U2 5 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 SEP PY 2010 VL 3 IS 9 BP 1168 EP 1175 DI 10.1158/1940-6207.CAPR-09-0155 PG 8 WC Oncology SC Oncology GA 646KH UT WOS:000281538400016 PM 20716633 ER PT J AU Saleiro, D Murillo, G Lubahn, DB Kopelovich, L Korach, KS Mehta, RG AF Saleiro, Diana Murillo, Genoveva Lubahn, Dennis B. Kopelovich, Levy Korach, Kenneth S. Mehta, Rajendra G. TI Enhanced Induction of Mucin-Depleted Foci in Estrogen Receptor beta Knockout Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID COLORECTAL-CANCER RISK; ER-BETA; COLON CARCINOGENESIS; EXPRESSION; GENE; LESIONS; IDENTIFICATION; TUMORIGENESIS; METHYLATION; DISRUPTION AB The role of the estrogen receptor beta (ER beta) in the colon has received considerable interest, yet in vivo models are needed to better define its protective actions. In the present study, wild-type (WT), ER alpha, and ER beta knockout (alpha ERKO and beta ERKO) mice were injected with azoxymethane, a colon chemical carcinogen. Fourteen weeks after azoxymethane exposure, the incidence of aberrant crypt foci (ACF) was assessed by methylene blue staining. beta ERKO mice showed significantly higher incidence (P < 0.001) of ACF (15.0 +/- 2.5) compared with alpha ERKO (3.4 +/- 1.0) and WT (4.6 +/- 1.0) mice. The colons in several beta ERKO mice had increased thickness and loss of normal morphology. It has been reported that ER beta plays a role in the maintenance of the colonic crypt architecture; this may explain the loss of crypt organization in the colonic epithelium of beta ERKO mice. The presence of mucin-depleted foci (MDF) has been shown, both in humans and in rodents, as an early event in colon cancer. Therefore, to surpass the limitations with ACF scoring, we performed Alcian blue-neutral red staining to assess the presence of MDF. This assay allowed the assessment of precancerous lesions on all the beta ERKO mice colons (38.3 +/- 4.0; P < 0.001), comparing to WT and alpha ERKO mice (6.6 +/- 1.5 and 10.0 +/- 1.9, respectively), and served to confirm the ACF results. Together, these data support the use of MDF staining as a biomarker for precancerous lesions and the protective role of ER beta in colon carcinogenesis. Cancer Prev Res; 3(9); 1198-204. (C) 2010 AACR. C1 [Saleiro, Diana; Murillo, Genoveva; Mehta, Rajendra G.] IIT Res Inst, Div Canc Biol, Chicago, IL 60616 USA. [Saleiro, Diana] Univ Porto, Grad Program Areas Basic & Appl Biol, P-4100 Oporto, Portugal. [Lubahn, Dennis B.] Univ Missouri, Columbia, MO USA. [Kopelovich, Levy] NCI, Bethesda, MD 20892 USA. [Korach, Kenneth S.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. RP Murillo, G (reprint author), IIT Res Inst, Div Canc Biol, 10 W 35th St, Chicago, IL 60616 USA. EM gmurillo@iitri.org OI Korach, Kenneth/0000-0002-7765-418X FU Business Development Agency-Global Portugal (AICEP); Fulbright Portugal Commission; FCT [MCET, FSE-SFRH/BD/33544/2008]; NIH [K01 CA103861] FX Business Development Agency-Global Portugal (AICEP), Fulbright Portugal Commission, and FCT (MCET and FSE-SFRH/BD/33544/2008; D. Saleiro), NIH K01 CA103861 (G. Murillo), R01 CA121157 (R. G. Mehta), and research support provided by the Division of Intramural Research of NIEHS/NIH (K. S. Korach). NR 38 TC 9 Z9 9 U1 0 U2 4 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 SEP PY 2010 VL 3 IS 9 BP 1198 EP 1204 DI 10.1158/1940-6207.CAPR-10-0044 PG 7 WC Oncology SC Oncology GA 646KH UT WOS:000281538400019 PM 20716634 ER PT J AU Kerkar, SP Muranski, P Kaiser, A Boni, A Sanchez-Perez, L Yu, ZY Palmer, DC Reger, RN Borman, ZA Zhang, L Morgan, RA Gattinoni, L Rosenberg, SA Trinchieri, G Restifo, NP AF Kerkar, Sid P. Muranski, Pawel Kaiser, Andrew Boni, Andrea Sanchez-Perez, Luis Yu, Zhiya Palmer, Douglas C. Reger, Robert N. Borman, Zachary A. Zhang, Ling Morgan, Richard A. Gattinoni, Luca Rosenberg, Steven A. Trinchieri, Giorgio Restifo, Nicholas P. TI Tumor-Specific CD8(+) T Cells Expressing Interleukin-12 Eradicate Established Cancers in Lymphodepleted Hosts SO CANCER RESEARCH LA English DT Article ID IFN-GAMMA PRODUCTION; INTERFERON-GAMMA; SUPPRESSOR-CELLS; IN-VIVO; ANTITUMOR IMMUNITY; MURINE TUMORS; GENE-THERAPY; IL-12; IMMUNOTHERAPY; CYTOKINE AB T-cell-based immunotherapies can be effective in the treatment of large vascularized tumors, but they rely on adoptive transfer of substantial numbers (similar to 20 million) of tumor-specific T cells administered together with vaccination and high-dose interleukin (IL)-2. In this study, we report that similar to 10,000 T cells gene-engineered to express a single-chain IL-12 molecule can be therapeutically effective against established tumors in the absence of exogenous IL-2 and vaccine. Although IL-12-engineered cells did not perist long-term in hosts, they exhibited enhanced functionality and were detected in higher numbers intratumorally along with increased numbers of endogenous natural killer and CD8(+) T cells just before regression. Importantly, transferred T cells isolated from tumors stably overproduced supraphysiologic amounts of IL-12, and the therapeutic effect of IL-12 produced within the tumor microenvironment could not be mimicked with high doses of exogenously provided IL-12. Furthermore, antitumor effects could be recapitulated by engineering wild-type open-repertoire splenocytes to express both the single-chain IL-12 and a recombinant tumor-specific T-cell receptor (TCR), but only when individual cells expressed both the TCR and IL-12, indicating that arrested migration of T cells at the tumor site was required for their activities. Successful tumor eradication was dependent on a lymphodepleting preconditioning regimen that reduced the number of intratumoral CD4(+) Foxp3(+) T regulatory cells. Our findings reveal an approach to genetically modify T cells to reduce the cell number needed, eliminate the need for vaccines or systemic IL-2, and improve immunotherapy efficacy based on adoptive transfer of gene-engineered T cells. Cancer Res; 70(17); 6725-34. (C)2010 AACR. C1 [Kerkar, Sid P.; Muranski, Pawel; Kaiser, Andrew; Boni, Andrea; Sanchez-Perez, Luis; Yu, Zhiya; Palmer, Douglas C.; Reger, Robert N.; Borman, Zachary A.; Zhang, Ling; Morgan, Richard A.; Gattinoni, Luca; Rosenberg, Steven A.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Trinchieri, Giorgio] NCI, Canc & Inflammat Program, NIH, Frederick, MD 21701 USA. RP Kerkar, SP (reprint author), NCI, Ctr Canc Res, NIH, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA. EM kerkars@mail.nih.gov; restifon@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Kaiser, Andrew/C-2617-2012; Palmer, Douglas/B-9454-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU NIH, National Cancer Institute, Center for Cancer Research FX Grant Support; Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 50 TC 104 Z9 104 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2010 VL 70 IS 17 BP 6725 EP 6734 DI 10.1158/0008-5472.CAN-10-0735 PG 10 WC Oncology SC Oncology GA 651GF UT WOS:000281914600006 PM 20647327 ER PT J AU Terzuoli, E Puppo, M Rapisarda, A Uranchimeg, B Cao, LA Burger, AM Ziche, M Melillo, G AF Terzuoli, Erika Puppo, Maura Rapisarda, Annamaria Uranchimeg, Badarch Cao, Liang Burger, Angelika M. Ziche, Marina Melillo, Giovanni TI Aminoflavone, a Ligand of the Aryl Hydrocarbon Receptor, Inhibits HIF-1 alpha Expression in an AhR-Independent Fashion SO CANCER RESEARCH LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; BREAST-CANCER CELLS; TUMOR-GROWTH; FACTOR 1-ALPHA; PROTEIN ACCUMULATION; DEPENDENT INHIBITION; CYTOCHROME P4501A1; SIGNALING PATHWAYS; ANTITUMOR AGENT; MESSENGER-RNA AB Aminoflavone (AF), the active component of a novel anticancer agent (AFP464) in phase I clinical trials, is a ligand of the aryl hydrocarbon receptor (AhR). AhR dimerizes with HIF-1 beta/AhR, which is shared with HIF-1 alpha, a transcription factor critical for the response of cells to oxygen deprivation. To address whether pharmacologic activation of the AhR pathway might be a potential mechanism for inhibition of HIF-1, we tested the effects of AF on HIF-1 expression. AF inhibited HIF-1 alpha transcriptional activity and protein accumulation in MCF-7 cells. However, inhibition of HIF-1 alpha by AF was independent from a functional AhR pathway. Indeed, AF inhibited HIF-1 alpha expression in Ah(R100) cells, in which the AhR pathway is functionally impaired, yet did not induce cytotoxicity, providing evidence that these effects are mediated by distinct signaling pathways. Moreover, AF was inactive in MDA-MB-231 cells, yet inhibited HIF-1 alpha in MDA-MB-231 cells transfected with the SULT1A1 gene. AF inhibited HIF-1 alpha mRNA expression by similar to 50%. Notably, actinomycin-D completely abrogated the ability of AF to downregulate HIF-1 alpha mRNA, indicating that active transcription was required for the inhibition of HIF-1 alpha expression. Finally, AF inhibited HIF-1a protein accumulation and the expression of HIF-1 target genes in MCF-7 xenografts. These results show that AF inhibits HIF-1 alpha in an AhR-independent fashion, and they unveil additional activities of AF that may be relevant for its further clinical development. Cancer Res; 70(17); 6837-48. (C)2010 AACR. C1 [Melillo, Giovanni] NCI, Dev Therapeut Program, Tumor Hypoxia Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. [Terzuoli, Erika; Ziche, Marina] Univ Siena, Dept Mol Biol, I-53100 Siena, Italy. [Puppo, Maura] G Gaslini Inst Children, Mol Biol Lab, Genoa, Italy. [Cao, Liang] NCI, Mol Targets Core Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Burger, Angelika M.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. RP Melillo, G (reprint author), NCI, Dev Therapeut Program, Tumor Hypoxia Lab, SAIC Frederick Inc, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@mail.nih.gov FU NCI, NIH [N01-CO-12400] FX Grant Support; Federal funds from the NCI, NIH, under contract no. N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. This research was supported by the Developmental Therapeutics Program, DCTD, of the NCI, NIH. NR 50 TC 37 Z9 37 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2010 VL 70 IS 17 BP 6837 EP 6848 DI 10.1158/0008-5472.CAN-10-1075 PG 12 WC Oncology SC Oncology GA 651GF UT WOS:000281914600017 PM 20736373 ER PT J AU Lan, Q Zhang, LP Tang, XJ Shen, M Smith, MT Qiu, CY Ge, YC Ji, ZY Xiong, J He, JA Reiss, B Hao, ZY Liu, SW Xie, YX Guo, WH Purdue, MP Galvan, N Xin, KX Hu, W Freeman, LEB Blair, AE Li, LY Rothman, N Vermeulen, R Huang, HL AF Lan, Qing Zhang, Luoping Tang, Xiaojiang Shen, Min Smith, Martyn T. Qiu, Chuangyi Ge, Yichen Ji, Zhiying Xiong, Jun He, Jian Reiss, Boris Hao, Zhenyue Liu, Songwang Xie, Yuxuan Guo, Weihong Purdue, Mark P. Galvan, Noe Xin, Kerry X. Hu, Wei Freeman, Laura E. Beane Blair, Aaron E. Li, Laiyu Rothman, Nathaniel Vermeulen, Roel Huang, Hanlin TI Occupational exposure to trichloroethylene is associated with a decline in lymphocyte subsets and soluble CD27 and CD30 markers SO CARCINOGENESIS LA English DT Article ID CANCER-RISK; ANTIRETROVIRAL THERAPY; MULTIPLE-SCLEROSIS; BONE-MARROW; ACTIVATION; WORKERS; CD27-CD70; COHORT; EXPRESSION; RESPONSES AB Occupational cohort and case-control studies suggest that trichloroethylene (TCE) exposure may be associated with non-Hodgkin lymphoma (NHL) but findings are not consistent. There is a need for mechanistic studies to evaluate the biologic plausibility of this association. We carried out a cross-sectional molecular epidemiology study of 80 healthy workers that used TCE and 96 comparable unexposed controls in Guangdong, China. Personal exposure measurements were taken over a three-week period before blood collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration Permissible Exposure Limit (100 p.p.m. 8 h time-weighted average), with a mean (SD) of 22.2 (36.0) p.p.m. The total lymphocyte count and each of the major lymphocyte subsets including CD4+ T cells, CD8+ T cells, natural killer (NK) cells and B cells were significantly decreased among the TCE-exposed workers compared with controls (P < 0.05), with evidence of a dose-dependent decline. Further, there was a striking 61% decline in sCD27 plasma level and a 34% decline in sCD30 plasma level among TCE-exposed workers compared with controls. This is the first report that TCE exposure under the current Occupational Safety and Health Administration workplace standard is associated with a decline in all major lymphocyte subsets and sCD27 and sCD30, which play an important role in regulating cellular activity in subsets of T, B and NK cells and are associated with lymphocyte activation. Given that altered immunity is an established risk factor for NHL, these results add to the biologic plausibility that TCE is a possible lymphomagen. C1 [Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Zhang, Luoping; Smith, Martyn T.; Ji, Zhiying; Guo, Weihong; Galvan, Noe; Xin, Kerry X.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Tang, Xiaojiang; Qiu, Chuangyi; Ge, Yichen; Xie, Yuxuan; Li, Laiyu; Huang, Hanlin] Guangdong Poison Control Ctr, Guangzhou 510300, Guangdong, Peoples R China. [Xiong, Jun] Dongguan Ctr Dis Control & Prevent, Dongguan 523016, Guangdong, Peoples R China. [He, Jian] Zhongshan Ctr Dis Control & Prevent, Zhongshan 528403, Guangdong, Peoples R China. [Reiss, Boris; Vermeulen, Roel] Univ Utrecht, NL-3508 TC Utrecht, Netherlands. [Hao, Zhenyue] Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada. [Hao, Zhenyue] Univ Hlth Network, Toronto, ON M5G 2C1, Canada. [Liu, Songwang] Qiaotou Hosp, Dongguan 523523, Guangdong, Peoples R China. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Hu, Wei/M-3524-2013; Vermeulen, Roel/F-8037-2011; Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015 OI Vermeulen, Roel/0000-0003-4082-8163; Purdue, Mark/0000-0003-1177-3108; Beane Freeman, Laura/0000-0003-1294-4124 FU National Institutes of Health and National Cancer Institute; National Institute of Environmental Health Sciences [P42ES04705, P30ES01896]; Northern California Center for Occupational and Environmental Health; Department of Science and Technology of Guangdong Province, China [2007A050100004]; Department of Science and Technology of Guangdong Province, People's Republic of China [2007A050100004] FX Intramural funds from the National Institutes of Health and National Cancer Institute; National Institute of Environmental Health Sciences (P42ES04705, P30ES01896); Northern California Center for Occupational and Environmental Health; Department of Science and Technology of Guangdong Province, China (2007A050100004); Department of Science and Technology of Guangdong Province, People's Republic of China (2007A050100004 to X. T.). NR 28 TC 21 Z9 25 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 2010 VL 31 IS 9 BP 1592 EP 1596 DI 10.1093/carcin/bgq121 PG 5 WC Oncology SC Oncology GA 646HP UT WOS:000281530400012 PM 20530238 ER PT J AU Nakamura, AJ Redon, CE Bonner, WM AF Nakamura, Asako J. Redon, Christophe E. Bonner, William M. TI gamma H2AX Applications for the evaluation of telomerase-based cancer therapy SO CELL CYCLE LA English DT Editorial Material ID CELLS C1 [Nakamura, Asako J.; Redon, Christophe E.; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Nakamura, AJ (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM nakamuraa@mail.nih.gov NR 11 TC 1 Z9 2 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD SEP 1 PY 2010 VL 9 IS 17 BP 3385 EP 3386 DI 10.4161/cc.9.17.13003 PG 2 WC Cell Biology SC Cell Biology GA 647MD UT WOS:000281621700001 PM 20703091 ER PT J AU Assayag, M Gerstenblith, G Stern, MD Horowitz, M AF Assayag, Miri Gerstenblith, Gary Stern, Michael D. Horowitz, Michal TI Long- but not short-term heat acclimation produces an apoptosis-resistant cardiac phenotype: a lesson from heat stress and ischemic/reperfusion insults SO CELL STRESS & CHAPERONES LA English DT Article DE Heat acclimation-mediated cross-tolerance; Apoptosis; Heat stress; Mitochondria; Ischemia/reperfusion ID ISCHEMIC CROSS-TOLERANCE; CELL-DEATH; MEMBRANE PERMEABILIZATION; THERMOREGULATORY ACTIVITY; RAT; HYPOHYDRATION; REPERFUSION; INHIBITION; MECHANISMS; RESPONSES AB Long-term heat acclimation (AC, 30d/34 degrees C) is a phenotypic adaptation leading to increased thermotolerance during heat stress (HS, 2 h 41 degrees C). AC also renders protection against ischemic/reperfusion (I/R, 30' global ischemia/40' reperfusion) insult via cross-tolerance mechanisms. In contrast to the protected AC phenotype, the onset of acclimation (34 degrees C, AC2d) is characterized by cellular perturbations, suggesting increased susceptibility to HS and I/R insults. In this investigation, we tested the hypothesis that apoptosis resistance is part of the AC repertoire and that, at the initial phase of acclimation (AC2d), cytoprotection is impaired. TUNEL staining and caspase 3 levels in HS and I/R insulted hearts affirmed this hypothesis. To examine the role of the mitochondria in life/death decision in AC2d and 30d AC settings vs. control hearts, we studied the Bcl-2 apoptotic cascade and found increased levels of the anti-apoptotic Bcl-X-L and decreased levels of the pro-apoptotic death promoter Bad in hearts from AC2d and AC animals. In these groups, cytochrome c (cyt c) was elevated in the mitochondria and remained unchanged in the cytosol. This adaptation was insufficient to negate apoptosis in AC2d rats. At this early acclimation phase (and in controls), increased caspase 8 activity confirmed activation of the extrinsic (Fas ligand) apoptosis pathway. In conclusion, the elevated Bcl-X-L/Bad ratio and decreased cyt c leakage to the cytosol are insufficient to protect the heart and interactions with additional cytoprotective pathways involved in acclimation (elevated HSP70, ROS, and sarcolemmal adaptations to abolish extrinsic apoptosis pathways) are required to induce the apoptosis-resistant AC phenotype. C1 [Horowitz, Michal] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Physiol, IL-91120 Jerusalem, Israel. [Assayag, Miri; Horowitz, Michal] Hebrew Univ Jerusalem, Fac Med Dent, Environm Physiol Lab, IL-91120 Jerusalem, Israel. [Gerstenblith, Gary] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA. [Stern, Michael D.] NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Horowitz, M (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Physiol, POB 12272, IL-91120 Jerusalem, Israel. EM horowitz@cc.huji.ac.il FU USA-Israel Binational Fund BSF [2003-298]; NIH National Institute on Aging FX This study was supported by the USA-Israel Binational Fund BSF Grant 2003-298 and (in part) by the Intramural Research Program of the NIH National Institute on Aging. NR 40 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1355-8145 EI 1466-1268 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD SEP PY 2010 VL 15 IS 5 BP 651 EP 664 DI 10.1007/s12192-010-0178-x PG 14 WC Cell Biology SC Cell Biology GA 636YQ UT WOS:000280781800018 PM 20221856 ER PT J AU Gardner, MK Sprague, BL Pearson, CG Cosgrove, BD Bicek, AD Bloom, K Salmon, ED Odde, DJ AF Gardner, Melissa K. Sprague, Brian L. Pearson, Chad G. Cosgrove, Benjamin D. Bicek, Andrew D. Bloom, Kerry Salmon, E. D. Odde, David J. TI Model Convolution: A Computational Approach to Digital Image Interpretation (vol 3, pg 163, 2010) SO CELLULAR AND MOLECULAR BIOENGINEERING LA English DT Correction C1 [Gardner, Melissa K.; Cosgrove, Benjamin D.; Bicek, Andrew D.; Odde, David J.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN 55455 USA. [Bloom, Kerry; Salmon, E. D.] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. [Sprague, Brian L.] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. [Pearson, Chad G.] Univ Colorado, MCD Biol, Boulder, CO 80309 USA. RP Odde, DJ (reprint author), Univ Minnesota, Dept Biomed Engn, 7-132 Nils Hasselmo Hall,312 Church St SE, Minneapolis, MN 55455 USA. EM oddex002@umn.edu RI Odde, David/H-4925-2011 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 1865-5025 J9 CELL MOL BIOENG JI Cell. Mol. Bioeng. PD SEP PY 2010 VL 3 IS 3 BP 331 EP 332 DI 10.1007/s12195-010-0126-y PG 2 WC Cell & Tissue Engineering; Biophysics; Cell Biology SC Cell Biology; Biophysics GA 638MZ UT WOS:000280900300012 ER PT J AU Malachowa, N DeLeo, FR AF Malachowa, Natalia DeLeo, Frank R. TI Mobile genetic elements of Staphylococcus aureus SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Mobile genetic elements; Staphylococcus aureus; Virulence; Antibiotic resistance; Horizontal gene transfer ID PANTON-VALENTINE LEUKOCIDIN; COAGULASE-NEGATIVE STAPHYLOCOCCI; CADMIUM RESISTANCE DETERMINANTS; CHEMOTAXIS INHIBITORY PROTEIN; COMPLETE NUCLEOTIDE-SEQUENCE; STREPTOGRAMIN-B RESISTANCE; LEVEL MUPIROCIN RESISTANCE; METHICILLIN-RESISTANT; PATHOGENICITY ISLANDS; BETA-LACTAMASE AB Bacteria such as Staphylococcus aureus are successful as commensal organisms or pathogens in part because they adapt rapidly to selective pressures imparted by the human host. Mobile genetic elements (MGEs) play a central role in this adaptation process and are a means to transfer genetic information (DNA) among and within bacterial species. Importantly, MGEs encode putative virulence factors and molecules that confer resistance to antibiotics, including the gene that confers resistance to beta-lactam antibiotics in methicillin-resistant S. aureus (MRSA). Inasmuch as MRSA infections are a significant problem worldwide and continue to emerge in epidemic waves, there has been significant effort to improve diagnostic assays and to develop new antimicrobial agents for treatment of disease. Our understanding of S. aureus MGEs and the molecules they encode has played an important role toward these ends and has provided detailed insight into the evolution of antimicrobial resistance mechanisms and virulence. C1 [Malachowa, Natalia; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank James M. Musser (The Methodist Hospital Research Institute, Houston TX, USA) for critical reading of the manuscript. This article was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 171 TC 114 Z9 129 U1 12 U2 60 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD SEP PY 2010 VL 67 IS 18 BP 3057 EP 3071 DI 10.1007/s00018-010-0389-4 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 644QY UT WOS:000281395800002 PM 20668911 ER PT J AU Bao, JJ Sack, MN AF Bao, Jianjun Sack, Michael N. TI Protein deacetylation by sirtuins: delineating a post-translational regulatory program responsive to nutrient and redox stressors SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Sirtuins; Lysine acetylation/deacetylation; Post-translational modifications; NAD(+); Biological functions ID DEPENDENT GENE-EXPRESSION; III HISTONE DEACETYLASE; NAD(+) SALVAGE PATHWAY; FATTY-ACID OXIDATION; DNA-DAMAGE RESPONSE; SIR2 HOMOLOG; CALORIE RESTRICTION; NEGATIVE REGULATOR; LYSINE ACETYLATION; LIFE-SPAN AB Lysine acetylation/deacetylation is increasingly being recognized as common post-translational modification that appears to be broadly operational throughout the cell. The functional roles of these modifications, outside of the nucleus, have not been extensively studied. Moreover, as acetyl-CoA donates the acetyl group for acetylation, nutrient availability and energetic status may be pivotal in this modification. Similarly, nutrient limitation is associated with the deacetylation reaction. This modification is orchestrated by a novel family of sirtuin deacetylases that function in a nutrient and redox dependent manner and targets non-histone protein deacetylation. In compartment-specific locations, candidate target proteins undergoing lysine-residue deacetylation are being identified. Through these investigations, the functional role of this post-translational modification is being delineated. We review the sirtuin family proteins, discuss their functional effects on target proteins, and postulate on potential biological programs and disease processes that may be modified by sirtuin-mediated deacetylation of target proteins. C1 [Bao, Jianjun; Sack, Michael N.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU National Heart Lung and Blood Institute of the National Institutes of Health FX The authors of this manuscript are funded by the Division of Intramural Research of the National Heart Lung and Blood Institute of the National Institutes of Health. NR 176 TC 33 Z9 34 U1 0 U2 4 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD SEP PY 2010 VL 67 IS 18 BP 3073 EP 3087 DI 10.1007/s00018-010-0402-y PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 644QY UT WOS:000281395800003 PM 20680393 ER PT J AU Mital, J Miller, NJ Fischer, ER Hackstadt, T AF Mital, Jeffrey Miller, Natalie J. Fischer, Elizabeth R. Hackstadt, Ted TI Specific chlamydial inclusion membrane proteins associate with active Src family kinases in microdomains that interact with the host microtubule network SO CELLULAR MICROBIOLOGY LA English DT Article ID INVASIVE CERVICAL-CANCER; TRACHOMATIS INFECTION; TYROSINE KINASES; DEVELOPMENTAL CYCLE; CELL PROTEINS; III SECRETION; PHOSPHORYLATION; DYNEIN; TRAFFICKING; DIVISION AB P>Chlamydiae are Gram-negative obligate intracellular bacteria that cause diseases with significant medical and economic impact. Chlamydia trachomatis replicates within a vacuole termed an inclusion, which is extensively modified by the insertion of a number of bacterial effector proteins known as inclusion membrane proteins (Incs). Once modified, the inclusion is trafficked in a dynein-dependent manner to the microtubule-organizing centre (MTOC), where it associates with host centrosomes. Here we describe a novel structure on the inclusion membrane comprised of both host and bacterial proteins. Members of the Src family of kinases are recruited to the chlamydial inclusion in an active form. These kinases display a distinct, localized punctate microdomain-like staining pattern on the inclusion membrane that colocalizes with four chlamydial inclusion membrane proteins (Incs) and is enriched in cholesterol. Biochemical studies show that at least two of these Incs stably interact with one another. Furthermore, host centrosomes associate with these microdomain proteins in C. trachomatis-infected cells and in uninfected cells exogenously expressing one of the chlamydial effectors. Together, the data suggest that a specific structure on the C. trachomatis inclusion membrane may be responsible for the known interactions of chlamydiae with the microtubule network and resultant effects on centrosome stability. C1 [Mital, Jeffrey; Miller, Natalie J.; Hackstadt, Ted] NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. [Fischer, Elizabeth R.] NIAID, Microscopy Unit, NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU NIAID/NIH FX This work was supported by the intramural research programme of the NIAID/NIH. We thank Janet Sager for technical assistance and Drs R. Heinzen and J. Celli for critical review of the manuscript. NR 63 TC 60 Z9 62 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD SEP PY 2010 VL 12 IS 9 BP 1235 EP 1249 DI 10.1111/j.1462-5822.2010.01465.x PG 15 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 639KB UT WOS:000280972600005 PM 20331642 ER PT J AU Kim, YS Harry, GJ Kang, HS Goulding, D Wine, RN Kissling, GE Liao, G Jetten, AM AF Kim, Yong-Sik Harry, G. Jean Kang, Hong Soon Goulding, David Wine, Rob N. Kissling, Grace E. Liao, Grace Jetten, Anton M. TI Altered Cerebellar Development in Nuclear Receptor TAK1/TR4 Null Mice Is Associated with Deficits in GLAST(+) Glia, Alterations in Social Behavior, Motor Learning, Startle Reactivity, and Microglia SO CEREBELLUM LA English DT Article DE Cerebellum; Behavior; GLAST; Granule cells; Motor activity; Prepulse startle ID NEURONAL MIGRATION; ORPHAN RECEPTOR; MOUSE CEREBELLUM; PREPULSE INHIBITION; GRANULE CELLS; MUTANT MICE; GENE; TR4; MODELS; AUTISM AB Previously, deficiency in the expression of the nuclear orphan receptor TAK1 was found to be associated with delayed cerebellar granule cell migration and Purkinje cell maturation with a permanent deficit in foliation of lobules VI-VII, suggesting a role for TAK1 in cerebellum development. In this study, we confirm that TAK1-deficient (TAK1(-/-)) mice have a smaller cerebellum and exhibit a disruption of lobules VI-VII. We extended these studies and show that at postnatal day 7, TAK1(-/-) mice exhibit a delay in monolayer maturation of dysmorphic calbindin 28K-positive Purkinje cells. The astrocyte-specific glutamate transporter (GLAST) was expressed within Bergmann fibers and internal granule cell layer at significantly lower levels in the cerebellum of TAK1(-/-) mice. At PND21, Golgi-positive Purkinje cells in TAK1(-/-) mice displayed a smaller soma (18%) and shorter distance to first branch point (35%). Neuronal death was not observed in TAK1(-/-) mice at PND21; however, activated microglia were present in the cerebellum, suggestive of earlier cell death. These structural deficits in the cerebellum were not sufficient to alter motor strength, coordination, or activity levels; however, deficits in acoustic startle response, prepulse startle inhibition, and social interactions were observed. Reactions to a novel environment were inhibited in a light/dark chamber, open-field, and home-cage running wheel. TAK1(-/-) mice displayed a plateau in performance on the running wheel, suggesting a deficit in learning to coordinate performance on a motor task. These data indicate that TAK1 is an important transcriptional modulator of cerebellar development and neurodevelopmentally regulated behavior. C1 [Kim, Yong-Sik; Kang, Hong Soon; Liao, Grace; Jetten, Anton M.] NIEHS, Lab Resp Biol, Cell Biol Sect, Div Intramural Res,NIH, Durham, NC 27709 USA. [Harry, G. Jean; Wine, Rob N.] NIEHS, Mol Toxicol Lab, Div Intramural Res, NIH, Durham, NC 27709 USA. [Goulding, David] NIEHS, Comparat Med Branch, Div Intramural Res, NIH, Durham, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Div Intramural Res, NIH, Durham, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Lab Resp Biol, Cell Biol Sect, Div Intramural Res,NIH, POB 12233, Durham, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 FU Division of Intramural Research at the National Institute of Environmental Health Sciences, NIH [Z01-ES-101586, Z01-ES-021164] FX The authors thank Dr. Randy Thresher, UNC/Chapel Hill, NC for generating TAK1-/- mice; Ms. Laura M. Degraff for technical assistance; Dr. Fu Du for the Golgi staining, and Drs. Gordon Flake (NIEHS) and Robert Berman (University of California/Davis) for comments. This research was supported by the Division of Intramural Research at the National Institute of Environmental Health Sciences, NIH (Z01-ES-101586; Z01-ES-021164). NR 62 TC 15 Z9 16 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD SEP PY 2010 VL 9 IS 3 BP 310 EP 323 DI 10.1007/s12311-010-0163-z PG 14 WC Neurosciences SC Neurosciences & Neurology GA 658SD UT WOS:000282508800007 PM 20393820 ER PT J AU da Guarda, SNF Cohen, LG Pinho, MDC Yamamoto, FI Marchiori, PE Scaff, M Conforto, AB AF Farias da Guarda, Suzete Nascimento Cohen, Leonardo G. Pinho, Marco da Cunha Yamamoto, Fabio Iuji Marchiori, Paulo Euripedes Scaff, Milberto Conforto, Adriana Bastos TI Interhemispheric Asymmetry of Corticomotor Excitability After Chronic Cerebellar Infarcts SO CEREBELLUM LA English DT Article DE Transcranial magnetic stimulation; Paired pulse; Cerebellar disease; Stroke ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR CORTEX EXCITABILITY; CHRONIC STROKE; MECHANISMS; MODULATION; PLASTICITY; HUMANS; SYSTEM; ATAXIA; SCALE AB Early after stroke, there is loss of intracortical facilitation (ICF) and increase in short-interval intracortical inhibition (SICI) in the primary motor cortex (M1) contralateral to a cerebellar infarct. Our goal was to investigate intracortical M1 function in the chronic stage following cerebellar infarcts (> 4 months). We measured resting motor threshold (rMT), SICI, ICF, and ratios between motor-evoked potential amplitudes (MEP) and supramaximal M response amplitudes (MEP/M; %), after transcranial magnetic stimulation was applied to the M1 contralateral (M1(contralesional)) and ipsilateral (M1(ipsilesional)) to the cerebellar infarct in patients and to both M1s of healthy age-matched volunteers. SICI was decreased in M1(contralesional) compared to M1(ipsilesional) in the patient group in the absence of side-to-side differences in controls. There were no significant interhemispheric or between-group differences in rMT, ICF, or MEP/M (%). Our results document disinhibition of M1(contralesional) in the chronic phase after cerebellar stroke. C1 [Farias da Guarda, Suzete Nascimento; Yamamoto, Fabio Iuji; Marchiori, Paulo Euripedes; Scaff, Milberto; Conforto, Adriana Bastos] Univ Sao Paulo, Clin Hospital, Dept Neurol, Sao Paulo, Brazil. [Farias da Guarda, Suzete Nascimento; Conforto, Adriana Bastos] Univ Sao Paulo, Clin Hospital, Neurostimulat Lab, Sao Paulo, Brazil. [Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Pinho, Marco da Cunha] Univ Sao Paulo, Dept Radiol, Clin Hospital, Sao Paulo, Brazil. [Conforto, Adriana Bastos] Inst Israelita Ensino & Pesquisa Albert Einstein, Sao Paulo, Brazil. RP da Guarda, SNF (reprint author), Rua Oito Dezembro,291 Ap 1202, BR-40150000 Salvador, Brazil. EM suzetefarias@terra.com.br OI Pinho, Marco/0000-0002-4645-1638 FU Fundacao Faculdade de Medicina, Clinics Hospital/Sao Paulo University FX Dr. Suzete N. Farias received a research scholarship from Fundacao Faculdade de Medicina, Clinics Hospital/Sao Paulo University. We thank Michael Dimyan for helpful comments and suggestions. NR 36 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1473-4222 J9 CEREBELLUM JI Cerebellum PD SEP PY 2010 VL 9 IS 3 BP 398 EP 404 DI 10.1007/s12311-010-0176-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 658SD UT WOS:000282508800014 ER PT J AU Mur, M Ruff, DA Bodurka, J Bandettini, PA Kriegeskorte, N AF Mur, Marieke Ruff, Douglas A. Bodurka, Jerzy Bandettini, Peter A. Kriegeskorte, Nikolaus TI Face-Identity Change Activation Outside the Face System: "Release from Adaptation" May Not Always Indicate Neuronal Selectivity SO CEREBRAL CORTEX LA English DT Article DE attention; face-identity; fMRI-adaptation; fusiform face area; neuronal representation ID HUMAN VISUAL-CORTEX; HUMAN FUSIFORM GYRUS; FMRI-ADAPTATION; DISTINCT REPRESENTATIONS; FUNCTIONAL ARCHITECTURE; ACQUIRED PROSOPAGNOSIA; PARAHIPPOCAMPAL CORTEX; REPETITION SUPPRESSION; SPATIAL ATTENTION; CORTICAL ACTIVITY AB Face recognition is a complex cognitive process that requires distinguishable neuronal representations of individual faces. Previous functional magnetic resonance imaging (fMRI) studies using the "fMRI-adaptation" technique have suggested the existence of face-identity representations in face-selective regions, including the fusiform face area (FFA). Here, we present face-identity adaptation findings that are not well explained in terms of face-identity representations. We performed blood-oxygen level-dependent (BOLD) fMRI measurements, while participants viewed familiar faces that were shown repeatedly throughout the experiment. We found decreased activation for repeated faces in face-selective regions, as expected based on previous studies. However, we found similar effects in regions that are not face-selective, including the parahippocampal place area (PPA) and early visual cortex (EVC). These effects were present for exact-image (same view and lighting) as well as different-image (different view and/or lighting) repetition, but more widespread for exact-image repetition. Given the known functional properties of PPA and EVC, it appears unlikely that they contain domain-specific face-identity representations. Alternative interpretations include general attentional effects and carryover of activation from connected regions. These results remind us that fMRI stimulus-change effects can have a range of causes and do not provide conclusive evidence for a neuronal representation of the changed stimulus property. C1 [Mur, Marieke; Ruff, Douglas A.; Bandettini, Peter A.; Kriegeskorte, Nikolaus] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. [Mur, Marieke] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, NL-6229 ER Maastricht, Netherlands. [Bodurka, Jerzy; Bandettini, Peter A.] NIMH, Funct Magnet Resonance Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Mur, M (reprint author), Univ Singel 40,Room 4-777, NL-6229 ER Maastricht, Netherlands. EM marieke.mur@maastrichtuniversity.nl OI Kriegeskorte, Nikolaus/0000-0001-7433-9005; Ruff, Douglas/0000-0001-7228-8822 FU National Institute of Mental Health at the National Institutes of Health FX Intramural Research Program of the National Institute of Mental Health at the National Institutes of Health. NR 76 TC 42 Z9 43 U1 2 U2 5 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 SEP PY 2010 VL 20 IS 9 BP 2027 EP 2042 DI 10.1093/cercor/bhp272 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 646RP UT WOS:000281560200002 PM 20051364 ER PT J AU Tanaka, S Honda, M Hanakawa, T Cohen, LG AF Tanaka, Satoshi Honda, Manabu Hanakawa, Takashi Cohen, Leonardo G. TI Differential Contribution of the Supplementary Motor Area to Stabilization of a Procedural Motor Skill Acquired through Different Practice Schedules SO CEREBRAL CORTEX LA English DT Article DE magnetic stimulation; memory and learning; motor cortex; motor learning; training ID TRANSCRANIAL MAGNETIC STIMULATION; EXPERIENCE-DEPENDENT CHANGES; MEDIAL FRONTAL-CORTEX; CONTEXTUAL INTERFERENCE; MEMORY CONSOLIDATION; TEMPORAL ORGANIZATION; SEQUENTIAL-PROCEDURES; INTERMANUAL TRANSFER; MULTIPLE MOVEMENTS; NEURONAL-ACTIVITY AB Behavioral studies have suggested that the stabilization of motor memory varies depending on the practice schedule. The neural substrates underlying this schedule-dependent difference in memory stabilization are not known. Here, we evaluated the effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied to different cortical regions and sham after one session of training (Day 1) of sequential motor skills acquired through blocked (each sequence was completely trained before training the next)-practice schedules and random (random training of 3 sequences)-practice schedules. The recall of sequences learned on Day 1 by Day 2 was measured in different groups of healthy volunteers. The rTMS over the supplementary motor area (SMA) but not over control regions or over the primary motor cortex (M1) immediately after practice or over SMA 6 h later reduced recall relative to sham only in the blocked-practice group. In contrast, recall in the random-practice group was unaffected by rTMS. These results document a differential contribution of the SMA to the stabilization of motor memories acquired through different practice schedules. More generally, they indicate that the anatomical substrates underlying motor-memory stabilization (or their temporal operation) do differ depending on the practice schedule. C1 [Tanaka, Satoshi; Cohen, Leonardo G.] NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, Bethesda, MD 20892 USA. [Tanaka, Satoshi; Honda, Manabu; Hanakawa, Takashi] Natl Inst Neurosci, Dept Cort Funct Disorders, Kodaira, Tokyo 1878502, Japan. [Honda, Manabu] Japan Sci & Technol Corp, Solut Oriented Res Sci & Technol, Saitama 3310012, Japan. [Hanakawa, Takashi] Japan Sci & Technol Corp, Precursory Res Embryon Sci & Technol, Saitama 3310012, Japan. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol & Stroke Neurorehabil Sect, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cohenl@ninds.nih.gov FU National Institute of Neurological Disorder and Stroke, National Institute of Health (NIH); Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH; Exploratory Research for Advanced Technology Shimojo Implicit Brain Function Project; Ministry of Education, Culture, Sports, Science and Technology, Japan [20019041, 20033030] FX Intramural Research Program of the National Institute of Neurological Disorder and Stroke, National Institute of Health (NIH); Japan Society for the Promotion of Science Research Fellowship for Japanese Biomedical and Behavioral Researchers at NIH; Exploratory Research for Advanced Technology Shimojo Implicit Brain Function Project; KAKENHI (20019041, 20033030) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. NR 65 TC 21 Z9 21 U1 1 U2 11 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 SEP PY 2010 VL 20 IS 9 BP 2114 EP 2121 DI 10.1093/cercor/bhp276 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 646RP UT WOS:000281560200009 PM 20038545 ER PT J AU Nelson, TM LopezJimenez, ND Tessarollo, L Inoue, M Bachmanov, AA Sullivan, SL AF Nelson, Theodore M. LopezJimenez, Nelson D. Tessarollo, Lino Inoue, Masashi Bachmanov, Alexander A. Sullivan, Susan L. TI Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene SO CHEMICAL SENSES LA English DT Article DE gene knockout; gustatory nerves; polycystic kidney disease-like ion channel; preference; taste; threshold ID GUSTATORY NEURAL RESPONSES; RECEPTOR-CELLS; SOUR-TASTE; CHORDA TYMPANI; 129P3/J MICE; SALT TASTE; NULL MICE; SACCHARIN PREFERENCE; ALLELIC VARIATION; MAMMALIAN TASTE AB Recent studies, both in vitro and in vivo, have suggested the involvement of the polycystic kidney disease-1 and -2 like genes, Pkd1l3 and Pkd2l1, in acid taste transduction. In mice, disruption of taste cells expressing PKD2L1 eliminates gustatory neural responses to acids. However, no previous data exist on taste responses in the absence of PKD1L3 or on behavioral responses in mice lacking either of these proteins. In order to assess the function of PKD1L3, we genetically engineered mice with a targeted mutation of the Pkd1l3 gene. We then examined taste responsiveness of mutant and wild-type mice using several different approaches. In separate groups of mice, we measured preference scores in 48-h 2-bottle tests, determined NaCl or citric acid taste thresholds using a conditioned taste aversion technique, and conducted electrophysiological recordings of activity in the chorda tympani and glossopharyngeal nerves. Multiple taste compounds representing all major taste qualities were used in the preference tests and nerve-recording experiments. We found no significant reduction in taste responsiveness in Pkd1l3 mutant mice in behavioral or electrophysiologic:al tests when compared with wild-type controls. Therefore, further studies are needed to elucidate the function of PKD1L3 in taste bud cells. C1 [Nelson, Theodore M.; Bachmanov, Alexander A.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [LopezJimenez, Nelson D.; Sullivan, Susan L.] Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, NIH, Rockville, MD 20850 USA. [Tessarollo, Lino] NCI, Neural Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Inoue, Masashi] Tokyo Univ Pharm & Life Sci, Dept Life Sci, Lab Cellular Neurobiol, Tokyo 1920392, Japan. RP Nelson, TM (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM tnelson@monell.org OI Bachmanov, Alexander/0000-0002-2861-3322 FU National Institutes of Health (NIH) [R01 DC00882, R01 AA11028]; NIH, National Cancer Institute; NIH, NIDCD FX This work was supported in part by National Institutes of Health (NIH) grants (R01 DC00882 and R01 AA11028 to A.A.B.) and Intramural Research Program of the NIH (National Cancer Institute to L.T. and NIDCD to S.L.S.). NR 61 TC 37 Z9 40 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD SEP PY 2010 VL 35 IS 7 BP 565 EP 577 DI 10.1093/chemse/bjq070 PG 13 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 647SJ UT WOS:000281639100006 PM 20605874 ER PT J AU Fushan, AA Simons, CT Slack, JP Drayna, D AF Fushan, Alexey A. Simons, Christopher T. Slack, Jay P. Drayna, Dennis TI Association between Common Variation in Genes Encoding Sweet Taste Signaling Components and Human Sucrose Perception SO CHEMICAL SENSES LA English DT Article DE association; genetic variations; gustducin; sucrose ID ALPHA-GUSTDUCIN; INSULIN-RESISTANCE; ESSENTIAL-HYPERTENSION; NATURAL-SELECTION; RECEPTOR-CELLS; TRAIT LOCUS; UMAMI TASTE; HAPLOTYPE; GENOME; SENSITIVITY AB Variation in taste perception of different chemical substances is a well-known phenomenon in both humans and animals. Recent advances in the understanding of sweet taste signaling have identified a number of proteins involved in this signal transduction. We evaluated the hypothesis that sequence variations occurring in genes encoding taste signaling molecules can influence sweet taste perception in humans. Our population consisted of unrelated individuals (n = 160) of Caucasian, African-American, and Asian descent. Threshold and suprathreshold sensitivities of participants for sucrose were estimated using a sorting test and signal detection analysis that produced cumulative R-index area under the curve (AUC) scores. Genetic association analysis revealed significant correlation of sucrose AUC scores with genetic variation occurring in the GNAT3 gene (single point P = 10(-3) to 10(-4)), which encodes the taste-specific Go, protein subunit gustducin. Subsequent sequencing identified additional GNAT3 variations having significant association with sucrose AUC scores. Collectively, GNAT3 polymorphisms explain 13% of the variation in sucrose perception. Our findings underscore the importance of common genetic variants influencing human taste perception. C1 [Fushan, Alexey A.; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. [Simons, Christopher T.; Slack, Jay P.] Givaudan Flavors Corp, Dept Sci & Technol, Cincinnati, OH 45216 USA. RP Drayna, D (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov RI Simons, Christopher/B-3036-2013 FU National Institute on Deafness and Other Communication Disorders/National Institutes of Health [Z01-000046-09]; Givaudan Flavors Corporation [CRADA DC-CR-06-01] FX This work was supported by National Institute on Deafness and Other Communication Disorders/National Institutes of Health (Z01-000046-09) and Givaudan Flavors Corporation (CRADA DC-CR-06-01). NR 55 TC 31 Z9 31 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD SEP PY 2010 VL 35 IS 7 BP 579 EP 592 DI 10.1093/chemse/bjq063 PG 14 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 647SJ UT WOS:000281639100007 PM 20660057 ER PT J AU Young, LR VanDyke, R Gulleman, PM Inoue, Y Brown, KK Schmidt, LS Linehan, WM Hajjar, F Kinder, BW Trapnell, BC Bissler, JJ Franz, DN McCormack, FX AF Young, Lisa R. VanDyke, Rhonda Gulleman, Peter M. Inoue, Yoshikazu Brown, Kevin K. Schmidt, Laura S. Linehan, W. Marston Hajjar, Fuad Kinder, Brent W. Trapnell, Bruce C. Bissler, John J. Franz, David N. McCormack, Francis X. TI Serum Vascular Endothelial Growth Factor-D Prospectively Distinguishes Lymphangioleiomyomatosis From Other Diseases SO CHEST LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; VEGF-D; CONSENSUS CONFERENCE; CELL CLUSTERS; LYMPHANGIOGENESIS; LAM; CT AB Objectives: The majority of women with lymphangioleiomyomatosis (LAM) present with cystic lung disease, and most require lung biopsy for definitive diagnosis. The purpose of this study was to determine the prospective diagnostic usefulness of a serologic test for vascular endothelial growth factor-D (VEGF-D), a lymphangiogenic growth factor. Methods: We prospectively measured serum VEGF-D levels by enzyme-linked immunoassay in 48 women presenting with cystic lung disease. Diagnostic test performance was determined from a cohort of 195 women, with tuberous sclerosis complex (TSC), TSC-LAM, sporadic LAM (S-LAM), and other cystic lung diseases in the differential diagnosis, including biopsy-proven or genetically proven pulmonary Langerhans cell histiocytosis, emphysema, Sjogren syndrome, or Birt-Hogg-Dube syndrome. Results: Serum VEGF-D levels were significantly greater in S-LAM (median 1,175 [interquartile range (IQR): 780-2,013] pg/mL; n = 56) than in other cystic lung diseases (median 281 [IQR 203-351] pg/mL; n=44, P <.001). In the cohort evaluated prospectively, 12 of the 15 individuals ultimately diagnosed with LAM by biopsy had VEGF-D levels of > 800 pg/mL, whereas levels were <600 pg/mL in all 18 subjects later diagnosed with other causes of cystic lung disease. Receiver operating characteristic curves demonstrated that VEGF-D effectively identified LAM, with an area under the curve of 0.961(95% CI, 0.923-0.992). A VEGF-D level of > 600 pg/mL was highly associated with a diagnosis of LAM (specificity 97.6%, likelihood ratio 35.2) and values >800 pg/mL were diagnostically specific. Serum VEGF-D levels were significantly elevated in women with TSC-LAM (median 3,465 [IQR 1,970-7,1951 pg/mL) compared with women with TSC only (median 370 [IQR 291-5201 pg/mL), P<.001). Conclusions: A serum VEGF-D level of > 800 pg/mL in a woman with typical cystic changes on high-resolution CT (HRCT) scan is diagnostically specific for S-LAM and identifies LAM in women with TSC. A negative VEGF-D result does not exclude the diagnosis of LAM. The usefulness of serum VEGF-D testing in men or in women who do not have cystic lung disease on HRCT scan is unknown. CHEST 2010; 138(3):674-681 C1 [Young, Lisa R.; Hajjar, Fuad; Kinder, Brent W.; McCormack, Francis X.] Univ Cincinnati, Coll Med, Div Pulm Crit Care & Sleep Med, Cincinnati, OH 45267 USA. [Young, Lisa R.; VanDyke, Rhonda; Gulleman, Peter M.] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Med, Cincinnati, OH USA. [VanDyke, Rhonda] Cincinnati Childrens Hosp, Med Ctr, Div Biostat, Cincinnati, OH USA. [Trapnell, Bruce C.] Cincinnati Childrens Hosp, Med Ctr, Div Pulm Biol, Cincinnati, OH USA. [Bissler, John J.] Cincinnati Childrens Hosp, Med Ctr, Div Nephrol, Cincinnati, OH USA. [Franz, David N.] Cincinnati Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH USA. [Inoue, Yoshikazu] Natl Hosp Org, Kinki Chuo Chest Med Ctr, Osaka, Japan. [Brown, Kevin K.] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Schmidt, Laura S.] SAIC Frederick Inc, NCI Frederick, Basic Res Program, Frederick, MD USA. [Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP McCormack, FX (reprint author), Univ Cincinnati, Coll Med, Div Pulm Crit Care & Sleep Med, 231 Albert Sabin Way,Med Sci Bldg,Room 6114,MLC 0, Cincinnati, OH 45267 USA. EM Frank.McCormack@uc.edu RI Szczesniak, Rhonda/M-4446-2015; OI McCormack, Francis/0000-0001-7168-9464 FU LAM Foundation; The Tante Mela Foundation; National institutes of Health, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Wyeth for clinical trials in LAM; [NIH/NHLB1 RR19498] FX This study was funded in pie by a pilot project grant from The LAM Foundation, The Tante Mela Foundation, and NIH/NHLB1 RR19498. This research was also supported in part by the Intramural Research Program of the National institutes of Health, National Cancer Institute, Center for Cancer Research. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E (to L. S. S.).; The authors have reported to CHEST the following conflicts of interest: Dr Kinder received grant monies of > $1.00,000 from the National Institutes of Health. Drs Young and McCormack have received federal and university grant monies and funding from Wyeth for clinical trials in LAM. They have filed a patent application for the development of the VEGF-D assay as a diagnostic tool. They have waived their rights to royalties generated by the performance of the assay. Mr Gulleman and Drs VanDyke, Inoue, Brown, Schmidt, Linehan, Hajjar, Trapnell, Bissler, and Franz have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 21 TC 64 Z9 67 U1 1 U2 4 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 674 EP 681 DI 10.1378/chest.10-0573 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500033 PM 20382711 ER PT J AU Castriotta, RJ Eldadah, BA Foster, WM Halter, JB Hazzard, WR Kiley, JP King, TE Horne, FM Nayfield, SG Reynolds, HY Schmader, KE Toews, GB High, KP AF Castriotta, Richard J. Eldadah, Basil A. Foster, W. Michael Halter, Jeffrey B. Hazzard, William R. Kiley, James P. King, Talmadge E., Jr. Horne, Frances McFarland Nayfield, Susan G. Reynolds, Herbert Y. Schmader, Kenneth E. Toews, Galen B. High, Kevin P. TI Workshop on Idiopathic Pulmonary Fibrosis in Older Adults SO CHEST LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; INTERSTITIAL LUNG-DISEASE; ALVEOLAR EPITHELIAL-CELLS; GASTROESOPHAGEAL-REFLUX DISEASE; GENE-EXPRESSION PROFILES; PLACEBO-CONTROLLED TRIAL; MESENCHYMAL STEM-CELLS; ARTERIAL-HYPERTENSION; ACUTE EXACERBATIONS; DIABETES-MELLITUS AB Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary, research, but these efforts have great potential to improve care for patients with IPF. CHEST 2010; 138(3):693-703 C1 [High, Kevin P.] Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Winston Salem, NC 27157 USA. [Castriotta, Richard J.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Eldadah, Basil A.] NIA, Bethesda, MD 20892 USA. [Foster, W. Michael] Duke Univ, Sch Med, Durham, NC USA. [Halter, Jeffrey B.; Toews, Galen B.] Univ Michigan, Sch Med, Ann Arbor, MI USA. [Hazzard, William R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Kiley, James P.; Reynolds, Herbert Y.] NHLBI, Bethesda, MD 20892 USA. [King, Talmadge E., Jr.] Univ Calif San Francisco, San Francisco Sch Med, San Francisco, CA USA. [Horne, Frances McFarland] Assoc Specialty Prof, Washington, DC USA. [Nayfield, Susan G.] Univ Florida, Sch Med, Gainesville, FL USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, Durham, NC USA. [Schmader, Kenneth E.] GRECC Durham VA Med Ctr, Durham, NC USA. RP High, KP (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM khigh@wfubmc.edu OI Castriotta, Richard/0000-0003-3502-4558 FU John A. Hartford Foundation [2006-0239]; Cephalon, Inc.; Merck; Wyeth; Pfizer; Optimer; Chimerix; Afexa Life Sciences FX This workshop was supported by a grant from the John A. Hartford Foundation to the Association of Specialty Professors [Grant 2006-0239].; The authors have reported to CHEST the following conflicts of interest: Dr Castriotta is a consultant for Blue Cross and Blue Shield of Texas and has received past research support from Cephalon, Inc. Dr Eldadah is a federal employee with the National Institutes of Health. Dr King serves as a consultant to the following pharmaceutical or medical device companies: Actelion, AstraZeneca, Boehringer Ingelheim, Centocor, Chronoger, CV Therapeutics, Domantis Limited, FibroGen, Genzyme, Human Genome Sciences, Huya Bioscience, InterMune, Millennium Pharmaceuticals, Merck, GlaxoSmithKline, Gilead, Novartis, Hoffman-La Roche, Inc., and Serono. He also serves on the advisory committees for Actelion and InterMune and on the data safety monitoring boards for Centocor and GlaxoSmithKline. Dr Nayfield is a federal employee with the National Institutes of Health. Dr Reynolds is a federal employee with the National Institutes of Health. Dr Schmader has received grant support from Merck and Wyeth and serves as a consultant for Merck and GlaxoSmithKline. Dr High has received grant support from Merck, Pfizer, Optimer, Chimerix, and Afexa Life Sciences, and serves as a consultant for Optimer and GlaxoSmithKline. Drs Foster, Halter, Hazzard, Kiley, McFarland Home, and Toews have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 106 TC 25 Z9 25 U1 1 U2 9 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD SEP PY 2010 VL 138 IS 3 BP 693 EP 703 DI 10.1378/chest.09-3006 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 659IZ UT WOS:000282561500035 PM 20822991 ER PT J AU Amaruchkul, K AF Amaruchkul, Kannapha TI Stochastic Orders in Risk-Based Overbooking SO CHIANG MAI JOURNAL OF SCIENCE LA English DT Article DE stochastic model applications; operations research; revenue management ID YIELD-MANAGEMENT; REVENUE MANAGEMENT; DECISION AB In this article, we propose a risk-based overbooking model, in which an overbooking limit is chosen such that an expected profit is maximized. We derive an optimality condition, when a show demand given a total number of reservations follows a binomial distribution. We also determine a directional change of the optimal overbooking limit with respect to various model parameters, such as a show-up probability, a per-unit revenue and a per-unit oversale cost. Finally, we show that the optimal expected profit decreases, if the show-up probability increases. C1 NIDA, Sch Appl Stat, Bangkok 10240, Thailand. RP Amaruchkul, K (reprint author), NIDA, Sch Appl Stat, 118 Serithai Rd, Bangkok 10240, Thailand. EM kamaruchkul@gmail.com NR 15 TC 0 Z9 0 U1 0 U2 2 PU CHIANG MAI UNIV PI CHIANG MAI PA FACULTY SCIENCE, CHIANG MAI, 50200, THAILAND SN 0125-2526 J9 CHIANG MAI J SCI JI Chiang Mai J. Sci. PD SEP PY 2010 VL 37 IS 3 BP 377 EP 383 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 669GO UT WOS:000283336100003 ER PT J AU Kulemzina, AI Trifonov, VA Perelman, PL Ferguson-Smith, MA Stanyon, R Yang, F Graphodatsky, AS AF Kulemzina, A. I. Trifonov, V. A. Perelman, P. L. Ferguson-Smith, M. A. Stanyon, R. Yang, F. Graphodatsky, A. S. TI Chromosome evolution in key Cetartiodactyl families SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 19th International Colloquium on animal cytogenetics and gene mapping CY JUN 06-09, 2010 CL Natl Res Inst Anim Prod, Krakow, POLAND HO Natl Res Inst Anim Prod C1 [Kulemzina, A. I.; Trifonov, V. A.; Graphodatsky, A. S.] Inst Chem Biol & Fundamental Med SB RAS, Dept Mol & Cell Biol, Novosibirsk, Russia. [Perelman, P. L.] NCI, Frederick, MA USA. [Ferguson-Smith, M. A.] Resource Ctr Comparat Genom, Dept Vet Med, Cambridge, England. [Stanyon, R.] Univ Florence, Dept Evolutionary Biol, Florence, Italy. [Yang, F.] Wellcome Trust Sanger Inst, Cambridge, England. RI Trifonov, Vladimir/E-4907-2012; Perelman, Polina/N-8088-2015; Kulemzina, Anastasia/N-8554-2015; Graphodatsky, Alexander/B-4922-2010 OI Trifonov, Vladimir/0000-0003-0454-8359; Perelman, Polina/0000-0002-0982-5100; Graphodatsky, Alexander/0000-0002-8282-1085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD SEP PY 2010 VL 18 IS 6 BP 722 EP 723 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 651NY UT WOS:000281935600033 ER PT J AU Trifonov, VA Kulemzina, AI Stanyon, R Perelman, PL Ferguson-Smith, MA Yang, F Graphodatsky, AS AF Trifonov, V. A. Kulemzina, A. I. Stanyon, R. Perelman, P. L. Ferguson-Smith, M. A. Yang, F. Graphodatsky, A. S. TI Chromosome evolution in Perissodactyla SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 19th International Colloquium on animal cytogenetics and gene mapping CY JUN 06-09, 2010 CL Natl Res Inst Anim Prod, Krakow, POLAND HO Natl Res Inst Anim Prod C1 [Trifonov, V. A.; Kulemzina, A. I.; Graphodatsky, A. S.] Inst Chem Biol & Fundamental Med SB RAS, Novosibirsk, Russia. [Stanyon, R.] Univ Florence, Dept Anim Biol & Genet, Florence, Italy. [Perelman, P. L.] NCI, Frederick, MA USA. [Ferguson-Smith, M. A.] Cambridge Resource Ctr Comparat Genom, Dept Vet Med, Cambridge, England. [Yang, F.] Wellcome Trust Sanger Inst, Cambridge, England. RI Trifonov, Vladimir/E-4907-2012; Perelman, Polina/N-8088-2015; Kulemzina, Anastasia/N-8554-2015; Graphodatsky, Alexander/B-4922-2010 OI Trifonov, Vladimir/0000-0003-0454-8359; Perelman, Polina/0000-0002-0982-5100; Graphodatsky, Alexander/0000-0002-8282-1085 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PD SEP PY 2010 VL 18 IS 6 BP 722 EP 722 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 651NY UT WOS:000281935600032 ER PT J AU Fox, CS Massaro, JM Schlett, CL Lehman, SJ Meigs, JB O'Donnell, CJ Hoffmann, U Murabito, JM AF Fox, Caroline S. Massaro, Joseph M. Schlett, Christopher L. Lehman, Sam J. Meigs, James B. O'Donnell, Christopher J. Hoffmann, Udo Murabito, Joanne M. TI Periaortic Fat Deposition Is Associated With Peripheral Arterial Disease The Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE obesity; atherosclerosis; peripheral vascular diseases ID NUTRITION EXAMINATION SURVEY; ANKLE-BRACHIAL INDEX; ADIPOSE-TISSUE; RISK-FACTORS; INTERMITTENT CLAUDICATION; METABOLIC SYNDROME; PERIVASCULAR FAT; NATIONAL-HEALTH; OBESITY; PREVALENCE AB Background-Central obesity is associated with peripheral arterial disease, suggesting that ectopic fat depots may be associated with localized diseases of the aorta and lower-extremity arteries. We hypothesized that persons with greater amounts of periaortic fat are more likely to have clinical PAD and a low ankle-brachial index. Methods and Results-We quantified periaortic fat surrounding the thoracic aorta using a novel volumetric quantitative approach in 1205 participants from the Framingham Heart Study Offspring cohort (mean age, 65.9 years; women, 54%); visceral abdominal fat also was measured. Clinical peripheral arterial disease was defined as a history of intermittent claudication, and ankle-brachial index was dichotomized as low (<= 0.9) or lower-extremity revascularization versus normal (>0.9 to <1.4). Regression models were created to examine the association between periaortic fat and intermittent claudication or low ankle-brachial index (n = 66). In multivariable logistic regression, per 1 SD increase in periaortic fat, the odds ratio for the combined end point was 1.52 (P = 0.004); these results were strengthened with additional adjustment for body mass index (odds ratio, 1.69; P = 0.002) or visceral abdominal fat (odds ratio, 1.67; P = 0.009), whereas no association was observed for visceral abdominal fat (P = 0.16). Similarly, per SD increase in body mass index or waist circumference, no association was observed after accounting for visceral abdominal fat (body mass index, P = 0.35; waist circumference, P = 0.49). Conclusions-Periaortic fat is associated with low ABI and intermittent claudication. (Circ Cardiovasc Imaging. 2010;3:515-519.) C1 [Fox, Caroline S.; O'Donnell, Christopher J.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [Fox, Caroline S.; O'Donnell, Christopher J.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Schlett, Christopher L.; Lehman, Sam J.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Cardiac MR PET CT, Boston, MA 02114 USA. [Massaro, Joseph M.] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. [Fox, Caroline S.; Schlett, Christopher L.; Lehman, Sam J.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Lehman, Sam J.] Flinders Univ S Australia, Dept Cardiol, Adelaide, SA 5001, Australia. [Massaro, Joseph M.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; General Clinical Research Centers Program [M01-RR-01066]; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK080140]; GlaxoSmithKline; Sanofi-Aventis FX This work was supported by the National Heart, Lung, and Blood Institute Framingham Heart Study (N01-HC-25195), the General Clinical Research Centers Program (grant number M01-RR-01066), and a Career Development Award from the American Diabetes Association and National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK080140) to Dr Massaro.; Dr Massaro currently has research grants from GlaxoSmithKline and Sanofi-Aventis, and has consulting agreements with Eli Lilly and Interleukin Genetics. The other authors report no conflicts. NR 24 TC 35 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2010 VL 3 IS 5 BP 515 EP 519 DI 10.1161/CIRCIMAGING.110.958884 PG 5 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649RH UT WOS:000281790000006 PM 20639302 ER PT J AU Berry, C Kellman, P Mancini, C Chen, MY Bandettini, WP Lowrey, T Hsu, LY Aletras, AH Arai, AE AF Berry, Colin Kellman, Peter Mancini, Christine Chen, Marcus Y. Bandettini, W. Patricia Lowrey, Tracy Hsu, Li-Yueh Aletras, Anthony H. Arai, Andrew E. TI Magnetic Resonance Imaging Delineates the Ischemic Area at Risk and Myocardial Salvage in Patients With Acute Myocardial Infarction SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE myocardial infarction; MRI; edema; myocardial ischemia ID AUTOMATED FEATURE ANALYSIS; CORONARY-ARTERY OCCLUSION; DELAYED ENHANCEMENT MRI; NO-REFLOW PHENOMENON; SIZING ALGORITHM; RELAXATION-TIMES; VALIDATION; REPERFUSION; EDEMA; SIZE AB Background-The area at risk (AAR) is a key determinant of myocardial infarction (MI) size. We investigated whether magnetic resonance imaging (MRI) measurement of AAR would be correlated with an angiographic AAR risk score in patients with acute MI. Methods and Results-Bright-blood, T2-prepared, steady-state, free-precession MRI was used to depict the AAR in 50 consecutive acute MI patients, whereas infarct size was measured on gadolinium late-contrast-enhancement images. AAR was also estimated by the APPROACH and DUKE angiographic jeopardy scores and ST-segment elevation score. Myocardial salvage was calculated as AAR minus infarct size. Results are mean +/- SD unless specified otherwise. Patients were 61 +/- 12 years of age, 76% had an ST-segment elevation MI, and 20% had a prior MI. All underwent MRI 4 +/- 2 days after initial presentation. The relation between MRI and the APPROACH angiographic estimates of AAR was similar (overall size relative to left ventricular mass was 32 +/- 12% vs 30 +/- 12%, respectively, P = 0.33), correlated well (r = 0.78, P < 0.0001), and had a 2.5% bias on Bland-Altman analysis. The DUKE jeopardy score underestimated AAR relative to infarct size and was correlated less well with MRI (r = 0.39, P = 0.0055). ST-segment elevation score underestimated infarct size in 19 subjects (50%) and was not correlated with MRI (r = 0.27, P = 0.06). Myocardial salvage varied according to Thrombolysis in Myocardial Infarction flow grade at the end of angiography/percutaneous coronary intervention (P = 0.04), and Thrombolysis in Myocardial Infarction flow grade was a univariable predictor of myocardial salvage (P = 0.011). In multivariable analyses, infarct size was predicted by T2-prepared, steady-state, free-precession MRI (P < 0.0001). Conclusions-T2-prepared, steady-state, free-precession MRI delineates the AAR and enables estimation of myocardial salvage when coupled with a measurement of infarct size. (Circ Cardiovasc Imaging. 2010;3:527-535.) C1 [Berry, Colin; Kellman, Peter; Chen, Marcus Y.; Bandettini, W. Patricia; Lowrey, Tracy; Hsu, Li-Yueh; Aletras, Anthony H.; Arai, Andrew E.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Berry, Colin] Univ Glasgow, Fac Med, Glasgow, Lanark, Scotland. RP Arai, AE (reprint author), NHLBI, NIH, US Dept HHS, Bldg 10,Room B1D 416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA. EM araia@nih.gov OI Aletras, Anthony/0000-0002-3786-3817 FU Division of Intramural Research of the National Institutes of Health; University of Glasgow; Scottish Funding Council FX This research was funded by the Division of Intramural Research of the National Institutes of Health. Dr Berry was supported by a University of Glasgow Lord Kelvin Adam Smith Fellowship (2005-2009) and is currently supported by a Senior Fellowship from the Scottish Funding Council. NR 30 TC 75 Z9 75 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2010 VL 3 IS 5 BP 527 EP 535 DI 10.1161/CIRCIMAGING.109.900761 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649RH UT WOS:000281790000008 PM 20631034 ER PT J AU Thanassoulis, G Massaro, JM Hoffmann, U Mahabadi, AA Vasan, RS O'Donnell, CJ Fox, CS AF Thanassoulis, George Massaro, Joseph M. Hoffmann, Udo Mahabadi, Amir A. Vasan, Ramachandran S. O'Donnell, Christopher J. Fox, Caroline S. TI Prevalence, Distribution, and Risk Factor Correlates of High Pericardial and Intrathoracic Fat Depots in the Framingham Heart Study SO CIRCULATION-CARDIOVASCULAR IMAGING LA English DT Article DE pericardial fat; obesity; epidemiology ID EPICARDIAL ADIPOSE-TISSUE; VISCERAL ABDOMINAL FAT; METABOLIC SYNDROME; OBESE SUBJECTS; DISEASE; MEN; ASSOCIATION; COMMUNITY AB Background-Pericardial and intrathoracic fat depots may represent novel risk factors for obesity-related cardiovascular disease. We sought to determine the prevalence, distribution, and risk factor correlates of high pericardial and intrathoracic fat deposits. Methods and Results-Participants from the Framingham Heart Study (n = 3312; mean age, 52 years; 48% women) underwent multidetector CT imaging in 2002 to 2005; high pericardial and high intrathoracic fat were defined on the basis of the sex-specific 90th percentile for these fat depots in a healthy reference sample. For men and women, the prevalence of high pericardial fat was 29.3% and 26.3%, respectively, and high intrathoracic fat was 31.4% and 35.3%, respectively. Overall, 22.1% of the sample was discordant for pericardial and intrathoracic fat depots: 8.3% had high pericardial but normal intrathoracic fat and 13.8% had high intrathoracic but normal pericardial fat. Higher body mass index, higher waist circumference, and increased prevalence of metabolic syndrome were more prevalent in participants with high intrathoracic fat depots than with high pericardial fat (P < 0.05 for all comparisons). High abdominal visceral adipose tissue was more frequent in participants with high intrathoracic adipose tissue compared with those with high pericardial fat (P < 0.001). Intrathoracic fat but not waist circumference was more highly correlated with visceral adipose tissue (r = 0.76 and 0.78 in men and women, respectively; P < 0.0001) than with subcutaneous adipose tissue (SAT) (r = 0.46 and 0.54 in men and women, respectively; P < 0.0001). Conclusions-Although prevalence of pericardial fat and intrathoracic fat were comparable at 30%, intrathoracic fat correlated more closely with metabolic risk and visceral fat. Intrathoracic fat may be a potential marker of metabolic risk and visceral fat on thoracic imaging. (Circ Cardiovasc Imaging. 2010;3:559-566.) C1 [Thanassoulis, George; Vasan, Ramachandran S.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Framingham Heart Study, Framingham, MA 01702 USA. [Thanassoulis, George] Boston Univ, Sch Med, Boston, MA 02118 USA. [Massaro, Joseph M.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Hoffmann, Udo; Mahabadi, Amir A.; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Div Endocrinol, Boston, MA USA. [O'Donnell, Christopher J.] NIH, Div Intramural Res, Bethesda, MD USA. [Fox, Caroline S.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, NIH, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI 王, 强/F-4212-2011; OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU Canadian Institute of Health Research; Fonds de Recherche en Sante du Quebec; National Institutes of Health [N01-HC-25195]; [R01-DK-080739] FX Dr Thanassoulis is supported by a Research Fellowship from the Canadian Institute of Health Research and the Fonds de Recherche en Sante du Quebec. The Framingham Heart Study is supported by National Institutes of Health Contract No. N01-HC-25195. Dr Vasan was supported in part by grant R01-DK-080739. NR 21 TC 32 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-9651 EI 1942-0080 J9 CIRC-CARDIOVASC IMAG JI Circ.-Cardiovasc. Imaging PD SEP PY 2010 VL 3 IS 5 BP 559 EP U85 DI 10.1161/CIRCIMAGING.110.956706 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 649RH UT WOS:000281790000012 PM 20525769 ER PT J AU Gray, TR Eiden, RD Leonard, KE Connors, GJ Shisler, S Huestis, MA AF Gray, Teresa R. Eiden, Rina D. Leonard, Kenneth E. Connors, Gerard J. Shisler, Shannon Huestis, Marilyn A. TI Identifying Prenatal Cannabis Exposure and Effects of Concurrent Tobacco Exposure on Neonatal Growth SO CLINICAL CHEMISTRY LA English DT Article ID MARIJUANA EXPOSURE; ORAL FLUID; MAJOR METABOLITES; FETAL-GROWTH; GENERATION R; MECONIUM; PREGNANCY; DELTA(9)-TETRAHYDROCANNABINOL; USERS; QUANTIFICATION AB BACKGROUND: Cannabis is the most frequently used illicit drug among pregnant women, but data describing the effects of prenatal cannabis exposure and concurrent nicotine and cannabis exposures on neonatal growth are inconsistent. Testing of meconium, the first neonatal feces, offers objective evidence of prenatal cannabis exposure, but the relative ability of meconium testing and maternal self-report to identify affected neonates remains unclear. METHODS: Eighty-six pregnant women provided detailed self-reports of daily cannabis and tobacco consumption throughout pregnancy. Cannabinoids and tobacco biomarkers were identified in oral fluid samples collected each trimester and quantified in meconium at birth. RESULTS: Cannabis-using women were significantly more likely to also consume tobacco, and smoked similar numbers of cigarettes as non-cannabis-using tobacco smokers. As pregnancy progressed, fewer women smoked cannabis and those who continued to use cannabis reported smoking a smaller number of cannabis joints, but positive maternal oral fluid tests cast doubt on the veracity of some maternal self-reports. More neonates were identified as cannabis exposed by maternal self-report than meconium analysis, because many women quit cannabis use after the first or second trimester; meconium was more likely to be positive if cannabis use continued into the third trimester. Cannabis exposure was associated with decreased birth weight, reduced length, and smaller head circumference, even after data were controlled for tobacco coexposure. CONCLUSIONS: Prenatal cannabis exposure was associated with fetal growth reduction. Meconium testing primarily identifies prenatal cannabis exposure occurring in the third trimester of gestation. (C) 2010 American Association for Clinical Chemistry C1 [Gray, Teresa R.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. [Eiden, Rina D.; Leonard, Kenneth E.; Connors, Gerard J.; Shisler, Shannon] SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, NIH; NIH [R01 DA 013190] FX This research was funded by the Intramural Research Program of the National Institute on Drug Abuse, NIH, and NIH extramural grant R01 DA 013190, given to the Growing Up Healthy Study. NR 33 TC 31 Z9 32 U1 1 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2010 VL 56 IS 9 BP 1442 EP 1450 DI 10.1373/clinchem.2010.147876 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 644SP UT WOS:000281400600014 PM 20628142 ER PT J AU Ray, S Chhabra, A Chakraborty, NG Hegde, U Dorsky, DI Chodon, T von Euw, E Comin-Anduix, B Koya, RC Ribas, A Economou, JS Rosenberg, SA Mukherji, B AF Ray, Swagatam Chhabra, Arvind Chakraborty, Nitya G. Hegde, Upendra Dorsky, David I. Chodon, Thinle von Euw, Erika Comin-Anduix, Begonya Koya, Richard C. Ribas, Antoni Economou, James S. Rosenberg, Steven A. Mukherji, Bijay CA UCLA-CALTECH-CHLA-USC-UCONN Consor TI MHC-I-restricted melanoma antigen specific TCR-engineered human CD4+T cells exhibit multifunctional effector and helper responses, in vitro SO CLINICAL IMMUNOLOGY LA English DT Article DE Cancer immunotherapy; TCR; Multi functional CD4 T cells ID CD4(+) T-CELLS; GENE-TRANSFER; DENDRITIC CELLS; ESTABLISHED MELANOMA; ANTITUMOR IMMUNITY; CANCER REGRESSION; REACTIVE TCR; LYMPHOCYTES; GENERATION; RECEPTOR AB MHC class I-restricted human melanoma epitope MART-1(27-35) specific TCR-engineered CD4+CD25- T cells synthesize Th1 type cytokines and exhibit cytolytic effector function upon cognate stimulation. A detailed characterization of such TCR-engineered CD4+CD25- T cells now reveals that they are multifunctional. For example, they undergo multiple rounds of division, synthesize cytokines (IFN-gamma, TNF-alpha, IL-2, and MIP1 beta), lyse target cells, and "help" the expansion of the MART-1(27-35) specific CD8+ T cells when stimulated by the MART-1(27-35) peptide pulsed DC. Multiparametric analyses reveal that a single TCR-engineered CD4+ T cell can perform as many as five different functions. Nearly 100% MART-1(27-35) specific TCR expressing CD4+ T cells can be generated through retroviral vector-based transduction and one round of in vitro stimulation by the peptide pulsed DC. MHC class I-restricted tumor epitope specific TCR transduced CD4+ T cells, therefore, could be useful in immunotherapeutic strategies for melanoma or other human malignancies. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ray, Swagatam; Chhabra, Arvind; Chakraborty, Nitya G.; Hegde, Upendra; Dorsky, David I.; Mukherji, Bijay] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. [Chodon, Thinle; von Euw, Erika; Comin-Anduix, Begonya; Koya, Richard C.; Ribas, Antoni; Economou, James S.] Univ Calif Los Angeles, Dept Surg, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Chodon, Thinle; von Euw, Erika; Comin-Anduix, Begonya; Koya, Richard C.; Ribas, Antoni; Economou, James S.] Univ Calif Los Angeles, Dept Med, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Economou, James S.] Univ Calif Los Angeles, Dept Microbiol, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Economou, James S.] Univ Calif Los Angeles, Dept Immunol & Mol Genet, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Economou, James S.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Chhabra, A (reprint author), Univ Connecticut, Ctr Hlth, Dept Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM arvindac@yahoo.com; mukherji@NSO2.uchc.edu FU PHS [CA 83130, CA 88059, CA 129816]; Dowling Foundation; Samuel Waxman Cancer Research Foundation; W.M. Keck Foundation; Joy and Jerry Monkarsh Fund; Breast Cancer Alliance; Connecticut; GCRC, UCHC [MO 1RR06192] FX The work was supported by PHS grants CA 83130 (BM), CA 88059 (BM), and CA 129816 (JSE) and grants from the Dowling Foundation (BM), Samuel Waxman Cancer Research Foundation, W.M. Keck Foundation, Joy and Jerry Monkarsh Fund (JSE for UCLA-CALTECH-CHLA-USC-UCONN Consortium on Translational Program in Engineered Immunity), Breast Cancer Alliance, Connecticut (AC) and MO 1RR06192 from GCRC, UCHC. NR 33 TC 28 Z9 28 U1 5 U2 5 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 SEP PY 2010 VL 136 IS 3 BP 338 EP 347 DI 10.1016/j.clim.2010.04.013 PG 10 WC Immunology SC Immunology GA 638PM UT WOS:000280907000004 PM 20547105 ER PT J AU Porter, BO Ouedraogo, GL Hodge, JN Smith, MA Pau, A Roby, G Kwan, R Bishop, RJ Rehm, C Mican, J Sereti, I AF Porter, Brian O. Ouedraogo, G. Laissa Hodge, Jessica N. Smith, Margo A. Pau, Alice Roby, Gregg Kwan, Richard Bishop, Rachel J. Rehm, Catherine Mican, JoAnn Sereti, Irini TI D-Dimer and CRP levels are elevated prior to antiretroviral treatment in patients who develop IRIS (vol 136, pg 42, 2010) SO CLINICAL IMMUNOLOGY LA English DT Correction C1 [Sereti, Irini] NIAID, NIH, Ctr Clin, Bethesda, MD 20892 USA. [Ouedraogo, G. Laissa] NCI, Clin Monitoring Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Bishop, Rachel J.] NEI, NIH, Bethesda, MD 20892 USA. [Smith, Margo A.] Washington Hosp Ctr, Washington, DC 20010 USA. RP Sereti, I (reprint author), NIAID, NIH, Ctr Clin, Bldg 10,Room 11B07A,10 Ctr Dr, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD SEP PY 2010 VL 136 IS 3 BP 462 EP 462 DI 10.1016/j.clim.2010.06.009 PG 1 WC Immunology SC Immunology GA 638PM UT WOS:000280907000019 ER PT J AU Zaoutis, TE Prasad, PA Localio, AR Coffin, SE Bell, LM Walsh, TJ Gross, R AF Zaoutis, Theoklis E. Prasad, Priya A. Localio, A. Russell Coffin, Susan E. Bell, Louis M. Walsh, Thomas J. Gross, Robert TI Risk Factors and Predictors for Candidemia in Pediatric Intensive Care Unit Patients: Implications for Prevention SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COLONIZATION RESISTANCE; SURGICAL PATIENTS; CANCER-PATIENTS; EPIDEMIOLOGY; THERAPY; STATES; INFECTIONS; CHILDREN; LEUKEMIA; SPECTRUM AB Background. Candida species are the leading cause of invasive fungal infections in hospitalized children and are the third most common isolates recovered from patients with healthcare-associated bloodstream infection in the United States. Few data exist on risk factors for candidemia in pediatric intensive care unit (PICU) patients. Methods. We conducted a population-based case-control study of PICU patients at Children's Hospital of Philadelphia during the period from 1997 through 2004. Case patients were identified using laboratory records, and control patients were selected from PICU rosters. Control patients were matched to case patients by incidence density sampling, adjusting for time at risk. Following conditional multivariate analysis, we performed weighted multivariate analysis to determine predicted probabilities for candidemia given certain risk factor combinations. Results. We identified 101 case patients with candidemia (incidence, 3.5 cases per 1000 PICU admissions). Factors independently associated with candidemia included presence of a central venous catheter (odds ratio [OR], 30.4; 95% confidence interval [CI], 7.7-119.5), malignancy (OR, 4.0; 95% CI, 1.23-13.1), use of vancomycin for >3 days in the prior 2 weeks (OR, 6.2; 95% CI, 2.4-16), and receipt of agents with activity against anaerobic organisms for >3 days in the prior 2 weeks (OR, 3.5; 95% CI, 1.5-8.4). Predicted probability of having various combinations of the aforementioned factors ranged from 10.7% to 46%. The 30-day mortality rate was 44% among case patients and 14% among control patients (OR, 4.22; 95% CI, 2.35-7.60). Conclusions. To our knowledge, this is the first study to evaluate independent risk factors and to determine a population of children in PICUs at high risk for developing candidemia. Future efforts should focus on validation of these risk factors identified in a different PICU population and development of interventions for prevention of candidemia in critically ill children. C1 [Zaoutis, Theoklis E.] Childrens Hosp Philadelphia, Div Infect Dis, CHOP N, Philadelphia, PA 19104 USA. [Zaoutis, Theoklis E.; Coffin, Susan E.] Childrens Hosp Philadelphia, Ctr Pediat Clin Effectiveness, Philadelphia, PA 19104 USA. [Zaoutis, Theoklis E.; Coffin, Susan E.; Bell, Louis M.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Zaoutis, Theoklis E.; Localio, A. Russell; Gross, Robert] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Zaoutis, TE (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, CHOP N, 34th & Civ Ctr Blvd,Ste 1527, Philadelphia, PA 19104 USA. EM Zaoutis@email.chop.edu FU National Institutes of Health [1K23 AI0629753-01]; Merck; National Cancer Institute; Enzon; Schering-Plough; AstraZeneca; Wyeth-Ayerst Laboratories; Cephalon FX Financial support. National Institutes of Health (grant 1K23 AI0629753-01 to T.E.Z); Merck Research Funding; the intramural research program of the National Cancer Institute.; Potential conflicts of interest. T.E.Z reports that he has received research funding from Merck, Enzon, Schering-Plough, AstraZeneca, and Wyeth-Ayerst Laboratories and has received speaking honoraria from Cephalon. All other authors: no conflicts. NR 39 TC 59 Z9 65 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2010 VL 51 IS 5 BP E38 EP E45 DI 10.1086/655698 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 634ZC UT WOS:000280623900031 PM 20636126 ER PT J AU Chawla, V Greene, T Beck, GJ Kusek, JW Collins, AJ Sarnak, MJ Menon, V AF Chawla, Varun Greene, Tom Beck, Gerald J. Kusek, John W. Collins, Allan J. Sarnak, Mark J. Menon, Vandana TI Hyperlipidemia and Long-Term Outcomes in Nondiabetic Chronic Kidney Disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC RENAL-DISEASE; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; CHOLESTEROL LEVEL; DIALYSIS PATIENTS; MORTALITY RISK; LIPID-LEVELS; ASSOCIATION; DEATH AB Background and objectives: Dyslipidemia confers a paradoxical survival advantage in patients with kidney failure. Data are limited in the earlier stages of chronic kidney disease (CKD). Design, setting, participants, and measurements: This was a cohort study in 840 subjects with stage 3 to 4 CKD enrolled in the Modification of Diet in Renal Disease study. Cox models were used to examine the relationship of total cholesterol (TC), non-HDL-cholesterol (NHDL-C), triglycerides (TG), and HDL-cholesterol (HDL-C) with all-cause and cardiovascular disease (CVD) mortality and progression to kidney failure. Results: During a mean follow-up of 10 years, there were 208 deaths, 128 deaths from CVD, and 554 subjects reached kidney failure. There was no association between tertiles of any of the lipid variables and mortality; the lowest HDL-C tertile (1.44, 1.18 to 1.78) had increased risk of kidney failure but covariate adjustment abolished this association. In analyses with lipids as continuous variables, there was a significant association with all-cause mortality for TC (hazard ratio [HR] per 10-mg/dl increase, 95% confidence intervals [CI] = 1.03, 1.0 to 1.06) that disappeared with covariate adjustment; there was no association of TG, HDL-C, and NHDL-C as continuous variables with all-cause or CVD mortality. There was a significant inverse association between HDL-C and kidney failure (HR = 0.93, CI = 0.87 to 0.99) in an unadjusted Cox model that was attenuated after adjustment for covariates (HR = 0.98 CI = 0.91 to 1.06). Conclusions: In this cohort, with predominantly nondiabetic CKD patients, hyperlipidemia is not an independent predictor of long-term outcomes. Clin J Am Soc Nephrol 5: 1582-1587, 2010. doi: 10.2215/CJN.01450210 C1 [Sarnak, Mark J.; Menon, Vandana] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 USA. [Chawla, Varun] Mt Auburn Hosp, Dept Med, Cambridge, MA USA. [Greene, Tom] Univ Utah, Div Clin Epidemiol, Salt Lake City, UT USA. [Beck, Gerald J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Kusek, John W.] NIH, Bethesda, MD 20892 USA. [Collins, Allan J.] Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. RP Menon, V (reprint author), Tufts Med Ctr, Div Nephrol, 800 Washington St,Box 391, Boston, MA 02111 USA. EM vmenon@tuftsmedicalcenter.org FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK067303, K23DK02904, K24 DK078204] FX This study was supported through grants K23 DK067303, K23DK02904, and K24 DK078204 from the National Institute of Diabetes and Digestive and Kidney Diseases. Part of this material was presented in abstract form at the annual meeting of the American Society of to Nephrology; November 4 through 9, 2008; Philadelphia, PA. NR 24 TC 24 Z9 24 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2010 VL 5 IS 9 BP 1582 EP 1587 DI 10.2215/CJN.01450210 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 648II UT WOS:000281685600008 PM 20558558 ER PT J AU Pipkin, M Eggers, PW Larive, B Rocco, MV Stokes, JB Suri, RS Lockridge, RS AF Pipkin, Mary Eggers, Paul W. Larive, Brett Rocco, Michael V. Stokes, John B. Suri, Rita S. Lockridge, Robert S., Jr. CA Frequent Hemodialysis Network Tria TI Recruitment and Training for Home Hemodialysis: Experience and Lessons from the Nocturnal Dialysis Trial SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SELF-CARE DIALYSIS; CONVENTIONAL HEMODIALYSIS; PERSPECTIVES; ESRD AB Background and objectives: We assessed perceived barriers and incentives to home hemodialysis and evaluated potential correlates with the duration of home hemodialysis training. Design, settings, participants, & measurements: Surveys were sent to the principal investigator and study coordinator for each clinical center in the Frequent Hemodialysis Network Nocturnal Trial. Baseline data were obtained on medical comorbidities, cognitive and physical functioning, sessions required for home hemodialysis training, and costs of home renovations. Results: The most commonly perceived barriers included lack of patient motivation, unwillingness to change from in-center modality, and fear of self-cannulation. The most common incentives were greater scheduling flexibility and reduced travel time. The median costs for home renovations varied between $1191 and $4018. The mean number of home hemodialysis training sessions was 27.7 +/- 10.4 (11-59 days). Average training time was less for patients with experience in either self-care or both self-care and cannulation. The number of training sessions was unrelated to the score on the Modified Mini Mental Status or Trailmaking B tests or patient's education level. Training time also did not correlate with the SF-36 Physical Function subscale but did with the modified Charlson comorbidity score and older patient age. Conclusions: Lack of patient or family motivation and fear of the dialysis process are surmountable barriers for accepting home hemodialysis as a modality for renal replacement therapy. Formal education and scores on cognitive function tests are not predictors of training time. Clin J Am Soc Nephrol 5: 1614-1620, 2010. doi: 10.2215/CJN.02440310 C1 [Stokes, John B.] Univ Iowa, Dept Internal Med, Div Nephrol, Iowa City, IA 52242 USA. [Pipkin, Mary; Lockridge, Robert S., Jr.] Univ Virginia, Nephrol Clin Res Ctr, Charlottesville, VA USA. [Pipkin, Mary; Lockridge, Robert S., Jr.] Univ Virginia, Div Nephrol, Charlottesville, VA USA. [Pipkin, Mary; Lockridge, Robert S., Jr.] Lynchburg Nephrol Phys, Lynchburg, VA USA. [Eggers, Paul W.] NIDDKD, Bethesda, MD 20892 USA. [Larive, Brett] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. [Rocco, Michael V.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Stokes, John B.] VA Med Ctr, Iowa City, IA USA. [Suri, Rita S.] Univ Western Ontario, London, ON, Canada. RP Stokes, JB (reprint author), Univ Iowa, Dept Internal Med, Div Nephrol, 200 Hawkins Dr,E300 GH, Iowa City, IA 52242 USA. EM john-stokes@uiowa.edu RI Suri, Rita/G-3348-2011 OI Suri, Rita/0000-0002-0519-3927 FU National Institutes of Health (NIH) [DK66597, DK066480]; Centers for Medicare and Medicaid Services, Fresenius Medical Care; Renal Research Institute, Satellite Health Care, NKF of Iowa; NIH Foundation FX We thank Susan Sherer for assistance with the data analysis. Funding for this study was received from the National Institutes of Health (NIH; Grants DK66597 and DK066480), Centers for Medicare and Medicaid Services, Fresenius Medical Care, the Renal Research Institute, Satellite Health Care, NKF of Iowa, and a grant from the NIH Foundation. NR 21 TC 46 Z9 46 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2010 VL 5 IS 9 BP 1614 EP 1620 DI 10.2215/CJN.02440310 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 648II UT WOS:000281685600013 PM 20576829 ER PT J AU Chakkera, HA Knowler, WC Devarapalli, Y Weil, EJ Heilman, RL Dueck, A Mulligan, DC Reddy, KS Moss, AA Mekeel, KL Mazur, MJ Hamawi, K Castro, JC Cook, CB AF Chakkera, Harini A. Knowler, William C. Devarapalli, Yugandhara Weil, E. Jennifer Heilman, Raymond L. Dueck, Amylou Mulligan, David C. Reddy, Kunam S. Moss, Adyr A. Mekeel, Kristin L. Mazur, Marek J. Hamawi, Khaled Castro, Janna C. Cook, Curtiss B. TI Relationship between Inpatient Hyperglycemia and Insulin Treatment after Kidney Transplantation and Future New Onset Diabetes Mellitus SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; RENAL-ALLOGRAFT RECIPIENTS; LIFE-STYLE; CLINICAL INERTIA; CARE; PREVENTION; METFORMIN; RISK AB Background and objectives: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. Design, setting, participants, & measurements: A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose >= 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C >= 6.5%, fasting venous serum glucose >= 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. Results: The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Conclusion: Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT. Clin J Am Soc Nephrol 5: 1669-1675, 2010. doi: 10.2215/CJN.09481209 C1 [Chakkera, Harini A.; Devarapalli, Yugandhara; Heilman, Raymond L.; Mazur, Marek J.; Hamawi, Khaled] Mayo Clin, Div Nephrol & Transplantat, Phoenix, AZ USA. [Mulligan, David C.; Reddy, Kunam S.; Moss, Adyr A.; Mekeel, Kristin L.] Mayo Clin, Div Surg, Phoenix, AZ USA. [Castro, Janna C.; Cook, Curtiss B.] Mayo Clin, Div Endocrinol, Phoenix, AZ USA. [Dueck, Amylou] Mayo Clin, Div Biostat, Phoenix, AZ USA. [Knowler, William C.; Weil, E. Jennifer] NIDDKD, NIH, Phoenix, AZ USA. RP Chakkera, HA (reprint author), Mayo Clin Hosp, Div Transplantat, 5777 E Mayo Blvd, Phoenix, AZ 85054 USA. EM chakkera.harini@mayo.edu FU National Center for Research Resources (NCRR) [1 KL2 RR024151]; National Institutes of Health (NIH); NIH Roadmap for Medical Research; National Institute of Diabetes and Digestive and Kidney Diseases FX This publication was made possible by grant number 1 KL2 RR024151 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www. ncrr.nih.gov/. Additionally, this research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 21 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD SEP PY 2010 VL 5 IS 9 BP 1669 EP 1675 DI 10.2215/CJN.09481209 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 648II UT WOS:000281685600021 PM 20558559 ER PT J AU Reddy, UM AF Reddy, Uma M. TI Stillbirth Foreword SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [Reddy, Uma M.] NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Reddy, UM (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2010 VL 53 IS 3 BP 586 EP 587 DI 10.1097/GRF.0b013e3181eb6308 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 631TO UT WOS:000280371500011 PM 20661042 ER PT J AU McClure, EM Dudley, DJ Reddy, UM Goldenberg, RL AF McClure, Elizabeth M. Dudley, Donald J. Reddy, Uma M. Goldenberg, Robert L. TI Infectious Causes of Stillbirth: A Clinical Perspective SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE stillbirth; infection; chorioamnionitis ID SPONTANEOUS-ABORTION; PERINATAL-MORTALITY; CLASSIFICATION; PREGNANCY; COXSACKIE; SYPHILIS; VIRUSES; DEATHS; WOMEN AB Untreated infection may cause stillbirth by several mechanisms, including direct fetal infection, placental damage, and severe maternal illness. Many bacteria, viruses, and protozoa have been associated with stillbirth. In developed countries, up to 24% of stillbirths have been attributed to infection, although with increased availability of sophisticated diagnostics and rigorous screening, it appears likely that higher numbers may actually be associated with infection. In developed countries, ascending bacterial infection is usually the most common infectious cause of stillbirth, with a number of viral infections also an important factor. Screening, prevention, and treatment of maternal infections are important to reduce stillbirth risk. C1 [Goldenberg, Robert L.] Drexel Univ, Dept Obstet Gynecol, Coll Med, Philadelphia, PA 19102 USA. [McClure, Elizabeth M.] Univ N Carolina, Dept Epidemiol, Global Sch Publ Hlth, Chapel Hill, NC USA. [Dudley, Donald J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA. RP Goldenberg, RL (reprint author), Drexel Univ, Dept Obstet Gynecol, Coll Med, 245 N 15th St,17th Floor,Room 17113, Philadelphia, PA 19102 USA. EM rgoldenb@drexelmed.edu FU NICHD NIH HHS [U01 HD040607, U01 HD040636] NR 29 TC 9 Z9 9 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 EI 1532-5520 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2010 VL 53 IS 3 BP 635 EP 645 DI 10.1097/GRF.0b013e3181eb6620 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 631TO UT WOS:000280371500017 PM 20661048 ER PT J AU Reddy, UM AF Reddy, Uma M. TI Management of Pregnancy After Stillbirth SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article DE stillbirth; recurrence; management; risk factors ID ALPHA-FETOPROTEIN; RISK; SUBSEQUENT; POPULATION; RECURRENCE; BIRTHS; DEATH AB It is difficult for clinicians to counsel, evaluate, and manage subsequent pregnancies after stillbirth as little is known about pregnancy outcome after a stillbirth. In a significant number of cases, either the evaluation was incomplete or the prior stillbirth remains unexplained despite a complete work-up. In addition, there are important psychological and emotional issues when dealing with a pregnancy resulting in a stillbirth. The overall recurrence risk for stillbirth is increased 2 to 10 folds in the next pregnancy, depending on the circumstances. Understanding the circumstances of the previous stillbirth is important for counseling about stillbirth recurrence risk. Categorization of the cause of the previous stillbirth will allow better estimation of individual recurrence risk of the condition that is associated with stillbirth and help guide management. C1 [Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Reddy, UM (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 21 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD SEP PY 2010 VL 53 IS 3 BP 700 EP 709 DI 10.1097/GRF.0b013e3181eba25e PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 631TO UT WOS:000280371500023 PM 20661054 ER PT J AU Yang, MA Dunson, DB Baird, D AF Yang, Mingan Dunson, David B. Baird, Donna TI Semiparametric Bayes hierarchical models with mean and variance constraints SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Dirichlet process; Latent variables; Moment constraints; Nonparametric Bayes; Parameter expansion; Random effects ID LATENT VARIABLE MODELS; DIRICHLET PROCESS; NONPARAMETRIC-ESTIMATION; PRIOR DISTRIBUTIONS; MEDIAN REGRESSION; PRIORS; FUNCTIONALS; MIXTURES; OUTCOMES; DENSITY AB In parametric hierarchical models, it is standard practice to place mean and variance constraints on the latent variable distributions for the sake of identifiability and interpretability. Because incorporation of such constraints is challenging in semiparametric models that allow latent variable distributions to be unknown, previous methods either constrain the median or avoid constraints. In this article, we propose a centered stick-breaking process (CSBP), which induces mean and variance constraints on an unknown distribution in a hierarchical model. This is accomplished by viewing an unconstrained stick-breaking process as a parameter-expanded version of a CSBP. An efficient blocked Gibbs sampler is developed for approximate posterior computation. The methods are illustrated through a simulated example and an epidemiologic application. (C) 2010 Elsevier B.V. All rights reserved. C1 [Yang, Mingan] St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. [Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27706 USA. [Baird, Donna] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Yang, MA (reprint author), St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA. EM mingany@yahoo.com; dunson@stat.duke.edu; baird@niehs.nih.gov RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU NIEHS NIH HHS [R01 ES017240] NR 37 TC 20 Z9 20 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD SEP 1 PY 2010 VL 54 IS 9 BP 2172 EP 2186 DI 10.1016/j.csda.2010.03.025 PG 15 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 610IA UT WOS:000278723900010 PM 24363478 ER PT J AU Spencer, RG AF Spencer, Richard G. TI Equivalence of the Time-Domain Matched Filter and the Spectral-Domain Matched Filter in One-Dimensional NMR Spectroscopy SO CONCEPTS IN MAGNETIC RESONANCE PART A LA English DT Article DE matched filter; exponential multiplication; signal processing AB A type of 'matched filter' (MF), used extensively in the processing of one-dimensional spectra, is defined by multiplication of a free-induction decay (FID) by a decaying exponential with the same time constant as that of the FID. This maximizes, in a sense to be defined, the signal-to-noise ratio (SNR) in the spectrum obtained after Fourier transformation. However, a different entity known also as the MF was introduced by van Vleck in the context of pulse detection in the 1940's and has become widely integrated into signal processing practice. These two types of MFs appear to be quite distinct. In the NMR case, the 'filter', that is, the exponential multiplication, is defined by the characteristics of, and applied to, a time domain signal to achieve improved SNR in the spectral domain. In signal processing, the filter is defined by the characteristics of a signal in the spectral domain, and applied to improve the SNR in the temporal (pulse) domain. We reconcile these two distinct implementations of the MF, demonstrating that the NMR 'MF' is a special case of the MF more rigorously defined in the signal processing literature. In addition, two limitations on the use of the MF are highlighted. First, application of the MF distorts resonance ratios as defined by amplitudes, although not as defined by areas. Second, the MF maximizes SNR with respect to resonance amplitude, while intensity is often more appropriately defined by area. Maximizing the SNR with respect to area requires a somewhat different approach to matched filtering. (C) 2010 Wiley Periodicals, Inc(dagger) Concepts Magn Reson Part A 36A: 255-265, 2010. C1 NIA, NIH, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov FU National Institute on Aging of the NIH FX This work was supported by the Intramural Research Program of the National Institute on Aging of the NIH. NR 11 TC 4 Z9 4 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1546-6086 J9 CONCEPT MAGN RESON A JI Concepts Magn. Reson. Part A PD SEP PY 2010 VL 36A IS 5 BP 255 EP 265 DI 10.1002/cmr.a.20162 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 672WZ UT WOS:000283619000001 PM 21765806 ER PT J AU Rubinstein, YR Croft, SC AF Rubinstein, Yaffa R. Croft, Stephen C. TI Patient registry for the overlooked patient SO CONTEMPORARY CLINICAL TRIALS LA English DT Letter C1 [Rubinstein, Yaffa R.; Croft, Stephen C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. RP Rubinstein, YR (reprint author), NIH, Off Rare Dis Res, Bldg 10, Bethesda, MD 20892 USA. EM rubinsty@mail.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 393 EP 393 DI 10.1016/j.cct.2010.07.002 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000002 PM 20603228 ER PT J AU Rubinstein, YR Groft, SC Bartek, R Brown, K Christensen, RA Collier, E Farber, A Farmer, J Ferguson, JH Forrest, CB Lockhart, NC McCurdy, KR Moore, H Pollen, GB Richesson, R Miller, VR Hull, S Vaught, J AF Rubinstein, Yaffa R. Groft, Stephen C. Bartek, Ronald Brown, Kyle Christensen, Ronald A. Collier, Elaine Farber, Amy Farmer, Jennifer Ferguson, John H. Forrest, Christopher B. Lockhart, Nicole C. McCurdy, Kate R. Moore, Helen Pollen, Geraldine B. Richesson, Rachel Miller, Vanessa Rangel Hull, Sara Vaught, Jim TI Creating a global rare disease patient registry linked to a rare diseases biorepository database: Rare Disease-HUB (RD-HUB) SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Rare diseases; Patient registry; Disease registry; Rare disease; Patient advocacy; Biospecimen; Biospecimen repositories; Clinical data; Electronic health record AB A movement to create a global patient registry for as many as 7,000 rare diseases was launched at a workshop, "Advancing Rare Disease Research: The Intersection of Patient Registries, Biospecimen Repositories, and Clinical Data." http://rarediseases.info.nih.gov/PATIENT_REGISTRIES_WORKSHOP/. The workshop was sponsored by the Office of Rare Diseases Research (ORDR). The focus was the building of an infrastructure for an internet-based global registry linking to biorepositories. Such a registry would serve the patients, investigators, and drug companies. To aid researchers the participants suggested the creation of a centralized database of biorepositories for rare biospecimens (RD-HUB)http://biospecimens.ordr.info.nih.gov/ that could be linked to the registry. Over two days of presentations and breakout sessions, several hundred attendees discussed government rules and regulations concerning privacy and patients' rights and the nature and scope of data to be entered into a central registry as well as concerns about how to validate patient and clinician-entered data to ensure data accuracy. Mechanisms for aggregating data from existing registries were also discussed. The attendees identified registry best practices, model coding systems, international systems for recruiting patients into clinical trials and novel ways of using the internet directly to invite participation in research. They also speculated about who would bear ultimate responsibility for the informatics in the registry and who would have access to the information. Hurdles associated with biospecimen collection and how to overcome them were detailed. The development of the recommendations was, in itself, an indication of the commitment of the rare disease community as never before. Published by Elsevier Inc. C1 [Rubinstein, Yaffa R.; Groft, Stephen C.; Ferguson, John H.; Pollen, Geraldine B.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Bartek, Ronald; Farmer, Jennifer] FARA, Springfield, VA USA. [Brown, Kyle] Innolyst Inc, San Mateo, CA USA. [Christensen, Ronald A.] REGISTRAT MAPI, Scottsdale, AZ USA. [Collier, Elaine] NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. [Farber, Amy] LAM Treatment Alliance, Cambridge, MA USA. [Forrest, Christopher B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Forrest, Christopher B.] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. [Lockhart, Nicole C.; Moore, Helen; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, NIH, Bethesda, MD 20892 USA. [McCurdy, Kate R.] Barth Syndrome Fdn Inc, Larchmont, NY USA. [Richesson, Rachel] Univ S Florida, Coll Med, Dept Pediat, Div Bioinformat & Biostat, Tampa, FL 33612 USA. [Miller, Vanessa Rangel] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA. [Hull, Sara] NHGRI, Off Clin Director, Dept Bioeth, Ctr Clin,NIH, Bethesda, MD 20892 USA. RP Rubinstein, YR (reprint author), NIH, Off Rare Dis Res, 6100 Execut Blvd,Room 3A07,MSC 751, Bethesda, MD 20892 USA. EM rubinsty@mail.nih.gov; gropts2@od.nih.gov FU Intramural NIH HHS [Z99 OD999999] NR 0 TC 44 Z9 44 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 394 EP 404 DI 10.1016/j.cct.2010.06.007 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000003 PM 20609392 ER PT J AU Berger, VW AF Berger, Vance W. TI Minimization, by its nature, precludes allocation concealment, and invites selection bias SO CONTEMPORARY CLINICAL TRIALS LA English DT Letter DE Allocation concealment; Clinical trial; Masking; Minimization; Selection bias C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 4 TC 17 Z9 17 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 406 EP 406 DI 10.1016/j.cct.2010.05.001 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000005 PM 20457277 ER PT J AU Resnik, DB Miller, F AF Resnik, David B. Miller, Frank TI The ethics of sham surgery on research subjects with cognitive impairments that affect decision-making capacity SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Sham surgery; Ethics; Clinical trials; Vulnerable populations; Decision-making capacity ID PARKINSONS-DISEASE; CLINICAL-RESEARCH; PLACEBO SURGERY; TRIALS AB Populations recruited to participate in sham surgery clinical trials sometimes include patients with cognitive impairments that affect decision-making capacity. In this commentary we examine arguments for and against including these patients in sham surgery clinical trials. We argue that patients with cognitive impairments that affect decision-making capacity should not be excluded from a sham surgery clinical trial if there are scientific reasons for including them in the study and basic ethical requirements for clinical research are met. Published by Elsevier Inc. C1 [Resnik, David B.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. [Miller, Frank] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Resnik, DB (reprint author), Natl Inst Environm Hlth Sci, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU National Institute for Environmental Health Sciences; Department of Bioethics, National Institutes of Health FX This research was supported by the Intramural Programs of the National Institute for Environmental Health Sciences and the Department of Bioethics, National Institutes of Health. This research does not represent the views of the National Institutes of Health or the U.S. government. NR 22 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD SEP PY 2010 VL 31 IS 5 BP 407 EP 410 DI 10.1016/j.cct.2010.05.009 PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 657CX UT WOS:000282391000006 PM 20570755 ER PT J AU Kalil, AC Murthy, MH Hermsen, ED Neto, FK Sun, JF Rupp, ME AF Kalil, Andre C. Murthy, Madhu H. Hermsen, Elizabeth D. Neto, Felipe K. Sun, Junfeng Rupp, Mark E. TI Linezolid versus vancomycin or teicoplanin for nosocomial pneumonia: A systematic review and meta-analysis SO CRITICAL CARE MEDICINE LA English DT Article DE pneumonia; vancomycin; linezolid; teicoplanin ID RESISTANT STAPHYLOCOCCUS-AUREUS; GRAM-POSITIVE INFECTIONS; CRITICALLY-ILL PATIENTS; VENTILATOR-ASSOCIATED PNEUMONIA; RANDOMIZED CONTROLLED-TRIALS; DOUBLE-BLIND; LINING FLUID; MULTICENTER; PHARMACOKINETICS AB Introduction: Compared with glycopeptides, linezolid achieves higher lung epithelial lining fluid concentrations, which may correlate with improved efficacy in the treatment of nosocomial pneumonia. However, clinical superiority has not been demonstrated. Objective: To test the hypothesis that linezolid may be superior to glycopeptides. Methods: Prospective randomized trials that tested linezolid vs. vancomycin or teicoplanin for treatment of nosocomial pneumonia were included. Heterogeneity was analyzed by I(2) and Q statistics. Meta-analysis relative risks were based on fixed and random-effects models. Outcomes evaluated consisted of clinical cure, microbiological eradication, and side effects. Results: Nine linezolid trials (vancomycin [7]; teicoplanin [2]) were included (n = 2329). The linezolid vs. glycopeptide analysis shows clinical cure relative risk of 1.01 (95% confidence interval, 0.93-1.10; p = .83; I(2) = 0%) and microbiological eradication relative risk of 1.10 (95% confidence interval, 0.98-1.22; p = .10; I(2) = 0%). Methicillin-resistant Staphylococcus aureus subgroup analysis yielded a microbiological eradication relative risk of 1.10 (95% confidence interval, 0.87-1.38; p = .44; I(2) = 16%). If linezolid is compared with vancomycin only, then clinical cure relative risk is 1.00 (95% confidence interval, 0.90-1.12), microbiological eradication and methicillin-resistant Staphylococcus aureus relative risks are 1.07 (95% confidence interval, 0.90-1.26; p = .45) and 1.05 (95% confidence interval, 0.82-1.33; p = .71). The risks of thrombocytopenia (relative risk, 1.93; 95% confidence interval, 1.30-2.87; p = .001) and gastrointestinal events (relative risk, 2.02; 95% confidence interval, 1.10-3.70; p = .02) are higher with linezolid, but no differences are seen for renal dysfunction (relative risk, 0.89; 95% confidence interval, 0.56-1.43; p = .64) or all-cause mortality (relative risk, 0.95; 95% confidence interval, 0.76-1.18; p = .63). Conclusions: Our study does not demonstrate clinical superiority of linezolid vs. glycopeptides for the treatment of nosocomial pneumonia despite a statistical power of 95%. Linezolid shows a significant two-fold increase in the risk of thrombocytopenia and gastrointestinal events. Vancomycin and teicoplanin are not associated with more renal dysfunction than linezolid. (Crit Care Med 2010; 38:1802-1808) C1 [Kalil, Andre C.; Hermsen, Elizabeth D.] Univ Nebraska Med Ctr, Coll Med, Omaha, NE USA. [Murthy, Madhu H.] W Valley Hosp, Integrated Med Serv, Goodyear, AZ USA. [Hermsen, Elizabeth D.] Nebraska Med Ctr, Omaha, NE USA. [Hermsen, Elizabeth D.] Univ Nebraska Med Ctr, Coll Pharm, Omaha, NE USA. [Neto, Felipe K.] Pontificia Univ Catolica, Hosp San Lucas Da Pucrs, Porto Alegre, RS, Brazil. [Sun, Junfeng] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Rupp, Mark E.] Univ Nebraska Med Ctr, Dept Internal Med, Div Infect Dis, Omaha, NE USA. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Coll Med, Omaha, NE USA. EM akalil@unmc.edu NR 28 TC 64 Z9 83 U1 0 U2 14 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 SEP PY 2010 VL 38 IS 9 BP 1802 EP 1808 DI 10.1097/CCM.0b013e3181eb3b96 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 646RK UT WOS:000281559500005 PM 20639754 ER PT J AU Shaw, PA AF Shaw, Pamela A. TI Combination versus monotherapy for septic shock patients SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE septic shock; monotherapy; antibiotic; combination therapy; propensity scores; Cox model; multiple comparisons ID PROPENSITY SCORE; SEVERE SEPSIS; BIAS C1 NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. RP Shaw, PA (reprint author), NIAID, NIH, Biostat Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 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 SEP PY 2010 VL 38 IS 9 BP 1905 EP 1906 DI 10.1097/CCM.0b013e3181ee3549 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 646RK UT WOS:000281559500020 PM 20724887 ER PT J AU Fitzgerald, PJ AF Fitzgerald, P. J. TI Is Elevated Norepinephrine an Etiological Factor in Some Cases of Alzheimer's Disease? SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Dementia; tricyclic antidepressant; desipramine; clonidine; guanfacine; beta blocker; propranolol; bipolar disorder; hypertension; obesity; psychological stress ID ACTIVATED PROTEIN-KINASE; CEREBROSPINAL-FLUID NOREPINEPHRINE; VASCULAR RISK-FACTORS; LOCUS-COERULEUS DEGENERATION; BIPOLAR SPECTRUM DISORDERS; TYPE-2 DIABETES-MELLITUS; BODY-MASS INDEX; BLOOD-PRESSURE; DOUBLE-BLIND; PREFRONTAL CORTEX AB Loss of norepinephrine (NE) releasing neurons, in the locus coeruleus of the brainstem, is well documented to occur in Alzheimer's disease (AD). However, this process does not necessarily result in decreased release of NE, since compensatory mechanisms may produce increased release of this neurotransmitter. Independent of potential loss of locus coeruleus cells, brain NE levels may be elevated in some persons with AD, both before and during disease progression. Here I examine evidence that elevated, endogenous brain NE is an etiological factor in some cases of AD, and not merely an epiphenomenon of the disease. To explore this etiological hypothesis in AD, I examine the following eight lines of evidence: 1) direct evidence of elevated NE or its metabolites in AD; 2) studies of tricyclic antidepressants, which may principally boost NE; 3) studies of clonidine and other alpha2 adrenergic agonist drugs, which may principally lower the concentration of NE; 4) studies of beta adrenoceptor blocking drugs, including propranolol; 5) comorbidity of AD and bipolar disorder, where both disorders may involve elevated NE; 6) comorbidity of AD and hypertension; 7) comorbidity of AD and obesity; and 8) potential interaction between AD and psychological stress, where stressors are known to release NE. These lines of evidence tend to support the elevated NE etiological hypothesis. C1 [Fitzgerald, P. J.] Johns Hopkins Univ, Zanvyl Krieger Mind Bran Inst, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA. RP Fitzgerald, PJ (reprint author), NIAAA, 5625 Fishers Lane,Room 2N09, Rockville, MD 20852 USA. EM pfitz@mbi.mb.jhu.edu NR 133 TC 15 Z9 16 U1 2 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD SEP PY 2010 VL 7 IS 6 BP 506 EP 516 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633SK UT WOS:000280525100003 PM 20626335 ER PT J AU Ozbabacan, SEA Gursoy, A Keskin, O Nussinov, R AF Ozbabacan, Saliha Ece Acuner Gursoy, Attila Keskin, Ozlem Nussinov, Ruth TI Conformational ensembles, signal transduction and residue hot spots: Application to drug discovery SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE Allosteric; cellular pathway; conformational selection; drug design; drug target; molecular recognition; pharmacological research; protein dynamics; protein network; signaling ID PROTEIN-PROTEIN INTERACTIONS; P53 TUMOR-SUPPRESSOR; NITRIC-OXIDE SYNTHASE; NERVE GROWTH-FACTOR; SMALL-MOLECULE; STRUCTURAL BASIS; BINDING-SITE; MODULAR ARCHITECTURE; CONSERVED RESIDUES; ENERGY LANDSCAPES AB A key step in drug development is the identification of both a protein target and its topological cellular network location and interactions, with regard to information flow in disease-causing events and to medication effects. Information flow involves a cascade of binding or covalent modification processes, with each step being affected by those that occur previously. Proteins are flexible, and information flows via dynamic changes in the distribution of conformational protein ensembles; molecular recognition is mainly determined by these changes. Drug discovery often focuses on signaling proteins situated at the crossroads of cellular networks; such signaling proteins have multiple partners that bind through shared binding sites. This review highlights these shared binding sites, and describes research to suggest that partners binding at these sites could at least partly interact via different energetically dominant 'hot-spot' residues. The data also indicate that, despite dynamic changes in the distribution of the conformational ensembles, the hot-spot conformations are retained in their pre-organized states. C1 [Nussinov, Ruth] NCI, SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Ozbabacan, Saliha Ece Acuner; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. [Ozbabacan, Saliha Ece Acuner; Gursoy, Attila; Keskin, Ozlem] Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, 1050 Boyles St, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov RI Acuner Ozbabacan, Saliha Ece/I-3464-2012; Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU Turkish Academy of Sciences; Scientific and Technological Research Council of Turkey [109T343, 109E207]; NCI [HHSN261200800001E]; NIH, NCI, Center for Cancer Research FX The authors' research is supported by a Turkish Academy of Sciences Distinguished Young Investigator Award (awarded to Ozlem Keskin); the Scientific and Technological Research Council of Turkey Fellowship (awarded to Saliha Ece Acuner Ozbabacan; Grant Numbers 109T343 and 109E207); Federal funds from the NCI, under contract number HHSN261200800001E; and, in part, by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 95 TC 35 Z9 35 U1 2 U2 11 PU THOMSON REUTERS (SCIENTIFIC) LTD PI LONDON PA 77 HATTON GARDEN, LONDON, EC1N 8JS, ENGLAND SN 1367-6733 EI 2040-3437 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD SEP PY 2010 VL 13 IS 5 BP 527 EP 537 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 645DI UT WOS:000281430700002 ER PT J AU Rerks-Ngarm, S Pitisuttithum, P Ganguly, N Zhang, LQ Tamashiro, H Cooper, DA Vun, MC Bela, B Ditangco, R Kinh, NV Bernstein, A Osmanov, S Mathieson, B Kent, SJ Shao, YM AF Rerks-Ngarm, Supachai Pitisuttithum, Punnee Ganguly, Nirmal Zhang, Linqi Tamashiro, Hiko Cooper, David A. Mean Chhi Vun Bela, Budiman Ditangco, Rossana Nguyen Van Kinh Bernstein, Alan Osmanov, Saladin Mathieson, Bonnie Kent, Stephen J. Shao, Yiming TI Defining the objectives of the AIDS vaccine for Asia network: report of the WHO-UNAIDS/Global HIV vaccine enterprise regional consultation on expanding AIDS vaccine research and development capacity in Asia SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE AIDS; Asia; HIV; vaccine ID VIRUS-VACCINE; SUBTYPE; IMMUNOGENICITY; THAILAND; SAFETY; TRIAL; BOOST; DNA; CANDIDATE; RESPONSES C1 [Kent, Stephen J.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. [Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Bangkok 10700, Thailand. [Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand. [Ganguly, Nirmal] Indian Council Med Res, New Delhi, India. [Zhang, Linqi] Tsinghua Univ, Chinese Acad Med Sci, Beijing 100084, Peoples R China. [Zhang, Linqi] Peking Union Med Coll, Beijing 100021, Peoples R China. [Tamashiro, Hiko] Hokkaido Univ, Sapporo, Hokkaido, Japan. [Cooper, David A.] Univ NSW, Sydney, NSW, Australia. [Mean Chhi Vun] Natl Ctr HIV AIDS Dermatol & STIs NCHADS, Phnom Penh, Cambodia. [Bela, Budiman] Univ Indonesia, Jakarta, Indonesia. [Ditangco, Rossana] Res Inst Trop Med, Manila, Philippines. [Nguyen Van Kinh] Natl Inst Infect & Trop Dis NIITD, Hanoi, Vietnam. [Bernstein, Alan] Global HIV Vaccine Enterprise, New York, NY USA. [Osmanov, Saladin] Joint United Nations Programme HIV AIDS, WHO, Geneva, Switzerland. [Mathieson, Bonnie] Off AIDS Res, NIH, Washington, DC USA. [Shao, Yiming] Natl Ctr AIDS STD Control & Prevent, Beijing, Peoples R China. RP Kent, SJ (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. EM skent@unimelb.edu.au RI Tamashiro, Hidehiko/B-2403-2013; OI Kent, Stephen/0000-0002-8539-4891 FU World Health Organization; National Institutes of Health Office of AIDS Research; Global HIV Vaccine Enterprise (GHVE); China AIDS Vaccine Initiative (CAVI); Deirdre FX The Beijing meeting was sponsored by the World Health Organization, the National Institutes of Health Office of AIDS Research, the Global HIV Vaccine Enterprise (GHVE), and the China AIDS Vaccine Initiative (CAVI). The World Health Organization and the Joint United Nations Programme on HIV/AIDS (WHO-UNAIDS) and the Global HIV Vaccine Enterprise (GHVE) are extremely grateful to all participants who made this regional consultation a fruitful and successful meeting, in particular to the Ministry of Health of the People's Republic of China, to the Chinese Centre for Disease Control and Prevention for hosting this meeting. Thanks are also given to Michael Benenson, Jorge Flores, Deirdre Grant, Sonali Kochhar, Zarifah Reed, Candace Rosen, and Yiming Shao who served as rapporteurs. The organizers also thank Jean Louis Excler for his assistance at the meeting and preparing the first draft of the meeting report. The authors also acknowledge the help of Tim France (iniscommunication.com) for technical editing of the paper. NR 31 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD SEP PY 2010 VL 5 IS 5 BP 435 EP 452 DI 10.1097/COH.0b013e32833c95c1 PG 18 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 828NO UT WOS:000295508900013 PM 20978386 ER PT J AU Henderson, C Goldbach-Mansky, R AF Henderson, Cailin Goldbach-Mansky, Raphaela TI Monogenic autoinflammatory diseases: new insights into clinical aspects and pathogenesis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE autoinflammatory diseases; cryopyrin-associated periodic syndromes; deficiency of the IL-1 receptor antagonist; familial Mediterranean fever; hyperimmunoglobulinemia D with periodic fevers syndrome; IL-1; inflammasome; TNF-receptor-associated periodic syndrome ID FAMILIAL MEDITERRANEAN FEVER; RECURRENT MULTIFOCAL OSTEOMYELITIS; PEDIATRIC GRANULOMATOUS ARTHRITIS; KAPPA-B ACTIVATION; HYPERIMMUNOGLOBULINEMIA-D SYNDROME; RILONACEPT INTERLEUKIN-1 TRAP; RECEPTOR ANTAGONIST ANAKINRA; ENCODING MEVALONATE KINASE; EARLY-ONSET SARCOIDOSIS; LOW-LEVEL MOSAICISM AB Purpose of review The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases. Recent findings The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor-associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease. Summary The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development. C1 [Goldbach-Mansky, Raphaela] NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, Translat Autoinflammatory Dis Sect, NIH, MSC 1616,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov RI e-, a/F-9947-2012 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases program FX Dr Henderson and Dr Goldbach-Mansky are employees of the National Institutes of Health. Their research is funded through the intramural National Institute of Arthritis and Musculoskeletal and Skin Diseases program and they report no financial conflicts of interest. NR 96 TC 41 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD SEP PY 2010 VL 22 IS 5 BP 567 EP 578 DI 10.1097/BOR.0b013e32833ceff4 PG 12 WC Rheumatology SC Rheumatology GA 632VS UT WOS:000280457800016 PM 20671522 ER PT J AU Colbert, RA AF Colbert, Robert A. TI Early axial spondyloarthritis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE ankylosing spondylitis; axial; classification; preradiographic; spondyloarthritis ID SOCIETY CLASSIFICATION CRITERIA; JUVENILE IDIOPATHIC ARTHRITIS; INFLAMMATORY BACK-PAIN; ANKYLOSING-SPONDYLITIS; EVIDENT SACROILIITIS; EARLY DISEASE; WHOLE-BODY; SPONDYLARTHRITIS; VALIDATION; CYTOKINES AB Purpose of review To summarize recent advances in the classification of preradiographic axial spondyloarthritis (SpA). Recent findings Inflammation in the sacroiliac joints precedes radiographic damage that is necessary to establish a diagnosis of ankylosing spondylitis (AS). Preradiographic axial SpA refers to patients with SpA who exhibit signs and symptoms of axial involvement, but lack criteria for AS. Patients with axial SpA can have remarkably similar clinical features and disease activity as those with early AS. MRI is a sensitive method for detecting sacroiliac joint inflammation, which is useful in predicting the development of AS. Whole-body MRI has emerged as a means to visualize additional areas of involvement. However, it may be less sensitive than conventional MRI, and thus its added value will need to be further assessed. The incorporation of MRI evaluation of the sacroiliac joints and HLA-B27 testing into criteria for identifying individuals with preradiographic axial disease has led to the development of criteria for classifying axial SpA. Summary The development of classification criteria for axial SpA will aid in the identification of patients suitable for clinical trials testing whether early intervention will slow the development and/or progression of structural changes in that lead to AS. C1 NIAMSD, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA. RP Colbert, RA (reprint author), NIAMSD, Pediat Translat Res Branch, NIH, Bldg 10,Room 1-5142,10 Ctr Dr, Bethesda, MD 20892 USA. EM colbertr@mail.nih.gov FU National Institute of Arthritis Musculoskeletal and Skin Diseases at the NIH FX R.A.C. is supported by the Intramural Research Program of the National Institute of Arthritis Musculoskeletal and Skin Diseases at the NIH. He thanks Dr M. Ward for critical evaluation of the manuscript. There are no conflicts of interest. NR 34 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD SEP PY 2010 VL 22 IS 5 BP 603 EP 607 DI 10.1097/BOR.0b013e32833c7255 PG 5 WC Rheumatology SC Rheumatology GA 632VS UT WOS:000280457800021 PM 20592602 ER PT J AU Roederer, M Tarnok, A AF Roederer, Mario Tarnok, Attila TI OMIPs-Orchestrating Multiplexity In Polychromatic science SO CYTOMETRY PART A LA English DT Editorial Material ID FLOW-CYTOMETRY; B-CELLS; MIFLOWCYT C1 [Tarnok, Attila] Univ Leipzig, Ctr Heart, Dept Pediat Cardiol, D-04289 Leipzig, Germany. [Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Tarnok, A (reprint author), Univ Leipzig, Heart Ctr Leipzig, Dept Pediat Cardiol, Strumpellstr 39, D-04289 Leipzig, Germany. EM tarnok@medizin.uni-leipzig.de NR 7 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2010 VL 77A IS 9 BP 811 EP 812 DI 10.1002/cyto.a.20959 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 646AU UT WOS:000281508100001 PM 20722007 ER PT J AU Mahnke, Y Chattopadhyay, P Roederer, M AF Mahnke, Yolanda Chattopadhyay, Pratip Roederer, Mario TI Publication of Optimized Multicolor Immunofluorescence Panels SO CYTOMETRY PART A LA English DT Letter ID FLOW-CYTOMETRY C1 [Mahnke, Yolanda; Chattopadhyay, Pratip; Roederer, Mario] NIAID, ImmunoTechnoloy Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, ImmunoTechnoloy Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov RI Chattopadhyay, Pratip/B-9227-2008; OI Chattopadhyay, Pratip/0000-0002-5457-9666 NR 6 TC 13 Z9 14 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2010 VL 77A IS 9 BP 814 EP 818 DI 10.1002/cyto.a.20916 PG 5 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 646AU UT WOS:000281508100002 PM 20722004 ER PT J AU Mahnke, YD Roederer, M AF Mahnke, Yolanda D. Roederer, Mario TI OMIP-001: Quality and Phenotype of Ag-Responsive Human T-Cells SO CYTOMETRY PART A LA English DT Article C1 [Mahnke, Yolanda D.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mahnke, YD (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM mahnkey@mail.nih.gov NR 3 TC 20 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2010 VL 77A IS 9 BP 819 EP 820 DI 10.1002/cyto.a.20944 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 646AU UT WOS:000281508100003 PM 20722005 ER PT J AU Chattopadhyay, PK Roederer, M Price, DA AF Chattopadhyay, Pratip K. Roederer, Mario Price, David A. TI OMIP-002: Phenotypic Analysis of Specific Human CD8+ T-Cells Using Peptide-MHC Class I Multimers for Any of Four Epitopes SO CYTOMETRY PART A LA English DT Article C1 [Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Price, David A.] Cardiff Univ Sch Med, Dept Infect Immun & Biochem, Cardiff, S Glam, Wales. RP Chattopadhyay, PK (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM pchattop@mail.nih.gov RI Chattopadhyay, Pratip/B-9227-2008; Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Chattopadhyay, Pratip/0000-0002-5457-9666 FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [G0501963] NR 3 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD SEP PY 2010 VL 77A IS 9 BP 821 EP 822 DI 10.1002/cyto.a.20945 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 646AU UT WOS:000281508100004 PM 20722006 ER PT J AU Kursawe, R Eszlinger, M Narayan, D Liu, T Bazuine, M Cali, AMG D'Adamo, E Shaw, M Pierpont, B Shulman, GI Cushman, SW Sherman, A Capriol, S AF Kursawe, Romy Eszlinger, Markus Narayan, Deepak Liu, Teresa Bazuine, Merlijn Cali, Anna M. G. D'Adamo, Ebe Shaw, Melissa Pierpont, Bridget Shulman, Gerald I. Cushman, Samuel W. Sherman, Arthur Capriol, Sonia TI Cellularity and Adipogenic Profile of the Abdominal Subcutaneous Adipose Tissue From Obese Adolescents: Association With Insulin Resistance and Hepatic Steatosis SO DIABETES LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; TYPE-2 DIABETES-MELLITUS; CELL-SIZE; ADIPOCYTE DIFFERENTIATION; IMPAIRED ADIPOGENESIS; LIPOPROTEIN-LIPASE; ETHNIC-DIFFERENCES; GLUCOSE-TOLERANCE; LIPIN EXPRESSION; IN-VITRO AB OBJECTIVE We explored whether the distribution of adipose cell size, the estimated total number of adipose cells, and the expression of adipogenic genes in subcutaneous adipose tissue are linked to the phenotype of high visceral and low subcutaneous fat depots in obese adolescents. RESEARCH DESIGN AND METHODS A total of 38 adolescents with similar degrees of obesity agreed to have a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test and hyperinsulinemic euglycemic clamp) and imaging studies (MRI, DEXA, (1)H-NMR). Subcutaneous periumbilical adipose cell-size distribution and the estimated total number of subcutaneous adipose cells were obtained from tissue biopsy samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. The adipogenic capacity was measured by Affymetrix Gene Chip and quantitative RT-PCR. RESULTS Subjects were divided into two groups: high versus low ratio of visceral to visceral + subcutaneous fat (VAT/[VAT+SAT]). The cell-size distribution curves were significantly different between the high and low VAT/(VAT+SAT) groups, even after adjusting for age, sex, and ethnicity (MANOVA P = 0.035). Surprisingly, the fraction of large adipocytes was significantly lower (P < 0.01) in the group with high VAT/(VAT+SAT), along with the estimated total number of large adipose cells (P < 0.05), while the mean diameter was increased (P < 0.01). From the microarray analyses emerged a lower expression of lipogenesis/adipogenesis markers (sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase) in the group with high VAT/(VAT+SAT), which was confirmed by RT-PCR. CONCLUSIONS A reduced lipo-/adipogenic capacity, fraction, and estimated number of large subcutaneous adipocytes may contribute to the abnormal distribution of abdominal fat and hepatic steatosis, as well as to insulin resistance in obese adolescents. Diabetes 59:2288-2296, 2010 C1 [Kursawe, Romy; Cali, Anna M. G.; D'Adamo, Ebe; Shaw, Melissa; Pierpont, Bridget; Capriol, Sonia] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Eszlinger, Markus] Univ Leipzig, Dept Endocrinol, Leipzig, Germany. [Narayan, Deepak] Yale Univ, Sch Med, Dept Plast Surg, New Haven, CT USA. [Liu, Teresa; Bazuine, Merlijn; Cushman, Samuel W.] NIDDK, Diabet Branch, NIH, Bethesda, MD USA. [Shulman, Gerald I.] Yale Univ, Sch Med, Dept Internal Med & Cellular & Mol Physiol, New Haven, CT USA. [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RP Capriol, S (reprint author), Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. EM sonia.caprio@yale.edu OI Eszlinger, Markus/0000-0002-4732-2934 FU National Institutes of Health [R01-HD-40787, R01-HD-28016, K24-HD-01464]; National Center for Research Resources (NCRR), National Institutes of Health [UL1-RR-0249139]; American Diabetes Association [R01-EB-006494]; National Institutes of Health, NIDDK FX This study was supported by grants from the National Institutes of Health (R01-HD-40787, R01-HD-28016, and K24-HD-01464) to S.C. and by CTSA Grant No. UL1-RR-0249139 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health; and R01-EB-006494 (Bioimage Suite), and Distinguished Clinical Scientist Awards from the American Diabetes Association (S.C.). T.L., M.B., A.S., and S.W.C. were supported by the Intramural Research Program of the National Institutes of Health, NIDDK. No potential conflicts of interest relevant to this article were reported. NR 45 TC 44 Z9 45 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2010 VL 59 IS 9 BP 2288 EP 2296 DI 10.2337/db10-0113 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647IN UT WOS:000281612000026 PM 20805387 ER PT J AU Klingensmith, GJ Pyle, L Arslanian, S Copeland, KC Cuttler, L Kaufman, F Laffel, L Marcovina, S Tollefsen, SE Weinstock, RS Linder, B AF Klingensmith, Georgeanna J. Pyle, Laura Arslanian, Silva Copeland, Kenneth C. Cuttler, Leona Kaufman, Francine Laffel, Lori Marcovina, Santica Tollefsen, Sherida E. Weinstock, Ruth S. Linder, Barbara CA TODAY Study Grp TI The Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype Results from the TODAY study SO DIABETES CARE LA English DT Article ID CHILDREN; ADOLESCENTS; AUTOIMMUNITY; MELLITUS; EUROPE; TRENDS; ONSET AB OBJECTIVE - To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings. RESEARCH DESIGN AND METHODS - Children (10-17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations. RESULTS - Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects. CONCLUSIONS - Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes. C1 [Klingensmith, Georgeanna J.] Univ Colorado Denver, Barbara Davis Ctr, Aurora, CO 80202 USA. [Klingensmith, Georgeanna J.] Univ Colorado Denver, Childrens Hosp, Aurora, CO USA. [Pyle, Laura] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Arslanian, Silva] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Copeland, Kenneth C.] Univ Oklahoma, Coll Med, Oklahoma City, OK 73190 USA. [Cuttler, Leona] Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA. [Kaufman, Francine] Univ So Calif, Los Angeles, CA USA. [Kaufman, Francine] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Laffel, Lori] Harvard Univ, Sch Med, Boston, MA USA. [Marcovina, Santica] Univ Washington, Dept Med, Seattle, WA USA. [Tollefsen, Sherida E.] St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. [Weinstock, Ruth S.] SUNY Upstate Med Univ, Syracuse, NY USA. [Weinstock, Ruth S.] Dept Vet Affairs Med Ctr, Syracuse, NY USA. [Linder, Barbara] NIDDKD, NIH, Bethesda, MD 20892 USA. RP Klingensmith, GJ (reprint author), Univ Colorado Denver, Barbara Davis Ctr, Aurora, CO 80202 USA. EM georgeanna.klingensmith@ucdenver.edu FU NIDDK, NIH [U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, U01-DK-61254]; National Center for Research Resources General Clinical Research Centers [M01-RR-00036, M01-RR-00043-45, M01-RR-00069, M01-RR-00084, M01-RR-01066, M01-RR-00125, M01-RR14467] FX This work was completed with funding from NIDDK, NIH (grants U01-DK-61212, U01-DK-61230, U01-DK-61239, U01-DK-61242, and U01-DK-61254) and from the National Center for Research Resources General Clinical Research Centers Program (grant M01-RR-00036 [Washington University in St. Louis School of Medicine], M01-RR-00043-45 [Children's Hospital Los Angeles], M01-RR-00069 [University of Colorado Health Sciences Center], M01-RR-00084 [Children's Hospital of Pittsburgh], M01-RR-01066 [Massachusetts General Hospital], M01-RR-00125 [Yale University], and M01-RR14467 [University of Oklahoma Health Sciences Center]). NR 19 TC 46 Z9 50 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 SEP PY 2010 VL 33 IS 9 BP 1970 EP 1975 DI 10.2337/dc10-0373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 659IN UT WOS:000282560300014 PM 20519658 ER PT J AU Calles-Escandon, J Light, L Lovato, L Getaneh, A Simmons, D Kirk, J Bonds, D Banerji, MA Green, JB Menon, L Moogali, A Bergenstal, RM AF Calles-Escandon, J. Light, L. Lovato, L. Getaneh, A. Simmons, D. Kirk, J. Bonds, D. Banerji, M. A. Green, J. B. Menon, L. Moogali, A. Bergenstal, R. M. TI Glycaemia management of minority participants in ACCORD SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Calles-Escandon, J.; Light, L.; Lovato, L.; Kirk, J.; Menon, L.; Moogali, A.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Getaneh, A.] Columbia Univ, New York, NY USA. [Simmons, D.] Univ Arkansas, Little Rock, AR 72204 USA. [Bonds, D.] NHLBI, Washington, DC USA. [Banerji, M. A.] State Univ, Brooklyn, NY USA. [Green, J. B.] Duke Univ, Durham, NC 27706 USA. [Bergenstal, R. M.] ADA, Alexandria, VA USA. 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 31 BP S19 EP S19 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700032 ER PT J AU Levetan, CS Peters, AJ Novelli, KJ Marks, BE Katz, AE Peterson, RG Upham, LV AF Levetan, C. S. Peters, A. J. Novelli, K. J. Marks, B. E. Katz, A. E. Peterson, R. G. Upham, L. V. TI Impact of a stabilized human reg3a protein on islet neogenesis and glycaemic control SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Levetan, C. S.] Chestnut Hill Hosp, Philadelphia, PA USA. [Peters, A. J.] NIH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. [Novelli, K. J.] Cabrini Coll, Rosemont, PA USA. [Marks, B. E.; Katz, A. E.] Thomas Jefferson Univ, Sch Med, Philadelphia, PA 19107 USA. [Peterson, R. G.] Univ Notre Dame, South Bend, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 529 BP S215 EP S215 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700530 ER PT J AU Mather, KJ Christophi, CA Jablonski, KA Knowler, WC Goldberg, RB Kahn, SE Pi-Sunyer, FX Pollin, TI Florez, JC Franks, PW AF Mather, K. J. Christophi, C. A. Jablonski, K. A. Knowler, W. C. Goldberg, R. B. Kahn, S. E. Pi-Sunyer, F. X. Pollin, T. I. Florez, J. C. Franks, P. W. CA Diabet Prevention Program Res Grp TI Associations of common variants of ADIPOQ, ADIPOR1 and ADIPOR2 with adiponectin concentration and diabetes incidence in the Diabetes Prevention Program SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Mather, K. J.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Christophi, C. A.; Jablonski, K. A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Knowler, W. C.] NIDDKD, Phoenix, AZ USA. [Goldberg, R. B.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Kahn, S. E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Pi-Sunyer, F. X.] St Lukes Roosevelt Hosp, New York, NY 10025 USA. [Pollin, T. I.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Florez, J. C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Franks, P. W.] Umea Univ Hosp, S-90185 Umea, Sweden. 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 303 BP S130 EP S131 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700304 ER PT J AU Rees, MG Turner, C Facio, FM Beer, NL McCarthy, MI Biesecker, LG Gloyn, AL Collins, FS AF Rees, M. G. Turner, C. Facio, F. M. Beer, N. L. McCarthy, M. I. Biesecker, L. G. Gloyn, A. L. Collins, F. S. CA NISC Comparative Sequencing Progra TI Insights into glucokinase regulatory protein regulation from the cellular and kinetic characterisation of rare coding variants SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Rees, M. G.; Beer, N. L.; McCarthy, M. I.; Gloyn, A. L.] Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Rees, M. G.; Turner, C.; Facio, F. M.; Biesecker, L. G.; Collins, F. S.] NIH, Bethesda, MD 20892 USA. 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 54 BP S29 EP S29 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700055 ER PT J AU Schafer, MK Eiden, LE Weihe, E AF Schafer, M. K. Eiden, L. E. Weihe, E. TI Vesicular monoamine transporter 2 gene expression in beta cells of primates but not of rodents: implications for developing radioligands for imaging of beta cell mass in animal models SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Schafer, M. K.; Weihe, E.] Univ Marburg, Inst Anat & Cell Biol, D-35032 Marburg, Germany. [Eiden, L. E.] NIMH, Mol Neurosci Sect, Bethesda, MD 20892 USA. 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 477 BP S195 EP S196 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689700478 ER PT J AU Gonzalez, N Ramos-Alvarez, I Martin-Duce, A Moreno, P Nuche-Berenguer, B Sanz, R Portal-Nunez, S Jensen, RT Villanueva-Penacarrillo, ML AF Gonzalez, N. Ramos-Alvarez, I. Martin-Duce, A. Moreno, P. Nuche-Berenguer, B. Sanz, R. Portal-Nunez, S. Jensen, R. T. Villanueva-Penacarrillo, M. L. TI Bombesin receptor subtype-3 signalling and its role on glucose transport in human myocytes SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Gonzalez, N.; Ramos-Alvarez, I.; Moreno, P.; Nuche-Berenguer, B.; Sanz, R.; Portal-Nunez, S.; Villanueva-Penacarrillo, M. L.] HS Fdn Jimenez Diaz, Madrid, Spain. [Martin-Duce, A.] Univ Alcala de Henares, Madrid, Spain. [Jensen, R. T.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 702 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701145 ER PT J AU Gradmark, A Pomeroy, J Renstrom, F Steiginga, S Wright, A Kahn, SE Mogren, I Domellof, M Franks, PW AF Gradmark, A. Pomeroy, J. Renstrom, F. Steiginga, S. Wright, A. Kahn, S. E. Mogren, I. Domellof, M. Franks, P. W. TI Physical activity may offset pregnancy-related insulin resistance SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Gradmark, A.; Renstrom, F.; Steiginga, S.; Franks, P. W.] GECRG, Umea, Sweden. [Pomeroy, J.] NIDDK, NIH, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Wright, A.] MRC Human Nutr Res, Cambridge, England. [Kahn, S. E.] Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [Mogren, I.] Dept Clin Sci Obstet & Gynecol, Umea, Sweden. [Domellof, M.] Dept Pediat, Umea, Sweden. RI Domellof, Magnus/E-5307-2011 OI Domellof, Magnus/0000-0002-0726-7029 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 688 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701131 ER PT J AU Simila, ME Kontto, JP Valsta, LM Albanes, D Virtamo, J AF Simila, M. E. Kontto, J. P. Valsta, L. M. Albanes, D. Virtamo, J. TI Carbohydrate substitution for protein, fat, and their subtypes and risk of type 2 diabetes in men SO DIABETOLOGIA LA English DT Meeting Abstract CT 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD) CY SEP 20-24, 2010 CL Stockholm, SWEDEN SP European Assoc Study Diabetes C1 [Simila, M. E.; Kontto, J. P.; Valsta, L. M.; Virtamo, J.] Natl Inst Hlth & Welf, Helsinki, Finland. [Albanes, D.] NCI, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 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 0012-186X J9 DIABETOLOGIA JI Diabetologia PD SEP PY 2010 VL 53 SU 1 MA 937 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 635XA UT WOS:000280689701379 ER PT J AU Turkbey, B Thomasson, D Pang, YX Bernardo, M Choyke, PL AF Turkbey, Baris Thomasson, David Pang, Yuxi Bernardo, Marcelino Choyke, Peter L. TI The role of dynamic contrast-enhanced MRI in cancer diagnosis and treatment SO DIAGNOSTIC AND INTERVENTIONAL RADIOLOGY LA English DT Review DE pathologic angiogenesis; angiogenic inhibitors; magnetic resonance imaging ID TUMOR ANGIOGENESIS; KINETIC-PARAMETERS; BREAST-CANCER; MICROCIRCULATION; BEVACIZUMAB AB Angiogenesis is a key step in the pathophysiology of tumor growth and metastatic spread. Recently, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has emerged as a method for assessing angiogenesis both during the initial diagnosis and for follow up of anti-angiogenic therapies. In this review, we discuss the technical aspects of implementing DCE-MRI in clinical practice with emphasis on acquisition methods and analytic techniques. C1 [Turkbey, Baris; Bernardo, Marcelino; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Thomasson, David] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Pang, Yuxi] Philips Healthcare, Cleveland, OH USA. RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM bturkbey@yahoo.com FU Intramural NIH HHS [Z01 BC010714-03] NR 20 TC 40 Z9 46 U1 0 U2 7 PU TURKISH SOC RADIOLOGY PI ANKARA PA HOSDERE CAD, GUZELKENT SOK, CANKAYA EVLERI, F-2, ANKARA, 06540, TURKEY SN 1305-3825 J9 DIAGN INTERV RADIOL JI Diagn. Interv. Radiol. PD SEP PY 2010 VL 16 IS 3 BP 186 EP 192 DI 10.4261/1305-3825.DIR.2537-08.1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 642RC UT WOS:000281232900003 PM 19885783 ER PT J AU Matsuda, KM Nobrega, R Quezado, M Schrump, DS Filie, AC AF Matsuda, Kant M. Nobrega, Raissa Quezado, Martha Schrump, David S. Filie, Armando C. TI Melanocytic Bronchopulmonary Carcinoid Tumor in a Patient With Multiple Endocrine Neoplasia Syndrome Type 1: A Case Report With Emphasis on Intraoperative Cytological Findings SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE melanocytic bronchopulmonary carcinoid tumor; multiple endocrine neoplasia syndrome type 1; melanin; intra-operative cytology consultation; touch preparation ID GERMLINE MUTATIONS; THYMIC CARCINOIDS; APUD SERIES; MEN1 GENE; PATHOGENESIS; FEATURES; LESIONS; ORIGIN; CELLS AB We present the cytological features along with histologic and imaging findings of a melanocytic bronchopulmonary carcinoid tumor in a patient with multiple endocrine neoplasia syndrome type 1 (MEN-1). Intraoperative touch preparations of the lung tumor showed single spindle cells and loosely cohesive aggregates of spindle cells with oval to elongated nuclei, "salt and pepper" chromatin pattern and inconspicuous nucleoli. The spindle cells occasionally contained cytoplasmic pigment, which revealed to be melanin by Fontana Masson stain on permanent processed material. Immunohistochemical stains for both synaptophysin and chromogranin were strongly positive in the spindle cells. The findings were consistent with melanocytic bronchopulmonary carcinoid tumor, which is relatively uncommon in MEN-1. Diagn. Cytopathol. 2010;38:669-674. (C) 2010 Wiley-Liss, Inc. C1 [Matsuda, Kant M.; Nobrega, Raissa; Quezado, Martha; Filie, Armando C.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Schrump, David S.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Bldg 10 Room 2A19, Bethesda, MD 20892 USA. EM afilie@mail.nih.gov FU NIH, National Cancer Institute FX We thank the Clinical Imaging Processing (CIP) Department, Clinical Center, National Institutes of Health for the 3D reconstruction images. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 30 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8755-1039 EI 1097-0339 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD SEP PY 2010 VL 38 IS 9 BP 669 EP 674 DI 10.1002/dc.21296 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 645XE UT WOS:000281498700009 PM 20196165 ER PT J AU Schug, TT AF Schug, Thaddeus T. TI The skinny on SIRT1 regulation SO DISEASE MODELS & MECHANISMS LA English DT Editorial Material ID CALORIE RESTRICTION; PGC-1-ALPHA; DEACETYLASE; DBC1 C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Schug, TT (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. EM schugt@niehs.nih.gov NR 17 TC 0 Z9 0 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2010 VL 3 IS 9-10 BP 507 EP 508 DI 10.1242/dmm.005629 PG 2 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 678FR UT WOS:000284060000001 PM 20483999 ER PT J AU Ayala, JE Samuel, VT Morton, GJ Obici, S Croniger, CM Shulman, GI Wasserman, DH McGuinness, OP AF Ayala, Julio E. Samuel, Varman T. Morton, Gregory J. Obici, Silvana Croniger, Colleen M. Shulman, Gerald I. Wasserman, David H. McGuinness, Owen P. CA NIH Mouse Metab Phenotyping Ctr Co TI Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice SO DISEASE MODELS & MECHANISMS LA English DT Review ID MUSCLE INSULIN SENSITIVITY; DIET-INDUCED OBESITY; HIGH-FAT-DIET; OB-OB MICE; IN-VIVO; SKELETAL-MUSCLE; RECEPTOR SUBSTRATE-1; LIPOATROPHIC MICE; TRANSGENIC MICE; BLOOD-GLUCOSE AB The Mouse Metabolic Phenotyping Center (MMPC) Consortium was established to address the need to characterize the growing number of mouse models of metabolic diseases, particularly diabetes and obesity. A goal of the MMPC Consortium is to propose standard methods for assessing metabolic phenotypes in mice. In this article, we discuss issues pertaining to the design and performance of various tests of glucose metabolism. We also propose guidelines for the description of methods, presentation of data and interpretation of results. The recommendations presented in this article are based on the experience of the MMPC Consortium and other investigators. C1 [Ayala, Julio E.; Wasserman, David H.; McGuinness, Owen P.] Vanderbilt NIH Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. [Ayala, Julio E.] Sanford Burnham Med Res Inst Lake Nona, Orlando, FL 32827 USA. [Samuel, Varman T.; Shulman, Gerald I.] Yale NIH Mouse Metab Phenotyping Ctr, New Haven, CT 06520 USA. [Morton, Gregory J.] Univ Washington, NIH Mouse Metab Phenotyping Ctr, Seattle, WA 98109 USA. [Obici, Silvana] Univ Cincinnati, NIH Mouse Metab Phenotyping Ctr, Cincinnati, OH 45267 USA. [Croniger, Colleen M.] Case Western Reserve Univ, NIH Mouse Metab Phenotyping Ctr, Cleveland, OH 44106 USA. RP Ayala, JE (reprint author), Vanderbilt NIH Mouse Metab Phenotyping Ctr, Nashville, TN 37232 USA. EM jayala@sanfordburnham.org FU NIH [5-U24-DK059637-10, 5-U24-DK076169-05, 5-U24-DK076126-05, 5-U24DK059630-10] FX We thank Stephen C. Woods for his editorial assistance in preparing this manuscript. This work was supported by the following NIH grants: 5-U24-DK059637-10 (Vanderbilt University MMPC), 5-U24-DK076169-05 (Yale University MMPC and Case Western Reserve University MMPC), 5-U24-DK076126-05 (University of Washington MMPC) and 5-U24DK059630-10 (University of Cincinnati MMPC). Deposited in PMC for release after 12 months. NR 62 TC 183 Z9 185 U1 5 U2 38 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2010 VL 3 IS 9-10 BP 525 EP 534 DI 10.1242/dmm.006239 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 678FR UT WOS:000284060000008 PM 20713647 ER PT J AU McMains, VC Myre, M Kreppel, L Kimmel, AR AF McMains, Vanessa C. Myre, Michael Kreppel, Lisa Kimmel, Alan R. TI Dictyostelium possesses highly diverged presenilin/gamma-secretase that regulates growth and cell-fate specification and can accurately process human APP: a system for functional studies of the presenilin/gamma-secretase complex SO DISEASE MODELS & MECHANISMS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; C-TERMINAL FRAGMENT; GAMMA-SECRETASE; INTRAMEMBRANE PROTEOLYSIS; BETA-CATENIN; TRANSMEMBRANE ASPARTATES; INTRACELLULAR DOMAIN; LINKED MUTATIONS; DISCOIDEUM AB Presenilin (PS) is the catalytic moiety of the gamma-secretase complex. PS and other gamma-secretase components are well conserved among metazoa, but their presence and function in more-distant species are not resolved. Because inappropriate gamma-secretase processing of amyloid precursor protein (APP) in humans is associated with familial Alzheimer's disease, understanding essential elements within each gamma-secretase component is crucial to functional studies. Diverged proteins have been identified in primitive plants but experiments have failed to demonstrate gamma-secretase activity. We have identified highly diverged orthologs for each gamma-secretase component in the ancient eukaryote Dictyostelium, which lacks equivalents of APP, Notch and other characterized PS/gamma-secretase substrates. We show that wild-type (WT) Dictyostelium is capable of amyloidogenic processing of ectopically expressed human APP to generate amyloid-beta peptides A beta(40) and A beta(42); strains deficient in gamma-secretase cannot produce A beta peptides but accumulate processed intermediates of APP that co-migrate with the C-terminal fragments alpha-and beta-CTF of APP that are found in mammalian cells. We further demonstrate that Dictyostelium requires PS for phagocytosis and cell-fate specification in a cell-autonomous manner, and show that regulation of phagocytosis requires an active gamma-secretase, a pathway suggested, but not proven, to occur in mammalian and Drosophila cells. Our results indicate that PS signaling is an ancient process that arose prior to metazoan radiation, perhaps independently of Notch. Dictyostelium might serve to identify novel PS/gamma-secretase signaling targets and provide a unique system for high-throughput screening of small-molecule libraries to select new therapeutic targets for diseases associated with this pathway. C1 [McMains, Vanessa C.; Kreppel, Lisa; Kimmel, Alan R.] NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. [McMains, Vanessa C.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Myre, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Richard B Simches Res Ctr, Boston, MA 02114 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov FU National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases FX We thank Xiuli Huang, Xin-Hua Liao, Collette Young, Marielle Young, Jonathan Buggey, Joseph Brzostowski and Taruna Khurana for insightful discussions and expert technical advice. We also thank Konstantin Chumakov for guidance on phylogenic analyses, and appreciate the generosity of Wilma Wasco. This research was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Diabetes and Digestive and Kidney Diseases. Deposited in PMC for release after 12 months. NR 66 TC 20 Z9 20 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 1754-8403 J9 DIS MODEL MECH JI Dis. Model. Mech. PD SEP-OCT PY 2010 VL 3 IS 9-10 BP 581 EP 594 DI 10.1242/dmm.004457 PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 678FR UT WOS:000284060000014 PM 20699477 ER PT J AU Conway, KP Levy, J Vanyukoy, M Chandler, R Rutter, J Swan, GE Neale, M AF Conway, Kevin P. Levy, Janet Vanyukoy, Michael Chandler, Redonna Rutter, Joni Swan, Gary E. Neale, Michael TI Measuring addiction propensity and severity: The need for a new instrument SO DRUG AND ALCOHOL DEPENDENCE LA English DT Review DE Tobacco; Cannabis assessment; Individual differences; Adolescents ID SUBSTANCE USE DISORDERS; ENVIRONMENTAL RISK-FACTORS; ITEM RESPONSE THEORY; ALCOHOL DEPENDENCE SCALE; GENOME-WIDE ASSOCIATION; DRUG-ABUSE; NICOTINE DEPENDENCE; BEHAVIORAL DISINHIBITION; GENETIC INFLUENCES; DSM-IV AB Drug addiction research requires but lacks a valid and reliable way to measure both the risk (propensity) to develop addiction and the severity of manifest addiction. This paper argues for a new measurement approach and instrument to quantify propensity to and severity of addiction, based on the testable assumption that these constructs can be mapped onto the same dimension of liability to addiction. The case for this new direction becomes clear from a critical review of empirical data and the current instrumentation. The many assessment instruments in use today have proven utility, reliability, and validity, but they are of limited use for evaluating individual differences in propensity and severity. The conceptual and methodological shortcomings of instruments currently used in research and clinical practice can be overcome through the use of new technologies to develop a reliable, valid, and standardized assessment instrument(s) to measure and distinguish individual variations in expression of the underlying latent trait(s) that comprises propensity to and severity of drug addiction. Such instrumentation would enhance our capacity for drug addiction research on linkages and interactions among familial, genetic, psychosocial, and neurobiological factors associated with variations in propensity and severity. It would lead to new opportunities in substance abuse prevention, treatment, and services research, as well as in interventions and implementation science for drug addiction. Published by Elsevier Ireland Ltd. C1 [Conway, Kevin P.; Chandler, Redonna] NIDA, DESPR, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Levy, Janet] Duke Univ, Sch Nursing, Durham, NC 27710 USA. [Vanyukoy, Michael] Univ Pittsburgh, SALK 528, Dept Pharmaceut Sci, Pittsburgh, PA 15260 USA. [Vanyukoy, Michael] Univ Pittsburgh, SALK 528, Dept Psychiat, Pittsburgh, PA 15260 USA. [Vanyukoy, Michael] Univ Pittsburgh, SALK 528, Dept Human Genet, Pittsburgh, PA 15260 USA. [Rutter, Joni] NIDA, Div Basic Neurosci & Behav Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Swan, Gary E.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA. [Neale, Michael] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. RP Conway, KP (reprint author), NIDA, DESPR, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd,Suite 5185, Bethesda, MD 20892 USA. EM kconway@nida.nih.gov OI Rutter, Joni/0000-0002-6502-2361; Conway, Kevin/0000-0002-7638-339X FU Intramural NIH HHS [Z99 DA999999] NR 126 TC 18 Z9 19 U1 9 U2 20 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 SEP 1 PY 2010 VL 111 IS 1-2 BP 4 EP 12 DI 10.1016/j.drugalcdep.2010.03.011 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 658FU UT WOS:000282476700003 PM 20462706 ER PT J AU Levin, KH Copersino, ML Heishman, SJ Liu, F Kelly, DL Boggs, DL Gorelick, DA AF Levin, Kenneth H. Copersino, Marc L. Heishman, Stephen J. Liu, Fang Kelly, Deanna L. Boggs, Douglas L. Gorelick, David A. TI Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Cannabis; Marijuana; Withdrawal; Tolerance; Relapse ID SUBSTANCE USE DISORDERS; LONG-TERM USERS; MARIJUANA WITHDRAWAL; ABSTINENCE SYMPTOMS; TREATMENT SEEKERS; FOLLOW-UP; DEPENDENCE; ADOLESCENTS; POPULATION; RELAPSE AB Background: Cannabis withdrawal is not recognized in DSM-IV because of doubts about its clinical significance. Objectives: Assess the phenomenon of cannabis withdrawal and its relationship to relapse in non-treatment-seeking adults. Subjects: Convenience sample of 469 adult cannabis smokers who had made a quit attempt while not in a controlled environment. Methods: Subjects completed a 176-item Marijuana Quit Questionnaire collecting information on sociodemographic characteristics, cannabis use history, and their "most difficult" cannabis quit attempt. Results: 42.4% of subjects had experienced a lifetime withdrawal syndrome, of whom 70.4% reported using cannabis in response to withdrawal. During the index quit attempt, 95.5% of subjects reported >= 1 individual withdrawal symptom (mean [SD] 9.5 [6.1], median 9.0); 43.1% reported >= 10. Number of withdrawal symptoms was significantly associated with greater frequency and amount of cannabis use, but symptoms occurred even in those using less than weekly. Symptoms were usually of >= moderate intensity and often prompted actions to relieve them. Alcohol (41.5%) and tobacco (48.2%) were used more often than cannabis (33.3%) for this purpose. There was little change during withdrawal in use of other legal or illegal substances. Conclusions: Cannabis withdrawal is a common syndrome among adults not seeking treatment. The intention to relieve withdrawal symptoms can drive relapse during quit attempts, giving cannabis withdrawal clinical significance as a target of treatment. Published by Elsevier Ireland Ltd. C1 [Gorelick, David A.] NIDA, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Copersino, Marc L.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02478 USA. [Liu, Fang; Kelly, Deanna L.; Boggs, Douglas L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. RP Gorelick, DA (reprint author), NIDA, NIH, Intramural Res Program, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural Research Program; National Institutes of Health; National Institute on Drug Abuse; NIDA Residential Research Support Services [HHSN271200599091CADB] FX This study was supported by the Intramural Research Program, National Institutes of Health, National Institute on Drug Abuse, and NIDA Residential Research Support Services Contract HHSN271200599091CADB. The funding sources had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. NR 55 TC 19 Z9 19 U1 4 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP 1 PY 2010 VL 111 IS 1-2 BP 120 EP 127 DI 10.1016/j.drugalcdep.2010.04.010 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 658FU UT WOS:000282476700018 PM 20510550 ER PT J AU Okuda, M Hasin, DS Olfson, M Khan, SS Nunes, EV Montoya, I Liu, SM Grant, BF Blanco, C AF Okuda, Mayumi Hasin, Deborah S. Olfson, Mark Khan, Sharaf S. Nunes, Edward V. Montoya, Ivan Liu, Shang-Min Grant, Bridget F. Blanco, Carlos TI Generalizability of clinical trials for cannabis dependence to community samples SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Epidemiology; Generalizability; Cannabis dependence; Clinical trials; Eligibility criteria; Inclusion criteria; Exclusion criteria ID NATIONAL-EPIDEMIOLOGIC-SURVEY; ALCOHOL-USE DISORDER; RANDOMIZED CONTROLLED-TRIAL; ANTIDEPRESSANT EFFICACY TRIALS; INTERVIEW SCHEDULE AUDADIS; DRUG-USE DISORDERS; DSM-IV ALCOHOL; EXCLUSION CRITERIA; UNITED-STATES; SUBSTANCE USE AB There is growing concern that results of tightly controlled clinical trials may not generalize to broader community samples. To assess the proportion of community dwelling adults with cannabis dependence who would have been eligible for a typical cannabis dependence treatment study, we applied a standard set of eligibility criteria commonly used in cannabis outcome studies to a large (N = 43,093) representative US adult sample interviewed face-to-face, the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Approximately 80% of the community sample of adults with a diagnosis of cannabis dependence (N = 133) would be excluded from participating in clinical trials by one or more of the common eligibility criteria. Individual study criteria excluded from 0% to 41.0% of the community sample. Legal problems, other illicit drug use disorders, and current use of fewer than 5 joints/week excluded the largest percentage of individuals. These results extend to cannabis dependence concerns that typical clinical trials likely exclude most community dwelling adults with the disorder. The results also support the notion that clinical trials tend to recruit highly selective samples, rather than adults who are representative of typical patients. Clinical trials should carefully evaluate the effects of eligibility criteria on the generalizability of their results. Even in efficacy trials, stringent exclusionary criteria could limit the representativeness of study results. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Okuda, Mayumi; Hasin, Deborah S.; Olfson, Mark; Khan, Sharaf S.; Nunes, Edward V.; Liu, Shang-Min; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Montoya, Ivan] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Blanco, C (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr,Unit 69, New York, NY 10032 USA. EM cb255@columbia.edu RI Blanco, Carlos/I-4906-2013; Okuda, Mayumi/L-6210-2013 OI Blanco, Carlos/0000-0001-6187-3057; Okuda, Mayumi/0000-0002-3479-5599 FU National Institute on Alcohol Abuse and Alcoholism; NIAAA, National Institutes of Health; National Institute of Drug Abuse; American Foundation for Suicide Foundation; New York State Psychiatric Institute 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 Intramural Program, NIAAA, National Institutes of Health, with supplementary funding from the National Institute of Drug Abuse. This study was supported by a grant from the American Foundation for Suicide Foundation (Dr. Blanco) and the New York State Psychiatric Institute (Drs. Blanco, Olfson, Nunes and Hasin). NR 60 TC 28 Z9 29 U1 3 U2 4 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 SEP 1 PY 2010 VL 111 IS 1-2 BP 177 EP 181 DI 10.1016/j.drugalcdep.2010.04.009 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 658FU UT WOS:000282476700027 PM 20537813 ER PT J AU Griffin, JA AF Griffin, James A. TI Research on the implementation of preschool intervention programs: Learning by doing SO EARLY CHILDHOOD RESEARCH QUARTERLY LA English DT Editorial Material DE Implementation research; Early intervention; School readiness ID PROFESSIONAL-DEVELOPMENT; SCHOOL READINESS; BEHAVIOR; TRIAL C1 [Griffin, James A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Bethesda, MD USA. RP Griffin, JA (reprint author), NICHD, NIH, Child Dev & Behav Branch, 6100 Execut Blvd,Suite 4B05, Rockville, MD 20852 USA. EM james.griffin@nih.gov FU Intramural NIH HHS [Z99 HD999999] NR 14 TC 7 Z9 7 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-2006 J9 EARLY CHILD RES Q JI Early Childhood Res. Q. PD SEP PY 2010 VL 25 IS 3 BP 267 EP 269 DI 10.1016/j.ecresq.2010.03.004 PG 3 WC Education & Educational Research; Psychology, Developmental SC Education & Educational Research; Psychology GA 616ML UT WOS:000279213400001 PM 20657800 ER PT J AU Greenberg, DE Shoffner, AR Zelazny, AM Fenster, ME Zarember, KA Stock, F Ding, L Marshall-Batty, KR Wasserman, RL Welch, DF Kanakabandi, K Sturdevant, DE Virtaneva, K Porcella, SF Murray, PR Malech, HL Holland, SM AF Greenberg, David E. Shoffner, Adam R. Zelazny, Adrian M. Fenster, Michael E. Zarember, Kol A. Stock, Frida Ding, Li Marshall-Batty, Kimberly R. Wasserman, Richard L. Welch, David F. Kanakabandi, Kishore Sturdevant, Dan E. Virtaneva, Kimmo Porcella, Stephen F. Murray, Patrick R. Malech, Harry L. Holland, Steven M. TI Recurrent Granulibacter bethesdensis Infections and Chronic Granulomatous Disease SO EMERGING INFECTIOUS DISEASES LA English DT Article ID ACETIC-ACID BACTERIUM; ASAIA-BOGORENSIS; SEQUENCE-ANALYSIS; REINFECTION; PATIENT; TUBERCULOSIS; BACTEREMIA; CHILD AB Chronic granulomatous disease (CGD)is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patients with CGD from North and Central America. Genomic typing showed that 3 patients had recurrent infection months to years after apparent clinical cure. Two patients were infected with the same strain as previously isolated, and 1 was infected with a genetically distinct strain. This organism is multidrug resistant, and therapy required surgery and combination antimicrobial drugs, including long-term ceftriaxone. G. bethesdensis causes necrotizing lymphadenitis in COD, which may recur or relapse. C1 [Greenberg, David E.] NIAID, Labs Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Wasserman, Richard L.; Welch, David F.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Welch, David F.] Childrens Med Ctr, Dallas, TX 75235 USA. [Welch, David F.] Med City Dallas Hosp, Dallas, TX USA. [Kanakabandi, Kishore; Sturdevant, Dan E.; Virtaneva, Kimmo; Porcella, Stephen F.] NIH, Hamilton, MT USA. RP Greenberg, DE (reprint author), NIAID, Labs Clin Infect Dis, NIH, 33 North Dr,2W10A3, Bethesda, MD 20892 USA. EM degreenberg@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU Baxter Healthcare; CSL Behring; Talecris Biotherapeutics; Nabi Biopharmaceuticals; Prodesse (Gen-Probe); National Institute of Allergy and Infectious Diseases, NIH FX David E. Greenberg, MD; Adam R. Shoffner, BS; Adrian M. Zelazny, PhD; Michael E. Fenster, MD; Kol A. Zarember, PhD, BSc; Frida Stock, BS; Li Ding, MD; Kimberly R. Marshall-Batty, PhD, MS, BS; Kishore Kanakabandi; Dan E. Sturdevant, PhD; Kimmo Virtaneva; Stephen F. Porcella, PhD; Patrick R. Murray, PhD; Harry L. Malech, MD; and Steven M. Holland, MD, have disclosed no relevant financial relationships. Richard L. Wasserman, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Baxter Healthcare, CSL Behring, Talecris Biotherapeutics; served as a speaker or a member of a speakers bureau for Baxter Healthcare, CSL Behring, Talecris Biotherapeutics; received grants for clinical research from Baxter Healthcare, CSL Behring, Talecris Biotherapeutics, Nabi Biopharmaceuticals. David F. Welch, PhD, has disclosed the following relevant financial relationships: received grants for clinical research from: Prodesse (Gen-Probe); owns stock, stock options, or bonds from Cepheid, Luminex Corporation, Merck & Co., Inc., Eli Lilly and Company, Boston Scientific Corporation; Becton, Dickinson and Company.; This study was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. NR 19 TC 22 Z9 22 U1 0 U2 3 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2010 VL 16 IS 9 BP 1341 EP 1348 DI 10.3201/eid1609.091800 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 643YT UT WOS:000281338000001 PM 20735916 ER PT J AU Lajous, M Danon, L Lopez-Ridaura, R Astley, CM Miller, JC Dowell, SF O'Hagan, JJ Goldstein, E Lipsitch, M AF Lajous, Martin Danon, Leon Lopez-Ridaura, Ruy Astley, Christina M. Miller, Joel C. Dowell, Scott F. O'Hagan, Justin J. Goldstein, Edward Lipsitch, Marc TI Mobile Messaging as Surveillance Tool during Pandemic (H1N1) 2009, Mexico SO EMERGING INFECTIOUS DISEASES LA English DT Letter C1 [Lajous, Martin] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Lajous, Martin; Lopez-Ridaura, Ruy] Natl Inst Publ Hlth, Ctr Populat Hlth Res, Cuernavaca, Morelos, Mexico. [Danon, Leon] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Miller, Joel C.] NIH, Bethesda, MD 20892 USA. [Dowell, Scott F.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Lajous, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM mlajous@hsph.harvard.edu RI Danon, Leon/J-6324-2012; Miller, Joel/C-4229-2015; OI Danon, Leon/0000-0002-7076-1871; Miller, Joel/0000-0003-4426-0405; Lipsitch, Marc/0000-0003-1504-9213 FU NIGMS NIH HHS [U01 GM076497] NR 5 TC 7 Z9 7 U1 0 U2 2 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD SEP PY 2010 VL 16 IS 9 BP 1488 EP 1489 DI 10.3201/eid1609.100671 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 643YT UT WOS:000281338000026 PM 20735942 ER PT J AU Lodish, MB Adams, KT Huynh, TT Prodanov, T Ling, A Chen, C Shusterman, S Jimenez, C Merino, M Hughes, M Cradic, KW Milosevic, D Singh, RJ Stratakis, CA Pacak, K AF Lodish, Maya B. Adams, Karen T. Huynh, Thanh T. Prodanov, Tamara Ling, Alex Chen, Clara Shusterman, Suzanne Jimenez, Camilo Merino, Maria Hughes, Marybeth Cradic, Kendall W. Milosevic, Dragana Singh, Ravinder J. Stratakis, Constantine A. Pacak, Karel TI Succinate dehydrogenase gene mutations are strongly associated with paraganglioma of the organ of Zuckerkandl SO ENDOCRINE-RELATED CANCER LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMAS; FUNCTIONAL PARAGANGLIOMA; FAMILIAL PARAGANGLIOMA; GERMLINE MUTATIONS; SUBUNIT-B; SDHB; SUSCEPTIBILITY; PENETRANCE; NEOPLASIA; DISTINCT AB Organ of Zuckerkandl paragangliomas (PGLs) are rare neuroendocrine tumors that are derived from chromaffin cells located around the origin of the inferior mesenteric artery extending to the level of the aortic bifurcation. Mutations in the genes encoding succinate dehydrogenase subunits (SDH) B, C, and D (SDHx) have been associated with PGLs, but their contribution to PGLs of the organ of Zuckerkandl PGLs is not known. We aimed to describe the clinical presentation of patients with PGLs of the organ of Zuckerkandl and investigate the prevalence of SDHx mutations and other genetic defects among them. The clinical characteristics of 14 patients with PGL of the organ of Zuckerkandl were analyzed retrospectively; their DNA was tested for SDHx mutations and deletions. Eleven out of 14 (79%) patients with PGLs of the organ of Zuckerkandl were found to have mutations in the SDHB (9) or SDHD (2) genes; one patient was found to have the Carney-Stratakis syndrome (CSS), and his PGL was discovered during surgery for gastrointestinal stromal tumor. Our results show that SDHx mutations are prevalent in pediatric and adult PGLs of the organ of Zuckerkandl. Patients with PGLs of the organ of Zuckerkandl should be screened for SDHx mutations and the CSS; in addition, asymptomatic carriers of an SDHx mutation among the relatives of affected patients may benefit from tumor screening for early PGL detection. Endocrine-Related Cancer (2010) 17 581-588 C1 [Lodish, Maya B.; Stratakis, Constantine A.] Natl Inst Child Hlth & Human Dev NICHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,CRC, Bethesda, MD 20892 USA. [Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod Biol & Adult Endocrinol Program, NIH,CRC, Bethesda, MD 20892 USA. [Ling, Alex; Chen, Clara] NIH, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Shusterman, Suzanne] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jimenez, Camilo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Merino, Maria] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. [Hughes, Marybeth] NCI, Dept Surg, NIH, Bethesda, MD 20892 USA. [Cradic, Kendall W.; Milosevic, Dragana; Singh, Ravinder J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod Biol & Adult Endocrinol Program, NIH,CRC, Bldg 10,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX This work was supported by the Intramural Research funding of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. NR 37 TC 14 Z9 15 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2010 VL 17 IS 3 BP 581 EP 588 DI 10.1677/ERC-10-0004 PG 8 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 657VE UT WOS:000282445100009 PM 20418362 ER PT J AU Meyer-Rochow, GY Jackson, NE Conaglen, JV Whittle, DE Kunnimalaiyaan, M Chen, H Westin, G Sandgren, J Stalberg, P Khanafshar, E Shibru, D Duh, QY Clark, OH Kebebew, E Gill, AJ Clifton-Bligh, R Robinson, BG Benn, DE Sidhu, SB AF Meyer-Rochow, Goswin Y. Jackson, Nicole E. Conaglen, John V. Whittle, Denis E. Kunnimalaiyaan, Muthusamy Chen, Herbert Westin, Gunnar Sandgren, Johanna Stalberg, Peter Khanafshar, Elham Shibru, Daniel Duh, Quan-Yang Clark, Orlo H. Kebebew, Electron Gill, Anthony J. Clifton-Bligh, Rory Robinson, Bruce G. Benn, Diana E. Sidhu, Stan B. TI MicroRNA profiling of benign and malignant pheochromocytomas identifies novel diagnostic and therapeutic targets SO ENDOCRINE-RELATED CANCER LA English DT Article ID NON-TUMOROUS TISSUES; HUMAN OVARIAN-CANCER; HEPATOCELLULAR-CARCINOMA; DOWN-REGULATION; ADRENOCORTICAL TUMORS; EXPRESSION PROFILES; THYROID-CARCINOMA; GENE-EXPRESSION; PROSTATE-CANCER; LUNG-CANCER AB MicroRNAs (miRNAs) are small RNAs (similar to 22 bp) that post-transcriptionally regulate protein expression and are found to be differentially expressed in a number of human cancers. There is increasing evidence to suggest that miRNAs could be useful in cancer diagnosis, prognosis, and therapy. We performed miRNA microarray expression profiling on a cohort of 12 benign and 12 malignant pheochromocytomas and identified a number of differentially expressed miRNAs. These results were validated in a separate cohort of ten benign and ten malignant samples using real-time quantitative RT-PCR; benign samples had a minimum follow-up of at least 2 years. It was found that IGF2 as well as its intronic miR-483-5p was over-expressed, while miR-15a and miR-16 were under-expressed in malignant tumours compared with benign tumours. These miRNAs were found to be diagnostic and prognostic markers for malignant pheochromocytoma. The functional role of miR-15a and miR-16 was investigated in vitro in the rat PC12 pheochromocytoma cell line, and these miRNAs were found to regulate cell proliferation via their effect on cyclin D1 and apoptosis. These data indicate that miRNAs play a pivotal role in the biology of malignant pheochromocytoma, and represent an important class of diagnostic and prognostic biomarkers and therapeutic targets warranting further investigation. Endocrine-Related Cancer (2010) 17 835-846 C1 [Meyer-Rochow, Goswin Y.; Jackson, Nicole E.; Clifton-Bligh, Rory; Robinson, Bruce G.; Benn, Diana E.; Sidhu, Stan B.] Royal N Shore Hosp, Kolling Inst Med Res, Canc Genet Hormones & Canc Grp, St Leonards, NSW 2065, Australia. [Sidhu, Stan B.] Royal N Shore Hosp, Dept Endocrine & Oncol Surg, St Leonards, NSW 2065, Australia. [Clifton-Bligh, Rory; Robinson, Bruce G.] Royal N Shore Hosp, Dept Endocrinol, St Leonards, NSW 2065, Australia. [Gill, Anthony J.] Royal N Shore Hosp, Dept Anat Pathol, St Leonards, NSW 2065, Australia. [Meyer-Rochow, Goswin Y.; Jackson, Nicole E.; Gill, Anthony J.; Clifton-Bligh, Rory; Robinson, Bruce G.; Benn, Diana E.; Sidhu, Stan B.] Univ Sydney, Fac Med, Sydney, NSW 2006, Australia. [Meyer-Rochow, Goswin Y.; Whittle, Denis E.] Univ Auckland, Dept Surg, Fac Med & Hlth Sci, Waikato Clin Sch, Auckland 1142, New Zealand. [Conaglen, John V.] Univ Auckland, Dept Endocrinol, Fac Med & Hlth Sci, Waikato Clin Sch, Auckland 1142, New Zealand. [Kunnimalaiyaan, Muthusamy; Chen, Herbert] Univ Wisconsin, Endocrine Surg Res Labs, Dept Surg, Madison, WI USA. [Kunnimalaiyaan, Muthusamy; Chen, Herbert] UW Carbone Canc Ctr, Madison, WI USA. [Westin, Gunnar; Sandgren, Johanna; Stalberg, Peter] Univ Hosp, Dept Surg Sci, SE-75185 Uppsala, Sweden. [Khanafshar, Elham; Shibru, Daniel; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 93143 USA. [Khanafshar, Elham; Shibru, Daniel; Duh, Quan-Yang; Clark, Orlo H.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 93143 USA. [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. RP Sidhu, SB (reprint author), AMA House,202-69 Christie St, St Leonards, NSW 2065, Australia. EM stansidhu@nebsc.com.au RI Gill, Anthony/D-4215-2015 OI Gill, Anthony/0000-0002-9447-1967 FU National Health and Medical Research Council (NHMRC, Australia); Cancer Institute of New South Wales (CINSW, Australia); Royal Australasian College of Surgeons (RACS); Hillcrest Foundation FX G Y Meyer-Rochow is a recipient of the National Health and Medical Research Council (NHMRC, Australia) Postgraduate Research Scholarship, the Cancer Institute of New South Wales (CINSW, Australia) Postgraduate Scholarship and the Royal Australasian College of Surgeons (RACS) Surgeon Scientist Scholarships. S B Sidhu is a NSW Cancer Institute Clinical Research Fellow. D E Benn is supported by the Hillcrest Foundation. NR 46 TC 40 Z9 42 U1 1 U2 7 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2010 VL 17 IS 3 BP 835 EP 846 DI 10.1677/ERC-10-0142 PG 12 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 657VE UT WOS:000282445100029 PM 20621999 ER PT J AU Lodish, MB Stratakis, CA AF Lodish, Maya B. Stratakis, Constantine A. TI Endocrine side effects of broad-acting kinase inhibitors SO ENDOCRINE-RELATED CANCER LA English DT Review ID RENAL-CELL CARCINOMA; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; GASTROINTESTINAL STROMAL TUMOR; PHASE-II TRIAL; SUNITINIB INDUCES HYPOTHYROIDISM; MEDULLARY-THYROID CANCER; IMATINIB MESYLATE; BONE-FORMATION; SECONDARY HYPERPARATHYROIDISM AB Targeted therapy in oncology consists of drugs that specifically interfere with abnormal signaling pathways that are dysregulated in cancer cells. Tyrosine kinase inhibitors (TKIs) take advantage of unique oncogenes that are activated in certain types of cancer, and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. However, many kinase inhibitors for cancer therapy are somewhat nonselective, and most have additional mechanisms of action at the cellular level, which are not completely understood. The use of these agents has increased our knowledge of important side effects, of which the practicing clinician must be aware. Recently, proposed endocrine-related side effects of these agents include alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, and glucose metabolism, and adrenal function. This review summarizes the most recent data on the endocrine side effects of TKIs. Endocrine-Related Cancer (2010) 17 R233-R244 C1 [Lodish, Maya B.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol Genet, Bethesda, MD 20892 USA. [Lodish, Maya B.; Stratakis, Constantine A.] NIH, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA. RP Lodish, MB (reprint author), 10 Ctr Dr,CRC Room 1-3330, Bethesda, MD 20892 USA. EM lodishma@mail.nih.gov FU Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported by the Intramural Research Division of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 88 TC 19 Z9 19 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 EI 1479-6821 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SEP PY 2010 VL 17 IS 3 BP R233 EP R244 DI 10.1677/ERC-10-0082 PG 12 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 657VE UT WOS:000282445100006 PM 20603395 ER PT J AU Voutetakis, A Cotrim, AP Rowzee, A Zheng, CY Rathod, T Yanik, T Loh, YP Baum, BJ Cawley, NX AF Voutetakis, Antonis Cotrim, Ana P. Rowzee, Anne Zheng, Changyu Rathod, Trushar Yanik, Tulin Loh, Y. Peng Baum, Bruce J. Cawley, Niamh X. TI Systemic Delivery of Bioactive Glucagon-Like Peptide 1 after Adenoviral-Mediated Gene Transfer in the Murine Salivary Gland SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT INSULINOTROPIC POLYPEPTIDE; RAPAMYCIN CONTROL; IN-VIVO; IV; DEFICIENCY; EXPRESSION; VECTOR; PEPTIDE-1(7-36)AMIDE; THERAPEUTICS; TRAFFICKING AB Anadenoviral (Ad) vector that expresses bioactive glucagon-like peptide 1 (GLP-1) was generated, and its effectiveness at modulating glucose homeostasis was evaluated after transduction of murine salivary glands. The construct was engineered with the signal sequence of mouse GH to direct the peptide into the secretory pathway, followed by a furin cleavage site and the GLP-1(7-37) sequence encoding an Ala to Gly substitution at position 8 to achieve resistance to degradation. When expressed in Neuro2A and COS7 cells, an active form of GLP-1 was specifically detected by RIA in the conditioned medium of transduced cells, showed resistance to degradation by dipeptidyl-peptidase IV, and induced the secretion of insulin from NIT1 pancreatic beta-cells in vitro. In vivo studies demonstrated that healthy mice transduced with Ad-GLP-1 in both submandibular glands had serum GLP-1 levels approximately 3 times higher than mice transduced with the control Ad-luciferase vector. In fasted animals, serum glucose levels were similar between Ad-GLP-1 and Ad-luciferase transduced mice in keeping with GLP-1's glucose-dependent action. However, when challenged with glucose, Ad-GLP-1 transduced mice cleared the glucose significantly faster than control mice. In an animal model of diabetes induced by alloxan, progression of hyperglycemia was significantly attenuated in mice given the Ad-GLP-1 vector compared with control mice. These studies demonstrate that the bioactive peptide hormone, GLP-1, normally secreted from endocrine cells in the gut through the regulated secretory pathway, can be engineered for secretion into the circulatory system from exocrine cells of the salivary gland to affect glucose homeostasis. (Endocrinology 151: 4566-4572, 2010) C1 [Voutetakis, Antonis; Cotrim, Ana P.; Rowzee, Anne; Zheng, Changyu; Baum, Bruce J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Physiol & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rathod, Trushar; Yanik, Tulin; Loh, Y. Peng; Cawley, Niamh X.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rathod, Trushar; Yanik, Tulin; Loh, Y. Peng; Cawley, Niamh X.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cawley, NX (reprint author), 49 Convent Dr,Room 5A22, Bethesda, MD 20892 USA. EM cawleyn@mail.nih.gov OI Rowzee, Anne/0000-0003-1969-9133 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Dental and Craniofacial Research, National Institutes of Health (Bethesda, MD) FX This work was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Dental and Craniofacial Research, National Institutes of Health (Bethesda, MD). NR 34 TC 9 Z9 9 U1 1 U2 1 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 SEP PY 2010 VL 151 IS 9 BP 4566 EP 4572 DI 10.1210/en.2010-0193 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 642WP UT WOS:000281252000052 PM 20610567 ER PT J AU Robertson, RP AF Robertson, R. Paul TI Update on Transplanting Beta Cells for Reversing Type 1 Diabetes SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article DE Pancreas transplantation; Islet transplantation; Type 1 diabetes; Beta cells ID QUALITY-OF-LIFE; PANCREAS-KIDNEY TRANSPLANTATION; CLINICAL ISLET TRANSPLANTATION; STEROID-FREE IMMUNOSUPPRESSION; AUTONOMIC NEUROPATHY; SYMPTOM RECOGNITION; FOLLOW-UP; MELLITUS; INSULIN; HYPOGLYCEMIA AB Whole pancreas has been used successfully for transplantation for more than 30 years, and islets have been used reproducibly with success for 10 years; both procedures require drugs for immunosuppression. Success is judged by discontinuation of exogenous insulin-based treatment and maintenance of normal or nearly normal hemoglobin A1c. Successful pancreas transplantation has beneficial effects on retinopathy, nephropathy, neuropathy, macrovascular disease, and quality of life. Such findings are suggested for islet transplantation, but insufficient information is available to draw firm conclusions. Because of the paucity of annual pancreas donations, research for human beta cell surrogates is essential to provide a transplantation approach to therapy for a greater number of recipients. C1 Univ Washington, NIH, Div Endocrinol & Metab, Pacific NW Diabet Res Inst, Seattle, WA 98122 USA. RP Robertson, RP (reprint author), Univ Washington, NIH, Div Endocrinol & Metab, Pacific NW Diabet Res Inst, 720 Broadway, Seattle, WA 98122 USA. EM rpr@pnri.org FU National Institutes of Health [NIDDK RO1 39994] FX This work was supported by Grant No. NIDDK RO1 39994 from the National Institutes of Health. NR 47 TC 13 Z9 13 U1 4 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2010 VL 39 IS 3 BP 655 EP + DI 10.1016/j.ecl.2010.05.010 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 654CM UT WOS:000282146100014 PM 20723826 ER PT J AU Lee, YC Cook, MB Bhatia, S Chow, WH El-Omar, EM Goto, H Lin, JT Li, YQ Rhee, PL Sharma, P Sung, JJY Wong, JYY Wu, JCY Ho, KY AF Lee, Y. C. Cook, M. B. Bhatia, S. Chow, W. H. El-Omar, E. M. Goto, H. Lin, J. T. Li, Y. Q. Rhee, P. L. Sharma, P. Sung, J. J. Y. Wong, J. Y. Y. Wu, J. C. Y. Ho, K. Y. CA Asian Barrett's Consortium TI Interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus: an Asian multinational study SO ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; LOS-ANGELES CLASSIFICATION; SQUAMOUS-CELL CARCINOMA; RISK-FACTORS; M CRITERIA; PRAGUE C; ESOPHAGOGASTRIC JUNCTION; CHINESE POPULATION; METABOLIC SYNDROME; PALISADE VESSELS AB Background and study aim: The establishment of precise and valid diagnostic criteria is important for any disease. We determined the interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus. Patients and methods: Video clips of endoscopy in 21 patients with/without Barrett's esophagus were used for training (n = 3) and for diagnosis/grading (n = 18) of Barrett's esophagus by endoscopists from seven hospitals in Asia. Barrett's esophagus was graded using the Prague C & M Criteria whereby the circumferential extent of the Barrett's segment (C value), maximum extent of Barrett's segment (M value), location of the gastroesophageal junction, and location of the diaphragmatic hiatus were scored. The intraclass correlation coefficients (ICC) were calculated as a measure of interobserver reliability. Results: A total of 34 endoscopists participated. ICC values for the scores of the C value, M value, location of the gastroesophageal junction, and location of the diaphragmatic hiatus were: 0.92 (95% confidence interval [CI] 0.88-0.97), 0.94 (95%CI 0.90-0.98), 0.86 (95%CI 0.78-0.94), and 0.81 (95%CI 0.71-0.92), respectively, indicating excellent interobserver agreement. The differences in region/country, endoscopists' experience, case volume of participating centers, or primary practice type had no significant effect on the reliability. The ICC values for recognition of Barrett's esophagus of >= 1 cm were 0.90 (95%CI 0.80-1.00) and 0.92 (95%CI 0.87-0.98) for the C and M values, respectively, whereas the corresponding ICC values for Barrett's segment of < 1 cm were 0.18 (95%CI 0.03-0.32) and 0.21 (95%CI 0.00-0.51), respectively. Conclusions: Despite the uncommon occurrence of Barrett's esophagus in Asia, our endoscopists exhibited excellent agreement in the endoscopic diagnosis and grading of Barrett's esophagus using the Prague C & M Criteria. However, in view of the low interobserver reliability in recognizing Barrett's segments of < 1 cm, future studies in Asia should take this into account when selecting the study population. C1 [Wong, J. Y. Y.; Ho, K. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 65, Singapore. [Lee, Y. C.] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. [Cook, M. B.; Chow, W. H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Bhatia, S.] Seth GS Med Coll, Dept Gastroenterol, Bombay, Maharashtra, India. [Bhatia, S.] King Edward Mem Hosp, Bombay, Maharashtra, India. [El-Omar, E. M.] Univ Aberdeen, Div Appl Med, Inst Med Sci, Aberdeen, Scotland. [Goto, H.] Nagoya Univ, Grad Sch Med, Dept Gastroenterol, Nagoya, Aichi 4648601, Japan. [Lin, J. T.] E DA Hosp, Dept Internal Med, Yan Chau Shiang, Kaohsiung Cty, Taiwan. [Lin, J. T.] I Shou Univ, Yan Chau Shiang, Kaohsiung Cty, Taiwan. [Li, Y. Q.] Shandong Univ, Qilu Hosp, Dept Gastroenterol, Jinan 250100, Peoples R China. [Rhee, P. L.] Sungkyunkwan Univ, Sch Med, Dept Med, Samsung Med Ctr, Seoul, South Korea. [Sharma, P.] Vet Affairs Med Ctr, Div Gastroenterol & Hepatol, Kansas City, MO USA. [Sharma, P.] Univ Kansas, Sch Med, Kansas City, MO USA. [Sung, J. J. Y.; Wu, J. C. Y.] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. [Lee, Y. C.] Natl Taiwan Univ, Coll Publ Hlth, Div Biostat, Taipei 10764, Taiwan. RP Ho, KY (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, 5 Lower Kent Ridge Rd, Singapore 65, Singapore. EM khek_yu_ho@nuhs.edu.sg RI Rhee, Poong Lyul/C-9655-2011; Hossain, Sarah /C-7332-2009; Cook, Michael/A-5641-2009; Wu, Justin/N-6916-2015; OI Hossain, Sarah /0000-0003-1355-0979; Cook, Michael/0000-0002-0533-7302; LEE, YI-CHIA/0000-0002-8160-1216 FU Intramural NIH HHS [ZIA CP010136-15] NR 53 TC 23 Z9 23 U1 0 U2 6 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD SEP PY 2010 VL 42 IS 9 BP 699 EP 704 DI 10.1055/s-0030-1255629 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 644WT UT WOS:000281413400002 PM 20806154 ER PT J AU Cao, Y Blount, BC Valentin-Blasini, L Bernbaum, JC Phillips, TM Rogan, WJ AF Cao, Yang Blount, Benjamin C. Valentin-Blasini, Liza Bernbaum, Judy C. Phillips, Terry M. Rogan, Walter J. TI Goitrogenic Anions, Thyroid-Stimulating Hormone, and Thyroid Hormone in Infants SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE infant; iodide; nitrate; perchlorate; thiocyanate; thyrotropin; thyroxine ID TANDEM MASS-SPECTROMETRY; SODIUM-IODIDE SYMPORTER; PERCHLORATE EXPOSURE; DRINKING-WATER; ENVIRONMENTAL PERCHLORATE; HUMAN-URINE; CONGENITAL HYPOTHYROIDISM; ION CHROMATOGRAPHY; US POPULATION; UNITED-STATES AB BACKGROUND: Environmental exposure of infants to perchlorate, thiocyanate, nitrate, might interfere with thyroid function. U.S. women with higher background perchlorate exposure have higher thyroid-stimulating hormone (TSH) and lower thyroxine (T-4). There are no studies with individual measures of thyroid function and these goitrogens available in infants. OBJECTIVE: We examined the association of urinary perchlorate, nitrate, iodide, and thiocyanate with urinary T-4 and TSH in infants and whether that association differed by sex or iodide status. METHODS: We used data and samples from the Study of Estrogen Activity and Development, which assessed hormone levels of full-term infants over the first 12 months of life. The study included 92 full-term infants between birth and 1 year of age seen up to four times. Perchlorate, thiocyanate, nitrate, and iodide were measured in 206 urine samples; TSH and T-4 and were measured in urines and in 50 blood samples. RESULTS: In separate mixed models, adjusting for creatinine, age, sex, and body mass index, infants with higher urinary perchlorate, nitrate or thiocyanate had higher urinary TSH. With all three modeled, children with higher nitrate and thiocyanate had higher TSH, but higher perchlorate was associated with TSH only in children with low iodide. Unexpectedly, exposure to the three chemicals was generally associated with higher T-4. CONCLUSIONS: The association of perchlorate exposure with increased urinary TSH in infants with low urinary iodide is consistent with previous findings. Higher thiocyanate and nitrate exposure were also associated with higher TSH in infants. C1 [Cao, Yang; Rogan, Walter J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Cao, Yang] Second Mil Med Univ, Fac Hlth Serv, Dept Hlth Stat, Shanghai, Peoples R China. [Blount, Benjamin C.; Valentin-Blasini, Liza] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Bernbaum, Judy C.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Lab, Bethesda, MD USA. RP Rogan, WJ (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Cao, Yang/0000-0002-3552-9153 FU National Institutes of Health FX This work was supported in part by the Intramural Research Program of the National Institutes of Health. NR 37 TC 15 Z9 17 U1 0 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2010 VL 118 IS 9 BP 1332 EP 1337 DI 10.1289/ehp.0901736 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 647MB UT WOS:000281621500024 PM 20439182 ER PT J AU Hirschfeld, S Kramer, B Guttmacher, A AF Hirschfeld, Steven Kramer, Barnett Guttmacher, Alan TI Current Status of the National Children's Study SO EPIDEMIOLOGY LA English DT Editorial Material C1 [Hirschfeld, Steven] NICHD, Natl Childrens Hlth Study, NIH, Bethesda, MD 20814 USA. [Kramer, Barnett] NIH, Off Director, Bethesda, MD 20892 USA. [Guttmacher, Alan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, Bethesda, MD USA. RP Hirschfeld, S (reprint author), NICHD, Natl Childrens Hlth Study, NIH, 31 Ctr Dr,Room 2A03, Bethesda, MD 20814 USA. EM hirschfs@mail.nih.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 1 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2010 VL 21 IS 5 BP 605 EP 606 DI 10.1097/EDE.0b013e3181ea603b PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 640BC UT WOS:000281021100006 PM 20631619 ER PT J AU Zelner, JL King, AA Moe, CL Eisenberg, JNS AF Zelner, Jonathan L. King, Aaron A. Moe, Christine L. Eisenberg, Joseph N. S. TI How Infections Propagate After Point-Source Outbreaks An Analysis of Secondary Norovirus Transmission SO EPIDEMIOLOGY LA English DT Article ID VIRAL GASTROENTERITIS; NORWALK VIRUS; FOOD HANDLERS; DISEASE; PARAMETERS; HOUSEHOLD; MODELS AB Background: Secondary transmission after point-source outbreaks is an integral feature of the epidemiology of gastrointestinal pathogens such as norovirus. The household is an important site of these secondary cases. It can become the source of further community transmission as well as new point-source outbreaks. Consequently, time-series data from exposed households provide information for risk assessment and intervention. Methods: Analysis of these data requires models that can address (1) dependencies in infection transmission, (2) random variability resulting from households with few members, and (3) unobserved state variables important to transmission. We use Monte Carlo maximum likelihood via data augmentation for obtaining estimates of the transmission rate and infectious period from household outbreaks with the 3 above features. Results: We apply this parameter estimation technique to 153 infection sequences within households from a norovirus outbreak in Sweden and obtain maximum likelihood estimates of the daily rate of transmission ((beta) over cap = 0.14, 95% confidence interval [CI] = 0.08-0.24) and average infectious period (1/(gamma) over cap = 1.17 days, 95% CI = 1.00-1.88). We also demonstrate the robustness of the estimates to missing household sizes and asymptomatic infections. Conclusions: Maximum likelihood techniques such as these can be used to estimate transmission parameters under conditions of unobserved states and missing household size data, and to aid in the understanding of secondary risks associated with point-source outbreaks. C1 [Zelner, Jonathan L.; King, Aaron A.; Eisenberg, Joseph N. S.] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA. [Zelner, Jonathan L.] Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. [Zelner, Jonathan L.] Univ Michigan, Gerald R Ford Sch Publ Policy, Ann Arbor, MI 48109 USA. [King, Aaron A.] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA. [King, Aaron A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA. [Eisenberg, Joseph N. S.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Moe, Christine L.] Emory Univ, Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. [King, Aaron A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Zelner, JL (reprint author), Univ Michigan, Ctr Study Complex Syst, 321A W Hall,1085 S Univ Ave, Ann Arbor, MI 48109 USA. EM jzelner@umich.edu RI Moe, Christine/G-6118-2012; King, Aaron/B-8092-2012 OI King, Aaron/0000-0001-6159-3207 FU US Environmental Protection Agency (EPA) [RD83172701]; Department of Homeland Security (DHS); EPA [RD83236201]; Science & Technology Directorate, Department of Homeland Security; Fogarty International Center of the National Institutes of Health FX Supported by US Environmental Protection Agency (EPA) STAR Grant # RD83172701(to J.L.Z., C. L. M. and J.N.S.) and by CAMRA program of the Department of Homeland Security (DHS) and EPA Grant # RD83236201(to J.L.Z. and J.N.S.). RAPIDD program of the Science & Technology Directorate, Department of Homeland Security and the Fogarty International Center of the National Institutes of Health (to A. A. K.). NR 32 TC 11 Z9 11 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2010 VL 21 IS 5 BP 711 EP 718 DI 10.1097/EDE.0b013e3181e5463a PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 640BC UT WOS:000281021100024 PM 20508526 ER PT J AU Bharti, N Djibo, A Ferrari, MJ Grais, RF Tatem, AJ McCabe, CA Bjornstad, ON Grenfell, BT AF Bharti, N. Djibo, A. Ferrari, M. J. Grais, R. F. Tatem, A. J. McCabe, C. A. Bjornstad, O. N. Grenfell, B. T. TI Measles hotspots and epidemiological connectivity SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Infectious disease control; infectious disease epidemiology; measles (rubeola); spatial modelling; vaccine-preventable diseases ID MASS VACCINATION; DYNAMICS; EPIDEMICS; MODEL; TRANSMISSION; PERSISTENCE; ENGLAND; IMPACT; WALES; NIGER AB Though largely controlled in developed countries, measles remains a major global public health issue. Regional and local transmission patterns are rooted in human mixing behaviour across spatial scales. Identifying spatial interactions that contribute to recurring epidemics helps define and predict outbreak patterns. Using spatially explicit reported cases from measles outbreaks in Niger, we explored how regional variations in movement and contact patterns relate to patterns of measles incidence. Because we expected to see lower rates of re-introductions in small, compared to large, populations, we measured the population-size corrected proportion of weeks with zero cases across districts to understand relative rates of measles re-introductions. We found that critical elements of spatial disease dynamics in Niger are agricultural seasonality, transnational contact clusters, and roads networks that facilitate host movement and connectivity. These results highlight the need to understand local patterns of seasonality, demographic characteristics, and spatial heterogeneities to inform vaccination policy. C1 [Bharti, N.] Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. [Bharti, N.; Ferrari, M. J.; Bjornstad, O. N.; Grenfell, B. T.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Djibo, A.] Minist Hlth, Niamey, Niger. [Grais, R. F.] Epicentre, Paris, France. [Tatem, A. J.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA. [Tatem, A. J.] Univ Florida, Dept Geog, Gainesville, FL USA. [McCabe, C. A.] Penn State Univ, Dept Geog, University Pk, PA 16802 USA. [McCabe, C. A.] Penn State Univ, GeoVISTA Ctr, University Pk, PA 16802 USA. [Bjornstad, O. N.] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Bjornstad, O. N.; Grenfell, B. T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Bharti, N (reprint author), Penn State Univ, Dept Biol, Mueller Lab 208, University Pk, PA 16802 USA. EM nita@psu.edu RI Bjornstad, Ottar/I-4518-2012 FU Bill and Melinda Gates Foundation [49446]; Science & Technology Directorate, Department of Homeland Security; Forgarty International Center, National Institutes of Health FX This study was supported by the Bill and Melinda Gates Foundation. M.J.F., O.N.B. and B.G. were also supported by the RAPIDD programme of the Science & Technology Directorate, Department of Homeland Security, and the Forgarty International Center, National Institutes of Health. A.J.T. is supported by a grant from the Bill and Melinda Gates Foundation (no. 49446). We thank Paolo Palermo from UNOCHA for his assistance. NR 38 TC 16 Z9 16 U1 0 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD SEP PY 2010 VL 138 IS 9 BP 1308 EP 1316 DI 10.1017/S0950268809991385 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 643DT UT WOS:000281275300013 PM 20096146 ER PT J AU Koh, K Quon, M AF Koh, K. Quon, M. TI Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT ESC Congress CY AUG 28-SEP 01, 2010 CL Stockholm, SWEDEN C1 [Koh, K.] Gachon Univ, Inchon, South Korea. [Quon, M.] NIH, Diabet Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2010 VL 31 SU 1 BP 175 EP 176 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 646ID UT WOS:000281531901173 ER PT J AU Kostek, MC Devaney, JM Gordish-Dressman, H Harris, TB Thompson, PD Clarkson, PM Angelopoulos, TJ Gordon, PM Moyna, NM Pescatello, LS Visich, PS Zoeller, RF Seip, RL Garcia, M Li, RL Zmuda, JM Delmonico, MJ Kanaya, A Hoffman, EP AF Kostek, Matthew C. Devaney, Joseph M. Gordish-Dressman, Heather Harris, Tamara B. Thompson, Paul D. Clarkson, Priscilla M. Angelopoulos, Theodore J. Gordon, Paul M. Moyna, Niall M. Pescatello, Linda S. Visich, Paul S. Zoeller, Robert F. Seip, Richard L. Garcia, Melissa Li, Rongling Zmuda, Joseph M. Delmonico, Matthew J. Kanaya, Alka Hoffman, Eric P. TI A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE IGF1; Muscle; Body composition; Bone mineral density; Elderly; SNP ID GROWTH-FACTOR-I; COMMON GENETIC-VARIATION; PROSTATE-CANCER RISK; BONE-MINERAL DENSITY; FAT-FREE MASS; SKELETAL-MUSCLE; OLDER-ADULTS; MYOFIBER HYPERTROPHY; PHYSICAL FUNCTION; TRANSGENIC MICE AB Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, -C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70-79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females. C1 [Devaney, Joseph M.; Gordish-Dressman, Heather; Hoffman, Eric P.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Kostek, Matthew C.] Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. [Harris, Tamara B.; Garcia, Melissa] NIA, NIH, Bethesda, MD 20892 USA. [Thompson, Paul D.; Seip, Richard L.] Hartford Hosp, Div Cardiol, Henry Low Heart Ctr, Hartford, CT 06115 USA. [Clarkson, Priscilla M.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA. [Angelopoulos, Theodore J.] Univ Cent Florida, Ctr Lifestyle Med, Orlando, FL 32816 USA. [Gordon, Paul M.] Univ Michigan, Dept Phys Med & Rehabil, Ann Arbor, MI USA. [Moyna, Niall M.] Dublin City Univ, Dept Sport Sci & Hlth, Dublin 9, Ireland. [Pescatello, Linda S.] Univ Connecticut, Dept Kinesiol, Sch Educ, Storrs, CT USA. [Visich, Paul S.] Cent Michigan Univ, Human Performance Lab, Mt Pleasant, MI 48859 USA. [Zoeller, Robert F.] Florida Atlantic Univ, Dept Exercise Sci & Hlth Promot, Davie, FL USA. [Li, Rongling] Univ Tennessee, Dept Prevent Med, Memphis, TN USA. [Zmuda, Joseph M.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [Delmonico, Matthew J.] Univ Rhode Isl, Dept Kinesiol, Kingston, RI 02881 USA. [Kanaya, Alka] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Hoffman, EP (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. EM ericphoffman@gmail.com RI gordon, paul/E-3862-2015 OI gordon, paul/0000-0003-4403-0888 FU NIH, National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA contract numbers: N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106). NR 38 TC 12 Z9 14 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD SEP PY 2010 VL 110 IS 2 BP 315 EP 324 DI 10.1007/s00421-010-1500-0 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 644MD UT WOS:000281380800011 PM 20490824 ER PT J AU Wong, HL Peters, U Hayes, RB Huang, WY Schatzkin, A Bresalier, RS Velie, EM Brody, LC AF Wong, Hui-Lee Peters, Ulrike Hayes, Richard B. Huang, Wen-Yi Schatzkin, Arthur Bresalier, Robert S. Velie, Ellen M. Brody, Lawrence C. TI Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Adenomatous polyposis coli; SNPs; Advanced adenoma; Colorectal cancer ID HORMONE-REPLACEMENT-THERAPY; CANCER SCREENING TRIAL; SPORADIC BREAST-CANCER; CALCIUM SUPPLEMENTATION; ASYMPTOMATIC ADULTS; HAPLOTYPE ANALYSIS; SOMATIC MUTATIONS; RANDOMIZED-TRIAL; COMMON VARIANTS; E1317Q VARIANT AB While germline mutations in the adenomatous polyposis coli (APC) gene cause the hereditary colon cancer syndrome (familial adenomatous polyposis (FAP)), the role of common germline APC variants in sporadic adenomatous polyposis remains unclear. We studied the association of eight APC single nucleotide polymorphisms (SNPs), possibly associated with functional consequences, and previously identified gene-environment (dietary fat intake and hormone replacement therapy (HRT) use) interactions, in relation to advanced colorectal adenoma in 758 cases and 767 sex- and race-matched controls, randomly selected from the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cases had at least one verified advanced adenoma of the distal colon; controls, a negative sigmoidoscopy. We did not observe an association between genotypes for any of the eight APC SNPs and advanced distal adenoma risk (P(global) (gene-based) = 0.92). Frequencies of identified common haplotypes did not differ between cases and controls (P(global) (haplotype test) = 0.97). However, the risk for advanced distal adenoma was threefold higher for one rare haplotype (cases: 2.7%; controls: 1.6%) (odds ratio (OR) = 3.27; 95% confidence interval (CI) = 1.08-9.88). The genetic association between D1822V and advanced distal adenoma was confined to persons consuming a high-fat diet(P(interaction) = 0.03). Similar interactions were not observed with HRT use. In our large, nested case-control study of advanced distal adenoma and clinically verified adenoma-free controls, we observed no association between specific APC SNPs and advanced adenoma. Fat intake modified the APC D1822V-adenoma association, but further studies are warranted. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Velie, Ellen M.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Wong, Hui-Lee; Peters, Ulrike; Hayes, Richard B.; Huang, Wen-Yi; Schatzkin, Arthur] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. [Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Bresalier, Robert S.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Gastrointestinal Med & Nutr, Houston, TX 77030 USA. [Velie, Ellen M.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Brody, Lawrence C.] NHGRI, Dept Hlth & Human Serv, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Velie, EM (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM velie@epi.msu.edu FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. 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 organisations imply endorsement by the US Government. NR 67 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2010 VL 46 IS 13 BP 2457 EP 2466 DI 10.1016/j.ejca.2010.04.020 PG 10 WC Oncology SC Oncology GA 652HJ UT WOS:000281994100018 PM 20510605 ER PT J AU Freedman, ND Derakhshan, MH Abnet, CC Schatzkin, A Hollenbeck, AR McColl, KEL AF Freedman, N. D. Derakhshan, M. H. Abnet, C. C. Schatzkin, A. Hollenbeck, A. R. McColl, K. E. L. TI Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Oesophageal adenocarcinoma; Gastric cancer; Male predominance; Smoking ID HELICOBACTER-PYLORI INFECTION; GASTRIC-CANCER RISK; LUNG-CANCER; REPRODUCTIVE FACTORS; PROSPECTIVE COHORT; HISTOLOGIC TYPE; POPULATION; ESOPHAGEAL; ALCOHOL; HEALTH AB Background: Adenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance. As smoking is a well-established risk factor, we investigated the role of tobacco smoking in the male predominance of UGI adenocarcinomas in the United States NIH-AARP Diet and Health Study. Method: A questionnaire was completed by 281,422 men and 186,133 women in 1995-1996 who were followed until 31st December 2003. Incident UGI adenocarcinomas were identified by linkage to state cancer registries. We present age-standardised cancer incidence rates per 100,000-person years and male/female ratios (M/F) calculated from age-adjusted Cox proportional hazards models, both with 95% confidence intervals (Cl). Results: After 2013,142-person years follow-up, 338 adenocarcinomas of the oesophagus, 261 of gastric cardia and 222 of gastric non-cardia occurred in men. In women, 23 tumours of oesophagus, 36 of gastric cardia and 88 of gastric non-cardia occurred in 1351,958-person years follow-up. The age-standardised incidence rate of all adenocarcinoma sites was 40.5 (37.8-43.3) and 11.0 (9.2-12.8) in men and women, respectively. Among smokers, the M/F of all UGI adenocarcinomas was 3.4 (2.7-4.1), with a M/F of 7.3 (4.6-11.7) for tumours in oesophagus, 3.7 (2.5-5.4) for gastric cardia and 1.7 (1.2-2.3) for gastric non-cardia. In nonsmokers, M/F ratios were 14.2 (5.1-39.5) for oesophagus, 6.1 (2.6-14.7) for gastric cardia and 1.3 (0.8-2.0) for gastric non-cardia. The overall M/F ratio was 3.0 (2.2-4.3). Conclusion: The male predominance was similar in smokers and non-smokers for these cancer sites. These results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories. (C) 2010 Elsevier Ltd. All rights reserved. C1 [McColl, K. E. L.] Univ Glasgow, Western Infirm, Gastroenterol Sect, Div Cardiovasc & Med Sci, Glasgow G11 6NT, Lanark, Scotland. [Freedman, N. D.; Abnet, C. C.; Schatzkin, A.] Natl Canc Inst, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. [Hollenbeck, A. R.] AARP, Washington, DC USA. RP McColl, KEL (reprint author), Univ Glasgow, Western Infirm, Gastroenterol Sect, Div Cardiovasc & Med Sci, Glasgow G11 6NT, Lanark, Scotland. EM k.e.l.mccoll@clinmed.gla.ac.uk RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Derakhshan, Mohammad/K-8694-2016 OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; FU Chief Scientist Office [CZB/4/709]; Intramural NIH HHS [ZIA CP000185-08] NR 40 TC 19 Z9 21 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2010 VL 46 IS 13 BP 2473 EP 2478 DI 10.1016/j.ejca.2010.05.005 PG 6 WC Oncology SC Oncology GA 652HJ UT WOS:000281994100020 PM 20605442 ER PT J AU Wang, L Carr, T Xiong, YM Wildt, KF Zhu, JF Feigenbaum, L Bendelac, A Bosselut, R AF Wang, Lie Carr, Tiffany Xiong, Yumei Wildt, Kathryn F. Zhu, Jinfang Feigenbaum, Lionel Bendelac, Albert Bosselut, Remy TI The sequential activity of Gata3 and Thpok is required for the differentiation of CD1d-restricted CD4(+) NKT cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+) T cells; NKT cells; Thymic selection; Transcription ID CD4-CD8 LINEAGE DIFFERENTIATION; T-CELLS; EXPRESSION; COMMITMENT; RECEPTORS; SELECTION; DIRECTS; CHOICE; CKROX; FATE AB While most CD4(+) T cells are MHC class II-restricted, a small subset, including the CD1d-restricted 'invariant' NKT (iNKT) cells, are selected on non-classical MHC-I or MHC-I-like molecules. We previously showed that the sequential activity of two zinc finger transcription factors, Gata3 and Thpok, promotes the differentiation of conventional, MHC II-restricted thymocytes into CD4(+) T cells. In the current study, we show that a Gata3-Thpok cascade is required for the differentiation of CD4(+) iNKT cells. Gata3 is required for iNKT cells to express Thpok, whereas Thpok is needed for proper NKT cell differentiation, and notably for NKT cells to maintain CD4 and terminate CD8 expression. These findings identify the sequential activity of Gata3 and Thpok as a hallmark of CD4(+) T-cell differentiation, regardless of MHC restriction. C1 [Bosselut, Remy] NCI, Lab Immune Cell Biol, CCR, NIH, Bethesda, MD 20892 USA. [Carr, Tiffany; Bendelac, Albert] Univ Chicago, Howard Hughes Med Inst, Dept Pathol, Comm Immunol, Chicago, IL 60637 USA. [Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Feigenbaum, Lionel] NCI, SAIC, Frederick, MD 21701 USA. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, CCR, NIH, Bldg 37,Room 3015,37 Convent Dr, Bethesda, MD 20892 USA. EM remy@helix.nih.gov RI Zhu, Jinfang/B-7574-2012 FU National Cancer Institute, Center for Cancer Research, and of the National Institute of Allergy and Infectious Diseases, NIH; NIH [R01 AI038339] FX The authors thank Ehydel Castro for expert mouse technical assistance, Barbara Taylor for help with flow cytometry, Takeshi Egawa for insight on the control of Cd4 expression, Renaud Lesourne, Paul Love and Bill Paul for helpful discussions and reagents, and B.J. Fowlkes, Paul Love and Al Singer for reading the manuscript. This work was supported in part by the Intramural Research Programs of the National Cancer Institute, Center for Cancer Research, and of the National Institute of Allergy and Infectious Diseases, NIH and by NIH Grant R01 AI038339. NR 29 TC 31 Z9 32 U1 0 U2 0 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 SEP PY 2010 VL 40 IS 9 BP 2385 EP 2390 DI 10.1002/eji.201040534 PG 6 WC Immunology SC Immunology GA 656DD UT WOS:000282305400007 PM 20706986 ER PT J AU Benninger, D Berman, B Houdayer, E Pal, N Luckenbaugh, D Schneider, L Miranda, S Hallett, M AF Benninger, D. Berman, B. Houdayer, E. Pal, N. Luckenbaugh, D. Schneider, L. Miranda, S. Hallett, M. TI Intermittent theta-burst transcranial magnetic stimulation for the treatment of Parkinson's disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Benninger, D.; Berman, B.; Houdayer, E.; Pal, N.; Luckenbaugh, D.; Schneider, L.; Miranda, S.; Hallett, M.] NINDS, NIH, Bethesda, MD 20892 USA. RI Benninger, David/A-8157-2015 OI Benninger, David/0000-0002-1049-9533 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 22 EP 22 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331100045 ER PT J AU Giacone, S Moglia, C Calvo, A Cammarosano, S Ilardi, A Gallo, S Canosa, A Montuschi, A Restagno, G Ossola, I Brunetti, M Cistaro, A Ticca, A Borghero, G Traynor, BJ Chio, A AF Giacone, S. Moglia, C. Calvo, A. Cammarosano, S. Ilardi, A. Gallo, S. Canosa, A. Montuschi, A. Restagno, G. Ossola, I. Brunetti, M. Cistaro, A. Ticca, A. Borghero, G. Traynor, B. J. Chio, A. TI TARDBP A382T mutation and frontotemporal dementia: description of three ALS families SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Giacone, S.; Moglia, C.; Calvo, A.; Cammarosano, S.; Ilardi, A.; Gallo, S.; Canosa, A.; Montuschi, A.; Chio, A.] Univ Turin, Dept Neurosci, I-10124 Turin, Italy. [Restagno, G.; Ossola, I.; Brunetti, M.] ASO OIRM St Anna, Mol Genet Lab, Turin, Italy. [Cistaro, A.] IRMET, Positron Emiss Tomog Ctr, Turin, Italy. [Ticca, A.] AO San Francesco, Nuoro, Italy. [Borghero, G.] Univ Cagliari, Cagliari, Italy. [Traynor, B. J.] NIA, Neuromuscular Dis Res Grp, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 290 EP 290 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331100546 ER PT J AU Sailer, A Paisa-Puiz, C Li, A Paudel, R Scholz, SW Ahmed, Z Revesz, T Mathias, CJ Wood, NW Holton, J Hardy, J Houlden, H AF Sailer, A. Paisa-Puiz, C. Li, A. Paudel, R. Scholz, S. W. Ahmed, Z. Revesz, T. Mathias, C. J. Wood, N. W. Holton, J. Hardy, J. Houlden, H. TI Genetic analysis of the MAPT locus in multiple system atrophy SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 14th Congress of European-Federation-of-Neurological-Societies CY SEP, 2010 CL Geneva, SWITZERLAND SP European Federat Neurol Soc C1 [Sailer, A.; Paisa-Puiz, C.; Li, A.; Paudel, R.; Ahmed, Z.; Revesz, T.; Mathias, C. J.; Wood, N. W.; Holton, J.; Hardy, J.; Houlden, H.] Inst Neurol, London WC1N 3BG, England. [Scholz, S. W.] NIH, Bethesda, MD 20892 USA. RI Holton, Janice/F-6831-2011; Hardy, John/C-2451-2009; Houlden, Henry/C-1532-2008 OI Holton, Janice/0000-0002-3882-5249; Houlden, Henry/0000-0002-2866-7777 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD SEP PY 2010 VL 17 SU 3 SI SI BP 598 EP 598 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 800BD UT WOS:000293331101472 ER PT J AU Hu, HL Lu, WN Zhang, M Zhang, XL Argall, AJ Patel, S Lee, GE Kim, YC Jacobson, KA Laties, AM Mitchell, CH AF Hu, Huiling Lu, Wennan Zhang, Mei Zhang, Xiulan Argall, Arthur J. Patel, Shaun Lee, Ga Eun Kim, Yong-Chul Jacobson, Kenneth A. Laties, Alan M. Mitchell, Claire H. TI Stimulation of the P2X(7) receptor kills rat retinal ganglion cells in vivo SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE P2X receptor; A(3) adenosine receptor; purinergic signaling; retinal ganglion cells; neuroprotection; in vivo models ID A(3) ADENOSINE RECEPTOR; MULLER GLIAL-CELLS; BRILLIANT-BLUE-G; INTRAOCULAR-PRESSURE; PHARMACOLOGICAL CHARACTERIZATION; ATP; NUCLEOSIDES; INVOLVEMENT; INHIBITION; ASTROCYTES AB The P2X(7) receptor is associated with the death of many cell types, and growing evidence supports its presence on neurons. Activation of the P2X(7) receptor on isolated retinal ganglion cells increases intracellular calcium levels and can kill the cells. Within the intact eye, however, glia and other cell types surrounding the ganglion cells may provide protection and attenuate the effects of receptor stimulation. This investigation thus asks whether stimulation of the P2X(7) receptor can actually kill retinal ganglion cells in vivo. Drugs were injected intravitreally into the superior/nasal region of Long Evans rats. Cell survival was determined by counting the number of remaining ganglion cells labeled with amino-stilbamidine. The P2X(7) receptor agonist BzATP reduced ganglion cell survival as compared to eyes injected with saline solution. Ganglion cell death was inhibited by co-injection of the P2X(7) antagonists Brilliant Blue G and MRS 2540. The loss of ganglion cells following activation of the P2X(7) receptor was also prevented by the adenosine A(3) adenosine receptor agonist MRS 3558. In conclusion, stimulation of the P2X(7) receptor can kill retinal ganglion cells in vivo. The neuroprotective effects of A(3) receptor activation identified in isolated ganglion cells are also apparent in vivo. This implies that the balance between extracellular ATP and its protective metabolite adenosine can influence ganglion cell survival in the living eye. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lu, Wennan; Argall, Arthur J.; Patel, Shaun; Mitchell, Claire H.] Univ Penn, Dept Physiol, Sch Med, Philadelphia, PA 19104 USA. [Hu, Huiling; Zhang, Mei; Laties, Alan M.] Univ Penn, Dept Ophthalmol, Sch Med, Philadelphia, PA 19104 USA. [Lu, Wennan; Argall, Arthur J.; Mitchell, Claire H.] Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, Philadelphia, PA 19104 USA. [Hu, Huiling; Zhang, Xiulan] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510060, Guangdong, Peoples R China. [Lee, Ga Eun; Kim, Yong-Chul] Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. [Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mitchell, CH (reprint author), Univ Penn, Dept Physiol, Sch Med, 3700 Hamilton Walk, Philadelphia, PA 19104 USA. EM chm@mail.med.upenn.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIH [EY015537, EY013434]; Vision Research Core Grant [EY001583]; Research to Prevent Blindness; Paul and Evanina Bell Mackall Foundation; Jody Sack Fund; National Natural Science Foundation of China [30872831]; NIDDK, NIH, Bethesda; Ministry of Education, Science and Technology [2009-0074289] FX This work is supported by grants from the NIH EY015537 and EY013434 (CHM), Vision Research Core Grant EY001583 (CHM and AML). Research to Prevent Blindness (AML), the Paul and Evanina Bell Mackall Foundation Trust (AML), the Jody Sack Fund (HH, MZ and XZ), the National Natural Science Foundation of China 30872831(XZ), by support from the Intramural Research Program of NIDDK, NIH, Bethesda, MD (KAJ), and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (YCK : grant number 2009-0074289). The authors would like to thank Mary Leonard and Gabriel Baltazar for help with the illustrations. NR 36 TC 50 Z9 54 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD SEP PY 2010 VL 91 IS 3 BP 425 EP 432 DI 10.1016/j.exer.2010.06.017 PG 8 WC Ophthalmology SC Ophthalmology GA 645XY UT WOS:000281500700013 PM 20599962 ER PT J AU Cokic, V Bhattacharya, B Beleslin-Cokic, B Noguchi, C Puri, R Schechter, A AF Cokic, V. Bhattacharya, B. Beleslin-Cokic, B. Noguchi, C. Puri, R. Schechter, A. TI GLOBIN GENES VERSUS COMMON GENES EXPRESSION PROFILING IN ERYTHROID CELLS DURING ONTOGENY SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Cokic, V.] Inst Med Res, Belgrade, Serbia. [Bhattacharya, B.; Puri, R.] US FDA, Ctr Biol Eval & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. [Beleslin-Cokic, B.] Inst Endocrinol Diabet & Dis Metab, Belgrade, Serbia. [Noguchi, C.; Schechter, A.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 060 BP S29 EP S29 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900059 ER PT J AU Slape, CI Saw, J Aplan, PD Jane, SM Curtis, DJ AF Slape, C. I. Saw, J. Aplan, P. D. Jane, S. M. Curtis, D. J. TI OVEREXPRESSION OF BCL2 RESCUES APOPTOSIS, CYTOPENIAS AND LEUKEMIC TRANSFORMATION IN MURINE MYELODYSPLASTIC SYNDROME SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 39th Annual Scientific Meeting of the ISEH - Society-for-Hematology-and-Stem-Cells CY SEP 15-18, 2010 CL Melbourne, AUSTRALIA SP Soc Hematol Stem Cell C1 [Slape, C. I.; Saw, J.; Jane, S. M.; Curtis, D. J.] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Aplan, P. D.] NCI, Bethesda, MD 20892 USA. RI Jane, Stephen/D-6659-2011; Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD SEP PY 2010 VL 38 IS 9 SU 1 MA 098 BP S46 EP S47 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 641YM UT WOS:000281168900094 ER PT J AU Airavaara, M Chiocco, MJ Howard, DB Zuchowski, KL Peranen, J Liu, C Fang, SY Hoffer, BJ Wang, Y Harvey, BK AF Airavaara, Mikko Chiocco, Matt J. Howard, Doug B. Zuchowski, Katie L. Peranen, Johan Liu, Chao Fang, Shengyun Hoffer, Barry J. Wang, Yun Harvey, Brandon K. TI Widespread cortical expression of MANF by AAV serotype 7: Localization and protection against ischemic brain injury SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Gene therapy; Stroke; AAV; MANF; Neurotrophic factor; Mesencephalic astrocyte-derived neurotrophic factor; ARMET; CDNF ID ADENOASSOCIATED VIRUS VECTORS; UNFOLDED PROTEIN RESPONSE; AGE-RELATED OBESITY; NEUROTROPHIC FACTOR; CELL-LINE; ENDOPLASMIC-RETICULUM; CEREBRAL-ISCHEMIA; IN-VIVO; RAT MODEL; STROKE AB Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secreted protein which reduces endoplasmic reticulum (ER) stress and has neurotrophic effects on dopaminergic neurons. Intracortical delivery of recombinant MANF protein protects tissue from ischemic brain injury in vivo. In this study, we examined the protective effect of adeno-associated virus serotype 7 encoding MANF in a rodent model of stroke. An AAV vector containing human MANF cDNA (AAV-MANF) was constructed and verified for expression of MANF protein. AAV-MANF or an AAV control vector was administered into three sites in the cerebral cortex of adult rats. One week after the vector injections, the right middle cerebral artery (MCA) was ligated for 60 min. Behavioral monitoring was conducted using body asymmetry analysis, neurological testing, and locomotor activity. Standard immunohistochemical and western blotting procedures were conducted to study MANF expression. Our data showed that AAV-induced MANF expression is redistributed in neurons and glia in cerebral cortex after ischemia. Pretreatment with AAV-MANF reduced the volume of cerebral infarction and facilitated behavioral recovery in stroke rats. In conclusion, our data suggest that intracortical delivery of AAV-MANF increases MANF protein production and reduces ischemic brain injury. Ischemia also caused redistribution of MV-mediated MANF protein suggesting an injury-induced release. Published by Elsevier Inc. C1 [Airavaara, Mikko; Chiocco, Matt J.; Howard, Doug B.; Zuchowski, Katie L.; Hoffer, Barry J.; Wang, Yun; Harvey, Brandon K.] NIDA, Neural Protect & Regenerat Sect, IRP, NIH, Baltimore, MD 21201 USA. [Peranen, Johan] Univ Helsinki, Viikki Bioctr, Inst Biotechnol, FIN-00014 Helsinki, Finland. [Liu, Chao; Fang, Shengyun] Univ Maryland, Ctr Biomed Engn & Technol, Baltimore, MD 21201 USA. RP Harvey, BK (reprint author), NIDA, Neural Protect & Regenerat Sect, IRP, NIH, Baltimore, MD 21201 USA. EM bharvey@intra.nida.nih.gov RI Fang, Shengyun/H-3802-2011; OI Airavaara, Mikko/0000-0002-2026-1609 FU NIDA; DHHS; NIH FX This research was supported by the intramural research program at NIDA, NIH, and DHHS. The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript. NR 37 TC 22 Z9 22 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2010 VL 225 IS 1 SI SI BP 104 EP 113 DI 10.1016/j.expneurol.2010.05.020 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 643ZD UT WOS:000281339300016 PM 20685313 ER PT J AU Lanuza, MA Besalduch, N Gonzalez, C Santafe, MM Garcia, N Tomas, M Nelson, PG Tomas, J AF Lanuza, Maria A. Besalduch, Nuria Gonzalez, Carmen Santafe, Manel M. Garcia, Neus Tomas, Marta Nelson, Phillip G. Tomas, Josep TI Decreased phosphorylation of delta and epsilon subunits of the acetylcholine receptor coincides with delayed postsynaptic maturation in PKC theta deficient mouse SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Synapse elimination; Synaptogenesis; PKC theta; Neuromuscular junction; nAChR clustering; KO mouse ID PROTEIN-KINASE-C; NERVE MUSCLE JUNCTIONS; NEUROMUSCULAR-JUNCTION; SYNAPSE ELIMINATION; SKELETAL-MUSCLE; IN-VITRO; POSTNATAL MATURATION; NEURAL INFLUENCE; PHORBOL ESTER; NEONATAL-RAT AB Protein kinase C (PKC) activity is involved in the nicotinic acetylcholine receptor (nAChR) redistribution at the neuromuscular junction in vivo during postnatal maturation. Here we studied, in PKC theta (PKC theta) deficient mice (KO), how the theta isoform of PKC is involved in the nAChR cluster maturation that is accompanied by the developmental activity-dependent neuromuscular synapse elimination process. We found that axonal elimination and dispersion of nAChR from the postsynaptic plaques and its redistribution to form the mature postsynaptic apparatus were delayed but not totally suppressed in PKC theta deficient mice. Moreover, the delay in the maturation of the morphology of the nAChR clusters during the early postnatal synapse elimination period in the PKC theta deficient mice coincides with a reduction in the PKC theta-mediated phosphorylation on the delta subunit of the nAChR. In addition, we show evidence for PKC theta regulation of PKA in normally phosphorylating the epsilon subunit of nAChR. We have also found that the theta isoform of PKC is located on the postsynaptic component of the neuromuscular junction but is also expressed by motoneurons in the spinal cord and in the motor nerve terminals. The results allow us to hypothesize that a spatially specific and opposing action of PKC theta and PICA may result in activity-dependent alterations to synaptic connectivity at both the nerve inputs and the postsynaptic nAChR clusters. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lanuza, Maria A.; Besalduch, Nuria; Gonzalez, Carmen; Santafe, Manel M.; Garcia, Neus; Tomas, Marta; Tomas, Josep] Univ Rovira & Virgili, Fac Med & Ciencies Salut, UHN, Reus 43201, Spain. [Nelson, Phillip G.] NICHHD, NIH, Bethesda, MD 20892 USA. RP Lanuza, MA (reprint author), Univ Rovira & Virgili, Fac Med & Ciencies Salut, UHN, Carrer St Llorenc 21, Reus 43201, Spain. EM mariaangel.lanuza@urv.cat; josepmaria.tomas@urv.cat OI Santafe, Manel/0000-0002-5462-5108 FU MEC [SAF 2008-02836]; Catalan Government (Generalitat) [2009SGR01248] FX This work was supported by a grant from MEC (SAF 2008-02836) and a grant from the Catalan Government (Generalitat) (2009SGR01248). NR 36 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2010 VL 225 IS 1 SI SI BP 183 EP 195 DI 10.1016/j.expneurol.2010.06.014 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 643ZD UT WOS:000281339300024 PM 20599977 ER PT J AU Kelly, RJ Giaccone, G AF Kelly, Ronan J. Giaccone, Giuseppe TI The role of talactoferrin alfa in the treatment of non-small cell lung cancer SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE dendritic cell; immunotherapy; non small cell lung cancer; talactoferrin alpha ID LACTOFERRIN INHIBITS GROWTH; CYCLIN-DEPENDENT KINASES; BOVINE LACTOFERRIN; ORAL LACTOFERRIN; SOLID TUMORS; MICE; CARCINOMA; RECEPTOR; EPITHELIUM; ARREST AB Importance of the field: Immunotherapeutic approaches to treating NSCLC via either adoptive transfer of immunity or stimulation of the endogenous immune system have shown increasing promise in recent years. Areas covered in this review: Talactoferrin alfa is an oral immunomodulatory agent currently in late-stage clinical trials that acts through dendritic cell recruitment and activation in the gut-associated lymphoid tissue. What the reader will gain: Talactoferrin is a recombinant human lactoferrin that is a member of the transferrin family of iron-binding glycoproteins. Lactoferrins have multiple known biological activities including cancer protection, cellular growth and differentiation and antimicrobial and anti-inflammatory properties. This review discusses the proposed mechanism of action of talactoferrin-alfa and outlines the pre-clinical, Phase I and II data in NSCLC. The ongoing Phase III trials are discussed. Take home message: The current role of Talactoferrin alpha in the treatment of NSCLC is described and we explore potential future roles for this drug in both early stage and advanced stage disease. C1 [Kelly, Ronan J.; Giaccone, Giuseppe] NCI, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 32 TC 9 Z9 10 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 EI 1744-7682 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2010 VL 10 IS 9 BP 1379 EP 1386 DI 10.1517/14712598.2010.512914 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 647JJ UT WOS:000281614500008 PM 20684737 ER PT J AU Hedrick, MN Lonsdorf, AS Hwang, ST Farber, JM AF Hedrick, Michael N. Lonsdorf, Anke S. Hwang, Sam T. Farber, Joshua M. TI CCR6 as a possible therapeutic target in psoriasis SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE autoimmune disease; chemokines; inflammation; psoriasis ID NATURAL-KILLER-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; INTERLEUKIN-12/23 MONOCLONAL-ANTIBODY; INFLAMMATORY PROTEIN 3-ALPHA; CHEMOKINE RECEPTOR CCR6; MEMORY T-CELLS; HUMAN B-CELLS; DENDRITIC CELLS; ATOPIC-DERMATITIS; IN-VIVO AB Importance of the field: Psoriasis is a common, chronic autoimmune disease of the skin. Despite a number of effective treatments, new therapies are needed with enhanced efficacy, safety and convenience. Chemokine receptors are GPCRs that control leukocyte trafficking, and like other GPCRs, are good potential drug targets. The chemokine receptor CCR6 is expressed on the T(H)17 subset of CD4(+) T cells, which produces IL-17A/F, IL-22, TNF-alpha and other cytokines, and which has been implicated in the pathogenesis of psoriasis. CCR6 and its ligand, CCL20/MIP-3 alpha, are highly expressed in psoriatic skin and CCR6 is necessary for the pathology induced in a mouse model of psoriasis-like inflammation. Areas covered in this review: This review summarizes the evidence for the importance of the IL-23/T(H)17 axis, and in particular CCR6 and CCL20 in psoriasis, dating from 2000 to the present, and discusses the possibility of inhibiting CCR6 as a treatment for the disease. What the reader will gain: The review informs the reader of the current thinking on the mechanisms of inflammation in psoriasis and the possible roles for CCR6 (and CCL20) in disease pathogenesis. Take home message: We conclude that CCR6 should be investigated as a potential therapeutic target in psoriasis. C1 [Hedrick, Michael N.; Farber, Joshua M.] NIAID, NIH, Lab Mol Immunol, Inflammat Biol Sect, Bethesda, MD 20892 USA. [Lonsdorf, Anke S.] Univ Heidelberg Hosp, Dept Dermatol, Heidelberg, Germany. [Hwang, Sam T.] Med Coll Wisconsin, Dept Dermatol, Froedtert Clin E, Milwaukee, WI 53226 USA. RP Farber, JM (reprint author), NIAID, NIH, Lab Mol Immunol, Inflammat Biol Sect, Bldg 10,Rm 11N112, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov FU NIH, NIAID; National Institutes of Health; German Research Foundation; NCI FX This work was supported by the Intramural Research Program of the NIH, NIAID and NCI, and an NIH/DFG Research Career Transition Award of the National Institutes of Health and the German Research Foundation to AS Lonsdorf. NR 155 TC 25 Z9 28 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD SEP PY 2010 VL 14 IS 9 BP 911 EP 922 DI 10.1517/14728222.2010.504716 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 647JM UT WOS:000281614800004 PM 20629596 ER PT J AU Vaccari, M Poonam, P Franchini, G AF Vaccari, Monica Poonam, Poonam Franchini, Genoveffa TI Phase III HIV vaccine trial in Thailand: a step toward a protective vaccine for HIV SO EXPERT REVIEW OF VACCINES LA English DT Article DE gp120; HIV; neutralizing antibodies; Phase III; prime-boost; T-cell responses; vaccine trial ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSES; RECOMBINANT CANARYPOX; SIMIAN-IMMUNODEFICIENCY; RHESUS MACAQUES; ALVAC-HIV; IMMUNE-RESPONSES; SERONEGATIVE ADULTS; POXVIRUS VECTORS; DOUBLE-BLIND AB The large human efficacy trail in Thailand, RV144, was concluded in the summer of 2009. This is the first Phase III trial to show limited, but significant, efficacy in preventing HIV acquisition. This trial represents the first sign that a preventive vaccine for HIV may be feasible. The vaccine regimen tested in Thailand consisted of priming with a Canarypox vector carrying three synthetic HIV genes. The priming was followed by booster inoculations with two recombinant envelope proteins from HIV, clade B and E. The need to understand the role in protection from HIV acquisition of the new responses, induced by this vaccine combination, has brought together many researchers with the common goal of improving the development of a safe and effective vaccine for HIV. C1 [Vaccari, Monica; Poonam, Poonam; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccine Sect, NIH, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 77 TC 33 Z9 33 U1 1 U2 3 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 SEP PY 2010 VL 9 IS 9 BP 997 EP 1005 DI 10.1586/ERV.10.104 PG 9 WC Immunology SC Immunology GA 653SO UT WOS:000282117200008 PM 20822342 ER PT J AU Yi, H Xue, L Guo, MX Ma, JA Zeng, Y Wang, W Cai, JY Hu, HM Shu, HB Shi, YB Li, WX AF Yi, Hong Xue, Lu Guo, Ming-Xiong Ma, Jian Zeng, Yan Wang, Wei Cai, Jin-Yang Hu, Hai-Ming Shu, Hong-Bing Shi, Yun-Bo Li, Wen-Xin TI Gene expression atlas for human embryogenesis SO FASEB JOURNAL LA English DT Article DE human embryonic development; gene regulation database; organogenesis; microarrays; maternal genes ID HUMAN OOCYTES; HUMAN EMBRYO; DIFFERENTIATION; TRANSCRIPTOME; FEATURES; BIOLOGY; ZNF268; CELLS AB Human embryogenesis is believed to involve an integrated set of complex yet coordinated development of different organs and tissues mediated by the changes in the spatiotemporal expression of many genes. Here, we report a genome-wide expression analysis during wk 4-9 of human embryogenesis, a critical period when most organs develop. About half of all human genes are expressed, and 18.6% of the expressed genes were significantly regulated during this important period. We further identified >5000 regulated genes, most of which previously were not known to be associated with animal development. Our study fills an important gap in mammalian developmental studies by identifying functional pathways involved in this critical but previously not studied period. Our study also revealed that the genes involved here are distinct from those during early embryogenesis, which include three groups of maternal genes. Furthermore, we discovered that genes in a given developmental process are regulated coordinately. This led us to develop an easily searchable database of this entire collection of gene expression profiles, allowing for the identification new genes important for a particular developmental process/pathway and deducing the potential function of a novel gene. The validity of the predictions from the database was demonstrated with two examples through spatiotemporal analyses of the two novel genes. Such a database should serve as a highly valuable resource for the molecular analysis of human development and pathogenesis.-Yi, H., Xue, L., Guo, M.-X. Ma, J., Zeng, Y., Wang, W., Cai, J.-Y. Hu, H.-M., Shu, H.-B. Shi, Y.-B., Li, W.-X. Gene expression atlas for human embryogenesis. FASEB J. 24, 3341-3350 (2010). www.fasebj.org C1 [Li, Wen-Xin] Wuhan Univ, State Key Lab Virol, Coll Life Sci, Wuhan 430072, Peoples R China. [Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Li, WX (reprint author), Wuhan Univ, State Key Lab Virol, Coll Life Sci, Wuhan 430072, Peoples R China. EM shi@helix.nih.gov; liwxlab@whu.edu.cn FU National High Technology Research and Development Program of China (863 Program) [2006AA02A306]; National Natural Science Foundation of China [30871245]; Program of Introducing Talents of Discipline to Universities [B06018]; National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by National High Technology Research and Development Program of China (863 Program) grant 2006AA02A306, National Natural Science Foundation of China grant 30871245, Program of Introducing Talents of Discipline to Universities grant B06018. Y.-B. S. was supported by the National Institute of Child Health and Human Development Intramural Research Program, National Institutes of Health. NR 33 TC 17 Z9 17 U1 4 U2 10 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 SEP PY 2010 VL 24 IS 9 BP 3341 EP 3350 DI 10.1096/fj.10-158782 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 645IK UT WOS:000281446400022 PM 20430792 ER PT J AU Goetzl, EJ Huang, MC Kon, J Patel, K Schwartz, JB Fast, K Ferrucci, L Madara, K Taub, DD Longo, DL AF Goetzl, Edward J. Huang, Mei-Chuan Kon, Junko Patel, Kalpesh Schwartz, Janice B. Fast, Katharine Ferrucci, Luigi Madara, Karen Taub, Dennis D. Longo, Dan L. TI Gender specificity of altered human immune cytokine profiles in aging SO FASEB JOURNAL LA English DT Article DE T cells; monocytes; immunodeficiency; autoimmunity ID REGULATORY T-CELLS; INTERFERON-GAMMA-PRODUCTION; IFN-GAMMA; CLONAL EXPANSIONS; ELDERLY-PEOPLE; OLD SUBJECTS; IN-VITRO; AGE; LYMPHOCYTES; ACTIVATION AB Cytokine generation by T cells and monocytes was determined for 50 subjects aged 65 yr or older and concurrently studied young subjects individually matched to each old subject for sex, race, and national origin. Highly significant differences between cytokine levels of old and young subjects all were gender specific. For T cells stimulated with anti-CD3 plus anti-CD28 antibodies, mean ratios of IFN-gamma generation for healthy old to young subjects were 0.22 for men (P<0.001; n=15) and 3.35 for women (P<0.001; n=13), and those of IL-17 were 0.30 for men (P<0.001) and no difference for women. CD8 T cells were the source of high IFN-gamma in healthy old women. For old men with an inflammatory or immune disease (n=10), mean old to young ratios of T-cell-generated IFN-gamma and IL-17 increased with disease severity up to 5.78 and 2.97 (both P<0.01), respectively, without changes for old women with similar diseases (n=12). For differentiated LPS-stimulated monocytes, old to young ratios of TNF-alpha and IL-6 generation were high only in women with immune or inflammatory disease (2.38, P<0.05 and 1.62, P<0.01, respectively), whereas ratios of IFN-gamma-evoked IP-10 chemokine were low in all groups. Alterations in immune cytokine profiles with aging show significant gender specificity.-Goetzl, E. J., Huang, M.-C., Kon, J., Patel, K., Schwartz, J. B., Fast, K., Ferrucci, L., Madara, K., Taub, D. D., Longo, D. L. Gender specificity of altered human immune cytokine profiles in aging. FASEB J. 24, 3580-3589 (2010). www.fasebj.org C1 [Goetzl, Edward J.; Huang, Mei-Chuan; Kon, Junko; Schwartz, Janice B.; Fast, Katharine] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Goetzl, Edward J.; Huang, Mei-Chuan; Kon, Junko; Schwartz, Janice B.; Fast, Katharine] Univ Calif San Francisco, Dept Microbiol Immunol, San Francisco, CA 94143 USA. [Goetzl, Edward J.; Patel, Kalpesh; Ferrucci, Luigi; Madara, Karen; Taub, Dennis D.; Longo, Dan L.] NIA, NIH, Baltimore, MD 21224 USA. RP Goetzl, EJ (reprint author), Univ Calif San Francisco, Dept Med, Rm UB8B,UC Box 0711,533 Parnassus & 4th Ave, San Francisco, CA 94143 USA. EM edward.goetzl@ucsf.edu RI Patel, Kalpesh/G-6685-2012 OI Patel, Kalpesh/0000-0002-2952-6773 FU National Institute on Aging; Kenneth Rainin Foundation; National Institutes of Health [HL31809] FX This research was supported by the Intramural Research Program of the National Institute on Aging, a grant from the Kenneth Rainin Foundation, and National Institutes of Health RO-1 grant HL31809. E.J.G., M. C. H., J.B.S., D. D. T., and D. L. L. designed research; E.J.G., J.B.S., K. F., L. F., and K. M. evaluated and selected subjects; E.J.G., M. C. H., J.K., and K. P. performed laboratory research; E.J.G., M. C. H., J.B.S., and D. L. L. analyzed data and wrote the paper. The authors are grateful to Judith H. Goetzl for preparation of the figures and tables. NR 37 TC 39 Z9 39 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 SEP PY 2010 VL 24 IS 9 BP 3580 EP 3589 DI 10.1096/fj.10-160911 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 645IK UT WOS:000281446400045 PM 20453111 ER PT J AU Wu, YL Brosh, RM AF Wu, Yuliang Brosh, Robert M., Jr. TI G-quadruplex nucleic acids and human disease SO FEBS JOURNAL LA English DT Review DE BLM; Bloom's syndrome; FANCJ; Fanconi anemia; genomic instability; G-quadruplex; helicase; telomere; Werner syndrome; WRN ID FRAGILE-X-SYNDROME; REPLICATION PROTEIN-A; FAMILIAL BREAST-CANCER; TELOMERIC G-QUADRUPLEXES; WERNER-SYNDROME HELICASE; SYNDROME DNA HELICASE; BONE-MARROW FAILURE; HUMAN KRAS PROMOTER; CROSS-LINK REPAIR; IN-VITRO AB Alternate DNA structures that deviate from B-form double-stranded DNA such as G-quadruplex (G4) DNA can be formed by sequences that are widely distributed throughout the human genome. G-quadruplex secondary structures, formed by the stacking of planar quartets composed of four guanines that interact by Hoogsteen hydrogen bonding, can affect cellular DNA replication and transcription, and influence genomic stability. The unique metabolism of G-rich chromosomal regions that potentially form quadruplexes may influence a number of biological processes including immunoglobulin gene rearrangements, promoter activation and telomere maintenance. A number of human diseases are characterized by telomere defects, and it is proposed that G-quadruplex structures which form at telomere ends play an important role in telomere stability. Evidence from cellular studies and model organisms suggests that diseases with known defects in G4 DNA helicases are likely to be perturbed in telomere maintenance and cellular DNA replication. In this minireview, we discuss the connections of G-quadruplex nucleic acids to human genetic diseases and cancer based on the recent literature. C1 [Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, NIH Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov FU NIH, National Institute on Aging; Fanconi Anemia Research Fund FX This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging and the Fanconi Anemia Research Fund (RMB). NR 173 TC 118 Z9 122 U1 9 U2 84 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2010 VL 277 IS 17 BP 3470 EP 3488 DI 10.1111/j.1742-4658.2010.07760.x PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 639TB UT WOS:000280996300004 PM 20670277 ER PT J AU Pivovarova, NB Andrews, SB AF Pivovarova, Natalia B. Andrews, S. Brian TI Calcium-dependent mitochondrial function and dysfunction in neurons SO FEBS JOURNAL LA English DT Review DE calcium buffering; calcium deregulation; cell death; electron microscopy; electron probe microanalysis; energy filtering electron microscopy; excitotoxicity; hippocampal neurons; mitochondria; permeability transition ID CEREBELLAR GRANULE CELLS; ACUTE GLUTAMATE EXCITOTOXICITY; PERMEABILITY TRANSITION PORE; SPARE RESPIRATORY CAPACITY; NMDA RECEPTOR ACTIVATION; RAT HIPPOCAMPAL-NEURONS; ISCHEMIC BRAIN-INJURY; CYTOCHROME-C RELEASE; OXIDATIVE STRESS; CNS MITOCHONDRIA AB Calcium is an extraordinarily versatile signaling ion, encoding cellular responses to a wide variety of external stimuli. In neurons, mitochondria can accumulate enormous amounts of calcium, with the consequence that mitochondrial calcium uptake, sequestration and release play pivotal roles in orchestrating calcium-dependent responses as diverse as gene transcription and cell death. In this review, we consider the basic chemistry of calcium as a 'sticky' cation, which leads to extremely high bound/free ratios, and discuss areas of current interest or controversy. Topics addressed include methodologies for measuring local intracellular calcium, mitochondrial calcium buffering and loading capacity, mitochondrially directed spatial calcium gradients, and the role of calcium overload-dependent mitochondrial dysfunction in glutamate-evoked excitotoxic injury and neurodegeneration. Finally, we consider the relationship between delayed calcium de-regulation, the mitochondrial permeability transition and the generation of reactive oxygen species, and propose a unified view of the 'source specificity' and 'calcium overload' models of N-methyl-d-aspartate (NMDA) receptor-dependent excitotoxicity. Non-NMDA receptor mechanisms of excitotoxicity are discussed briefly. C1 [Pivovarova, Natalia B.; Andrews, S. Brian] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Andrews, SB (reprint author), NINDS, Neurobiol Lab, NIH, 49-3A62,49 Convent Dr, Bethesda, MD 20892 USA. EM sba@helix.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX The authors are indebted to the staff of the National Institute of Neurological Disorders and Stroke Electron Microscopy facility (Director Dr Jung-Hwa Tao-Cheng) for excellent technical assistance. This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 129 TC 86 Z9 92 U1 2 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD SEP PY 2010 VL 277 IS 18 BP 3622 EP 3636 DI 10.1111/j.1742-4658.2010.07754.x PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 646PX UT WOS:000281555600002 PM 20659161 ER PT J AU Beisel, CL Storz, G AF Beisel, Chase L. Storz, Gisela TI Base pairing small RNAs and their roles in global regulatory networks SO FEMS MICROBIOLOGY REVIEWS LA English DT Review DE sRNAs; regulatory circuits; gene regulation; Hfq; network motifs ID BACTERIAL SMALL RNA; SM-LIKE PROTEIN; ESCHERICHIA-COLI; GENE-EXPRESSION; MESSENGER-RNA; NEGATIVE FEEDBACK; VIBRIO-HARVEYI; NONCODING RNA; SOLUBLE-RNA; TRANSCRIPTIONAL REGULATION AB Bacteria use a range of RNA regulators collectively termed small RNAs (sRNAs) to help respond to changes in the environment. Many sRNAs regulate their target mRNAs through limited base-pairing interactions. Ongoing characterization of base-pairing sRNAs in bacteria has started to reveal how these sRNAs participate in global regulatory networks. These networks can be broken down into smaller regulatory circuits that have characteristic behaviors and functions. In this review, we describe the specific regulatory circuits that incorporate base-pairing sRNAs and the importance of each circuit in global regulation. Because most of these circuits were originally identified as network motifs in transcriptional networks, we also discuss why sRNAs may be used over protein transcription factors to help transduce environmental signals. C1 [Beisel, Chase L.; Storz, Gisela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. RP Storz, G (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Bethesda, MD 20892 USA. EM storz@helix.nih.gov RI Beisel, Chase/D-4823-2015; OI Beisel, Chase/0000-0003-0650-9943; Storz, Gisela/0000-0001-6698-1241 FU NICHD FX We thank S. Gottesman, M. Goulian, B. Janson, M. Thomason, O. Venturelli and L. Waters for their comments on this review. C.L.B. is a Gordon and Betty Moore Foundation Fellow of the Life Sciences Research Foundation. Work carried out in the laboratory of G.S. is supported by the intramural program of NICHD. NR 83 TC 133 Z9 137 U1 1 U2 26 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0168-6445 J9 FEMS MICROBIOL REV JI Fems Microbiol. Rev. PD SEP PY 2010 VL 34 IS 5 BP 866 EP 882 DI 10.1111/j.1574-6976.2010.00241.x PG 17 WC Microbiology SC Microbiology GA 635CP UT WOS:000280633500013 PM 20662934 ER PT J AU Choi, YH Ngamskulrungroj, P Varma, A Sionov, E Hwang, SM Carriconde, F Meyer, W Litvintseva, AP Lee, WG Shin, JH Kim, EC Lee, KW Choi, TY Lee, YS Kwon-Chung, KJ AF Choi, Young Hwa Ngamskulrungroj, Popchai Varma, Ashok Sionov, Edward Hwang, Soo Myung Carriconde, Fabian Meyer, Wieland Litvintseva, Anastasia P. Lee, Wee Gyo Shin, Jong Hee Kim, Eui-Chong Lee, Kyung Won Choi, Tae Yeal Lee, Yeong Seon Kwon-Chung, Kyung J. TI Prevalence of the VNIc genotype of Cryptococcus neoformans in non-HIV-associated cryptococcosis in the Republic of Korea SO FEMS YEAST RESEARCH LA English DT Article DE epidemiology; cryptococcosis; Cryptococcus neoformans; Cryptococcus gattii; molecular type; MLST ID GRUBII SEROTYPE-A; VANCOUVER-ISLAND; VAR. GRUBII; GENETIC DIVERSITY; BRITISH-COLUMBIA; SEXUAL CYCLE; GATTII; OUTBREAK; CANADA; CHINA AB PCR fingerprinting and multilocus sequence typing were applied to determine the major molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex in the Republic of Korea. Of the 78 strains isolated from patients diagnosed with cryptococcosis between 1990 and 2008, 96% were C. neoformans serotype A, mating type MAT alpha and molecular type VNI. The remaining 4% were C. gattii, serotype B, mating type MAT alpha and either molecular type VGIIb or VGIII. Of the 62 strains with known HIV status, only 14 (22.6%) were isolated from HIV-positive patients and belonged to molecular type VNI. Remarkably, 93% of the C. neoformans isolates had identical PCR fingerprint profiles with the VNIc genotype that has been identified recently as the major genotype among C. neoformans strains in China. Most strains (81.8%) of the VNIc genotype were associated with non-HIV patients compared with strains of the non-VNIc genotype (20%) (P=0.009). Unlike the Chinese strains, a majority (60%) of the non-HIV patients infected with strains of the VNIc genotype in the Republic of Korea had serious underlying conditions, with cancer and liver disease being the most common. This study affirms VNIc to be the most prevalent genotype of C. neoformans isolated from non-HIV patients with cryptococcosis. C1 [Choi, Young Hwa; Ngamskulrungroj, Popchai; Varma, Ashok; Sionov, Edward; Kwon-Chung, Kyung J.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Hwang, Soo Myung] Catholic Univ Pusan, Dept Clin Lab Sci, Pusan, South Korea. [Carriconde, Fabian; Meyer, Wieland] Univ Sydney, Sydney Med Sch Western, Westmead Millennium Inst,Westmead Hosp, Mol Mycol Res Lab,Ctr Infect Dis & Microbiol, Sydney, NSW 2006, Australia. [Litvintseva, Anastasia P.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Lee, Wee Gyo] Ajou Univ, Sch Med, Dept Lab Med, Suwon 441749, South Korea. [Shin, Jong Hee] Chonnam Natl Univ, Coll Med, Dept Lab Med, Kwangju, South Korea. [Kim, Eui-Chong] Seoul Natl Univ, Dept Lab Med, Seoul, South Korea. [Lee, Kyung Won] Yonsei Univ, Dept Lab Med, Res Inst Bacterial Resistance, Seoul 120749, South Korea. [Choi, Tae Yeal] Hanyang Univ Hosp, Dept Lab Med, Seoul, South Korea. [Lee, Yeong Seon] Natl Inst Hlth, Ctr Infect Dis, Seoul, South Korea. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov RI Kim, Eu Chong/J-5424-2012; Meyer, Wieland/G-1204-2015 OI Meyer, Wieland/0000-0001-9933-8340 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health (K.J.K.-C.). NR 37 TC 41 Z9 41 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1567-1356 J9 FEMS YEAST RES JI FEMS Yeast Res. PD SEP PY 2010 VL 10 IS 6 BP 769 EP 778 DI 10.1111/j.1567-1364.2010.00648.x PG 10 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA 639TM UT WOS:000280997400013 PM 20561059 ER PT J AU Alford, CE Chen, GL Armstrong, AY AF Alford, Connie E. Chen, Grace L. Armstrong, Alicia Y. TI 2009 H1N1 influenza prevention and treatment: counseling infertility patients SO FERTILITY AND STERILITY LA English DT Editorial Material DE H1N1; H1N1 influenza virus; H1N1 influenza vaccine; H1N1 influenza treatment; pregnancy; infertility; preconception counseling ID ANTIBODY; IMMUNIZATION; INFANTS; PROTECTION; PREGNANCY; VACCINE AB It is known that pregnant women are at high risk for complications from the 2009 H1N1 influenza virus. Reproductive endocrinologists often have the opportunity to evaluate patients before conception and are able to counsel them before they become part of this high-risk obstetrics group. The 2009 H1N1 vaccine data and the current recommendations by the Centers for Disease Control and Prevention, American College of Obstetrics and Gynecology, and American Society of Reproductive Medicine are discussed. There is universal agreement in recommending vaccination for all pregnant women and all women attempting conception. Patients should be counseled regarding the vaccine and consider delaying conception until the immunization has been received. (Fertil Steril (R) 2010;94:1178-80. (C) 2010 by American Society for Reproductive Medicine.) C1 [Alford, Connie E.; Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Chen, Grace L.] NIAID, NIH, Bethesda, MD 20892 USA. RP Alford, CE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10 Clin Resource Ctr,Rm 1E-3140,10 Ctr Dr,MS, Bethesda, MD 20892 USA. EM alfordco@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX Supported, in part, by the Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 BP 1178 EP 1180 DI 10.1016/j.fertnstert.2010.04.056 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600002 PM 20579645 ER PT J AU Grossman, LC Michalakis, KG Browne, H Payson, MD Segars, JH AF Grossman, Lisa C. Michalakis, Konstantinos G. Browne, Hyacinth Payson, Mark D. Segars, James H. TI The pathophysiology of ovarian hyperstimulation syndrome: an unrecognized compartment syndrome SO FERTILITY AND STERILITY LA English DT Article DE Ovarian hyperstimulation syndrome (OHSS); abdominal compartment syndrome (ACS); intraabdominal pressure (IAP); intraabdominal hypertension (IAH); paracentesis ID ENDOTHELIAL GROWTH-FACTOR; IN-VITRO FERTILIZATION; STIMULATING-HORMONE RECEPTOR; JUGULAR-VEIN THROMBOSIS; MASSIVE VULVAR EDEMA; OF-THE-LITERATURE; ABDOMINAL COMPARTMENT; INTRAABDOMINAL HYPERTENSION; FACTOR VEGF; PARACENTESIS AB Objective: To compare and contrast the pathophysiology of ovarian hyperstimualtion syndrome (OHSS) with known syndromes of increased intraabdominal pressure (IAP), and to explore the relationship of increased IAP with symptom severity in OHSS. Design: Literature review. Main Outcome Measure(s): Correlation of OHSS symptoms with IAP; effects of paracentesis on IAP in patients with OHSS. Setting: Academic Research Institution. Intervention(s): None. Result(s): OHSS involves a rapid accumulation of volume (from 1.5-17 liters) in the peritoneal cavity that can lead to organ dysfunction, including respiratory impairment and oliguria. In published reports of 20 moderate-to-severe OHSS patients in whom IAP was measured, IAP was found to be elevated to a pathologic range. The increased IAP indicates that OHSS may be considered a compartment syndrome and meets criteria for abdominal compartment syndrome in advanced cases. For this reason, management of OHSS should include reduction of pressure by paracentesis to avoid morbidity and syndrome progression. In addition, measurement of IAP may help to classify the stage of OHSS. Conclusion(s): IAP was found to be elevated in the few cases of OHSS in which it was measured, substantiating the conclusion that OHSS may be considered a compartment syndrome. An understanding of the pathophysiology of increased intrabdominal pressure is useful in the management of OHSS. (Fertil Steril (R) 2010;94:1392-8. (C) 2010 by American Society for Reproductive Medicine.) C1 [Segars, James H.] NICHHD, Reprod Biol & Med Branch, NIH, CRC, Bethesda, MD 20892 USA. [Grossman, Lisa C.] Georgetown Univ, Sch Med, Washington, DC USA. [Payson, Mark D.] Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Segars, JH (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, CRC, 10 Ctr Dr,Bldg 10,1E-3140, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Reproductive Biology and Medicine Branch, NICHD, NIH FX Supported, in part, by the Intramural Research Program of the Reproductive Biology and Medicine Branch, NICHD, NIH. NR 68 TC 18 Z9 19 U1 1 U2 12 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 SEP PY 2010 VL 94 IS 4 BP 1392 EP 1398 DI 10.1016/j.fertnstert.2009.07.1662 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600038 PM 19836016 ER PT J AU Baker, VL Luke, B Brown, MB Alvero, R Frattarelli, JL Usadi, R Grainger, DA Armstrong, AY AF Baker, Valerie L. Luke, Barbara Brown, Morton B. Alvero, Ruben Frattarelli, John L. Usadi, Rebecca Grainger, David A. Armstrong, Alicia Y. TI Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System SO FERTILITY AND STERILITY LA English DT Article DE Assisted reproductive technology; in vitro fertilization; race; ethnicity; ART outcomes; IVF pregnancy rates; pregnancy loss; spontaneous abortion ID RATES; IVF AB Objective: To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004-2006. Design: Retrospective cohort. Setting: Clinic-based data. Patient(s): The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen. Intervention(s): None. Main Outcome Measure(s): Clinical intrauterine gestation (presence of gestational sac) and live birth (>= 22 weeks gestation and >= 300 g birth weight). Result(s): Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters. Conclusion(s): Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies. (Fertil Steril (R) 2010;94:1410-6. (C) 2010 by American Society for Reproductive Medicine.) C1 [Baker, Valerie L.] Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Stanford, CA 94305 USA. [Luke, Barbara] Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA. [Luke, Barbara] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Brown, Morton B.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Alvero, Ruben] Univ Colorado Denver, Dept Obstet & Gynecol, Div Reprod Endocrinol, Aurora, CO USA. [Frattarelli, John L.] Adv Reprod Med & Gynecol Hawaii, Oahu, HI USA. [Usadi, Rebecca] Carolinas Healthcare, Charlotte, NC USA. [Grainger, David A.] Univ Kansas, Ctr Reprod Med, Wichita, KS USA. [Armstrong, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol Branch, NIH, Bethesda, MD USA. RP Baker, VL (reprint author), Stanford Univ, Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, 300 Pasteur Dr,Room HH333, Stanford, CA 94305 USA. EM vlbaker@stanford.edu FU IBSA; Clinical Research/Reproductive Scientist Training (CREST) Program; Society for Assisted Reproductive Technology FX V.L.B. has received research support from IBSA. B.L. has nothing to disclose. M.B.B. has nothing to disclose. R.A. has nothing to disclose.; Supported by the Clinical Research/Reproductive Scientist Training (CREST) Program and the Society for Assisted Reproductive Technology. NR 16 TC 36 Z9 37 U1 0 U2 0 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 SEP PY 2010 VL 94 IS 4 BP 1410 EP 1416 DI 10.1016/j.fertnstert.2009.07.986 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600041 PM 19740463 ER PT J AU Jungheim, ES Ryan, GL Levens, ED Cunningham, AF Macones, GA Carson, KR Beltsos, AN Odem, RR AF Jungheim, Emily S. Ryan, Ginny L. Levens, Eric D. Cunningham, Alexandra F. Macones, George A. Carson, Kenneth R. Beltsos, Angeline N. Odem, Randall R. TI Embryo transfer practices in the United States: a survey of clinics registered with the Society for Assisted Reproductive Technology SO FERTILITY AND STERILITY LA English DT Article DE Embryo transfer practices; ASRM embryo transfer guidelines; single embryo transfer; IVF insurance coverage ID MULTIPLE GESTATION RATES; IN-VITRO FERTILIZATION; PREGNANCY RATES; PRETERM BIRTH; SINGLE; OUTCOMES; COST; IVF AB Objective: To gain a better understanding of factors influencing clinicians' embryo transfer practices. Design: Cross-sectional survey. Setting: Web-based survey conducted in December 2008 of individuals practicing IVF in centers registered with the Society for Assisted Reproductive Technology (SART). Patient(s): None. Intervention(s): None. Main Outcome Measure(s): Prevalence of clinicians reporting following embryo transfer guidelines recommended by the American Society for Reproductive Medicine (ASRM), prevalence among these clinicians to deviate from ASRM guidelines in commonly encountered clinical scenarios, and practice patterns related to single embryo transfer. Result(s): Six percent of respondents reported following their own, independent guidelines for the number of embryos to transfer after IVF. Of the 94% of respondents who reported routinely following ASRM embryo transfer guidelines, 52% would deviate from these guidelines for patient request, 51% for cycles involving the transfer of frozen embryos, and 70% for patients with previously failed IVF cycles. All respondents reported routinely discussing the risks of multiple gestations associated with standard embryo transfer practices, whereas only 34% reported routinely discussing single embryo transfer with all patients. Conclusion(s): Although the majority of clinicians responding to our survey reported following ASRM embryo transfer guidelines, at least half would deviate from these guidelines in a number of different situations. (Fertil Steril (R) 2010;94:1432-6. (C) 2010 by American Society for Reproductive Medicine.) C1 [Jungheim, Emily S.; Cunningham, Alexandra F.; Macones, George A.; Odem, Randall R.] Washington Univ, Dept Obstet & Gynecol, St Louis, MO 63108 USA. [Ryan, Ginny L.] Univ Iowa, Dept Obstet & Gynecol, Iowa City, IA 52242 USA. [Levens, Eric D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. [Carson, Kenneth R.] Washington Univ, Dept Internal Med, St Louis, MO 63108 USA. [Beltsos, Angeline N.] Fertil Ctr Illinois, Chicago, IL USA. RP Jungheim, ES (reprint author), Washington Univ, Dept Obstet & Gynecol, 4444 Forest Pk,Suite 3100,Campus Box 8513, St Louis, MO 63108 USA. EM jungheime@wudosis.wustl.edu FU Program in Reproductive and Adult Endocrinology of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD FX Supported in part by the Program in Reproductive and Adult Endocrinology of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. NR 30 TC 19 Z9 19 U1 0 U2 7 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 SEP PY 2010 VL 94 IS 4 BP 1432 EP 1436 DI 10.1016/j.fertnstert.2009.07.987 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600044 PM 19748089 ER PT J AU Pagidas, K Carson, SA McGovern, PG Barnhart, HX Myers, ER Legro, RS Diamond, MP Carr, BR Schlaff, WD Coutifaris, C Steinkampf, MP Cataldo, NA Nestler, JE Gosman, G Giudice, LC AF Pagidas, Kelly Carson, Sandra A. McGovern, Peter G. Barnhart, Huiman X. Myers, Evan R. Legro, Richard S. Diamond, Michael P. Carr, Bruce R. Schlaff, William D. Coutifaris, Christos Steinkampf, Michael P. Cataldo, Nicholas A. Nestler, John E. Gosman, Gabey Giudice, Linda C. CA Natl Inst Child Hlth Human Dev-Rep TI Intercourse compliance, ovulation, and treatment success in the National Institute of Child Health and Human Development-Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (PPCOS) Trial SO FERTILITY AND STERILITY LA English DT Article DE Intercourse timing; ovulation; intercourse frequency; polycystic ovary syndrome ID MENSTRUAL-CYCLE; CLOMIPHENE; METFORMIN; MOOD AB Objective: To investigate the relationship among intercourse compliance, ovulation, and the occurrence of pregnancy in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMNPPCOS) Trial. Design: Post hoc data analysis of subjects in the Reproductive Medicine Network PPCOS Trial. Setting: Academic medical centers. Intervention(s): None. Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome with a mean age of 28.1 +/- 4 years and mean body mass index of 35.2 +/- 8.7 kg/m(2). Main Outcome Measure(s): Intercourse compliance, ovulation, and pregnancy. Result(s): Data on 2925 cycles were included in the analysis, of which 1340 were ovulatory cycles and 1585 were nonovulatory cycles. The rates of intercourse compliance in the PPCOS trial were similar across all treatment groups at all cycles except cycle 4. Among cycles with known ovulation status, 81.2% of patients were compliant with intercourse instructions. Patients were more intercourse compliant in those cycles during which ovulation occurred (83.2% vs. 79.4%). With regard to ovulatory cycles, there was no difference in the occurrence of pregnancy when comparing intercourse compliant versus intercourse noncompliant cycles. Conclusion(s): Intercourse compliance was not associated with the occurrence of pregnancy in ovulatory cycles in the PPCOS Trial. The occurrence of ovulation still remains a critical predictor for the occurrence of pregnancy. (Fertil Steril (R) 2010;94:1444-6. (C) 2010 by American Society for Reproductive Medicine.) C1 [Pagidas, Kelly; Carson, Sandra A.] Brown Univ, Dept Obstet & Gynecol, Warren Alpert Med Sch, Providence, RI 02905 USA. [McGovern, Peter G.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA. [Barnhart, Huiman X.; Myers, Evan R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Carr, Bruce R.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Schlaff, William D.] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. [Coutifaris, Christos] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Steinkampf, Michael P.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Cataldo, Nicholas A.] Stanford Univ, Palo Alto, CA 94304 USA. [Nestler, John E.] Virginia Commonwealth Univ, Dept Med, Sch Med, Richmond, VA 23284 USA. [Giudice, Linda C.] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. [Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. RP Pagidas, K (reprint author), Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Obstet & Gynecol 101 Dudley St, Providence, RI 02905 USA. EM kpagidas@wihri.org OI Diamond, Michael/0000-0001-6353-4489 FU National Institutes of Health/National Institute of Child Health and Human Development [U10 HD27049, U01 HD38997, U10 HD39005, U10 HD27011, U10 HD33172, U10 HD38988, U10 HD38992, U10 HD38998, U10 HD38999, U54- HD29834]; General Clinical Research Center (GCRC) [MO1RR00056, MO1 RR 10732, C06 RR016499] FX Supported by National Institutes of Health/National Institute of Child Health and Human Development grant nos. U10 HD27049 (to C.C.), U01 HD38997 (to E.R.M.), U10 HD39005 (to M.P.D.), U10 HD27011 to S.A.C.), U10 HD33172 (to M.P.S.), U10 HD38988 (to B.R.C.), U10 HD38992 (to R.S.L.), U10 HD38998 (to W.D.S.), U10 HD38999 (to P.G.M.), and U54- HD29834 to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core; General Clinical Research Center (GCRC) grant no. MO1RR00056 to the University of Pittsburgh; and General Clinical Research Center (GCRC) grant no. MO1 RR 10732 and construction grant no. C06 RR016499 to Pennsylvania State University. NR 5 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 2010 VL 94 IS 4 BP 1444 EP 1446 DI 10.1016/j.fertnstert.2009.05.047 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600046 PM 19540477 ER PT J AU Pagidas, K Carson, SA McGovern, PG Barnhart, HX Myers, ER Legro, RS Diamond, MP Carr, BR Schlaff, WD Coutifaris, C Steinkampf, MP Cataldo, NA Nestler, JE Gosman, G Giudice, LC AF Pagidas, Kelly Carson, Sandra A. McGovern, Peter G. Barnhart, Huiman X. Myers, Evan R. Legro, Richard S. Diamond, Michael P. Carr, Bruce R. Schlaff, William D. Coutifaris, Christos Steinkampf, Michael P. Cataldo, Nicholas A. Nestler, John E. Gosman, Gabey Giudice, Linda C. CA Natl Inst Child Hlth Human Dev-Rep TI Body mass index and intercourse compliance SO FERTILITY AND STERILITY LA English DT Article DE Body mass index; intercourse frequency; ovulation; polycystic ovary syndrome AB Objective: To investigate the relationship between body mass index and intercourse compliance in the Reproductive Medicine Network's Pregnancy in Polycystic Ovary Syndrome (RMN PPCOS) Trial. Design: Post hoc data analysis of subjects in the RMN PPCOS Trial. Setting: Academic medical centers. Intervention(s): None. Patient(s): Six hundred twenty-six infertile women with polycystic ovary syndrome (PCOS) with a mean age of 28.1 +/- 4 years and mean body mass index (BMI) of 35.2 +/- 8.7 kg/m(2). Main Outcome Measure(s): Intercourse compliance and BMI. Result(s): Overall, body mass index was not associated with increased intercourse compliance. However, although patients with BMI >= 35 were less likely to ovulate than patients with BMI <35, they tend to be more compliant with intercourse frequency in ovulatory cycles than patients with BMI <35. Conclusion(s): BMI was not associated with intercourse compliance or noncompliance. An elevated BMI in infertile women with PCOS is not associated with poor intercourse compliance. (Fertil Steril (R) 2010;94:144750. (C) 2010 by American Society for Reproductive Medicine.) C1 [Pagidas, Kelly; Carson, Sandra A.] Brown Univ, Dept Obstet & Gynecol, Warren Alpert Med Sch, Providence, RI 02905 USA. [McGovern, Peter G.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA. [Barnhart, Huiman X.; Myers, Evan R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Myers, Evan R.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. [Carr, Bruce R.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Schlaff, William D.] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. [Coutifaris, Christos] Univ Penn, Sch Med, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Steinkampf, Michael P.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Cataldo, Nicholas A.] Stanford Univ, Palo Alto, CA 94304 USA. [Nestler, John E.] Virginia Commonwealth Univ, Sch Med, Dept Med, Richmond, VA 23284 USA. [Giudice, Linda C.] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. [Giudice, Linda C.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. RP Pagidas, K (reprint author), Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Obstet & Gynecol 101 Dudley St, Providence, RI 02905 USA. EM kpagidas@wihri.org OI Diamond, Michael/0000-0001-6353-4489 FU National Institutes of Health/National Institute of Child Health and Human Development [U10 HD27049, U01 HD38997, U10 HD39005, U10 HD27011, U10 HD33172, U10 HD38988, U10 HD38992, U10 HD38998, U10 HD38999, U54-HD29834]; General Clinical Research Center (GCRC) [MO1RR00056, MO1 RR 10732, C06 RR016499] FX Supported by National Institutes of Health/National Institute of Child Health and Human Development grant nos. U10 HD27049 (to C.C.), U01 HD38997 (to E. R. M.), U10 HD39005 (to M. P. D.), U10 HD27011 (to S.A.C.), U10 HD33172 (to M.P.S.), U10 HD38988 (to B.R.C.), U10 HD38992 (to R.S.L.), U10 HD38998 (to W.D.S.), U10 HD38999 (to P.G.M.), and U54-HD29834 to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core; General Clinical Research Center (GCRC) grant no. MO1RR00056 to the University of Pittsburgh; and General Clinical Research Center (GCRC) grant no. MO1 RR 10732 and construction grant no. C06 RR016499 to Pennsylvania State University. NR 5 TC 5 Z9 5 U1 0 U2 0 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 SEP PY 2010 VL 94 IS 4 BP 1447 EP 1450 DI 10.1016/j.fertnstert.2009.05.048 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 648FA UT WOS:000281674600047 PM 19540480 ER PT J AU Alford, CE Widra, EA Levy, MJ Segars, JH Richter, KS AF Alford, C. E. Widra, E. A. Levy, M. J. Segars, J. H. Richter, K. S. TI DOES OBESITY CAUSE ABNORMAL ENDOMETRIAL DEVELOPMENT? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S190 EP S190 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000649 ER PT J AU Alford, CE DeCherney, AH Armstrong, AY AF Alford, C. E. DeCherney, A. H. Armstrong, A. Y. TI ALL PATIENTS SEEKING INFERTILITY SERVICES SHOULD BE IMMUNIZED AGAINST H1N1: ESTIMATION OF THE IMPACT OF H1N1 IMMUNIZATION ON MATERNAL MORBIDITY AND MORTALITY IN INFERTILITY PATIENTS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Alford, C. E.; DeCherney, A. H.; Armstrong, A. Y.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S227 EP S227 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000778 ER PT J AU Alford, CE Csokmay, JM Segars, JH Armstrong, AY AF Alford, C. E. Csokmay, J. M. Segars, J. H. Armstrong, A. Y. TI COSTANALYSIS OF IN VITRO FERTILIZATION (IVF) VERSUS BILATERAL TUBAL REANASTOMOSIS (BTA) TO ACHIEVE A LIVE BIRTH. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Alford, C. E.; Csokmay, J. M.; Segars, J. H.; Armstrong, A. Y.] NICHHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S34 EP S34 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000114 ER PT J AU Banks, NK Norian, JM DeCherney, AH Henne, MB AF Banks, N. K. Norian, J. M. DeCherney, A. H. Henne, M. B. TI INSURANCE MANDATES AND ASSISTED REPRODUCTIVE TECHNOLOGY (ART): HOW WERE TREATMENTS AND OUTCOMES IMPACTED BY IMPLEMENTATION OF A MANDATE IN NEW JERSEY? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Reprod Biol & Med Branch, Bethesda, MD USA. Walter Reed Army Med Ctr, Assisted Reprod Technol Program, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S167 EP S167 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000568 ER PT J AU Catherino, WH Malik, M Britten, J Gilden, M Segars, J McCarthy-Keith, D AF Catherino, W. H. Malik, M. Britten, J. Gilden, M. Segars, J. McCarthy-Keith, D. TI LEIOMYOMA FIBROSIS INHIBITED BY LIAROZOLE, A RETINOIC ACID METABOLIC BLOCKING AGENT. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S32 EP S33 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000109 ER PT J AU Chason, RJ Richter, KS Widra, EA Segars, JH AF Chason, R. J. Richter, K. S. Widra, E. A. Segars, J. H. TI A DIAGNOSIS OF POLYCYSTIC OVARY SYNDROME (PCOS) IS ASSOCIATED WITH AN INCREASED LIKELIHOOD OF PREGNANCY LOSS WITH ASSISTED REPRODUCTION. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S25 EP S25 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000083 ER PT J AU Kearns, WG Benner, A Nguyen, KHD Chipko, C Widra, E Leach, R AF Kearns, W. G. Benner, A. Nguyen, K. -H. D. Chipko, C. Widra, E. Leach, R. TI VALIDATION OF SINGLE NUCLEOTIDE POLYMORPHISM (SNP) MICROARRAY PGD ON SINGLE CELL(S) FROM EMBRYOS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Shady Grove Ctr Preimplantat Genet, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S124 EP S124 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000420 ER PT J AU Khachikyan, I Sinaii, N Shah, J Ortiz, R Segars, J Stratton, P AF Khachikyan, I. Sinaii, N. Shah, J. Ortiz, R. Segars, J. Stratton, P. TI CNS SENSITIZATION AND MYOFASCIAL DYSFUNCTION IN PATIENTS WITH ENDOMETRIOSIS AND CHRONIC PELVIC PAIN. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. NIH, Biostatist & Clin Epidemiol Serv, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S40 EP S40 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000135 ER PT J AU Louis, GMB Kim, S Chen, Z Sweeney, AM Barr, D Schrader, SM AF Louis, G. M. Buck Kim, S. Chen, Z. Sweeney, A. M. Barr, D. Schrader, S. M. TI POLYCHLORINATED BIPHENYLS AND SEMEN QUALITY - LIFE STUDY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Texas A&M Rural Sch Publ Hlth, College Stn, TX USA. Emory Univ, Atlanta, GA 30322 USA. NIOSH, CDC, Cincinnati, OH 45226 USA. RI Schrader, Steven/E-8120-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S73 EP S74 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000251 ER PT J AU Louis, GMB Schisterman, EF Sweeney, AM Gore-Langton, R Lynch, CD Sundaram, R AF Louis, G. M. Buck Schisterman, E. F. Sweeney, A. M. Gore-Langton, R. Lynch, C. D. Sundaram, R. TI PRECONCEPTION RECRUITMENT OF COUPLES DESIRING PREGNANCY - CASE FOR THE EXPOSOME. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Texas A&M Rural Sch Publ Hlth, College Stn, TX USA. EMMES Corp, Rockville, MD USA. Ohio State Coll Publ Hlth, Columbus, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S229 EP S229 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000785 ER PT J AU Maguire, M Csokmay, J Hill, M Segars, J Armstrong, A AF Maguire, M. Csokmay, J. Hill, M. Segars, J. Armstrong, A. TI OBESITY IS ASSOCIATED WITH LOWER LIVE BIRTH RATES IN FRESH, BUT NOT FROZEN EMBRYO TRANSFER CYCLES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S18 EP S19 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000063 ER PT J AU Maguire, MF Sullivan, SD Vanderhoof, V Troendle, J DeCherney, A Nelson, L AF Maguire, M. F. Sullivan, S. D. Vanderhoof, V. Troendle, J. DeCherney, A. Nelson, L. TI PREGNANCY OUTCOME IN WOMEN WITH SPONTANEOUS 46,XX PRIMARY OVARIAN INSUFFICIENCY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Maguire, M. F.; Sullivan, S. D.; Vanderhoof, V.; Troendle, J.; DeCherney, A.; Nelson, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S178 EP S178 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000608 ER PT J AU Martinez, AM Chason, RJ DeCherney, AH Venkatesan, AM Elkas, J Armstrong, A AF Martinez, A. M. Chason, R. J. DeCherney, A. H. Venkatesan, A. M. Elkas, J. Armstrong, A. TI MEDICAL TREATMENT OF BENIGN METASTASIZING LEIOMYOMA: A CASE SERIES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 St Barnabas Hosp, Dept Obstet & Gynecol, Livingston, NJ USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. No Virginia Pelv Surg Associates, Annandale, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S220 EP S220 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000755 ER PT J AU McCarthy-Keith, DM Britten, J Malik, M Segars, JH Catherino, WH AF McCarthy-Keith, D. M. Britten, J. Malik, M. Segars, J. H. Catherino, W. H. TI AN ENHANCED LEIOMYOMA CELL RESPONSE TO OSMOTIC STRESS IS CENTRAL TO THE MECHANISM OF GONADOTROPIN RELEASING HORMONE ANALOGUE TREATMENT. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S75 EP S75 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000257 ER PT J AU Moon, KS Csokmay, JM Armstrong, AY Segars, JH Stegmann, BJ AF Moon, K. S. Csokmay, J. M. Armstrong, A. Y. Segars, J. H. Stegmann, B. J. TI ELEVATED ESTRADIOL LEVELS IN AFRICAN-AMERICAN WOMEN MAY EXPLAIN THE REDUCED LIVE BIRTH RATES FOLLOWING ASSISTED REPRODUCTION. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Univ Iowa, Hosp & Clin, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Iowa City, IA USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S242 EP S242 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000830 ER PT J AU Moon, KS Stegmann, BJ Yauger, BJ Segars, JH AF Moon, K. S. Stegmann, B. J. Yauger, B. J. Segars, J. H. TI ARE THERE PROVIDER-DEPENDENT DIFFERENCES IN THE LEARNING CURVE FOR PROFICIENCY WITH OOCYTE RETRIEVALS? SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Univ Iowa, Hosp & Clin, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Iowa City, IA USA. Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S242 EP S243 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000832 ER PT J AU Moon, KS Zhou, Y Mumford, S Segars, JH Armstrong, AY AF Moon, K. S. Zhou, Y. Mumford, S. Segars, J. H. Armstrong, A. Y. TI SERUM ANTI-MULLERIAN HORMONE LEVELS DO NOT CORRELATE WITH CYCLOPHOSPHAMIDE-INDUCED PRIMORDIAL FOLLICULAR DESTRUCTION IN MICE PRETREATED WITH CETRORELIX. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S104 EP S105 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000354 ER PT J AU Muneyyirci-Delale, O Sinaii, N Charles, C Dalloul, M Osei-Tutu, N Stratton, P AF Muneyyirci-Delale, O. Sinaii, N. Charles, C. Dalloul, M. Osei-Tutu, N. Stratton, P. TI PREVALENCE OF METABOLIC SYNDROME AND CHANGES IN LIPID PROFILE OF WOMEN WITH ENDOMETRIOSIS DURING TREATMENT. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Kings Cty Hosp Ctr, Brooklyn, NY USA. NIH Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD USA. NICHD, Program Reprod & Adult Endocrinol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S206 EP S206 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000705 ER PT J AU Muneyyirci-Delale, O Sinaii, N Charles, C Dalloul, M Osei-Tutu, N Stratton, P AF Muneyyirci-Delale, O. Sinaii, N. Charles, C. Dalloul, M. Osei-Tutu, N. Stratton, P. TI CHANGES IN QUALITY OF LIFE (QOL)IN WOMEN WITH SYMPTOMATIC ENDOMETRIOSIS BY PAIN TYPE DURING TREATMENT. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Kings Cty Hosp Ctr, Brooklyn, NY USA. NIH Clin Ctr, Bethesda, MD USA. NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S206 EP S206 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000703 ER PT J AU Nguyen, KHD Ross, R Benner, A Zhao, Y Brezina, P Kearns, WG AF Nguyen, D. K. -H Ross, R. Benner, A. Zhao, Y. Brezina, P. Kearns, W. G. TI SINGLE NUCLEOTIDE POLYMORPHISM (SNP) MICROARRAY PREIMPLANTATION GENETIC SCREENING (PGS): A COMPARISON BETWEEN ABNORMAL DAY-3 BLASTOMERES AND CORRESPONDING INNER CELL MASS AND TROPHECTODERM CELLS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 NHGRI, NIH, Bethesda, MD 20892 USA. La Jolla IVF, La Jolla, CA USA. Shady Grove Ctr Preimplantat Genet, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S80 EP S80 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000274 ER PT J AU Owen, CM Norian, JM Guo, XC Malik, M Catherino, WH Segars, JH AF Owen, C. M. Norian, J. M. Guo, X. C. Malik, M. Catherino, W. H. Segars, J. H. TI LEIOMYOMA CELLS SHOW ATTENUATED MECHANOSENSING, BUT AN INCREASED DEPENDENCE ON RHO-GEF ACTIVATION COMPARED TO MYOMETRIAL CELLS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Reprod & Adult Endocrinol, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 2010 VL 94 IS 4 SU 1 BP S76 EP S76 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000261 ER PT J AU Pulanic, TK Venkatesan, A Segars, J Partanen, A Merino, M Stratton, P AF Pulanic, T. Klepac Venkatesan, A. Segars, J. Partanen, A. Merino, M. Stratton, P. TI PILOT STUDY OF MR-GUIDED HIGH INTENSITY FOCUSED ULTRASOUND (MRGHIFU) ABLATION OF UTERINE FIBROIDS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. NIH, Dept Radiol & Imaging Serv, CC, Bethesda, MD 20892 USA. Philips Healthcare, Cleveland, OH USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S222 EP S222 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000760 ER PT J AU Schlaff, WD Legro, RS Diamond, MP Coutifaris, C Zhang, H AF Schlaff, W. D. Legro, R. S. Diamond, M. P. Coutifaris, C. Zhang, H. TI OVULATION INDUCTION WITH CLOMIPHENE, METFORMIN, OR A COMBINATION OF THE TWO DOES NOT AFFECT HIRSUTISM SCORE OVER A STANDARD COURSE OF TREATMENT IN WOMEN WITH POLYCYSTIC OVARY SYNDROME SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Univ Colorado, Reprod Med Network, Aurora, CO USA. Penn State Univ, Hershey, PA USA. Wayne State Univ, Detroit, MI USA. Univ Penn, Philadelphia, PA 19104 USA. Yale Univ, New Haven, CT USA. NICHD, Data Coordinating Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S192 EP S193 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000657 ER PT J AU Schlaff, WD Legro, RS Diamond, MP Coutifaris, C Zhang, H AF Schlaff, W. D. Legro, R. S. Diamond, M. P. Coutifaris, C. Zhang, H. TI IMPACT OF THE INSTITUTIONAL RESEARCH REVIEW PROCESS ON INITIATING A CLINICAL STUDY: THE REPRODUCTIVE MEDICINE NETWORK (RMN) EXPERIENCE WITH PREGNANCY IN POLYCYSTIC OVARY SYNDROME I AND II SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Univ Colorado, Dept Obstet & Gynecol, Reprod Med Network, Aurora, CO USA. Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Yale Univ, New Haven, CT USA. NICHD, Data Coordinating Ctr, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S196 EP S197 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000671 ER PT J AU Smith, KM Alnifaidy, R Wei, Q Neiman, L AF Smith, K. M. Alnifaidy, R. Wei, Q. Neiman, L. TI ENDOMETRIAL INDIAN HEDGEHOG EXPRESSION IS DECREASED IN WOMEN WITH ENDOMETRIOSIS SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Smith, K. M.; Alnifaidy, R.; Wei, Q.; Neiman, L.] NICHHD, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S200 EP S200 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000682 ER PT J AU Steiner, AZ Herring, AH Hoberman, S Stanczyk, FZ Baird, DD AF Steiner, A. Z. Herring, A. H. Hoberman, S. Stanczyk, F. Z. Baird, D. D. TI SERUM MARKERS OF OVARIAN AGING ARE ASSOCIATED WITH NATURAL FERTILITY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Univ N Carolina, Chapel Hill, NC USA. Univ So Calif, Los Angeles, CA USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S98 EP S99 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000334 ER PT J AU Steiner, AZ Herring, A Kesner, J Meadows, JW Hoberman, S Baird, DD AF Steiner, A. Z. Herring, A. Kesner, J. Meadows, J. W. Hoberman, S. Baird, D. D. TI URINARY MARKERS OF OVARIAN AGING AND PREDICTING NATURAL FERTILITY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Univ N Carolina, Chapel Hill, NC USA. NIOSH, Cincinnati, OH 45226 USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S45 EP S45 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000154 ER PT J AU Wolff, EF Csokmay, J Segars, JH Richter, KS Widra, EA AF Wolff, E. F. Csokmay, J. Segars, J. H. Richter, K. S. Widra, E. A. TI ASSOCIATION BETWEEN ETHNICITY AND PEAK ENDOMETRIAL THICKNESS IN INTRAUTERINE INSEMINATION CYCLES. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S209 EP S209 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000714 ER PT J AU Wolff, EF Segars, JH Richter, KS Widra, EA AF Wolff, E. F. Segars, J. H. Richter, K. S. Widra, E. A. TI DEFINING "ENDOMETRIAL FACTOR'' INFERTILITY: PREGNANCY RATES FOLLOWING 2,090 INTRAUTERINE INSEMINATION CYCLES CORRELATE WITH ENDOMETRIAL THICKNESS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 66th Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproduct Med C1 NICHD, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S209 EP S209 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000715 ER PT J AU Yu, B Sullivan, S Vanderhoof, VH Segars, JH DeCherney, A Nelson, LM AF Yu, B. Sullivan, S. Vanderhoof, V. H. Segars, J. H. DeCherney, A. Nelson, L. M. TI MEAN SERUM FREE TESTOSTERONE AND ESTRADIOL LEVELS IN WOMEN WITH SPONTANEOUS 46, XX PRIMARY OVARIAN INSUFFICIENCY REMAIN RELATIVELY STABLE AS THE TIME SINCE ONSET OF MENSTRUAL IRREGULARITY LENGTHENS. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 [Yu, B.; Sullivan, S.; Vanderhoof, V. H.; Segars, J. H.; DeCherney, A.; Nelson, L. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S181 EP S182 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000620 ER PT J AU Yu, B Chipko, C Richter, KS Widra, EA DeCherney, A Kearns, WG AF Yu, B. Chipko, C. Richter, K. S. Widra, E. A. DeCherney, A. Kearns, W. G. TI IMPROVEMENT IN DIAGNOSTIC ACCURACY USING SINGLE NUCLEOTIDE POLYMORPHISM (SNP) MICROARRAYS VERSUS FLUORESCENCE IN SITU HYBRIDIZATION (FISH) IN PREIMPLANTATION GENETIC SCREENING (PGS) FOR ANEUPLOIDY. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. Shady Grove Ctr Preimplantat Genet, Rockville, MD USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S126 EP S126 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000426 ER PT J AU Yu, B Richter, KS Widra, EA DeCherney, A Segars, JH AF Yu, B. Richter, K. S. Widra, E. A. DeCherney, A. Segars, J. H. TI THE INCIDENCE OF GENUINE EMPTY FOLLICLE SYNDROME. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Reproductive-Medicine (ASRM 2010) CY OCT 23-27, 2010 CL Denver, CO SP Amer Soc Reproductive Med C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Adult & Reprod Endocrinol, NIH, Bethesda, MD USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2010 VL 94 IS 4 SU 1 BP S95 EP S95 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 645GR UT WOS:000281441000324 ER PT J AU Wang, ST Zderic, V Frenkel, V AF Wang, Shutao Zderic, Vesna Frenkel, Victor TI Extracorporeal, low-energy focused ultrasound for noninvasive and nondestructive targeted hyperthermia SO FUTURE ONCOLOGY LA English DT Review DE computer simulation; focused ultrasound; heat-sensitive liposome; heat shock protein promoter; hyperthermia tissue; mimicking phantom ID TEMPERATURE-SENSITIVE LIPOSOMES; TISSUE-MIMICKING MATERIAL; GENE-EXPRESSION; DRUG-DELIVERY; IN-VIVO; LOCAL HYPERTHERMIA; THERMAL THERAPY; SPATIOTEMPORAL CONTROL; TEMPORAL CONTROL; CONTRAST AGENT AB The benefits of hyperthermia are well known as both a primary treatment modality and adjuvant therapy for treating cancer. Among the different techniques available, high-intensity focused ultrasound is the only noninvasive modality that can provide local hyperthermia precisely at a targeted location at any depth inside the body using image guidance, Traditionally, focused ultrasound exposures have been provided at high rates of energy deposition for thermal ablation of benign and malignant tumors. At present, exposures are being evaluated in pulsed mode, which lower the rates of energy deposition and generate primarily mechanical effects for enhancing tissue permeability to improve local drug delivery. These pulsed exposures can be modified for low-level hyperthermia as an adjuvant therapy for drug and gene delivery applications, as well as for more traditional applications such as radiosensitization. In this review, we discuss the manner by which focused ultrasound exposures at low rates of energy deposition are being developed for a variety of clinically translatable applications for the treatment of cancer. Specific preclinical studies will be highlighted. Additional information will also be provided for optimizing these exposures, including computer modeling and simulations. Various techniques for monitoring temperature elevations generated by focused ultrasound will also be reviewed. C1 [Wang, Shutao; Frenkel, Victor] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [Wang, Shutao; Zderic, Vesna] George Washington Univ, Dept Elect & Comp Engn, Washington, DC USA. RP Frenkel, V (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 96 TC 11 Z9 11 U1 3 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD SEP PY 2010 VL 6 IS 9 BP 1497 EP 1511 DI 10.2217/FON.10.101 PG 15 WC Oncology SC Oncology GA 666JG UT WOS:000283110400016 PM 20919832 ER PT J AU Noureddin, M Ghany, MG AF Noureddin, Mazen Ghany, Marc G. TI Pharmacokinetics and Pharmacodynamics of Peginterferon and Ribavirin: Implications for Clinical Efficacy in the Treatment of Chronic Hepatitis C SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Pharmacokinetics; Pharmacodynamics; Peginterferon alfa-2a; Peginterferon alfa-2b; Ribavirin; Chronic hepatitis C ID ALPHA-2B PLUS RIBAVIRIN; PEGYLATED INTERFERON-ALPHA-2B; RANDOMIZED-TRIAL; VIROLOGICAL RESPONSE; TREATMENT DURATION; INITIAL TREATMENT; VIRUS-INFECTION; VIRAL DYNAMICS; NAIVE PATIENTS; PEG-IFN AB The pharmacokinetics and pharmacodynamics of standard interferon alfa-2a and interferon alfa-2b are substantially altered by pegylation The size geometry and site of attachment of the PEG moiety affect the pharmacokinetics and pharmacodynamics as evidenced by the different absorption volume of distribution, and clearance of the linear 12-kDa peginterferon alfa-2b and the branched 40-kDa peginterferon alfa-2a Despite these differences the clinical efficacy safety and tolerability of the 2 peginterferons are similar However evidence exists that peginterferon alfa-2 plus ribavirin is associated with small but significantly higher sustained virological response rates compared with peginterferon alfa-2b This article discusses the pharmacokinetics and pharmacodynamics of the 2 peginterferons and their combination with ribavirin C1 [Noureddin, Mazen; Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, Liver Dis Branch, NIH, Bldg 10,Room 9B 16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health FX This work was supported by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Liver Diseases Branch National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health Building 10 Room 9B 16 10 Center Drive MSC 1800 Bethesda MD 20892 1800 USA NR 33 TC 4 Z9 6 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2010 VL 39 IS 3 BP 649 EP + DI 10.1016/j.gtc.2010.08.008 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 681DP UT WOS:000284291900015 PM 20951922 ER PT J AU Vohanka, J Simeckova, K Machalova, E Behensky, F Krause, MW Kostrouch, Z Kostrouchova, M AF Vohanka, Jaroslav Simeckova, Katerina Machalova, Eliska Behensky, Frantisek Krause, Michael W. Kostrouch, Zdenek Kostrouchova, Marta TI Diversification of fasting regulated transcription in a cluster of duplicated nuclear hormone receptors in C. elegans SO GENE EXPRESSION PATTERNS LA English DT Article DE Caenorhabditis elegans; Caenorhabditis briggsae; Nuclear hormone receptor; Gene expression; Fasting ID EARLY LARVAL DEVELOPMENT; CAENORHABDITIS-ELEGANS; NEMATODES; SUPERFAMILY; NHR-40 AB The genome of Caenorhabditis elegans encodes more than 280 nuclear hormone receptors (NHRs) in contrast to the 48 NHRs in humans and 18 NHRs in Drosophila. The majority of the C. elegans NHRs are categorized as supplementary nuclear receptors (supnrs) that evolved by successive duplications of a single ancestral gene. The evolutionary pressures that lead to the expansion of NHRs in nematodes, as well as the function of the majority of supnrs, are not known. Here, we have studied the expression of seven genes organized in a cluster on chromosome V: nhr-206, nhr-208, nhr-207, nhr-209, nhr-154, nhr-153 and nhr-136. Reverse transcription-quantitative PCR and analyses using transgenic lines carrying GFP fusion genes with their putative promoters revealed that all seven genes of this cluster are expressed and five have partially overlapping expression patterns including in the pharynx, intestine, certain neurons, the anal sphincter muscle, and male specific cells. Four genes in this cluster are conserved between C. elegans and Caenorhabditis briggsae whereas three genes are present only in C elegans, the apparent result of a relatively recent expansion. Interestingly, we find that a subset of the conserved and non-conserved genes in this cluster respond transcriptionally to fasting in tissue-specific patterns. Our results reveal the diversification of the temporal, spatial, and metabolic gene expression patterns coupled with evolutionary drift within supnr family members. (C) 2010 Elsevier B.V. All rights reserved. C1 [Vohanka, Jaroslav; Simeckova, Katerina; Machalova, Eliska; Behensky, Frantisek; Kostrouchova, Marta] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, CZ-12801 Prague 2, Czech Republic. [Kostrouch, Zdenek] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Pathol, CZ-12801 Prague, Czech Republic. [Krause, Michael W.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kostrouchova, M (reprint author), Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Lab Mol Biol & Genet, Ke Karlovu 2, CZ-12801 Prague 2, Czech Republic. EM marta.kostrouchova@lf1.cuni.cz OI Krause, Michael/0000-0001-6127-3940 FU Czech Science Foundation [304/08/0970, 304/07/0529]; Ministry of Education, Youth and Sports of the Czech Republic [0021620806]; National Institutes of Health, USA FX We thank Dr. A. Fire for vectors pPD95.67, L4440 and HT115 cells host. The work was supported by Grant 304/08/0970, Grant 304/07/0529 from the Czech Science Foundation and by Grant 0021620806 from the Ministry of Education, Youth and Sports of the Czech Republic. M.W.K. was supported by the Intramural Research Program of the National Institutes of Health, USA. NR 26 TC 5 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD SEP PY 2010 VL 10 IS 6 BP 227 EP 236 DI 10.1016/j.gep.2010.05.001 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 638RT UT WOS:000280914300001 PM 20460175 ER PT J AU Shi, Q Nguyen, AT Angell, Y Deng, D Na, CR Burgess, K Roberts, DD Brunicardi, FC Templeton, NS AF Shi, Q. Nguyen, A. T. Angell, Y. Deng, D. Na, C-R Burgess, K. Roberts, D. D. Brunicardi, F. C. Templeton, N. S. TI A combinatorial approach for targeted delivery using small molecules and reversible masking to bypass nonspecific uptake in vivo SO GENE THERAPY LA English DT Article DE non-viral delivery; liposomes; targeted delivery; tumor vascular microenvironment; anticancer therapeutics; reversible masking ID IMMUNODEFICIENCY-VIRUS TYPE-1; TUMOR ENDOTHELIAL MARKERS; ANTI-ANGIOGENIC THERAPIES; GROWTH-FACTOR VEGF; BETA-TURN MIMICS; GENE-THERAPY; SYSTEMIC DELIVERY; ANTITUMOR-ACTIVITY; ENVELOPE PROTEIN; CELLS AB We have developed a multi-disciplinary approach combining molecular biology, delivery technology, combinatorial chemistry and reversible masking to create improved systemic, targeted delivery of plasmid DNA while avoiding nonspecific uptake in vivo. We initially used a well-characterized model targeting the asialolglycoprotein receptor in the liver. Using our bilamellar invaginated vesicle (BIV) liposomal delivery system with reversible masking, we increased expression in the liver by 76-fold, nearly equaling expression in first-pass organs using non-targeted complexes, with no expression in other organs. The same technology was then applied to efficiently target delivery to a human tumor microenvironment model. We achieved efficient, targeted delivery by attachment of specific targeting ligands to the surface of our BIV complexes in conjunction with reversible masking to bypass nonspecific tissues and organs. We identified ligands that target a human tumor microenvironment created in vitro by co-culturing primary human endothelial cells with human lung or pancreatic cancer cells. The model was confirmed by increased expression of tumor endothelial phenotypes including CD31 and vascular endothelial growth factor-A, and prolonged survival of endothelial capillary-like structures. The co-cultures were used for high-throughput screening of a specialized small molecule library to identify ligands specific for human tumor-associated endothelial cells in vitro. We identified small molecules that enhanced the transfection efficiency of tumor-associated endothelial cells, but not normal human endothelial cells or cancer cells. Intravenous (i.v.) injection of our targeted, reversibly masked complexes into mice, bearing human pancreatic tumor and endothelial cells, specifically increased transfection to this tumor microenvironment approximately 200-fold. Efficacy studies using our optimized targeted delivery of a plasmid encoding thrombospondin-1 eliminated tumors completely after five i.v. injections administered once every week. Gene Therapy (2010) 17, 1085-1097; doi:10.1038/gt.2010.55; published online 13 May 2010 C1 [Shi, Q.; Templeton, N. S.] Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. [Nguyen, A. T.; Deng, D.; Na, C-R; Brunicardi, F. C.; Templeton, N. S.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Angell, Y.; Burgess, K.] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. [Roberts, D. D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Templeton, NS (reprint author), Gradalis Inc, Delivery Syst, 2545 Golden Bear Dr,Suite 110, Carrollton, TX 75006 USA. EM ntempleton@gradalisinc.com RI Roberts, David/A-9699-2008; Burgess, Kevin/B-5372-2015 OI Roberts, David/0000-0002-2481-2981; Burgess, Kevin/0000-0001-6597-1842 FU GeneExcel, Inc. (now part of Gradalis, Inc.); National Institutes of Health [MH070040, GM076261]; NIH, NCI, Center for Cancer Research; Robert A Welch Foundation FX We thank GeneExcel, Inc. (now part of Gradalis, Inc.), the National Institutes of Health (MH070040, GM076261), the Intramural Research Program of the NIH, NCI, Center for Cancer Research, and the Robert A Welch Foundation for the financial support of this project. NR 68 TC 11 Z9 11 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2010 VL 17 IS 9 BP 1085 EP 1097 DI 10.1038/gt.2010.55 PG 13 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 649HC UT WOS:000281757900003 PM 20463761 ER PT J AU Das, B Matsuda, H Fujimoto, K Sun, GH Matsuura, K Shi, YB AF Das, Biswajit Matsuda, Hiroki Fujimoto, Kenta Sun, Guihong Matsuura, Kazuo Shi, Yun-Bo TI Molecular and genetic studies suggest that thyroid hormone receptor is both necessary and sufficient to mediate the developmental effects of thyroid hormone SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology CY 2009 CL Leibniz-Inst Freshwater Ecol & Inland Fisheries, Berlin, GERMANY HO Leibniz-Inst Freshwater Ecol & Inland Fisheries DE Thyroid hormone receptor; Chromatin; Histone acetylation; Postembryonic development; Metamorphosis; Xenopus laevis; Xenopus tropicalis ID RETINOIC ACID RECEPTORS; XENOPUS-LAEVIS; AMPHIBIAN METAMORPHOSIS; NUCLEAR RECEPTOR; BETA GENE; POSTEMBRYONIC DEVELOPMENT; COREPRESSOR COMPLEXES; EMBRYONIC-DEVELOPMENT; FROG METAMORPHOSIS; NONGENOMIC ACTIONS AB Thyroid hormone (TH) affects diverse biological processes and can exert its effects through both gene regulation via binding the nuclear TH receptors (TRs) and non-genomic actions via binding to cell surface and cytoplasmic proteins. The critical importance of TH in vertebrate development has long been established, ranging from the formation of human cretins to the blockage of frog metamorphosis due the TH deficiency. How TH affects vertebrate development has been difficult to study in mammals due to the complications associated with the uterus-enclosed mammalian embryos. Anuran metamorphosis offers a unique opportunity to address such an issue. Using Xenopus as a model, we and others have shown that the expression of TRs and their heterodimerization partners RXRs (9-cis retinoic acid receptors) correlates temporally with metamorphosis in different organs in two highly related species, Xenopus laevis and Xenopus tropicalis. In vivo molecular studies have shown that TR and RXR are bound to the TH response elements (TREs) located in TH-inducible genes in developing tadpoles of both species. More importantly, transgenic studies in X. laevis have demonstrated that TR function is both necessary and sufficient for mediating the metamorphic effects of TH. Thus, the non-genomic effects of TH have little or no roles during metamorphosis and likely during vertebrate development in general. Published by Elsevier Inc. C1 [Das, Biswajit; Matsuda, Hiroki; Fujimoto, Kenta; Sun, Guihong; Matsuura, Kazuo; Shi, Yun-Bo] NICHD, Lab Gene Regulat & Dev, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHD, Lab Gene Regulat & Dev, Program Cellular Regulat & Metab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov FU Intramural NIH HHS [Z01 HD001901-13] NR 81 TC 16 Z9 21 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD SEP 1 PY 2010 VL 168 IS 2 SI SI BP 174 EP 180 DI 10.1016/j.ygcen.2010.01.019 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 641AF UT WOS:000281095000003 PM 20138179 ER PT J AU Heimeier, RA Shi, YB AF Heimeier, Rachel A. Shi, Yun-Bo TI Amphibian metamorphosis as a model for studying endocrine disruption on vertebrate development: Effect of bisphenol A on thyroid hormone action SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Amphibian and Reptilian Endocrinology and Neurobiology CY 2009 CL Leibniz-Inst Freshwater Ecol & Inland Fisheries, Berlin, GERMANY HO Leibniz-Inst Freshwater Ecol & Inland Fisheries DE Thyroid hormone receptor; Bisphenol A; Endocrine disrupting compound; Xenopus laevis; Metamorphosis ID XENOPUS-LAEVIS METAMORPHOSIS; IODINE-DEFICIENCY DISORDER; GENE-EXPRESSION INDICATORS; IN-VITRO; TRANSCRIPTIONAL REGULATION; POSTEMBRYONIC DEVELOPMENT; ENVIRONMENTAL CHEMICALS; INTESTINAL EPITHELIUM; RECEPTOR SUPERFAMILY; MOLECULAR-MECHANISMS AB Thyroid hormone (TH) is essential for proper development in vertebrates. TH deficiency during gestation and early postnatal development produces severe neurological, skeletal, metabolism and growth abnormalities. It is therefore important to consider environmental chemicals that may interfere with TH signaling. Exposure to environmental contaminants that disrupt TH action may underlie the increasing incidence of human developmental disorders worldwide. One contaminant of concern is the xenoestrogen bisphenol A (BPA), a chemical widely used to manufacture polycarbonate plastics and epoxy resins. The difficulty in studying uterus-enclosed mammalian embryos has hampered the analysis on the direct effects of BPA during vertebrate development. As TH action at the cellular level is highly conserved across vertebrate species, amphibian metamorphosis serves as an important TH-dependent in vivo vertebrate model for studying potential contributions of BPA toward human developmental disorders. Using Xenopus laevis as a model, we and others have demonstrated the inhibitory effects of BPA exposure on metamorphosis. Genome-wide gene expression analysis revealed that surprisingly. BPA primarily targets the TH-signaling pathway essential for metamorphosis in Xenopus laevis. Given the importance of the genomic effects of TH during metamorphosis and the conservation in its regulation in higher vertebrates, these observations suggest that the effect of BPA in human embryogenesis is through the inhibition of the TH pathway and warrants further investigation. Our findings further argue for the critical need to use in vivo animal models coupled with systematic molecular analysis to determine the developmental effects of endocrine disrupting compounds. Published by Elsevier Inc. C1 [Heimeier, Rachel A.] Karolinska Inst, Inst Environm Med IMM, S-17177 Stockholm, Sweden. [Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA. RP Heimeier, RA (reprint author), Karolinska Inst, Inst Environm Med IMM, Nobels Vag 13, S-17177 Stockholm, Sweden. EM rachel.heimeier@ki.se; shi@helix.nih.gov FU Intramural NIH HHS NR 115 TC 22 Z9 23 U1 2 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD SEP 1 PY 2010 VL 168 IS 2 SI SI BP 181 EP 189 DI 10.1016/j.ygcen.2010.02.016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 641AF UT WOS:000281095000004 PM 20178801 ER PT J AU Chambers, DA Wang, PS Insel, TR AF Chambers, David A. Wang, Philip S. Insel, Thomas R. TI Maximizing efficiency and impact in effectiveness and services research SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material C1 [Chambers, David A.; Wang, Philip S.; Insel, Thomas R.] NIMH, Bethesda, MD 20892 USA. RP Chambers, DA (reprint author), NIMH, Bethesda, MD 20892 USA. EM dchamber@mail.nih.gov NR 11 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2010 VL 32 IS 5 BP 453 EP 455 DI 10.1016/j.genhosppsych.2010.07.011 PG 3 WC Psychiatry SC Psychiatry GA 657CT UT WOS:000282390500001 PM 20851264 ER PT J AU Lagomasino, IT Zatzick, DF Chambers, DA AF Lagomasino, Isabel T. Zatzick, Douglas F. Chambers, David A. TI Efficiency in mental health practice and research SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Improving the Efficiency of Research and Mental Health Service Delivery CY MAR 20, 2009 CL Natl Inst Mental Hlth, Bethesda, MD HO Natl Inst Mental Hlth DE Efficiency; Mental health; Health services research; Intervention development; Implementation ID CARE; ILLNESS; INJURY AB Limited financial resources, escalating mental health-related costs and opportunities for capitalizing on advances in health information technologies have brought the theme of efficiency to the forefront of mental health services research and clinical practice. In this introductory article to the journal series stemming from the 20th NIMH Mental Health Services Research Conference, we first delineate the need for a new focus on efficiency in both research and clinical practice. Second, we provide preliminary definitions of efficiency for the field and discuss issues related to measurement. Finally, we explore the interface between efficiency in mental health services research and practice and the NIMH strategic objectives of developing improved interventions for diverse populations and enhancing the public health impact of research. Case examples illustrate how perspectives from dissemination and implementation research may be used to maximize efficiencies in the development and implementation of new service delivery models. Allowing findings from the dissemination and implementation field to permeate and inform clinical practice and research may facilitate more efficient development of interventions and enhance the public health impact of research. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lagomasino, Isabel T.] Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Zatzick, Douglas F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. [Chambers, David A.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Lagomasino, IT (reprint author), Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. EM lagomasi@usc.edu FU NIMH NIH HHS [P30 MH082760-04, P30 MH082760, R01 MH067949, R01 MH067949-04] NR 18 TC 10 Z9 10 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD SEP-OCT PY 2010 VL 32 IS 5 BP 477 EP 483 DI 10.1016/j.genhosppsych.2010.06.005 PG 7 WC Psychiatry SC Psychiatry GA 657CT UT WOS:000282390500004 PM 20851267 ER PT J AU Laurie, CC Doheny, KF Mirel, DB Pugh, EW Bierut, LJ Bhangale, T Boehm, F Caporaso, NE Cornelis, MC Edenberg, HJ Gabriel, SB Harris, EL Hu, FB Jacobs, KB Kraft, P Landi, MT Lumley, T Manolio, TA McHugh, C Painter, I Paschall, J Rice, JP Rice, KM Zheng, XW Weir, BS AF Laurie, Cathy C. Doheny, Kimberly F. Mirel, Daniel B. Pugh, Elizabeth W. Bierut, Laura J. Bhangale, Tushar Boehm, Frederick Caporaso, Neil E. Cornelis, Marilyn C. Edenberg, Howard J. Gabriel, Stacy B. Harris, Emily L. Hu, Frank B. Jacobs, Kevin B. Kraft, Peter Landi, Maria Teresa Lumley, Thomas Manolio, Teri A. McHugh, Caitlin Painter, Ian Paschall, Justin Rice, John P. Rice, Kenneth M. Zheng, Xiuwen Weir, Bruce S. CA GENEVA Investigators TI Quality Control and Quality Assurance in Genotypic Data for Genome-Wide Association Studies SO GENETIC EPIDEMIOLOGY LA English DT Article DE GWAS; DNA sample quality; genotyping artifact; Hardy-Weinberg equilibrium; chromosome aberration ID DIFFERENTIAL BIAS; COLLABORATION; SUBSTRUCTURE; INFORMATION; GENE AB Genome-wide scans of nucleotide variation in human subjects are providing an increasing number of replicated associations with complex disease traits. Most of the variants detected have small effects and, collectively, they account for a small fraction of the total genetic variance. Very large sample sizes are required to identify and validate findings. In this situation, even small sources of systematic or random error can cause spurious results or obscure real effects. The need for careful attention to data quality has been appreciated for some time in this field, and a number of strategies for quality control and quality assurance (QC/QA) have been developed. Here we extend these methods and describe a system of QC/QA for genotypic data in genome-wide association studies (GWAS). This system includes some new approaches that (1) combine analysis of allelic probe intensities and called genotypes to distinguish gender misidentification from sex chromosome aberrations, (2) detect autosomal chromosome aberrations that may affect genotype calling accuracy, (3) infer DNA sample quality from relatedness and allelic intensities, (4) use duplicate concordance to infer SNP quality, (5) detect genotyping artifacts from dependence of Hardy-Weinberg equilibrium test P-values on allelic frequency, and (6) demonstrate sensitivity of principal components analysis to SNP selection. The methods are illustrated with examples from the "Gene Environment Association Studies" (GENEVA) program. The results suggest several recommendations for QC/QA in the design and execution of GWAS. Genet. Epidemiol. 34 :591-602, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Laurie, Cathy C.; Bhangale, Tushar; Boehm, Frederick; Lumley, Thomas; McHugh, Caitlin; Rice, Kenneth M.; Zheng, Xiuwen; Weir, Bruce S.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Doheny, Kimberly F.; Pugh, Elizabeth W.] Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA. [Mirel, Daniel B.; Gabriel, Stacy B.] Broad Inst & Harvard, Cambridge, MA USA. [Bierut, Laura J.; Rice, John P.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Caporaso, Neil E.; Jacobs, Kevin B.; Landi, Maria Teresa] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Cornelis, Marilyn C.; Hu, Frank B.] Harvard Univ, Dept Nutr, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Edenberg, Howard J.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Harris, Emily L.] NIDCR, Div Extramural Res, Bethesda, MD USA. [Kraft, Peter] Harvard Univ, Program Mol & Genet Epidemiol, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Manolio, Teri A.] NHGRI, Off Populat Gen, Bethesda, MD 20892 USA. [Paschall, Justin] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Weir, BS (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM bsweir@u.washington.edu RI Weir, Bruce/A-2894-2013; Rice, Kenneth/A-4150-2013; OI Rice, Kenneth/0000-0001-5779-4495; Boehm, Frederick/0000-0002-1644-5931; Painter, Ian/0000-0001-7643-1200; Zheng, Xiuwen/0000-0002-1390-0708; Edenberg, Howard/0000-0003-0344-9690 FU NIH [U01HG004422, HHSN268200782096C]; NIAAA [U10AA008401]; NIDA [P01CA089392, R01DA013423, T2D, U01HG004399]; NIH GEI [HG-06-033-NCI-01, U01HG04424]; National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; Johns Hopkins University Center for Inherited Disease Research [U01HG004438]; [U01 HG 004446] FX Funding support has been provided through the NIH Genes, Environment and Health Initiative. Additional funding sources for projects are: ( 1) Addiction, PI Laura J. Bierut, U01HG004422, NIAAA: U10AA008401, NIDA: P01CA089392, R01DA013423; ( 2) T2D, PI Frank B. Hu, U01HG004399; and ( 3) Lung Cancer, PI Neil Caporaso, NIH GEI: HG-06-033-NCI-01 and the Intramural Research Program of National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics.; Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). The GENEVA Coordinating Center receives support from U01 HG 004446 ( PI Bruce S Weir). Assistance with data cleaning was provided by the National Center for Biotechnology Information; this work was supported by the Intramural Research Program of the NIH, National Library of Medicine. LJ Bierut and JP Rice are inventors on the patent "Markers for Addiction" (US 20070258898) covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction. Dr. Bierut served as a consultant for Pfizer Inc. in 2008. NR 30 TC 142 Z9 144 U1 0 U2 21 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 SEP PY 2010 VL 34 IS 6 BP 591 EP 602 DI 10.1002/gepi.20516 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 652VG UT WOS:000282038200009 PM 20718045 ER PT J AU Abedi-Ardekani, B Kamangar, F Hewitt, SM Hainaut, P Sotoudeh, M Abnet, CC Taylor, PR Boffetta, P Malekzadeh, R Dawsey, SM AF Abedi-Ardekani, Behnoush Kamangar, Farin Hewitt, Stephen M. Hainaut, Pierre Sotoudeh, Masoud Abnet, Christian C. Taylor, Philip R. Boffetta, Paolo Malekzadeh, Reza Dawsey, Sanford M. TI Polycyclic aromatic hydrocarbon exposure in oesophageal tissue and risk of oesophageal squamous cell carcinoma in north-eastern Iran SO GUT LA English DT Article ID MONOCLONAL-ANTIBODIES; GASTRIC CANCERS; DNA ADDUCTS; TOOTH LOSS; POPULATION; BENZOPYRENE; TOBACCO; AREA; IMMUNOHISTOCHEMISTRY; BIOMARKERS AB Objective To evaluate the association between polycyclic aromatic hydrocarbon (PAH) exposure in oesophageal epithelial tissue and oesophageal squamous cell carcinoma (ESCC) case status in an ESCC case-control study in a high-risk population in north-eastern Iran. Methods Tissue microarrays (TMAs) of non-tumoral oesophageal biopsies from patients with biopsy-proven ESCC and gastrointestinal clinic patients with no endoscopic or biopsy evidence of ESCC (control subjects) in a rural region in north-eastern Iran were immunohistochemically stained. Immunohistochemistry was performed using monoclonal antibodies 8E11 and 5D11 raised against benzo[ a] pyrene (B[ a] P) diol epoxide (BPDE)-I-modified guanosine and BPDE-I-modified DNA, respectively. Staining intensity was quantified by image analysis and the average staining in three replicates was calculated. The main outcome measure was adjusted ORs with 95% CIs for the association between antibody staining intensity and ESCC case status. Results Cultured ESCC cells exposed to B[ a] P in vitro showed dose-dependent staining with 8E11 but not with 5D11. With 8E11, sufficient epithelial tissue was available in the TMA cores to analyse 91 cases and 103 controls. Compared with the lowest quintile of 8E11 staining in the controls, adjusted ORs for the 2nd to 5th quintiles were 2.42, 5.77, 11.3 and 26.6 (95% CI 5.21 to 135), respectively (p for trend <0.001). With 5D11, 89 cases and 101 controls were analysed. No association between staining and case status was observed (ORs for the 2nd to 5th quintiles were 1.26, 0.88, 1.06 and 1.63 (95% CI 0.63 to 4.21), p for trend=0.40). Conclusions Dramatically higher levels of 8E11 staining were observed in non-tumoral oesophageal epithelium from patients with ESCC than from control subjects. This finding strengthens the evidence for a causal role for PAHs in oesophageal carcinogenesis in north-eastern Iran. C1 [Abedi-Ardekani, Behnoush; Kamangar, Farin; Abnet, Christian C.; Taylor, Philip R.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Abedi-Ardekani, Behnoush; Kamangar, Farin; Sotoudeh, Masoud; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. [Abedi-Ardekani, Behnoush; Hainaut, Pierre; Boffetta, Paolo] Int Agcy Res Canc, F-69372 Lyon, France. [Abedi-Ardekani, Behnoush] Social Secur Org, Tehran, Iran. [Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21239 USA. [Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Dawsey, SM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 3018, Bethesda, MD 20892 USA. EM dawseys@mail.nih.gov RI Hainaut, Pierre /B-6018-2012; Abnet, Christian/C-4111-2015; Abedi-Ardekani, Behnoush/O-7829-2016; OI Hainaut, Pierre /0000-0002-1303-1610; Abnet, Christian/0000-0002-3008-7843; Abedi-Ardekani, Behnoush/0000-0002-0980-0587; Hewitt, Stephen/0000-0001-8283-1788; Malekzadeh, Reza/0000-0003-1043-3814 FU Digestive Disease Research Center of Tehran University of Medical Sciences; National Cancer Institute at the National Institutes of Health; International Agency for Research on Cancer FX This work was supported by intramural funds from the Digestive Disease Research Center of Tehran University of Medical Sciences, the National Cancer Institute at the National Institutes of Health and the International Agency for Research on Cancer. NR 34 TC 26 Z9 27 U1 1 U2 3 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 SEP PY 2010 VL 59 IS 9 BP 1178 EP 1183 DI 10.1136/gut.2010.210609 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 654SA UT WOS:000282187100008 PM 20584779 ER PT J AU Tumblin, A Tailor, A Hoehn, GT Mack, AK Mendelsohn, L Freeman, L Xu, XL Remaley, AT Munson, PJ Suffredini, AF Kato, GJ AF Tumblin, Ashaunta Tailor, Anitaben Hoehn, Gerard T. Mack, A. Kyle Mendelsohn, Laurel Freeman, Lita Xu, Xiuli Remaley, Alan T. Munson, Peter J. Suffredini, Anthony F. Kato, Gregory J. TI Apolipoprotein A-I and serum amyloid A plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE acute painful episode; immunoassay; sickle cell disease ID ACUTE-PHASE RESPONSE; VASOOCCLUSIVE CRISIS; STEADY-STATE; ANEMIA; HDL; HYDROXYUREA; EXPRESSION; FREQUENCY; PROTEIN; MICE AB Background Acute painful episodes are the clinical hallmark of sickle cell disease and have been linked to morbidity and mortality in the sickle cell population. Design and Methods We undertook exploratory proteomic studies on paired plasma samples collected from a cohort of 26 adult sickle cell patients during steady state and on the first day of an acute painful episode. We screened for changes in abundance of specific protein peaks via surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), and confirmed the identify of candidate protein peaks by specific immunoassays. Results The levels of hemoglobin, hematocrit, total protein, and albumin were lower and the levels of lactate dehydrogenase and absolute reticulocytes higher during acute painful episodes than during the steady state. Surface-enhanced laser desorption/ionization time of flight mass spectrometry spectral analysis consistently showed a mass-to-charge peak at 11.7 kDa with elevated intensities during acute painful episodes, which correlated significantly with the serum amyloid A immunoassay. Serum amyloid A levels were significantly elevated during acute painful episodes, especially in four patients with marked end-organ complications of such episodes. A second, recurring peak, less abundant during acute painful episodes, was present at 28.1 kDa; this peak was correlated significantly with immunoassay measurements of apolipoprotein A1. Conclusions On the average, plasma serum amyloid A rises and apolipoprotein AI falls during acute painful episodes. The serum amyloid A/apolipoprotein AI ratio increased in 81% of the patients during acute painful episodes, potentially making it a useful objective marker of such episodes. We propose that these protein alterations, known to contribute to endothelial dysfunction in other settings, might do likewise acutely in acute painful episodes and present a new target for therapeutic intervention in sickle cell disease. C1 [Hoehn, Gerard T.; Suffredini, Anthony F.; Kato, Gregory J.] NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Mack, A. Kyle] NCI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Munson, Peter J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Kato, GJ (reprint author), NHLBI, Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10 CRC,Room 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU NIH Division of Intramural Research through the National Heart, Lung and Blood Institute; NIH Clinical Center; NIH Center for Information Technology FX Funding: research funding was provided by the NIH Division of Intramural Research through the National Heart, Lung and Blood Institute, the NIH Clinical Center, and the NIH Center for Information Technology. NR 36 TC 9 Z9 10 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD SEP PY 2010 VL 95 IS 9 BP 1467 EP 1472 DI 10.3324/haematol.2009.018044 PG 6 WC Hematology SC Hematology GA 651NA UT WOS:000281933200007 PM 20378559 ER PT J AU Nierenberg, K Byrne, MM Fleming, LE Stephan, W Reich, A Backer, LC Tanga, E Dalpra, DR Kirkpatrick, B AF Nierenberg, Kate Byrne, Margaret M. Fleming, Lora E. Stephan, Wendy Reich, Andrew Backer, Lorraine C. Tanga, Elvira Dalpra, Dana R. Kirkpatrick, Barbara TI Florida red tide perception: Residents versus tourists SO HARMFUL ALGAE LA English DT Article DE Communication tools; Evaluation of outreach and education; Florida red tide; Harmful algal blooms and public knowledge; Karenia brevis; Outreach and education; Resident risk perception; Seafood safety; Tourist risk perception ID TOXINS BREVETOXINS; EXPOSURE; ASTHMA; RISK; FISH AB The west coast of Florida has annual blooms of the toxin-producing dinoflagellate, Karenia brevis with Sarasota, FL considered the epicenter for these blooms. Numerous outreach materials, including Frequently Asked Question (FAQ) cards, exhibits for local museums and aquaria, public beach signs, and numerous websites have been developed to disseminate information to the public about this natural hazard. In addition, during intense onshore blooms, a great deal of media attention, primarily via newspaper (print and web) and television, is focused on red tide. However to date, the only measure of effectiveness of these outreach methods has been counts of the number of people exposed to the information, e.g., visits to a website or number of FAQ cards distributed. No formal assessment has been conducted to determine if these materials meet their goal of informing the public about Florida red tide. Also, although local residents have the opinion that they are very knowledgeable about Florida red tide, this has not been verified empirically. This study addressed these issues by creating and administering an evaluation tool for the assessment of public knowledge about Florida red tide. A focus group of Florida red tide outreach developers assisted in the creation of the evaluation tool. The location of the evaluation was the west coast of Florida, in Sarasota County. The objective was to assess the knowledge of the general public about Florida red tide. This assessment identified gaps in public knowledge regarding Florida red tides and also identified what information sources people want to use to obtain information on Florida red tide. The results from this study can be used to develop more effective outreach materials on Florida red tide. (c) 2010 Elsevier B.V. All rights reserved. C1 [Nierenberg, Kate] Mote Marine Lab, Environm Hlth Program, Sarasota, FL 34236 USA. [Byrne, Margaret M.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Fleming, Lora E.; Stephan, Wendy] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF & NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA. [Fleming, Lora E.; Stephan, Wendy] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. [Reich, Andrew] Florida Dept Hlth & Rehabil Serv, Tallahassee, FL 32399 USA. [Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30329 USA. [Tanga, Elvira] Wesleyan Coll, Macon, GA 31210 USA. RP Nierenberg, K (reprint author), Mote Marine Lab, Environm Hlth Program, 1600 Ken Thompson Pkwy, Sarasota, FL 34236 USA. EM knierenberg@mote.org FU National Science Foundation [0453955]; DHHS NIH of the National Institute of Environmental Health Sciences [P01 ES 10594]; National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School [NSF OCE0432368, NSF OCE0911373]; NIEHS [1 P50 ES12736]; Centers for Disease Control and Prevention; Florida Department of Health [U50/CCU423360-02] FX Thanks to Erin Griswold and all the Mote Marine Laboratory volunteers who took time to administer this survey. This research was supported by the National Science Foundation under The Research Experience for Undergraduate Program, grant number 0453955 and the P01 ES 10594, DHHS NIH of the National Institute of Environmental Health Sciences. Additional support was received from the National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School (NSF OCE0432368 and NSF OCE0911373); (NIEHS 1 P50 ES12736), as well as by the Centers for Disease Control and Prevention and the Florida Department of Health (Cooperative Agreement: U50/CCU423360-02). [SS] NR 31 TC 7 Z9 7 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 EI 1878-1470 J9 HARMFUL ALGAE JI Harmful Algae PD SEP PY 2010 VL 9 IS 6 BP 600 EP 606 DI 10.1016/j.hal.2010.04.010 PG 7 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 652JC UT WOS:000281999300009 PM 20824108 ER PT J AU Zarate, C Machado-Vieira, R Henter, I Ibrahim, L Diazgranados, N Salvadore, G AF Zarate, Carlos, Jr. Machado-Vieira, Rodrigo Henter, Ioline Ibrahim, Lobna Diazgranados, Nancy Salvadore, Giacomo TI Glutamatergic Modulators: The Future of Treating Mood Disorders? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID MAJOR DEPRESSIVE DISORDER; D-ASPARTATE ANTAGONIST; OPEN-LABEL TRIAL; MAGNETIC-RESONANCE SPECTROSCOPY; SEROTONIN REUPTAKE INHIBITORS; CELLULAR PLASTICITY CASCADES; ANTERIOR CINGULATE ACTIVITY; BIPOLAR AFFECTIVE-DISORDER; GAMMA-AMINOBUTYRIC-ACID; MEDIAL TEMPORAL-LOBE AB Mood disorders such as bipolar disorder and major depressive disorder are common, chronic, and recurrent conditions affecting millions of individuals worldwide. Existing antidepressants and mood stabilizers used to treat these disorders are insufficient for many. Patients continue to have low remission rates, delayed onset of action, residual subsyndromal symptoms, and relapses. New therapeutic agents able to exert faster and sustained antidepressant or mood-stabilizing effects are urgently needed to treat these disorders. In this context, the glutamatergic system has been implicated in the pathophysiology of mood disorders in unique clinical and neurobiological ways. In addition to evidence confirming the role of the glutamatergic modulators riluzole and ketamine as proof-of-concept agents in this system, trials with diverse glutamatergic modulators are under way. Overall, this system holds considerable promise for developing the next generation of novel therapeutics for the treatment of bipolar disorder and major depressive disorder.3H]Ibogaine, ibogaine, and phencyclidine, and to Paulina Iacoban for their technical assistance. Xiao Juan Yuan was supported by a Student Summer Fellowship, Western University of Health Sciences (Pomona, CA, USA). NR 43 TC 10 Z9 10 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD SEP PY 2010 VL 42 IS 9 BP 1525 EP 1535 DI 10.1016/j.biocel.2010.05.011 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 639IE UT WOS:000280967700020 PM 20684041 ER PT J AU Jiang, WD Wang, XW Unger, T Forgues, M Kim, JW Hussain, SP Bowman, E Spillare, EA Lipsky, MM Meck, JM Cavalli, LR Haddad, BR Harris, CC AF Jiang, Weidong Wang, Xin Wei Unger, Tamar Forgues, Marshonna Kim, Jin Woo Hussain, S. Perwez Bowman, Elise Spillare, Elisa A. Lipsky, Michael M. Meck, Jeanne M. Cavalli, Luciane R. Haddad, Bassem R. Harris, Curtis C. TI Cooperation of tumor-derived HBx mutants and p53-249(ser) mutant in regulating cell proliferation, anchorage-independent growth and aneuploidy in a telomerase-immortalized normal human hepatocyte-derived cell line SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE p53; HBx; cell proliferation; anchorage-independent growth ID HEPATITIS-B-VIRUS; HUMAN HEPATOCELLULAR CARCINOMAS; BRONCHIAL EPITHELIAL-CELLS; X-PROTEIN; LIVER-CANCER; GENE-EXPRESSION; TRANSGENIC MICE; P53 GENE; MUTATIONS; APOPTOSIS AB Hepatocellular carcinoma (HCC) is a common cancer, and hepatitis B virus (HBV) is a major etiological agent. Convincing epidemiological and experimental evidence also links HCC to aflatoxin, a naturally occurring mycotoxin that produces a signature p53-249(ser) mutation. Recently, we have reported that tumor-derived HBx variants encoded by HBV exhibited attenuated transactivation and proapoptotic functions but retained their ability to block p53-mediated apoptosis. These results indicate that mutations in HBx may contribute to the development of HCC. In this study, we determined whether tumor-derived HBx mutants along, or in cooperation with p53-249(ser), could alter cell proliferation and chromosome stability of normal human hepatocytes. To test this hypothesis, we established a telomerase immortalized normal human hepatocycte line HHT4 that exhibited a near diploid karyotype and expressed many hepatocyte-specific genes. We found that overexpression one of the tumor-derived HBx mutants, CT, significantly increased colony forming efficiency (CFE) while its corresponding wild-type allele CNT significantly decreased CFE in HHT4 cells. p53-249(ser) rescued CNT-mediated inhibition of colony formation. Although HHT4 cells lacked an anchorage independent growth capability as they did not form any colonies in soft agar, the CT-expressing HHT4 cells could form colonies, which could be significantly enhanced by p53-249(ser). Induction of aneuploidy could be observed in HHT4 cells expressing CT, but additionally recurring chromosome abnormalities could only be detected in cells coexpressing CT and p53-249(ser) Our results are consistent with the hypothesis that certain mutations in HBx and p53 at codon 249 may cooperate in contributing to liver carcinogenesis. C1 [Jiang, Weidong; Wang, Xin Wei; Forgues, Marshonna; Kim, Jin Woo; Hussain, S. Perwez; Bowman, Elise; Spillare, Elisa A.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. [Unger, Tamar] Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. [Lipsky, Michael M.] Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. [Meck, Jeanne M.; Cavalli, Luciane R.; Haddad, Bassem R.] Georgetown Univ, Dept Oncol, Washington, DC USA. [Meck, Jeanne M.; Cavalli, Luciane R.; Haddad, Bassem R.; Harris, Curtis C.] Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. [Meck, Jeanne M.; Cavalli, Luciane R.; Haddad, Bassem R.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. RP Harris, CC (reprint author), Room 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM harrisc@mail.nih.gov RI Cavalli, Luciane/J-6100-2012; Wang, Xin/B-6162-2009 FU NIH; Intramural Research Program FX Grant sponsor: NIH; Grant number: Intramural Research Program NR 46 TC 21 Z9 23 U1 0 U2 2 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 SEP 1 PY 2010 VL 127 IS 5 BP 1011 EP 1020 DI 10.1002/ijc.25118 PG 10 WC Oncology SC Oncology GA 635KK UT WOS:000280653800002 PM 20017137 ER PT J AU Swoboda, RK Somasundaram, R Caputo, L Berencsi, K von Franzke, P Taylor, DD Marincola, FM Meropol, NJ Sigurdson, E Miller, E Herlyn, D AF Swoboda, Rolf K. Somasundaram, Rajasekharan Caputo, Laura Berencsi, Klara von Franzke, Paul Taylor, Douglas D. Marincola, Francesco M. Meropol, Neal J. Sigurdson, Elin Miller, Eric Herlyn, Dorothee TI Nucleophosmin is recognized by a cytotoxic T cell line derived from a rectal carcinoma patient SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colorectal carcinoma patients; cytotoxic T cells; antigens; tumor immunity ID MALIGNANT-MELANOMA; COLORECTAL-CANCER; LYMPHOCYTE CLONE; COLON-CANCER; TUMOR-CELLS; EXPRESSION; GENES; NPM; IDENTIFICATION; PROLIFERATION AB Immunotherapy of colorectal carcinoma (CRC) has great promise as the presence of T lymphocytes in CRC tissues in situ is correlated with reduced recurrence and increased survival. Thus, identification of the antigens recognized by T cells of CRC patients may permit development of vaccines with potential benefit for these patients. Using expression cloning, we identified the antigen, nucleophosmin (Npm), recognized by an HLA-A1 restricted cytotoxic T lymphocyte (CTL) line derived from the peripheral blood mononuclear cells (PBMC) of a rectal cancer patient. A decamer peptide derived from the Npm sequence sensitized peptide-pulsed HLA-A1 positive cells to lysis by the CTL line. The peptide also induced proliferative and cytotoxic T lymphocytes in the PBMC of 4 of 6 CRC patients, which lysed HLA-A1 positive peptide-pulsed target cells and CRC cells endogenously expressing Npm. Overexpression of Npm by tumors of various histological types, recognition of the antigen by T cells derived from different CRC patients and association of the antigen with poor prognostic outcome make it a promising target for immunotherapeutic intervention in cancer patients. C1 [Swoboda, Rolf K.; Somasundaram, Rajasekharan; Caputo, Laura; Berencsi, Klara; von Franzke, Paul; Herlyn, Dorothee] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. [Taylor, Douglas D.] Univ Louisville, Dept Obstet Gynecol & Womens Hlth, Louisville, KY 40292 USA. [Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus, Bethesda, MD 20892 USA. [Meropol, Neal J.] Univ Hosp Case Med Ctr, Div Hematol Oncol, Cleveland, OH USA. [Sigurdson, Elin] Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. [Miller, Eric] Virtua Mem Hosp, Mt Holly, NJ USA. RP Herlyn, D (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM dherlyn@wistar.org FU NIH [CA74294, CA10815]; Pennsylvania Department of Health; National Cancer Institute [CA98166]; Kentucky Science and Technology Corporation FX Grant sponsors: NIH; Grant numbers: CA74294, CA10815; Grant sponsor: Pennsylvania Department of Health (Commonwealth Universal Research Enhancement Program), National Cancer Institute; Grant number: CA98166; Grant sponsor: Kentucky Science and Technology Corporation NR 29 TC 4 Z9 4 U1 0 U2 0 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 SEP 1 PY 2010 VL 127 IS 5 BP 1124 EP 1130 DI 10.1002/ijc.25133 PG 7 WC Oncology SC Oncology GA 635KK UT WOS:000280653800013 PM 20027629 ER PT J AU Ebbesson, SOE Tejero, ME Lopez-Alvarenga, JC Harris, WS Ebbesson, LOE Devereux, RB MacCluer, JW Wenger, C Laston, S Fabsitz, RR Howard, BV Comuzzie, AG AF Ebbesson, Sven O. E. Tejero, M. Elizabeth Lopez-Alvarenga, Juan Carlos Harris, William S. Ebbesson, Lars O. E. Devereux, Richard B. MacCluer, Jean W. Wenger, Charlotte Laston, Sandra Fabsitz, Richard R. Howard, Barbara V. Comuzzie, Anthony G. TI Individual saturated fatty acids are associated with different components of insulin resistance and glucose metabolism: the GOCADAN study SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article DE myristic acid; palmitic acid; stearic acid; Inuit; Alaska Natives; diabetes; saturated fat ID DIABETES-MELLITUS; ALASKA NATIVES; ESKIMO; SENSITIVITY; OMEGA-3-FATTY-ACIDS; PREVENTION; TOLERANCE; DISEASE AB Objectives. Type 2 diabetes and the consumption of saturated fatty acids (FAs) are on the rise among Alaska Inuits. This analysis, based on a cross-sectional study, explores the possible associations of saturated FA content in red blood cells (RBCs) and parameters of glucose metabolism in a sample of Alaska Natives. Study design and methods. The sample included 343 women and 282 men aged 35-74. Statistical analyses explored the associations of selected RBC (myristic, palmitic and stearic acids) FAs with fasting glucose (plasma), fasting insulin (plasma), 2h glucose (2-hour glucose tolerance test), 2h insulin and homeostasis model assessment (HOMA) index. The models included sex and glucose metabolism status as fixed factors and age, body mass index (BMI), waist circumference, physical activity (METS) and FA content in RBCs as covariates. Measures of insulin, glucose and HOMA index were used as dependent variables. Results. Myristic acid was positively associated with fasting insulin (beta=0.47, p < 0.001), 2h insulin (beta=0.53, p=0.02) and HOMA index (beta=0.455, p < 0.001). Palmitic acid was associated with 2h glucose (beta=2.3x10-2, p < 0.001) and 2h insulin (beta=5.6x10-2, p=0.002) and stearic acid was associated with fasting glucose (beta=4.8x10-3, p=0.006). Conclusions. These results strongly support the hypothesis that saturated fatty acids are associated with insulin resistance and glucose intolerance and that saturated fatty acids are significant risk factors for type 2 diabetes. (Int J Circumpolar Health 2010; 69(4):344-351) C1 [Ebbesson, Sven O. E.] Norton Sound Hlth Corp, GOCADAN Dept, Nome, AK 99762 USA. [Tejero, M. Elizabeth; Lopez-Alvarenga, Juan Carlos; MacCluer, Jean W.; Wenger, Charlotte; Laston, Sandra; Comuzzie, Anthony G.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Harris, William S.] S Dakota Hlth Res Fdn, Sioux Falls, SD USA. [Ebbesson, Lars O. E.] Univ Bergen, Dept Biol, Bergen, Norway. [Devereux, Richard B.] Weill Cornell Med Coll, New York, NY USA. NHLBI, Bethesda, MD 20892 USA. [Fabsitz, Richard R.; Howard, Barbara V.] MedStar Res Inst, Hyattsville, MD USA. RP Ebbesson, SOE (reprint author), Norton Sound Hlth Corp, GOCADAN Dept, POB 966, Nome, AK 99762 USA. EM soebbesson@alaska.edu RI Ebbesson, Lars/F-9385-2011 FU National Heart Lung and Blood Institute of the National Institutes of Health, Bethesda, MD [RO1-HL64244, U01 HL082458, U01 HL082490, MI 0RR0047-34]; Research Resources of the National Institutes of Health, Bethesda, MD [CO06-RR013556, C06-RR017515] FX The authors are grateful to the Norton Sound Health Corporation (NSHC) and the participants of villages participating in this study. The study was approved by the Research Ethics Review Board of the NSHC, the Institutional Review Boards of MedStar Research Institute and the University of Texas Health Science Center, San Antonio. The study was funded by grants RO1-HL64244, U01 HL082458, U01 HL082490, and MI 0RR0047-34 (GCRC) from National Heart Lung and Blood Institute of the National Institutes of Health, Bethesda, MD. Work at the Southwest Foundation for Biomedical Research was conducted in facilities provided in part by grants CO06-RR013556 and C06-RR017515 from Research Resources of the National Institutes of Health, Bethesda, MD. NR 26 TC 23 Z9 24 U1 0 U2 3 PU INT ASSOC CIRCUMPOLAR HEALTH PUBL PI OULU PA AAPISTIE1, OULU, FIN-90220, FINLAND SN 1239-9736 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PD SEP PY 2010 VL 69 IS 4 BP 344 EP 351 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 674AL UT WOS:000283705400005 PM 20719107 ER PT J AU Black, D Riskind, JH Kleiman, EM AF Black, David Riskind, John H. Kleiman, Evan M. TI Lifetime History of Anxiety and Mood Disorders Predicted by Cognitive Vulnerability to Anxiety SO INTERNATIONAL JOURNAL OF COGNITIVE THERAPY LA English DT Article ID LOOMING MALADAPTIVE STYLE; SENSITIVITY; DEPRESSION; SELF; INVENTORY; DIMENSIONS; DEPLETION; COMORBIDITY; VALIDATION; RESOURCE AB A retrospective behavioral high-risk design with used to test hypotheses about cognitive vulnerability to anxiety with college students who were free of current anxiety or mood disorders. Cognitive risk groups were selected on the basis of two currently studied factors that have conceptualized as cognitive vulnerabilities, looming cognitive style (LCS; Riskind et al., 2000) and anxiety sensitivity (ASI; Reiss & McNally, 1985). Consistent with cognitive vulnerability hypotheses, participants at high cognitive risk had far higher lifetime prevalence (approximately 65%) of anxiety disorders than participants at low cognitive risk (approximately 8%) and were approximately 11 times more likely to have a prior anxiety disorder. When LCS and ASI were looked at separately as risk group factors they had no significant effect on anxiety disorders. Secondary analyses were also done on the whole sample using data from the full continuum of scores. Total cognitive risk on these continuous data no effect on anxiety disorders in general but had a small significant effect on social anxiety disorder. When LCS and ASI were looked at separately as continuous scores, the only finding to emerge was that LCS but not ASI had a significant but small effect on past prevalence of anxiety disorders. Consistent with cognitive specificity predictions, no effects similar to those on lifetime anxiety disorders were found for mood disorders. C1 [Riskind, John H.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Black, David] NIMH, Bethesda, MD 20892 USA. RP Riskind, JH (reprint author), George Mason Univ, Dept Psychol, Mail Stop 3F5, Fairfax, VA 22030 USA. EM jriskind@gmu.edu OI Kleiman, Evan/0000-0001-8002-1167 NR 36 TC 7 Z9 7 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 1937-1209 J9 INT J COGN THER JI Int. J. Cogn. Ther. PD SEP PY 2010 VL 3 IS 3 BP 215 EP 227 PG 13 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 654II UT WOS:000282161300003 ER PT J AU Jehan, I Zaidi, S Rizvi, S Mobeen, N McClure, EM Munoz, B Pasha, O Wright, LL Goldenberg, RL AF Jehan, Imtiaz Zaidi, Shahida Rizvi, Sameera Mobeen, Naushaba McClure, Elizabeth M. Munoz, Breda Pasha, Omrana Wright, Linda L. Goldenberg, Robert L. TI Dating gestational age by last menstrual period, symphysis-fundal height, and ultrasound in urban Pakistan SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Gestational age; Last menstrual period; Pakistan; Symphysis-fundal height; Ultrasound ID GROWTH-RETARDATION; PREGNANCY; WOMEN; GRAVIDOGRAM; LENGTH AB Objective: To compare the accuracy of the reported date of the last menstrual period (LMP) with that of symphysis-fundal height (SFH) in the estimation of gestational age (GA), using an ultrasound (US) scan as reference. Methods: Gestational age was concurrently assessed by the 3 methods in this prospective, population-based, pregnancy-outcome study conducted in Hyderabad, Pakistan, from June 18. 2003, through August 31, 2005, with 1128 women between 20 and 26 weeks of a singleton pregnancy. Results: The mean GA was less by ultrasound than by SFH measurement or the reported LMP, and the mean differences with the US result were statistically significant (P<0.001 for both). At delivery, about 75% of the GA values estimated by SFH measurement were within 7 days and almost 91% were within 14 days of the estimation by ultrasound, compared with 65% and 82% for the GA estimated by the reported LMP. Moreover, using the US as reference, the SFH correctly classified 84% of the term, 68% of the preterm, and 86% of the post-term deliveries (weighted kappa=0.58) compared with the corresponding 79%, 61%, and 55% predicted by the reported LMP (Weighted kappa=0.44). Conclusion: The SFH measurement was found to be more accurate than the reported LMP as a tool to estimate GA and therefore date of delivery, but neither were as accurate as a US scan. (C) 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Jehan, Imtiaz] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan. [McClure, Elizabeth M.; Munoz, Breda] Res Triangle Inst, Durham, NC USA. [Wright, Linda L.] NICHHD, Bethesda, MD 20892 USA. [Goldenberg, Robert L.] Drexel Univ, Philadelphia, PA 19104 USA. RP Jehan, I (reprint author), Aga Khan Univ, Dept Community Hlth Sci, Stadium Rd,POB 3500, Karachi, Pakistan. EM Imtiaz.jehan@aku.edu FU Global Network for Women's and Children's Health Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; Bill and Melinda Gates Foundation FX This study was supported by grants from the Global Network for Women's and Children's Health Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and from the Bill and Melinda Gates Foundation. NR 25 TC 19 Z9 20 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD SEP PY 2010 VL 110 IS 3 BP 231 EP 234 DI 10.1016/j.ijgo.2010.03.030 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 643AV UT WOS:000281265500013 PM 20537328 ER PT J AU Beydoun, HA Dail, J Ugwu, B Boueiz, A Beydoun, MA AF Beydoun, Hind A. Dail, Jessica Ugwu, Bethrand Boueiz, Adel Beydoun, May A. TI Socio-demographic and behavioral correlates of herpes simplex virus type 1 and 2 infections and co-infections among adults in the USA SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE Epidemiology; Infection; Herpes simplex virus; Prevalence; Sexually transmitted diseases ID SEXUALLY-TRANSMITTED-DISEASE; RISK-FACTORS; UNITED-STATES; PREGNANT-WOMEN; SENSATION SEEKING; GENITAL HERPES; ALCOHOL-USE; DRUG-USERS; PREVALENCE; HIV AB Objectives: Although herpes simplex virus (HSV)-1 and HSV-2 may co-exist and interact, some epidemiologic features including geographical distribution, secular trends, route of transmission, and established risk factors may distinguish these HSV sub-types. With recent data indicating a link between genital herpes and either strain, a re-evaluation of risk factors for HSV-1/HSV-2 infection and co-infection is needed. Methods: We used the 1999-2004 National Health and Nutrition Examination Study (NHANES) data and logistic regression modeling to identify socio-demographic and behavioral risk factors that can independently predict HSV-1/HSV-2 infection and co-infection. Results: Approximately 48% were positive for HSV-1 alone, 7% were positive for HSV-2 alone and 12% were co-infected with HSV-1 and HSV-2. History of genital herpes was found in individuals infected with either or both HSV sub-types. Whereas age, sex, race, and level of education independently predicted all three outcomes, lifetime sexual activity as well as use of tobacco products and recreational drugs mainly correlated with HSV-2 infection and HSV-1/HSV-2 co-infection. Lifetime use of alcohol was not consistently associated with HSV-1/HSV-2 infection and co-infection. Conclusions: Sexual activity played an important role for HSV-2 and was potentially important for HSV-1, with implications for healthcare practice and vaccine development. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Beydoun, Hind A.; Dail, Jessica; Ugwu, Bethrand] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Boueiz, Adel] Johns Hopkins Univ, Dept Internal Med, Baltimore, MD USA. [Beydoun, May A.] Natl Inst Aging Intramural Res Program, Baltimore, MD USA. RP Beydoun, HA (reprint author), Eastern Virginia Med Sch, Grad Program Publ Hlth, 700 W Olney Rd,POB 1980, Norfolk, VA 23501 USA. EM baydouha@evms.edu FU NIH, National Institute on Aging FX No funding was provided for this project. However, this research was supported in part by the intramural research program of the NIH, National Institute on Aging. We would like to thank the Brickell Library at Eastern Virginia Medical School for providing access to peer-reviewed journals. NR 41 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD SEP PY 2010 VL 14 SU 3 BP E154 EP E160 DI 10.1016/j.ijid.2009.12.007 PG 7 WC Infectious Diseases SC Infectious Diseases GA 660LA UT WOS:000282643000031 PM 20418142 ER PT J AU Mussi-Pinhata, MM Motta, F Freimanis-Hance, L de Souza, R Szyld, E Succi, RCM Christie, CDC Rolon, MJ Ceriotto, M Read, JS AF Mussi-Pinhata, Marisa M. Motta, Fabrizio Freimanis-Hance, Laura de Souza, Ricardo Szyld, Edgardo Succi, Regina C. M. Christie, Celia D. C. Rolon, Maria J. Ceriotto, Mariana Read, Jennifer S. TI Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE HIV-exposed; Infancy; Infections; Latin America ID SYNCYTIAL VIRUS; IMMUNE-RESPONSES; PREGNANT-WOMEN; LATIN-AMERICAN; BIRTH COHORT; RISK-FACTORS; HIV; CHILDREN; MORBIDITY; MOTHERS AB Objectives: To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants. Methods: HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight >2500 g were followed from birth until 6 months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed. Results: Of 547 infants, 103 (18.8%) experienced 116 episodes of LRTI (incidence = 0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. The odds of LRTI in infants whose mothers had CD4% <14 at enrollment were 4.4 times those of infants whose mothers had CD4% >= 29 (p = 0.003). The odds of LRTI in infants with a CD4+ count (cells/ mm(3)) <750 at hospital discharge were 16.0 times those of infants with CD4+ >= 750 (p = 0.002). Maternal CD4+ decline and infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before 6 months of age. Conclusions: Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged 6 months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed. (C) 2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. C1 [Mussi-Pinhata, Marisa M.; Motta, Fabrizio] Univ Sao Paulo, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, Brazil. [Freimanis-Hance, Laura] WESTAT Corp, Rockville, MD 20850 USA. [de Souza, Ricardo] Univ Caxias Sul, Rio Grande Do Sul, Brazil. [Szyld, Edgardo] Hosp Diego Paroissien, Buenos Aires, DF, Argentina. [Succi, Regina C. M.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Christie, Celia D. C.] Univ W Indies, Kingston 7, Jamaica. [Rolon, Maria J.] Hosp Juan Fernandez, Buenos Aires, DF, Argentina. [Ceriotto, Mariana] Hosp Agudos Dra Cecilia Grierson, Buenos Aires, DF, Argentina. [Read, Jennifer S.] NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH,DHHS, Bethesda, MD USA. RP Mussi-Pinhata, MM (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM mmmpinha@fmrp.usp.br RI Mussi-Pinhata, Marisa/G-6568-2012; Inca, Inct/K-2204-2013 FU NICHD [N01-HD-3-3345, HHSN267200800001C, N01-DK-8-0001] FX This study was supported financially by NICHD Contract No. N01-HD-3-3345 and No. HHSN267200800001C (NICHD Control No. N01-DK-8-0001). NR 30 TC 19 Z9 19 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD SEP PY 2010 VL 14 SU 3 BP E176 EP E182 DI 10.1016/j.ijid.2010.01.006 PG 7 WC Infectious Diseases SC Infectious Diseases GA 660LA UT WOS:000282643000035 PM 20452798 ER PT J AU Moya, PR Murphy, DL McMahon, FJ Wendland, JR AF Moya, Pablo R. Murphy, Dennis L. McMahon, Francis J. Wendland, Jens R. TI Increased gene expression of diacylglycerol kinase eta in bipolar disorder SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID GENOME-WIDE ASSOCIATION C1 [Wendland, Jens R.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bethesda, MD 20892 USA. [Moya, Pablo R.; Murphy, Dennis L.; Wendland, Jens R.] NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Wendland, JR (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bldg 35,Room 1A207, Bethesda, MD 20892 USA. EM wendlandj@mail.nih.gov RI Wendland, Jens/A-1809-2012; OI McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS [ZIA MH000336-30] NR 10 TC 16 Z9 16 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1461-1457 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD SEP PY 2010 VL 13 IS 8 SI SI BP 1127 EP 1128 DI 10.1017/S1461145710000593 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 651HS UT WOS:000281919200013 PM 20519059 ER PT J AU Hsu, JCF Yamada, KM AF Hsu, Jeff Chi-Feng Yamada, Kenneth M. TI Salivary Gland Branching Morphogenesis - Recent Progress and Future Opportunities SO INTERNATIONAL JOURNAL OF ORAL SCIENCE LA English DT Review DE salivary gland; epithelium; branching morphogenesis; fibronectin; E-cadherin; growth factor ID MOUSE SUBMANDIBULAR-GLAND; GROWTH-FACTOR RECEPTOR; EPITHELIAL MORPHOGENESIS; E-CADHERIN; GENE-EXPRESSION; CLEFT FORMATION; IN-VITRO; EGF; CELL; TISSUE AB Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process. C1 [Hsu, Jeff Chi-Feng; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, NIH, Lab Cell & Dev Biol, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Lab Cell & Dev Biol, Bldg 30,Room 426,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM kenneth.yamada@nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU National Institute of Dental and Craniofacial Research, NIH FX Supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research, NIH. NR 49 TC 22 Z9 22 U1 0 U2 2 PU SICHUAN UNIV PI CHENGDU PA SICHUAN UNIV, CHENGDU, SICHUAN, 610064 00000, PEOPLES R CHINA SN 1674-2818 J9 INT J ORAL SCI JI Int. J. Oral Sci. PD SEP PY 2010 VL 2 IS 3 BP 117 EP 126 DI 10.4248/IJOS10042 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 662HQ UT WOS:000282798700001 PM 21125789 ER PT J AU Mettu, P Agron, E Samtani, S Chew, EY Wong, WT AF Mettu, Pradeep Agron, Elvira Samtani, Sonia Chew, Emily Y. Wong, Wai T. TI Genotype-Phenotype Correlation in Ocular von Hippel-Lindau (VHL) Disease: The Effect of Missense Mutation Position on Ocular VHL Phenotype SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; GERMLINE MUTATIONS; CAPILLARY HEMANGIOMAS; ELONGIN-C; PROTEIN; CANCER; BINDING; HEMANGIOBLASTOMAS; IDENTIFICATION AB PURPOSE. von Hippel-Lindau (VHL) disease is a dominantly inherited, multisystemic tumor syndrome caused by mutations in the VHL gene. This study was conducted to establish genotype-phenotype correlations between the positions of disease-causing missense mutations and the ocular phenotypes of VHL disease. METHODS. Participants with clinically defined VHL disease and documented germline missense mutations in the VHL gene were identified in a cross-sectional study (n = 412). Statistical analysis was used to correlate the position of the missense mutation in either the alpha- or beta-domain of the VHL protein with the ocular disease phenotype. RESULTS. Missense mutations among study participants were located in 47 of the 213 possible codons in the VHL gene. Almost all mutations (98.5%) were located in one of two structural domains of the VHL protein: the alpha- and beta-domains. alpha-Domain mutations were significantly associated with a higher prevalence of retinal capillary hemangioblastomas (RCHs) compared with the beta-domain mutations (P = 0.016). Among patients with RCHs, the prevalence of the lesions in the juxtapapillary position was also significantly higher in patients with beta-domain mutations (P = 0.0017). Conversely, beta-domain mutations correlated with a higher prevalence of peripherally located RCHs (P = 0.0104). CONCLUSIONS. The location of missense mutations in the VHL gene correlates significantly with the prevalence and phenotype of ocular disease, and as such, influences the risk of visual loss in affected patients. These genotype-phenotype correlations can assist in the prognostic counseling and follow-up of VHL patients and may provide a basis for molecular inferences on ocular VHL disease pathogenesis. (Invest Ophthalmol Vis Sci. 2010;51:4464-4470) DOI:10.1167/iovs.10-5223 C1 [Mettu, Pradeep; Samtani, Sonia; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, Off Sci Director, NIH, Bethesda, MD 20892 USA. [Mettu, Pradeep; Agron, Elvira; Chew, Emily Y.] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, Off Sci Director, NIH, 7 Mem Dr,Room 217, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU NEI; NIH; Pfizer, Inc. FX Supported by the NEI Intramural Research Program. PM is supported by the Clinical Research Training Program, a public-private partnership supported jointly by the NIH and Pfizer, Inc. NR 39 TC 13 Z9 15 U1 0 U2 0 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 SEP PY 2010 VL 51 IS 9 BP 4464 EP 4470 DI 10.1167/iovs.10-5223 PG 7 WC Ophthalmology SC Ophthalmology GA 645YS UT WOS:000281502700016 PM 20375333 ER PT J AU Meade, CS Weiss, RD Fitzmaurice, GM Poole, SA Subramaniam, GA Patkar, AA Connery, HS Woody, GE AF Meade, Christina S. Weiss, Roger D. Fitzmaurice, Garrett M. Poole, Sabrina A. Subramaniam, Geetha A. Patkar, Ashwin A. Connery, Hilary S. Woody, George E. TI HIV Risk Behavior in Treatment-Seeking Opioid-Dependent Youth: Results From a NIDA Clinical Trials Network Multisite Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE buprenorphine treatment; gender differences; HIV risk; injection drug use; opioid dependence; youth ID INJECTION-DRUG USERS; GENDER-DIFFERENCES; BUPRENORPHINE-NALOXONE; SEXUAL-BEHAVIORS; RANDOMIZED-TRIAL; PREVENTION INTERVENTIONS; MAINTENANCE TREATMENT; SENSATION-SEEKING; HEROIN DEPENDENCE; ADOLESCENT BRAIN AB Objective: To assess baseline rates of and changes in HIV drug and sexual risk behavior as a function of gender and treatment in opioid-dependent youth. Methods: One hundred fifty participants were randomly assigned to extended buprenorphine/naloxone therapy (BUP) for 12 weeks or detoxification for 2 weeks; all received drug counseling for 12 weeks. HIV risk was assessed at baseline and 4-week, 8-week, and 12-week follow-ups. Behavioral change was examined using generalized estimating equations. Results: Baseline rates of past-month HIV risk for females/males were 51%/45% for injection drug use (IDU) (ns), 77%/35% for injection risk (P < 0.001), 82%/74% for sexual activity (ns), 14%/24% for multiple partners (ns), and 68%/65% for unprotected intercourse (ns). IDU decreased over time (P < 0.001), with greater decreases in BUP versus detoxification (P < 0.001) and females versus males in BUP (P < 0.05). Injection risk did not change for persistent injectors. Sexual activity decreased in both genders and conditions (P < 0.01), but sexual risk did not. Conclusions: Overall, IDU and sexual activity decreased markedly, particularly in BUP patients and females, but injection and sexual risk behaviors persisted. Although extended BUP seems to have favorable effects on HIV risk behavior in opioid-dependent youth, risk reduction counseling may be necessary to extend its benefits. C1 [Meade, Christina S.; Patkar, Ashwin A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Weiss, Roger D.; Fitzmaurice, Garrett M.; Connery, Hilary S.] Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. [Weiss, Roger D.; Fitzmaurice, Garrett M.; Connery, Hilary S.] McLean Hosp, Belmont, MA 02178 USA. [Poole, Sabrina A.; Woody, George E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Poole, Sabrina A.; Woody, George E.] Treatment Res Inst, Philadelphia, PA USA. [Subramaniam, Geetha A.] NIDA, Div Clin Neurosci & Behav Res, Bethesda, MD 20892 USA. RP Meade, CS (reprint author), Duke Global Hlth Inst, Box 90519, Durham, NC 27708 USA. EM christina.meade@duke.edu FU National Institutes of Health [P30-AI064518, U10-DA013711, K05-DA017009, U10-DA013043, K24-DA022288, U10-DA015831, U10-013034, K12-DA000357, U10-DA015833] FX Supported by the following grants from the National Institutes of Health: P30-AI064518 (Weinhold) and U10-DA013711 (Hubbard) to Duke University, K05-DA017009 (Woody) and U10-DA013043 (Woody) to University of Pennsylvania, K24-DA022288 (Weiss) and U10-DA015831 (Weiss) to Harvard University, U10-013034 (Stitzer) and K12-DA000357 (Riggs) to Johns Hopkins University, and U10-DA015833 (Miller) to University of New Mexico. NR 68 TC 12 Z9 13 U1 0 U2 1 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 SEP 1 PY 2010 VL 55 IS 1 BP 65 EP 72 DI 10.1097/QAI.0b013e3181d916db PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 641YY UT WOS:000281170500008 PM 20393347 ER PT J AU Moster, D Wilcox, AJ Vollset, SE Markestad, T Lie, RT AF Moster, Dag Wilcox, Allen J. Vollset, Stein Emil Markestad, Trond Lie, Rolv Terje TI Cerebral Palsy Among Term and Postterm Births SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GESTATIONAL-AGE; EPIDEMIOLOGIC RESEARCH; PERINATAL FACTORS; PRETERM BIRTH; ANTECEDENTS; OUTCOMES; CHILDREN; COMPLICATIONS; PREVALENCE; INFANTS AB Context Although preterm delivery is a well-established risk factor for cerebral palsy (CP), preterm deliveries contribute only a minority of affected infants. There is little information on the relation of CP risk to gestational age in the term range, where most CP occurs. Objective To determine whether timing of birth in the term and postterm period is associated with risk of CP. Design, Setting, and Participants Population-based follow-up study using the Medical Birth Registry of Norway to identify 1 682 441 singleton children born in the years 1967-2001 with a gestational age of 37 through 44 weeks and no congenital anomalies. The cohort was followed up through 2005 by linkage to other national registries. Main Outcome Measures Absolute and relative risk of CP for children surviving to at least 4 years of age. Results Of the cohort of term and postterm children, 1938 were registered with CP in the National Insurance Scheme. Infants born at 40 weeks had the lowest risk of CP, with a prevalence of 0.99/1000 (95% confidence interval [CI], 0.90-1.08). Risk for CP was higher with earlier or later delivery, with a prevalence at 37 weeks of 1.91/1000 (95% CI, 1.58-2.25) and a relative risk (RR) of 1.9 (95% CI, 1.6-2.4), a prevalence at 38 weeks of 1.25/1000 (95% CI, 1.07-1.42) and an RR of 1.3 (95% CI, 1.1-1.6), a prevalence at 42 weeks of 1.36/1000 (95% CI, 1.19-1.53) and an RR of 1.4 (95% CI, 1.2-1.6), and a prevalence after 42 weeks of 1.44 (95% CI, 1.15-1.72) and an RR of 1.4 (95% CI, 1.1-1.8). These associations were even stronger in a subset with gestational age based on ultrasound measurements: at 37 weeks the prevalence was 1.17/1000 (95% CI, 0.30-2.04) and the relative risk was 3.7 (95% CI, 1.5-9.1). At 42 weeks the prevalence was 0.85/1000 (95% CI, 0.33-1.38) and the relative risk was 2.4 (95% CI, 1.1-5.3). Adjustment for infant sex, maternal age, and various socioeconomic measures had little effect. Conclusion Compared with delivery at 40 weeks' gestation, delivery at 37 or 38 weeks or at 42 weeks or later was associated with an increased risk of CP. JAMA. 2010; 304(9): 976-982 www.jama.com C1 [Moster, Dag; Vollset, Stein Emil; Lie, Rolv Terje] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, N-5020 Bergen, Norway. [Markestad, Trond] Univ Bergen, Dept Clin Med, Sect Pediat, N-5020 Bergen, Norway. [Moster, Dag; Markestad, Trond] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway. [Wilcox, Allen J.] NIEHS, Epidemiol Branch, NIH, Durham, NC USA. [Vollset, Stein Emil; Lie, Rolv Terje] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. RP Moster, D (reprint author), Univ Bergen, Dept Publ Hlth & Primary Hlth Care, POB 7804, N-5020 Bergen, Norway. EM Dag.Moster@smis.uib.no OI Wilcox, Allen/0000-0002-3376-1311 FU National Institutes of Health, National Institute of Environmental Health Sciences; Unger-Vetlesen Charitable Fund; US-Norway Fulbright Foundation; Norwegian Society of Pediatricians; University of Bergen; Research Council of Norway FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences; the Unger-Vetlesen Charitable Fund; The US-Norway Fulbright Foundation; the Norwegian Society of Pediatricians; the University of Bergen; and the Research Council of Norway. NR 39 TC 48 Z9 48 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 1 PY 2010 VL 304 IS 9 BP 976 EP 982 DI 10.1001/jama.2010.1271 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 645AD UT WOS:000281422400023 PM 20810375 ER PT J AU Hertzano, R Puligilla, C Chan, SL Timothy, C Depireux, DA Ahmed, Z Wolf, J Eisenman, DJ Friedman, TB Riazuddin, S Kelley, MW Strome, SE AF Hertzano, Ronna Puligilla, Chandrakala Chan, Siaw-Lin Timothy, Caroline Depireux, Didier A. Ahmed, Zubair Wolf, Jeffrey Eisenman, David J. Friedman, Thomas B. Riazuddin, Sheikh Kelley, Matthew W. Strome, Scott E. TI CD44 is a Marker for the Outer Pillar Cells in the Early Postnatal Mouse Inner Ear SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE CD44; FGFR3; cochlea; outer pillar cells; deafness ID HEARING-LOSS; HAIR-CELLS; EXPRESSION; GENE; ORGAN; CORTI; COCHLEA; DIFFERENTIATION; EPITHELIA; DEAFNESS AB Cluster of differentiation antigens (CD proteins) are classically used as immune cell markers. However, their expression within the inner ear is still largely undefined. In this study, we explored the possibility that specific CD proteins might be useful for defining inner ear cell populations. mRNA expression profiling of microdissected auditory and vestibular sensory epithelia revealed 107 CD genes as expressed in the early postnatal mouse inner ear. The expression of 68 CD genes was validated with real-time RT-PCR using RNA extracted from microdissected sensory epithelia of cochleae, utricles, saccules, and cristae of newborn mice. Specifically, CD44 was identified as preferentially expressed in the auditory sensory epithelium. Immunohistochemistry revealed that within the early postnatal organ of Corti, the expression of CD44 is restricted to outer pillar cells. In order to confirm and expand this finding, we characterized the expression of CD44 in two different strains of mice with loss- and gain-of-function mutations in Fgfr3 which encodes a receptor for FGF8 that is essential for pillar cell development. We found that the expression of CD44 is abolished from the immature pillar cells in homozygous Fgfr3 knockout mice. In contrast, both the outer pillar cells and the aberrant Deiters' cells in the Fgfr3 (P244R/) (+) mice express CD44. The deafness phenotype segregating in DFNB51 families maps to a linkage interval that includes CD44. To study the potential role of CD44 in hearing, we characterized the auditory system of CD44 knockout mice and sequenced the entire open reading frame of CD44 of affected members of DFNB51 families. Our results suggest that CD44 does not underlie the deafness phenotype of the DFNB51 families. Finally, our study reveals multiple potential new cell type-specific markers in the mouse inner ear and identifies a new marker for outer pillar cells. C1 [Hertzano, Ronna; Chan, Siaw-Lin; Timothy, Caroline; Wolf, Jeffrey; Eisenman, David J.; Strome, Scott E.] Univ Maryland, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. [Puligilla, Chandrakala; Kelley, Matthew W.] Natl Inst Deafness & Other Commun Disorders, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Depireux, Didier A.] Univ Maryland, Sch Engn, Syst Res Inst, College Pk, MD 20742 USA. [Ahmed, Zubair] Childrens Hosp Res Fdn, Div Pediat Ophthalmol, Cincinnati, OH 45229 USA. [Ahmed, Zubair] Univ Cincinnati, Dept Ophthalmol, Cincinnati, OH 45229 USA. [Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. [Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. RP Hertzano, R (reprint author), Univ Maryland, Dept Otorhinolaryngol Head & Neck Surg, 16 S Eutaw St,Suite 500, Baltimore, MD 21201 USA. EM rhertzano@smail.umaryland.edu FU American Academy of Otolaryngology-Head and Neck Surgery Foundation; Deafness Research Foundation; NIDCD [1-Z01-000070, 1-Z01-000039] FX We are grateful to Janice K. Babus, Yadong Ji, Amiel A. Dror and Dr. Weise Chang for technical assistance, Dr. Suzi Mansour and Chaoying Li for sending us the Fgfr3-P244R mutant mice. We thank Dr. Karen B. Avraham for sharing unpublished data, and Dr. Tomoko Makishima for critically reviewing this manuscript. Finally, we thank Dr. Strome's laboratory members for their technical help and advice. This research was supported by a resident research grant provided by the American Academy of Otolaryngology-Head and Neck Surgery Foundation (R.H.), a Deafness Research Foundation grant (R.H.) and by funds from the Intramural Program at NIDCD 1-Z01-000070 (M.W.K), and 1-Z01-000039 (T.B.F). NR 41 TC 16 Z9 16 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD SEP PY 2010 VL 11 IS 3 BP 407 EP 418 DI 10.1007/s10162-010-0211-x PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 634QO UT WOS:000280598300006 PM 20386946 ER PT J AU Jesus, AA Oliveira, JB Hilario, MOE Terreri, MTRA Fujihira, E Watase, M Carneiro-Sampaio, M Silva, CAA AF Jesus, Adriana Almeida Oliveira, Joao Bosco Esteves Hilario, Maria Odete Terreri, Maria Teresa R. A. Fujihira, Erika Watase, Mariana Carneiro-Sampaio, Magda Almeida Silva, Clovis Artur TI Pediatric hereditary autoinflammatory syndromes SO JORNAL DE PEDIATRIA LA English DT Review DE Autoinflammatory syndromes; child; familial Mediterranean fever; cryopyrinopathies; TRAPS; NOMID ID FAMILIAL MEDITERRANEAN FEVER; HYPER-IGD SYNDROME; MEVALONATE KINASE-DEFICIENCY; RECURRENT MULTIFOCAL OSTEOMYELITIS; PERIODIC SYNDROME TRAPS; MUCKLE-WELLS-SYNDROME; CONGENITAL DYSERYTHROPOIETIC ANEMIA; HYPERIMMUNOGLOBULINEMIA-D SYNDROME; NERVOUS-SYSTEM INVOLVEMENT; TNF RECEPTOR AB Objective: To describe the most prevalent pediatric hereditary autoinflammatory syndromes. Sources: A review of the literature including relevant references from the PubMed and SciELO was carried out using the keywords autoinflammatory syndromes and child. Summary of the findings: The hereditary autoinflammatory syndromes are caused by monogenic defects of innate immunity and are classified as primary immunodeficiencies. These syndromes are characterized by recurrent or persistent systemic inflammatory symptoms and must be distinguished from infectious diseases, autoimmune diseases, and other primary immunodeficiencies. This review describes the epidemiological, clinical and laboratory features, prognosis, and treatment of the main autoinflammatory syndromes, namely: familial Mediterranean fever; TNF receptor associated periodic syndrome; the cryopyrinopathies; mevalonate kinase deficiency; pediatric granulomatous arthritis; pyogenic arthritis, pyoderma gangrenosum and acne syndrome; Majeed syndrome; and deficiency of interleukin 1 receptor antagonist. The cryopyrinopathies discussed include neonatal-onset multisystem inflammatory disease (also known as chronic infantile neurologic, cutaneous and articular syndrome) Muckle-Wells syndrome, and familial cold autoinflammatory syndrome. Conclusions: Pediatricians must recognize the clinical features of the most prevalent autoinflammatory syndromes. Early referral to a pediatric rheumatologist may allow early diagnosis and institution of treatment, with improvement in the quality of life of these patients. C1 [Almeida Silva, Clovis Artur] Univ Sao Paulo, Fac Med, Hosp Clin, Inst Crianca,Unidade Reumatol Pediat,Disciplina R, BR-09500900 Sao Paulo, Brazil. [Oliveira, Joao Bosco] NIH, Human Disorders Lymphocyte Homeostasis Unit, Serv Immunol, DLM,CC, Bethesda, MD 20892 USA. [Esteves Hilario, Maria Odete; Terreri, Maria Teresa R. A.] Univ Fed Sao Paulo, Disciplina Alergia Imunol & Reumatol, Setor Reumatol Pediat, Sao Paulo, Brazil. [Fujihira, Erika; Watase, Mariana] Univ Sao Paulo, Fac Med, Dept Dermatol, Secao Genet & Imunol Mol,Lab Invest Med 56, BR-09500900 Sao Paulo, Brazil. [Carneiro-Sampaio, Magda] Univ Sao Paulo, Fac Med, Hosp Clin, Inst Crianca,Unidade Alergia & Imunol Pediat, BR-09500900 Sao Paulo, Brazil. RP Silva, CAA (reprint author), Rua Araioses 152-81, BR-05442010 Sao Paulo, Brazil. EM clovis.silva@icr.usp.br OI Oliveira, Joao/0000-0001-9388-8173 FU Sao Paulo State Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP) [0568/09]; National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq) [300248/2008-3] FX This study was supported by grants from the Sao Paulo State Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP; grant no. 0568/09; recipient, CAAS) and the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq; grant no. 300248/2008-3; recipient, CAAS). NR 129 TC 4 Z9 4 U1 0 U2 2 PU SOC BRASIL PEDIATRIA PI RIO DE JANEIRO, RJ PA RUA SANTA CLARA 292, RIO DE JANEIRO, RJ, CEP 22401-01, BRAZIL SN 0021-7557 EI 1678-4782 J9 J PEDIAT-BRAZIL JI J. Pediatr. PD SEP-OCT PY 2010 VL 86 IS 5 BP 353 EP 366 DI 10.2223/JPED.2015 PG 14 WC Pediatrics SC Pediatrics GA 680NQ UT WOS:000284241400003 PM 20938587 ER PT J AU Hernandez, ML Lay, JC Harris, B Esther, CR Brickey, WJ Bromberg, PA Diaz-Sanchez, D Devlin, RB Kleeberger, SR Alexis, NE Peden, DB AF Hernandez, Michelle L. Lay, John C. Harris, Bradford Esther, Charles R., Jr. Brickey, W. June Bromberg, Philip A. Diaz-Sanchez, David Devlin, Robert B. Kleeberger, Steven R. Alexis, Neil E. Peden, David B. TI Atopic asthmatic subjects but not atopic subjects without asthma have enhanced inflammatory response to ozone SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Ozone; innate immunity; asthma; atopy; hyaluronic acid; environmental airways disease; IL-1 beta; IL-10 ID TOLL-LIKE RECEPTOR-4; MILD ALLERGIC-ASTHMA; 0.16 PPM OZONE; AIRWAY INFLAMMATION; LUNG INJURY; HEALTHY-VOLUNTEERS; INNATE IMMUNITY; IN-VIVO; EXPOSURE; HYALURONAN AB Background: Asthma is a known risk factor for acute ozone-associated respiratory disease. Ozone causes an immediate decrease in lung function and increased airway inflammation. The role of atopy and asthma in modulation of ozone-induced inflammation has not been determined. Objective: We sought to determine whether atopic status modulates ozone response phenotypes in human subjects. Methods: Fifty volunteers (25 healthy volunteers, 14 atopic nonasthmatic subjects, and 11 atopic asthmatic subjects not requiring maintenance therapy) underwent a 0.4-ppm ozone exposure protocol. Ozone response was determined based on changes in lung function and induced sputum composition, including airway inflammatory cell concentration, cell-surface markers, and cytokine and hyaluronic acid concentrations. Results: All cohorts experienced similar decreases in lung function after ozone. Atopic and atopic asthmatic subjects had increased sputum neutrophil numbers and IL-8 levels after ozone exposure; values did not significantly change in healthy volunteers. After ozone exposure, atopic asthmatic subjects had significantly increased sputum IL-6 and IL-1 beta levels and airway macrophage Toll-like receptor 4, Fc epsilon RI, and CD23 expression; values in healthy volunteers and atopic nonasthmatic subjects showed no significant change. Atopic asthmatic subjects had significantly decreased IL-10 levels at baseline compared with healthy volunteers; IL-10 levels did not significantly change in any group with ozone. All groups had similar levels of hyaluronic acid at baseline, with increased levels after ozone exposure in atopic and atopic asthmatic subjects. Conclusion: Atopic asthmatic subjects have increased airway inflammatory responses to ozone. Increased Toll-like receptor 4 expression suggests a potential pathway through which ozone generates the inflammatory response in allergic asthmatic subjects but not in atopic subjects without asthma. (J Allergy Clin Immunol 2010;126:537-44.) C1 [Hernandez, Michelle L.; Lay, John C.; Harris, Bradford; Esther, Charles R., Jr.; Alexis, Neil E.; Peden, David B.] Univ N Carolina, Dept Pediat, Sch Med, Chapel Hill, NC 27599 USA. [Hernandez, Michelle L.; Lay, John C.; Harris, Bradford; Alexis, Neil E.; Peden, David B.] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Sch Med, Chapel Hill, NC 27599 USA. [Bromberg, Philip A.; Peden, David B.] Univ N Carolina, Dept Med, Sch Med, Chapel Hill, NC 27599 USA. [Brickey, W. June; Peden, David B.] Univ N Carolina, Dept Microbiol Immunol, Chapel Hill, NC 27599 USA. [Kleeberger, Steven R.] Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. [Diaz-Sanchez, David; Devlin, Robert B.] US EPA, Environm Publ Hlth Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. RP Hernandez, ML (reprint author), Univ N Carolina, Dept Pediat, Sch Med, 104 Mason Farm Rd,CB 7310, Chapel Hill, NC 27599 USA. EM Michelle_Hernandez@med.unc.edu RI Lay, John/A-6380-2012 FU National Institute of Environmental Health Sciences [R01ES012706, P30ES010126]; National Institute for Allergy and Infectious Diseases [U19AI077437]; National Center for Complementary and Alternative Medicine [P01AT002620]; National Institutes of Health [KL2RR025746, M01RR00046, UL1RR025747]; US Environmental Protection Agency [CR 83346301]; Center for Environmental Medicine and Lung Biology at the University of North Carolina at Chapel Hill; Environmental Protection Agency FX Supported in part by grants R01ES012706 and P30ES010126 from the National Institute of Environmental Health Sciences, U19AI077437 from the National Institute for Allergy and Infectious Diseases, P01AT002620 from the National Center for Complementary and Alternative Medicine, and KL2RR025746, M01RR00046, and UL1RR025747 from the National Center of Research Resources of the National Institutes of Health, as well as CR 83346301 from the US Environmental Protection Agency.; Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency through cooperative agreement CR 83346301 with the Center for Environmental Medicine and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the Agency's required peer and policy review and therefore does not necessarily reflect the views of the Agency, and no official endorsement should be inferred.; Disclosure of potential conflict of interest: P. A. Bromberg has received research support from the US Environmental Protection Agency. D. B. Peden is a consultant for Funxional Therapeutics and GlaxoSmithKline and has received research support from the National Institutes of Health and the Environmental Protection Agency. The rest of the authors have declared that they have no conflict of interest. NR 58 TC 39 Z9 41 U1 0 U2 3 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 SEP PY 2010 VL 126 IS 3 BP 537 EP U228 DI 10.1016/j.jaci.2010.06.043 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 646CF UT WOS:000281512500020 PM 20816188 ER PT J AU Merenstein, DJ Hu, HH Robison, E Levine, AM Greenblatt, R Schwartz, R Weber, K Young, M Sharp, G Liu, CL AF Merenstein, Daniel J. Hu, Haihong Robison, Esther Levine, Alexandra M. Greenblatt, Ruth Schwartz, Rebecca Weber, Kathleen Young, Mary Sharp, Gerald Liu, Chenglong TI Relationship Between Complementary/Alternative Treatment Use and Illicit Drug Use Among a Cohort of Women with, or at Risk for, HIV Infection SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; ALTERNATIVE MEDICINE USE; SUBSTANCE-ABUSE; AURICULAR ACUPUNCTURE; DISEASE PROGRESSION; INTERAGENCY HIV; ADHERENCE; ASSOCIATION; COCAINE AB Objectives: Two of the most pressing public health challenges in the United States are treating human immunodeficiency virus (HIV) infection and illegal substance use. High rates of complementary and alternative medicine (CAM) use have been reported by individuals who suffer from both of these diseases. The goal of this study was to examine the relationship between CAM use and illegal substance use in a cohort of women with HIV or at risk for HIV disease. Based on previous research, it was hypothesized that CAM use may decrease substance use. Design: This was a longitudinal cohort study. Subjects: The subjects comprised Women in the Women's Interagency HIV Study. Outcome measures: The role of CAM use in illegal substance use was examined. Due to the hierarchical structure of the dataset, logistic regression analysis adjusting for repeated measurements (generalized estimating equation model) was carried out to assess associations of CAM use and illicit drug use. Results: There were 2176 women included in the analysis. After excluding for marijuana use, CAM use was associated with less drug use (odds ratio 0.82; 95% confidence interval: 0.73, 0.90). Conclusions: The results supported our hypothesis that CAM users are more health conscious and thus less likely to use illicit drugs. Future studies should target both specific drugs and CAM modalities to help finalize this association. C1 [Merenstein, Daniel J.] Georgetown Univ, Med Ctr, Dept Family Med, Washington, DC 20007 USA. [Hu, Haihong; Young, Mary; Liu, Chenglong] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Robison, Esther] Montefiore Med Ctr, Dept Med, Div Gen Internal Med, Bronx, NY 10467 USA. [Levine, Alexandra M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Greenblatt, Ruth] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schwartz, Rebecca] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Weber, Kathleen] CORE Ctr John H Stroger Jr Hosp Cook Cty, Chicago, IL USA. [Sharp, Gerald] NIAID, Basic Sci Program, NIH, Bethesda, MD 20892 USA. RP Merenstein, DJ (reprint author), Georgetown Univ, Med Ctr, Dept Family Med, 417 Kober Cogan Hall 3800 Reservoir Rd NW, Washington, DC 20007 USA. EM djm23@georgetown.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]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [UL1 RR024131] FX Data in this article 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 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). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 37 TC 4 Z9 4 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2010 VL 16 IS 9 BP 989 EP 993 DI 10.1089/acm.2009.0584 PG 5 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 650TG UT WOS:000281874700012 PM 20738164 ER PT J AU Ahn, AC Nahin, RL Calabrese, C Folkman, S Kimbrough, E Shoham, J Haramati, A AF Ahn, Andrew C. Nahin, Richard L. Calabrese, Carlo Folkman, Susan Kimbrough, Elizabeth Shoham, Jacob Haramati, Aviad TI Applying Principles from Complex Systems to Studying the Efficacy of CAM Therapies SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID B-CELL LYMPHOMA; MORTALITY; SURVIVAL; DYNAMICS AB In October 2007, a National Center for Complementary and Alternative Medicine (NCCAM)-sponsored workshop, entitled "Applying Principles from Complex Systems to Studying the Efficacy of CAM Therapies,'' was held at Georgetown University in Washington, DC. Over a 2-day period, the workshop engaged a small group of experts from the fields of complementary and alternative medicine (CAM) research and complexity science to discuss and examine ways in which complexity science can be applied to CAM research. After didactic presentations and small-group discussions, a number of salient themes and ideas emerged. This paper article describes the workshop program and summarizes these emergent ideas, which are divided into five broad categories: (1) introduction to complexity; (2) challenges to CAM research; (3) applications of complexity science to CAM; (4) CAM as a model of complexity applied to medicine; and (5) future directions. This discusses possible benefits and challenges associated with applying complexity science to CAM research. By providing an introductory framework for this collaboration and exchange, it is hoped that this article may stimulate further inquiry into this largely unexplored area of research. C1 [Ahn, Andrew C.] Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02215 USA. [Ahn, Andrew C.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Nahin, Richard L.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Calabrese, Carlo] Natl Coll Nat Med, Helfgott Res Inst, Portland, OR USA. [Folkman, Susan] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Kimbrough, Elizabeth] Univ Maryland, Ctr Integrat Med, Baltimore, MD 21201 USA. [Shoham, Jacob] Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. [Haramati, Aviad] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. [Haramati, Aviad] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. RP Ahn, AC (reprint author), Harvard Univ, Sch Med, Div Res & Educ Complementary & Integrat Med Thera, 401 Pk Dr Suite 22A W, Boston, MA 02215 USA. EM aahn@hms.harvard.edu OI Nahin, Richard/0000-0002-3682-4816 FU National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health [R25-AT00419]; Institute for Integrative Health FX Support for convening the 21/2-dayworkshop was provided by a grant (R25-AT00419) from the National Center for Complementary and Alternative Medicine (NCCAM) at the National Institutes of Health, funds from the Institute for Integrative Health, a nonprofit organization located in Baltimore, MD, that aims to catalyze innovative ideas in health care, and Georgetown University School of Medicine, in Washington, DC. NR 17 TC 8 Z9 8 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD SEP PY 2010 VL 16 IS 9 BP 1015 EP 1022 DI 10.1089/acm.2009.0593 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 650TG UT WOS:000281874700017 PM 20715978 ER PT J AU Hild, SA Attardi, BJ Koduri, S Till, BA Reel, JR AF Hild, Sheri Ann Attardi, Barbara J. Koduri, Sailaja Till, Bruce A. Reel, Jerry R. TI Effects of Synthetic Androgens on Liver Function Using the Rabbit as a Model SO JOURNAL OF ANDROLOGY LA English DT Article DE Dimethandrolone-17 beta-undecanoate,11 beta-methyl-19-nortestosterone-17 beta-dodecylcarbonate; bromsulfonphthalein; hepatotoxicity ID PERFUSED-RAT-LIVER; GLUTAMIC PYRUVIC TRANSAMINASE; ORALLY-ACTIVE ANDROGEN; SORBITOL DEHYDROGENASE; ANABOLIC-STEROIDS; HEPATIC DISEASE; HEPATOTOXICITY; BROMOSULFOPHTHALEIN; TOXICITY; METHYLTESTOSTERONE AB The objective of this study was to determine whether the rabbit was a suitable model to test new synthetic androgens for potential liver toxicity within a short dosing interval. Adult male rabbits were dosed orally daily on days 0-13 with 17 alpha-methyltes-tosterone (MT) as a positive control and testosterone (T) as a negative control to validate this model. Synthetic androgens tested were: 7 alpha-methyl-19-nortestosterone (MENT), dimethandrolone-un-decanote (DMAU), and 11 beta-methyl-19-nortestosterone-17 beta-dodecylcarbonate (11 beta-MNTDC). Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and sorbitol dehydrogenase (SDH), as well as clearance of intravenous injected bromsulfonphthalein (BSP) from serum on days 0, 7, and 14, were determined. As expected, T (10 mg/kg/d) did not adversely affect BSP retention or serum liver enzymes. MT (10 mg/kg/d) increased BSP retention, and AST, ALT, GGT, and SDH levels, indicating that this model could detect androgens known to be hepatotoxic. DMAU and MENT (10 mg/kg/d) increased BSP retention and all 4 serum liver enzymes as well, but the effects were less than those observed with MT at the same dose. All parameters returned to baseline 2 weeks after cessation of dosing. 11 beta-MNTDC at 10 mg/kg/d did not have an effect on BSP retention or liver enzymes, but a slight increase in serum GGT levels was observed in rabbits treated with 25 mg/kg/d. For the androgens that exhibited liver toxicity at 10 mg/kg/d (MT, DMAU, and MENT), a no-observed-effect level of 1 mg/kg/d was established. Overall ranking of the synthetic androgens from most to least hepatotoxic on the basis of percent BSP retention was: MT >> MAU > MENT > 11 beta-MNTDC. Hence, the rabbit appears to be a promising model for detection of potential liver toxicity by synthetic androgens using BSP clearance and serum liver enzyme levels as early indicators of injury. C1 [Hild, Sheri Ann; Attardi, Barbara J.; Koduri, Sailaja; Till, Bruce A.; Reel, Jerry R.] BIOQUAL Inc, Div Reprod Endocrinol & Toxicol, Rockville, MD USA. RP Hild, SA (reprint author), NIH, Off Review, Natl Ctr Res Resources, 6701 Democracy Blvd,Room 1082, Bethesda, MD 20892 USA. EM hildsa@mail.nih.gov FU National Institute of Child Health and Human Development [NO1-HD-2-3338] FX This work was supported by the National Institute of Child Health and Human Development contract NO1-HD-2-3338 awarded to BIOQUAL Inc. NR 38 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD SEP-OCT PY 2010 VL 31 IS 5 BP 472 EP 481 DI 10.2164/jandrol.109.009365 PG 10 WC Andrology SC Endocrinology & Metabolism GA 676ER UT WOS:000283893400008 PM 20378929 ER PT J AU Visness, CM London, SJ Daniels, JL Kaufman, JS Yeatts, KB Siega-Riz, AM Calatroni, A Zeldin, DC AF Visness, Cynthia M. London, Stephanie J. Daniels, Julie L. Kaufman, Jay S. Yeatts, Karin B. Siega-Riz, Anna-Maria Calatroni, Agustin Zeldin, Darryl C. TI Association of Childhood Obesity With Atopic and Nonatopic Asthma: Results From the National Health and Nutrition Examination Survey 1999-2006 SO JOURNAL OF ASTHMA LA English DT Article DE asthma; atopy; BMI; obesity ID BODY-MASS INDEX; C-REACTIVE PROTEIN; CHILDREN; OVERWEIGHT; SEVERITY; SYMPTOMS; SAMPLE; COHORT; ADULTS; RISK AB Background. Obesity and asthma prevalence have both risen among children over the last several decades, and research efforts increasingly suggest that obesity is associated with asthma. Some, but not all, studies have shown that the effect of obesity on asthma is stronger among nonatopic individuals than among those with atopy. Systemic inflammation may be a factor in this relationship. Objective. To examine the association of obesity with atopic and nonatopic asthma among U. S. children and to assess the role of C-reactive protein. Design. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the relationship of weight to current asthma using logistic regression. Overweight was defined as >= 85th percentile of body mass index (BMI)-for-age and obesity was defined as >= 95th percentile of BMI-for-age. The presence of at least one positive allergen-specific immunoglobulin E (IgE) was used to stratify the relationship by atopic status in 2005-2006 data (n = 3387). Setting and Participants. Stratified, multistage probability sampling was used to identify survey participants. This analysis includes children ages 2-19 (n = 16,074) from the 1999-2006 NHANES who have information on BMI and current asthma. Main Outcome Measure. Self-report of doctor-diagnosed current asthma. Results. Obesity was significantly related to current asthma among children and adolescents (odds ratio [OR]: 1.68, 95% confidence interval [CI]: 1.33, 2.12). The association was stronger in nonatopic children (OR: 2.46, 95% CI: 1.21, 5.02) than in atopic children (OR: 1.34, 95% CI: 0.70, 2.57) (interaction p value = .09). C-reactive protein levels were associated with current asthma in nonatopic children, but not after adjusting for BMI. Conclusion. Excess weight in children is associated with higher rates of asthma, especially asthma that is not accompanied by allergic disease. C1 [Visness, Cynthia M.; Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA. [Visness, Cynthia M.; Daniels, Julie L.; Kaufman, Jay S.; Yeatts, Karin B.; Siega-Riz, Anna-Maria] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [London, Stephanie J.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, Res Triangle Pk, NC USA. [Kaufman, Jay S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada. RP Visness, CM (reprint author), Rho Fed Syst Div Inc, 6330 Quadrangle Dr,Suite 500, Chapel Hill, NC 27517 USA. EM cindy_visness@rhoworld.com OI Kaufman, Jay/0000-0003-1606-401X; London, Stephanie/0000-0003-4911-5290 FU National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [Z01 ES025041]; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health [N01 AI-25482] FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS), under grant number Z01 ES025041 and by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, under contract number N01 AI-25482. NR 30 TC 80 Z9 85 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PD SEP PY 2010 VL 47 IS 7 BP 822 EP 829 DI 10.3109/02770903.2010.489388 PG 8 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 658VR UT WOS:000282519500019 PM 20707763 ER PT J AU Baudino, L Yoshinobu, K Dunand-Sauthier, I Evans, LH Izui, S AF Baudino, Lucie Yoshinobu, Kumiko Dunand-Sauthier, Isabelle Evans, Leonard H. Izui, Shozo TI TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Toll-like receptor; Systemic lupus etythematosus; Endogenous retrovirus; Acute phase protein ID MURINE LEUKEMIA-VIRUS; TOLL-LIKE RECEPTORS; NEW-ZEALAND MICE; BXSB MICE; ENVELOPE GLYCOPROTEIN; AUTOIMMUNE-DISEASE; IMMUNE-COMPLEXES; DNA METHYLATION; GENE-EXPRESSION; AUTOANTIBODY PRODUCTION AB The endogenous retroviral envelope glycoprotein, gp70, implicated in murine systemic lupus erythematosus (SLE), has been considered to be a product of xenotropic, polytropic (PT) and modified PT (mPT) endogenous retroviruses. It is secreted by hepatocytes like an acute phase protein, but its response is under a genetic control. Given critical roles of TLR7 and TLR9 in the pathogenesis of SLE, we assessed their contribution to the acute phase expression of serum gp70, and defined a pivotal role of the Sgp3 (serum gp70 production 3) and Sgp4 loci in this response. Our results demonstrated that serum levels of gp70 were up-regulated in lupus-prone NZB mice injected with TLR7 or TLR9 agonist at levels comparable to those induced by injection of IL-1, IL-6 or TNF. In addition, studies of C57BL/6 Sgp3 and/or Sgp4 congenic mice defined the major roles of these two loci in up-regulated production of serum gp70 during acute phase responses. Finally, the analysis of Sgp3 congenic mice strongly suggests the presence of at least two distinct genetic factors in the Sgp3 interval, one of which controlled the basal-level expression of xenotropic, PT and mPT gp70 and the other which controlled the up-regulated production of xenotropic and mPT gp70 during acute phase responses. Our results uncovered an additional pathogenic role of TLR7 and TLR9 in murine lupus nephritis by promoting the expression of nephritogenic gp70 autoantigen. Furthermore, they revealed the involvement of multiple regulatory genes for the expression of gp70 autoantigen under steady-state and inflammatory conditions in lupus-prone mice. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Baudino, Lucie; Yoshinobu, Kumiko; Dunand-Sauthier, Isabelle; Izui, Shozo] Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. [Evans, Leonard H.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Izui, S (reprint author), Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland. EM Shozo.Izui@unige.ch FU Swiss National Foundation for Scientific Research; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX We thank Mr Guy Brighouse and Ms Montserrat Alvarez for their excellent technical assistance. This work was supported by a grant from the Swiss National Foundation for Scientific Research. L.H.E. was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 46 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 EI 1095-9157 J9 J AUTOIMMUN JI J. Autoimmun. PD SEP PY 2010 VL 35 IS 2 BP 153 EP 159 DI 10.1016/j.jaut.2010.06.001 PG 7 WC Immunology SC Immunology GA 652EX UT WOS:000281986100007 PM 20619604 ER PT J AU Shen, Y Bax, A AF Shen, Yang Bax, Ad TI SPARTA plus : a modest improvement in empirical NMR chemical shift prediction by means of an artificial neural network SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Electric field; Hydrogen bonding; Torsion angles; SHIFTX; Structure database; Camshift; SPARTA ID PROTEIN-STRUCTURE DETERMINATION; C-13 NMR; SEQUENCE HOMOLOGY; TORSION ANGLES; NUCLEIC-ACIDS; C-ALPHA; CONFORMATION; DYNAMICS; DATABASE; C-13(ALPHA) AB NMR chemical shifts provide important local structural information for proteins and are key in recently described protein structure generation protocols. We describe a new chemical shift prediction program, SPARTA+, which is based on artificial neural networking. The neural network is trained on a large carefully pruned database, containing 580 proteins for which high-resolution X-ray structures and nearly complete backbone and (13)C(beta) chemical shifts are available. The neural network is trained to establish quantitative relations between chemical shifts and protein structures, including backbone and side-chain conformation, H-bonding, electric fields and ring-current effects. The trained neural network yields rapid chemical shift prediction for backbone and (13)C(beta) atoms, with standard deviations of 2.45, 1.09, 0.94, 1.14, 0.25 and 0.49 ppm for delta(15)N, delta(13)C, delta(13)C(alpha), delta(13)C(beta), delta(1)H(alpha) and delta(1)H(N), respectively, between the SPARTA+ predicted and experimental shifts for a set of eleven validation proteins. These results represent a modest but consistent improvement (2-10%) over the best programs available to date, and appear to be approaching the limit at which empirical approaches can predict chemical shifts. C1 [Shen, Yang; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA. EM bax@nih.gov RI Shen, Yang/C-3064-2008 OI Shen, Yang/0000-0003-1408-8034 FU NIDDK; NIH; Office of the Director of the NIH FX This work was supported by the Intramural Research Program of the NIDDK, NIH, and by the Intramural AIDS-Targeted Antiviral Program of the Office of the Director of the NIH. NR 41 TC 175 Z9 175 U1 1 U2 38 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2010 VL 48 IS 1 BP 13 EP 22 DI 10.1007/s10858-010-9433-9 PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 653OT UT WOS:000282102300002 PM 20628786 ER PT J AU Butterfoss, GL DeRose, EF Gabel, SA Perera, L Krahn, JM Mueller, GA Zheng, XH London, RE AF Butterfoss, Glenn L. DeRose, Eugene F. Gabel, Scott A. Perera, Lalith Krahn, Joseph M. Mueller, Geoffrey A. Zheng, Xunhai London, Robert E. TI Conformational dependence of C-13 shielding and coupling constants for methionine methyl groups SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Methionine; [methyl-C-13] methionine; Calmodulin; NMR; Karplus relation; (3)J(CSCC); Scalar coupling constants ID NUCLEAR-MAGNETIC-RESONANCE; CARDIAC TROPONIN-C; DNA-POLYMERASE-DELTA; SEQUENCE-INDEPENDENT RECOGNITION; HIV-1 REVERSE-TRANSCRIPTASE; SPERM-WHALE MYOGLOBIN; MYELIN BASIC-PROTEIN; NMR CHEMICAL-SHIFTS; HUMAN TRANSFERRIN; SIDE-CHAINS AB Methionine residues fulfill a broad range of roles in protein function related to conformational plasticity, ligand binding, and sensing/mediating the effects of oxidative stress. A high degree of internal mobility, intrinsic detection sensitivity of the methyl group, and low copy number have made methionine labeling a popular approach for NMR investigation of selectively labeled protein macromolecules. However, selective labeling approaches are subject to more limited information content. In order to optimize the information available from such studies, we have performed DFT calculations on model systems to evaluate the conformational dependence of (3)J(CSCC), (3)J(CSCH), and the isotropic shielding, sigma(iso). Results have been compared with experimental data reported in the literature, as well as data obtained on [methyl-C-13]methionine and on model compounds. These studies indicate that relative to oxygen, the presence of the sulfur atom in the coupling pathway results in a significantly smaller coupling constant, (3)J(CSCC)/(3)J(COCC) similar to 0.7. It is further demonstrated that the (3)J(CSCH) coupling constant depends primarily on the subtended CSCH dihedral angle, and secondarily on the CSCC dihedral angle. Comparison of theoretical shielding calculations with the experimental shift range of the methyl group for methionine residues in proteins supports the conclusion that the intra-residue conformationally-dependent shift perturbation is the dominant determinant of delta C-13(epsilon). Analysis of calmodulin data based on these calculations indicates that several residues adopt non-standard rotamers characterized by very large similar to 100 degrees chi(3) values. The utility of the delta C-13(epsilon) as a basis for estimating the gauchel trans ratio for chi(3) is evaluated, and physical and technical factors that limit the accuracy of both the NMR and crystallographic analyses are discussed. C1 [DeRose, Eugene F.; Gabel, Scott A.; Perera, Lalith; Krahn, Joseph M.; Mueller, Geoffrey A.; Zheng, Xunhai; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Butterfoss, Glenn L.] NYU, Courant Inst Math Sci, New York, NY 10003 USA. [Butterfoss, Glenn L.] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, MR 01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM London@niehs.nih.gov RI perera, Lalith/B-6879-2012; Zheng, Xunhai/G-1187-2015 OI perera, Lalith/0000-0003-0823-1631; Zheng, Xunhai/0000-0003-0390-2491 FU National Institutes of Health [Z01-ES050111]; NIEHS [HHSN273200700046U] FX This research was supported by Research Project Z01-ES050111 (R.E.L.) in the Intramural Research Program of the National Institutes of Health. The contributions of E.F.D. and J.M.K. were funded in whole with Federal funds from NIEHS, under Delivery Order HHSN273200700046U to SRA International, Inc. The authors also wish to thank Prof. Richard Bonneau (NYU) for supporting some of the computations included in this study. NR 101 TC 13 Z9 13 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2010 VL 48 IS 1 BP 31 EP 47 DI 10.1007/s10858-010-9436-6 PG 17 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 653OT UT WOS:000282102300004 PM 20734113 ER PT J AU Arenella, C Yox, S Eckstein, DS Ousley, A AF Arenella, Cheryl Yox, Susan Eckstein, Daniel S. Ousley, Anita TI Expanding the Reach of a Cancer Palliative Care Curriculum Through Web-Based Dissemination: A Public-Private Collaboration SO JOURNAL OF CANCER EDUCATION LA English DT Article DE Cancer; Palliative care; End-of-life care; Palliative care education; Health professionals; Web-based continuing education; Online ID MEDICAL-EDUCATION AB Deficiencies in palliative and end-of-life care have been well documented by the Institute of Medicine. The National Cancer Institute (NCI), in partnership with Northwestern University, developed an educational curriculum for clinicians who deal with end-of-life issues, the Education in Palliative and End-of-Life Care for Oncology. A live meeting was held to distribute the curriculum to institutional leaders who could take it back to their organizations for broader distribution. To further distribute the materials and ensure they were available whenever a clinician wanted to view them, NCI collaborated with a leading online medical education provider whose websites are visited by over 1,500,000 physicians per month (http://cme.medscape.com) to post one module of the curriculum as an online activity certified for physician and nurse continuing education credit. The module is entitled "Last Hours of Living: Practical Advice for Clinicians." A descriptive analysis of the first 7 months of publication was performed. Twenty thousand sixty-one health professionals completed the activity during this time period and earned continuing education credit. Eighty-four percent completed the post-activity evaluation survey. Satisfaction was very high among participants, and many indicated their intention to incorporate new knowledge into practice. Collaboration with a commonly used online medical education provider such as Medscape is effective at broadly disseminating palliative care education to health professionals. C1 [Arenella, Cheryl] NCI, Off Communicat & Educ, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. [Yox, Susan] Medscape LLC, New York, NY 10001 USA. [Eckstein, Daniel S.] NOVA Res Co, Bethesda, MD 20814 USA. [Ousley, Anita] NCI, Off Commun & Educ, Dept Hlth & Human Serv, NIH, Rockville, MD 20852 USA. RP Arenella, C (reprint author), NCI, Off Communicat & Educ, Dept Hlth & Human Serv, NIH, 6116 Execut Blvd,Suite 410 Room 4104, Rockville, MD 20852 USA. EM arenellac@mail.nih.gov NR 14 TC 4 Z9 4 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SEP PY 2010 VL 25 IS 3 BP 418 EP 421 DI 10.1007/s13187-010-0066-1 PG 4 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 666HQ UT WOS:000283105800027 PM 20237885 ER PT J AU Kim, C McGlynn, KA McCorkle, R Zheng, TZ Erickson, RL Niebuhr, DW Ma, SG Zhang, YQ Bai, YN Dai, L Graubard, BI Kilfoy, B Barry, KH Zhang, YW AF Kim, Christopher McGlynn, Katherine A. McCorkle, Ruth Zheng, Tongzhang Erickson, Ralph L. Niebuhr, David W. Ma, Shuangge Zhang, Yaqun Bai, Yana Dai, Li Graubard, Barry I. Kilfoy, Briseis Barry, Kathryn Hughes Zhang, Yawei TI Fertility among testicular cancer survivors: a case-control study in the US SO JOURNAL OF CANCER SURVIVORSHIP-RESEARCH AND PRACTICE LA English DT Article DE Fertility; Testicular cancer; Epidemiology ID GERM-CELL TUMORS; CHEMOTHERAPY; INFERTILITY AB Introduction Testicular germ cell tumors (TGCT) disproportionately affect men between the ages of 15 and 49 years, when reproduction is typical. Although TGCT treatment directly affects gonadal tissues, it remains unclear whether there are long-term effects on fertility. Methods To examine post-TGCT treatment fertility, study participants in a previously conducted case-control study were contacted. The men were initially enrolled in the US Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) study between 2002 and 2005. A total of 246 TGCT cases and 236 controls participated in the current study and completed a self-administered questionnaire in 2008-2009. Results TGCT cases were significantly more likely than controls to experience fertility distress (OR 5.23; 95% CI 1.99-13.76) and difficulty in fathering children (OR 6.41; 2.72-15.13). Cases were also more likely to be tested for infertility (OR 3.65; 95% CI 1.55-8.59). Cases, however, did not differ from controls in actually fathering children (OR 1.37; 95% CI 0.88-2.15). These findings were predominantly observed among nonseminoma cases and cases treated with surgery only or surgery-plus-chemotherapy. Discussion While expressing greater fertility distress, higher likelihood of fertility testing, and difficulty fathering children, these data suggest that TGCT survivors are no less likely to father children than are other men. It is possible that treatment for TGCT does not permanently affect C1 [Kim, Christopher; Ma, Shuangge; Zhang, Yaqun; Bai, Yana; Dai, Li; Barry, Kathryn Hughes; Zhang, Yawei] Yale Univ, Yale Sch Publ Hlth, New Haven, CT 06520 USA. [McGlynn, Katherine A.; Zheng, Tongzhang; Graubard, Barry I.; Kilfoy, Briseis; Barry, Kathryn Hughes] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. [McCorkle, Ruth] Yale Univ, Yale Sch Nursing, New Haven, CT 06520 USA. [Erickson, Ralph L.; Niebuhr, David W.] Walter Reed Army Inst Res, Forest Glen, MD USA. [Zhang, Yawei] Gansu Prov Design & Res Inst Environm Sci, Lanzhou, Gansu, Peoples R China. [Bai, Yana] Lanzhou Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Lanzhou 730000, Peoples R China. [Dai, Li] Sichuan Univ, W China Univ Hosp 2, Natl Ctr Birth Defect Monitoring, Chengdu 610064, Peoples R China. RP Zhang, YW (reprint author), Yale Univ, Yale Sch Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Aschebrook-Kilfoy, Briseis/A-2537-2012 FU National Cancer Institute (NCI) [CA130110]; National Institute of Health (NIH) [1D43TW008323-01, 1D43TW007864-01]; National Center for Research Resources (NCRR), NIH [UL1 RR024139] FX This study is supported by grant CA130110 from the National Cancer Institute (NCI) and by Fogarty training grants 1D43TW008323-01 and 1D43TW007864-01 from the National Institute of Health (NIH). This publication was made possible by CTSA Grant number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the NIH and NHL roadmap for medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR. The authors are greatly indebted to the Study participants, without whom, there would have been no study. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. NR 23 TC 6 Z9 7 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1932-2259 J9 J CANCER SURVIV JI J. Cancer Surviv.-Res. Pract. PD SEP PY 2010 VL 4 IS 3 BP 266 EP 273 DI 10.1007/s11764-010-0134-x PG 8 WC Oncology; Social Sciences, Biomedical SC Oncology; Biomedical Social Sciences GA 788TZ UT WOS:000292468600009 PM 20571931 ER PT J AU Pischke, CR Elliott-Eller, M Li, MM Mendell, N Ornish, D Weidner, G AF Pischke, Claudia R. Elliott-Eller, Melanie Li, Minmin Mendell, Nancy Ornish, Dean Weidner, Gerdi TI Clinical Events in Coronary Heart Disease Patients With an Ejection Fraction of 40% or Less 3-Year Follow-up Results SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE asymptomatic reduced left ventricular ejection fraction; clinical events; coronary heart disease; lifestyle ID VENTRICULAR SYSTOLIC DYSFUNCTION; STYLE DEMONSTRATION PROJECT; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; ARTERY-DISEASE; RISK-FACTORS; FAILURE; MANAGEMENT; CARE; GUIDELINES AB Background and Research Objective: It is unclear whether lifestyle changes can delay the need for surgical procedures in coronary heart disease (CHD) patients with asymptomatic reduced left ventricular ejection fraction (LVEF). The aim of this pilot study was to examine whether lifestyle changes can delay the need for surgical procedures in this population. Subjects and Methods: We compared 3-year clinical events in 27 CHD patients eligible to receive revascularization (by insurance standards), but underwent lifestyle changes (low-fat diet, exercise, stress management) instead (intervention group [IG], LVEF <= 40%), with those of a historically matched (age, gender, LVEF, and stenosis of the 3 major coronary arteries) control group receiving usual care (UCG; n = 13) who received revascularization at study entry. Both IG and UCG patients were enrolled in the health insurance companies participating in the Multicenter Lifestyle Demonstration Project, an insurance-sponsored, community-based, secondary prevention study implemented at 8 hospital sites in the United States. Results and Conclusion: At 3 months, there were more cardiac events in the UCG (6 events) than in the IG (1 event; P < .006; odds ratio = 13.27; confidence interval = 1.57-111.94). This difference was maintained over 3 years (P < .06; odds ratio = 2.75; confidence interval = 1.05-7.19). Of the 26 surviving (1 cardiac death) IG patients, 23 did not require primary revascularization. In conclusion, CHD patients with asymptomatic reduced LVEF may be able to safely delay revascularization by making changes in lifestyle with no increased risk for cardiac events or overt heart failure over 3 years. C1 [Pischke, Claudia R.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Pischke, Claudia R.] NCI, Bethesda, MD 20892 USA. [Elliott-Eller, Melanie] Palm Drive Hosp, Sebastopol, CA USA. [Li, Minmin; Mendell, Nancy] SUNY Stony Brook, Dept Appl Math & Stat, New York, NY USA. [Ornish, Dean] Res Inst Prevent Med, Sausalito, CA USA. [Weidner, Gerdi] San Francisco State Univ, Romberg Tiburon Ctr, Dept Biol, Tiburon, CA 94920 USA. [Weidner, Gerdi] Johannes Gutenberg Univ Mainz, Mainz, Germany. RP Pischke, CR (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St,LW703, Boston, MA 02115 USA. EM pischcl@gmx.net; gweidner@sfsu.edu FU NCI NIH HHS [R25 CA 057713-05]; NIMH NIH HHS [MH0711523] NR 31 TC 1 Z9 1 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD SEP-OCT PY 2010 VL 25 IS 5 BP E8 EP E15 DI 10.1097/JCN.0b013e3181d51f9e PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 641GK UT WOS:000281112600059 PM 20714228 ER PT J AU Shi, SL Liang, Y Li, QF Liu, QR Jing, GJ Wang, SY Zhang, XY Wu, FY AF Shi, Song-Lin Liang, Ying Li, Qi-Fu Liu, Qing-Rong Jing, Guang-Jun Wang, San-Ying Zhang, Xiu-Yan Wu, Fu-Yun TI Localization of Nucleophosmin in Nuclear Matrix and Changes in Its Expression During the Differentiation of Human Neuroblastoma Induced by Retinoic Acid SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE NUCLEOPHOSMIN; NUCLEAR MATRIX; HUMAN NEUROBLASTOMA; CELL DIFFERENTIATION ID C-MYC; TRANSCRIPTIONAL ACTIVATION; PROTEIN; CELLS; CANCER; STABILITY; P53 AB In this article, we selectively extracted the nuclear matrix and intermediate filament system of human neuroblastoma SK-N-SH cells pre- and post-treated with retinoic acid (RA). The distribution of nucleophosmin (NPM) in the nuclear matrix and its colocalization with several products of related genes were investigated. Results from two-dimensional gel electrophoresis and MALDI-TOF showed that NPM was a component of the nuclear matrix and its expression in SK-N-SH cells post-treated with RA was down-regulated Immunofluorescent microscopy observations further showed that NPM was localized in the nuclear matrix of SK-N-SH cells, and its expression level and distribution were altered after treatment with RA. The colocalization of NPM with c-myc. c-fos, p53, and Rb in SK-N-SH cells was observed under a laser scanning confocal microscope, but the colocalization region was changed by RA Our results prove that NPM is a nuclear matrix protein, which is localized in nuclear matrix fibers. The colocalization of NPM with its related genes and oncogenes affect the differentiation of SK-N-SH cells. The expression of NPM and its distribution in the process of cell differentiation deserve more intensive investigation. J Cell. Biochem 111 67-74. 2010. (C) 2010 whey-Liss, Inc C1 [Shi, Song-Lin; Liang, Ying; Li, Qi-Fu; Jing, Guang-Jun; Wang, San-Ying; Zhang, Xiu-Yan; Wu, Fu-Yun] Xiamen Univ, Sch Life Sci, Minist Educ Cell Biol & Tumor Cell Engn, Key Lab, Xiamen 361005, Fujian Province, Peoples R China. [Shi, Song-Lin] Xiamen Univ, Coll Med, Xiamen 361005, Peoples R China. [Liu, Qing-Rong] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH,DHSS, Baltimore, MD 21224 USA. RP Li, QF (reprint author), Xiamen Univ, Sch Life Sci, Minist Educ Cell Biol & Tumor Cell Engn, Key Lab, Xiamen 361005, Fujian Province, Peoples R China. RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU National Natural Science Foundation of China [30871241] FX Grant sponsor. National Natural Science Foundation of China. Grant number 30871241 NR 19 TC 1 Z9 2 U1 0 U2 3 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 SEP 1 PY 2010 VL 111 IS 1 BP 67 EP 74 DI 10.1002/jcb.22663 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 648JU UT WOS:000281690500009 PM 20506166 ER PT J AU Hou, SX AF Hou, Steven X. TI Intestinal Stem Cell Asymmetric Division in the Drosophila Posterior Midgut SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Review ID JAK/STAT; PROTEIN; NOTCH; GENE; IDENTIFICATION; PROLIFERATION; MAINTENANCE; MECHANISMS; PATHWAYS; RECEPTOR AB Over the past 2 years, our understanding of intestinal stem cells in the Drosophila posterior midgut has advanced greatly. In this review, I will focus on the establishment of these stem cells in their niche during development and the molecular mechanisms that regulate their asymmetric division in adults. J. Cell. Physiol. 224: 581-584, 2010. Published 2010 Wiley-Liss, Inc. C1 NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Hou, SX (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM hous@mail.nih.gov NR 30 TC 15 Z9 15 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2010 VL 224 IS 3 BP 581 EP 584 DI 10.1002/jcp.22194 PG 4 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 634YG UT WOS:000280621600003 PM 20578235 ER PT J AU Zeng, XK Singh, SR Hou, D Hou, SX AF Zeng, Xiankun Singh, Shree Ram Hou, David Hou, Steven X. TI Tumor Suppressors Sav/Scrib and Oncogene Ras Regulate Stem-Cell Transformation in Adult Drosophila Malpighian Tubules SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID BACTERIAL-INFECTION; PROMOTES APOPTOSIS; MYELOID-LEUKEMIA; HIPPO PATHWAY; SELF-RENEWAL; CANCER; PROLIFERATION; GROWTH; IDENTIFICATION; DIVISION AB An increasing body of evidence suggests that tumors might originate from a few transformed cells that share many properties with normal stem cells. However, it remains unclear how normal stem cells are transformed into cancer stem cells (CSCs). Here, we demonstrated that mutations causing the loss of tumor suppressor Salvador (Say) or Scribble (Scrib) or activation of the oncogene Ras transform normal stem cells into CSCs through a multistep process in the adult Drosophila Malpighian Tubules (MTs). In wild-type MTs, each stem cell generates one self-renewing and one differentiating daughter cell. However, in flies with loss-of-function say or scrib or gain-of-function Ras mutations, both daughter cells grew and behaved like stem cells, leading to the formation of tumors in MTs. Ras functioned downstream of Say and Scrib in regulating the stem-cell transformation. The Ras-transformed stem cells exhibited many of the hallmarks of cancer, such as increased proliferation, reduced cell death, and failure to differentiate. We further demonstrated that several signal transduction pathways (including MEK/MAPK, RhoA, PKA, and TOR) mediate Ras' function in the stem-cell transformation. Therefore, we have identified a molecular mechanism that regulates stem-cell transformation, and this finding may lead to strategies for preventing tumor formation in certain organs. J. Cell. Physiol. 224: 766-774, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Zeng, Xiankun; Singh, Shree Ram; Hou, David; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Zeng, XK (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM zengx2@mail.nih.gov; hous@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 45 TC 10 Z9 10 U1 4 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2010 VL 224 IS 3 BP 766 EP 774 DI 10.1002/jcp.22179 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 634YG UT WOS:000280621600026 PM 20432470 ER PT J AU Fleming, JM Miller, TC Meyer, MJ Ginsburg, E Vonderhaar, BK AF Fleming, Jodie M. Miller, Tyler C. Meyer, Matthew J. Ginsburg, Erika Vonderhaar, Barbara K. TI Local Regulation of Human Breast Xenograft Models SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ATHYMIC NUDE-MICE; NORMAL MAMMARY-GLANDS; HUMAN-MELANOMA CELLS; CANCER-CELLS; IN-VIVO; PROMOTER HYPERMETHYLATION; PROGESTERONE-RECEPTORS; GROWTH-CHARACTERISTICS; IMMUNODEFICIENT MICE; TUMORS AB Breast cancer studies implant human cancer cells under the renal capsule, subcutaneously, or orthotopically and often use estrogen supplementation and immune suppressants (etoposide) in xenograft mouse models. However, cell behavior is significantly impacted by signals from the local microenvironment. Therefore, we investigated how the combinatorial effect of the location of injection and procedural differences affected xenograft characteristics. Patient-derived breast cancer cells were injected into mouse abdominal or thoracic mammary glands +/- estrogen and/or etoposide pretreatment. Abdominal xenografts had increased tumor incidence and volume, and decreased latency (P < 0.001) compared to thoracic tumors. No statistically significant difference in tumor volume was found in abdominal xenografts treated estrogen or etoposide; however, etoposide suppressed tumor volume in thoracic xenografts (P < 0.02). The combination of estrogen and etoposide significantly decreased tumor incidence in both sites. In addition, mice treated +/- estradiol were injected orthotopically or subcutaneously with well-characterized breast cancer cell lines (MCF7, ZR75-1, MDA MB-231, or MCF10Calh). Orthotopic injection increased tumor volume; growth varied with estrogen supplementation. Location also altered methylation status of several breast cancer-related gene promoters. Lastly, vascularization of orthotopic tumors was significantly enhanced compared to subcutaneous tumors. These data suggest that optimal xenograft success occurs with orthotopic abdominal injections and illustrate molecular details of the compelling influence of the local microenvironment on in vivo models. J. Cell. Physiol. 224: 795-806, 2010. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Fleming, Jodie M.; Miller, Tyler C.; Meyer, Matthew J.; Ginsburg, Erika; Vonderhaar, Barbara K.] NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Vonderhaar, BK (reprint author), 37 Convent Dr,Bldg 37,Room 1106A1, Bethesda, MD 20892 USA. EM bv10w@nih.gov FU Center for Cancer Research; National Cancer Institute; Breast Cancer Research FX This research was supported by the Center for Cancer Research, an Intramural Research Program of the National Cancer Institute and by Breast Cancer Research Stamp proceeds awarded through competitive peer review. NR 57 TC 20 Z9 20 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2010 VL 224 IS 3 BP 795 EP 806 DI 10.1002/jcp.22190 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 634YG UT WOS:000280621600029 PM 20578247 ER PT J AU Samuel, W Kutty, RK Vijayasarathy, C Pascual, I Duncan, T Redmond, TM AF Samuel, William Kutty, R. Krishnan Vijayasarathy, Camasamudram Pascual, Iranzu Duncan, Todd Redmond, T. Michael TI Decreased Expression of Insulin-Like Growth Factor Binding Protein-5 During N-(4-Hydroxyphenyl) Retinamide-Induced Neuronal Differentiation of ARPE-19 Human Retinal Pigment Epithelial Cells: Regulation by CCAAT/Enhancer-Binding Protein SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID INTESTINAL SMOOTH-MUSCLE; FACTOR-I; GENE-EXPRESSION; IGF-I; ADIPOCYTE DIFFERENTIATION; PHYSIOLOGICAL FUNCTIONS; TRANSCRIPTION FACTORS; NEUROBLASTOMA-CELLS; MAP KINASE; IGFBP-5 AB Insulin-like growth factor (IGF)-binding protein-5 (IGFBP5), an important member of the IGF axis involved in regulating cell growth and differentiation, acts by modulating IGF signaling and also by IGF-independent mechanisms. We identified IGFBP5 by microarray analysis as a gene differentially regulated during N-(4-hydroxyphenyl)retinamide (4HPR)-induced neuronal differentiation of human retinal pigment epithelial (RPE) cells. IGFBP5 is expressed in human RPE cells, and its expression, mRNA as well as protein, is greatly decreased during the 4HPR-induced neuronal differentiation. Exogenous IGFBP5 does not block the neuronal differentiation indicating that IGFBP5 down-regulation may not be a prerequisite for the neuronal differentiation. IGFBP5 down-regulation, similar to neuronal differentiation, is mediated by the MAPK pathway since U0126, an inhibitor of MEK1/2, effectively blocked it. The overexpression of transcription factor CCAAT/enhancer binding protein-beta (C/EBP beta) inhibited the 4HPR-induced down-regulation of IGFBP5 expression and the neuronal differentiation of RPE cells. Interestingly, the binding of C/EBP beta to the IGFBP5 promoter was decreased by the 4HPR treatment as indicated by gel shift and chromatin immunoprecipitation analyses. Further, the deletion of C/EBP response element from IGFBP5 promoter markedly decreased the basal promoter activity and abolished its responsiveness to 4HPR treatment in reporter assays, suggesting that the expression of IGFBP5 is regulated by C/EBP. Thus, our results clearly demonstrate that the IGFBP5 expression is down-regulated during 4HPR-induced neuronal differentiation of human RPE cells through a MAPK signal transduction pathway involving C/EBP beta. J. Cell. Physiol. 224: 827-836, 2010. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Samuel, William; Kutty, R. Krishnan; Pascual, Iranzu; Duncan, Todd; Redmond, T. Michael] NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Vijayasarathy, Camasamudram] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Samuel, W (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Room 112A,6 Ctr Dr, Bethesda, MD 20892 USA. EM samuelw@nei.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 FU National Eye Institute, National Institutes of Health FX This research work was supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health. NR 47 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2010 VL 224 IS 3 BP 827 EP 836 DI 10.1002/jcp.22191 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 634YG UT WOS:000280621600032 PM 20583135 ER PT J AU Hawkins, BT Rigor, RR Miller, DS AF Hawkins, Brian T. Rigor, Robert R. Miller, David S. TI Rapid loss of blood-brain barrier P-glycoprotein activity through transporter internalization demonstrated using a novel in situ proteolysis protection assay SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; endothelium; pharmacology; physiology; vascular biology ID PHOSPHORYLATION; LOCALIZATION; MICROVESSELS; MODULATION; ABCB1 AB Blood-brain barrier (BBB) P-glycoprotein activity is rapidly reduced by vascular endothelial growth factor (VEGF) acting via Src and by tumor necrosis factor-a acting via protein kinase C (PKC)beta 1. To probe underlying mechanism(s), we developed an in vivo, immunoblot-based proteinase K (PK) protection assay to assess the changes in the P-glycoprotein content of the BBB's luminal membrane. Infusion of PK into the brain vasculature selectively cleaved luminal membrane P-glycoprotein, leaving intracellular proteins intact. Intracerebroventricular injection of VEGF partially protected P-glycoprotein from proteolytic cleavage, consistent with transporter internalization. Activation of PKC beta 1 did not protect P-glycoprotein. Thus, VEGF and PKC beta 1 reduce P-glycoprotein activity by distinct mechanisms. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 1593-1597; doi:10.1038/jcbfm.2010.117; published online 14 July 2010 C1 [Hawkins, Brian T.; Miller, David S.] NIEHS, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Rigor, Robert R.] Univ Calif Davis, Sch Med, Dept Surg, Sacramento, CA 95817 USA. RP Miller, DS (reprint author), NIEHS, Lab Toxicol & Pharmacol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov OI Rigor, Robert/0000-0001-6234-1992; Hawkins, Brian/0000-0001-6719-5402 FU National Institutes of Health, National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 13 TC 18 Z9 18 U1 0 U2 0 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 SEP PY 2010 VL 30 IS 9 BP 1593 EP 1597 DI 10.1038/jcbfm.2010.117 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 646SF UT WOS:000281562300006 PM 20628400 ER PT J AU Morra, G Neves, MAC Plescia, CJ Tsustsumi, S Neckers, L Verkhivker, G Altieri, DC Colombo, G AF Morra, Giulia Neves, Marco A. C. Plescia, Christopher J. Tsustsumi, Shinji Neckers, Len Verkhivker, Gennady Altieri, Dario C. Colombo, Giorgio TI Dynamics-Based Discovery of Allosteric Inhibitors: Selection of New Ligands for the C-terminal Domain of Hsp90 SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID MOLECULAR-DYNAMICS; NOVOBIOCIN ANALOGS; PROTEINS; CHAPERONE; SITES; FLUCTUATIONS; MODULATION; SIMULATION; MECHANICS; ALGORITHM AB The study of allosteric functional modulation in dynamic proteins is attracting increasing attention. In particular, the discovery of new allosteric sites may generate novel opportunities and strategies for drug development, overcoming the limits of classical active-site oriented drug design. In this paper, we report on the results of a novel, ab initio, fully computational approach for the discovery of allosteric inhibitors based on the physical characterization of signal propagation mechanisms in proteins and apply it to the important molecular chaperone Hsp90. We first characterize the allosteric "hot spots" involved in interdomain communication pathways from the nucleotide-binding site in the N-domain to the distal C-domain. On this basis, we develop dynamic pharmacophore models to screen drug libraries in the search for small molecules with the functional and conformational properties necessary to bind these "hot spot" allosteric sites. Experimental tests show that the selected moelcules bind the Hsp90 C-domain, exhibit antiproliferative activity in different tumor cell lines, while not affecting proliferation of normal human cells, destabilize Hsp90 client proteins, and disrupt association with several cochaperones known to bind the N- and M-domains of Hsp90. These results prove that the hits alter Hsp90 function by affecting its conformational dynamics and recognition properties through an allosteric mechanism. These findings provide us with new insights on the discovery and development of new allosteric inhibitors that are active on important cellular pathways through computational biology. Though based on the specific case of Hsp90, our approach is general and can readily be extended to other target proteins and pathways. C1 [Morra, Giulia; Neves, Marco A. C.; Colombo, Giorgio] CNR, Ist Chim Riconoscimento Mol, I-20131 Milan, Italy. [Plescia, Christopher J.; Altieri, Dario C.] Univ Massachusetts, Dept Canc Biol, Sch Med, Worcester, MA 01605 USA. [Tsustsumi, Shinji; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Verkhivker, Gennady] Univ Kansas, Dept Pharmaceut Chem, Sch Pharm, Lawrence, KS 66047 USA. [Verkhivker, Gennady] Univ Kansas, Ctr Bioinformat, Lawrence, KS 66047 USA. RP Colombo, G (reprint author), CNR, Ist Chim Riconoscimento Mol, Via Mario Bianco 9, I-20131 Milan, Italy. EM giorgio.colombo@icrm.cnr.it RI Neves, Marco/K-6630-2012; Colombo, Giorgio/A-2730-2012; Morra, Giulia/O-2311-2015 OI Colombo, Giorgio/0000-0002-1318-668X; Morra, Giulia/0000-0002-9681-7845 FU Associazione Italiana Ricerca sul Cancro (AIRC) FX This work was supported by a grant from Associazione Italiana Ricerca sul Cancro (AIRC) to G.C. G.M. gratefully acknowledges support from a "L'Oreal-Unesco for Women in Science" grant. NR 43 TC 28 Z9 28 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD SEP PY 2010 VL 6 IS 9 BP 2978 EP 2989 DI 10.1021/ct100334n PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 648KQ UT WOS:000281693000038 PM 26616092 ER PT J AU Nieman, LK AF Nieman, Lynnette K. TI Approach to the Patient with an Adrenal Incidentaloma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SUBCLINICAL CUSHINGS-SYNDROME; CLINICAL-PRACTICE GUIDELINE; NIGHT SALIVARY CORTISOL; TERM-FOLLOW-UP; LAPAROSCOPIC ADRENALECTOMY; PRIMARY ALDOSTERONISM; COMPUTED-TOMOGRAPHY; MASS INCIDENTALOMA; DIAGNOSIS; MANAGEMENT AB Unsuspected adrenal masses, or incidentalomas, are increasingly found with the widespread use of thoracic and abdominal imaging. These masses may be hormonally active or nonfunctional and malignant or benign. Clinicians must determine the nature of the mass to decide what treatment, if any, is needed. Measurement of precontrast Hounsfield units (HU) and contrast washout on computed tomography scan provide useful diagnostic information. All patients should undergo biochemical testing for pheochromocytoma, either with plasma or urinary catecholamine measurements. This is particularly important before surgical resection, which is routinely recommended for masses larger than 4 cm in diameter without a clear-cut diagnosis and for others with hormonal secretion or ominous imaging characteristics. Hypertensive patients should undergo biochemical testing for hyperaldosteronism. Patients with features consistent with Cushing's syndrome, such as glucose intolerance, weight gain, and unexplained osteopenia, should be evaluated for cortisol excess. Here, the dexamethasone suppression test and late-night salivary cortisol may be preferred over measurement of urine cortisol. The ability of surgical resection to reverse features of mild hypercortisolism is not well established. For masses that appear to be benign (<10 HU; washout, >50%), small (<3 cm), and completely nonfunctioning, imaging and biochemical reevaluation (pheochromocytoma and hypercortisolism only) at 1-2 yr (or more) is appropriate. For more indeterminate lesions, repeat evaluation for growth after 3-12 months is useful, with subsequent testing intervals based on the rate of growth. (J Clin Endocrinol Metab 95: 4106-4113, 2010) C1 [Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), Bldg 10-CRC 1 E Room 3140,10 Cent Dr, Bethesda, MD 20892 USA. EM niemanl@nih.gov NR 50 TC 93 Z9 101 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4106 EP 4113 DI 10.1210/jc.2010-0457 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300022 PM 20823463 ER PT J AU Speiser, PW Azziz, R Baskin, LS Ghizzoni, L Hensle, TW Merke, DP Meyer-Bahlburg, HFL Miller, WL Montori, VM Oberfield, SE Ritzen, M White, PC AF Speiser, Phyllis W. Azziz, Ricardo Baskin, Laurence S. Ghizzoni, Lucia Hensle, Terry W. Merke, Deborah P. Meyer-Bahlburg, Heino F. L. Miller, Walter L. Montori, Victor M. Oberfield, Sharon E. Ritzen, Martin White, Perrin C. TI Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TANDEM MASS-SPECTROMETRY; BONE-MINERAL DENSITY; QUALITY-OF-LIFE; DECREASED EPINEPHRINE RESERVE; TOTAL UROGENITAL MOBILIZATION; EARLY-PRENATAL DEXAMETHASONE; HIGH-INTENSITY EXERCISE; FETAL SEX DETERMINATION; EMILIA-ROMAGNA REGION; DRIED BLOOD SPOTS AB Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing's syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients' quality of life, consulting mental health professionals as appropriate. At thetransition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH. (J Clin Endocrinol Metab 95: 4133-4160, 2010) C1 [Speiser, Phyllis W.] Cohen Childrens Med Ctr, New York, NY 11040 USA. [Speiser, Phyllis W.] Hofstra Univ, Sch Med, New York, NY 11040 USA. [Azziz, Ricardo] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Baskin, Laurence S.; Miller, Walter L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ghizzoni, Lucia] Univ Turin, I-10129 Turin, Italy. [Hensle, Terry W.] Columbia Univ, New York, NY 10032 USA. [Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth Clin Ctr, Bethesda, MD 20892 USA. [Meyer-Bahlburg, Heino F. L.] Columbia Univ, New York State Psychiat Inst, New York, NY 10032 USA. [Oberfield, Sharon E.] Childrens Hosp New York Presbyterian, New York, NY 10032 USA. [Oberfield, Sharon E.] Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. [Montori, Victor M.] Mayo Clin, Rochester, MN 55905 USA. [Ritzen, Martin] Karolinska Inst, S-17176 Stockholm, Sweden. [White, Perrin C.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Speiser, PW (reprint author), Cohen Childrens Med Ctr, New York, NY 11040 USA. RI Miller, Walter/J-3696-2012; Azziz, Ricardo/N-7229-2014; OI Azziz, Ricardo/0000-0002-3917-0483; Montori, Victor/0000-0003-0595-2898 FU Pediatric Endocrine Society; Society for Pediatric Research; American Association of Clinical Endocrinologists; Significant Financial Interest or Leadership Position: Medical Advisory Board; CARES Foundation; National Adrenal Diseases Foundation; Phoqus Pharmaceuticals; American Psychiatric Association; National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Biopartners AG; Acta Paediatrica; National Institutes of Health FX Phyllis W. Speiser, M.D. (chair) - Financial or Business/Organizational Interests: Pediatric Endocrine Society, Society for Pediatric Research, and American Association of Clinical Endocrinologists; Significant Financial Interest or Leadership Position: Medical Advisory Board, CARES Foundation, and National Adrenal Diseases Foundation; Ricardo Azziz, M.B.A., M.D., M.P.H. - Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared; Laurence S. Baskin, M.D. - Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared; Lucia Ghizzoni, M.D., Ph.D. - Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared; Terry W. Hensle, M.D. - Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared; * Deborah P. Merke, MS, M.D. - Financial of Business/Organizational Interests: Phoqus Pharmaceuticals and CARES Foundation; Significant Financial Interest or Leadership Position: none declared; Heino F. L. Meyer-Bahlburg, Dr. rer. Nat. - Financial of Business/Organizational Interests: Pediatric Endocrine Society, World Professional Association of Transgender Health, and Gender Identity Disorders for DSM-V of the American Psychiatric Association; Significant Financial Interest or Leadership Position: none declared; Walter L. Miller, M.D. - Financial or Business/Organizational Interests: CARES Foundation and Pediatric Endocrine Society; Significant Financial Interest or Leadership Position: Medical Advisory Board and CARES Foundation; dagger Victor M. Montori, M.D.-Financial or Business/Organizational Interests: KERUnit (Mayo Clinic); Significant Financial Interest or Leadership Position: none declared; Sharon E. Oberfield, M.D. - Financial or Business/Organizational Interests: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; Significant Financial Interest or Leadership Position: Pediatric Endocrine Society, Medical Advisory Board, and CARES Foundation; Martin Ritzen, M.D. - Financial or Business/Organizational Interests: Biopartners AG and Acta Paediatrica; Significant Financial Interest or Leadership Position: none declared; Perrin C. White, M.D. - Financial or Business/Organizational Interests: none declared; Significant Financial Interest or Leadership Position: none declared.; This work was supported by the Intramural Research Program of the National Institutes of Health. NR 275 TC 342 Z9 390 U1 4 U2 29 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4133 EP 4160 DI 10.1210/jc.2009-2631 PG 28 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300025 PM 20823466 ER PT J AU Lonser, RR Kindzelski, BA Mehta, GU Jane, JA Oldfield, EH AF Lonser, Russell R. Kindzelski, Bogdan A. Mehta, Gautam U. Jane, John A., Jr. Oldfield, Edward H. TI Acromegaly without Imaging Evidence of Pituitary Adenoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMORS; DIAGNOSIS AB Context: GH-secreting pituitary adenomas are nearly always visible on conventional magnetic resonance (MR) imaging. However, management and outcome of acromegalic patients lacking imaging evidence of GH-secreting pituitary adenomas are undefined. Objective: The aim was to evaluate surgical exploration for MR-invisible GH-secreting pituitary adenomas. Design and Setting: We conducted a retrospective review at two tertiary care centers. Patients or Other Participants: Consecutive acromegalic patients without imaging evidence of a pituitary adenoma on pre- and postcontrast, spin echo T1-weighted MR imaging and who lacked evidence of an ectopic (nonpituitary) source causing GH excess were included. Interventions: Surgical exploration with identification and resection of a pituitary adenoma was performed. Main Outcome Measures: Laboratory values (GH, IGF-I), surgical findings, and clinical outcome were analyzed. Results: Six patients (three males, three females; 3% of all patients) with suspected GH-secreting adenomas did not demonstrate imaging evidence of pituitary adenoma on conventional MR imaging. Three patients underwent a postcontrast, volumetric interpolated breath-hold examination MR-imaging sequence (1.2-mm slice thickness), which revealed a 4-mm pituitary adenoma not seen on the spin echo T1-weighted MR imaging in one patient. A pituitary adenoma was identified and removed in all patients (mean diameter, 5.6 mm; range, 5 to 6.7 mm). Histological analysis confirmed that the lesions were GH-secreting adenomas. All patients achieved biochemical remission after surgical resection. Conclusion: Acromegaly can be caused by GH-secreting pituitary adenomas that are not evident on conventional MR imaging. Adenomas in some of these patients become evident using volumetric interpolated breath-hold examination MR imaging. Surgical exploration of the pituitary gland in acromegalic patients with endocrine findings consistent with a GH-secreting adenoma but negative MR imaging can lead to identification and removal of an adenoma. (J Clin Endocrinol Metab 95: 4192-4196, 2010) C1 [Lonser, Russell R.; Kindzelski, Bogdan A.; Mehta, Gautam U.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Jane, John A., Jr.; Oldfield, Edward H.] Univ Virginia, Univ Virginia Hlth Syst, Dept Neurosurgery, Charlottesville, VA 22908 USA. RP Lonser, RR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov OI Mehta, Gautam/0000-0002-8009-6430 FU National Institute of Neurological Disorders and Stroke at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 16 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP 4192 EP 4196 DI 10.1210/jc.2010-0570 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300031 PM 20610592 ER PT J AU Lee, DC Romero, R Kim, JS Yoo, W Lee, J Mittal, P Kusanovic, JP Hassan, SS Yoon, BH Kim, CJ AF Lee, Deug-Chan Romero, Roberto Kim, Jung-Sun Yoo, Wonsuk Lee, JoonHo Mittal, Pooja Kusanovic, Juan Pedro Hassan, Sonia S. Yoon, Bo Hyun Kim, Chong Jai TI Evidence for a Spatial and Temporal Regulation of Prostaglandin-Endoperoxide Synthase 2 Expression in Human Amnion in Term and Preterm Parturition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN FETAL MEMBRANES; DECIDUAL CELLS; SPONTANEOUS LABOR; GENE-EXPRESSION; CYCLOOXYGENASE-2; FLUID; INFECTION; TYPE-2; COX-2; ONSET AB Context: Prostaglandin-endoperoxide synthase 2 (PTGS2) is a key enzyme involved in parturition. PTGS2 mRNA was found to be differentially expressed between placental amnion (amnion overlying the placental disc) and reflected amnion (amnion of the extraplacental chorioamniotic membranes) in term placentas. Objective: The aim was to evaluate the spatial and temporal regulation of PTGS2 expression in the amnion and the chorion-decidua. Design: PTGS2 expression was analyzed in the amnion and chorion-decidua obtained from 32 women: term not in labor (n = 12), term in labor (n = 12), and preterm labor (n = 8), by immunoblotting and densitometry. Prostaglandin E(2) (PGE(2)) in the amnion and chorion-decidua was measured by a specific immunoassay. Results: Compared to preterm labor cases, PTGS2 expression increased at term before the onset of labor far more prominently in placental amnion (4.5-fold; P = 0.002) than in reflected amnion (1.4-fold; P = 0.007). There was a significant increase in PTGS2 expression in reflected amnion (2.9-fold; P < 0.01) but not in placental amnion with labor at term. PTGS2 expression was higher in reflected amnion than in chorion-decidua in labor at term (2.9-fold; P < 0.01). PTGS2 was barely detected in amnion and chorion-decidua with preterm labor. Expression of PGE2 showed a good correlation with PTGS2 expression (r = 0.722; P < 0.001). Conclusion: PTGS2 expression in the amnion shows a distinct spatial and temporal regulation. Spontaneous labor at term and pathological preterm labor clearly differ in amniotic PTGS2 and PGE2 abundance. Our observations underscore the biological significance of the amnion and amniotic fluid in human parturition. (J Clin Endocrinol Metab 95: E86-E91, 2010) C1 [Kim, Jung-Sun; Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Yoo, Wonsuk] Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. [Mittal, Pooja; Kusanovic, Juan Pedro; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110799, South Korea. [Lee, Deug-Chan; Romero, Roberto; Lee, JoonHo] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lee, Deug-Chan; Romero, Roberto; Lee, JoonHo] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI 48201 USA. RP Kim, CJ (reprint author), Wayne State Univ, Sch Med, Hutzel Womens Hosp, Dept Pathol, 3990 John R St, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu; cjkim@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This work was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 22 TC 11 Z9 11 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP E86 EP E91 DI 10.1210/jc.2010-0203 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300015 PM 20519349 ER PT J AU Lindstrom, S Ma, J Altshuler, D Giovannucci, E Riboli, E Albanes, D Allen, NE Berndt, SI Boeing, H Bueno-de-Mesquita, HB Chanock, SJ Dunning, AM Feigelson, HS Gaziano, JM Haiman, CA Hayes, RB Henderson, BE Hunter, DJ Kaaks, R Kolonel, LN Le Marchand, L Martinez, C Overvad, K Siddiq, A Stampfer, M Stattin, P Stram, DO Thun, MJ Trichopoulos, D Tumino, R Virtamo, J Weinstein, SJ Yeager, M Kraft, P Freedman, ML AF Lindstroem, Sara Ma, Jing Altshuler, David Giovannucci, Edward Riboli, Elio Albanes, Demetrius Allen, Naomi E. Berndt, Sonja I. Boeing, Heiner Bueno-de-Mesquita, H. Bas Chanock, Stephen J. Dunning, Alison M. Feigelson, Heather Spencer Gaziano, J. Michael Haiman, Christopher A. Hayes, Richard B. Henderson, Brian E. Hunter, David J. Kaaks, Rudolf Kolonel, Laurence N. Le Marchand, Loic Martinez, Carmen Overvad, Kim Siddiq, Afshan Stampfer, Meir Stattin, Paer Stram, Daniel O. Thun, Michael J. Trichopoulos, Dimitrios Tumino, Rosario Virtamo, Jarmo Weinstein, Stephanie J. Yeager, Meredith Kraft, Peter Freedman, Matthew L. TI A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CAG-REPEAT POLYMORPHISM; GROWTH-FACTOR-I; MULTIETHNIC COHORT; GENETIC-VARIATION; REGULATING GENES; STEROID-HORMONES; MEN; NUTRITION; LENGTH; ASSOCIATION AB Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. Along-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes. Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels. Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 x 10(-5)) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively). Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol. (J Clin Endocrinol Metab 95: E121-E127, 2010) C1 [Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Lindstroem, Sara; Stampfer, Meir; Trichopoulos, Dimitrios; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward; Stampfer, Meir] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Ma, Jing; Hunter, David J.; Stampfer, Meir] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. [Altshuler, David] Broad Inst Massachusetts Inst Technol MIT & Harva, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England. [Albanes, Demetrius; Berndt, Sonja I.; Chanock, Stephen J.; Hayes, Richard B.; Weinstein, Stephanie J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Allen, Naomi E.] Univ Oxford, Canc Epidemiol Unit, Oxford, England. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Dunning, Alison M.] Univ Cambridge, Dept Oncol, Cambridge, England. [Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Feigelson, Heather Spencer] Kaiser Permanente, Denver, CO USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Haiman, Christopher A.; Henderson, Brian E.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hayes, Richard B.] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA. [Kaaks, Rudolf] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Martinez, Carmen] Ctr Invest Biomed Red Epidemiol & Salud Publ, Granada, Spain. [Martinez, Carmen] Andalusian Sch Publ Hlth, Granada, Spain. [Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark. [Stattin, Paer] Umea Univ, Umea, Sweden. [Tumino, Rosario] Canc Registry Azienda Osped Civile MP Arezzo, Ragusa, Italy. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Freedman, Matthew L.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM mfreedman@partners.org RI Altshuler, David/A-4476-2009; Albanes, Demetrius/B-9749-2015; OI Altshuler, David/0000-0002-7250-4107; Dunning, Alison Margaret/0000-0001-6651-7166; Hayes, Richard/0000-0002-0918-661X FU National Cancer Institute [UO1-CA98233, UO1-CA98710, UO1-CA98216, UO1-CA98758]; National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics; Swedish Research Council (Vetenskapsradet) FX This work was supported by National Cancer Institute cooperative agreements UO1-CA98233, UO1-CA98710, UO1-CA98216, and UO1-CA98758, and by the Intramural Research Program of National Institutes of Health/National Cancer Institute, Division of Cancer Epidemiology and Genetics. S. \L. is supported by the Swedish Research Council (Vetenskapsradet). NR 32 TC 26 Z9 27 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP E121 EP E127 DI 10.1210/jc.2009-1911 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300020 PM 20534771 ER PT J AU Mumford, SL Schisterman, EF Siega-Riz, AM Browne, RW Gaskins, AJ Trevisan, M Steiner, AZ Daniels, JL Zhang, CL Perkins, NJ Wactawski-Wende, J AF Mumford, Sunni L. Schisterman, Enrique F. Siega-Riz, Anna Maria Browne, Richard W. Gaskins, Audrey J. Trevisan, Maurizio Steiner, Anne Z. Daniels, Julie L. Zhang, Cuilin Perkins, Neil J. Wactawski-Wende, Jean TI A Longitudinal Study of Serum Lipoproteins in Relation to Endogenous Reproductive Hormones during the Menstrual Cycle: Findings from the BioCycle Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; PLASMA-LIPIDS; SR-BI; CHOLESTEROL; METABOLISM; DISEASE; TRIAL AB Context: Exogenous estrogens have been shown to affect the lipid profile, leading to the hypothesis that endogenous estrogens may have similar effects. Objective: The objective of the study was to evaluate the association between endogenous estrogen and serum lipoproteins across the menstrual cycle. Design: This was a prospective cohort study. Setting: The study was conducted at the University at Buffalo, 2005-2007. Participants: Participants included 259 healthy, regularly menstruating women aged 18-44 yr. Main Outcome Measures: Serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides measured up to eight times per cycle for up to two cycles were measured. Results: Total and LDL cholesterol were lower during the luteal phase as compared with the follicular phase (P < 0.001), and HDL levels were highest around ovulation (P < 0.001). More women were classified above the desirable range (LDL >= 130 mg/dl or total cholesterol >= 200 mg/dl) when measured during the follicular phase. Estradiol was positively associated with HDL in acute effects models [beta = 0.019, 95% confidence interval (CI) 0.015, 0.022] and inversely associated with total (beta = -0.017, 95% CI -0.020, -0.014) and LDL cholesterol (beta = -0.023, 95% CI -0.027, -0.018) and triglycerides (beta = -0.041, 95% CI -0.054, -0.029) in persistent effects models. Conclusions: Endogenous estrogen, like exogenous estrogen, appears to have beneficial effects on the lipid profile. Because lipoprotein cholesterol levels vary across the menstrual cycle, cyclic variations in lipoprotein levels may need to be considered in the design and interpretation of studies in reproductive-age women and in the clinical management of women's cholesterol. (J Clin Endocrinol Metab 95: E80-E85, 2010) C1 [Mumford, Sunni L.; Schisterman, Enrique F.; Gaskins, Audrey J.; Zhang, Cuilin; Perkins, Neil J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Mumford, Sunni L.; Siega-Riz, Anna Maria; Daniels, Julie L.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Steiner, Anne Z.] Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA. [Browne, Richard W.; Trevisan, Maurizio; Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. [Trevisan, Maurizio] Univ Nevada Hlth Sci Syst, Las Vegas, NV 89103 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd 7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 20 TC 22 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2010 VL 95 IS 9 BP E80 EP E85 DI 10.1210/jc.2010-0109 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 647SU UT WOS:000281640300014 PM 20534764 ER PT J AU Xiao, TS AF Xiao, Tsan Sam TI Subversion of Innate Immune Signaling Through Molecular Mimicry SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE Microbial subversion of innate signaling; TIR domain; PYD domain; molecular mimicry ID TOLL/INTERLEUKIN-1 RECEPTOR DOMAIN; BRUTONS TYROSINE KINASE; TIR-DOMAIN; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; VACCINIA VIRUS; PROTEIN; ADAPTER; FAMILY; BRUCELLA AB Innate immune signaling is mediated by a number of membrane-anchored or cytosolic receptor or sensor molecules. Several receptor families utilize conserved signaling domains such as the Toll/interleukin-1 receptor (TIR) domain and Pyrin domain (PYD) to link microbe recognition to induction of proinflammatory cytokines and interferons. Recent studies have identified a number of bacterial and viral TIR domains and PYD domains that directly target the signaling function of their host homologues. Emerging biochemical and structural studies of these microbial TIR and PYD domains suggest that they are mimics of their host counterparts at the sequence and structure levels. Unraveling the mechanisms of such molecular mimicry is crucial to our understanding and clinical intervention of infectious diseases and inflammatory disorders. C1 NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Xiao, TS (reprint author), NIAID, Struct Immunobiol Unit, Immunol Lab, NIH, 4 Mem Dr,Bldg 4,Room 138, Bethesda, MD 20892 USA. EM Xiaot@niaid.nih.gov RI Xiao, Tsan/I-7616-2013; Xiao, Tsan/A-8590-2010 OI Xiao, Tsan/0000-0001-9688-475X; FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX The author is supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 32 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2010 VL 30 IS 5 BP 638 EP 642 DI 10.1007/s10875-010-9435-0 PG 5 WC Immunology SC Immunology GA 648KX UT WOS:000281693700004 PM 20589422 ER PT J AU Caspi, RR AF Caspi, Rachel R. TI A look at autoimmunity and inflammation in the eye SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID REGULATORY T-CELLS; KOYANAGI-HARADA-DISEASE; HLA CLASS-II; ENDOTOXIN-INDUCED UVEITIS; HLA-A29 TRANSGENIC MICE; RETINAL S-ANTIGEN; NEO-SELF ANTIGEN; BIRDSHOT RETINOCHOROIDOPATHY; OCULAR AUTOIMMUNITY; THYMIC EXPRESSION AB Autoimmune and inflammatory uveitis are a group of potentially blinding intraocular inflammatory diseases that arise without a known infectious trigger and are often associated with immunological responses to unique retinal proteins. In the United States, about 10% of the cases of severe visual handicap are attributed to this group of disorders. As I discuss here, experimental models of ocular autoimmunity targeting retinal proteins have brought about a better understanding of the basic immunological mechanisms involved in the pathogenesis of uveitis and are serving as templates for the development of novel therapies. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov OI Caspi, Rachel/0000-0002-7140-7671 NR 122 TC 132 Z9 136 U1 1 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2010 VL 120 IS 9 BP 3073 EP 3083 DI 10.1172/JCI42440 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 645LJ UT WOS:000281458800009 PM 20811163 ER PT J AU Land, SR Kopec, JA Julian, TB Brown, AM Anderson, SJ Krag, DN Christian, NJ Costantino, JP Wolmark, N Ganz, PA AF Land, Stephanie R. Kopec, Jacek A. Julian, Thomas B. Brown, Ann M. Anderson, Stewart J. Krag, David N. Christian, Nicholas J. Costantino, Joseph P. Wolmark, Norman Ganz, Patricia A. TI Patient-Reported Outcomes in Sentinel Node-Negative Adjuvant Breast Cancer Patients Receiving Sentinel-Node Biopsy or Axillary Dissection: National Surgical Adjuvant Breast and Bowel Project Phase III Protocol B-32 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CLINICAL-TRIAL; UPPER-LIMB MORBIDITY; LONG-TERM MORBIDITY; RACS SNAC TRIAL; LYMPH-NODE; ARM MORBIDITY; WOMENS CHOICE; STAGE-I; MULTICENTER AB Purpose Sentinel lymph node resection (SNR) may reduce morbidity while providing the same clinical utility as conventional axillary dissection (AD). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 is a randomized phase III trial comparing SNR immediately followed by AD (SNAD) to SNR and subsequent AD if SN is positive. We report the definitive patient-reported outcomes (PRO) comparisons. Patients and Methods Eligible patients had clinically node-negative, operable invasive breast cancer. The PRO substudy included all SN-negative participants enrolled May 2001 to February 2004 at community institutions in the United States (n = 749; 78% age >= 50; 87% clinical tumor size <= 2.0 cm; 84% lumpectomy; 87% white). They completed questionnaires presurgery, 1 and 2 to 3 weeks postoperatively, and every 6 months through year 3. Arm symptoms, arm use avoidance, activity limitations, and quality of life (QOL) were compared with intent-to-treat two-sample t-tests and repeated measures analyses. Results Arm symptoms were significantly more bothersome for SNAD compared with SNR patients at 6 months (mean, 4.8 v 3.0; P < .001) and at 12 months (3.6 v 2.5; P = .006). Longitudinally, SNAD patients were more likely to experience ipsilateral arm and breast symptoms, restricted work and social activity, and impaired QOL (P <= .002 all items). From 12 to 36 months, fewer than 15% of either SNAD or SNR patients reported moderate or greater severity of any given symptom or activity limitation. Conclusion Arm morbidity was greater with SNAD than with SNR. Despite considerable fears about complications from AD for breast cancer, this study demonstrates that initial problems with either surgery resolve over time. C1 [Land, Stephanie R.] Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Dept Biostat,Operat & Biostat Ctr, Pittsburgh, PA 15213 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ British Columbia, Arthritis Res Ctr Canada, Vancouver, BC V5Z 1M9, Canada. Univ Vermont, Coll Med, Burlington, VT USA. Univ Vermont, Breast Care Ctr, Burlington, VT USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Land, SR (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Natl Surg Adjuvant Breast & Bowel Project, Dept Biostat,Operat & Biostat Ctr, 201 N Craig St,Suite 350, Pittsburgh, PA 15213 USA. EM land@pitt.edu OI Anderson, Stewart/0000-0001-8948-0650 FU National Cancer Institute, Department of Health and Human Services, Public Health Service [U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974, 5RO1-CA-074137]; Vermont Cancer Center [P30 CA22435] FX Supported by the Grants No. U10-CA-12027, U10-CA-69651, U10-CA-37377, U10-CA-69974, and 5RO1-CA-074137 (D.N.K.) from the National Cancer Institute, Department of Health and Human Services, Public Health Service, and by Grant No. P30 CA22435 from the Vermont Cancer Center. NR 41 TC 53 Z9 56 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2010 VL 28 IS 25 BP 3929 EP 3936 DI 10.1200/JCO.2010.28.2491 PG 8 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500008 PM 20679600 ER PT J AU O'Connell, MJ Lavery, I Yothers, G Paik, S Clark-Langone, KM Lopatin, M Watson, D Baehner, FL Shak, S Baker, J Cowens, JW Wolmark, N AF O'Connell, Michael J. Lavery, Ian Yothers, Greg Paik, Soonmyung Clark-Langone, Kim M. Lopatin, Margarita Watson, Drew Baehner, Frederick L. Shak, Steven Baker, Joffre Cowens, J. Wayne Wolmark, Norman TI Relationship Between Tumor Gene Expression and Recurrence in Four Independent Studies of Patients With Stage II/III Colon Cancer Treated With Surgery Alone or Surgery Plus Adjuvant Fluorouracil Plus Leucovorin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLORECTAL-CANCER; THYMIDYLATE SYNTHASE; DUKES-B; DIHYDROPYRIMIDINE DEHYDROGENASE; MICROSATELLITE-INSTABILITY; PREDICT RECURRENCE; PROGNOSTIC VALUE; MISMATCH REPAIR; CHROMOSOME 18Q; BREAST-CANCER AB Purpose These studies were conducted to determine the relationship between quantitative tumor gene expression and risk of cancer recurrence in patients with stage II or III colon cancer treated with surgery alone or surgery plus fluorouracil (FU) and leucovorin (LV) to develop multigene algorithms to quantify the risk of recurrence as well as the likelihood of differential treatment benefit of FU/LV adjuvant chemotherapy for individual patients. Patients and Methods We performed quantitative reverse transcription polymerase chain reaction (RT-qPCR) on RNA extracted from fixed, paraffin-embedded (FPE) tumor blocks from patients with stage II or III colon cancer who were treated with surgery alone (n = 270 from National Surgical Adjuvant Breast and Bowel Project [NSABP] C-01/C-02 and n = 765 from Cleveland Clinic [CC]) or surgery plus FU/LV (n = 308 from NSABP C-04 and n = 508 from NSABP C-06). Overall, 761 candidate genes were studied in C-01/C-02 and C-04, and a subset of 375 genes was studied in CC/C-06. Results A combined analysis of the four studies identified 48 genes significantly associated with risk of recurrence and 66 genes significantly associated with FU/LV benefit (with four genes in common). Seven recurrence-risk genes, six FU/LV-benefit genes, and five reference genes were selected, and algorithms were developed to identify groups of patients with low, intermediate, and high likelihood of recurrence and benefit from FU/LV. Conclusion RT-qPCR of FPE colon cancer tissue applied to four large independent populations has been used to develop multigene algorithms for estimating recurrence risk and benefit from FU/LV. These algorithms are being independently validated, and their clinical utility is being evaluated in the Quick and Simple and Reliable (QUASAR) study. C1 [O'Connell, Michael J.] Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, Pittsburgh, PA 15212 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Project, Ctr Stat, Pittsburgh, PA USA. Cleveland Clin, Cleveland, OH 44106 USA. Genom Hlth Inc, Redwood City, CA USA. RP O'Connell, MJ (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Allegheny Ctr 4, 5th Floor, Pittsburgh, PA 15212 USA. EM michael.oconnell@nsabp.org OI Yothers, Greg/0000-0002-7965-7333 FU National Cancer Institute, National Institutes of Health, Department of Health and Human Services [U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651]; Genomic Health, Inc. FX Supported by Public Health Service Grants No. U10-CA-37377, U10-CA-69974, U10-CA-12027, and U10-CA-69651 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by Genomic Health, Inc. NR 57 TC 128 Z9 131 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2010 VL 28 IS 25 BP 3937 EP 3944 DI 10.1200/JCO.2010.28.9538 PG 8 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500009 PM 20679606 ER PT J AU Widemann, BC Balis, FM Kim, A Boron, M Jayaprakash, N Shalabi, A O'Brien, M Eby, M Cole, DE Murphy, RF Fox, E Ivy, P Adamson, PC AF Widemann, Brigitte C. Balis, Frank M. Kim, AeRang Boron, Matthew Jayaprakash, Nalini Shalabi, Aiman O'Brien, Michelle Eby, Michelle Cole, Diane E. Murphy, Robert F. Fox, Elizabeth Ivy, Percy Adamson, Peter C. TI Glucarpidase, Leucovorin, and Thymidine for High-Dose Methotrexate-Induced Renal Dysfunction: Clinical and Pharmacologic Factors Affecting Outcome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARBOXYPEPTIDASE G2 RESCUE; CANCER-PATIENTS; INDUCED NEPHROTOXICITY; G(2) RESCUE; ELIMINATION; FAILURE; THERAPY; PHARMACOKINETICS; TOXICITY; PATIENT AB Purpose To assess the role of the recombinant bacterial enzyme, glucarpidase (carboxypeptidase-G(2)), leucovorin, and thymidine in the management and outcome of patients with high-dose methotrexate (HDMTX)-induced nephrotoxicity. Methods Patients with HDMTX-induced nephrotoxicity received one to three doses of intravenous (IV) glucarpidase and leucovorin rescue. The initial cohort (n = 35) also received thymidine by continuous IV infusion. Subsequently, thymidine was restricted to patients with prolonged exposure (> 96 hours) to methotrexate (MTX) or with substantial MTX toxicity at study entry. Plasma MTX, leucovorin, and 5-methyltetrahydrofolate (5-mTHF) concentrations were measured pre- and postglucarpidase. Toxicities were monitored, and logistic regression analysis was used to assess the relationship of baseline characteristics to the development of severe toxicity and death. Results Glucarpidase was administered at a median of 96 hours (receiving thymidine, n = 44) and 66 hours (not receiving thymidine, n = 56) after the start of the MTX infusion. Plasma MTX concentrations decreased within 15 minutes of glucarpidase by 98.7%. Plasma 5-mTHF concentrations also decreased more than 98% after administration of glucarpidase. Of 12 deaths, six were directly attributed to irreversible MTX toxicity. Presence of grade 4 toxicity before administration of glucarpidase, inadequate initial increase in leucovorin dosing, and administration of glucarpidase more than 96 hours after the start of the MTX infusion were associated with development of grade 4 and 5 toxicity. Conclusion Early intervention with the combination of leucovorin and glucarpidase is highly effective in patients who develop HDMTX-induced renal dysfunction. Severe toxicity and mortality occurred in patients in whom glucarpidase rescue was delayed and occurred despite thymidine administration. C1 [Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750, Bethesda, MD 20892 USA. EM widemanb@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, Bethesda, MD. NR 28 TC 34 Z9 37 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2010 VL 28 IS 25 BP 3979 EP 3986 DI 10.1200/JCO.2009.25.4540 PG 8 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500015 PM 20679598 ER PT J AU Thomas, MB Jaffe, D Choti, MM Belghiti, J Curley, S Fong, YM Gores, G Kerlan, R Merle, P O'Neil, B Poon, R Schwartz, L Tepper, J Yao, F Haller, D Mooney, M Venook, A AF Thomas, Melanie B. Jaffe, Deborah Choti, Michael M. Belghiti, Jacques Curley, Steven Fong, Yuman Gores, Gregory Kerlan, Robert Merle, Phillipe O'Neil, Bert Poon, Ronnie Schwartz, Lawrence Tepper, Joel Yao, Francis Haller, Daniel Mooney, Margaret Venook, Alan TI Hepatocellular Carcinoma: Consensus Recommendations of the National Cancer Institute Clinical Trials Planning Meeting SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; ENDOTHELIAL GROWTH-FACTOR; TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; ACTIVATED PROTEIN-KINASES; MULTIDETECTOR-ROW CT; PRIMARY LIVER-CANCER; CHRONIC HEPATITIS-C; LONG-TERM SURVIVAL; DISEASE MELD SCORE; PHASE-II TRIAL AB Hepatocelluar carcinoma (HCC) is the most common primary malignancy of the liver in adults and the third most common cause of cancer death worldwide. The incidence of HCC in the United States is rising steadily because of the prevalence of hepatitis C viral infection and other causes of hepatic cirrhosis. The majority of patients have underlying hepatic dysfunction, which complicates patient management and the search for safe and effective therapies. The Clinical Trials Planning Meeting (CTPM) in HCC was convened by the National Cancer Institute's Gastrointestinal Cancer Steering Committee to identify the key knowledge gaps in HCC and define clinical research priorities. The CTPM structured its review according to current evidence-based treatment modalities in HCC and prioritized the recommendations on the basis of the patient populations representing the greatest unmet medical need. C1 [Thomas, Melanie B.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Mayo Clin, Rochester, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Hop Hotel Dieu, Paris, France. Univ N Carolina, Chapel Hill, NC USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Univ Penn, Philadelphia, PA 19104 USA. RP Thomas, MB (reprint author), Med Univ S Carolina, Hollings Canc Ctr, 86 Jonathan Lucas St,Suite 118K, Charleston, SC 29425 USA. EM thomasmb@musc.edu FU Genentech BioOncology; Bayer Pharmaceuticals; Genentech; Pfizer FX Research Funding: Melanie B. Thomas, Genentech BioOncology; Michael M. Choti, Bayer Pharmaceuticals; Bert O'Neil, Bayer Pharmaceuticals; Alan Venook, Genentech, Bayer Pharmaceuticals, Pfizer NR 148 TC 165 Z9 168 U1 2 U2 15 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2010 VL 28 IS 25 BP 3994 EP 4005 DI 10.1200/JCO.2010.28.7805 PG 12 WC Oncology SC Oncology GA 645YQ UT WOS:000281502500017 PM 20679622 ER PT J AU Jobes, ML Epstein, DH Preston, KL AF Jobes, Michelle L. Epstein, David H. Preston, Kenzie L. TI EFFECTS OF CLONIDINE ON COCAINE CRAVING IN RESPONSE TO STRESS- AND DRUG-RELATED SCRIPTS SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 39th Annual Meeting on American-College-of-Clinical-Pharmacology CY SEP 12-14, 2010 CL Baltimore, MD SP Amer coll Pharmacol C1 [Jobes, Michelle L.; Epstein, David H.; Preston, Kenzie L.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2010 VL 50 IS 9 MA 138 BP 1089 EP 1089 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650OD UT WOS:000281858000133 ER PT J AU Post, RM Altshuler, LL Frye, MA Suppes, T Keck, PE McElroy, SL Leverich, GS Luckenbaugh, DA Rowe, M Pizzarello, S Kupka, RW Grunze, H Nolen, WA AF Post, Robert M. Altshuler, Lori L. Frye, Mark A. Suppes, Trisha Keck, Paul E., Jr. McElroy, Susan L. Leverich, Gabriele S. Luckenbaugh, David A. Rowe, Michael Pizzarello, Scott Kupka, Ralph W. Grunze, Heinz Nolen, Willem A. TI Complexity of Pharmacologic Treatment Required for Sustained Improvement in Outpatients With Bipolar Disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TREATMENT ENHANCEMENT PROGRAM; I DISORDER; ANTIDEPRESSANT DISCONTINUATION; CLINICAL-TRIALS; DOUBLE-BLIND; MAINTENANCE TREATMENT; DEPRESSED-PATIENTS; 18-MONTH TRIAL; STEP-BD; ILLNESS AB Objective: To evaluate the clinical correlates of and types of naturalistic treatments associated with sustained improvement/remission for at least 6 months in outpatients with bipolar disorder. Method: Five hundred twenty-five outpatients with bipolar disorder (77.7% bipolar 1) gave informed consent, had their mood rated daily on the National Institute of Mental Health Life Chart Method for a minimum of at least 1 year, and recorded all medications. Demographics and clinical characteristics of patients with a "sustained response" (ratings of "improved" or "very much improved" on the Clinical Global Impressions-Bipolar Version for a period of at least 6 months) versus nonresponders were compared. The study was conducted from 1996 to 2002. Results: Of the 429 patients who were ill at study entry, 195 (45.5%) showed a sustained response; 54.5% showed no or insufficient response. A mean of 2.98 medications was given at time of improvement, which occurred after a mean of 18 months of participation in the study. Lithium and valproate were the medications most frequently prescribed at the time of improvement and had among the highest overall success rates. Equally complex regimens were employed in the nonresponders who, however, had a more adverse clinical course prior to network entry. Nonresponders were ultimately exposed to more antidepressants and antipsychotics than the sustained responders. Conclusions: A mean of 1.5 years and at times highly complex medication regimens were required to achieve a sustained response for 6 months during naturalistic outpatient treatment of bipolar disorder. Delineating the clinical and biologic correlates of individual response to combination treatment is a very high clinical research priority, as is developing new treatment strategies for the large proportion of patients who fail to respond in a sustained fashion. J Clin Psychiatry 2010;71(9):1176-1186 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Post, Robert M.; Rowe, Michael] Bipolar Collaborat Network, Dept Biostat, Bethesda, MD 20814 USA. [Post, Robert M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA. [Altshuler, Lori L.] Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. [Altshuler, Lori L.] Vet Affairs Med Ctr, Los Angeles, CA USA. [Frye, Mark A.] Mayo Clin, Dept Psychiat, Rochester, MN USA. [Suppes, Trisha] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Suppes, Trisha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Keck, Paul E., Jr.; McElroy, Susan L.] Univ Cincinnati, Coll Med, Dept Psychiat & Neurosci, Cincinnati, OH USA. [Keck, Paul E., Jr.; McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA. [Luckenbaugh, David A.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Pizzarello, Scott] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Kupka, Ralph W.] Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. [Grunze, Heinz] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9700 AB Groningen, Netherlands. [Kupka, Ralph W.] Free Univ Amsterdam, Dept Psychiat, Med Ctr, NL-1007 MC Amsterdam, Netherlands. RP Post, RM (reprint author), Bipolar Collaborat Network, Dept Biostat, 5415 W Cedar Lane,Suite 201B, Bethesda, MD 20814 USA. EM robert.post@speakeasy.net RI Nolen, Willem/E-9006-2014; OI Grunze, Heinz/0000-0003-4712-8979 FU Abbott; Pfizer; AstraZeneca; NIMH; Stanley Medical Research Institute; JDS Pharmaceuticals; CME Outfitters; Medscape; Wolters Kluwer Pharma Solutions (CNS Drug Supplement); Jones and Bartlett (formerly Compact Clinicals); Alkermes; Cephalon; GlaxoSmithKline; Eli Lilly; Epi-Q; Jazz; Marriott Foundation; Orexigen; Shire; Bristol-Myers Squibb; Forest; Takeda; Johnson & Johnson Pharmaceutical Research Development; UCB Belgium; Stanley Foundation; NHS National Institute for Health Research/Medical Research Council UK; The Netherlands Organization for Health Research and Development; European Union; The Stanley Medical Research Institute; Wyeth; Servier; The Stanley Medical Research Institute, Chevy Chase, Maryland; NIMH, Bethesda, Maryland FX Dr Post has been a consultant to and has been a member of the speakers or advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb, and GlaxoSmithKline. Dr Altshuler has received grant/research support from Abbott; has received honoraria from Abbott, Forest, and GlaxoSmithKline; is a member of the advisory board of Abbott and Forest; and is a member of the speakers board of Forest and GlaxoSmithKline. Dr Frye has received grant support from Pfizer; has been a consultant to Cephalon, Dainippon Sumitomo, Ortho McNeil/Janssen, Johnson & Johnson, Schering-Plough, and Pfizer; and has participated in supported CME activities for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Otsuka, Pfizer, and Schering-Plough. Dr Suppes, from January 2008 to December 2009, received grant support or clinical study medications from AstraZeneca, NIMH, Stanley Medical Research Institute, Abbott, and JDS Pharmaceuticals; had consulting agreements with or served on the advisory board for Orexigen; received honoraria or speakers fees from CME Outfitters, Medscape, and Wolters Kluwer Pharma Solutions (CNS Drug Supplement); received support for travel from AstraZeneca; and received royalties from Jones and Bartlett (formerly Compact Clinicals). Dr Keck is presently or has been in the past year a principal or co-investigator on research studies sponsored by Alkermes, AstraZeneca, Cephalon, GlaxoSmithKline, Eli Lilly, Epi-Q, Jazz, Marriott Foundation, NIMH, Orexigen, Pfizer, and Shire; has been reimbursed for consulting to Sepracor, Medco, GlaxoSmithKline, Schering-Plough, Bristol-Myers Squibb, Pfizer, and QuantiaMD; and is a co-inventor on US patent no. 6,387,956: Shapira NA, Goldsmith TD, Keck PE Jr. (University of Cincinnati). Methods of treating obsessive-compulsive spectrum disorder comprises the step of administering an effective amount of tramadol to an individual. Filed March 25, 1999; approved May 14, 2002. Dr Keck has received no financial gain from this patent. Dr McElroy is a consultant to or member of the scientific advisory boards of AstraZeneca, Eli Lilly, and Schering-Plough and is a principal or coinvestigator on research studies sponsored by Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Jazz, NIMH, Orexigen, Pfizer, and Takeda. Dr McElroy is also inventor on US Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and, along with the patent's assignee, the University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson Pharmaceutical Research & Development, which has exclusive rights under the patent. Dr Kupka has been a member of the speakers or advisory boards of Eli Lilly and AstraZeneca. During the past 3 years, Dr Grunze has received honoraria for consultancies, advisory boards, and paid speaker engagements from AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Pfizer, Sanofi-Aventis, Schering-Plough, Servier, and UBC and has received research grants from AstraZeneca, UCB Belgium, Stanley Foundation, NHS National Institute for Health Research/Medical Research Council UK, and Pfizer. Dr Nolen has received grants from The Netherlands Organization for Health Research and Development, the European Union, The Stanley Medical Research Institute, AstraZeneca, Eli Lilly, GlaxoSmithKline, and Wyeth; has received honoraria or speaker's fees from AstraZeneca, Eli Lilly, Pfizer, Servier, and Wyeth; and has served on the advisory boards of AstraZeneca, Cyberonics, Pfizer, and Servier.; Dr Rowe, Ms Leverich, ad Mssrs Luckenbaugh and Pizzarello have no personal affiliations or financial relationships with any commercial interest to disclose relative to the article.; The conduct of this study was supported by The Stanley Medical Research Institute, Chevy Chase, Maryland. Data analysis was supported by NIMH, Bethesda, Maryland. NR 44 TC 54 Z9 54 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2010 VL 71 IS 9 BP 1176 EP 1186 DI 10.4088/JCP.08m04811yel PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 661EF UT WOS:000282705700010 PM 20923622 ER PT J AU Alegria, AA Hasin, DS Nunes, EV Liu, SM Davies, C Grant, BF Blanco, C AF Alegria, Analucia A. Hasin, Deborah S. Nunes, Edward V. Liu, Shang-Min Davies, Carrie Grant, Bridget F. Blanco, Carlos TI Comorbidity of Generalized Anxiety Disorder and Substance Use Disorders: Results From the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DSM-III-R; DRUG-USE DISORDERS; PSYCHIATRIC RESEARCH INTERVIEW; SAMPLE HEAVY DRINKERS; BIPOLAR I DISORDER; UNITED-STATES; MENTAL-DISORDERS; PERSONALITY-DISORDERS; SCHEDULE AUDADIS; DEPRESSIVE-DISORDERS AB Objective: Prior research has consistently documented a strong association between generalized anxiety disorder (GAD) and substance use disorder (SUD). Comorbidity of GAD and SUD (GAD-SUD) represents clinical challenges, as the patients' symptoms are often more severe and are frequently prolonged, making their management more complex when compared with individuals with GAD only. The purpose of this study was to examine whether individuals with GAD-SUD differ meaningfully from individuals with GAD and no SUD comorbidity (GAD-NSUD) in terms of demographic characteristics, risk factors, psychiatric comorbidity, and clinical correlates. Method: Data were derived from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (N = 43,093). Diagnoses were made using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Results: We found that the lifetime prevalence rate of GAD-SUD is about 2.04%, while that of GAD-NSUD is 2.10%. Individuals with GAD-SUD showed higher psychiatric comorbidity rates than those with GAD-NSUD. Treatment-seeking rates for GAD are equally low in individuals with GAD-SUD and GAD-NSUD. Both groups were as likely to receive pharmacologic treatment for anxiety. Conclusions: The findings of our study indicate that individuals with GAD-SUD constitute half of the lifetime prevalence of GAD and that GAD-SUD is associated with high overall vulnerability for additional psychopathology, particularly in the externalizing spectrum; higher disability; and, higher use of alcohol and drugs to relieve anxiety symptoms. J Clin Psychiatry 2010;71(9):1187-1195 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Alegria, Analucia A.; Hasin, Deborah S.; Nunes, Edward V.; Liu, Shang-Min; Davies, Carrie; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Hasin, Deborah S.; Nunes, Edward V.; Blanco, Carlos] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013; OI Blanco, Carlos/0000-0001-6187-3057; Alegria, Analucia /0000-0001-6044-3311 FU GlaxoSmithKline; Eli Lilly; Pfizer; NIAAA, NIH; NIH [DA019606, DA020783, DA023200, MH076051, R01AA08159, K05AA00161, K24 DA022412]; American Foundation for Suicide Prevention; New York State Psychiatric Institute; NIAAA FX Dr Blanco has received grant/research support from GlaxoSmithKline, Eli Lilly, and Pfizer. Mss Alegria, Liu, and Davies and Drs Hasin, Nunes, and Grant have no personal affiliations or financial relationships with any commercial interest to disclose relative to the article.; The National Epidemiologic Survey on Alcohol and Related Conditions was sponsored by the NIAAA and was funded, in part, by the Intramural Program, NIAAA, NIH. This study was supported by NIH grants DA019606, DA020783, DA023200, and MH076051 (Dr Blanco); R01AA08159 and K05AA00161 (Dr Hasin); and K24 DA022412 (Dr Nunes); the American Foundation for Suicide Prevention (Dr Blanco); and the New York State Psychiatric Institute (Drs Blanco, Nunes, and Hasin). NR 79 TC 31 Z9 32 U1 1 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2010 VL 71 IS 9 BP 1187 EP 1195 DI 10.4088/JCP.09m05328gry PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 661EF UT WOS:000282705700011 PM 20923623 ER PT J AU Blanco, C Alegria, AA Petry, NM Grant, JE Simpson, HB Liu, SM Grant, BF Hasin, DS AF Blanco, Carlos Alegria, Analucia A. Petry, Nancy M. Grant, Jon E. Simpson, H. Blair Liu, Shang-Min Grant, Bridget F. Hasin, Deborah S. TI Prevalence and Correlates of Fire-Setting in the United States: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID GENERAL-POPULATION SAMPLE; PSYCHIATRIC DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; IMPULSE CONTROL DISORDERS; SUBSTANCE USE DISORDERS; FAMILY-HISTORY; RELIABILITY; DISABILITIES; PERSONALITY; CONCORDANCE AB Objective: To estimate the prevalence, sociodemographic correlates, comorbidity, and rates of mental health service utilization of fire-setters in the general population. Method: A face-to-face survey of more than 43,000 adults aged 18 years and older residing in households was conducted during the 2001-2002 period. Diagnoses of mood, anxiety, substance use disorders, and personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version (AUDADIS-IV). Results: The prevalence of lifetime fire-setting in the US population was 1.13 (95% CI, 1.0-1.3). Being male, never married, and US-born and having a yearly income over $70,000 were risk factors for lifetime fire-setting, while being Asian or Hispanic and older than 30 years were protective factors for lifetime fire-setting. The strongest associations with fire-setting were with disorders often associated with deficits in impulse control, such as antisocial personality disorder (ASPD) (odds ratio [OR] = 21.8; CI, 6.6-28.5), drug dependence (OR = 7.6; 95% CI, 5.2-10.9), bipolar disorder (OR = 5.6; 95% CI, 4.0-7.9), and pathological gambling (OR = 4.8; 95% CI, 2.4-9.5). Associations between fire-setting and all antisocial behaviors were positive and significant. A lifetime history of fire-setting, even in the absence of an ASPD diagnosis, was strongly associated with substantial rates of Axis I comorbidity, a history of antisocial behavior, a family history of other antisocial behaviors, decreased functioning, and higher treatment-seeking rates. Conclusions: Our findings suggest that fire-setting may be better understood as a behavioral manifestation of a broader impaired control syndrome and part of the externalizing spectrum. Fire-setting and other antisocial behaviors tend to be strongly associated with each other and increase the risk of lifetime and current psychiatric disorders, even in the absence of a DSM-IV diagnosis of ASPD. J Clin Psychiatry 2010;71(9):1218-1225 (C) Copyright 2010 Physicians Postgraduate Press, Inc. C1 [Blanco, Carlos; Alegria, Analucia A.; Simpson, H. Blair; Liu, Shang-Min; Hasin, Deborah S.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. [Petry, Nancy M.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Grant, Jon E.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Grant, Jon E.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Blanco, C (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr,Box 69, New York, NY 10032 USA. EM cb255@columbia.edu RI Blanco, Carlos/I-4906-2013; OI Blanco, Carlos/0000-0001-6187-3057; Alegria, Analucia /0000-0001-6044-3311 FU Pfizer; GlaxoSmithKline; Forest; Somaxon; Janssen; NIH [DA019606, DA020783, DA023200, MH076051, AA014223]; American Foundation for Suicide Prevention; New York State Psychiatric Institute; NIAAA FX Dr Blanco has received grant/research support from Pfizer and GlaxoSmithKline. Dr Jon Grant has received grant/research support from Forest, Somaxon, and GlaxoSmithKline. Dr Simpson has received grant/research support and study medication from Janssen and has been a member of the Scientific Advisory Board for Jazz. Drs Bridget Grant, Hasin, and Petry and Mss Alegria and Liu report no financial or other relationship relevant to the subject of this article.; This study is supported by NIH grants DA019606, DA020783, DA023200, MH076051 (Dr Blanco) and AA014223 (Dr Hasin), a grant from the American Foundation for Suicide Prevention (Dr Blanco), and the New York State Psychiatric Institute (Drs Blanco, Hasin, and Simpson). The National Epidemiologic Survey on Alcohol and Related Conditions was funded by the NIAAA, with supplemental support from the National Institute on Drug Abuse. NR 45 TC 19 Z9 20 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2010 VL 71 IS 9 BP 1218 EP 1225 DI 10.4088/JCP.08m04812gry PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 661EF UT WOS:000282705700015 PM 20361899 ER PT J AU Hsu, CH Zhang, Y Hardison, RC Green, ED Miller, W AF Hsu, Chih-Hao Zhang, Yu Hardison, Ross C. Green, Eric D. Miller, Webb CA NISC Comparative Sequencing Progra TI An Effective Method for Detecting Gene Conversion Events in Whole Genomes SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE algorithms; computational molecular biology; evolution ID DUPLICATION; MOUSE; DISEASE AB Gene conversion events are often overlooked in analyses of genome evolution. In a conversion event, an interval of DNA sequence (not necessarily containing a gene) overwrites a highly similar sequence. The event creates relationships among genomic intervals that can confound attempts to identify orthologs and to transfer functional annotation between genomes. Here we examine 1,616,329 paralogous pairs of mouse genomic intervals, and detect conversion events in about 7.5% of them. Properties of the putative gene conversions are analyzed, such as the lengths of the paralogous pairs and the spacing between their sources and targets. Our approach is illustrated using conversion events in primate CCL gene clusters. Source code for our program is included in the 3SEQ_2D package, which is freely available at www.bx.psu.edu/miller_lab/. C1 [Hsu, Chih-Hao; Zhang, Yu; Hardison, Ross C.; Miller, Webb] Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. [Green, Eric D.] NISC, NIH, Intramural Sequencing Ctr, Bethesda, MD 20892 USA. [Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Hsu, CH (reprint author), Penn State Univ, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. EM cxh503@psu.edu RI Hardison, Ross/G-1142-2010 OI Hardison, Ross/0000-0003-4084-7516 FU Intramural NIH HHS; NHGRI NIH HHS [HG02238]; NIDDK NIH HHS [DK065806, R01 DK065806] NR 21 TC 8 Z9 8 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD SEP PY 2010 VL 17 IS 9 BP 1281 EP 1297 DI 10.1089/cmb.2010.0103 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 655UL UT WOS:000282275800013 PM 20874409 ER PT J AU Hammoud, DA Munter, FM Brat, DJ Pomper, MG AF Hammoud, Dima A. Munter, Fletcher M. Brat, Daniel J. Pomper, Martin G. TI Magnetic Resonance Imaging Features of Pituicytomas: Analysis of 10 Cases SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pituicytoma; neurohypophyseal tumor; MRI ID POSTERIOR PITUITARY; BENIGN-TUMOR; NEUROHYPOPHYSIS; ASTROCYTOMA AB Objective: To describe the magnetic resonance imaging features of pituicytomas and identify any specific features that could differentiate this tumor from other sellar/suprasellar masses. Methods: Magnetic resonance images, clinical histories, and pathological findings of 10 patients with pituicytoma were retrospectively reviewed. Reports of clinical history, pathology, and magnetic resonance imaging findings were reviewed for 28 additional histologically proven pituicytoma cases, previously reported in the literature. Results: Pituicytomas were mostly round or oval, sharply defined, and located in the sellar and/or suprasellar region. Tumors were generally isointense to gray matter on T1-weighted images and isointense to slightly hyperintense on T2-weighted images, and they enhanced intensely. Conclusions: Magnetic resonance imaging features of pituicytomas overlap with those of other, more common lesions that occur in the region. With the exception of a purely suprasellar-enhancing mass or a clearly defined neurohypophyseal mass separate from the anterior pituitary, the similarity to common tumors such as macroadenomas and meningiomas probably precludes effective prospective diagnosis of pituicytomas. C1 [Hammoud, Dima A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Munter, Fletcher M.] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Brat, Daniel J.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Pomper, Martin G.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21205 USA. RP Hammoud, DA (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Room 1C336, Bethesda, MD 20892 USA. EM hammoudd@cc.nih.gov RI Hammoud, Dima/C-2286-2015 NR 20 TC 20 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2010 VL 34 IS 5 BP 757 EP 761 DI 10.1097/RCT.0b013e3181e289c0 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 653OD UT WOS:000282100400019 PM 20861781 ER PT J AU Stern, ST Hall, JB Yu, LL Wood, LJ Paciotti, GF Tamarkin, L Long, SE McNeil, SE AF Stern, Stephan T. Hall, Jennifer B. Yu, Lee L. Wood, Laura J. Paciotti, Giulio F. Tamarkin, Lawrence Long, Stephen E. McNeil, Scott E. TI Translational considerations for cancer nanomedicine SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 7th InternatIional NanoDDS Meeting CY OCT 05-06, 2009 CL Indianapolis, IN DE Nanotechnology; Biological potency; Modeling and simulation; Clinical starting dose; Allometry ID IN-VITRO; MONOCLONAL-ANTIBODIES; INTRAVENOUS-INJECTION; SILICA NANOPARTICLES; ANTITUMOR EFFICACY; TOXICITY DATA; PBPK MODEL; BIODISTRIBUTION; TUMOR; VIVO AB There are many important considerations during preclinical development of cancer nanomedicines, including: 1) unique aspects of animal study design; 2) the difficulties in evaluating biological potency, especially for complex formulations; 3) the importance of analytical methods that can determine platform stability in vivo, and differentiate bound and free active pharmaceutical ingredient (API) in biological matrices; and 4) the appropriateness of current dose scaling techniques for estimation of clinical first-in-man dose from preclinical data. Biologics share many commonalities with nanotechnology products with regard to complexity and biological attributes, and can, in some cases, provide context for dealing with these preclinical issues. In other instances, such as the case of in vivo stability analysis, new approaches are required. This paper will discuss the significance of these preclinical issues, and present examples of current methods and best practices for addressing them. Where possible, these recommendations are justified using the existing regulatory guidance literature. (C) 2010 Elsevier B.V. All rights reserved. C1 [Stern, Stephan T.; Hall, Jennifer B.; McNeil, Scott E.] NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. [Yu, Lee L.; Wood, Laura J.; Long, Stephen E.] NIST, Gaithersburg, MD 20899 USA. [Paciotti, Giulio F.; Tamarkin, Lawrence] CytImmune Sci, Rockville, MD 20850 USA. RP Stern, ST (reprint author), NCI, Nanotechnol Characterizat Lab, Adv Technol Program, SAIC Frederick Inc, POB B, Frederick, MD 21702 USA. EM sternstephan@mail.nih.gov; halljennifer@mail.nih.gov; lee.yu@nist.gov; laura.wood@nist.gov; gpaciotti@cytimmune.com; ltamarkin@cytimune.com; stephen.long@nist.gov; ncl@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012; Yu, Lee/N-7263-2015 OI Yu, Lee/0000-0002-8043-6853 FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [HHSN261200800001E] NR 60 TC 50 Z9 51 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD SEP 1 PY 2010 VL 146 IS 2 SI SI BP 164 EP 174 DI 10.1016/j.jconrel.2010.04.008 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 642ZS UT WOS:000281261900002 PM 20385183 ER PT J AU Tao, JA Yang, ZDA Blumberg, PM AF Tao, Juan Yang, Zhi D. A. Blumberg, Peter M. TI RasGRP3-a new therapeutic target in human melanoma SO JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract C1 [Tao, Juan] Huazhong Univ Sci & Technol, Dept Dermatol, Wuhan, Hubei, Peoples R China. [Tao, Juan; Yang, Zhi D. A.; Blumberg, Peter M.] NCI, Ctr Canc Res, 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 0385-2407 J9 J DERMATOL JI J. Dermatol. PD SEP PY 2010 VL 37 SU 1 BP 42 EP 43 PG 2 WC Dermatology SC Dermatology GA 648ZF UT WOS:000281733400149 ER PT J AU Gentile, JK Tan, WH Horowitz, LT Bacino, CA Skinner, SA Barbieri-Welge, R Bauer-Carlin, A Beaudet, AL Bichell, TJ Lee, HS Sahoo, T Waisbren, SE Bird, LM Peters, SU AF Gentile, Jennifer K. Tan, Wen-Hann Horowitz, Lucia T. Bacino, Carlos A. Skinner, Steven A. Barbieri-Welge, Rene Bauer-Carlin, Astrid Beaudet, Arthur L. Bichell, Terry Jo Lee, Hye-Seung Sahoo, Trilochan Waisbren, Susan E. Bird, Lynne M. Peters, Sarika U. TI A Neurodevelopmental Survey of Angelman Syndrome With Genotype-Phenotype Correlations SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE Angelman syndrome; development; behavior; phenotype ID PRADER-WILLI-SYNDROME; FRAGILE-X-SYNDROME; MOUSE MODEL; MOLECULAR CHARACTERIZATION; CLINICAL-FEATURES; ADAPTIVE-BEHAVIOR; DOWN-SYNDROME; DELETION; CHILDREN; PROFILES AB Objective: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a deletion on chromosome 15, uniparental disomy, imprinting defect, or UBE3A mutation. It is characterized by intellectual disability with minimal speech and certain behavioral characteristics. We used standardized measures to characterize the developmental profile and to analyze genotype-phenotype correlations in AS. Method: The study population consisted of 92 children, between 5 months and 5 years of age, enrolled in a Natural History Study. Each participant was evaluated using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), the Vineland Adaptive Behavior Scales, Second Edition (VABS-II), and the Aberrant Behavior Checklist. Results: Seventy-four percent had a deletion and 26% had uniparental disomy, an imprinting defect or a UBE3A mutation ("nondeletion"). The mean +/- standard deviation BSID-III cognitive scale developmental quotient (DQ) was 40.5 +/- 15.5. Participants with deletions were more developmentally delayed than the non-deletion participants in all BSID-III domains except in expressive language skills. The cognitive DQ was higher than the DQ in each of the other domains, and the receptive language DQ was higher than the expressive language DQ. VABS-II, deletion participants had weaker motor and language skills than the non-deletion participants. Conclusion: Children with AS have a distinct developmental and behavioral profile; their cognitive skills are stronger than their language and motor skills, and their receptive language skills are stronger than expressive language skills. Developmental outcomes are associated with genotype, with deletion patients having worse outcomes than non-deletion patients. C1 [Peters, Sarika U.] Vanderbilt Univ, Kennedy Ctr Res Human Dev, Nashville, TN 37203 USA. [Gentile, Jennifer K.; Waisbren, Susan E.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Gentile, Jennifer K.; Tan, Wen-Hann; Waisbren, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Tan, Wen-Hann] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Gentile, Jennifer K.; Tan, Wen-Hann; Horowitz, Lucia T.; Bacino, Carlos A.; Skinner, Steven A.; Barbieri-Welge, Rene; Bauer-Carlin, Astrid; Beaudet, Arthur L.; Bichell, Terry Jo; Lee, Hye-Seung; Sahoo, Trilochan; Waisbren, Susan E.; Bird, Lynne M.] NIH, Rare Dis Clin Res Network, Angelman Rett & Prader Willi Syndromes Consortium, Bethesda, MD USA. [Horowitz, Lucia T.; Skinner, Steven A.; Bauer-Carlin, Astrid] Greenwood Genet Ctr, Greenwood, SC 29646 USA. [Bacino, Carlos A.; Beaudet, Arthur L.; Sahoo, Trilochan] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Barbieri-Welge, Rene] Rady Childrens Hosp San Diego, Dev Serv, San Diego, CA USA. [Bichell, Terry Jo] Vanderbilt Univ, Vanderbilt Kennedy Ctr, Nashville, TN 37203 USA. [Lee, Hye-Seung] Univ S Florida, Data Management Coordinating Ctr, Tampa, FL USA. [Bird, Lynne M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Bird, Lynne M.] Rady Childrens Hosp San Diego, Div Genetics Dysmorphol, San Diego, CA USA. RP Peters, SU (reprint author), Vanderbilt Univ, Kennedy Ctr Res Human Dev, PMB 40,230 Appleton Pl, Nashville, TN 37203 USA. EM sarika.u.peters@vanderbilt.edu OI Bichell, Terry Jo Vetters/0000-0002-1055-4993 FU NIH [U54 RR019478]; National Center for Research Resources (NCRR), National Institutes of Health (NIH); Angelman Syndrome Foundation; NCRR FX The project described was supported by Grant Number NIH U54 RR019478 (awarded to ALB) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the Angelman Syndrome Foundation-Western Area Chapter. Funding through NCRR was through the cooperative agreement mechanism. NR 38 TC 36 Z9 36 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD SEP PY 2010 VL 31 IS 7 SI SI BP 592 EP 601 DI 10.1097/DBP.0b013e3181ee408e PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 646SA UT WOS:000281561700010 PM 20729760 ER PT J AU Xie, T Chen, M Weinstein, LS AF Xie, Tao Chen, Min Weinstein, Lee S. TI Pancreas-specific G(s)alpha deficiency has divergent effects on pancreatic alpha- and beta-cell proliferation SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID EXPRESSION PATTERN; GLUCAGON-SECRETION; INSULIN-SECRETION; RAT; MOUSE; GLUCOSE; GENE; ENDOCRINE; RECEPTOR; ISLETS AB The ubiquitously expressed G protein a-subunit G(s)alpha mediates the intracellular cAMP response to glucagon-like peptide 1 (GLP1) and other incretin hormones in pancreatic islet cells. We have shown previously that mice with beta-cell-specific G(s)alpha deficiency (beta GsKO) develop severe early- onset insulin-deficient diabetes with a severe defect in beta-cell proliferation. We have now generated mice with G(s)alpha deficiency throughout the whole pancreas by mating G(s)alpha-floxed mice with Pdx1-cre transgenic mice (PGsKO). PGsKO mice also developed severe insulin-deficient diabetes at a young age, confirming the important role of G(s)alpha signaling in beta-cell growth and function. Unlike in beta GsKO mice, islets in PGsKO mice had a relatively greater proportion of alpha-cells, which were spread throughout the interior of the islet. Similar findings were observed in mice with pancreatic islet cell-specific G(s)alpha deficiency using a neurogenin 3 promoter-cre recombinase transgenic mouse line. Studies in the alpha-cell line alpha TC1 confirmed that reduced cAMP signaling increased cell proliferation while increasing cAMP produced the opposite effect. Therefore, it appears that G(s)alpha/cAMP signaling has opposite effects on pancreatic alpha- and beta-cell proliferation, and that impaired GLP1 action in alpha- and beta-cells via G(s)alpha signaling may be an important contributor to the reciprocal effects on insulin and glucagon observed in type 2 diabetics. In addition, PGsKO mice show morphological changes in exocrine pancreas and evidence for malnutrition and dehydration, indicating an important role for G(s)alpha in the exocrine pancreas as well. Journal of Endocrinology (2010) 206, 261-269 C1 [Xie, Tao; Chen, Min; Weinstein, Lee S.] NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDK, Signal Transduct Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@mail.nih.gov FU National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services FX This work was supported by the Intramural Research Program of the National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services. NR 36 TC 13 Z9 13 U1 0 U2 2 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 2010 VL 206 IS 3 BP 261 EP 269 DI 10.1677/JOE-10-0030 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 657YK UT WOS:000282455100002 PM 20543009 ER PT J AU Thomas, KW Dosemeci, M Coble, JB Hoppin, JA Sheldon, LS Chapa, G Croghan, CW Jones, PA Knott, CE Lynch, CF Sandler, DP Blair, AE Alavanja, MC AF Thomas, Kent W. Dosemeci, Mustafa Coble, Joseph B. Hoppin, Jane A. Sheldon, Linda S. Chapa, Guadalupe Croghan, Carry W. Jones, Paul A. Knott, Charles E. Lynch, Charles F. Sandler, Dale P. Blair, Aaron E. Alavanja, Michael C. TI Assessment of a pesticide exposure intensity algorithm in the agricultural health study SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE 2,4-D; chlorpyrifos; exposure measurement; occupational exposure; Agricultural Health Study ID CANCER INCIDENCE; APPLICATORS; INFORMATION; HERBICIDES; WORKERS; MATRIX; COHORT AB The accuracy of the exposure assessment is a critical factor in epidemiological investigations of pesticide exposures and health in agricultural populations. However, few studies have been conducted to evaluate questionnaire-based exposure metrics. The Agricultural Health Study (AHS) is a prospective cohort study of pesticide applicators who provided detailed questionnaire information on their use of specific pesticides. A field study was conducted for a subset of the applicators enrolled in the AHS to assess a pesticide exposure algorithm through comparison of algorithm intensity scores with measured exposures. Pre- and post-application urinary biomarker measurements were made for 2,4-D (n = 69) and chlorpyrifos (n = 17) applicators. Dermal patch, hand wipe, and personal air samples were also collected. Intensity scores were calculated using information from technician observations and an interviewer-administered questionnaire. Correlations between observer and questionnaire intensity scores were high (Spearman's r = 0.92 and 0.84 for 2,4-D and chlorpyrifos, respectively). Intensity scores from questionnaires for individual applications were significantly correlated with post-application urinary concentrations for both 2,4-D (r = 0.42, P<0.001) and chlorpyrifos (r = 0.53, P = 0.035) applicators. Significant correlations were also found between intensity scores and estimated hand loading, estimated body loading, and air concentrations for 2,4-D applicators (r-values 0.28-0.50, P-values <0.025). Correlations between intensity scores and dermal and air measures were generally lower for chlorpyrifos applicators using granular products. A linear regression model indicated that the algorithm factors for individual applications explained 24% of the variability in post-application urinary 2,4-D concentration, which increased to 60% when the pre-application urine concentration was included. The results of the measurements support the use of the algorithm for estimating questionnaire-based exposure intensities in the AHS for liquid pesticide products. Refinement of the algorithm may be possible using the results from this and other measurement studies. Journal of Exposure Science and Environmental Epidemiology (2010) 20, 559-569; doi:10.1038/jes.2009.54; published online 4 November 2009 C1 [Thomas, Kent W.; Sheldon, Linda S.; Chapa, Guadalupe; Croghan, Carry W.; Jones, Paul A.] US EPA, Natl Exposure Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Dosemeci, Mustafa; Coble, Joseph B.; Blair, Aaron E.; Alavanja, Michael C.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. [Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Knott, Charles E.] Battelle Ctr Publ Hlth Res, Durham, NC USA. [Knott, Charles E.] Battelle Ctr Evaluat, Durham, NC USA. [Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Thomas, KW (reprint author), US EPA, Natl Exposure Res Lab, Off Res & Dev, MD E205-04, Res Triangle Pk, NC 27711 USA. EM thomas.kent@epa.gov OI Sandler, Dale/0000-0002-6776-0018 FU US Environmental Protection Agency [68-D99-011, 68-D99-012, DW-75-93912801-0]; NIH, National Cancer Institute [Z01-CP010119]; National Institute of Environmental Health Sciences [Z01-ES049030] FX The authors thank the AHS cohort members participating in this study for their considerable time and effort. Several EPA researchers provided significant contribution to the study including Ruth Allen, Ross Highsmith, and William Steen. Nyla Logsden-Sackett and Patti Gillette at the University of Iowa AHS Field Station and Joy Herrington, at the Battelle North Carolina AHS Field Station led participant screening activities. We thank Sydney Gordon at Battelle, Stephen Reynolds and Martin Jones at the University of Iowa, and James Raymer and Gerald Akland at the RTI International for leading the field studies. This work has been funded in part by the US Environmental Protection Agency under Contracts 68-D99-011 and 68-D99-012, through Interagency Agreement DW-75-93912801-0. It has been subjected to Agency administrative review and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. This work has been supported in part by the Intramural Research Program of the NIH, National Cancer Institute (Z01-CP010119) and National Institute of Environmental Health Sciences (Z01-ES049030). NR 34 TC 23 Z9 23 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD SEP PY 2010 VL 20 IS 6 BP 559 EP 569 DI 10.1038/jes.2009.54 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 647NL UT WOS:000281625100010 PM 19888312 ER PT J AU Bagiella, E Novack, TA Ansel, B Diaz-Arrastia, R Dikmen, S Hart, T Temkin, N AF Bagiella, Emilia Novack, Thomas A. Ansel, Beth Diaz-Arrastia, Ramon Dikmen, Sureyya Hart, Tessa Temkin, Nancy TI Measuring Outcome in Traumatic Brain Injury Treatment Trials: Recommendations From the Traumatic Brain Injury Clinical Trials Network SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE clinical trial; global test procedure; outcome measures; traumatic brain injury ID POSTTRAUMATIC SEIZURES; RANDOMIZED-TRIAL; SCALE; MISCLASSIFICATION; PREVENTION; PHENYTOIN; VALPROATE; 1-YEAR AB Background: Traumatic brain injury (TBI) involves several aspects of a patient's condition, including physical, mental, emotional, cognitive, social, and functional changes. Therefore, a clinical trial with individuals with TBI should consider outcome measures that reflect their global status. Methods: We present the work of the National Institute of Child Health and Development-sponsored Traumatic Brain Injury Clinical Trials Network Outcome Measures subcommittee and its choice of outcome measures for a phase III clinical trial of patients with complicated mild to severe TBI. Results: Onthe basis of theoretical and practical considerations, the subcommittee recommended the adoption of a core of 9 measures that cover 2 different areas of recovery: functional and cognitive. These measures are the Extended Glasgow Outcome Scale; the Controlled Oral Word Association Test; the Trail Making Test, Parts A and B; the California Verbal Learning Test-II; the Wechsler Adult Intelligence Scale-III Digit Span subtest; the Wechsler Adult Intelligence Scale-III Processing Speed Index; and the Stroop Color-Word Matching Test, Parts 1 and 2. Conclusions: The statistical methods proposed to analyze these measures using a global test procedure, along with research and methodological and regulatory issues involved with the use of multiple outcomes in a clinical trial, are discussed. C1 [Bagiella, Emilia] Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, New York, NY 10032 USA. [Novack, Thomas A.] Univ Alabama Birmingham, Birmingham, AL USA. [Ansel, Beth] NICHHD, Natl Ctr Med Rehabil Res, Bethesda, MD 20892 USA. [Diaz-Arrastia, Ramon] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA. [Dikmen, Sureyya] Univ Washington, Sch Med, Dept Rehabil Med, Div Clin Psychol & Neuropsychol, Seattle, WA 98195 USA. [Temkin, Nancy] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Temkin, Nancy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Hart, Tessa] Moss Rehabil Res Inst, Philadelphia, PA USA. RP Bagiella, E (reprint author), Columbia Univ, Dept Biostat, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA. EM eb51@columbia.edu FU National Institute of Child Health and Development [U01HD042823, U01HD042738, U01HD042687, U01HD042736, U01HD042678, U01HD042686, U01HD042653, U01HD042689, U01HD042652] FX The work of the Traumatic Brain Injury Clinical Trials Network Outcome Measures Subcommittee is supported by National Institute of Child Health and Development grants U01HD042823, U01HD042738, U01HD042687, U01HD042736, U01HD042678, U01HD042686, U01HD042653, U01HD042689, and U01HD042652 to 8 clinical sites and a data-coordinating center. NR 43 TC 45 Z9 45 U1 5 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD SEP-OCT PY 2010 VL 25 IS 5 BP 375 EP 382 DI 10.1097/HTR.0b013e3181d27fe3 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 649JR UT WOS:000281765400011 PM 20216459 ER PT J AU Marquardt, JU Factor, VM Thorgeirsson, SS AF Marquardt, J. U. Factor, V. M. Thorgeirsson, S. S. TI Epigenetic regulation of cancer stem cells in liver cancer: Current concepts and clinical implications SO JOURNAL OF HEPATOLOGY LA English DT Review DE Liver cancer; Cancer stem cells; Epigenetics; Side population ID HUMAN HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION SIGNATURE; HUMAN PANCREATIC-CANCER; SIDE POPULATION CELLS; PROGENITOR CELLS; STEM/PROGENITOR CELLS; DRUG-RESISTANCE; TUMOR-GROWTH; FUNCTIONAL GENOMICS; SIGNALING PATHWAYS AB The two dominant models of carcinogenesis postulate stochastic (clonal evolution) or hierarchic organization of tumor (cancer stem cell model). According to the latter, at the germinal center of tumor evolution is a cancer stem cell (CSC) which, similar to normal adult stem cells, possesses the capacity of self-renewal and a differentiation potential. Over the past few years, compelling evidence has emerged in support of the hierarchic cancer model for many solid tumors including hepatocellular cancers. The CSCs are posited to be responsible not only for tumor initiation but also for the generation of distant metastasis and relapse after therapy. These characteristics are particularly relevant for a multi-resistant tumor entity like human hepatocellular carcinoma and may herald a paradigm shift in the management of this deadly disease. Identification and detailed characterization of liver CSCs is therefore imperative for improving prevention approaches, enhancing early detection, and extending the limited treatment options. Despite the current progress in understanding the contribution of CSCs to the generation of heterogeneity of tumors, the molecular complexity and exact regulation of CSCs is poorly understood. This review focuses on the genetic and epigenetic mechanisms that regulate and define the unique CSC properties with an emphasis on key regulatory pathways of liver CSCs and their clinical significance. (C) 2010 Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Marquardt, J. U.; Factor, V. M.; Thorgeirsson, S. S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors thank the LEC members for their input and valuable contribution to this work. NR 161 TC 46 Z9 49 U1 1 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD SEP PY 2010 VL 53 IS 3 BP 568 EP 577 DI 10.1016/j.jhep.2010.05.003 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 652EV UT WOS:000281985900023 PM 20646772 ER PT J AU Parker, HG Chase, K Cadieu, E Lark, KG Ostrander, EA AF Parker, Heidi G. Chase, Kevin Cadieu, Edouard Lark, Karl Gordon Ostrander, Elaine A. TI An Insertion in the RSPO2 Gene Correlates with Improper Coat in the Portuguese Water Dog SO JOURNAL OF HEREDITY LA English DT Article DE fur; furnishings; genetics; morphology; mutation ID CANINE GENOME AB We recently showed that genes at 3 loci account for the majority of variation in canine fur. Allelic variation at genes controlling length of fur, texture, and curl is responsible for the striking phenotypic variety observed among purebred dogs in the United States today. In this paper, we investigate the phenomenon of "improper coat" (IC) or a coat that is not typical of the breed. IC is occasionally observed among specific breeds, such as the Portuguese Water Dog (PWD), and is characterized by short hair on the head, face, and lower legs, rather than a thick and even coat covering the whole body. The IC is reminiscent of that observed on the curly or flat-coated retriever, thus making such dogs unable to compete effectively in conformation events. We have found that the presence of the wild-type allele, rather than the expected variant allele at the R-spondin 2 (RSPO2) gene, accounts for this phenotype. The development of a genetic test that distinguishes these 2 allelic types would allow breeders to easily avoid producing PWD with ICs. C1 [Parker, Heidi G.; Cadieu, Edouard; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Chase, Kevin; Lark, Karl Gordon] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU National Institutes of Health [GM063056]; National Human Genome Research Institute FX National Institutes of Health (GM063056) to K.C. and K.G.L.; Intramural program of the National Human Genome Research Institute. NR 11 TC 7 Z9 7 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 2010 VL 101 IS 5 BP 612 EP 617 DI 10.1093/jhered/esq068 PG 6 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 630ZS UT WOS:000280316600009 PM 20562213 ER PT J AU Peng, YY Zeng, YY Qiu, GYS Cai, LS Pike, VW AF Peng, Yi-Yuan Zeng, Yuyun Qiu, Ganyinsheng Cai, Lisheng Pike, Victor W. TI A Convenient One-Pot Procedure for the Synthesis of 2-Aryl Quinazolines Using Active MnO2 as Oxidant SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE; ACRIDONE ALKALOIDS; INHIBITORS; QUINOLINE; AGENTS; TAUTOMERISM AB A variety of 2-aryl quinazolines were synthesized from the condensation of 2-aminobenzylamines and aryl aldehydes to form 2-aryl-1,2,3,4-tetrahydroquinazolines and subsequent oxidation of the intermediates with MnO2. C1 [Peng, Yi-Yuan; Zeng, Yuyun; Qiu, Ganyinsheng] Jiangxi Normal Univ, Dept Chem, Key Lab Green Chem, Nanchang 330022, Jiangxi, Peoples R China. [Cai, Lisheng; Pike, Victor W.] NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Peng, YY (reprint author), Jiangxi Normal Univ, Dept Chem, Key Lab Green Chem, Nanchang 330022, Jiangxi, Peoples R China. EM yiyuanpeng@yahoo.com FU National Science Foundation of China [20462003, 20862009, 20962010]; National Science Foundation of Jiangxi province [2008GQH0026] FX We are grateful to the support from the National Science Foundation of China (No. 20462003, 20862009, and 20962010) and the National Science Foundation of Jiangxi province (No. 2008GQH0026). NR 38 TC 24 Z9 24 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD SEP PY 2010 VL 47 IS 5 BP 1240 EP 1245 DI 10.1002/jhet.444 PG 6 WC Chemistry, Organic SC Chemistry GA 658KP UT WOS:000282489200038 ER PT J AU Sezgin, E Drosdak, A McIntosh, C Kessing, B Lautenberger, JA Goedert, JJ Phair, JP Troyer, JL Smith, MW O'Brien, SJ AF Sezgin, Efe Drosdak, Alyssa McIntosh, Carl Kessing, Bailey Lautenberger, James A. Goedert, James J. Phair, John P. Troyer, Jennifer L. Smith, Michael W. O'Brien, Stephen J. TI Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup I SO JOURNAL OF HUMAN GENETICS LA English DT Article DE AIDS progression; CD24L4/DDX3Y; population growth; population structure; selection; Y chromosome ID FREQUENCY-SPECTRUM; STATISTICAL TESTS; MITOCHONDRIAL-DNA; MUTATION-RATES; POLYMORPHISM; SINGLE; ASSOCIATION; NEUTRALITY; GROWTH; GENES AB We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease-based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted. Journal of Human Genetics (2010) 55, 613-620; doi:10.1038/jhg.2010.77; published online 24 June 2010 C1 [Sezgin, Efe; Drosdak, Alyssa; McIntosh, Carl; Lautenberger, James A.; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. [Kessing, Bailey; Troyer, Jennifer L.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21702 USA. [Goedert, James J.] NCI, Viral Epidemiol Branch, Rockville, MD USA. [Phair, John P.] Northwestern Univ, Sch Med, Comprehens AIDS Ctr, Chicago, IL USA. [Smith, Michael W.] SAIC Frederick, Adv Technol Program, Frederick, MD USA. RP Sezgin, E (reprint author), NCI, Lab Genom Divers, Bldg 560,Room 21-42, Frederick, MD 21702 USA. EM sezginef@mail.nih.gov RI Smith, Michael/B-5341-2012; Sezgin, Efe/B-8418-2012 OI Sezgin, Efe/0000-0002-8000-7485 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E, N01-CO-12400] FX We thank the individuals and staff of all the participating cohorts in the study. San Francisco City Cohort samples were provided by Susan Buchbinder. We also thank Michael Malasky and Mary Thompson for their assistance. 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. The project described in this paper has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract Nos. HHSN261200800001E and N01-CO-12400. NR 41 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD SEP PY 2010 VL 55 IS 9 BP 613 EP 620 DI 10.1038/jhg.2010.77 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 653ZM UT WOS:000282137900011 PM 20574427 ER PT J AU Veillette, A Bookman, MA Horak, EM Bolen, JB AF Veillette, Andre Bookman, Michael A. Horak, Eva M. Bolen, Joseph B. TI The CD4 and CD8 T Cell Surface Antigens are Associated with the Internal Membrane Tyrosine-Protein Kinase p56(lck) (Reprinted from Cell, vol 77, pg 301-308, 1994) SO JOURNAL OF IMMUNOLOGY LA English DT Reprint ID DIFFERENTIATION ANTIGENS; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; RECEPTOR; ACTIVATION; EXPRESSION; COMPLEX; CLONES; L3T4; MOLECULE AB The CD4 and CD8 T cell antigens are thought to transduce an independent signal during the process of T cell activation. We report our evaluation of the possible involvement of the lymphocyte-specific tyrosine kinase p56(lck) in these transduction pathways. Our data demonstrate that p56(lck) is specifically modulated with either CD4 or CD8 following antibody-mediated cross-linking of these molecules and that a large fraction of the total cellular lck protein can be coimmunoprecipitated with these surface glycoproteins. These results suggest that p56(lck) is functionally and physically associated with CD4/CD8 in normal murine T lymphocytes and support the concept that an independent signal is transduced by the interaction of these surface molecules with major histocompatibility complex determinants. C1 [Veillette, Andre; Bolen, Joseph B.] NCI, Tumor Virus Biol Lab, Bethesda, MD 20892 USA. [Bookman, Michael A.; Horak, Eva M.] NCI, Med Branch, Bethesda, MD 20892 USA. RP Veillette, A (reprint author), NCI, Tumor Virus Biol Lab, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 2650 EP 2657 PG 8 WC Immunology SC Immunology GA 641JX UT WOS:000281122600004 PM 20724731 ER PT J AU Cannons, JL Wu, JZ Gomez-Rodriguez, J Zhang, JY Dong, BX Liu, Y Shaw, S Siminovitch, KA Schwartzberg, PL AF Cannons, Jennifer L. Wu, Julie Z. Gomez-Rodriguez, Julio Zhang, Jinyi Dong, Baoxia Liu, Yin Shaw, Stephen Siminovitch, Katherine A. Schwartzberg, Pamela L. TI Biochemical and Genetic Evidence for a SAP-PKC-theta Interaction Contributing to IL-4 Regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KINASE-C-THETA; CD4(+) T-CELLS; LINKED LYMPHOPROLIFERATIVE-DISEASE; FOLLICULAR HELPER-CELLS; HUMORAL IMMUNITY; PRODUCT SAP; MOLECULAR DISSECTION; SIGNAL-TRANSDUCTION; CYTOKINE REGULATION; IN-VIVO AB Signaling lymphocytic activation molecule-associated protein (SAP), an adaptor molecule that recruits Fyn to the signaling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors, is mutated in X-linked lymphoproliferative disease. CD4(+) T cells from SAP-deficient mice have defective TCR-induced and follicular Th cell IL-4 production and impaired T cell-mediated help for germinal center formation; however, the downstream intermediates contributing to these defects remain unclear. We previously found that SAP-deficient CD4(+) T cells exhibit decreased protein kinase C (PKC)-theta recruitment upon TCR stimulation. We demonstrate in this paper using GST pulldowns and coimmunoprecipitation studies that SAP constitutively associates with PKC-theta in T cells. SAP-PKC-theta interactions required R78 of SAP, a residue previously implicated in Fyn recruitment, yet SAP's interactions with PKC-theta occurred independent of phosphotyrosine binding and Fyn. Overexpression of SAP in T cells increased and sustained PKC-theta recruitment to the immune synapse and elevated IL-4 production in response to TCR plus SLAM-mediated stimulation. Moreover, PKC-theta, like SAP, was required for SLAM-mediated increases in IL-4 production, and, conversely, membrane-targeted PKC-theta mutants rescued IL-4 expression in SAP(-/-) CD4(+) T cells, providing genetic evidence that PKC-theta is a critical component of SLAM/SAP-mediated pathways that influence TCR-driven IL-4 production. The Journal of Immunology, 2010, 185: 2819-2827. C1 [Cannons, Jennifer L.; Wu, Julie Z.; Gomez-Rodriguez, Julio; Schwartzberg, Pamela L.] NHGRI, NIH, Bethesda, MD 20892 USA. [Liu, Yin; Shaw, Stephen] NCI, NIH, Bethesda, MD 20892 USA. [Zhang, Jinyi; Dong, Baoxia; Siminovitch, Katherine A.] Univ Toronto, Dept Med, Mt Sinai Hosp Samuel Lunenfeld, Toronto, ON, Canada. [Zhang, Jinyi; Dong, Baoxia; Siminovitch, Katherine A.] Univ Toronto, Dept Immunol, Mt Sinai Hosp Samuel Lunenfeld, Toronto, ON, Canada. [Zhang, Jinyi; Dong, Baoxia; Siminovitch, Katherine A.] Univ Toronto, Dept Med Genet & Microbiol, Mt Sinai Hosp Samuel Lunenfeld, Toronto, ON, Canada. Toronto Gen Hosp, Res Inst, Toronto, ON, Canada. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM pams@mail.nih.gov RI Siminovitch, Katherine/K-1475-2013 FU National Human Genome Research Institute; National Cancer Institute; Pharmacology Research Associate Training program FX This work was supported by funding from the intramural programs of the National Human Genome Research Institute and the National Cancer Institute and by the Pharmacology Research Associate Training program (to J.Z.W.). NR 66 TC 27 Z9 27 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 2819 EP 2827 DI 10.4049/jimmunol.0902182 PG 9 WC Immunology SC Immunology GA 641JX UT WOS:000281122600024 PM 20668219 ER PT J AU Rausch, MP Irvine, KR Antony, PA Restifo, NP Cresswell, P Hastings, KT AF Rausch, Matthew P. Irvine, Kari R. Antony, Paul A. Restifo, Nicholas P. Cresswell, Peter Hastings, K. Taraszka TI GILT Accelerates Autoimmunity to the Melanoma Antigen Tyrosinase-Related Protein 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYSOSOMAL THIOL REDUCTASE; CD4(+) T-CELLS; LARGE ESTABLISHED MELANOMA; NORMAL HUMAN MELANOCYTES; GAMMA-INTERFERON; TRANSGENIC MICE; VITILIGO PATIENTS; DENDRITIC CELLS; DISULFIDE BONDS; SELF-ANTIGEN AB Melanocyte differentiation Ags, including tyrosinase-related protein (TRP) 1, are relevant to both autoimmune skin depigmentation (vitiligo) and tumor immunity, because they are expressed by both benign melanocytes and many malignant melanomas. Melanoma patients generate CD4(+) T cells that specifically recognize these proteins. TRP1 contains internal disulfide bonds and is presented by MHC class II molecules. gamma-IFN-inducible lysosomal thiol reductase (GILT) facilitates the generation of class II-binding peptides by the endocytic reduction of protein disulfide bonds. We show in this study that GILT is required for efficient MHC class II-restricted processing of a TRP1 epitope in vitro and accelerates the onset of vitiligo in TRP1-specific TCR transgenic mice. The presence of GILT confers a small increase in the percentage of autoreactive T cells with an effector memory phenotype that may contribute to earlier disease onset. The onset of vitiligo is associated with a greater increase in the percentage of autoreactive T cells with an effector memory phenotype. Given that many self and tumor Ags have disulfide bonds and are presented on MHC class II, GILT is likely to be important in the pathogenesis of other CD4(+) T cell-mediated autoimmune diseases and for the development of effective cancer immunotherapy. The Journal of Immunology, 2010, 185: 2828-2835. C1 [Rausch, Matthew P.; Hastings, K. Taraszka] Univ Arizona, Coll Med, Dept Basic Med Sci, Phoenix, AZ 85004 USA. [Rausch, Matthew P.; Hastings, K. Taraszka] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. [Hastings, K. Taraszka] Univ Arizona, Coll Med, Dept Immunobiol, Tucson, AZ 85724 USA. [Irvine, Kari R.; Antony, Paul A.; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Cresswell, Peter] Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA. [Cresswell, Peter] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. RP Hastings, KT (reprint author), Univ Arizona, Coll Med, Dept Basic Med Sci, 425 N 5th St, Phoenix, AZ 85004 USA. EM peter.cresswell@yale.edu; khasting@email.arizona.edu RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Dermatology Foundation; National Institutes of Health [T32-AR007016, R25-CA078447, K08-AR054388]; Arizona Cancer Center; American Cancer Society; Melanoma Research Foundation; National Institutes of Health FX This work was supported by a Dermatology Foundation Dermatologist Investigator Research Fellowship, National Institutes of Health Grants T32-AR007016, R25-CA078447, and K08-AR054388, the Arizona Cancer Center, an American Cancer Society Institutional Cancer Research grant, a Melanoma Research Foundation Career Development Research Award (to K.T.H.), and National Institutes of Health Grants R37-AI23081 (to P.C.) and T32 CA09213 (to M.P.R.). NR 50 TC 24 Z9 24 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 2828 EP 2835 DI 10.4049/jimmunol.1000945 PG 8 WC Immunology SC Immunology GA 641JX UT WOS:000281122600025 PM 20668223 ER PT J AU Gross, CC Brzostowski, JA Liu, DF Long, EO AF Gross, Catharina C. Brzostowski, Joseph A. Liu, Dongfang Long, Eric O. TI Tethering of Intercellular Adhesion Molecule on Target Cells Is Required for LFA-1-Dependent NK Cell Adhesion and Granule Polarization SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; IMMUNE SYNAPSES; LIPID RAFTS; IMMUNOLOGICAL SYNAPSE; KILLER-CELLS; CLASS-I; NATURAL CYTOTOXICITY; INHIBITORY RECEPTORS; CYTOPLASMIC DOMAIN; ALPHA-ACTININ AB alpha(L)beta(2) integrin (LFA-1) has an important role in the formation of T cell and NK cell cytotoxic immunological synapses and in target cell killing. Binding of LFA-1 to ICAM on target cells promotes not only adhesion but also polarization of cytolytic granules in NK cells. In this study, we tested whether LFA-1-dependent NK cell responses are regulated by the distribution and mobility of ICAM at the surface of target cells. We show that depolymerization of F-actin in NK-sensitive target cells abrogated LFA-1-dependent conjugate formation and granule polarization in primary NK cells. Degranulation, which is not controlled by LFA-1, was not impaired. Fluorescence recovery after photobleaching experiments and particle tracking by total internal reflection fluorescence microscopy revealed that ICAM-1 and ICAM-2 were distributed in largely immobile clusters. ICAM clusters were maintained and became highly mobile after actin depolymerization. Moreover, reducing ICAM-2 mobility on an NK-resistant target cell through expression of ezrin, an adaptor molecule that tethers proteins to the actin cytoskeleton, enhanced LFA-1-dependent adhesion and granule polarization. Finally, although NK cells kept moving over freely diffusible ICAM-1 on a lipid bilayer, they bound and spread over solid-phase ICAM-1. We conclude that tethering, rather than clustering of ICAM, promotes proper signaling by LFA-1 in NK cells. Our findings suggest that the lateral diffusion of integrin ligands on cells may be an important determinant of susceptibility to lysis by cytotoxic lymphocytes. The Journal of Immunology, 2010, 185: 2918-2926. C1 [Gross, Catharina C.; Liu, Dongfang; Long, Eric O.] NIAID, Mol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Brzostowski, Joseph A.] NIAID, Imaging Facil, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Mol & Cellular Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM eLong@nih.gov RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 60 TC 27 Z9 27 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 2918 EP 2926 DI 10.4049/jimmunol.1000761 PG 9 WC Immunology SC Immunology GA 641JX UT WOS:000281122600034 PM 20675589 ER PT J AU Sugalski, JM Rodriguez, B Moir, S Anthony, DD AF Sugalski, Julia M. Rodriguez, Benigno Moir, Susan Anthony, Donald D. TI Peripheral Blood B Cell Subset Skewing Is Associated with Altered Cell Cycling and Intrinsic Resistance to Apoptosis and Reflects a State of Immune Activation in Chronic Hepatitis C Virus Infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MIXED CRYOGLOBULINEMIA; BCL-2 REARRANGEMENT; LYMPHOCYTES; INDIVIDUALS; RESPONSES; NAIVE; MANIFESTATIONS; COINFECTION; EXPANSION; ANTIGENS AB Chronic hepatitis C virus (HCV) infection is associated with B cell activation, although underlying mechanisms are unclear. To investigate B cell regulation during HCV infection, we measured bulk B cell CpG and Staphylococcus aureus Cowan-induced IgG Ab-secreting cell (ASC) frequency, HCV and tetanus-specific ASC frequency, BCR- and CD40L-dependent CD80/CD86 expression, and activation of memory CD4 cells. Immature transitional, naive, resting memory, mature activated, tissue-like memory, and plasma B cell subset frequencies, cell cycling, and intrinsic apoptosis were quantified. We observed intact or enhanced tetanus-specific and total IgG ASC frequency, serum IgG, BCR- and CD40L-dependent CD80/CD86 expression, and CD40L-dependent bulk B cell activation of memory CD4 cells in HCV infection. HCV-specific ASCs were observed in HCV-infected but not control subjects, although frequencies were lower compared with tetanus-specific cells. Immature transitional and mature activated B cell subset frequencies were increased in HCV-infected subjects, with immature transitional frequency associated with liver inflammation and serum B cell-activating factor. Mature activated B cells less commonly expressed Ki67, more commonly expressed Bcl2, and were more intrinsically resistant to apoptosis, whereas immature transitional B cells more commonly expressed Ki67, the latter associated with plasma HCV level. Taken together, these results indicate that in the setting of chronic HCV infection, a state of activation results in B cell subset skewing that is likely the result of alterations in homeostasis, cell cycling, and intrinsic resistance to apoptosis and that results in an overall intact or enhanced B cell response to BCR and CD40L. The Journal of Immunology, 2010, 185: 3019-3027. C1 [Sugalski, Julia M.; Rodriguez, Benigno; Anthony, Donald D.] Case Western Reserve Univ, Ctr AIDS Res, Dept Med, Cleveland, OH 44106 USA. [Sugalski, Julia M.; Rodriguez, Benigno; Anthony, Donald D.] Case Western Reserve Univ, Ctr AIDS Res, Dept Pathol, Cleveland, OH 44106 USA. VA Med Ctr, Cleveland, OH 44106 USA. [Moir, Susan] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Anthony, DD (reprint author), Case Western Reserve Univ, Ctr AIDS Res, Dept Med, Biomed Res Bldg 1028,2109 Adelbert Rd, Cleveland, OH 44106 USA. EM dda3@case.edu RI Rodriguez, Benigno/C-3365-2009 OI Rodriguez, Benigno/0000-0001-9736-7957 FU National Institutes of Health [AI 36219]; National Institute of Allergy and Infectious Diseases [1R21 AI066957]; National Institute of Diabetes and Digestive and Kidney Diseases [DK068361]; Case Western Reserve University Center for AIDS Research core facilities FX This work was supported by National Institutes of Health Grant AI 36219, National Institute of Allergy and Infectious Diseases Grant 1R21 AI066957, National Institute of Diabetes and Digestive and Kidney Diseases Grant DK068361, and the Case Western Reserve University Center for AIDS Research core facilities. NR 36 TC 26 Z9 27 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 3019 EP 3027 DI 10.4049/jimmunol.1000879 PG 9 WC Immunology SC Immunology GA 641JX UT WOS:000281122600045 PM 20656924 ER PT J AU Frolich, D Giesecke, C Mei, HE Reiter, K Daridon, C Lipsky, PE Dorner, T AF Froelich, Daniela Giesecke, Claudia Mei, Henrik E. Reiter, Karin Daridon, Capucine Lipsky, Peter E. Doerner, Thomas TI Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE REPERTOIRE; SOMATIC HYPERMUTATION; CHEMOKINE RECEPTOR; IMMUNE-RESPONSE; INFLUENZA-VIRUS; CHAIN; AFFINITY; BLOOD; DIFFERENTIATION; EXPRESSION AB Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6-7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of V(H)DJ(H) rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their V(H) genes. The Journal of Immunology, 2010, 185: 3103-3110. C1 [Froelich, Daniela; Giesecke, Claudia; Mei, Henrik E.; Reiter, Karin; Daridon, Capucine; Doerner, Thomas] Charite, Dept Med Rheumatol & Clin Immunol, D-10117 Berlin, Germany. [Froelich, Daniela; Giesecke, Claudia; Mei, Henrik E.; Reiter, Karin; Daridon, Capucine; Doerner, Thomas] Deutsch Rheumaforschungszentrum Berlin, Berlin, Germany. [Lipsky, Peter E.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Charite, Dept Med Rheumatol & Clin Immunol, Charitepl 1, D-10117 Berlin, Germany. EM thomas.doerner@charite.de FU Deutsche Forschungsgemeinschaft [Do491/7-1, D0491/7-2, DO 491/5-4, TP16] FX This work was supported by Deutsche Forschungsgemeinschaft Projects Do491/7-1,2 and DO 491/5-4 and Sonderforschungsbereich 650 Project TP16. NR 44 TC 33 Z9 34 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2010 VL 185 IS 5 BP 3103 EP 3110 DI 10.4049/jimmunol.1000911 PG 8 WC Immunology SC Immunology GA 641JX UT WOS:000281122600055 PM 20693426 ER PT J AU Kalbasi, A Shrimali, RK Chinnasamy, D Rosenberg, SA AF Kalbasi, Anusha Shrimali, Rajeev K. Chinnasamy, Dhanalakshmi Rosenberg, Steven A. TI Prevention of Interleukin-2 Withdrawal-Induced Apoptosis in Lymphocytes Retrovirally Cotransduced With Genes Encoding an Antitumor T-cell Receptor and an Antiapoptotic Protein SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immunotherapy; adoptive transfer; gene therapy; tumor immunology; melanoma; IL-2 withdrawal ID CANCER REGRESSION; IN-VIVO; BCL-X; ANTIGEN; IL-2; IMMUNOTHERAPY; EXPRESSION; THERAPY; TRANSDUCTION; SURVIVAL AB Adoptive cell transfer using autologous tumor infiltrating lymphocytes or lymphocytes transduced with antitumor T-cell receptor (TCR) is an effective therapy for patients with metastatic melanoma. A limiting factor in the effectiveness of this treatment is the apoptosis of the transferred cells when Interleukin-2 (IL-2) administration is withdrawn. In an attempt to improve persistence of the transferred lymphocytes, we cotransduced human peripheral blood lymphocytes with retroviruses encoding Bcl-2 or Bcl-xL, antiapoptotic genes of the BCL2 family, and the MART-1 melanoma tumor antigen-specific TCR, DMF5. Lymphocytes were cotransduced with 38% to 64% cotransduction efficiency, and exhibited a marked delay in apoptosis after IL-2 withdrawal. Cotransduction with Bcl-2 or Bcl-xL did not affect cytokine secretion or lytic ability of the DMF5-transduced lymphocytes. After 5 days of IL-2 withdrawal, cotransduced lymphocytes produced similar levels of IFN-gamma per cell as DMF5-alone transduced lymphocytes in response to tumor cells. Cotransduction did not alter the phenotype of lymphocytes with respect to a panel of T-cell differentiation markers. In a mouse model of melanoma, adoptively transferred T cells transduced with Bcl-2 persisted better in vivo at the site of tumor, 13 and 21 days after adoptive transfer (P=0.0064 and 0.041, respectively), with evidence of enrichment of the Bcl-2-transduced population over time (P<0.0001). Thus, by coexpressing Bcl-2 or Bcl-xL with a tumor-specific TCR, we have engineered a lymphocyte that resists apoptosis owing to IL-2 withdrawal without altering its tumor-specific function or phenotype, and thus may show improved antitumor effectiveness in vivo after cell transfer. C1 [Rosenberg, Steven A.] NCI, Surg Branch, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. [Kalbasi, Anusha] Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Clin Res Ctr, NIH, Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM sar@nih.gov OI Kalbasi, Anusha/0000-0001-8692-1457 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This research was supported by the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 32 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 2010 VL 33 IS 7 BP 672 EP 683 DI 10.1097/CJI.0b013e3181e475cd PG 12 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 629ZG UT WOS:000280239500003 PM 20664359 ER PT J AU Zaharoff, DA Hance, KW Rogers, CJ Schlom, J Greiner, JW AF Zaharoff, David A. Hance, Kenneth W. Rogers, Connie J. Schlom, Jeffrey Greiner, John W. TI Intratumoral Immunotherapy of Established Solid Tumors With Chitosan/IL-12 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE IL-12; paracrine delivery; immunotherapy; chitosan; intratumoral ID RECOMBINANT HUMAN INTERLEUKIN-12; PERIPHERAL-BLOOD LYMPHOCYTES; SYSTEMIC ANTITUMOR IMMUNITY; IFN-GAMMA PRODUCTION; T-CELLS; BIODEGRADABLE MICROSPHERES; LOADED MICROSPHERES; IN-VIVO; IL-12; CANCER AB IL-12 is a potent antitumor cytokine that exhibits significant clinical toxicities after systemic administration. We hypothesized that intratumoral (i.t.) administration of IL-12 coformulated with the biodegradable polysaccharide chitosan could enhance the antitumor activity of IL-12 while limiting its systemic toxicity. Noninvasive imaging studies monitored local retention of IL-12, with and without chitosan coformulation, after i.t. injection. Antitumor efficacy of IL-12 alone and IL-12 coformulated with chitosan (chitosan/IL-12) was assessed in mice bearing established colorectal (MC32a) and pancreatic (Panc02) tumors. Additional studies involving depletion of immune cell subsets, tumor rechallenge, and CTL activity were designed to elucidate mechanisms of regression and tumor-specific immunity. Coformulation with chitosan increased local IL-12 retention from 1 to 2 days to 5 to 6 days. Weekly i.t. injections of IL-12 alone eradicated <= 10% of established MC32a and Panc02 tumors, while i.t. chitosan/IL-12 immunotherapy caused complete tumor regression in 80% to 100% of mice. Depletion of CD4(+) or Gr-1(+) cells had no impact on chitosan/IL-12-mediated tumor regression. However, CD8(+) or NK cell depletion completely abrogated antitumor activity. I.t. chitosan/IL-12 immunotherapy generated systemic tumor-specific immunity, as >80% of mice cured with i.t. chitosan/IL-12 immunotherapy were at least partially protected from tumor rechallenge. Furthermore, CTLs from spleens of cured mice lysed MC32a and gp70 peptide-loaded targets. Chitosan/IL-12 immunotherapy increased local retention of IL-12 in the tumor microenvironment, eradicated established, aggressive murine tumors, and generated systemic tumor-specific protective immunity. Chitosan/IL-12 is a well-tolerated, effective immunotherapy with considerable potential for clinical translation. C1 [Zaharoff, David A.; Hance, Kenneth W.; Rogers, Connie J.; Schlom, Jeffrey; Greiner, John W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM jg117s@nih.gov OI Zaharoff, David/0000-0001-6885-6727 FU Intramural NIH HHS [ZIA BC010969-03] NR 48 TC 18 Z9 19 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 2010 VL 33 IS 7 BP 697 EP 705 DI 10.1097/CJI.0b013e3181eb826d PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 629ZG UT WOS:000280239500005 PM 20664357 ER PT J AU Janka, JJ Koita, OA Traore, B Traore, JM Mzayek, F Sachdev, V Wang, XD Sanogo, K Sangare, L Mendelsohn, L Masur, H Kato, GJ Gladwin, MT Krogstad, DJ AF Janka, Jacqueline J. Koita, Ousmane A. Traore, Broulaye Traore, Josepha M. Mzayek, Fawaz Sachdev, Vandana Wang, Xunde Sanogo, Kassoum Sangare, Lansana Mendelsohn, Laurel Masur, Henry Kato, Gregory J. Gladwin, Mark T. Krogstad, Donald J. TI Increased Pulmonary Pressures and Myocardial Wall Stress in Children with Severe Malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SICKLE-CELL-DISEASE; NITRIC-OXIDE PRODUCTION; SEVERE FALCIPARUM-MALARIA; CEREBRAL MALARIA; ENDOTHELIAL DYSFUNCTION; INVERSE RELATIONSHIP; ADHESION MOLECULES; RISK-FACTOR; BLOOD; HYPERTENSION AB Background. Chronic intravascular hemolysis leads to nitric oxide (NO) depletion and pulmonary hypertension in sickle cell disease. To test whether this pathophysiology occurs in malaria, we examined in Mali 53 children who were admitted to the hospital with severe malaria (excluding cerebral malaria) and 31 age-matched controls. Methods. Severity of hemolysis was assessed from plasma levels of free hemoglobin and arginase-1. NO metabolism was assessed by whole-blood nitrite levels and plasma NO consumption. Effects on the cardiovascular system and endothelial function were assessed by using echocardiography to measure peak tricuspid regurgitant jet velocity and by evaluating plasma levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and soluble vascular cell adhesion molecule 1. Results. Children with severe malaria had higher plasma levels of hemoglobin and arginase-1, reduced whole-blood levels of nitrite, and increased NO consumption relative to controls. They also had increased pulmonary arterial pressures (P < .05) with elevated levels of NT-proBNP and soluble vascular cell adhesion molecule-1 (P < .001). Conclusion. Children with severe malaria have increased pulmonary pressures and myocardial wall stress. These complications are consistent with NO depletion from intravascular hemolysis, and they indicate that the pathophysiologic cascade from intravascular hemolysis to NO depletion and its cardiopulmonary effects is activated in children with severe malaria. C1 [Janka, Jacqueline J.; Sachdev, Vandana; Wang, Xunde; Mendelsohn, Laurel; Masur, Henry; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. [Janka, Jacqueline J.; Sachdev, Vandana; Wang, Xunde; Mendelsohn, Laurel; Masur, Henry; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Pulm Branch, NIH, Bethesda, MD 20892 USA. [Janka, Jacqueline J.; Sachdev, Vandana; Wang, Xunde; Mendelsohn, Laurel; Masur, Henry; Kato, Gregory J.; Gladwin, Mark T.] NHLBI, Vasc Med & Translat Med Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Hematol & Vasc Biol Res Inst, Pittsburgh, PA USA. [Mzayek, Fawaz; Krogstad, Donald J.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA USA. [Mzayek, Fawaz; Krogstad, Donald J.] Tulane Univ, Sch Publ Hlth & Trop Med, Ctr Infect Dis, New Orleans, LA USA. [Koita, Ousmane A.; Traore, Broulaye; Traore, Josepha M.; Sanogo, Kassoum; Sangare, Lansana] Univ Bamako, Fac Med, Bamako, Mali. [Koita, Ousmane A.; Traore, Broulaye; Traore, Josepha M.; Sanogo, Kassoum; Sangare, Lansana] Univ Bamako, Fac Sci, Bamako, Mali. [Koita, Ousmane A.; Traore, Broulaye; Traore, Josepha M.; Sanogo, Kassoum; Sangare, Lansana] Hop Gabriel Toure, Serv Pediat, Bamako, Mali. RP Krogstad, DJ (reprint author), 1430 Tulane Ave,SL 17,JB Johnston Bldg,Rm 510, New Orleans, LA 70112 USA. EM krogstad@tulane.edu RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Critical Care Medicine Division of the Clinical Center; National Heart, Lung, and Blood Institute (National Institutes of Health); Faculties of Medicine and Science of the University of Bamako; National Institute of Allergy and Infectious Diseases; Tulane University FX Critical Care Medicine Division of the Clinical Center and the National Heart, Lung, and Blood Institute (National Institutes of Health); the Faculties of Medicine and Science of the University of Bamako and the SEREFO Project in Bamako, Mali, supported by the National Institute of Allergy and Infectious Diseases; and Tulane University research enhancement grants (to F. M. and D.J.K.). The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of the manuscript. NR 48 TC 29 Z9 29 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2010 VL 202 IS 5 BP 791 EP 800 DI 10.1086/655225 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 634ZB UT WOS:000280623800018 PM 20662718 ER PT J AU Winkler, CA An, P Buchbinder, S Donfield, S Goedert, J Johnson, R Kirk, G Nelson, GW Yu, XF AF Winkler, Cheryl A. An, Ping Buchbinder, Susan Donfield, Sharyne Goedert, James Johnson, Randall Kirk, Gregory Nelson, George W. Yu, Xiao-Fang TI No Evidence of an Association between the APOBEC3B Deletion Polymorphism and Susceptibility to HIV Infection and AIDS in Japanese and Indian Populations Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Winkler, Cheryl A.; An, Ping; Johnson, Randall; Nelson, George W.] NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD 21702 USA. [Goedert, James] NCI, Infect & Immunoepidemiol Branch, Bethesda, MD 20892 USA. [Kirk, Gregory] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Yu, Xiao-Fang] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. [Buchbinder, Susan] San Francisco Dept Publ Hlth, San Francisco, CA USA. [Donfield, Sharyne] Rho, Chapel Hill, NC USA. RP Winkler, CA (reprint author), NCI, Lab Genom Divers, SAIC Frederick, Bldg 560,Room 21-19, Frederick, MD 21702 USA. EM winkler@ncifcrf.gov RI Johnson, Randall/B-1517-2014 OI Johnson, Randall/0000-0001-7754-0847 NR 8 TC 1 Z9 1 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2010 VL 202 IS 5 BP 816 EP 817 DI 10.1086/655228 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 634ZB UT WOS:000280623800022 ER PT J AU Armah, GE Hoshino, Y Santos, N Binka, F Damanka, S Adjei, R Honma, S Tatsumi, M Manful, T Anto, F AF Armah, George E. Hoshino, Yasutaka Santos, Norma Binka, Fred Damanka, Susana Adjei, Rosemary Honma, Shinjiro Tatsumi, Masatoshi Manful, Theresa Anto, Francis TI The Global Spread of Rotavirus G10 Strains: Detection in Ghanaian Children Hospitalized with Diarrhea SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROUP-A ROTAVIRUS; POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODIES; CAPSID PROTEIN; NUCLEIC-ACID; SEROTYPE G6; INFECTION; VP7; G9; IDENTIFICATION AB From October 2003 through September 2004, a total of 289 stool samples were collected from children <5 years of age who had severe diarrhea at admission to or when visiting the emergency department at the Navrongo War Memorial Hospital in rural Ghana during a study on rotavirus disease burden. Rotavirus antigen was detected in 115 stool samples (39.8%) tested for rotavirus. Four rotavirus-positive samples were found to bear G10P[6] specificity by reverse-transcription polymerase chain reaction, polymerase chain reaction-enzyme-linked immunosorbent assay, and oligonucleotide microarray hybridization. Two of these strains further exhibited serotype G10 specificity by neutralization and subgroup II specificity by enzyme immunoassay and possessed long electropheretic patterns by polyacrylamide gel electrophoresis. Their VP7 genes shared a much closer nucleotide identity with other African human G10 strains (197%) than with human G10 strain from Asia or South America (<86%) or animal strains (<85%). The VP8(star) genes of the Ghanaian G10 strains exhibited >94% identity to that of human P[6] virus strains and belonged to the P[6] lineage 1a. The deduced VP7 amino acid sequence showed that the Ghanaian strains were more closely related to human G10 strains than to animal G10 strains. The possession of the typical human subgroup II specificity and the P[6] specificity (frequently found in Ghana and the rest of Africa) and the marked similarity in the VP7 antigenic sites suggest that these G10 strains may have evolved through genetic reassortment between bovine and human strains C1 [Armah, George E.; Damanka, Susana; Adjei, Rosemary; Manful, Theresa] Univ Ghana, Noguchi Mem Inst Med Res, Coll Hlth Sci, Dept Electron Microscopy & Histopathol, Legon, Ghana. [Hoshino, Yasutaka; Honma, Shinjiro; Tatsumi, Masatoshi] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Binka, Fred; Anto, Francis] Navrongo Hlth Res Ctr, Navrongo, Ghana. [Santos, Norma] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, BR-21941 Rio De Janeiro, Brazil. RP Armah, GE (reprint author), Univ Ghana, Noguchi Mem Inst Med Res, Coll Hlth Sci, Dept Electron Microscopy & Histopathol, POB LG 581, Legon, Ghana. EM garmah@noguchi.mimcom.net RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU Rotavirus Vaccine Programme; PATH; MIE Hospital; World Health Organization; National Institute of Allergy and Infectious Diseases, National Institutes of Health; GAVI Alliance FX The Rotavirus Vaccine Programme, PATH, MIE Hospital Diarrhoea Research Programme, the World Health Organization, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.; This article is part of a supplement entitled "Rotavirus Infection in Africa: Epidemiology, Burden of Disease, and Strain Diversity," which was prepared as a project of the Rotavirus Vaccine Program, a partnership among PATH, the World Health Organization, and the US Centers for Disease Control and Prevention, and was funded in full or in part by the GAVI Alliance. NR 51 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2010 VL 202 SU 1 BP S231 EP S238 DI 10.1086/653572 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 634ZA UT WOS:000280623700033 PM 20684709 ER PT J AU Esona, MD Steele, D Kerin, T Armah, G Peenze, I Geyer, A Page, N Nyangao, J Agbaya, VA Trabelsi, A Tsion, B Aminu, M Sebunya, T Dewar, J Glass, R Gentsch, J AF Esona, Mathew Dioh Steele, Duncan Kerin, Tara Armah, George Peenze, Ina Geyer, Annelise Page, Nicola Nyangao, James Agbaya, Veronique Akran Trabelsi, Abdelhalim Tsion, Bizuneh Aminu, Maryam Sebunya, Theresia Dewar, John Glass, Roger Gentsch, Jon TI Determination of the G and P Types of Previously Nontypeable Rotavirus Strains from the African Rotavirus Network, 1996-2004: Identification of Unusual G Types SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GROUP-A ROTAVIRUS; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODIES; ENZYME-IMMUNOASSAY; BRAZILIAN CHILDREN; SEQUENCE-ANALYSIS; GUINEA-BISSAU; SEROTYPE G6; RT-PCR AB A total of 215 nontypeable rotavirus samples collected from children <5 years of age by members of the African Rotavirus Network were characterized using reverse-transcription polymerase chain reaction analysis and sequencing. The most predominant strain identified was P[8]G1 (46.9%). Genotypes P[8]G10, P[8]G8, P[6]G8, and P[7]G5 were also detected at frequencies varying from 0.5% to 2.3%. This study suggests that reassortment of unusual G types into a background of globally common genotype P[8] strains may be a major mechanism of generating rotavirus diversity. Nucleotide substitutions at the P[8], P[6], and G1 primer binding sites accounted for the failure to type these strains initially. Hence, these findings highlight the need for regular evaluation of rotavirus genotyping methods. C1 [Esona, Mathew Dioh] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Steele, Duncan] PATH, Seattle, WA USA. [Glass, Roger] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Armah, George] Noguchi Mem Res Inst Accra, Accra, Ghana. [Peenze, Ina; Geyer, Annelise; Dewar, John] Univ Limpopo, MRC, Diarrhoeal Pathogens Res Unit, Pretoria, South Africa. [Page, Nicola] Natl Inst Communicable Dis, Viral Gastroenteritis Unit, Johannesburg, South Africa. [Nyangao, James] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Agbaya, Veronique Akran] Inst Pasteur Cote Ivoire, Dept Virus Epidem, Abidjan, Cote Ivoire. [Trabelsi, Abdelhalim] Univ Hosp Sahloul, Lab Bacteriol Virol, Sousse, Tunisia. [Tsion, Bizuneh] Ethiopian Inst Virol, Addis Ababa, Ethiopia. [Aminu, Maryam] Ahmadu Bello Univ Zaria, Dept Microbiol, Zaria, Nigeria. [Sebunya, Theresia] Univ Botswana, Dept Biol Sci, Gaborone, Botswana. RP Esona, MD (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Natl Ctr Immunizat & Resp Dis, MS G04,1600 Clifton Rd, Atlanta, GA 30333 USA. EM mdi4@cdc.gov OI Page, Nicola/0000-0001-5845-4417 FU Rotavirus Vaccine Program; Centers for Disease Control and Prevention FX The postdoctoral fellowship of Dr Esona was provided through the Rotavirus Vaccine Program, a collaboration between the Program for Appropriate Technology in Health, the World Health Organization, and the Centers for Disease Control and Prevention. Our sincere thanks also go to all the staff of the Medical Research Council Diarrhoeal Pathogens Research Unit, University of Limpopo, and the Gastroenteritis and Respiratory Viruses Laboratory Branch at the Centers for Disease Control and Prevention, Atlanta, for their immense assistance. NR 46 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2010 VL 202 SU 1 BP S49 EP S54 DI 10.1086/653552 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 634ZA UT WOS:000280623700007 PM 20684717 ER PT J AU Mohammed, J Ryscavage, A Perez-Lorenzo, R Gunderson, AJ Blazanin, N Glick, AB AF Mohammed, Javed Ryscavage, Andrew Perez-Lorenzo, Rolando Gunderson, Andrew J. Blazanin, Nicholas Glick, Adam B. TI TGF beta 1-Induced Inflammation in Premalignant Epidermal Squamous Lesions Requires IL-17 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; DELTA T-CELLS; PROMOTE TUMOR-GROWTH; TGF-BETA; BREAST-CANCER; KERATINOCYTE DIFFERENTIATION; SKIN CARCINOGENESIS; IMMUNE-RESPONSES; IFN-GAMMA; MICE AB Overexpression of transforming growth factor-beta 1 (TGF beta 1) in the normal epidermis can provoke an inflammatory response, but whether this occurs within a developing tumor is not clear. To test this, we used an inducible transgenic mouse to overexpress TGF beta 1 in premalignant squamous lesions. Within 48 hours of TGFb1 induction, there was an increase in IL-17 production by both CD4(+) and gamma delta(+) T cells, together with increased expression of T-helper-17 (Th17)-polarizing cytokines. Induction of TGF beta 1 in premalignant primary keratinocytes elevated the expression of proinflammatory and Th17-polarizing cytokines, and the keratinocyte-conditioned media caused IL-17 production by naive T cells that was dependent on T-cell TGF beta 1 signaling. Microarray analysis showed significant upregulation of proinflammatory genes 2 days after TGF beta 1 induction, and this was followed by increased MPO(+), F4/80(+), and CD8(+) cells in tumors, increased CD8(+) effectors and IFN gamma(+) cells in skin-draining LNs, and tumor regression. In parallel, the percentage of tumor CD11b(+)Ly6G(+) neutrophils was reduced. Neutralization of IL-17 blocked TGF beta 1-induced CD11 beta(+) Ly6G(-) tumor infiltration but did not alter the reduction of neutrophils or tumor regression. Thus, TGF beta 1 overexpression causes IL-17-dependent and IL-17-independent changes in the premalignant tumor inflammatory microenvironment. C1 [Mohammed, Javed; Perez-Lorenzo, Rolando; Gunderson, Andrew J.; Blazanin, Nicholas; Glick, Adam B.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16801 USA. [Ryscavage, Andrew] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. RP Glick, AB (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, 201 Life Sci Blvd, University Pk, PA 16801 USA. EM abg11@psu.edu RI Mohammed, Javed/G-3193-2012 FU NCI [CA117957, 122109] FX We thank Dr Stuart Yuspa for support in the initial stages of this project, the NCI Center for Information Technology for advice on analysis of microarray data, the Huck Institute Flow Cytometry Core Facility for help with flow cytometry, and Dr Surojit Sarkar for advice on flow analysis of tumor-infiltrating leukocytes. This study was funded by grants CA117957 and 122109 to AG from the NCI. NR 50 TC 13 Z9 13 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2010 VL 130 IS 9 BP 2295 EP 2303 DI 10.1038/jid.2010.92 PG 9 WC Dermatology SC Dermatology GA 638RA UT WOS:000280912100018 PM 20410912 ER PT J AU Mascia, F Lam, G Threadgill, D Yuspa, S AF Mascia, Francesca Lam, Gary Threadgill, David Yuspa, Stuart TI Epidermal EGFR signaling controls leukocyte infiltration in the skin and prevents systemic disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Society-for-Dermatological-Research (ESDR 2010) CY SEP 08-11, 2010 CL Helsinki, FINLAND SP European Soc Dermatolog Res C1 [Mascia, Francesca; Lam, Gary; Yuspa, Stuart] NCI, NIH, Bethesda, MD 20892 USA. [Threadgill, David] UNC, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2010 VL 130 SU 2 BP S3 EP S3 PG 1 WC Dermatology SC Dermatology GA 641FL UT WOS:000281110100016 ER PT J AU Nikolic, D Lehmann, M Felts, R Garcia, E Blanchet, F Subramaniam, S Pigeut, V AF Nikolic, Damjan Lehmann, Martin Felts, Richard Garcia, Eduardo Blanchet, Fabien Subramaniam, Sriram Pigeut, Vincent TI HIV-1 activates Cdc42 and induces filopodia in immature dendritic cells to facilitate cell-to-cell virus propagation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the European-Society-for-Dermatological-Research (ESDR 2010) CY SEP 08-11, 2010 CL Helsinki, FINLAND SP European Soc Dermatolog Res C1 [Nikolic, Damjan; Lehmann, Martin; Garcia, Eduardo; Blanchet, Fabien; Pigeut, Vincent] Univ Geneva, Fac Med, Dept Microbiol & Mol Med, Geneva, Switzerland. [Nikolic, Damjan; Lehmann, Martin; Garcia, Eduardo; Blanchet, Fabien; Pigeut, Vincent] Univ Hosp Geneva, Dept Dermatol & Venereol, Geneva, Switzerland. [Felts, Richard; Subramaniam, Sriram] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2010 VL 130 SU 2 BP S92 EP S92 PG 1 WC Dermatology SC Dermatology GA 641FL UT WOS:000281110100543 ER PT J AU Kaneski, CR Schiffmann, R Brady, RO Murray, GJ AF Kaneski, Christine R. Schiffmann, Raphael Brady, Roscoe O. Murray, Gary J. TI Use of lissamine rhodamine ceramide trihexoside as a functional assay for alpha-galactosidase A in intact cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Fabry disease; lysosomal storage disorder; fluorescent substrate; globotriaosylceramide ID FABRY-DISEASE; SKIN FIBROBLASTS; GAUCHER-DISEASE; NATURAL-HISTORY; IN-VITRO; FEMALES; GENE; METABOLISM; REGISTRY; STORAGE AB Fabry disease is an X-linked disorder caused by mutations in the GLA gene encoding for alpha-galactosidase A (AGA, EC 3.2.1.22). Measurement of AGA enzyme activity using cell homogenates can easily identify men with Fabry disease, but in women, the degree of X-inactivation in the tested tissue may produce activities in homogenates that are indistinguishable from normal. Monti et al. developed a series of lissamine rhodamine-labeled glycosphingolipid substrates that can be used to measure clearance of these lipids in intact cells (1). We report here that one of these substrates, lissamine rhodamine ceramide trihexoside (LR-CTH), can be used as a probe for functional activity of AGA in intact fibroblasts, endothelial cells, and T-lymphocytes from patients with Fabry disease. By utilizing standard detection techniques, such as microscopic imaging, fluorescence microplate spectrophotometry, and flow cytometry, cells with impaired AGA activity can easily be distinguished from wild-type (WT) cells, and these two cell types can be isolated into separate populations using fluorescence-activated cell sorting (FACS). The assay we report here can be adapted to evaluate new therapies by high-throughput screening, can aid in the study of AGA activity in living cells, and can assist in the diagnosis of women with the Fabry trait.-Kaneski, C. R., R. Schiffmann, R. O. Brady, and G. J. Murray. Use of lissamine rhodamine ceramide trihexoside as a functional assay for alpha-galactosidase A in intact cells. J. Lipid Res. 2010. 51: 2808-2817. C1 [Kaneski, Christine R.; Brady, Roscoe O.] NINDS, NIH, Bethesda, MD 20892 USA. [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. [Murray, Gary J.] NIAAA, Div Metab & Hlth Effect, NIH, Rockville, MD 20852 USA. RP Kaneski, CR (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM Christine.Kaneski@baylorhealth.edu OI Kaneski, Christine/0000-0003-1453-2502 FU Intramural Research Division of the National Institutes of Neurological Disorders and Stroke, National Institutes of Health; Baylor Research Institute FX This work was supported by the Intramural Research Division of the National Institutes of Neurological Disorders and Stroke, National Institutes of Health. This work was also supported by the Baylor Research Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or other granting agencies. NR 27 TC 4 Z9 4 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2010 VL 51 IS 9 BP 2808 EP 2817 DI 10.1194/jlr.D007294 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 637FA UT WOS:000280800200032 PM 20526001 ER PT J AU Haacke, EM Duhaime, AC Gean, AD Riedy, G Wintermark, M Mukherjee, P Brody, DL DeGraba, T Duncan, TD Elovic, E Hurley, R Latour, L Smirniotopoulos, JG Smith, DH AF Haacke, E. Mark Duhaime, Ann Christine Gean, Alisa D. Riedy, Gerard Wintermark, Max Mukherjee, Pratik Brody, David L. DeGraba, Thomas Duncan, Timothy D. Elovic, Elie Hurley, Robin Latour, Lawrence Smirniotopoulos, James G. Smith, Douglas H. TI Common Data Elements in Radiologic Imaging of Traumatic Brain Injury SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE traumatic brain injury; common data elements; characterization of TBI; multi-modality imaging of TBI; TBI imaging database ID DIFFUSE AXONAL INJURY; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; ROUTINE CLINICAL-PRACTICE; PROTON MR SPECTROSCOPY; SEVERE HEAD TRAUMA; WHITE-MATTER INJURY; PERFUSION-CT; FUNCTIONAL MRI; TECHNETIUM-99M-HMPAO SPECT AB Traumatic brain injury (TBI) has a poorly understood pathology. Patients suffer from a variety of physical and cognitive effects that worsen as the type of trauma worsens. Some noninvasive insights into the pathophysiology of TBI are possible using magnetic resonance imaging (MRI), computed tomography (CT), and many other forms of imaging as well A recent workshop was convened to evaluate the common data elements (CDEs) that cut across the imaging field and given the charge to review the contributions of the various imaging modalities to TBI and to prepare an overview of the various clinical manifestations of TBI and their interpretation. Technical details regarding state-of-the-art protocols for both MRI and CT are also presented with the hope of guiding current and future research efforts as to what is possible in the field. Stress was also placed on the potential to create a database of CDEs as a means to best record information from a given patient from the reading of the images. C1 [Haacke, E. Mark] Wayne State Univ, MR Res Facil, Dept Radiol & Biomed Engn, Detroit, MI 48201 USA. [Duhaime, Ann Christine] Dartmouth Hitchcock Med Ctr, Dept Pediat Neurosurg, Lebanon, NH 03766 USA. [Gean, Alisa D.] San Francisco Gen Hosp, Dept Radiol, Brain & Spinal Cord Injury Ctr, San Francisco, CA 94110 USA. [Riedy, Gerard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Wintermark, Max; Mukherjee, Pratik] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Mukherjee, Pratik] Univ Calif San Francisco, Dept Bioengn, San Francisco, CA 94143 USA. [Brody, David L.] Washington Univ, Dept Neurol, St Louis, MO USA. [DeGraba, Thomas] Natl Naval Med Ctr, Bethesda, MD USA. [Duncan, Timothy D.] Naval Med Ctr San Diego, Dept Radiol, San Diego, CA USA. [Elovic, Elie] Univ Utah, Hlth Sci Ctr, Div Phys Med & Rehabil, Salt Lake City, UT USA. [Hurley, Robin] Hefner VA Med Ctr, Salisbury, NC USA. [Latour, Lawrence] NINDS, Stroke Diagnost & Therapeut Sect, Stroke Branch, Bethesda, MD 20892 USA. [Smirniotopoulos, James G.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD USA. [Smith, Douglas H.] Univ Penn, Dept Neurosurg, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. RP Haacke, EM (reprint author), Wayne State Univ, MR Res Facil, Dept Radiol & Biomed Engn, 3990 John R Rd, Detroit, MI 48201 USA. EM nmrimaging@aol.com RI smith, douglas/A-1321-2007; Smirniotopoulos, James/D-3726-2011; Mukherjee, Pratik/A-5446-2008; OI Mukherjee, Pratik/0000-0001-7473-7409; Wintermark, Max/0000-0002-6726-3951 NR 128 TC 37 Z9 41 U1 2 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2010 VL 32 IS 3 BP 516 EP 543 DI 10.1002/jmri.22259 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 646IK UT WOS:000281532700002 PM 20815050 ER PT J AU Chaiworapongsa, T Kusanovic, JP Savasan, ZA Mazaki-Tovi, S Kim, SK Vaisbuch, E Tarca, AL Mittal, P Ogge, G Madan, I Dong, Z Yeo, L Hassan, SS Romero, R AF Chaiworapongsa, Tinnakorn Kusanovic, Juan Pedro Savasan, Zeynep Alpay Mazaki-Tovi, Shali Kim, Sun Kwon Vaisbuch, Edi Tarca, Adi L. Mittal, Pooja Ogge, Giovanna Madan, Ichchha Dong, Zhong Yeo, Lami Hassan, Sonia S. Romero, Roberto TI Fetal death: A condition with a dissociation in the concentrations of soluble vascular endothelial growth factor receptor-2 between the maternal and fetal compartments SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Amniotic fluid; angiogenesis; angiogenic factor; congenital anomaly; intrauterine demise; sKDR; maternal plasma; preeclampsia; stillbirth; unexplained fetal death; sVEGF-R2 ID FOR-GESTATIONAL-AGE; CIRCULATING ANGIOGENIC FACTORS; LATE-ONSET PREECLAMPSIA; UTERINE ARTERY DOPPLER; AMNIOTIC-FLUID VOLUME; TYROSINE KINASE-1; INTRAMEMBRANOUS ABSORPTION; SERUM CONCENTRATIONS; SVEGFR-2 LEVELS; BIRTH-WEIGHT AB Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design. Maternal plasma was obtained from patients with fetal death (n = 59) and normal pregnant women (n 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term (n 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Nonparametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women (p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women (p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4-7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group (p50.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5-164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). Conclusion. Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus. C1 [Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Savasan, Zeynep Alpay; Mazaki-Tovi, Shali; Kim, Sun Kwon; Vaisbuch, Edi; Tarca, Adi L.; Mittal, Pooja; Ogge, Giovanna; Madan, Ichchha; Dong, Zhong; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, Hutzel Womens Hosp,NIH,DHHS, Detroit, MI 48201 USA. [Chaiworapongsa, Tinnakorn; Kusanovic, Juan Pedro; Savasan, Zeynep Alpay; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Madan, Ichchha; Yeo, Lami; Hassan, Sonia S.; Romero, Roberto] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Tarca, Adi L.] Wayne State Univ, Dept Comp Sci, 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, Perinatol Res Branch, NICHD, Hutzel Womens Hosp,NIH,DHHS, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Ogge, Giovanna/G-6109-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX This research was supported by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 78 TC 7 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD SEP PY 2010 VL 23 IS 9 BP 960 EP 972 DI 10.3109/14767050903410664 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 653HP UT WOS:000282080400003 PM 20158395 ER PT J AU Barker, CM Eldridge, BF Reisen, WK AF Barker, Christopher M. Eldridge, Bruce F. Reisen, William K. TI Seasonal Abundance of Culex tarsalis and Culex pipiens omplex Mosquitoes (Diptera: Culicidae) in California SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Culex tarsalis; Culex pipiens; Culex quinquefasciatus; seasonality; California ID WEST-NILE-VIRUS; ST-LOUIS ENCEPHALITIS; KERN-COUNTY; SOUTHEASTERN CALIFORNIA; QUINQUEFASCIATUS DIPTERA; COACHELLA-VALLEY; NORTH-AMERICA; TRANSMISSION; POPULATIONS; DIAPAUSE AB Large-scale patterns in the seasonal abundance profiles of the arboviral mosquito vectors Culex tarsalis Coquillett and the species of the Culex pipiens complex were described based on a decade of counts from 868 New Jersey light traps located throughout the urban and agricultural areas of California. Mean seasonal abundance profiles varied markedly among hydrologic regions. For all species, abundance increased earlier and declined later in drier, warmer southern regions, but variation could not be explained fully by latitude. The observed patterns may be driven by temperature, availability of larval habitats, and for the Cx. pipiens complex, the taxonomic composition of local populations. C1 [Barker, Christopher M.; Reisen, William K.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Barker, Christopher M.] Univ Calif Davis, Ctr Vectorborne Dis, Davis, CA 95616 USA. RP Barker, CM (reprint author), Univ Calif Davis, Ctr Vectorborne Dis, Old Davis Rd, Davis, CA 95616 USA. EM cmbarker@ucdavis.edu FU National Aeronautics and Space Administration [00-543]; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX We thank the member agencies of the Mosquito and Vector Control Association of California and other local vector control agencies for providing mosquito collection records used in this study (see Table 1). This work was supported by National Aeronautics and Space Administration Earth-Sun Science Applied Sciences Program Research Opportunities in Space and Earth Science, Decision Support through Earth-Sun Science Research Results RM08-6044 for NNA06CN02A, and National Oceanic and Atmospheric Administration Office of Global Programs, Climate Variability and Human Health Grant 00-543. C.M.B. and W.K.R. also acknowledge funding support from the Research and Policy in Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 53 TC 13 Z9 14 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-2585 EI 1938-2928 J9 J MED ENTOMOL JI J. Med. Entomol. PD SEP PY 2010 VL 47 IS 5 BP 759 EP 768 DI 10.1603/ME09139 PG 10 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 649CK UT WOS:000281744600006 PM 20939368 ER PT J AU Dao, A Kassogue, Y Adamou, A Diallo, M Yaro, AS Traore, SF Lehmann, T AF Dao, Adama Kassogue, Yaya Adamou, Abdoulaye Diallo, Moussa Yaro, Alpha Seydou Traore, Sekou F. Lehmann, Tovi TI Reproduction-Longevity Trade-Off in Anopheles gambiae (Diptera: Culicidae) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Anopheles gambiae; survival; body size; cost of reproduction; mating ID DROSOPHILA-MELANOGASTER; MOLECULAR-FORMS; GEOGRAPHIC-VARIATION; SAO-TOME; COSTS; MOSQUITO; FEMALES; SYSTEM; MALES; SEXES AB Reduced survival and future reproduction due to of current reproduction is a trade-off known as the cost of reproduction. Surprisingly, only a few studies have assessed the cost of reproduction in arthropod disease vectors, despite its effect on longevity, and thus on vectorial capacity. We evaluated the cost of reproduction on survival of Anopheles gambiae Giles by comparing mosquitoes that were denied exposure to the other sex, hereafter named virgins, and those that were allowed exposure to the other sex and mating, hereafter named mated. Merely 6 d of exposure to females with mating activity reduced male survival from a median of 17 d in virgins to 15 d in mated, indicating that male mating cost is substantial. The increase in mortality of mated males began several days after the exposure to females ended, indicating that mating is not associated with immediate mortality risk. Notably, body size was negatively correlated with male mortality in mated males, but not in virgins. The rate of insemination declined after 4 d of exposure to females, indicating that male mating capacity is limited and further supporting the hypothesis that mating is costly for males. Consistent with previous studies, female survival on sugar alone (median = 16 d) was shorter than on blood and sugar (median = 19 d), regardless if she was mated or virgin. Overall, survival of mated females was lower than that of virgins on a diet of blood and sugar, but no difference was found on a diet of sugar only. However, the cost of reproduction in females remains ambiguous because the difference in survival between virgin mid mated females was driven by the difference between virgin (median = 19 d) and uninseminated females exposed to males (median = 17 d), rather than between virgin and inseminated females (median = 19 d). Accordingly, sperm and seminal fluid, egg development, and oviposition have negligible cost in terms of female survival. Only exposure to males without insemination decreased female survival. Nonetheless, if exposure to males under natural conditions is also associated with reduced survival, it might explain why females remain monogamous. C1 [Lehmann, Tovi] NIAID, NIH, Lab Malaria & Vector Res, Rockville, MD 20852 USA. [Dao, Adama; Kassogue, Yaya; Adamou, Abdoulaye; Diallo, Moussa; Yaro, Alpha Seydou; Traore, Sekou F.] Univ Mali, Malaria Res & Training Ctr, Bamako, Mali. RP Lehmann, T (reprint author), NIAID, NIH, Lab Malaria & Vector Res, MS 8132,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM tlehmann@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX We are grateful to the residents of Bancoumana who accommodate our studies, and Drs. Diana Huestis, Nick Manoukis, Alvaro Molina-Cruz, and Diabate Abdoulaye for helpful discussions and comments on previous versions of this manuscript. We thank Robert Gwadz for ongoing support and facilitation of our projects. This work was supported by the Intramural Research Program at National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 47 TC 16 Z9 16 U1 4 U2 18 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD SEP PY 2010 VL 47 IS 5 BP 769 EP 777 DI 10.1603/ME10052 PG 9 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 649CK UT WOS:000281744600007 PM 20939369 ER PT J AU Florin, DA Lawyer, P Rowton, E Schultz, G Wilkerson, R Davies, SJ Lipnick, R Keep, L AF Florin, David A. Lawyer, Phillip Rowton, Edgar Schultz, George Wilkerson, Richard Davies, Stephen J. Lipnick, Robert Keep, Lisa TI Morphological Anomalies in Two Lutzomyia (Psathyromyia) shannoni (Diptera: Psychodidae: Phlebotominae) Specimens Collected From Fort Rucker, Alabama, and Fort Campbell, Kentucky SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Lutzomya shannoni; gonostylus; morphologic anomalies; molecular markers ID INTROGRESSION; INTERMEDIA; LEISHMANIA; VECTORS AB This report describes two male specimens of the sand fly species Lutzomyia shannoni (Dyar) (Diptera: Psychodidae: Phlebotominae) collected at Fort Rucker, AL, and Fort Campbell, KY, in dry ice-baited light traps during September 2005. The specimens were observed to have anomalies to the number of spines on the gonostyli. The taxonomic keys of Young and Perkins (Mosq. News 44: 263-285; 1984) use the number of spines on the gonostylus in the first couplet to differentiate two major groupings of North American sand flies. The two anomalous specimens were identified as L. shannoni based on the following criteria: 1) both specimens possess antennal ascoids with long, distinct proximal spurs (a near diagnostic character of L. shannoni in North America), 2) the sequences of the partial cytochrome c oxidase subunit 1 gene from both specimens indicated L. shannoni, and 3) the sequences of the internal transcribed spacer 2 molecular marker from both specimens indicated L. shannoni. The anomalous features are fundamentally different from each other as the Fort Rucker specimen possesses a fifth spine (basally located) on just one gonostylus, whereas the Fort Campbell specimen possesses five spines (extra spines subterminally located) on both gonostyli. Because the gonostyli are part of the external male genitalia, anomalies in the number of spines on the gonostyli may have serious biological consequences, such as reduced reproductive success, for the possessors. These anomalies are of taxonomic interest as the specimens could easily have been misidentified using available morphological keys. C1 [Florin, David A.; Schultz, George; Davies, Stephen J.; Keep, Lisa] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Lawyer, Phillip] Natl Inst Allergy & Infect Dis, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Rowton, Edgar; Wilkerson, Richard] Walter Reed Army Inst Res, Dept Entomol, Silver Spring, MD 20910 USA. [Lipnick, Robert] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD 20910 USA. RP Florin, DA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM david.florin@usuhs.mil RI Rowton, Edgar/A-4474-2012; Rowton, Edgar/A-1975-2011 OI Rowton, Edgar/0000-0002-1979-1485 FU Uniformed Services University of the Health Sciences [R087WB] FX This research was funded by Uniformed Services University of the Health Sciences intramural grant R087WB: Risk for domestic transmission of leishmaniasis acquired by U.S. service members in Iraq/Afghanistan. NR 10 TC 4 Z9 4 U1 0 U2 1 PU ENTOMOLOGICAL SOC AMER PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD SEP PY 2010 VL 47 IS 5 BP 952 EP 956 DI 10.1603/ME10088 PG 5 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 649CK UT WOS:000281744600032 PM 20939394 ER PT J AU Aronova, MA Sousa, AA Zhang, G Leapman, RD AF Aronova, M. A. Sousa, A. A. Zhang, G. Leapman, R. D. TI Limitations of beam damage in electron spectroscopic tomography of embedded cells SO JOURNAL OF MICROSCOPY LA English DT Article DE Biological applications; cell nucleus; EFTEM; electron tomography; elemental mapping; energy filtering transmission electron microscopy; nitrogen; phosphorus ID ENERGY-LOSS SPECTROSCOPY; BIOLOGICAL STRUCTURES; RESOLUTION; MICROANALYSIS; SPECIMENS; DISTRIBUTIONS; PHOSPHORUS; ELEMENTS; EFTEM AB P>Elemental mapping in the energy filtering transmission electron microscope (EFTEM) can be extended into three dimensions (3D) by acquiring a series of two-dimensional (2D) core-edge images from a specimen oriented over a range of tilt angles, and then reconstructing the volume using tomographic methods. EFTEM has been applied to imaging the distribution of biological molecules in 2D, e.g. nucleic acid and protein, in sections of plastic-embedded cells, but no systematic study has been undertaken to assess the extent to which beam damage limits the available information in 3D. To address this question, 2D elemental maps of phosphorus and nitrogen were acquired from unstained sections of plastic-embedded isolated mouse thymocytes. The variation in elemental composition, residual specimen mass and changes in the specimen morphology were measured as a function of electron dose. Whereas 40% of the total specimen mass was lost at doses above 106 e-/nm2, no significant loss of phosphorus or nitrogen was observed for doses as high as 108 e-/nm2. The oxygen content decreased from 25 +/- 2 to 9 +/- 2 atomic percent at an electron dose of 104 e-/nm2, which accounted for a major component of the total mass loss. The specimen thickness decreased by 50% after a dose of 108 e-/nm2, and a lateral shrinkage of 9.5 +/- 2.0% occurred from 2 x 104 to 108 e-/nm2. At doses above 107 e-/nm2, damage could be observed in the bright field as well in the core edge images, which is attributed to further loss of oxygen and carbon atoms. Despite these artefacts, electron tomograms obtained from high-pressure frozen and freeze-substituted sections of C. elegans showed that it is feasible to obtain useful 3D phosphorus and nitrogen maps, and thus to reveal quantitative information about the subcellular distributions of nucleic acids and proteins. C1 [Aronova, M. A.; Sousa, A. A.; Zhang, G.; Leapman, R. D.] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Heath FX We are grateful to Dr. Y. Kim for helpful discussions and to Dr. M. J. Kruhlak for providing cells used in this study. We also thank A. A. Azari for providing reconstructions of tomographic data. This work was supported by the intramural program of the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Heath. NR 35 TC 4 Z9 4 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.. PD SEP PY 2010 VL 239 IS 3 BP 223 EP 232 DI 10.1111/j.1365-2818.2010.03376.x PG 10 WC Microscopy SC Microscopy GA 639SN UT WOS:000280994900006 PM 20701660 ER PT J AU Elster, EA Hawksworth, JS Cheng, O Leeser, DB Ring, M Tadaki, DK Kleiner, DE Eberhardt, JS Brown, TS Mannon, RB AF Elster, Eric A. Hawksworth, Jason S. Cheng, Orlena Leeser, David B. Ring, Michael Tadaki, Douglas K. Kleiner, David E. Eberhardt, John S., III Brown, Trevor S. Mannon, Roslyn B. TI Probabilistic (Bayesian) Modeling of Gene Expression in Transplant Glomerulopathy SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID CHRONIC ALLOGRAFT NEPHROPATHY; GROWTH-FACTOR-BETA; RENAL-TRANSPLANTATION; FUTURE-DIRECTIONS; ACUTE REJECTION; T-CELLS; RECIPIENTS; BIOPSIES; INJURY; C4D AB Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR, and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0.05). The Bayesian analysis identified critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7, and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when derived from either immune function (area under the curve [95% confidence interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks. Critical pathways in the Bayesian models were also analyzed by using the Fisher exact test and had P values <0.005. This study demonstrates that evaluating quantitative gene expression profiles with Bayesian modeling can identify significant transcriptional associations that have the potential to support the diagnostic capability of allograft histology. This integrated approach has broad implications in the field of transplant diagnostics. (J Mol Diagn 2010, 12:653-663; DOI: 10.2353/jmoldx.2010.090101) C1 [Elster, Eric A.; Hawksworth, Jason S.; Tadaki, Douglas K.; Brown, Trevor S.] USN, Med Res Ctr, Regenerat Med Dept, Silver Spring, MD 20910 USA. [Elster, Eric A.; Hawksworth, Jason S.] Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. [Elster, Eric A.; Cheng, Orlena; Ring, Michael; Mannon, Roslyn B.] NIDDK, NIH, Washington, DC USA. [Elster, Eric A.] Natl Naval Med Ctr, Dept Surg, Silver Spring, MD USA. [Leeser, David B.] Weill Cornell Med Ctr, Dept Surg, New York, NY USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Eberhardt, John S., III] Decis Q Corp, Washington, DC USA. RP Elster, EA (reprint author), USN, Med Res Ctr, Regenerat Med Dept, Silver Spring, MD 20910 USA. EM eric.elster1@med.navy.mil RI Brown, Trevor/K-4703-2012; Brown, Trevor/F-7392-2015; OI Brown, Trevor/0000-0001-7042-785X; Brown, Trevor/0000-0001-7042-785X; Kleiner, David/0000-0003-3442-4453 FU US Navy Bureau of Medicine and Surgery; National Institute of Diabetes Digestive and Kidney Diseases [Z01-DK062008] FX Supported in part by the US Navy Bureau of Medicine and Surgery and by the intramural research program of the National Institute of Diabetes Digestive and Kidney Diseases Z01-DK062008 (R.B.M.). NR 47 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD SEP PY 2010 VL 12 IS 5 BP 653 EP 663 DI 10.2353/jmoldx.2010.090101 PG 11 WC Pathology SC Pathology GA 648JW UT WOS:000281690800014 PM 20688906 ER PT J AU Williams, PM Li, R Johnson, NA Wright, G Heath, JD Gascoyne, RD AF Williams, P. Mickey Li, Rui Johnson, Nathalie A. Wright, George Heath, Joe-Don Gascoyne, Randy D. TI A Novel Method of Amplification of FFPET-Derived RNA Enables Accurate Disease Classification with Microarrays SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID B-CELL LYMPHOMA; GENE-EXPRESSION; MOLECULAR SUBTYPES; HYBRIDIZATION; PREDICTION; TARGETS; CDNA AB A new method for amplification and labeling of RNA is assessed that permits gene expression microarray analysis of formalin-fixed paraffin-embedded tissue (FFPET) samples. Valid biological data were obtained using gene expression microarrays of diffuse large B-cell lymphoma (DLBCL) FFPET samples. We examined 59 matched DLBCL patient samples, FFPET, and fresh/frozen. The samples contained both prognostic subgroups of DLBCL: germinal center B-cell (GCB) and activated B-cell (ABC). Fresh/frozen (FF) samples were amplified by both the traditional Eberwine oligo-dT method and a new method described herein. The matching FFPET samples were also amplified using the new method. Here we detail the comparison of results from all three datasets of matched samples. An established classification model built from previous data accurately classified these new samples. This new method provides a useful technology advance for microarray analysis of FFPET archival samples. (J Mol Diagn 2010, 12:680-686; DOI: 10.2353/jmoldx.2010.090164) C1 [Williams, P. Mickey; Li, Rui] Roche Mol Diagnost, Pleasanton, CA USA. [Johnson, Nathalie A.; Gascoyne, Randy D.] British Columbia Canc Agcy, Vancouver, BC, Canada. [Wright, George] NCI, Biometr Res Branch, Div Canc Treatment, Ctr Canc Res, Bethesda, MD 20892 USA. [Wright, George] NCI, Diag & Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Heath, Joe-Don] Nugen Technol, San Carlos, CA USA. RP Williams, PM (reprint author), NCI, Patient Characterizat Ctr, SAIC, Frederick, MD 21702 USA. EM mickey.williams@nih.gov FU National Cancer Institute of Canada; Terry Fox Foundation [19001]; NCI Strategic Partnering to Evaluate Cancer Signatures [U01-CA-114778] FX Supported by a National Cancer Institute of Canada, Terry Fox Foundation Program Project grant # 19001 (ROD.). R.G.D. and G.W. are supported by an NCI Strategic Partnering to Evaluate Cancer Signatures grant (U01-CA-114778). NR 26 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD SEP PY 2010 VL 12 IS 5 BP 680 EP 686 DI 10.2353/jmoldx.2010.090164 PG 7 WC Pathology SC Pathology GA 648JW UT WOS:000281690800017 PM 20688907 ER PT J AU Kengyel, A Wolf, WA Chisholm, RL Sellers, JR AF Kengyel, Andras Wolf, Wendy A. Chisholm, Rex L. Sellers, James R. TI Nonmuscle myosin IIA with a GFP fused to the N-terminus of the regulatory light chain is regulated normally SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Article DE GFP; Nonmuscle myosin; Regulatory light chain; Enzymatic activity; In vitro motility ID SMOOTH-MUSCLE MYOSIN; HEAVY-MEROMYOSIN; MOTOR DOMAIN; PHOSPHORYLATION; SUBFRAGMENT-1; MIGRATION; REVEALS; KINASE; CELLS; STATE AB Nonmuscle myosin II plays a crucial role in a variety of cellular processes (e. g., polarity formation, cell motility, and cytokinesis). It is composed of two heavy chains, two regulatory light chains and two essential light chains. The ATPase activity of the myosin II motor domain is regulated through phosphorylation of the regulatory light chain (RLC) by myosin light chain kinase. To study myosin function and localization in cellular processes, GFP-fused RLCs are widely used; however, the exact kinetic properties of myosins with bound GFP-RLC are poorly described. More importantly, it has not been shown that a regulatory light chain fused at its N-terminus with GFP can maintain the normal phosphorylation-dependent regulation of nonmuscle myosin or serve as a substrate for myosin light chain kinase. We coexpressed N-terminal GFP-RLC with a heavy meromyosin (HMM)-like fragment of nonmuscle myosin IIA and essential light chain to characterize the phosphorylation dynamics and in vitro kinetic properties of the resulting HMM. Myosin light chain kinase phosphorylates the GFP-RLC bound to HMM IIA with the same V(max) as it does the wild type RLC bound to HMM IIA, but the K(m) is about two fold higher for the GFP fusion protein, meaning that it is a somewhat poorer substrate. The steady-state actin-activated MgATPase activity of the GFP-RLC HMM is very low in the absence of phosphorylation demonstrating that the GFP moiety does not prevent formation of the off state. The actin-activated MgATPase activity of phosphorylated GFP-RLC-HMM and is about half that of wild type phosphorylated HMM. The ability of phosphorylated GFP-RLC-HMM to move actin filaments in the actin gliding assay is also slightly compromised. These data indicate that despite some kinetic differences the N-terminal GFP fusion to the regulatory light chain is a reasonable model system for studying myosin function in vivo. C1 [Kengyel, Andras; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Wolf, Wendy A.; Chisholm, Rex L.] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA. [Kengyel, Andras] Univ Pecs, Fac Med, Dept Biophys, Pecs, Hungary. RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bldg 50,Room 3523, Bethesda, MD 20892 USA. EM Sellersj@nhlbi.nih.gov FU NIH [GM39264] FX RLC acknowledges the support of NIH grant GM39264. NR 30 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD SEP PY 2010 VL 31 IS 3 BP 163 EP 170 DI 10.1007/s10974-010-9220-y PG 8 WC Cell Biology SC Cell Biology GA 702XU UT WOS:000285930000002 PM 20711642 ER PT J AU Usami, Y Nakagawa-Goto, K Lang, JY Kim, Y Lai, CY Goto, M Sakurai, N Taniguchi, M Akiyama, T Morris-Natschke, SL Bastow, KF Cragg, G Newman, DJ Fujitake, M Takeya, K Hung, MC Lee, EYHP Lee, KH AF Usami, Yoshihide Nakagawa-Goto, Kyoko Lang, Jing-Yu Kim, Yoon Lai, Chin-Yu Goto, Masuo Sakurai, Nobuko Taniguchi, Masahiko Akiyama, Toshiyuki Morris-Natschke, Susan L. Bastow, Kenneth F. Cragg, Gordon Newman, David J. Fujitake, Mihoyo Takeya, Koichi Hung, Mien-Chie Lee, Eva Y. -H. P. Lee, Kuo-Hsiung TI Antitumor Agents. 282. 2 '-(R)-O-Acetylglaucarubinone, a Quassinoid from Odyendyea gabonensis As a Potential Anti-Breast and Anti-Ovarian Cancer Agent SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PROTEIN-SYNTHESIS; CELLS; BRUCEANTIN; BRUSATOL; (-)-GLAUCARUBOLONE; (-)-CHAPARRINONE; DIFFERENTIATION; SIMAROUBACEAE; INHIBITION; ALKALOIDS AB A new quassinoid, designated 2'-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre]. The structure of 1 was determined by spectroscopic analysis and by semisynthesis from glaucarubolone. Complete H-1 and C-13 NMR assignments of compounds 1-8 were also established from detailed analysis of two-dimensional NMR spectra, and the reported configurations in odyendene (7) and odyendane (8) were corrected. Compound 1 showed potent cytotoxicity against multiple cancer cell lines. Further investigation using various types of breast and ovarian cancer cell lines suggested that 1 does not target the estrogen receptor or progesterone receptor. When tested against mammary epithelial proliferation in vivo using a Brcal/p53-deficient mice model, 1 also caused significant reduction in mammary duct branching. C1 [Usami, Yoshihide; Nakagawa-Goto, Kyoko; Lai, Chin-Yu; Sakurai, Nobuko; Taniguchi, Masahiko; Akiyama, Toshiyuki; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung] Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Lang, Jing-Yu; Hung, Mien-Chie] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kim, Yoon; Lee, Eva Y. -H. P.] Univ Calif Irvine, Coll Med, Irvine, CA 92697 USA. [Goto, Masuo] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. [Bastow, Kenneth F.] Univ N Carolina, Div Med Chem & Nat Prod, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Cragg, Gordon; Newman, David J.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Fujitake, Mihoyo] Osaka Univ Pharmaceut Sci, Takatsu Ki, Osaka 5691094, Japan. [Takeya, Koichi] Tokyo Univ Pharm & Life Sci, Tokyo 1920355, Japan. [Lee, Kuo-Hsiung] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan. RP Lee, KH (reprint author), Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM khlee@unc.edu RI GOTO, Kyoko/D-8389-2015 OI GOTO, Kyoko/0000-0002-1642-6538 FU National Cancer Institute [CA 17625] FX This study was supported in part by a grant from the National Cancer Institute (CA 17625) awarded to K.H.L. We are grateful to Dr. K. Koshlap of the University of North Carolina at Chapel Hill for the 2D NMR experiments and Dr. Y. Sakurai of our laboratory for useful advice. We also acknowledge Dr. G. McPherson, of the Missouri Botanical Garden, and the Centre National de la Recherche Scientifique et Technologique in Libreville, Gabon, for their collaboration in the plant collection. NR 28 TC 7 Z9 7 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2010 VL 73 IS 9 BP 1553 EP 1558 DI 10.1021/np100406d PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 652VL UT WOS:000282038800016 PM 20738103 ER PT J AU Li, X Li, J Gardner, EL Xi, ZX AF Li, Xia Li, Jie Gardner, Eliot L. Xi, Zheng-Xiong TI Activation of mGluR7s inhibits cocaine-induced reinstatement of drug-seeking behavior by a nucleus accumbens glutamate-mGluR2/3 mechanism in rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMN082; cocaine; dopamine; glutamate; mGluR7; reinstatement; relapse ID CUE-INDUCED REINSTATEMENT; BRAIN REWARD FUNCTION; SQUIRREL-MONKEYS; RECEPTOR ANTAGONISTS; DOPAMINE-RECEPTORS; MESSENGER-RNA; RELAPSE; NICOTINE; SHELL; AGONIST AB P>The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown. Using a rat relapse model, we found that systemic administration of AMN082, a selective mGluR7 allosteric agonist, dose-dependently inhibits cocaine-induced reinstatement of drug-seeking behavior. Intracranial microinjections of AMN082 into the nucleus accumbens (NAc) or ventral pallidum, but not the dorsal striatum, also inhibited cocaine-primed reinstatement, an effect that was blocked by local co-administration of MMPIP, a selective mGluR7 antagonist. In vivo microdialysis demonstrated that cocaine priming significantly increased extracellular dopamine in the NAc, ventral pallidum and dorsal striatum, while increasing extracellular glutamate in the NAc only. AMN082 alone failed to alter extracellular dopamine, but produced a slow-onset long-lasting increase in extracellular glutamate in the NAc only. Pre-treatment with AMN082 dose-dependently blocked both cocaine-enhanced NAc glutamate and cocaine-induced reinstatement, an effect that was blocked by MMPIP or LY341497 (a selective mGluR2/3 antagonist). These data suggest that mGluR7 activation inhibits cocaine-induced reinstatement of drug-seeking behavior by a glutamate-mGluR2/3 mechanism in the NAc. The present findings support the potential use of mGluR7 agonists for the treatment of cocaine addiction. C1 [Li, Xia; Li, Jie; Gardner, Eliot L.; Xi, Zheng-Xiong] NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. RP Xi, ZX (reprint author), NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 51 TC 37 Z9 37 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2010 VL 114 IS 5 BP 1368 EP 1380 DI 10.1111/j.1471-4159.2010.06851.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 635GQ UT WOS:000280644000011 PM 20534005 ER PT J AU Seipel, AT Yakel, JL AF Seipel, Andrew T. Yakel, Jerrel L. TI The frequency-dependence of the nicotine-induced inhibition of dopamine is controlled by the alpha 7 nicotinic receptor SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alpha 7 receptor; beta 2 receptor; dopamine; nicotine; striatum; voltammetry ID ACETYLCHOLINE-RECEPTORS; SUBUNIT COMPOSITION; PARKINSONS-DISEASE; NUCLEUS-ACCUMBENS; IN-VITRO; RELEASE; STRIATUM; DISCOVERY; RAT; SUBTYPES AB Voltammetric analyses show that low (100-500 nM) doses of nicotine regulate striatal dopamine by inhibiting release evoked by a single stimulation to a greater extent than release evoked by high frequency stimulations. This frequency-dependent inhibition is because of nicotine desensitizing heteromeric beta 2 subunit-containing nicotinic acetylcholine receptor (nAChR) subtypes. Surprisingly, a high dose of nicotine (2 mu M; capable of interacting with additional nAChR subtypes) produced an inhibition of dopamine evoked by high frequency stimulation, an effect that was not seen with the low dose of nicotine or the beta 2 antagonist, dihydro-beta-erythroidine hydrobromide. This inhibition was replicated by application of 7 nAChR antagonists methyllcaconitine citrate or -bungarotoxin in conjunction with the low dose of nicotine or dihydro-beta-erythroidine hydrobromide. Blocking 7 receptor function alone produced a modest increase in dopamine evoked by single pulse stimulation while not affecting dopamine evoked by high frequency stimulation. The antagonist results were mimicked using selective 7 agonists PHA 543613 and PNU 282987. The frequency dependence of the low dose nicotine inhibition therefore requires functional 7 nAChRs, and may arise from differing levels of endogenous acetylcholine evoked by the stimulation. C1 [Seipel, Andrew T.; Yakel, Jerrel L.] Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), Natl Inst Environm Hlth Sci, Neurobiol Lab, NIH, Dept Hlth & Human Serv, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU NIEHS/NIH FX Research was supported by the Intramural Research Program of the NIEHS/NIH. We are grateful to Drs. Christian Erxleben and Steve Simons for valuable suggestions in the writing of this manuscript. NR 25 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2010 VL 114 IS 6 BP 1659 EP 1666 DI 10.1111/j.1471-4159.2010.06883.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 646NQ UT WOS:000281549600012 PM 20598018 ER PT J AU Soldan, SS Jacobson, S AF Soldan, Samantha S. Jacobson, Steven TI Viral Infections of the Central Nervous System: Pathogenesis to Therapeutics SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Editorial Material DE neurovirology; HIV-1; antivirals; HAART; HTLV-I; HERVs; PML; alphaherpesvirus; TMEV; measles; arbovirus; encephalitides; MHV; multiple sclerosis; coronavirus; neuroinflammation; immunomodulatory C1 [Soldan, Samantha S.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Soldan, SS (reprint author), Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. EM sssoldan@mail.med.upenn.edu; jacobsons@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003040-01, Z01 NS002817-19, Z01 NS002817-18]; NIAID NIH HHS [1R01AI074626-01, R01 AI074626] NR 15 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2010 VL 5 IS 3 BP 267 EP 270 DI 10.1007/s11481-010-9231-x PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 634QJ UT WOS:000280597700001 PM 20658202 ER PT J AU Matsuura, E Yamano, Y Jacobson, S AF Matsuura, Eiji Yamano, Yoshihisa Jacobson, Steven TI Neuroimmunity of HTLV-I Infection SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE HTLV; HTLV-1; HAM/TSP; myelopathy; uveitis; myositis; alveolitis; neuropathy; cytotoxic T lymphocyte; CTL; proviral load; pathology; immunology ID VIRUS-TYPE-I; T-CELL LEUKEMIA; TROPICAL SPASTIC PARAPARESIS; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD LESIONS; BLOOD MONONUCLEAR-CELLS; INCLUSION-BODY MYOSITIS; POLYMERASE-CHAIN-REACTION; PROVIRAL DNA LOAD; CEREBROSPINAL-FLUID AB Human T-lymphotrophic virus type I (HTLV-I) is an oncogenic retrovirus and its infection is associated with a variety of human diseases including HTLV-I-associated myelopathy/tropic spastic paraparesis (HAM/TSP). Large numbers of epidemiological, virological, immunological, and clinical studies on HTLV-I- and HTLV-I-associated diseases have been published, although the pathogenesis of HAM/TSP remains to be fully understood. In the last several years, researchers have shown that several key factors are important in HTLV-I-associated neurologic disease including high HTLV-I proviral load and a strong immune response to HTLV-I. Here, we review pathophysiological findings on HAM/TSP and focus on viral-host immune responses to the virus in HTLV-I infected individuals. In particular, the role of HTLV-I-specific CD8+ T cell response is highlighted. C1 [Matsuura, Eiji; Yamano, Yoshihisa; Jacobson, Steven] NIH, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Matsuura, E (reprint author), NIH, Viral Immunol Sect, Neuroimmunol Branch, Bldg 10,Room 5C-103, Bethesda, MD 20892 USA. EM eiji.matsuura@gmail.com RI MATSUURA, EIJI/E-1231-2013 OI MATSUURA, EIJI/0000-0001-8215-8853 FU Intramural NIH HHS [Z01 NS003040-01, Z01 NS002817-19, Z01 NS002817-18] NR 163 TC 34 Z9 37 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2010 VL 5 IS 3 BP 310 EP 325 DI 10.1007/s11481-010-9216-9 PG 16 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 634QJ UT WOS:000280597700005 PM 20437106 ER PT J AU Kang, SS McGavern, DB AF Kang, Silvia S. McGavern, Dorian B. TI Microbial Induction of Vascular Pathology in the CNS SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE LCMV; brain; vasculature; blood vessel; blood brain barrier; malaria; Theiler's virus; Ebola virus; Lassa fever virus; Dengue virus; hemorrhagic fevers; ventricles; cerebral spinal fluid; neutrophils; monocytes; T cells ID BLOOD-BRAIN-BARRIER; TUMOR-NECROSIS-FACTOR; LYMPHOCYTIC-CHORIOMENINGITIS-VIRUS; MURINE ENCEPHALOMYELITIS VIRUS; CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; EXPERIMENTAL CEREBRAL MALARIA; JUNCTIONAL ADHESION MOLECULE; EBOLA HEMORRHAGIC-FEVER; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS AB The central nervous system (CNS) is a finely tuned organ that participates in nearly every aspect of our day-to-day function. Neurons lie at the core of this functional unit and maintain an active dialogue with one another as well as their fellow CNS residents (e.g. astrocytes, oligodendrocytes, microglia). Because of this complex dialogue, it is essential that the CNS milieu be tightly regulated in order to permit uninterrupted and efficient neural chemistry. This is accomplished in part by anatomical barriers that segregate vascular components from the cerebral spinal fluid (CSF) and brain parenchyma. These barriers impede entry of noxious materials and enable the CNS to maintain requisite protein and ionic balances for constant electrochemical signaling. Under homeostatic conditions, the CNS is protected by the presence of specialized endothelium/epithelium, the blood brain barrier (BBB), and the blood-CSF barrier. However, following CNS infection these protective barriers can be comprised, sometimes resulting in severe neurological complications triggered by an imbalance or blockage of neural chemistry. In some instances, these disruptions are severe enough to be fatal. This review focuses on a selection of microbes (both viruses and parasites) that compromise vascular barriers and induce neurological complications upon gaining access to the CNS. Emphasis is placed on CNS diseases that result from a pathogenic interplay between host immune defenses and the invading microbe. C1 [Kang, Silvia S.; McGavern, Dorian B.] NINDS, NIH, Bethesda, MD 20892 USA. RP McGavern, DB (reprint author), NINDS, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM mcgavernd@mail.nih.gov OI McGavern, Dorian/0000-0001-9568-545X FU National Institutes of Health; National Research Service Award [NS061447-01] FX This work was supported by National Institutes of Health intramural program. S.S.K. is supported by a National Research Service Award (NS061447-01). We would like to thank Drs. Jiyun Kim and Michael Dustin at New York University for providing the images shown in Figs. 1b-d and 2b-c as well as Dr. Bernd Zinselmeyer for the image shown in Fig. 1a. NR 205 TC 14 Z9 14 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2010 VL 5 IS 3 BP 370 EP 386 DI 10.1007/s11481-010-9208-9 PG 17 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 634QJ UT WOS:000280597700009 PM 20401700 ER PT J AU Marshall, LJ Major, EO AF Marshall, Leslie J. Major, Eugene O. TI Molecular Regulation of JC Virus Tropism: Insights into Potential Therapeutic Targets for Progressive Multifocal Leukoencephalopathy SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Review DE JC virus; progressive multifocal leukoencephalopathy; virus latency; virus tropism; molecular regulation; host cell-virus interactions ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN POLYOMAVIRUS JC; NUCLEAR FACTOR-I; OF-THE-LITERATURE; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW-TRANSPLANTATION; HUMAN NEUROTROPIC VIRUS; DNA-BINDING PROTEIN; TRANSCRIPTIONAL CONTROL REGION; REMITTING MULTIPLE-SCLEROSIS AB Progressive multifocal leukoencephalopathy (PML) is a growing concern for patients undergoing immune modulatory therapies for treatment of autoimmune diseases such as multiple sclerosis. Currently, there are no drugs approved for the treatment of PML that have been demonstrated in the patient to effectively and reproducibly alter the course of disease progression. The human polyoma virus JC is the causative agent of PML. JC virus (JCV) dissemination is tightly controlled by regulation of viral gene expression from the promoter by cellular transcription factors expressed in cells permissive for infection. JCV infection likely occurs during childhood, and latent virus containing PML-associated promoter sequences is maintained in lymphoid cells within the bone marrow. Because development of PML is tightly linked to suppression and or modulation of the immune system as in development of hematological malignancies, AIDS, and monoclonal antibody treatments, further scrutiny of the course of JCV infection in immune cells will be essential to our understanding of development of PML and identification of new therapeutic targets. C1 [Marshall, Leslie J.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, Mol Med & Virol Sect, NIH, Bethesda, MD 20892 USA. RP Marshall, LJ (reprint author), NINDS, Lab Mol Med & Neurosci, Mol Med & Virol Sect, NIH, 10 Ctr Dr,Bldg 10 Room 3B14 MSC 1295, Bethesda, MD 20892 USA. EM marshalllj@ninds.nih.gov NR 209 TC 36 Z9 37 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2010 VL 5 IS 3 BP 404 EP 417 DI 10.1007/s11481-010-9203-1 PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 634QJ UT WOS:000280597700011 PM 20401541 ER PT J AU Yao, KR Graham, J Akahata, Y Oh, U Jacobson, S AF Yao, Karen Graham, Jhanelle Akahata, Yoshimi Oh, Unsong Jacobson, Steven TI Mechanism of Neuroinflammation: Enhanced Cytotoxicity and IL-17 Production via CD46 Binding SO JOURNAL OF NEUROIMMUNE PHARMACOLOGY LA English DT Article DE CD46; HHV-6; IL-17; multiple sclerosis ID REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; T(H)17 CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; HUMAN HERPESVIRUS-6; EFFECTOR FUNCTIONS; HUMAN ASTROCYTES; RECEPTOR; INTERLEUKIN-17; EXPRESSION AB The membrane co-factor protein CD46 is the cellular receptor for a number of pathogens including the human herpesvirus 6 (HHV-6). In addition to its function as an inhibitory complement receptor, engagement of CD46 in the context of T-cell receptor (TCR) signaling influences T-cell activation. Simultaneous cross-linking of the CD3/CD46 molecules led to differentiation of a unique population of CD4+ T-cell subset characterized by enhanced expressions of IFN-gamma, IL-10, granzyme B, adhesion molecule MAdCAM-1 (alpha-4-beta-7), surface-bound cytokine LIGHT, and chemokine receptor CCR9. Multiple sclerosis is a chronic inflammatory neurodegenerative disorder of the central nervous system (CNS) with unknown etiology. The HHV-6 is a candidate pathogen in MS and uses the CD46 molecule as its receptor. We hypothesize that binding of the HHV-6 glycoprotein to CD46 may trigger a pro-inflammatory response that could contribute to CNS tissue damage. To address this question, we examined immunological parameters such as proliferation, cytokine production and cytotoxic functions in CD4+ T cells of healthy individuals and MS patients following CD3/CD46 co-engagement by using anti-CD3 and anti-CD46 monoclonal antibodies as surrogates to mimic T-cell receptor and CD46 signaling. Our results demonstrated that CD3/CD46 cross-linking induced expression of IL-1 beta and IL-17A in multiple sclerosis patient T cells. Additionally, increase in transient surface expression of lysosomal associated protein CD107a suggested enhanced CD4+ T-cell cytotoxic functions following CD3/CD46 co-stimulation. Collectively, this study demonstrated evidence to suggest a potential mechanism of virus-induced neuroinflammation that may be involved in MS disease pathogenesis. C1 [Yao, Karen; Graham, Jhanelle; Akahata, Yoshimi; Oh, Unsong; Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. [Yao, Karen] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU Intramural NIH HHS [Z01 NS003040-01, Z01 NS002817-19, Z01 NS002817-18] NR 48 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1890 J9 J NEUROIMMUNE PHARM JI J. Neuroimmune Pharm. PD SEP PY 2010 VL 5 IS 3 BP 469 EP 478 DI 10.1007/s11481-010-9232-9 PG 10 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 634QJ UT WOS:000280597700016 PM 20661655 ER PT J AU Chang, SE Synnestvedt, A Ostuni, J Ludlow, CL AF Chang, Soo-Eun Synnestvedt, Anna Ostuni, John Ludlow, Christy L. TI Similarities in speech and white matter characteristics in idiopathic developmental stuttering and adult-onset stuttering SO JOURNAL OF NEUROLINGUISTICS LA English DT Article DE Adult-onset stuttering; Developmental stuttering; DTI; White matter; Speech ID RIGHT-HEMISPHERE LESION; SUBJECT DIFFUSION DATA; HUMAN BRAIN; SPATIAL STATISTICS; ARCUATE FASCICULUS; VOXELWISE ANALYSIS; FIBER DENSITY; ASYMMETRY; INFARCTION; STROKE AB Adult-onset stuttering (AS) typically occurs following neurological and/or psychological trauma, considered different from developmental stuttering (DS), which starts during early childhood with few if any new cases reported after adolescence. Here we report four cases of AS, two with apparent psychological trigger and two without, none with evidence of neurological injury, and none conforming to previously reported characteristics of psychogenic stuttering. we asked whether this group of AS would have similar speech and neuroanatomical characteristics to those with DS. We conducted blinded analyses of speech samples in four AS cases and 14 cases of DS on type, frequency, and loci of disfiuencies. Diffusion tensor imaging (DTI) was conducted to compare white matter tracts using fractional anisotropy (FA). We found that AS did not differ significantly from DS in any of the speech characteristics measured. On DTI, DS had significantly increased FA relative to controls in the right superior longitudinal tract. AS cases showed a similar trend for increases in these regions when compared to controls. The results of this study suggest that symptoms of idiopathic stuttering can begin during adulthood, and that similar neuroanatomical differences from controls may be associated with both developmental and adult-onset idiopathic stuttering. Published by Elsevier Ltd. C1 [Chang, Soo-Eun; Synnestvedt, Anna; Ludlow, Christy L.] NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Ostuni, John] NINDS, Clin Neurosci Program, NIH, Bethesda, MD 20892 USA. RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr MSC 1416,Bldg 10,Room 5D38, Bethesda, MD 20892 USA. EM ludlowc@ninds.nih.gov OI Ludlow, Christy/0000-0002-2015-6171 FU National Institute of Neurological Disorders and Stroke (NINDS) FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS). The authors wish to thank Dr. Edythe Wiggs for her help in conducting neuropsychology evaluations and Sandra Martin for her help in conducting speech-language-hearing evaluations. NR 63 TC 11 Z9 11 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD SEP PY 2010 VL 23 IS 5 SI SI BP 455 EP 469 DI 10.1016/j.jneuroling.2008.11.004 PG 15 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 635MI UT WOS:000280659400003 PM 20640049 ER PT J AU Crowe, DA Averbeck, BB Chafee, MV AF Crowe, David A. Averbeck, Bruno B. Chafee, Matthew V. TI Rapid Sequences of Population Activity Patterns Dynamically Encode Task-Critical Spatial Information in Parietal Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID PREFRONTAL CORTEX; WORKING-MEMORY; OLFACTORY NETWORK; FRONTAL-CORTEX; STABLE STATES; NEURONS; REPRESENTATIONS; TIME; COMPUTATION; MONKEYS AB We characterized the temporal dynamics of population activity in parietal cortex of monkeys as they solved a spatial cognitive problem posed by an object construction task. We applied pattern classification techniques to characterize patterns of activity coding object-centered side, a task-defined variable specifying whether an object component was located on the left or right side of a reference object, regardless of its retinocentric position. During a period in which the value of object-centered side, as defined by task events, remained constant, parietal cortex represented this variable using a dynamic neural code by activating neurons with the same spatial preference in rapid succession so that the pattern of active neurons changed dramatically while the spatial information they collectively encoded remained stable. Furthermore, if the neurons shared the same spatial preference, then their pretrial activity ( measured before objects were shown) was correlated to a degree that scaled as a positive linear function of how close together in time the neurons would be activated later in the trial. Finally, we found that while parietal cortex represented task-critical spatial information using a dynamic neural code, it simultaneously represented task-irrelevant spatial information using a stationary neural code. These data demonstrate that dynamic spatial representations exist in parietal cortex, provide novel insight into the synaptic mechanisms that generate them, and suggest they may preferentially encode task-critical spatial information. C1 [Chafee, Matthew V.] Univ Minnesota, Vet Adm Med Ctr, Brain Sci Ctr, Dept Neurosci, Minneapolis, MN 55417 USA. [Crowe, David A.] Augsburg Coll, Dept Biol, Minneapolis, MN 55454 USA. [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Chafee, Matthew V.] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA. [Chafee, Matthew V.] Univ Minnesota, Ctr Cognit Sci, Minneapolis, MN 55455 USA. [Crowe, David A.; Chafee, Matthew V.] Vet Adm Med Ctr, Brain Sci Ctr, Minneapolis, MN 55417 USA. RP Chafee, MV (reprint author), Univ Minnesota, Vet Adm Med Ctr, Brain Sci Ctr, Dept Neurosci, 11B,1 Vet Dr, Minneapolis, MN 55417 USA. EM chafe001@umn.edu FU United States Public Health Service; National Institutes of Health [R01 MH077779, R24 MH069675]; Whitehall Foundation [2005-08-44-APL]; Department of Veterans Affairs; American Legion Brain Sciences Chair FX This work was supported by United States Public Health Service, National Institutes of Health Grants R01 MH077779 and R24 MH069675, Whitehall Foundation Grant 2005-08-44-APL, the Department of Veterans Affairs, and the American Legion Brain Sciences Chair. We thank Apostolos Georgopoulos for his intellectual contribution to and steadfast support of this work. We thank Adam Johnson for helpful discussions, Bagrat Amirikian and Sofia Sakellaridi for insightful comments regarding data analysis, and Dale Boeff and Dean Evans for excellent technical support. NR 30 TC 43 Z9 43 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2010 VL 30 IS 35 BP 11640 EP 11653 DI 10.1523/JNEUROSCI.0954-10.2010 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 647GV UT WOS:000281607300011 PM 20810885 ER PT J AU Sun, T Wu, XS Xu, JH McNeil, BD Pang, ZP Yang, WJ Bai, L Qadri, S Molkentin, JD Yue, DT Wu, LG AF Sun, Tao Wu, Xin-Sheng Xu, Jianhua McNeil, Benjamin D. Pang, Zhiping P. Yang, Wanjun Bai, Li Qadri, Syed Molkentin, Jeffery D. Yue, David T. Wu, Ling-Gang TI The Role of Calcium/Calmodulin-Activated Calcineurin in Rapid and Slow Endocytosis at Central Synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SYNAPTIC VESICLE ENDOCYTOSIS; CLATHRIN-MEDIATED ENDOCYTOSIS; FROG NEUROMUSCULAR-JUNCTION; DEPENDENT BULK ENDOCYTOSIS; ADRENAL CHROMAFFIN CELLS; MOTOR-NERVE TERMINALS; RETINAL BIPOLAR CELLS; A-BETA; HIPPOCAMPAL SYNAPSES; CALCIUM-DEPENDENCE AB Although the calcium/calmodulin-activated phosphatase calcineurin may dephosphorylate many endocytic proteins, it is not considered a key molecule in mediating the major forms of endocytosis at synapses-slow, clathrin-dependent and the rapid, clathrin-independent endocytosis. Here we studied the role of calcineurin in endocytosis by reducing calcium influx, inhibiting calmodulin with pharmacological blockers and knockdown of calmodulin, and by inhibiting calcineurin with pharmacological blockers and knock-out of calcineurin. These manipulations significantly inhibited both rapid and slow endocytosis at the large calyx-type synapse in 7- to 10-d-old rats and mice, and slow, clathrin-dependent endocytosis at the conventional cultured hippocampal synapse of rats and mice. These results suggest that calcium influx during nerve firing activates calcium/calmodulin-dependent calcineurin, which controls the speed of both rapid and slow endocytosis at synapses by dephosphorylating endocytic proteins. The calcium/calmodulin/calcineurin signaling pathway may underlie regulation of endocytosis by nerve activity and calcium as reported at many synapses over the last several decades. C1 [Sun, Tao; Wu, Xin-Sheng; Xu, Jianhua; McNeil, Benjamin D.; Bai, Li; Qadri, Syed; Wu, Ling-Gang] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. [Pang, Zhiping P.] Stanford Univ, Dept Mol & Cellular Physiol, Palo Alto, CA 94304 USA. [Yang, Wanjun; Yue, David T.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Molkentin, Jeffery D.] Univ Cincinnati, Dept Pediat, Cincinnati Childrens Hosp, Med Ctr,Howard Hughes Med Inst, Cincinnati, OH 45229 USA. RP Wu, LG (reprint author), Natl Inst Neurol Disorders & Stroke, 35 Convent Dr,Bldg 35,Room 2B-1012, Bethesda, MD 20892 USA. EM wul@ninds.nih.gov OI Xu, Jianhua/0000-0003-0084-8856; Pang, Zhiping/0000-0002-6183-1233 FU National Institute of Neurological Disorders and Stroke FX This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program. We thank Drs. Jonathan G. Seidman (Harvard Medical School, Boston, MA) and Jennifer L. Gooch (Emory University School of Medicine, Atlanta, GA) for providing us with calcineurin Aalpha+/- mice. We thank Dr. Gero Miesenbock (University of Oxford, Oxford, UK) for providing us with the synaptopHluorin plasmid. NR 57 TC 53 Z9 54 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2010 VL 30 IS 35 BP 11838 EP 11847 DI 10.1523/JNEUROSCI.1481-10.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 647GV UT WOS:000281607300029 PM 20810903 ER PT J AU Gaskins, AJ Mumford, SL Rovner, AJ Zhang, GL Chen, LW Wactawski-Wende, J Perkins, NJ Schisterman, EF AF Gaskins, Audrey J. Mumford, Sunni L. Rovner, Alisha J. Zhang, Guilin Chen, Liwei Wactawski-Wende, Jean Perkins, Neil J. Schisterman, Enrique F. CA BioCycle Study Group TI Whole Grains Are Associated with Serum Concentrations of High Sensitivity C-Reactive Protein among Premenopausal Women SO JOURNAL OF NUTRITION LA English DT Article ID AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR-DISEASE; MENSTRUAL-CYCLE; INSULIN-RESISTANCE; DIABETES-MELLITUS; RISK; INFLAMMATION; MARKERS; INTERLEUKIN-6; BIOCYCLE AB In premenopausal women, elevated C-reactive protein (CRP) concentrations have been associated with an increased risk of negative reproductive outcomes. Whole grain consumption has been associated with lower CRP concentrations in older women; however, less is known about this relationship in younger women. We investigated whether whole grain intake was associated with serum high sensitivity CRP (hs-CRP) concentrations in young women. BioCycle was a prospective cohort study conducted at the University of Buffalo from 2005 to 2007, which followed 259 healthy women aged 18-44 y for <= 2 menstrual cycles. hs-CRP concentrations were measured longitudinally <= 8 times/cycle with visits standardized to menstrual cycle phase. Whole grain intake was estimated by 24-h recalls <= 4 times/cycle. Servings were defined as 16 g or 125 mL of a 100% whole grain food. Whole grain intake was inversely associated with hs-CRP concentrations after adjusting for age, race, BMI, illness, and antiinflammatory drug use. Consumers of between 0 and 1 serving/d of whole grains had, on average, 11.5% lower hs-CRP concentrations (P = 0.02) and consumers of >= 1 serving/d had 12.3% lower hs-CRP concentrations (P = 0.02) compared with nonconsumers. Women who consumed >= 1 serving/d of whole grain had a lower probability of having moderate (P = 0.008) or elevated (P = 0.001) hs-CRP according to the AHA criteria compared with nonconsumers. Given that elevated concentrations of hs-CRP have been linked to adverse reproductive outcomes and pregnancy complications, interventions targeting whole grain consumption may have the potential to improve health status among young women. J. Nutr. 140: 1669-1676, 2010. C1 [Gaskins, Audrey J.; Mumford, Sunni L.; Rovner, Alisha J.; Zhang, Guilin; Perkins, Neil J.; Schisterman, Enrique F.] Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. [Chen, Liwei] Louisiana State Univ, Hlth Sci Ctr, Sch Publ Hlth, Dept Epidemiol, New Orleans, LA 70112 USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20852 USA. EM schistee@mail.nih.gov RI Schliep, Karen/A-2803-2012; OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. NR 34 TC 25 Z9 25 U1 2 U2 8 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2010 VL 140 IS 9 BP 1669 EP 1676 DI 10.3945/jn.110.124164 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 642KE UT WOS:000281210800021 PM 20668255 ER PT J AU Ashwell, MS Ceddia, RP House, RL Cassady, JP Eisen, EJ Eling, TE Collins, JB Grissom, SF Odle, J AF Ashwell, Melissa S. Ceddia, Ryan P. House, Ralph L. Cassady, Joseph P. Eisen, Eugene J. Eling, Thomas E. Collins, Jennifer B. Grissom, Sherry F. Odle, Jack TI Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE Gene expression; Mice; Liver, Conjugated linoleic acid; Obesity, Hepatic steatosis, Fatty liver ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; STEAROYL-COA DESATURASE; ADIPOSE-TISSUE; BODY-FAT; DEPENDENT MECHANISM; MICROARRAY ANALYSIS; ENERGY-EXPENDITURE; MOUSE-LIVER; OXIDATION; TRANSCRIPTION AB The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation, however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of 01, and 775 were considered significant using a false discovery rate (FDR) threshold of 05 While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4 alpha, a transcription factor important in controlling liver metabolic status. (C) 2010 Elsevier Inc All rights reserved C1 [Ashwell, Melissa S.; Ceddia, Ryan P.; House, Ralph L.; Cassady, Joseph P.; Eisen, Eugene J.; Odle, Jack] N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. [Eling, Thomas E.] NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. [Collins, Jennifer B.; Grissom, Sherry F.] NIEHS, Microarray Grp, Res Triangle Pk, NC 27709 USA. RP Odle, J (reprint author), N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. OI Ceddia, Ryan/0000-0001-7743-1755; Odle, Jack/0000-0003-4965-2096 FU North Carolina Agricultural Research Service; NIH-NIEHS FX This work was funded in part by the North Carolina Agricultural Research Service and the NIH-NIEHS Intramural Research Program. NR 57 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD SEP PY 2010 VL 21 IS 9 BP 848 EP 855 DI 10.1016/j.jnutbio.2009.06.013 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 648RD UT WOS:000281710700009 PM 19800780 ER PT J AU Chapman, CR Lipschitz, DL Angst, MS Chou, R Denisco, RC Donaldson, GW Fine, PG Foley, KM Gallagher, RM Gilson, AM Haddox, JD Horn, SD Inturrisi, CE Jick, SS Lipman, AG Loeser, JD Noble, M Porter, L Rowbotham, MC Schoelles, KM Turk, DC Volinn, E Von Korff, MR Webster, LR Weisner, CM AF Chapman, C. Richard Lipschitz, David L. Angst, Martin S. Chou, Roger Denisco, Richard C. Donaldson, Gary W. Fine, Perry G. Foley, Kathleen M. Gallagher, Rollin M. Gilson, Aaron M. Haddox, J. David Horn, Susan D. Inturrisi, Charles E. Jick, Susan S. Lipman, Arthur G. Loeser, John D. Noble, Meredith Porter, Linda Rowbotham, Michael C. Schoelles, Karen M. Turk, Dennis C. Volinn, Ernest Von Korff, Michael R. Webster, Lynn R. Weisner, Constance M. TI Opioid Pharmacotherapy for Chronic Non-Cancer Pain in the United States: A Research Guideline for Developing an Evidence-Base SO JOURNAL OF PAIN LA English DT Article DE Opioid pharmacotherapy; chronic pain; evidence-based medicine; guideline; effectiveness; efficacy ID CHRONIC NONMALIGNANT PAIN; LOW-BACK-PAIN; CLINICAL-PRACTICE GUIDELINE; PRIMARY-CARE PHYSICIANS; DRUG-RELATED BEHAVIORS; TORSADES-DE-POINTES; INDUCED HYPERALGESIA; MORPHINE REQUIREMENTS; WORKERS-COMPENSATION; RANDOMIZED-TRIALS AB This document reports the consensus of an interdisciplinary panel of research and clinical experts charged with reviewing the use of opioids for chronic noncancer pain (CNCP) and formulating guidelines for future research. Prescribing opioids for chronic noncancer pain has recently escalated in the United States. Contrasting with increasing opioid use are: 1) The lack of evidence supporting long-term effectiveness; 2) Escalating misuse of prescription opioids including abuse and diversion; and 3) Uncertainty about the incidence and clinical salience of multiple, poorly characterized adverse drug events (ADEs) including endocrine dysfunction, immunosuppression and infectious disease, opioid-induced hyperalgesia and xerostomia, overdose, falls and fractures, and psychosocial complications. Chief among the limitations of current evidence are: 1) Sparse evidence on long-term opioid effectiveness in chronic pain patients due to the short-term time frame of clinical trials; 2) Insufficiently comprehensive outcome assessment; and 3) Incomplete identification and quantification of ADEs. The panel called for a strategic interdisciplinary approach to the problem domain in which basic scientists and clinicians cooperate to resolve urgent issues and generate a comprehensive evidence base. It offered 4 recommendations in 3 areas: 1) A research strategy for studying the effectiveness of long-term opioid pharmacotherapy; 2) Improvements in evidence-generation methodology; and 3) Potential research topics for generating new evidence. Perspective: Prescribing opioids for CNCP has outpaced the growth of scientific evidence bearing on the benefits and harms of these interventions. The need for a strong evidence base is urgent. This guideline offers a strategic approach to creating a comprehensive evidence base to guide safe and effective management of CNCP. (C) 2010 by the American Pain Society C1 [Chapman, C. Richard] Univ Utah, Pain Res Ctr, Dept Anesthesiol, Sch Med, Salt Lake City, UT 84108 USA. [Angst, Martin S.] Stanford Univ, Dept Anesthesiol, Palo Alto, CA 94304 USA. [Chou, Roger] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. [Denisco, Richard C.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD USA. [Foley, Kathleen M.; Inturrisi, Charles E.] Mem Sloan Kettering Canc Ctr, Pain & Palliat Care Serv, New York, NY 10021 USA. [Gallagher, Rollin M.] Univ Penn, Sch Med, Dept Psychiat, Penn Pain Med Ctr, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Penn Pain Med Ctr, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gilson, Aaron M.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Inturrisi, Charles E.] Cornell Univ, Dept Pharmacol, Joan & Sanford I Weill Med Sch, New York, NY 10021 USA. [Haddox, J. David] Purdue Pharma, Risk Management & Hlth Policy, Stamford, CT USA. [Jick, Susan S.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. [Horn, Susan D.] Univ Utah, Sch Med, Dept Med Informat, ICOR, Salt Lake City, UT 84108 USA. [Horn, Susan D.] Univ Utah, Sch Med, Dept Med Informat, Int Sever Informat Syst Inc, Salt Lake City, UT 84108 USA. [Lipman, Arthur G.] Univ Utah, Dept Pharmacotherapy, LS Skaggs Pharm, Salt Lake City, UT 84108 USA. [Loeser, John D.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Porter, Linda] Natl Inst Neurol Disorders & Stroke Syst & Cognit, NIH, Bethesda, MD USA. [Rowbotham, Michael C.] Univ Calif San Francisco, Pain Clin Res Ctr, San Francisco, CA 94143 USA. [Noble, Meredith; Schoelles, Karen M.] ECRI Inst, Plymouth Meeting, PA USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Von Korff, Michael R.] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. [Webster, Lynn R.] Lifetree Pain Clin, Salt Lake City, UT USA. [Weisner, Constance M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Chapman, CR (reprint author), Univ Utah, Pain Res Ctr, Dept Anesthesiol, Sch Med, 615 Arapeen Dr,Suite 200, Salt Lake City, UT 84108 USA. EM crc20@utah.edu RI Inturrisi, Charles/E-7365-2013; OI Jick, Susan/0000-0002-2215-1067 FU Milbank Foundation; Mayday Fund FX Supported by a grant to the first author from the Milbank Foundation. A grant from The Mayday Fund supported the work necessary for this document. NR 143 TC 79 Z9 81 U1 3 U2 14 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2010 VL 11 IS 9 BP 807 EP 829 DI 10.1016/j.jpain.2010.02.019 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 652TW UT WOS:000282033900001 PM 20430701 ER PT J AU Moore, RJ Hallenbeck, J AF Moore, Rhonda J. Hallenbeck, James TI Narrative Empathy and How Dealing with Stories Helps: Creating a Space for Empathy in Culturally Diverse Care Settings SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article ID LUNG-CANCER; COMMUNICATION; MEDICINE; PAIN; SIMULATION; DECISIONS; OTHERS; BRAIN; MODEL C1 [Moore, Rhonda J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Hallenbeck, James] Stanford Sch Med, Dept Med, Div Gen Internal Med, Palo Alto, CA USA. [Hallenbeck, James] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Moore, RJ (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404,Room 4041, Bethesda, MD 20892 USA. EM Rhonda.Moore@hhs.gov FU VA Palo Alto Health Care System FX The views expressed in this article do not represent the views of or endorsement by the United States Government, The US Department of Health and Human Services, the National Institutes of Health, or the VA Palo Alto Health Care System. Dr. Hallenbeck's work is supported by the VA Palo Alto Health Care System. NR 58 TC 8 Z9 8 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD SEP PY 2010 VL 40 IS 3 BP 471 EP 476 DI 10.1016/j.jpainsymman.2010.03.013 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 652TJ UT WOS:000282032500013 PM 20678897 ER PT J AU Arnott, D Emmert-Buck, MR AF Arnott, David Emmert-Buck, Michael R. TI Proteomic profiling of cancer-opportunities, challenges, and context SO JOURNAL OF PATHOLOGY LA English DT Editorial Material DE proteomics; SELDI-TOF MS; HNSCC; pharynx and oesophagus carcinoma; field cancerization; biomarker protein profiles ID PHASE PROTEIN MICROARRAYS; MASS-SPECTROMETRY; BIOMARKER DISCOVERY; PLASMA-PROTEOME; FIELD CANCERIZATION; OVARIAN-CANCER; HEAD; ASSAYS; SERUM; BIOINFORMATICS AB The article by Roesch-Ely and colleagues in a recent issue of The Journal of Pathology describes the use of proteomic techniques to examine mucosal biopsies in patients with head and neck squamous cell cancer (HNSCC) and in corresponding control samples. The authors were able to determine the anatomical site of origin of the biopsies based on modelling of multiplex protein datasets, and to use the information to analyse field cancerization as a means of predicting tumour recurrence. Although the study included only a relatively small number of cases, and will require future validation in a larger patient cohort, the results point to the potential of proteomics to increase our understanding of cancer biology, and in this instance to offer clinical value. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 [Arnott, David] Genentech Inc, Dept Prot Chem, Microchem & Proteom Lab, San Francisco, CA 94080 USA. [Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Arnott, D (reprint author), Genentech Inc, Dept Prot Chem, Microchem & Proteom Lab, San Francisco, CA 94080 USA. EM arnott.david@gene.com; buckm@mail.nih.gov NR 47 TC 1 Z9 1 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2010 VL 222 IS 1 BP 16 EP 20 DI 10.1002/path.2750 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 638FQ UT WOS:000280879300002 PM 20623483 ER PT J AU Obarzanek, E Wu, CO Cutler, JA Kavey, REW Pearson, GD Daniels, SR AF Obarzanek, Eva Wu, Colin O. Cutler, Jeffrey A. Kavey, Rae-Ellen W. Pearson, Gail D. Daniels, Stephen R. TI Prevalence and Incidence of Hypertension in Adolescent Girls SO JOURNAL OF PEDIATRICS LA English DT Article ID BODY-MASS INDEX; SCHOOL-AGED CHILDREN; CARDIOVASCULAR-DISEASE RISK; BLOOD-PRESSURE; PHYSICAL-ACTIVITY; NHLBI GROWTH; NATIONAL-HEART,-LUNG,-AND-BLOOD-INSTITUTE GROWTH; METABOLIC SYNDROME; UNITED-STATES; HEALTH AB Objective To estimate the prevalence and incidence of hypertension and prehypertension and associated factors in adolescent girls. Study design A total of 2368 girls (49% Caucasian, 51% African-American) aged 9 or 10 years enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study had blood pressure, height, and weight measured at annual visits through age 18 to 19 years. Prevalence and incidence of hypertension and prehypertension were calculated. Results On the basis of 2 visits, hypertension prevalence was approximately 1% to 2% in African-American girls and 0.5% in Caucasian girls. Incidence in 8 years was 5.0% and 2.1%, respectively. Obese girls had higher prevalence (approximately 6-fold higher) and incidence (aprroximately 2- to 3-fold higher) compared with girls of normal weight. Similar patterns were found for prehypertension, except that prehypertension occurred more in older girls than younger girls. Dietary factors (lower intake of fiber, potassium, magnesium, and calcium, and higher intake of caffeine and calories) were each associated with hypertension incidence (all P < .05). In multivariate analysis, higher body mass index (P < .001) and lower potassium intake (P = .023) were independently associated with incidence of hypertension. Conclusions Hypertension occurred early in childhood and was related to obesity and other modifiable lifestyle factors. Clinicians should monitor blood pressure during childhood and provide focused diet and physical activity guidance to minimize the development of hypertension. (J Pediatr 2010; 157: 461-7). C1 [Wu, Colin O.] NHLBI, NIH, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Kavey, Rae-Ellen W.] NHLBI, Div Applicat Res Discoveries, Bethesda, MD 20892 USA. [Daniels, Stephen R.] Univ Colorado, Sch Med, Childrens Hosp, Denver, CO USA. RP Wu, CO (reprint author), NHLBI, NIH, Div Cardiovasc Sci, Rockledge 2,6701 Rockledge Dr,Room 9212, Bethesda, MD 20892 USA. EM wuc@nhlbi.nih.gov NR 43 TC 17 Z9 20 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 2010 VL 157 IS 3 BP 461 EP U155 DI 10.1016/j.jpeds.2010.03.032 PG 12 WC Pediatrics SC Pediatrics GA 641HT UT WOS:000281116100025 PM 20488454 ER PT J AU Lazarus, H Balboni, G Salvadori, S Marczak, ED AF Lazarus, H. Balboni, G. Salvadori, S. Marczak, E. D. TI Dual Acting mu-/delta-Opioid Antagonist, H-Dmt-Tic-Lys-NH-CH2-Ph, Ameliorates Obesity-Related Factors SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Lazarus, H.; Marczak, E. D.] NIEHS, Res Triangle Pk, NC 27709 USA. [Balboni, G.] Univ Cagliari, Cagliari, Italy. [Salvadori, S.] Univ Ferrara, I-44100 Ferrara, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PD SEP PY 2010 VL 16 SU 1 BP 122 EP 122 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 647IC UT WOS:000281610800311 ER PT J AU DiGiulio, DB Gervasi, MT Romero, R Vaisbuch, E Mazaki-Tovi, S Kusanovic, JP Seok, KS Gomez, R Mittal, P Gotsch, F Chaiworapongsa, T Oyarzun, E Kim, CJ Relman, DA AF DiGiulio, Daniel B. Gervasi, Maria Teresa Romero, Roberto Vaisbuch, Edi Mazaki-Tovi, Shali Kusanovic, Juan Pedro Seok, Kimberley S. Gomez, Ricardo Mittal, Pooja Gotsch, Francesca Chaiworapongsa, Tinnakorn Oyarzun, Enrique Kim, Chong Jai Relman, David A. TI Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE 16S rRNA; chorioamnionitis; cytokines; FIRS; IL-6; intra-amniotic infection; intra-amniotic inflammation; molecular microbiology; PCR; pregnancy; SGA ID FETAL-GROWTH RESTRICTION; NECROSIS-FACTOR-ALPHA; PORPHYROMONAS-GINGIVALIS INFECTION; PRETERM PREMATURE RUPTURE; POLYMERASE-CHAIN-REACTION; EPSTEIN-BARR-VIRUS; REAL-TIME PCR; INTRAAMNIOTIC INFECTION; CLINICAL-SIGNIFICANCE; UREAPLASMA-UREALYTICUM AB Objective: Microbial invasion of the amniotic cavity (MIAC) has been detected in women with preterm labor, preterm prelabor rupture of membranes (PROM), and in patients at term with PROM or in spontaneous labor. Intrauterine infection is recognized as a potential cause of fetal growth restriction; yet, the frequency of MIAC in pregnancies with small-for-gestational-age (SGA) fetuses is unknown. The aim of this study was to determine the frequency, diversity and relative abundance of microbes in amniotic fluid (AF) of women with an SGA neonate using a combination of culture and molecular methods. Method: AF from 52 subjects with an SGA neonate was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad-range and group-specific PCR assays targeted small subunit rDNA, or other gene sequences, from bacteria, fungi and archaea. Results of microbiologic studies were correlated with indices of the host inflammatory response. Results: 1) All AF samples (n=52) were negative for microorganisms based on cultivation techniques, whereas 6% (3/52) were positive based on PCR; and 2) intra-amniotic inflammation was detected in one of the three patients with a positive PCR result, as compared with three patients (6.1%) of the 49 with both a negative culture and a negative PCR (P=0.2). Conclusion: MIAC is detected by PCR in some patients with an SGA fetus who were not in labor at the time of AF collection. C1 [Romero, Roberto] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Detroit, MI 48201 USA. [Romero, Roberto; Vaisbuch, Edi; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, Bethesda, MD USA. [DiGiulio, Daniel B.; Relman, David A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [DiGiulio, Daniel B.; Seok, Kimberley S.; Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Gervasi, Maria Teresa] Azienda Osped Padova, Dept Obstet & Gynecol, Padua, Italy. [Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp,Detroit Med Ctr, Detroit, MI 48201 USA. [Romero, Roberto; Vaisbuch, Edi; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Mittal, Pooja; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP Ctr Perinatal Diag & Res, Santiago, Chile. [Gomez, Ricardo; Oyarzun, Enrique] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Relman, David A.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Box 4,3990 John R, 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; March of Dimes Foundation; NIH [NIH DP1OD000964] FX This work was supported, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, and by a grant from the March of Dimes Foundation to DAR. DAR is supported by an NIH Director's Pioneer Award (NIH DP1OD000964). We would like to thank the women who participated in the study. We would also like to thank Elies Bik, Stanford University, for helpful input and assistance during various phases of this study. NR 83 TC 27 Z9 28 U1 0 U2 7 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD SEP PY 2010 VL 38 IS 5 BP 495 EP 502 DI 10.1515/JPM.2010.076 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 646TT UT WOS:000281566600008 PM 20482466 ER PT J AU DiGiulio, DB Gervasi, M Romero, R Mazaki-Tovi, S Vaisbuch, E Kusanovic, JP Seok, KS Gomez, R Mittal, P Gotsch, F Chaiworapongsa, T Oyarzun, E Kim, CJ Relman, DA AF DiGiulio, Daniel B. Gervasi, MariaTeresa Romero, Roberto Mazaki-Tovi, Shali Vaisbuch, Edi Kusanovic, Juan Pedro Seok, Kimberley S. Gomez, Ricardo Mittal, Pooja Gotsch, Francesca Chaiworapongsa, Tinnakorn Oyarzun, Enrique Kim, Chong Jai Relman, David A. TI Microbial invasion of the amniotic cavity in preeclampsia as assessed by cultivation and sequence-based methods SO JOURNAL OF PERINATAL MEDICINE LA English DT Article DE IL-6; intra-amniotic infection; intra-amniotic inflammation; PCR; preeclampsia; pregnancy; 16S rRNA; Sneathia/Leptotrichia spp.; Ureaplasma urealyticum ID ENDOTHELIAL GROWTH-FACTOR; FOR-GESTATIONAL-AGE; TUMOR-NECROSIS-FACTOR; CIRCULATING ANGIOGENIC FACTORS; HEALTHY NULLIPAROUS WOMEN; POLYMERASE-CHAIN-REACTION; ELEVATED LIVER-ENZYMES; LOW PLATELETS SYNDROME; REAL-TIME PCR; NORMAL-PREGNANCY AB Objective: Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined. The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia. Method of study: Amniotic fluid (AF) from 62 subjects with preeclampsia, not in labor, was analyzed with both cultivation and molecular methods. Broad-range and group-specific PCR assays targeting small subunit ribosomal DNA, or other gene sequences, from bacteria, fungi and archaea were used. Results were correlated with measurements of host inflammatory response, including AF white blood cell count and AF concentrations of glucose, interleukin-6 (IL-6) and MMP-8. Results: 1) The rate of MIAC in preeclampsia was 1.6% (1/62) based on cultivation techniques, 8% (5/62) based on PCR, and 9.6% (6/62) based on the combined results of both methods; 2) among the six patients diagnosed with MIAC, three had a positive PCR for Sneathia/Leptotrichia spp.; and 3) patients with MIAC were more likely to have evidence of an inflammatory response in the amniotic cavity than those without MIAC, as determined by a higher median AF IL-6 [1.65 ng/mL interquartile range (IQR): 0.35-4.62 vs. 0.22 ng/mL IQR: 0.12-0.51; P=0.002). Conclusion: The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeclampsia. However, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation. C1 [Romero, Roberto] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Detroit, MI 48201 USA. [DiGiulio, Daniel B.; Relman, David A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [DiGiulio, Daniel B.; Seok, Kimberley S.; Relman, David A.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Gervasi, MariaTeresa] Azienda Osped Padova, Dept Obstet & Gynecol, Padua, Italy. [Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mittal, Pooja; Gotsch, Francesca; Chaiworapongsa, Tinnakorn; Kim, Chong Jai] NICHD, Perinatol Res Branch, NIH, Bethesda, MD USA. [Romero, Roberto; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kusanovic, Juan Pedro; Mittal, Pooja; Chaiworapongsa, Tinnakorn] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp,Detroit Med Ctr, Detroit, MI 48201 USA. [Romero, Roberto] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. [Gomez, Ricardo] Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP Ctr Perinatal Diag & Res, Santiago, Chile. [Gomez, Ricardo; Oyarzun, Enrique] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Santiago, Chile. [Kim, Chong Jai] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Relman, David A.] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD NIH DHHS, Box 4,3990 John R, 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; March of Dimes Foundation; NIH [NIH DP1OD000964]; Thomas C. and Joan M. Merigan Endowment at Stanford University FX This work was supported, in part, by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS, and by a grant from the March of Dimes Foundation to DAR. DAR is supported by an NIH Director's Pioneer Award (NIH DP1OD000964). DAR is supported by the Thomas C. and Joan M. Merigan Endowment at Stanford University. We would like to thank the women who participated in the study. We would also like to thank Elies Bik, Stanford University, for helpful input and assistance during various phases of this study. NR 146 TC 35 Z9 35 U1 0 U2 8 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD SEP PY 2010 VL 38 IS 5 BP 503 EP 513 DI 10.1515/JPM.2010.078 PG 11 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 646TT UT WOS:000281566600009 PM 20482470 ER PT J AU Kim, KR Park, KK Chun, KS Chung, WY AF Kim, Ki Rim Park, Kwang-Kyun Chun, Kyung-Soo Chung, Won-Yoon TI Honokiol Inhibits the Progression of Collagen-Induced Arthritis by Reducing Levels of Pro-inflammatory Cytokines and Matrix Metalloproteinases and Blocking Oxidative Tissue Damage SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE type II collagen-induced arthritis; tumor necrosis factor-alpha (TNF-alpha); interleukin-1 beta (IL-1 beta); matrix metalloproteinase (MMP); oxidative damage ID EARLY RHEUMATOID-ARTHRITIS; NITRIC-OXIDE PRODUCTION; STRESS MARKER LEVELS; NF-KAPPA-B; TNF-ALPHA; ACTIVATED MACROPHAGES; MAGNOLIA-OFFICINALIS; LIPID-PEROXIDATION; GENE-EXPRESSION; SYNOVIAL TISSUE AB Plant-derived compounds with potent anti-inflammatory activity have attracted a great deal of attention as a source for novel anti-arthritic agents with minimal side effects. We attempted to determine the anti-arthritic effects of orally administered honokiol isolated from Magnolia species. The oral administration of honokiol inhibited the progression and severity of type II collagen (CII)-induced arthritis (CIA) by reducing clinical arthritis scores and paw swelling. The histological analysis demonstrated preserved joint space; and the immunohistochemical data showed that the levels of interleukin (IL)-17, matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, and receptor activator for nuclear factor-kappa B ligand, as well as nitrotyrosine formation, were substantially suppressed in the honokiol-treated CIA mice. The elevated serum levels of tumor necrosis factor-alpha and IL-1 beta in the CIA mice were also restored to control levels via honokiol treatment. In the CIA mice, honokiol inhibited CII- or lipopolysaccharide-stimulated cytokine secretion in spleen cells, as well as CII-stimulated spleen cell proliferation. Furthermore, honokiol treatment reduced CIA-induced oxidative damage in the liver and kidney tissues of CIA mice. Collectively, the oral administration of honokiol inhibited CIA development by reducing the production of pro-inflammatory cytokines, MMP expressions, and oxidative stress. Thus, honokiol is an attractive candidate for an anti-arthritic agent. C1 [Kim, Ki Rim; Park, Kwang-Kyun; Chung, Won-Yoon] Yonsei Univ, Coll Dent, Dept Oral Biol, Res Ctr Orofacial Hard Tissue Regenerat, Seoul 120752, South Korea. [Kim, Ki Rim; Park, Kwang-Kyun; Chung, Won-Yoon] Yonsei Univ, Coll Dent, Brain Korea Project 21, Seoul 120752, South Korea. [Kim, Ki Rim; Park, Kwang-Kyun; Chung, Won-Yoon] Yonsei Univ, Dept Appl Life Sci, Grad Sch, Seoul 120749, South Korea. [Chun, Kyung-Soo] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Chung, WY (reprint author), Yonsei Univ, Coll Dent, Dept Oral Biol, Res Ctr Orofacial Hard Tissue Regenerat, 250 Seongsanno, Seoul 120752, South Korea. EM wychung@yuhs.ac FU Ministry of Education, Science, and Technology [R13-2003-013-03002-0] FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (R13-2003-013-03002-0). NR 49 TC 15 Z9 16 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD SEP PY 2010 VL 114 IS 1 BP 69 EP 78 DI 10.1254/jphs.10070FP PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 655LH UT WOS:000282251000009 PM 20703013 ER PT J AU Ide, S Fujiwara, S Fujiwara, M Sora, I Ikeda, K Minami, M Uhl, GR Ishihara, K AF Ide, Soichiro Fujiwara, Shunsuke Fujiwara, Masayuki Sora, Ichiro Ikeda, Kazutaka Minami, Masabumi Uhl, George R. Ishihara, Kumatoshi TI Antidepressant-Like Effect of Venlafaxine Is Abolished in mu-Opioid Receptor-Knockout Mice SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Article DE mu-opioid receptor; knockout mouse; antidepressant ID FORCED SWIM TEST; LOCUS-COERULEUS; IMMOBILITY; ANTAGONISM; RESPONSES; RATS AB Although the opioid system is known to modulate depression-like behaviors, its role in the effects of antidepressants is not yet clear. We investigated the role of mu-opioid receptors (MOPs) in the effects of venlafaxine, a serotonin and norepinephrine reuptake inhibitor, in the forced swim test using MOP-knockout (KO) mice. Venlafaxine reduced immobility time in wildtype mice (C57BL/6J), but not in MOP-KO mice, although no significant effects were observed on locomotor activity. These results suggest that MOPs play an important role in the antidepressant-like effects of venlafaxine. C1 [Ide, Soichiro; Fujiwara, Shunsuke; Fujiwara, Masayuki; Ishihara, Kumatoshi] Hiroshima Int Univ, Fac Pharmaceut Sci, Neuropharmacol Lab, Kure 7370112, Japan. [Ide, Soichiro; Minami, Masabumi] Hokkaido Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan. [Sora, Ichiro] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan. [Ikeda, Kazutaka] Tokyo Inst Psychiat, Div Psychobiol, Tokyo 1568585, Japan. [Uhl, George R.] Natl Inst Drug Abuse, Baltimore, MD 21224 USA. RP Ishihara, K (reprint author), Hiroshima Int Univ, Fac Pharmaceut Sci, Neuropharmacol Lab, Kure 7370112, Japan. EM ishihara@ps.hirokoku-u.ac.jp RI Ide, Soichiro/D-5472-2012; Minami, Masabumi/A-3883-2012; Ikeda, Kazutaka/I-4694-2013 OI Minami, Masabumi/0000-0002-0144-0679; Ikeda, Kazutaka/0000-0001-8342-0278 FU Naito Foundation; Suzuken Memorial Foundation; U.S. National Institute on Drug Abuse FX We thank M. Arends for editing the language of the manuscript. This study was supported by the Naito Foundation, the Suzuken Memorial Foundation, and the U.S. National Institute on Drug Abuse Intramural Research Program. NR 15 TC 12 Z9 14 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PD SEP PY 2010 VL 114 IS 1 BP 107 EP 110 DI 10.1254/jphs.10136SC PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 655LH UT WOS:000282251000014 PM 20703010 ER PT J AU Kim, BJ Zhou, J Martin, B Carlson, OD Maudsley, S Greig, NH Mattson, MP Ladenheim, EE Wustner, J Turner, A Sadeghi, H Egan, JM AF Kim, Byung-Joon Zhou, Jie Martin, Bronwen Carlson, Olga D. Maudsley, Stuart Greig, Nigel H. Mattson, Mark P. Ladenheim, Ellen E. Wustner, Jay Turner, Andrew Sadeghi, Homayoun Egan, Josephine M. TI Transferrin Fusion Technology: A Novel Approach to Prolonging Biological Half-Life of Insulinotropic Peptides SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; TYPE-2 DIABETES-MELLITUS; GLP-1 RECEPTOR AGONIST; GLYCEMIC CONTROL; GLUCOSE-HOMEOSTASIS; WEIGHT-GAIN; FOOD-INTAKE; IN-VIVO; EXENDIN-4; PANCREAS AB Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic beta-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides. C1 [Egan, Josephine M.] NIA, Diabet Sect, NIH, Baltimore, MD 21224 USA. [Wustner, Jay; Turner, Andrew; Sadeghi, Homayoun] BioRexis Pharmaceut Corp, King Of Prussia, PA USA. [Ladenheim, Ellen E.] Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. RP Egan, JM (reprint author), NIA, Diabet Sect, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM eganj@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 48 TC 28 Z9 30 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2010 VL 334 IS 3 BP 682 EP 692 DI 10.1124/jpet.110.166470 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641HH UT WOS:000281114900001 PM 20498254 ER PT J AU Xiao, B Li, XG Yan, JT Yu, XF Yang, GT Xiao, X Voltz, JW Zeldin, DC Wang, DW AF Xiao, Bin Li, Xuguang Yan, Jiangtao Yu, Xuefeng Yang, Guangtian Xiao, Xiao Voltz, James W. Zeldin, Darryl C. Wang, Dao Wen TI Overexpression of Cytochrome P450 Epoxygenases Prevents Development of Hypertension in Spontaneously Hypertensive Rats by Enhancing Atrial Natriuretic Peptide SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NITRIC-OXIDE SYNTHASE; DELIVERY ATTENUATES HYPERTENSION; EPOXIDE HYDROLASE INHIBITORS; ACTIVATED PROTEIN-KINASE; SENSITIVE K+ CHANNELS; ARACHIDONIC-ACID; EPOXYEICOSATRIENOIC ACIDS; CARDIAC-HYPERTROPHY; SIGNALING PATHWAYS; VENTRICULAR MYOCYTES AB Cytochrome P450 (P450)-derived epoxyeicosatrienoic acids (EETs) exert well recognized vasodilatory, diuretic, and tubular fluid-electrolyte transport actions that are predictive of a hypotensive effect. The study sought to determine the improvement of hypertension and cardiac function by overexpressing P450 epoxygenases in vivo. Long-term expression of CYP102 F87V or CYP2J2 in spontaneously hypertensive rats (SHR) was mediated by using a type 8 recombinant adeno-associated virus (rAAV8) vector. Hemodynamics was measured by a Millar Instruments, Inc. (Houston, TX) microtransducer catheter, and atrial natriuretic peptide (ANP) mRNA levels were tested by real-time polymerase chain reaction. Results showed that urinary excretion of 14,15-EET was increased at 2 and 6 months after injection with rAAV-CYP102 F87V and rAAV-CYP2J2 compared with controls (p < 0.05). During the course of the 6-month study, systolic blood pressure significantly decreased in P450 epoxygenase-treated rats, but the CYP2J2-specific inhibitor C26 blocked rAAV-CYP2J2-induced hypotension and the increase in EET production. Cardiac output was improved by P450 epoxygenase expression at 6 months (p < 0.05). Furthermore, cardiac collagen content was reduced in P450 epoxygenase-treated rats. ANP mRNA levels were up-regulated 6- to 14-fold in the myocardium, and ANP expression was significantly increased in both myocardium and plasma in P450 epoxygenase-treated rats. However, epidermal growth factor (EGF) receptor antagonist 4-(3'-chloroanilino)-6,7-dimethoxy-quinazoline (AG-1478) significantly attenuated the increase in the EET-induced expression of ANP in vitro. These data indicate that overexpression of P450 epoxygenases attenuates the development of hypertension and improves cardiac function in SHR, and that these effects may be mediated, at least in part, by ANP via activating EGF receptor. C1 [Xiao, Bin; Li, Xuguang; Yan, Jiangtao; Yu, Xuefeng; Yang, Guangtian; Xiao, Xiao; Wang, Dao Wen] Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, Wuhan 430030, Peoples R China. [Xiao, Bin; Li, Xuguang; Yan, Jiangtao; Yu, Xuefeng; Yang, Guangtian; Xiao, Xiao; Wang, Dao Wen] Huazhong Univ Sci & Technol, Inst Hypertens, Wuhan 430030, Peoples R China. [Xiao, Xiao] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Voltz, James W.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Dept Internal Med, Tongji Hosp, Tongji Med Coll, 1095 Jiefang Ave, Wuhan 430030, Peoples R China. EM dwwang@tjh.tjmu.edu.cn RI Xiao, Bin/E-1875-2015 FU National Natural Science Foundation of China [30430320, 30930039]; National "973" projects [2007CB512004]; International Collaboration and Wuhan City projects; National Institutes of Health National Institute of Environmental Health Sciences FX This work was supported in part by the National Natural Science Foundation of China [Grants 30430320, 30930039]; National "973" projects [Grant 2007CB512004]; International Collaboration and Wuhan City projects; and in part by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences. NR 49 TC 29 Z9 32 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2010 VL 334 IS 3 BP 784 EP 794 DI 10.1124/jpet.110.167510 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641HH UT WOS:000281114900012 PM 20501636 ER PT J AU McClain, JJ Hart, TL Getz, RS Tudor-Locke, C AF McClain, James J. Hart, Teresa L. Getz, Renee S. Tudor-Locke, Catrine TI Convergent Validity of 3 Low Cost Motion Sensors With the ActiGraph Accelerometer SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH LA English DT Article DE physical activity; objective assessment; intensity; adult ID FREE-LIVING CONDITIONS; PHYSICAL-ACTIVITY; ENERGY-EXPENDITURE; LIFECORDER EX; CALIBRATION; PEDOMETERS; CHILDREN; INTENSITY; ACCURACY; ADULTS AB Background: This study evaluated the utility of several lower cost physical activity (PA) assessment instruments for detecting PA volume (steps) and intensity (time in MVPA or activity time) using convergent methods of assessment Methods: Participants included 26 adults (9 male) age 27.3 +/- 7 1 years with a BMI of 23.8 +/- 2.8 kg/m(2) Instruments evaluated included the Omron HJ-151 (OM), New Lifestyles NL-1000 (NL), Walk4Life W4L Pro (W4L), and ActiGraph GTIM (AG). Participants wore all instruments during a laboratory phase. consisting of 10 single minute treadmill walking bouts ranging in speed from 40 to 112 m/min, and immediate following the laboratory phase and during the remainder of their free-living day (11.3 +/- 1.5 hours). Previously validated AG MVPA cutpoints were used for comparison with OM, NL, and W4L MVPA or activity time outputs during the laboratory and free-living phase. Results: OM and NL produced similar MVPA estimates during free-living to commonly used AG walking cutpoints, and W4L activity time estimates were similar to one AG lifestyle cutpoint evaluated. Conclusion: Current findings indicate that the OM, NL, and W4L, ranging in price from $15 to $49, can provide reasonable estimates of free-living MVPA or activity time in comparison with a range of AG walking and lifestyle cutpoints. C1 [McClain, James J.] Natl Canc Inst, Canc Prevent Fellowship Program, Bethesda, MD USA. [Hart, Teresa L.] Univ Wisconsin, Dept Human Movement Sci, Milwaukee, WI 53201 USA. [Getz, Renee S.] Arizona State Univ, Dept Exercise & Wellness, Mesa, AZ USA. [Tudor-Locke, Catrine] Pennington Biomed Res Ctr, Walking Behav Lab, Baton Rouge, LA USA. RP McClain, JJ (reprint author), Natl Canc Inst, Canc Prevent Fellowship Program, Bethesda, MD USA. NR 24 TC 12 Z9 12 U1 0 U2 6 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1543-3080 J9 J PHYS ACT HEALTH JI J. Phys. Act. Health PD SEP PY 2010 VL 7 IS 5 BP 662 EP 670 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 647YE UT WOS:000281656000014 PM 20864763 ER PT J AU Niu, SD Li, F Tan, DX Zhang, LR Idle, JR Gonzalez, FJ Ma, XC AF Niu, Sida Li, Feng Tan, Dun-Xian Zhang, Lirong Idle, Jeffrey R. Gonzalez, Frank J. Ma, Xiaochao TI Analysis of N1-acetyl-N2-formyl-5-methoxykynuramine/N1-acetyl-5-methoxy-kynuramine formation from melatonin in mice SO JOURNAL OF PINEAL RESEARCH LA English DT Article DE antioxidant; melatonin; metabolism; N1-acetyl-5-methoxy-kynuramine; N1-acetyl-N2-formyl-5-methoxykynuramine ID METABOLITE N-1-ACETYL-5-METHOXYKYNURAMINE; NEUROHORMONE MELATONIN; OXIDATIVE STRESS; IN-VITRO; ANTIOXIDANT; OXYGEN; N-1-ACETYL-N-2-FORMYL-5-METHOXYKYNURAMINE; HEPATOTOXICITY; DERIVATIVES; PRODUCTS AB The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxy-kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy-AMK and glucuronide-conjugated hydroxy-AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress. C1 [Niu, Sida; Li, Feng; Zhang, Lirong; Ma, Xiaochao] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. [Tan, Dun-Xian] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague, Czech Republic. [Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ma, XC (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, 4089 KLSIC,MS 1018,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM xma2@kumc.edu OI Idle, Jeff/0000-0002-6143-1520 FU NCRR NIH HHS [P20 RR021940, 5P20-RR021940] NR 36 TC 11 Z9 12 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3098 J9 J PINEAL RES JI J. Pineal Res. PD SEP PY 2010 VL 49 IS 2 BP 106 EP 114 DI 10.1111/j.1600-079X.2010.00771.x PG 9 WC Endocrinology & Metabolism; Neurosciences; Physiology SC Endocrinology & Metabolism; Neurosciences & Neurology; Physiology GA 635HH UT WOS:000280645700002 PM 20545825 ER PT J AU Miller, A Vo, H Huo, LA Roca, C Schmidt, PJ Rubinow, DR AF Miller, Alexandra Vo, Hoa Huo, Liang Roca, Catherine Schmidt, Peter J. Rubinow, David R. TI Estrogen receptor alpha (ESR-1) associations with psychological traits in women with PMDD and controls SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Estrogen receptor; Premenstrual dysphoric disorder; TPQ; 16PF; NEO; Estradiol; Mood ID PREMENSTRUAL DYSPHORIC DISORDER; TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; SEROTONIN TRANSPORTER GENE; GONADAL-STEROIDS; MENSTRUAL-CYCLE; SPOUSE RATINGS; HARM AVOIDANCE; SELF-REPORTS; SYMPTOMS; POLYMORPHISM AB Premenstrual Dysphoric Disorder (PMDD) is a mood disorder affecting about 5% of women and is associated with substantial morbidity. Albeit inconsistently, PMDD is described as being characterized by heritable personality traits. Although PMDD is a heritable disorder, it is unclear whether any of the heritable susceptibility to PMDD resides in heritable personality traits. In groups of carefully characterized women with PMDD (n = 68) and controls (n = 56), we attempted to determine whether diagnosis-related traits could be confirmed, as well as to determine whether such traits were associated with SNPs in estrogen receptor alpha (ESR-1) that we previously demonstrated were associated with PMDD. We observed 7/25 traits to be significantly different in patients and controls and further showed that 11/12 significant associations observed between these 7 traits and 16 ESR-1 SNPs involved the intron 4 SNPs previously shown to be the locus of the association with PMDD. While several interactions between genotype and diagnosis were observed, the effect of genotype in most instances was in the same direction in patients and controls. These data demonstrate affective state-independent personality traits that distinguish patients with PMDD from controls and further support the relevance of ESR-1 polymorphic variants in the regulation of non-reproductive behaviors. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Miller, Alexandra; Rubinow, David R.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA. [Vo, Hoa] Vet Affairs Hosp, Honolulu, HI USA. [Huo, Liang; Roca, Catherine; Schmidt, Peter J.; Rubinow, David R.] NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Huo, Liang] Synergy Amer Inc, Gaithersburg, MD USA. RP Rubinow, DR (reprint author), Univ N Carolina, Dept Psychiat, 10514 Neurosci Hosp,CB 7160, Chapel Hill, NC 27599 USA. EM drubinow@med.unc.edu FU NIH [1 z01 MH002765-09]; Foundation of Hope FX This study was conducted as part of our duties as employees of the federal government and hence is not subject to copyright. Funding for this study was provided under NIH research project #1 z01 MH002765-09, and by a grant from the Foundation of Hope. NR 51 TC 5 Z9 5 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD SEP PY 2010 VL 44 IS 12 BP 788 EP 794 DI 10.1016/j.jpsychires.2010.01.013 PG 7 WC Psychiatry SC Psychiatry GA 643WI UT WOS:000281330100008 PM 20172536 ER PT J AU Krieger, J Jacobs, DE Ashley, PJ Baeder, A Chew, GL Dearborn, D Hynes, HP Miller, JD Morley, R Rabito, F Zeldin, DC AF Krieger, James Jacobs, David E. Ashley, Peter J. Baeder, Andrea Chew, Ginger L. Dearborn, Dorr Hynes, H. Patricia Miller, J. David Morley, Rebecca Rabito, Felicia Zeldin, Darryl C. TI Housing Interventions and Control of Asthma-Related Indoor Biologic Agents: A Review of the Evidence SO JOURNAL OF PUBLIC HEALTH MANAGEMENT AND PRACTICE LA English DT Review DE allergens; asthma; cockroaches; dust; housing; mice; mites; moisture; prevention; rats ID DUST MITE ALLERGEN; RANDOMIZED CONTROLLED-TRIAL; GENE-ENVIRONMENT INTERACTIONS; HEALTH WORKER INTERVENTION; INTEGRATED PEST-MANAGEMENT; IMPERMEABLE BED COVERS; LOW-INCOME; COCKROACH ALLERGEN; MOUSE ALLERGEN; MECHANICAL VENTILATION AB Subject matter experts systematically reviewed evidence on the effectiveness of housing interventions that affect health outcomes, primarily asthma, associated with exposure to moisture, mold, and allergens. Three of the 11 interventions reviewed had sufficient evidence for implementation: multifaceted, in-home, tailored interventions for reducing asthma morbidity; integrated pest management to reduce cockroach allergen; and combined elimination of moisture intrusion and leaks and removal of moldy items to reduce mold and respiratory symptoms. Four interventions needed more field evaluation, 1 needed formative research, and 3 either had no evidence of effectiveness or were ineffective. The 3 interventions with sufficient evidence all applied multiple, integrated strategies. This evidence review shows that selected interventions that improve housing conditions will reduce morbidity from asthma and respiratory allergies. C1 [Krieger, James] Publ Health Seattle & King Cty, Chron Dis & Injury Prevent Sect, Seattle, WA 98104 USA. [Jacobs, David E.; Morley, Rebecca] Natl Ctr Healthy Housing, Columbia, MD USA. [Ashley, Peter J.] US Dept Housing & Urban Dev, Off Healthy Homes & Lead Hazard Control, Washington, DC USA. [Baeder, Andrea; Chew, Ginger L.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Dearborn, Dorr] Case Western Reserve Univ, Dept Environm Hlth Sci, Cleveland, OH 44106 USA. [Hynes, H. Patricia] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Miller, J. David] Carleton Univ, Ottawa, ON K1S 5B6, Canada. [Rabito, Felicia] Tulane Univ, Dept Epidemiol, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. [Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Krieger, J (reprint author), Publ Health Seattle & King Cty, Chron Dis & Injury Prevent Sect, Chinook Bldg,Ste 900,401 5th Ave, Seattle, WA 98104 USA. EM james.krieger@kingcounty.gov FU Intramural NIH HHS [ZIA ES025041-16]; NIEHS NIH HHS [P30 ES 009089, P30 ES009089] NR 99 TC 63 Z9 63 U1 0 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-4659 J9 J PUBLIC HEALTH MAN JI J. Public Health Manag. Pract. PD SEP-OCT PY 2010 VL 16 IS 5 SU S BP S11 EP S20 DI 10.1097/PHH.0b013e3181ddcbd9 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 641EQ UT WOS:000281108000004 PM 20689369 ER PT J AU Nemecek, D Heymann, JB Qiao, JA Mindich, L Steven, AC AF Nemecek, Daniel Heymann, J. Bernard Qiao, Jian Mindich, Leonard Steven, Alasdair C. TI Cryo-electron tomography of bacteriophage phi 6 procapsids shows random occupancy of the binding sites for RNA polymerase and packaging NTPase SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Electron cryo-tomography; RNA-dependent RNA polymerase; Packaging motor; Procapsid; Cystovirus ID 3 GENOMIC SEGMENTS; VIRUS; COMPLEX; MECHANISM; P4 AB Assembly of dsRNA bacteriophage phi 6 involves packaging of the three mRNA strands of the segmented genome into the procapsid, an icosahedrally symmetric particle with recessed vertices. The hexameric packaging NTPase (P4) overlies these vertices, and the monomeric RNA-dependent RNA polymerase (RdRP, P2) binds at sites inside the shell. P2 and P4 are present in substoichiometric amounts, raising the questions of whether they are recruited to the nascent procapsid in defined amounts and at specific locations, and whether they may co-localize to form RNA-processing assembly lines at one or more "special" vertices. We have used cryo-electron tomography to map both molecules on individual procapsids. The results show variable complements that accord with binomial distributions with means of 8 (P2) and 5 (P4), suggesting that they are randomly incorporated in copy numbers that simply reflect availability, i.e. their rates of synthesis. Analysis of the occupancy of potential binding sites (20 for P2; 12 for P4) shows no tendency to cluster nor for P2 and P4 to co-localize, suggesting that the binding sites for both proteins are occupied in random fashion. These observations indicate that although P2 and P4 act sequentially on the same substrates there is no direct physical coupling between their activities. Published by Elsevier Inc. C1 [Nemecek, Daniel; Heymann, J. Bernard; Steven, Alasdair C.] NIAMSD, NIH, Bethesda, MD 20892 USA. [Qiao, Jian; Mindich, Leonard] Univ Med & Dent New Jersey, Publ Hlth Res Inst Ctr, Dept Microbiol, Newark, NJ 07103 USA. RP Heymann, JB (reprint author), NIAMSD, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM bernard_heymann@nih.gov RI Heymann, Bernard/F-6825-2011 FU NIAMS; National Institutes of Health [GM34352] FX We thank Dr Dennis C. Winkler for assistance with electron cryo-tomography. This work was supported by the Intramural Research Program of NIAMS and by Grant GM34352 to LM. from the National Institutes of Health. NR 26 TC 17 Z9 17 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2010 VL 171 IS 3 BP 389 EP 396 DI 10.1016/j.jsb.2010.06.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 635TS UT WOS:000280680100016 PM 20538059 ER PT J AU Dawson, DA Compton, WM Grant, BF AF Dawson, Deborah A. Compton, Wilson M. Grant, Bridget F. TI Frequency of 5+/4+ Drinks as a Screener for Drug Use and Drug-Use Disorders SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; ALCOHOL-USE DISORDER; DSM-IV ALCOHOL; GENERAL-POPULATION SAMPLE; IDENTIFICATION-TEST CUDIT; DEPENDENCE SCALE SDS; PRIMARY-CARE; UNITED-STATES; TEST ASSIST; PSYCHOMETRIC PROPERTIES AB Objective: The objective of this study was to test the ability of a question on frequency of drinking 5+ (for men) or 4+ (for women) drinks to screen for drug use and drug-use disorders (DUDs) in a general population sample. Method: Using data collected in 2001-2002 from a representative U.S. adult population sample (N = 43,093), including a subsample of those with past-year emergency-department use (n = 8,525), past-year frequency of drinking 5+/4+ drinks was evaluated as a screener for drug use and DUDs for four categories of illicit drugs. Results: Sensitivities and specificities of the 5+/4+ drinks screener were 72.4% and 76.6% for any drug dependence, 71.9% and 77.3% for any DUD, and 63.3% and 78.9% for any drug use in the general population. Sensitivities and specificities were higher for marijuana and cocaine/crack and lowest for illicit prescription drugs. Optimal screening cut-points were once a month or more for cocaine/crack dependence, either once or more a month or seven or more times a year for cocaine/crack DUDs, seven or more times a year for cocaine/crack use, and once or more a year for the other drug use and DUD measures. Sensitivity and specificity were similar among adults who had visited an emergency department in the past year, and the optimal screening cutpoints were identical. Conclusions: Past-year frequency of drinking 5+/4+ drinks was quite accurate as a screener for past-year marijuana and cocaine/crack use and DUDs, but it was less accurate for illicit prescription drug use and DUDs. Its drug-screening potential can be thought of as "added value" from an item already likely to be asked in the interest of detecting problem drinking. Future work may consider using the alcohol consumption screener as a starting point, with follow-up questions to assess illicit drug use among those who screen positive. (J. Stud. Alcohol Drugs, 71, 751-760, 2010) C1 [Dawson, Deborah A.; Compton, Wilson M.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, 5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services; National Institute on Drug Abuse; National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The study on which this article is based, the National Epidemiologic Survey on Alcohol and Related Conditions, is sponsored by the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, U.S. Department of Health and Human Services, with supplemental support from the National Institute on Drug Abuse. This research was supported by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. All authors are federal government employees, and none of the authors has any financial conflict of interest to report. The views and opinions expressed in this article are those of the authors and should not be construed to represent the views of any of the sponsoring organizations, agencies, or the U.S. government. All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. NR 53 TC 10 Z9 10 U1 3 U2 4 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD SEP PY 2010 VL 71 IS 5 BP 751 EP 760 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 645UE UT WOS:000281490900015 PM 20731982 ER PT J AU Britton, JC Rauch, SL Rosso, IM Killgore, WDS Price, LM Ragan, J Chosak, A Hezel, DM Pine, DS Leibenluft, E Pauls, DL Jenike, MA Stewart, SE AF Britton, Jennifer C. Rauch, Scott L. Rosso, Isabelle M. Killgore, William D. S. Price, Lauren M. Ragan, Jennifer Chosak, Anne Hezel, Dianne M. Pine, Daniel S. Leibenluft, Ellen Pauls, David L. Jenike, Michael A. Stewart, S. Evelyn TI Cognitive Inflexibility and Frontal-Cortical Activation in Pediatric Obsessive-Compulsive Disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; set-shifting; fMRI; inferior frontal gyrus; striatum ID DEFICIT HYPERACTIVITY DISORDER; RESPONSE-INHIBITION DEFICITS; PREFRONTAL CORTEX; BRAIN ACTIVATION; NEUROPSYCHOLOGICAL PERFORMANCE; EXECUTIVE FUNCTIONS; TOURETTES-SYNDROME; MOTOR INHIBITION; FUNCTIONAL MRI; TIC SEVERITY AB Objective: Deficits in cognitive flexibility and response inhibition have been linked to perturbations in cortico-striatal-thalamic circuitry in adult obsessive-compulsive disorder (OCD). Although similar cognitive deficits have been identified in pediatric OCD, few neuroimaging studies have been conducted to examine its neural correlates in the developing brain. In this study, we tested hypotheses regarding group differences in the behavioral and neural correlates of cognitive flexibility in a pediatric OCD and a healthy comparison (HC) sample. Method: In this functional magnetic resonance imaging (fMRI) study, a pediatric sample of 10- to 17-year-old subjects, 15 with OCD and 20 HC, completed a set-shifting task. The task, requiring an extradimensional shift to identify a target, examines cognitive flexibility. Within each block, the dimension (color or shape) that identified the target either alternated (i.e., mixed) or remained unchanged (i.e., repeated). Results: Compared with the HC group, the OCD group tended to be slower to respond to trials within mixed blocks. Compared with the HC group, the OCD group exhibited less left inferior frontal gyrus/BA47 activation in the set-shifting contrast (i.e., HC > OCD, mixed versus repeated); only the HC group exhibited significant activation in this region. The correlation between set shifting-induced right caudate activation and shift cost (i.e., reaction time differential in response to mixed versus repeated trials) was significantly different between HC and OCD groups, in that we found a positive correlation in HC and a negative correlation in OCD. Conclusions: In pediatric OCD, less fronto-striatal activation may explain previously identified deficits in shifting cognitive sets. J. Am. Acad. Child Adolesc. Psychiatry, 2010;49(9): 944-953. C1 [Britton, Jennifer C.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Rauch, Scott L.; Rosso, Isabelle M.; Killgore, William D. S.; Price, Lauren M.] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Stewart, S. Evelyn] Massachusetts Gen Hosp, Dept Psychiat, Richard B Simches Res Ctr, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. RP Stewart, SE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Richard B Simches Res Ctr, Psychiat & Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA. EM estewart1@partners.org RI Britton, Jennifer/J-4501-2013; Stewart, Evelyn/K-6961-2014; OI Killgore, William/0000-0002-5328-0208; Stewart, S. Evelyn/0000-0002-0994-6383 FU Massachusetts General Hospital (MGH); Novartis; Neurogen; Sepracor; Primedia; Medtronics, Inc.; Board at the Massachusetts Society for Medical Research (MSMR); National Foundation of Mental Health (NFMH) Board; Department of Defense Contractor, GovSource, Inc.; Brain Institute, University of Utah; U.S. Army Medical Research and Material Command; Sleep History and Readiness Predictor (SHARP); U.S. Army Reserve; National Institutes of Health (National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health); Autism Consortium; Ellison Foundation; Anonymous Donor FX Dr. Rauch has received funds for research through Massachusetts General Hospital (MGH) from Medtronics, Cyberonics, and Cephalon. He has received honoraria from Novartis, Neurogen, Sepracor, Primedia, and Medtronics, Inc. Dr. Rauch is a trustee at Mclean Hospital and serves on the Board at the Massachusetts Society for Medical Research (MSMR) as well as on the National Foundation of Mental Health (NFMH) Board. Dr. Killgore works as a part-time contract researcher at the Department of Defense Contractor, GovSource, Inc., and does contract work for the Brain Institute, University of Utah. He has a U.S. Army Medical Research and Material Command grant and a patent pending: The Sleep History and Readiness Predictor (SHARP), a computer program developed for predicting cognitive performance from sleep and circadian rhythms. Dr. Killgore is affiliated with the U.S. Army Reserve. Dr. Pauls has obtained funds from the following sources: National Institutes of Health (National Institute of Neurological Disorders and Stroke, and National Institute of Mental Health), Autism Consortium, Ellison Foundation, Anonymous Donor, and has received an honorarium from the Mayo Clinic for giving course lectures. Drs. Britton, Rosso, Ragan, Chosak, Pine, Leibenluft, Jenike, and Stewart, and Ms. Price, and Ms. Hezel report no biomedical financial interests or potential conflicts of interest. NR 57 TC 29 Z9 30 U1 7 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2010 VL 49 IS 9 BP 944 EP 953 DI 10.1016/j.jaac.2010.05.006 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 643WT UT WOS:000281331400008 PM 20732630 ER PT J AU Boden, BP Sheehan, FT Torg, JS Hewett, TE AF Boden, Barry P. Sheehan, Frances T. Torg, Joseph S. Hewett, Timothy E. TI Noncontact Anterior Cruciate Ligament Injuries: Mechanisms and Risk Factors SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID KNEE INJURY; IN-VITRO; TIBIAL PLATEAU; ACL RUPTURE; JOINT; COMPRESSION; STRAIN; MUSCLE; FORCES; BIOMECHANICS AB Significant advances have recently been made in understanding the mechanisms involved in noncontact anterior cruciate ligament (ACL) injury. Most ACL injuries involve minimal to no contact. Female athletes sustain a two-to eightfold greater rate of injury than do their male counterparts. Recent videotape analyses demonstrate significant differences in average leg and trunk positions during injury compared with control subjects. These findings as well as those of cadaveric and MRI studies indicate that axial compressive forces are a critical component in noncontact ACL injury. A complete understanding of the forces and risk factors associated with noncontact ACL injury should lead to the development of improved preventive strategies for this devastating injury. C1 [Boden, Barry P.] Orthopaed Ctr, Rockville, MD USA. [Sheehan, Frances T.] NIH, Bethesda, MD 20892 USA. [Torg, Joseph S.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Hewett, Timothy E.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Hewett, Timothy E.] Univ Cincinnati, Coll Med, Dept Orthopaed Surg, Cincinnati, OH USA. [Hewett, Timothy E.] Univ Cincinnati, Coll Med, Dept Biomed Engn, Cincinnati, OH USA. RP Boden, BP (reprint author), Orthopaed Ctr, Rockville, MD USA. RI sheehan, frances/B-6962-2009; Hewett, Timothy/E-3241-2011 FU NIH/NIAMS [R01-AR049735, R01-AR05563, R01-AR056259] FX This work is supported in part by NIH/NIAMS R01-AR049735, R01-AR05563, and R01-AR056259 (T.E.H.). NR 41 TC 60 Z9 65 U1 11 U2 60 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD SEP PY 2010 VL 18 IS 9 BP 520 EP 527 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 645KL UT WOS:000281454900003 PM 20810933 ER PT J AU Saunders, D AF Saunders, D. TI Mouse Urine Collection Using Single Animal Method SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Saunders, D.] NHLBI, LMC, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 686 EP 686 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900116 ER PT J AU Cannon, CZ AF Cannon, C. Zegre TI Comparison of Analgesia Effects of Tramadol, Carprofen, or Multimodal Analgesia in Rats Undergoing Ventral Laparotomy SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Cannon, C. Zegre] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 692 EP 693 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900141 ER PT J AU Tubbs, JT Blankenship-Paris, T Travlos, G King-Herbert, AP Kissling, G Clark, J Goulding, D AF Tubbs, J. T. Blankenship-Paris, T. Travlos, G. King-Herbert, A. P. Kissling, G. Clark, J. Goulding, D. TI Buprenorphine, Meloxicam, and Flunixin Meglumine Postoperative Analgesia in Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Tubbs, J. T.; Travlos, G.; King-Herbert, A. P.] NIEHS, CMPB, Res Triangle Pk, NC 27709 USA. [Kissling, G.] NIEHS, BSB, Res Triangle Pk, NC 27709 USA. [Blankenship-Paris, T.; Clark, J.; Goulding, D.] NIEHS, CMB, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 692 EP 692 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900139 ER PT J AU Barnard, DE AF Barnard, D. E. TI Laboratory Animal Diet: An Environmental Factor that Affects Research SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Barnard, D. E.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 696 EP 696 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900152 ER PT J AU Brining, DL LaCasse, RA Kercher, L Rockx, B Safronetz, D Geisbert, TW Mattoon, JS Feldmann, H Parnell, MJ AF Brining, D. L. LaCasse, R. A. Kercher, L. Rockx, B. Safronetz, D. Geisbert, T. W. Mattoon, J. S. Feldmann, H. Parnell, M. J. TI The Utilization of Digital Thoracic Radiography as a Refinement Methodology for Animal Models of Infectious Diseases SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Brining, D. L.; LaCasse, R. A.; Kercher, L.; Parnell, M. J.] NIAID, Rocky Mt Vet Branch, Rocky Mt Labs, NIH, Hamilton, MT USA. [Rockx, B.; Safronetz, D.; Feldmann, H.] NIAID, Virol Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. [Geisbert, T. W.] Emerging Infect Dis Labs, Virol Lab, Boston, MA USA. [Mattoon, J. S.] Washington State Univ, Dept Vet Clin Sci, Pullman, WA 99164 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 723 EP 723 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900240 ER PT J AU Rivas, C AF Rivas, C. TI Comparison of Outbred Recipient Females for Embryo Transfer of 3.5-Day Blastocysts for the Generation of Transgenic Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Rivas, C.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 727 EP 727 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900253 ER PT J AU Darby, A Taylor, NS Shen, Z Thigpen, JE Whiteside, T Hinthorn, D Horvat, R Vonder Haar, RA Fox, JG AF Darby, A. Taylor, N. S. Shen, Z. Thigpen, J. E. Whiteside, T. Hinthorn, D. Horvat, R. Vonder Haar, R. A. Fox, J. G. TI Cytotoxic Klebsiella oxytoca Isolated from Mice and Humans SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Darby, A.; Taylor, N. S.; Shen, Z.; Fox, J. G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Thigpen, J. E.; Whiteside, T.] NIEHS, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. [Hinthorn, D.; Horvat, R.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA. [Vonder Haar, R. A.] Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 738 EP 738 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900286 ER PT J AU Handon, R Lu, K Cannons, J Reilley, J Schwartzberg, P AF Handon, R. Lu, K. Cannons, J. Reilley, J. Schwartzberg, P. TI Presence of Germinal Centers in the Intestine of SAP-l-Immune-Deficient Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Handon, R.; Lu, K.; Cannons, J.; Reilley, J.; Schwartzberg, P.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 738 EP 739 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900288 ER PT J AU Thigpen, J Kissling, G Caviness, GF Locklear, J Whiteside, T Padilla-Banks, L Hackney, S Grant, M Forsythe, D AF Thigpen, J. Kissling, G. Caviness, G. F. Locklear, J. Whiteside, T. Padilla-Banks, L. Hackney, S. Grant, M. Forsythe, D. TI Effects of Rodent Diets Containing High or Low Levels of Phytoestrogens on Time of Vaginal Opening in Four Rat Strains SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J.; Caviness, G. F.; Locklear, J.; Whiteside, T.; Padilla-Banks, L.; Hackney, S.; Grant, M.; Forsythe, D.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. [Kissling, G.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 741 EP 741 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900296 ER PT J AU Locklear, J Thigpen, J Glassbrook, N Caviness, GF Kissling, G Hackney, S Rooney, M Grant, M Forsythe, D AF Locklear, J. Thigpen, J. Glassbrook, N. Caviness, G. F. Kissling, G. Hackney, S. Rooney, M. Grant, M. Forsythe, D. TI Corncob Bedding Spiked with Zearalenone Significantly Advances the Timing of Vaginal Opening in Immature CD1 Hirsute and SKH-1 Nude Mice SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Locklear, J.; Thigpen, J.; Caviness, G. F.; Hackney, S.; Rooney, M.; Grant, M.; Forsythe, D.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. [Kissling, G.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Glassbrook, N.] NC State Univ, Dept Environm & Mol Toxicol, Raleigh, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 743 EP 743 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900302 ER PT J AU Thigpen, J Caviness, G Whiteside, T Locklear, J Grant, M Forsythe, D AF Thigpen, J. Caviness, G. Whiteside, T. Locklear, J. Grant, M. Forsythe, D. TI Impact of Bacterial Contaminants on Results of the ATP-Based System for the Detection of Mycoplasma Contaminants in Cell Cultures SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J.; Caviness, G.; Whiteside, T.; Locklear, J.; Grant, M.; Forsythe, D.] NIEHS, CMB QAL, Res Triangle Dr, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 748 EP 749 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900320 ER PT J AU Thigpen, J Kissling, G Collins, B Setchell, K Adsit, F Caviness, G Locklear, J Whiteside, T Grant, M Forsythe, D AF Thigpen, J. Kissling, G. Collins, B. Setchell, K. Adsit, F. Caviness, G. Locklear, J. Whiteside, T. Grant, M. Forsythe, D. TI The Impact of Rodent Diets and Bedding in Studies Evaluating the Estrogenic Activity of Endocrine Disruptor Compounds SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Thigpen, J.; Adsit, F.; Caviness, G.; Locklear, J.; Whiteside, T.; Grant, M.; Forsythe, D.] NIEHS, CMB QAL, Res Triangle Pk, NC 27709 USA. [Kissling, G.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Collins, B.] NIEHS, Natl Toxicol Branch, Res Triangle Pk, NC 27709 USA. [Setchell, K.] Childrens Hosp Med Ctr, Dept Pediat Gastroenterol, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD SEP PY 2010 VL 49 IS 5 BP 748 EP 748 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 652CG UT WOS:000281977900319 ER PT J AU Mollura, DJ Morens, DM Taubenberger, JK Bray, M AF Mollura, Daniel J. Morens, David M. Taubenberger, Jeffery K. Bray, Mike TI The Role of Radiology in Influenza: Novel H1N1 and Lessons Learned From the 1918 Pandemic SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Radiology; infectious disease imaging; influenza; great pandemic of 1918; epidemic; chest CT; plain film; chest radiograph; history; pulmonary infection ID A H1N1; CT FINDINGS; X-RAY; PNEUMONIA; EPIDEMIC; DISEASE; COMPLICATIONS; VIRUS; CHEST; INFECTIONS AB The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases, raising new opportunities for the further development of infectious disease imaging. To help define radiology's role in present and future influenza outbreaks, it is important to understand how radiologists have responded to past epidemics and how these outbreaks influenced the development of imaging science. The authors review the role of radiology in the most severe influenza outbreak in history, the "great pandemic" of 1918, which arrived only 23 years after the discovery of x-rays. In large part because of the coincidental increase in the radiologic capacity of military hospitals for World War I, the 1918 pandemic firmly reinforced the role of radiologists as collaborators with clinicians and pathologists at an early stage in radiology's development, in addition to producing a radical expansion of radiologic research on pulmonary infections. Radiology's solid foundation from the 1918 experience in medical practice and research now affords significant opportunities to respond to the current H1N1 pandemic and future epidemics through similar interdisciplinary strategies that integrate imaging science with pathology, virology, and clinical studies. The broad range of current imaging capabilities will make it possible to study influenza at the cellular level, in animal models, and in human clinical trials to elucidate the pathogenesis of severe illness and improve clinical outcomes. C1 [Mollura, Daniel J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Bray, Mike] NIAID, Integrated Res Facil, NIH, Bethesda, MD 20892 USA. RP Mollura, DJ (reprint author), NIH, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM daniel.mollura@nih.gov FU Intramural NIH HHS [ZIA AI000995-05] NR 75 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD SEP PY 2010 VL 7 IS 9 BP 690 EP 697 DI 10.1016/j.jacr.2010.01.007 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V23SS UT WOS:000208363100008 PM 20816630 ER PT J AU Mathur, A Kemp, CD Dutta, U Baid, S Ayala, A Chang, RE Steinberg, SM Papademetriou, V Lange, E Libutti, SK Pingpank, JF Alexander, HR Phan, GQ Hughes, M Linehan, WM Pinto, PA Stratakis, CA Kebebew, E AF Mathur, Aarti Kemp, Clinton D. Dutta, Utpal Baid, Smita Ayala, Alejandro Chang, Richard E. Steinberg, Seth M. Papademetriou, Vasilios Lange, Eileen Libutti, Steven K. Pingpank, James F. Alexander, H. Richard Phan, Giao Q. Hughes, Marybeth Linehan, W. Marston Pinto, Peter A. Stratakis, Constantine A. Kebebew, Electron TI Consequences of Adrenal Venous Sampling in Primary Hyperaldosteronism and Predictors of Unilateral Adrenal Disease SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID PRIMARY ALDOSTERONISM; DIAGNOSIS AB BACKGROUND: In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been advocated by some to be the gold standard for localization of the responsible lesion, but there remains a lack of consensus for the criteria and the standardization of technique. STUDY DESIGN: We performed a retrospective study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses were performed to determine what factors were associated with AVS lateralization, and which AVS values were the most accurate criteria for lateralization. RESULTS: Eighty-five patients underwent surgery at our institution for unilateral hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities on CT, AVS localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for lateralization was the post-ACTH stimulation value. Factors associated with AVS lateralization included a low renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass >= 3 cm on CT scan. CONCLUSIONS: Because 50% of patients would have been inappropriately managed based on CT scan findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation value. Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS selectively. (J Am Coll Surg 2010;211:384-390. (C) 2010 by the American College of Surgeons) C1 [Mathur, Aarti; Kemp, Clinton D.; Phan, Giao Q.; Hughes, Marybeth; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res, Bethesda, MD 20892 USA. [Linehan, W. Marston; Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Papademetriou, Vasilios] Georgetown Univ, Washington, DC USA. [Papademetriou, Vasilios] Vet Adm, Washington, DC USA. [Libutti, Steven K.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Surg, Bronx, NY 10467 USA. [Pingpank, James F.] Univ Pittsburgh, Div Surg Oncol, Inst Canc, Pittsburgh, PA USA. [Alexander, H. Richard] Univ Maryland, Sch Med, Dept Surg, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Kebebew, E (reprint author), NCI, Surg Branch CRC, Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. OI Papademetriou, Vasilios/0000-0002-2882-2757 FU 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 18 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2010 VL 211 IS 3 BP 384 EP 390 DI 10.1016/j.jamcollsurg.2010.05.006 PG 7 WC Surgery SC Surgery GA 648QH UT WOS:000281708500012 PM 20800196 ER PT J AU Rahbari, R Holloway, AK He, M Clark, OH AF Rahbari, Reza Holloway, Alisha K. He, Mei Clark, Orlo H. TI Parathyroid neoplasms have distinct microRNA gene expression profile SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Meeting Abstract CT Annual Clinical Congress of American-College-of-Surgeons CY 2010 CL Chicago, IL SP Amer Coll Surg C1 [Rahbari, Reza; Holloway, Alisha K.; He, Mei; Clark, Orlo H.] NCI, Bethesda, MD 20892 USA. RI Holloway, Alisha/H-9574-2013 OI Holloway, Alisha/0000-0001-9810-389X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 2010 VL 211 IS 3 SU S BP S122 EP S122 PG 1 WC Surgery SC Surgery GA 648QI UT WOS:000281708600278 ER PT J AU Rovner, AJ Mehta, SN Haynie, DL Robinson, EM Pound, HJ Butler, DA Laffel, LM Nansel, TR AF Rovner, Alisha J. Mehta, Sanjeev N. Haynie, Denise L. Robinson, Elizabeth M. Pound, Heidi J. Butler, Deborah A. Laffel, Lori M. Nansel, Tonja R. TI Perceived Benefits, Barriers, and Strategies of Family Meals among Children with Type 1 Diabetes Mellitus and Their Parents: Focus-Group Findings SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID MEALTIME INTERACTIONS; DIETARY-INTAKE; ADOLESCENTS; PATTERNS; QUALITY AB Dietary management of type 1 diabetes mellitus has become much less restrictive and more flexible in recent years due to contemporary insulin regimens, which may afford families of children with type 1 diabetes mellitus greater ease in sharing family meals. Although these treatment advancements might facilitate family meals, overall demands of diabetes management can influence family's perceived or actual ability to do so Youths with type 1 diabetes mellitus (ages 8 to 20 years) and parents participated in separate focus groups Thirty-five youths with type 1 diabetes mellitus (mean age=15 1 +/- 3 6 years) and their parents participated in 21 focus groups (12 youth groups, nine parent groups) Although there was substantial variability in how often family meals occurred, both parents and youths consistently perceived family meals as valuable and enjoyable. The major barrier to family meals discussed by both youths and parents was busy schedules Strategies for having family meals that were discussed by parents included shopping to ensure availability of the foods needed to prepare meals, planning, and cooking meals in advance, and using simplified cooking methods. These findings suggest that a family-focused approach to nutrition interventions in this population, as opposed to one targeting the child with diabetes only, can improve the chance for successful dietary change J AM Diet Assoc. 2010,110 1302-1306. C1 [Rovner, Alisha J.; Nansel, Tonja R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mehta, Sanjeev N.; Pound, Heidi J.; Laffel, Lori M.] Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. [Mehta, Sanjeev N.; Laffel, Lori M.] Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. [Mehta, Sanjeev N.; Butler, Deborah A.; Laffel, Lori M.] Harvard Univ, Sch Med, Boston, MA USA. [Butler, Deborah A.] Joslin Diabet Ctr, Pediat Programs, Boston, MA 02215 USA. [Robinson, Elizabeth M.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,7B13R,MSC 7510, Bethesda, MD 20892 USA. OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200703434C] FX This study was supported by the Intramural Research Program at the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, contract number HHSN267200703434C NR 15 TC 8 Z9 8 U1 2 U2 7 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 2010 VL 110 IS 9 BP 1302 EP 1306 DI 10.1016/j.jada.2010.06.010 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 645YG UT WOS:000281501500007 PM 20800121 ER PT J AU Ruby, CM Hanlon, JT Boudreau, RM Newman, AB Simonsick, EM Shorr, RI Bauer, DC Resnick, NM AF Ruby, Christine M. Hanlon, Joseph T. Boudreau, Robert M. Newman, Anne B. Simonsick, Eleanor M. Shorr, Ronald I. Bauer, Douglas C. Resnick, Neil M. CA Hlth Aging Body Composition Study TI The Effect of Medication Use on Urinary Incontinence in Community-Dwelling Elderly Women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE aged; urinary incontinence; medications; pharmacoepidemiology ID BODY-COMPOSITION; OLDER PERSONS; HEALTH; RISK; ESTROGEN; THERAPY; ADULTS AB OBJECTIVES To evaluate whether use of certain medications with potential urological effects is associated with development of incident urinary incontinence in community-resident older women. DESIGN Longitudinal cohort study. SETTING Pittsburgh, PA, and Memphis, TN. PARTICIPANTS Nine hundred fifty-nine healthy black and white women aged 65 and older enrolled in the Health, Aging and Body Composition Study without baseline (Year 1) self-reported urinary incontinence. MEASUREMENTS Use of alpha blockers, anticholinergics, central nervous system medications (opioids, benzodiazepines, antidepressants, antipsychotics), diuretics (thiazide, loop, potassium sparing), and estrogen (all dosage forms) was determined during Year 3 interviews. Self-reported incident (>= weekly) incontinence in during the previous 12 months was assessed at Year 4 interviews. RESULTS Overall, 20.5% of these women reported incident incontinence at Year 4 (3 years from baseline). The most common medication used with potential urological activity was a thiazide diuretic (24.3%), followed by estrogen (22.2%); alpha blockers were the least commonly used (2.3%). Multivariable logistic regression analyses revealed that current users of alpha blockers (adjusted odds ratio (AOR)=4.98, 95% confidence interval (CI)=1.96-12.64) and estrogen (AOR=1.60, 95% CI=1.08-2.36) had a greater risk of urinary incontinence than nonusers. There was no greater risk (P >.05) of urinary incontinence with the current use of anticholinergics, central nervous system medications, or diuretics. No statistically significant race-by-medication use interactions were found (all P >.05). CONCLUSION These results corroborate earlier reports that, in elderly women, use of alpha blockers or estrogens is associated with risk of self-reported incident urinary incontinence. C1 [Ruby, Christine M.; Hanlon, Joseph T.; Newman, Anne B.; Resnick, Neil M.] Univ Pittsburgh, Dept Geriatr Med, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Ruby, Christine M.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.; Boudreau, Robert M.; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Hanlon, Joseph T.] Pittsburgh Vet Affairs Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Hanlon, Joseph T.] Pittsburgh Vet Affairs Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. [Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Gainesville, FL USA. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Hanlon, JT (reprint author), Univ Pittsburgh, Dept Geriatr Med, Grad Sch Publ Hlth, Kaufman Med Bldg,Suite 514,3471 5th Ave, Pittsburgh, PA 15213 USA. EM jth14@pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187 FU National Institute of Aging [R01AG027017, P30AG024827, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, T32AG021885, K07AG033174, R01AG034056] FX This study was primarily supported by National Institute of Aging Grants R01AG027017, P30AG024827, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, T32AG021885, K07AG033174, and R01AG034056. This research was supported in part by the Intramural Research Program of the National Institute on Aging. NR 27 TC 16 Z9 17 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2010 VL 58 IS 9 BP 1715 EP 1720 DI 10.1111/j.1532-5415.2010.03006.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646NM UT WOS:000281549000013 PM 20670377 ER PT J AU Sallinen, J Stenholm, S Rantanen, T Heliovaara, M Sainio, P Koskinen, S AF Sallinen, Janne Stenholm, Sari Rantanen, Taina Heliovaara, Markku Sainio, Paivi Koskinen, Seppo TI Hand-Grip Strength Cut Points to Screen Older Persons at Risk for Mobility Limitation SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE muscle strength; functional capacity; mobility; body mass index; ROC analysis ID BODY-MASS INDEX; MUSCLE STRENGTH; WALKING LIMITATION; GRIP STRENGTH; HEALTH; ADULTS; WOMEN; DISABILITY; PREDICTOR; SPEED AB OBJECTIVES To determine optimal hand-grip strength cut points for likelihood of mobility limitation in older people and to study whether these cut points differ according to body mass index (BMI). DESIGN Cross-sectional analysis of data. SETTING Data collected in the Finnish population-based Health 2000 Survey. PARTICIPANTS One thousand eighty-four men and 1,562 women aged 55 and older with complete data on anthropometry, hand-grip strength and self-reported mobility. MEASUREMENTS Mobility limitation was defined as difficulty walking 0.5 km or climbing stairs. Receiver operating characteristic analysis was used to estimate hand-grip strength cut points for likelihood of mobility limitation. RESULTS The overall hand-grip strength cut points for likelihood of mobility limitation were 37 kg (sensitivity 62%; specificity 76%) for men and 21 kg (sensitivity 67%; specificity 73%) for women. The effect of the interaction between hand-grip strength and BMI on mobility limitation was significant in men (P=.02), but no such interaction was observed in women (P=.16). In men, the most-optimal cutoff points were 33 kg (sensitivity 73%; specificity 79%) for normal-weight men, 39 kg (sensitivity 67%; specificity 71%) for overweight men, and 40 kg (sensitivity 57%; specificity 68%) for obese men. In women, BMI-specific hand-grip strength cutoff values was not markedly more accurate than the overall cutoff value. CONCLUSION The hand-grip strength test is a useful tool to identify persons at risk of mobility limitation. In men, hand-grip strength cut points for mobility increased with BMI, whereas in women, only one hand-grip strength threshold was identified. C1 [Sallinen, Janne] VTT Tech Res Ctr Finland, FIN-70211 Kuopio, Finland. [Sallinen, Janne; Rantanen, Taina] Univ Jyvaskyla, Gerontol Res Ctr, Dept Hlth Sci, Jyvaskyla, Finland. [Stenholm, Sari; Heliovaara, Markku; Sainio, Paivi; Koskinen, Seppo] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Hlth, Helsinki, Finland. [Stenholm, Sari] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Sallinen, J (reprint author), VTT Tech Res Ctr Finland, POB 1199, FIN-70211 Kuopio, Finland. EM janne.sallinen@vtt.fi RI Stenholm, Sari/G-6940-2011; Rantanen, Taina/O-6579-2016 OI Rantanen, Taina/0000-0002-1604-1945 FU Ministry of Education, Finland; National Institutes of Health, National Institute on Aging; Finnish Academy [125494] FX Janne Sallinen was supported by a research grant from the Ministry of Education, Finland. This research was also supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging, and by a grant from the Finnish Academy (125494, Sari Stenholm). NR 29 TC 50 Z9 54 U1 3 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2010 VL 58 IS 9 BP 1721 EP 1726 DI 10.1111/j.1532-5415.2010.03035.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646NM UT WOS:000281549000014 PM 20863331 ER PT J AU Mork, JG Bodenreider, O Demner-Fushman, D Dogan, RI Lang, FM Lu, ZY Neveol, A Peters, L Shooshan, SE Aronson, AR AF Mork, James G. Bodenreider, Olivier Demner-Fushman, Dina Dogan, Rezarta Islamaj Lang, Francois-Michel Lu, Zhiyong Neveol, Aurelie Peters, Lee Shooshan, Sonya E. Aronson, Alan R. TI Extracting Rx information from clinical narrative SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID SYSTEM AB Objective The authors used the i2b2 Medication Extraction Challenge to evaluate their entity extraction methods, contribute to the generation of a publicly available collection of annotated clinical notes, and start developing methods for ontology-based reasoning using structured information generated from the unstructured clinical narrative. Design Extraction of salient features of medication orders from the text of de-identified hospital discharge summaries was addressed with a knowledge-based approach using simple rules and lookup lists. The entity recognition tool, Meta Map, was combined with dose, frequency, and duration modules specifically developed for the Challenge as well as a prototype module for reason identification. Measurements Evaluation metrics and corresponding results were provided by the Challenge organizers. Results The results indicate that robust rule-based tools achieve satisfactory results in extraction of simple elements of medication orders, but more sophisticated methods are needed for identification of reasons for the orders and durations. Limitations Owing to the time constraints and nature of the Challenge, some obvious follow-on analysis has not been completed yet. Conclusions The authors plan to integrate the new modules with Meta Map to enhance its accuracy. This integration effort will provide guidance in retargeting existing tools for better processing of clinical text. C1 [Mork, James G.; Bodenreider, Olivier; Demner-Fushman, Dina; Lang, Francois-Michel; Peters, Lee; Shooshan, Sonya E.; Aronson, Alan R.] NIH, LHNCBC, US Natl Lib Med, Bethesda, MD 20892 USA. [Dogan, Rezarta Islamaj; Lu, Zhiyong; Neveol, Aurelie] NIH, NCBI, US Natl Lib Med, Bethesda, MD 20892 USA. RP Aronson, AR (reprint author), Natl Lib Med, Bldg 38A,Room 9N-905,8600 Rockville Pike,MSC-3826, Bethesda, MD 20894 USA. EM alan@nlm.nih.gov FU National Library of Medicine [U54LM008748] FX This work was supported by the Intramural Research Program of the NIH, National Library of Medicine. The project described was supported in part by the i2b2 initiative, Award Number U54LM008748 from the National Library of Medicine. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine or the National Institutes of Health. NR 19 TC 11 Z9 11 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2010 VL 17 IS 5 BP 536 EP 539 DI 10.1136/jamia.2010.003970 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 652AM UT WOS:000281972200010 PM 20819859 ER PT J AU Wilcke, JR Green, JM Spackman, KA Martin, MK Case, JT Santamaria, SL Zimmerman, K AF Wilcke, Jeffrey R. Green, Julie M. Spackman, Kent A. Martin, Michael K. Case, James T. Santamaria, Suzanne L. Zimmerman, Kurt TI Concerning SNOMED-CT content for public health case reports SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Letter C1 [Wilcke, Jeffrey R.; Green, Julie M.; Santamaria, Suzanne L.; Zimmerman, Kurt] Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. [Spackman, Kent A.] Int Hlth Terminol SOD, Copenhagen, Denmark. [Martin, Michael K.] Clemson Livestock Poultry Hlth, Columbia, SC USA. [Case, James T.] NIH, SNOMED CT, Natl Lib Med, Bethesda, MD 20892 USA. RP Wilcke, JR (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. EM jwilcke@vt.edu RI zimmerman, Kurt/J-5601-2016 OI zimmerman, Kurt/0000-0002-8899-2301 NR 1 TC 3 Z9 3 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2010 VL 17 IS 5 BP 613 EP 613 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 652AM UT WOS:000281972200025 PM 20842802 ER PT J AU Florin, DA Lawyer, P Rowton, E Schultz, G Wilkerson, R Davies, SJ Lipnick, R Keep, L AF Florin, David A. Lawyer, Phillip Rowton, Edgar Schultz, George Wilkerson, Richard Davies, Stephen J. Lipnick, Robert Keep, Lisa TI POPULATION DYNAMICS OF LUTZOMYIA SHANNONI (DIPTERA: PSYCHODIDAE) AT THE PATUXENT NATIONAL WILDLIFE RESEARCH REFUGE, MARYLAND SO JOURNAL OF THE AMERICAN MOSQUITO CONTROL ASSOCIATION LA English DT Article DE Sand fly; Lutzomyia shannoni; seasonal abundance; Patuxent NWRR; Ossabaw Island; San Felasco Hammock Preserve State Park AB The seasonal abundance and temporal patterns of the adult sand fly (Lutzomyia shannoni Dyar) were examined at the Patuxent National Wildlife Research Refuge, MD, from August 3, 2005, to July 29, 2006. A total of 138 (53 males, 85 females) L. shannoni was collected from 4 dry ice-baited traps set at the same 4 locations throughout the study. The male: female ratio was 1: 2.4. All 4 traps, separated by a maximum distance of approximately 1.6 km, operated simultaneously on the collection dates. The collection dates were spaced apart by near weekly intervals during the months of expected sand fly activity. No collections occurred in December-February. August was clearly the period of peak adult abundance as the numbers collected were significantly greater during this month than any other month of collection. Results indicate the existence of a unimodal pattern of abundance with adult emergence beginning in June and ending by September. The temporal pattern and abundance differ from what has been observed for the species on Ossabaw Island, a barrier island located along coastal Georgia, and at San Felasco Hammock Preserve State Park, Gainesville, FL. Continued research is needed to compile multiyear data to confirm the temporal abundance patterns of this species in Maryland. C1 [Florin, David A.; Schultz, George; Davies, Stephen J.; Keep, Lisa] Univ Hlth Sci, Uniformed Serv, Dept Prevent Med & Biometr, Bethesda, MD USA. [Lawyer, Phillip] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Rowton, Edgar; Wilkerson, Richard] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. [Lipnick, Robert] Armed Forces Hlth Surveillance Ctr, Silver Spring, MD 20910 USA. RP Florin, DA (reprint author), Univ Hlth Sci, Uniformed Serv, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD USA. FU United States Fish and Wildlife Service; Uniformed Services University of the Health Sciences [R087WB] FX We gratefully acknowledge Holliday H. Obrecht III, Wildlife Biologist, United States Fish and Wildlife Service, Region 5, Patuxent Research Refuge, for his assistance and support of this project. This research was funded by the Uniformed Services University of the Health Sciences intramural grant R087WB: Risk for domestic transmission of leishmaniasis acquired by US service members in Iraq/Afghanistan. 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 Navy, Department of Defense, or the US Government. This work was prepared as part of official military duties of the lead author. Title 17 U.S.C. 1105 provides that 'Copyright protection under this title is not available for any work of the United States Government.' Title 17 U.S.C. 1101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person's official duties. NR 13 TC 0 Z9 0 U1 0 U2 3 PU AMER MOSQUITO CONTROL ASSOC PI MOUNT LAUREL PA 15000 COMMERCE PARKWAY, SUITE C, MOUNT LAUREL, NJ 08054 USA SN 8756-971X J9 J AM MOSQUITO CONTR JI J. Am. Mosq. Control Assoc. PD SEP PY 2010 VL 26 IS 3 BP 337 EP 339 DI 10.2987/10-6022.1 PG 3 WC Entomology SC Entomology GA V24DP UT WOS:000208391400015 PM 21033063 ER PT J AU Freedman, BI Kopp, JB Langefeld, CD Genovese, G Friedman, DJ Nelson, GW Winkler, CA Bowden, DW Pollak, MR AF Freedman, Barry I. Kopp, Jeffrey B. Langefeld, Carl D. Genovese, Giulio Friedman, David J. Nelson, George W. Winkler, Cheryl A. Bowden, Donald W. Pollak, Martin R. TI The Apolipoprotein L1 (APOL1) Gene and Nondiabetic Nephropathy in African Americans SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; MYH9; POLYMORPHISMS; HYPERTENSION AB Mapping by admixture linkage disequilibrium (LD) detected strong association between nonmuscle myosin heavy chain 9 gene (MYH9) variants on chromosome 22 and nondiabetic nephropathy in African Americans. MYH9-related variants were posited to be the probable, but not necessarily the definitive, causal variants as a result of impressive statistical evidence of association, renal expression, and a role in autosomal dominant MYH9 disorders characterized by progressive glomerulosclerosis (Epstein and Fechtner syndromes). Dense mapping within MYH9 revealed striking LD patterns and racial variation in risk allele frequencies, suggesting population genetic factors such as selection may be operative in this region. Genovese and colleagues examined large chromosomal regions adjacent to MYH9 using genome-wide association methods and non-HapMap single nucleotide polymorphisms identified in Yoruba from the 1000 Genomes project. Statistically stronger associations were detected between two independent sequence variants in the Apolipoprotein L1 gene (APOL1) and nondiabetic nephropathy in African Americans, with odds ratios of 10.5 in idiopathic FSGS and 7.3 in hypertension-attributed ESRD. These kidney disease risk variants likely rose to high frequency in Africa because they confer resistance to trypanosomal infection and protect from African sleeping sickness. Risk variants in MYH9 and APOL1 are in strong LD, and the genetic risk that was previously attributed to MYH9 may reside, in part or in whole, in APOL1, although more complex models of risk cannot be excluded. This association likely explains racial disparities in nondiabetic nephropathy as a result of the high prevalence of risk alleles in individuals of African ancestry. C1 [Freedman, Barry I.] Wake Forest Univ, Nephrol Sect, Sch Med, Dept Internal Med Nephrol, Winston Salem, NC 27157 USA. [Langefeld, Carl D.] Wake Forest Univ, Dept Publ Hlth Sci Biostat Sci, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Dept Biochem, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Ctr Diabet Res, Sch Med, Winston Salem, NC 27157 USA. [Bowden, Donald W.] Wake Forest Univ, Ctr Human Genom, Sch Med, Winston Salem, NC 27157 USA. [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. [Genovese, Giulio; Friedman, David J.] Beth Israel Deaconess Med Ctr, Dept Internal Med Nephrol, Boston, MA 02215 USA. [Genovese, Giulio; Friedman, David J.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Winkler, Cheryl A.] NIH, Basic Res Lab, Frederick, MD USA. [Nelson, George W.] SAIC Natl Canc Inst, NIH, Frederick, MD USA. [Pollak, Martin R.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. RP Freedman, BI (reprint author), Wake Forest Univ, Nephrol Sect, Sch Med, Dept Internal Med Nephrol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM bfreedma@wfubmc.edu; mpollak@bidmc.harvard.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU National Institutes of Health [RO1 DK54931, K08-DK076868, RO1 DK066358, RO1 DK053591, RO1 HL56266, RO1 DK070941, RO1 DK084149]; NIDDK; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; Genes Environment and Health Initiative FX This work was supported by grants from the National Institutes of Health (RO1 DK54931 to M.R.P.; K08-DK076868 to D.J.F.; RO1 DK066358 and RO1 DK053591 to D.W.B.; and RO1 HL56266, RO1 DK070941, and RO1 DK084149 to B.I.F.) and funding from the NIDDK Intramural Research Program (J.B.K.). This project was also been funded in part by federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E and by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, and a Genes Environment and Health Initiative Award (C.A.W.). NR 18 TC 127 Z9 132 U1 3 U2 6 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2010 VL 21 IS 9 BP 1422 EP 1426 DI 10.1681/ASN.2010070730 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 669JZ UT WOS:000283345000008 PM 20688934 ER PT J AU Hurst, FP Abbott, KC Raj, D Krishnan, M Palant, CE Agodoa, LY Jindal, RM AF Hurst, Frank P. Abbott, Kevin C. Raj, Dominic Krishnan, Mahesh Palant, Carlos E. Agodoa, Lawrence Y. Jindal, Rahul M. TI Arteriovenous Fistulas among Incident Hemodialysis Patients in Department of Defense and Veterans Affairs Facilities SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VASCULAR ACCESS USE; UNITED-STATES; COST-ANALYSIS; SURVIVAL; CARE; OUTCOMES; QUALITY; CHOICE; SYSTEM; IMPACT AB A higher proportion of patients initiate hemodialysis (HD) with an arteriovenous fistula (AVF) in countries with universal health care systems compared with the United States. Because federally sponsored national health care organizations in the United States, such as the Department of Veterans Affairs (DVA) and the Department of Defense (DoD), are similar to a universal health care model, we studied AVF use within these organizations. We used the US Renal Data System database to perform a cross-sectional analysis of patients who initiated HD between 2005 and 2006. Patients who received predialysis nephrology care had 10-fold greater odds of initiating dialysis with an AVF (adjusted odds ratio [aOR] 10.3; 95% confidence interval [CI] 9.6 to 11.1). DVA/DoD insurance also independently associated with initiating HD with an AVF (aOR 1.4; 95% CI 1.2 to 1.5). Fewer patients initiated HD at a DoD facility, but these patients were also approximately twice as likely to use an AVF (aOR 2.3; 95% CI 1.2 to 4.6). In conclusion, patients in DVA/DoD systems are significantly more likely to use an AVF at initiation of HD than patients with other insurance types, including Medicare. Further study of these federal systems may identify practices that could improve processes of care across health care systems to increase the number of patients who initiate HD with an AVF. C1 [Hurst, Frank P.] Walter Reed Army Med Ctr, Dept Med Nephrol, Serv Nephrol, Washington, DC 20037 USA. [Jindal, Rahul M.] Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20037 USA. [Hurst, Frank P.; Abbott, Kevin C.; Jindal, Rahul M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. [Raj, Dominic; Palant, Carlos E.; Jindal, Rahul M.] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC USA. [Krishnan, Mahesh] Davita Clin Res, Washington, DC USA. [Palant, Carlos E.] Vet Affairs Med Ctr, Serv Nephrol, Washington, DC 20422 USA. [Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Jindal, Rahul M.] Brookdale Univ, Dept Surg, Med Ctr, Brooklyn, NY USA. RP Hurst, FP (reprint author), Walter Reed Army Med Ctr, Dept Med Nephrol, Serv Nephrol, 6900 Georgia Ave NW, Washington, DC 20037 USA. EM frank.hurst@us.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 24 TC 19 Z9 19 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2010 VL 21 IS 9 BP 1571 EP 1577 DI 10.1681/ASN.2010010025 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 669JZ UT WOS:000283345000024 PM 20705713 ER PT J AU Linnoila, RI AF Linnoila, R. Ilona TI From Nicotine to Breast Cancer, Implications of Cholinergic Receptor Pathway SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LUNG-CANCER; ACETYLCHOLINE-RECEPTORS; CELLS; EXPRESSION; LOCUS; SMOKE C1 NCI, Expt Pathol Sect, Cell & Canc Biol Branch, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA. RP Linnoila, RI (reprint author), NCI, Expt Pathol Sect, Cell & Canc Biol Branch, Ctr Canc Res,Natl Inst Hlth, Convent Dr 37,Rm 1056B, Bethesda, MD 20892 USA. EM linnoili@mail.nih.gov NR 23 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP PY 2010 VL 102 IS 17 BP 1298 EP U11 DI 10.1093/jnci/djq314 PG 2 WC Oncology SC Oncology GA 648UK UT WOS:000281719600001 PM 20733119 ER PT J AU Cook, MB Kamangar, F Whiteman, DC Freedman, ND Gammon, MD Bernstein, L Brown, LM Risch, HA Ye, W Sharp, L Pandeya, N Webb, PM Wu, AH Ward, MH Giffen, C Casson, AG Abnet, CC Murray, LJ Corley, DA Nyren, O Vaughan, TL Chow, WH AF Cook, Michael B. Kamangar, Farin Whiteman, David C. Freedman, Neal D. Gammon, Marilie D. Bernstein, Leslie Brown, Linda M. Risch, Harvey A. Ye, Weimin Sharp, Linda Pandeya, Nirmala Webb, Penelope M. Wu, Anna H. Ward, Mary H. Giffen, Carol Casson, Alan G. Abnet, Christian C. Murray, Liam J. Corley, Douglas A. Nyren, Olof Vaughan, Thomas L. Chow, Wong-Ho TI Cigarette Smoking and Adenocarcinomas of the Esophagus and Esophagogastric Junction: A Pooled Analysis From the International BEACON Consortium SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GASTRIC CARDIA CARCINOMAS; MODELING TOTAL EXPOSURE; GASTROESOPHAGEAL-REFLUX; UNITED-STATES; LUNG-CANCER; RISK-FACTORS; BARRETTS-ESOPHAGUS; TOBACCO USE; BODY-MASS; ALCOHOL AB Background Previous studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose-response, and duration of cigarette smoking cessation. Methods We used primary data from 10 population-based case-control studies and two cohort studies from the Barrett's Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided. Results The summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose-response association between pack-years of cigarette smoking and each outcome (P < .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (< 10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and >= 10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar. Conclusions Cigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks. C1 [Cook, Michael B.; Kamangar, Farin; Freedman, Neal D.; Ward, Mary H.; Abnet, Christian C.; Chow, Wong-Ho] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD 20852 USA. [Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA. [Whiteman, David C.; Pandeya, Nirmala; Webb, Penelope M.] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia. [Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Duarte, CA 91010 USA. [Bernstein, Leslie] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Brown, Linda M.] RTI Int, Stat & Epidemiol Div, Rockville, MD USA. [Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Ye, Weimin; Nyren, Olof] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Sharp, Linda] Natl Canc Registry Ireland, Cork, Ireland. [Wu, Anna H.] USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. [Giffen, Carol] Informat Management Serv Inc, Bethesda, MD USA. [Casson, Alan G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada. [Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res, Belfast, Antrim, North Ireland. [Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA. [Corley, Douglas A.] Kaiser Permanente, Oakland Med Ctr, Oakland, CA USA. [Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Natl Inst Hlth,Dept Hlth & Human Serv, 6120 Execut Blvd EPS,Ste 550,Rm 5030, Bethesda, MD 20852 USA. EM michael.cook@nih.gov RI Whiteman, David/P-2728-2014; Pandeya, Nirmala/F-8054-2010; Cook, Michael/A-5641-2009; Webb, Penelope/D-5736-2013; Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015 OI Whiteman, David/0000-0003-2563-9559; Pandeya, Nirmala/0000-0003-1462-4968; Cook, Michael/0000-0002-0533-7302; Webb, Penelope/0000-0003-0733-5930; Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098 FU National Institutes of Health (NIH) [R01 DK063616, R21DKO77742]; Intramural Program of the NIH; Chief Scientist Office (Scotland); Locally Organised Research Scheme (East Anglia); Special Trustees of the Nottingham University Hospitals; Medical Research Council; California Tobacco-Related Research Program [3RT-0122, 10RT-0251]; National Cancer Institute [CA59636]; Nova Scotia Health Research Foundation [N419]; Northern Ireland Research and Development Office; Health Research Board, Ireland; Queensland Cancer Fund; National Health and Medical Research Council of Australia [199600]; [R01-CA30022]; [R37-CA41530]; [U01-CA57949]; [U01-CA57983]; [U01-CA57923]; [R01 CA57947-03] FX This work was supported in part by the Intramural Program of the National Institutes of Health (NIH). The Population Health Study was funded by the Intramural Program of the NIH. The Larynx, Esophagus, and Oral Cavity Study was funded by R01-CA30022 and R37-CA41530 (both awarded to T.L.V., David Thomas, Scott Davis, Bonnie Worthington Roberts, Ruth Little, and Mary Rogers). The US Multi-Center Study was funded by U01-CA57949 (awarded to T.L.V.), U01-CA57983 (awarded to M.D.G.), and U01-CA57923 (awarded to H.A.R). The Swedish Esophageal Cancer Study was funded by R01 CA57947-03 (awarded to O.N. and Hans-Olov Adami). The United Kingdom Study of Oesophageal Cancer in Women was funded by Chief Scientist Office (Scotland) (awarded to Patricia McKinney), the Locally Organised Research Scheme (East Anglia) (awarded to Nick E. Day), Special Trustees of the Nottingham University Hospitals (awarded to Clair Chilvers), and the Medical Research Council (awarded to Paula Cook Mozaffari). The Los Angeles County Multi-ethnic Case-control Study was funded by 3RT-0122 ("Smoking and Risk of Proximal Vs. Distal Gastric Cancer," awarded to A.H.W.) and 10RT-0251 ("Smoking, microsatellite instability & gastric cancers," awarded to A.H.W.) from the California Tobacco-Related Research Program and CA59636 (awarded to L.B.) from the National Cancer Institute. The Nebraska Health Study was funded by the Intramural Program of the NIH. The Nova Scotia Barrett Esophagus Study was supported by the Nova Scotia Health Research Foundation (" Molecular mechanisms and lifestyle risk factor interactions in the pathogenesis of human esophageal adenocarcinoma," N419, to A.G.C.). The Factors Influencing the Barrett's Adenocarcinoma Relationship Study was funded by an Ireland-Northern Ireland Co-operation Research Project Grant sponsored by the Northern Ireland Research and Development Office, and the Health Research Board, Ireland (All-Ireland case-control study of Oesophageal Adenocarcinoma and Barrett's Oesophagus, awarded to L.J.M. and Harry Comber); The Australian Cancer Study was supported by the Queensland Cancer Fund and the National Health and Medical Research Council of Australia (Program no. 199600, awarded to D.C.W., Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie, and Penelope M. Webb). NIH-AARP was funded by the Intramural Program of the NIH. Reported analyses with the Kaiser-Permanente Multiphasic Health Checkup Study were funded by NIH R01 DK063616 (Epidemiology and Incidence of Barrett's Esophagus, Kaiser Permanente, awarded to D.A.C.) and NIH R21DKO77742 (Barrett's Esophagus: Risk Factors in Women, awarded to D.A.C. and Nicholas J. Shaheen). NR 54 TC 99 Z9 101 U1 0 U2 7 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 SEP PY 2010 VL 102 IS 17 BP 1344 EP 1353 DI 10.1093/jnci/djq289 PG 10 WC Oncology SC Oncology GA 648UK UT WOS:000281719600010 PM 20716718 ER PT J AU Freedman, ND Cross, AJ McGlynn, KA Abnet, CC Park, Y Hollenbeck, AR Schatzkin, A Everhart, JE Sinha, R AF Freedman, Neal D. Cross, Amanda J. McGlynn, Katherine A. Abnet, Christian C. Park, Yikyung Hollenbeck, Albert R. Schatzkin, Arthur Everhart, James E. Sinha, Rashmi TI Association of Meat and Fat Intake With Liver Disease and Hepatocellular Carcinoma in the NIH-AARP Cohort SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; HEALTH-AMERICAN-ASSOCIATION; RETIRED-PERSONS DIET; HEPATITIS-C; IRON OVERLOAD; NATIONAL-INSTITUTES; UNITED-STATES; RISK-FACTORS; CANCER; CARCINOGENESIS AB Background Several plausible mechanisms, including fat, iron, heterocyclic amines, and N-nitroso compounds, link meat intake with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Few studies have investigated these associations. Methods We prospectively examined the relationship between meat and associated exposures with CLD mortality (n = 551; not including HCC) and HCC incidence (n = 338) in 495 006 men and women of the National Institutes of Health-AARP Diet and Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the fifth (Q5) vs the first (Q1) quintile were estimated from multivariable adjusted Cox proportional hazards regression models. All tests of statistical significance were two-sided. Results We found inverse associations between white meat and risk of CLD (HR = 0.52, 95% CI = 0.39 to 0.70, 7.5 vs 18.2 cases per 100 000 person-years) and HCC (HR = 0.52, 95% CI = 0.36 to 0.77, 5.8 vs 14.3 cases per 100 000 person-years). Red meat was associated with higher risk of CLD (HR = 2.59, 95% CI = 1.86 to 3.61, 22.3 vs 6.2 cases per 100 000 person-years) and HCC (HR = 1.74, 95% CI = 1.16 to 2.61, 14.9 vs 5.7 cases per 100 000 person-years). Among fat types, results were strongest for saturated fat (for CLD, HR = 3.50, 95% CI = 2.48 to 4.96, 23.0 vs 6.5 cases per 100 000 person-years; for HCC, HR = 1.87, 95% CI = 1.23 to 2.85, 14.5 vs 6.3 cases per 100 000 person-years). After mutual adjustment, risk estimates persisted for saturated fat, red meat, and white meat. Heme iron, processed meat, nitrate, and nitrite were positively associated with CLD but not with HCC. Individual heterocyclic amines, 2-amino-3,4,8-trimethylimidazo[4,5,-f] quinoxaline (DiMeIQx), 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b] pyridine (PhIP), were not associated with either outcome. Conclusion Our results suggest that red meat and saturated fat may be associated with increased CLD and HCC risk, whereas white meat may be associated with reduced risk. C1 [Freedman, Neal D.; Cross, Amanda J.; McGlynn, Katherine A.; Abnet, Christian C.; Park, Yikyung; Schatzkin, Arthur; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv,Nutr Epidemiol Branch, Rockville, MD 20852 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv,Nutr Epidemiol Branch, 6120 Execut Blvd,Rm 320,MSC 7361, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098; Park, Yikyung/0000-0002-6281-489X FU National Institutes of Health; Division of Cancer Epidemiology and Genetics; National Cancer Institute; Department of Health and Human Services FX Intramural Research Program of the National Institutes of Health, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services. NR 45 TC 38 Z9 39 U1 1 U2 8 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 SEP PY 2010 VL 102 IS 17 BP 1354 EP 1365 DI 10.1093/jnci/djq301 PG 12 WC Oncology SC Oncology GA 648UK UT WOS:000281719600011 PM 20729477 ER PT J AU Tosato, G Segarra, M Salvucci, O AF Tosato, Giovanna Segarra, Marta Salvucci, Ombretta TI Cytosolic Phospholipase A2 alpha and Cancer: A Role in Tumor Angiogenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID A(2); LUNG; MICE; CELLS; TUMORIGENESIS; ACTIVATION; A(2)-ALPHA; INHIBITORS; DEFICIENT; RESISTANT C1 [Tosato, Giovanna; Segarra, Marta; Salvucci, Ombretta] NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4124, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov NR 29 TC 20 Z9 20 U1 0 U2 2 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 SEP PY 2010 VL 102 IS 18 BP 1377 EP 1379 DI 10.1093/jnci/djq324 PG 3 WC Oncology SC Oncology GA 654OA UT WOS:000282176600002 PM 20729476 ER PT J AU Linkous, AG Yazlovitskaya, EM Hallahan, DE AF Linkous, Amanda G. Yazlovitskaya, Eugenia M. Hallahan, Dennis E. TI Cytosolic Phospholipase A2 and Lysophospholipids in Tumor Angiogenesis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CELL LUNG-CANCER; LYSOPHOSPHATIDIC ACID PRODUCTION; GROWTH-FACTOR EXPRESSION; ARACHIDONIC-ACID; IN-VIVO; SIGNALING PATHWAYS; ENDOTHELIAL-CELLS; MALIGNANT GLIOMAS; BLOOD-VESSELS; DRUG TARGETS AB Background Lung cancer and glioblastoma multiforme are highly angiogenic and, despite advances in treatment, remain resistant to therapy. Cytosolic phospholipase A2 (cPLA(2)) activation contributes to treatment resistance through transduction of prosurvival signals. We investigated cPLA(2) as a novel molecular target for antiangiogenesis therapy. Methods Glioblastoma (GL261) and Lewis lung carcinoma (LLC) heterotopic tumor models were used to study the effects of cPLA(2) expression on tumor growth and vascularity in C57/BL6 mice wild type for (cPLA(2)alpha(+/+)) or deficient in (cPLA(2)alpha(-/-)) cPLA(2)alpha, the predominant isoform in endothelium (n = 6-7 mice per group). The effect of inhibiting cPLA(2) activity on GL261 and LLC tumor growth was studied in mice treated with the chemical cPLA(2) inhibitor 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy] benzoic acid (CDIBA). Endothelial cell proliferation and function were evaluated by Ki-67 immunofluorescence and migration assays in primary cultures of murine pulmonary microvascular endothelial cells (MPMEC) isolated from cPLA(2)alpha(+/+) and cPLA(2)alpha(-/-) mice. Proliferation, invasive migration, and tubule formation were assayed in mouse vascular endothelial 3B-11 cells treated with CDIBA. Effects of lysophosphatidylcholine, arachidonic acid, and lysophosphatidic acid (lipid mediators of tumorigenesis and angiogenesis) on proliferation and migration were examined in 3B-11 cells and cPLA(2)alpha(-/-) MPMEC. All statistical tests were two-sided. Results GL261 tumor progression proceeded normally in cPLA(2)alpha(+/+) mice, whereas no GL261 tumors formed in cPLA(2)alpha(-/-) mice. In the LLC tumor model, spontaneous tumor regression was observed in 50% of cPLA(2)alpha(-/-) mice. Immunohistochemical examination of the remaining tumors from cPLA(2)alpha(-/-) mice revealed attenuated vascularity (P <= .001) compared with tumors from cPLA(2)alpha(+/+) mice. Inhibition of cPLA(2) activity by CDIBA resulted in a delay in tumor growth (eg, LLC model: average number of days to reach tumor volume of 700 mm(3), CDIBA vs vehicle: 16.8 vs 11.8, difference = 5, 95% confidence interval = 3.6 to 6.4, P = .04) and a decrease in tumor size (eg, GL261 model: mean volume on day 21, CDIBA vs vehicle: 40.1 vs 247.4 mm(3), difference = 207.3 mm(3), 95% confidence interval = 20.9 to 293.7 mm(3), P = .021). cPLA(2) deficiency statistically significantly reduced MPMEC proliferation and invasive migration (P = .002 and P = .004, respectively). Compared with untreated cells, cPLA(2)alpha(-/-) MPMEC treated with lysophosphatidylcholine and lysophosphatidic acid displayed increased cell proliferation (P = .011) and invasive migration (P < .001). Conclusions In these mouse models of brain and lung cancer, cPLA(2) and lysophospholipids have key regulatory roles in tumor angiogenesis. cPLA(2) inhibition may be a novel effective antiangiogenic therapy. C1 [Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA. [Yazlovitskaya, Eugenia M.] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Linkous, Amanda G.] NIH, Neurooncol Branch, Bethesda, MD 20892 USA. [Hallahan, Dennis E.] Washington Univ, Alvin Siteman Canc Ctr, St Louis, MO 63130 USA. [Hallahan, Dennis E.] Washington Univ, Dept Radiat Oncol, St Louis, MO USA. RP Yazlovitskaya, EM (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, C3210 Med Ctr N 1161 21st Ave S, Nashville, TN 37232 USA. EM eugenia.yazlovitskaya@vanderbilt.edu; dhallahan@radonc.wustl.edu FU National Institutes of Health (Washington, DC) [R01-140220, R01-CA112385, R01-CA88076]; Elsa U. Pardee foundation (Midland, MI) FX Elizabeth H. and James S. McDonnell Distinguished Professorship and National Institutes of Health (Washington, DC; R01-140220; R01-CA112385 and R01-CA88076 to D.E.H.); Elsa U. Pardee foundation (Midland, MI) (E.M.Y.). NR 66 TC 44 Z9 44 U1 2 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP PY 2010 VL 102 IS 18 BP 1398 EP 1412 DI 10.1093/jnci/djq290 PG 15 WC Oncology SC Oncology GA 654OA UT WOS:000282176600009 PM 20729478 ER PT J AU Petrim, I Zucali, PA Lee, HS Pineda, MA Meltzer, PS Walter-Rodriguez, B Roncalli, M Santoro, A Wang, YS Giaccone, G AF Petrim, Iacopo Zucali, Paolo A. Lee, Hye Seung Pineda, Marbin A. Meltzer, Paul S. Walter-Rodriguez, Beatriz Roncalli, Massimo Santoro, Armando Wang, Yisong Giaccone, Giuseppe TI Expression and Mutational Status of c-kit in Thymic Epithelial Tumors SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE c-kit; Thymic carcinoma; Thymoma ID GASTROINTESTINAL STROMAL TUMORS; CELL LUNG-CANCER; TYROSINE KINASE; IMATINIB MESYLATE; THYMOMA; CARCINOMA; RECEPTOR; OVEREXPRESSION; SPECTRUM; CD117 AB Background: Overexpression of c-kit, a tyrosine kinase receptor protein encoded by the protooncogene kit, has been previously reported in thymic epithelial tumors and in other neoplasms such as gastrointestinal stromal tumors, myeloproliferative disorders, melanoma, and seminoma Mutations in the kit gene have been related to response to imatinib in gastrointestinal stromal tumor and one case report of thymic carcinoma We studied expression of c-kit in a large retrospective series of thymic epithelial malignancies and sequenced the whole gene in a subset of patients Methods: Thymic epithelial tumors from 120 patients (13 thymic carcinomas and 107 thymomas) were examined Immunohistochemical staining with an antic-kit polyclonal antibody was performed on a tissue microarray Mutation analyses of exons 1 to 20 were conducted by direct DNA sequencing of polymerase chain reaction products in eight thymic carcinomas, five thymomas. and one thymic carcinoma cell line Results: The percentage of c-kit positive cells was significantly higher in thymic carcinoma (46%) than in thymoma (4%) Decreased disease-related survival and progression-flee survival were observed in c-kit positive tumors No mutations were detected Conclusion: c-kit expression is strongly but not exclusively related to thymic carcinoma histotype, and it is of prognostic value Mutations are very rare C1 [Giaccone, Giuseppe] NCI, Med Oncol Branch, Dept Med Oncol & Hematol, NIH, Bethesda, MD 20892 USA. [Zucali, Paolo A.; Roncalli, Massimo; Santoro, Armando] Ist Clin Humanitas IRCCS, Milan, Italy. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Dept Med Oncol & Hematol, NIH, Bethesda, MD 20892 USA. RI Lee, Hye Seung/G-6419-2011; Petrini, Iacopo/K-7316-2016; Giaccone, Giuseppe/E-8297-2017; OI Lee, Hye Seung/0000-0002-1667-7986; Petrini, Iacopo/0000-0002-7752-6866; Giaccone, Giuseppe/0000-0002-5023-7562; Roncalli, Massimo/0000-0002-7901-8910 FU NIH/NCI FX Supported by the NIH/NCI intramural program NR 36 TC 19 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1556-0864 EI 1556-1380 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD SEP PY 2010 VL 5 IS 9 BP 1447 EP 1453 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 647FJ UT WOS:000281602900021 PM 20651610 ER PT J AU Wing, RR West, DS Grady, D Creasman, JM Richter, HE Myers, D Burgio, KL Franklin, F Gorin, AA Vittinghoff, E Macer, J Kusek, JW Subak, LL AF Wing, Rena R. West, Delia Smith Grady, Deborah Creasman, Jennifer M. Richter, Holly E. Myers, Deborah Burgio, Kathryn L. Franklin, Frank Gorin, Amy A. Vittinghoff, Eric Macer, Judith Kusek, John W. Subak, Leslee L. TI Effect of Weight Loss on Urinary Incontinence in Overweight and Obese Women: Results at 12 and 18 Months SO JOURNAL OF UROLOGY LA English DT Article DE urinary incontinence; obesity; weight loss; behavior therapy; randomized controlled trial ID LIFE-STYLE INTERVENTION; QUALITY-OF-LIFE; RISK-FACTORS; PREVENTION; TRIAL; HEALTH AB Purpose: Initial weight loss improves urinary incontinence in overweight and obese women. In this study we examined the longer term effects of a weight loss intervention on urinary incontinence. Materials and Methods: Overweight and obese women (mean +/- SD age 53 +/- 10 years) with 10 or more urinary incontinence episodes weekly were randomized to an 18-month behavioral weight loss intervention (226) or control group (112). Outcome measures were collected at 12 and 18 months. Results: At baseline women had a mean body mass index of 36 +/- 6 kg/m(2) and reported a mean of 24 +/- 18 incontinence episodes weekly. Of the patients 86% completed 18-month measurements. The percent weight loss in the intervention group averaged 8.0%, 7.5% and 5.5% at 6, 12 and 18 months, respectively, vs approximately 1.5% in the control group (all values p <0.001). Compared with controls at 12 months the intervention group reported a greater percent reduction in weekly stress urinary incontinence episodes (65% vs 47%, p <0.001), and a greater proportion achieved at least a 70% decrease in weekly total and stress urinary incontinence episodes. At 18 months a greater proportion of women in the weight loss intervention group had more than 70% improvement in urge incontinence episodes but there were no significant differences between the groups for stress or total urinary incontinence. The intervention group also reported greater satisfaction with changes in urinary incontinence than the control group at 6, 12 and 18 months. Conclusions: Weight loss intervention reduced the frequency of stress incontinence episodes through 12 months and improved patient satisfaction with changes in incontinence through 18 months. Improving weight loss maintenance may provide longer term benefits for urinary incontinence. C1 [Wing, Rena R.] Brown Univ, Miriam Hosp, Providence, RI 02903 USA. [Wing, Rena R.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02903 USA. [Myers, Deborah] Brown Univ, Dept Obstet & Gynecol, Warren Alpert Med Sch, Providence, RI 02903 USA. [West, Delia Smith] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. [Grady, Deborah; Creasman, Jennifer M.; Macer, Judith] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Vittinghoff, Eric; Subak, Leslee L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Subak, Leslee L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Burgio, Kathryn L.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Burgio, Kathryn L.] Univ Alabama, Dept Vet Affairs, Birmingham, AL USA. [Franklin, Frank] Univ Alabama, Dept Maternal & Child Hlth, Birmingham, AL USA. [Gorin, Amy A.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. RP Wing, RR (reprint author), Brown Univ, Miriam Hosp, 196 Richmond St, Providence, RI 02903 USA. EM rwing@lifespan.org FU National Institute of Diabetes and Digestive and Kidney Diseases [U01DK067860, U01DK067861, U01 DK067862]; Office of Research on Women's Health FX Supported by Grants U01DK067860, U01DK067861 and U01 DK067862 from the National Institute of Diabetes and Digestive and Kidney Diseases, as well as by the Office of Research on Women's Health. NR 24 TC 32 Z9 34 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2010 VL 184 IS 3 BP 1005 EP 1010 DI 10.1016/j.juro.2010.05.031 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 636IP UT WOS:000280725600057 PM 20643425 ER PT J AU Singh, N Liu, KA Tian, L Criqui, MH Guralnik, JM Ferrucci, L Liao, YH McDermott, MM AF Singh, Nimarta Liu, Kiang Tian, Lu Criqui, Michael H. Guralnik, Jack M. Ferrucci, Luigi Liao, Yihua McDermott, Mary M. TI Leg strength predicts mortality in men but not in women with peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANKLE BRACHIAL INDEX; PHYSICAL-ACTIVITY; ASSOCIATION; PERFORMANCE AB Objective: To establish associations between kg strength and mortality in men and women with lower extremity peripheral arterial disease (PAD). Methods: This was an observational, prospective study of 410 men and women with PAD aged 55 and older recruited from Chicago-area medical centers and followed for a mean of 60 months. The participants were followed for a mean of 60.0 months. Isometric knee extension, knee flexion, hip extension, and hip flexion were measured at baseline. Primary outcomes were all-cause and cardiovascular disease mortality. Cox proportional hazards models were used to assess relations between leg strength and all-cause and cardiovascular disease mortality among men and women, adjusting for age, race, comorbidities, physical activity, smoking, body mass index, and the ankle brachial index. Results- Among the 246 male participants, poorer baseline strength for knee flexion (P trend =.029), knee extension (P trend = .010), and hip extension (P trend =.013) were each associated independently with higher all-cause mortality. Poorer strength for knee flexion (P trend = .042) and hip extension (P trend =.029) were associated with higher cardiovascular mortality. Compared with those in the fourth (best) baseline knee flexion quartile, hazard ratios for all-cause and cardiovascular disease mortality among men in the first (poorest) knee flexion quartile were 2.23 (95% confidence interval [CI], 102-4.87; P = .045) and 4.20 (95% Cl, 1.12-15.79; P =.044), respectively. No significant associations of leg strength and all-cause mortality were identified among women. Conclusions: Poorer leg strength is associated with increased mortality in men, but not women, with PAD. Future study is needed to determine whether interventions that increase leg strength improve survival in men with PAD. (J Vase Surg 2010;52:624-31.) C1 [Singh, Nimarta; Liu, Kiang; Liao, Yihua; McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA. [Tian, Lu] Stanford Univ, Stanford, CA 94305 USA. [Criqui, Michael H.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Guralnik, Jack M.; Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA. RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA. FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000048, RR-00048]; NHLBI NIH HHS [R01 HL064739-04, R01-HL076298, R01-HL58099, R01 HL058099-04, R01 HL071223, R01 HL071223-01, R01 HL071223-04, R01 HL076298-01A1, R01 HL076298-03, R01 HL058099, R01 HL058099-02, R01 HL064739-02, R01 HL076298-04, R01-HL071223, R01-HL64739, R01 HL076298-02, R01 HL071223-03, R01 HL064739-03, R01 HL064739-01A1, R01 HL064739, R01 HL058099-03, R01 HL076298] NR 16 TC 11 Z9 12 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2010 VL 52 IS 3 BP 624 EP 631 DI 10.1016/j.jvs.2010.03.066 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 646VB UT WOS:000281570100013 PM 20598471 ER PT J AU Jordan, MR Kearney, M Palmer, S Shao, W Maldarelli, F Coakley, EP Chappey, C Wanke, C Coffin, JM AF Jordan, Michael R. Kearney, Mary Palmer, Sarah Shao, Wei Maldarelli, Frank Coakley, Eoin P. Chappey, Colombe Wanke, Christine Coffin, John M. TI Comparison of standard PCR/cloning to single genome sequencing for analysis of HIV-1 populations SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV; Single genome sequencing (SGS); pro-pol diversity; Cloning and sequencing; Treatment naive ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANCE MUTATIONS; REVERSE-TRANSCRIPTASE; IN-VIVO; FIDELITY; INDIVIDUALS; MULTIPLE AB To compare standard PCR/cloning and single genome sequencing (SGS) in their ability to reflect actual intra-patient polymorphism of HIV-1 populations, a total of 530 HIV-1 pro-pol sequences obtained by both sequencing techniques from a set of 17 ART naive patient specimens was analyzed. For each specimen, 12 and 15 sequences, on average, were characterized by the two techniques. Using phylogenetic analysis, tests for panmixia and entropy, and Bland-Altman plots, no difference in population structure or genetic diversity was shown in 14 of the 17 subjects. Evidence of sampling bias by the presence of subsets of identical sequences was found by either method. Overall, the study shows that neither method was more biased than the other, and providing that an adequate number of PCR templates is analyzed, and that the bulk sequencing captures the diversity of the viral population, either method is likely to provide a similar measure of population diversity. (C) 2010 Elsevier B.V. All rights reserved. C1 [Jordan, Michael R.] Tufts Univ, Div Geog Med & Infect Dis, Tufts Med Ctr, Sch Med, Boston, MA 02111 USA. [Kearney, Mary; Palmer, Sarah; Shao, Wei; Maldarelli, Frank] NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. [Palmer, Sarah] Karolinska Inst, Swedish Inst Infect Dis Control, Stockholm, Sweden. [Coakley, Eoin P.] Monogram Biosci Inc, San Francisco, CA 94080 USA. [Chappey, Colombe] Genentech Inc, San Francisco, CA 94080 USA. RP Jordan, MR (reprint author), Tufts Univ, Div Geog Med & Infect Dis, Tufts Med Ctr, Sch Med, 800 Washington St,Box 41,136 Harrison Ave, Boston, MA 02111 USA. EM mjordan@tuftsmedicalcenter.org; kearneym@ncifcrf.gov; sarah.palmer@smi.ki.se; shaow@ncifcrf.gov; fmalli@mail.nih.gov; ecoakley@monogrambio.com; colombe.chappey@gmail.com; Christine.wanke@tufts.edu; john.coffin@tufts.edu FU National institute for Allergy and Infectious Disease [T32 AI07389, CFAAR 1P30A142853-10, K24 A1055293-06A1, K23 AI074423-03]; Center for Drug Abuse and AIDS Research [P30 DA013868]; George Kirby Foundation FX MRJ was supported by the National institute for Allergy and Infectious Disease: T32 AI07389; CFAAR 1P30A142853-10; K24 A1055293-06A1; and K23 AI074423-03; and the Center for Drug Abuse and AIDS Research: P30 DA013868. JMC was a Research Professor of the American Cancer Society, with support from the George Kirby Foundation. NR 21 TC 37 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2010 VL 168 IS 1-2 BP 114 EP 120 DI 10.1016/j.jviromet.2010.04.030 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 638CS UT WOS:000280869400020 PM 20451557 ER PT J AU Finzi, A Pacheco, B Zeng, X Do Kwon, Y Kwong, PD Sodroski, J AF Finzi, Andres Pacheco, Beatriz Zeng, Xin Do Kwon, Young Kwong, Peter D. Sodroski, Joseph TI Conformational characterization of aberrant disulfide-linked HIV-1 gp120 dimers secreted from overexpressing cells SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; Virus entry; CD4; Envelope glycoprotein; Conformational change ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN TRIMERS; TRANSMEMBRANE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; OLIGOMERIC STRUCTURE; RECEPTOR-BINDING; AIDS PATIENTS; INNER DOMAIN; T4 MOLECULE; HTLV-III AB The envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) mediate viral entry and are also the primary target of neutralizing antibodies. The gp160 envelope glycoprotein precursor undergoes proteolytic cleavage in the Golgi complex to produce the gp120 exterior glycoprotein and the gp41 transmembrane glycoprotein, which remain associated non-covalently in the trimeric Env complex. Monomeric soluble gp120 has been used extensively to investigate conformational states, structure, antigenicity and immunogenicity of the HIV-1 Env glycoproteins. Expression of gp120 alone (without gp41) leads to the accumulation not only of monomeric gp120 but also an aberrant dimeric form. The gp120 dimers were sensitive to reducing agents. The formation of gp120 dimers was disrupted by a single amino acid change in the inner domain, and was reduced by removal of the V1/V2 variable loops or the N and C termini. Epitopes on the gp120 inner domain and the chemokine receptor-binding surface were altered or occluded by gp120 dimerization. Awareness of the existence and properties of gp120 dimers should assist interpretation of studies of this key viral protein. (C) 2010 Elsevier B.V. All rights reserved. C1 [Finzi, Andres; Pacheco, Beatriz; Zeng, Xin; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Finzi, Andres; Pacheco, Beatriz; Sodroski, Joseph] Harvard Univ, Sch Med, Div Aids, Dept Pathol, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Do Kwon, Young; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,CLS 1010, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Kwon, Young Do/A-6957-2010 FU National Institutes of Health [AI24755, GM56550, AI67854]; International AIDS Vaccine Initiative FX The authors would like to thank Ms. Yvette McLaughlin and Ms. Elizabeth Carpelan for manuscript preparation. This work was supported by grants from the National Institutes of Health (AI24755, GM56550 and AI67854), by the International AIDS Vaccine Initiative, and by the late William F. McCarty-Cooper. The authors have no conflicts of interest to report. NR 47 TC 25 Z9 26 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2010 VL 168 IS 1-2 BP 155 EP 161 DI 10.1016/j.jviromet.2010.05.008 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 638CS UT WOS:000280869400027 PM 20471426 ER PT J AU Michelini, Z Galluzzo, CM Negri, DRM Leone, P Amici, R Bona, R Summa, V Di Santo, R Costi, R Pommier, Y Marchand, C Palmisano, L Vella, S Cara, A AF Michelini, Zuleika Galluzzo, Clementina Maria Negri, Donatella R. M. Leone, Pasqualina Amici, Roberta Bona, Roberta Summa, Vincenzo Di Santo, Roberto Costi, Roberta Pommier, Yves Marchand, Christophe Palmisano, Lucia Vella, Stefano Cara, Andrea TI Evaluation of HIV-1 integrase inhibitors on human primary macrophages using a luciferase-based single-cycle phenotypic assay SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Integrase; Integrase inhibitors; Macrophages; Lentiviral vectors; Luciferase ID RALTEGRAVIR; INFECTION; RESISTANCE; POTENT; ELVITEGRAVIR; DISCOVERY; DYNAMICS; THERAPY AB Macrophages represent an important site for productive infection of HIV-1 and the evaluation of integrase (IN) inhibitors on this cell subset is of fundamental importance. In this report, preclinical evaluation of IN inhibitors on primary human macrophages was attempted successfully using a 96-well microtiter phenotypic assay developed recently for the evaluation of IN inhibitors in a cell-based system by taking advantage of HIV-derived lentiviral vectors expressing luciferase. IN inhibitors were also tested using a lentiviral vector containing an IN with introduced T66I/S153Y mutations, known to affect the activity of azido-group-containing diketo acid (DKA) IN inhibitors. Utilizing different classes of HIV integrase inhibitors against the wild-type IN and the mutant mentioned above, some of the IN inhibitors used were also active on this particular mutant, suggesting that should HIV-1 develop additional or different mutations to become resistant to such anti-IN drugs, new drugs can be developed with a better resistance profile. This assay provides a standardized method for the preclinical evaluation of the efficacy of IN inhibitors on wild-type and mutated IN that can be adapted easily for the evaluation of anti-IN activity on IN sequences derived from patients. (C) 2010 Elsevier B.V. All rights reserved. C1 [Michelini, Zuleika; Galluzzo, Clementina Maria; Leone, Pasqualina; Amici, Roberta; Bona, Roberta; Palmisano, Lucia; Vella, Stefano; Cara, Andrea] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy. [Negri, Donatella R. M.] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Summa, Vincenzo] Ist Ric Biol Mol, Dept Med Chem, I-00040 Rome, Italy. [Di Santo, Roberto; Costi, Roberta] Fdn Cenci Bolognetti, Ist Pasteur, Dipartimento Studi Farmaceut, I-00185 Rome, Italy. [Pommier, Yves; Marchand, Christophe] NIH, Mol Pharmacol Lab, Bethesda, MD USA. RP Cara, A (reprint author), Ist Super Sanita, Dept Therapeut Res & Med Evaluat, Viale Regina Elena 299, I-00161 Rome, Italy. EM andrea.cara@iss.it RI palmisano, lucia/G-5577-2011; Cara, Andrea/M-4865-2015; Vella, Stefano/D-4912-2015; Michelini, Zuleika/J-9003-2016; Negri, Donatella/M-4362-2015; OI Cara, Andrea/0000-0003-4967-1895; Vella, Stefano/0000-0003-2347-5984; Michelini, Zuleika/0000-0001-6841-7396; Negri, Donatella/0000-0002-3437-9288; COSTI, Roberta/0000-0002-1314-9029; Di Santo, Roberto/0000-0002-4279-7666 FU Italian AIDS National Program FX We thank Alessia Petrocchi, Emanuela Nizi, Paola Pace, and Cristina Gardelli for synthesis of the Merck compounds and for providing the solid samples. We also thank Dr. Silvia Baroncelli for providing assistance in statistical analysis and Dr. Marina Franco for helping in manuscript reviewing and for providing editorial assistance. This work was funded by grants from the Italian AIDS National Program (to A.C.). NR 22 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2010 VL 168 IS 1-2 BP 272 EP 276 DI 10.1016/j.jviromet.2010.06.004 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 638CS UT WOS:000280869400047 PM 20558207 ER PT J AU Graef, KM Vreede, FT Lau, YF McCall, AW Carr, SM Subbarao, K Fodor, E AF Graef, Katy M. Vreede, Frank T. Lau, Yuk-Fai McCall, Amber W. Carr, Simon M. Subbarao, Kanta Fodor, Ervin TI The PB2 Subunit of the Influenza Virus RNA Polymerase Affects Virulence by Interacting with the Mitochondrial Antiviral Signaling Protein and Inhibiting Expression of Beta Interferon SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-C-VIRUS; SINGLE AMINO-ACID; A VIRUS; HOST-RANGE; ADAPTER PROTEIN; HUMAN-CELLS; PA SUBUNIT; H5N1; MICE; REPLICATION AB The PB2 subunit of the influenza virus RNA polymerase is a major virulence determinant of influenza viruses. However, the molecular mechanisms involved remain unknown. It was previously shown that the PB2 protein, in addition to its nuclear localization, also accumulates in the mitochondria. Here, we demonstrate that the PB2 protein interacts with the mitochondrial antiviral signaling protein, MAVS (also known as IPS-1, VISA, or Cardif), and inhibits MAVS-mediated beta interferon (IFN-beta) expression. In addition, we show that PB2 proteins of influenza viruses differ in their abilities to associate with the mitochondria. In particular, the PB2 proteins of seasonal human influenza viruses localize to the mitochondria while PB2 proteins of avian influenza viruses are nonmitochondrial. This difference in localization is caused by a single amino acid polymorphism in the PB2 mitochondrial targeting signal. In order to address the functional significance of the mitochondrial localization of the PB2 protein in vivo, we have generated two recombinant human influenza viruses encoding either mitochondrial or nonmitochondrial PB2 proteins. We found that the difference in the mitochondrial localization of the PB2 proteins does not affect the growth of these viruses in cell culture. However, the virus encoding the nonmitochondrial PB2 protein induces higher levels of IFN-beta and, in an animal model, is attenuated compared to the isogenic virus encoding a mitochondrial PB2. Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence. C1 [Graef, Katy M.; Lau, Yuk-Fai; McCall, Amber W.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Graef, Katy M.; Vreede, Frank T.; Carr, Simon M.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Lau, Yuk-Fai] DSO Natl Labs, DMERI, Med Countermeasures Biol Lab, Singapore 117510, Singapore. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 North Dr, Bethesda, MD 20892 USA. EM KSUBBARAO@niaid.nih.gov; ervin.fodor@path.ox.ac.uk OI Vreede, Frank/0000-0001-9935-2337 FU Wellcome Trust [084349]; MRC [G0700848]; National Institute of Allergy and Infectious Diseases, NIH; International Biomedical Research Alliance; NIH FX This study was supported by grants from the Wellcome Trust (084349), the MRC (G0700848), and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. K. M. G. was funded by the International Biomedical Research Alliance and OxCam Graduate Partnerships Program (NIH). NR 55 TC 90 Z9 95 U1 1 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2010 VL 84 IS 17 BP 8433 EP 8445 DI 10.1128/JVI.00879-10 PG 13 WC Virology SC Virology GA 634SJ UT WOS:000280605300007 PM 20538852 ER PT J AU Lau, YF Tang, LH McCall, AW Ooi, EE Subbarao, K AF Lau, Yuk-Fai Tang, Lay-Hoon McCall, Amber W. Ooi, Eng-Eong Subbarao, Kanta TI An Adjuvant for the Induction of Potent, Protective Humoral Responses to an H5N1 Influenza Virus Vaccine with Antigen-Sparing Effect in Mice SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; A H1N1 VACCINE; RESPIRATORY-TRACT; IMMUNE-RESPONSES; IN-VITRO; PANDEMIC INFLUENZA; RANDOMIZED-TRIAL; CROSS-PROTECTION; INFECTION; ANTIBODIES AB Intramuscular administration of inactivated influenza virus vaccine is the main vaccine platform used for the prevention of seasonal influenza virus infection. In clinical trials, inactivated H5N1 vaccines have been shown to be safe and capable of eliciting immune correlates of protection. However, the H5N1 vaccines are poorly immunogenic compared to seasonal influenza virus vaccines. Needle-free vaccination would be more efficient and economical in a pandemic, and the development of an effective and safe mucosal adjuvant will be an important milestone. A stabilized chemical analog of double-stranded RNA, PIKA, was previously reported to be a potent mucosal adjuvant in a murine model. While PIKA stimulates dendritic cells in vitro, little was known about its receptor and adjuvanting mechanism in vivo. In this study, we demonstrated that the immunostimulatory effect of PIKA resulted in an increased number of mature antigen-presenting cells, with the induction of proinflammatory cytokines at the inoculation site. In addition, coadministration of PIKA with a poorly immunogenic H5N1 subunit vaccine led to antigen sparing and quantitative and qualitative improvements of the immune responses over those achieved with an unadjuvanted vaccine in mice. The adjuvanted vaccine provided protection against lethal challenge with homologous and heterologous H5N1 wild-type viruses. Mice lacking functional TLR3 showed diminished cytokine production with PIKA stimulation, diminished antibody responses, and reduced protective efficacy against wild-type virus challenge following vaccination. These data suggest that TLR3 is important for the optimal performance of PIKA as an adjuvant. With its good safety profile and antigen-sparing effect, PIKA could be an attractive adjuvant for use in future pandemics. C1 [Lau, Yuk-Fai; McCall, Amber W.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Lau, Yuk-Fai; Tang, Lay-Hoon; Ooi, Eng-Eong] DSO Natl Labs, Med Countermeasures Biol Lab, DMERI, Singapore 117510, Singapore. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 33,Room 3E13C-1,33 North Dr, Bethesda, MD 20892 USA. EM KSUBBARAO@niaid.nih.gov OI Ooi, Eng Eong/0000-0002-0520-1544 FU NIAID, NIH; Future Systems Directorate, Ministry of Defense, the Republic of Singapore FX This research was supported by funds from the Intramural Research Program of the NIAID, NIH, and the Future Systems Directorate, Ministry of Defense, the Republic of Singapore. NR 52 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2010 VL 84 IS 17 BP 8639 EP 8649 DI 10.1128/JVI.00596-10 PG 11 WC Virology SC Virology GA 634SJ UT WOS:000280605300024 PM 20538850 ER PT J AU Fislova, T Thomas, B Graef, KM Fodor, E AF Fislova, Tatiana Thomas, Benjamin Graef, Katy M. Fodor, Ervin TI Association of the Influenza Virus RNA Polymerase Subunit PB2 with the Host Chaperonin CCT SO JOURNAL OF VIROLOGY LA English DT Article ID SINGLE AMINO-ACID; A VIRUS; NUCLEAR IMPORT; PA SUBUNIT; RIBONUCLEOPROTEIN COMPLEX; CYTOSOLIC CHAPERONIN; HIGH VIRULENCE; PROTEIN STI1; HUMAN-CELLS; REPLICATION AB The RNA polymerase of influenza A virus is a host range determinant and virulence factor. In particular, the PB2 subunit of the RNA polymerase has been implicated as a crucial factor that affects cell tropism as well as virulence in animal models. These findings suggest that host factors associating with the PB2 protein may play an important role during viral replication. In order to identify host factors that associate with the PB2 protein, we purified recombinant PB2 from transiently transfected mammalian cells and identified copurifying host proteins by mass spectrometry. We found that the PB2 protein associates with the cytosolic chaperonin containing TCP-1 (CCT), stress-induced phosphoprotein 1 (STIP1), FK506 binding protein 5 (FKBP5), alpha- and beta-tubulin, Hsp60, and mitochondrial protein p32. Some of these binding partners associate with each other, suggesting that PB2 might interact with these proteins in multimeric complexes. More detailed analysis of the interaction of the PB2 protein with CCT revealed that PB2 associates with CCT as a monomer and that the CCT binding site is located in a central region of the PB2 protein. PB2 proteins from various influenza virus subtypes and origins can associate with CCT. Silencing of CCT resulted in reduced viral replication and reduced PB2 protein and viral RNA accumulation in a ribonucleoprotein reconstitution assay, suggesting an important function for CCT during the influenza virus life cycle. We propose that CCT might be acting as a chaperone for PB2 to aid its folding and possibly its incorporation into the trimeric RNA polymerase complex. C1 [Fislova, Tatiana; Graef, Katy M.; Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Fislova, Tatiana] Slovak Acad Sci, Inst Virol, Bratislava, Slovakia. [Thomas, Benjamin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford Cent Prote Facil, Oxford OX1 3RE, England. [Graef, Katy M.; Fodor, Ervin] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Fodor, E (reprint author), Univ Oxford, Sir William Dunn Sch Pathol, S Parks Rd, Oxford OX1 3RE, England. EM ervin.fodor@path.ox.ac.uk FU European Commission; MRC [G0700848]; International Biomedical Research Alliance; NIH FX This work was supported by grants from the European Commission (FLUINNATE) and the MRC (grant G0700848). K.M.G. was funded by the International Biomedical Research Alliance and the OxCam Graduate Partnership Programme (NIH). NR 62 TC 32 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2010 VL 84 IS 17 BP 8691 EP 8699 DI 10.1128/JVI.00813-10 PG 9 WC Virology SC Virology GA 634SJ UT WOS:000280605300029 PM 20573828 ER PT J AU Cafaro, A Bellino, S Titti, F Maggiorella, MT Sernicola, L Wiseman, RW Venzon, D Karl, JA O'Connor, D Monini, P Robert-Guroff, M Ensoli, B AF Cafaro, Aurelio Bellino, Stefania Titti, Fausto Maggiorella, Maria Teresa Sernicola, Leonardo Wiseman, Roger W. Venzon, David Karl, Julie A. O'Connor, David Monini, Paolo Robert-Guroff, Marjorie Ensoli, Barbara TI Impact of Viral Dose and Major Histocompatibility Complex Class IB Haplotype on Viral Outcome in Mauritian Cynomolgus Monkeys Vaccinated with Tat upon Challenge with Simian/Human Immunodeficiency Virus SHIV89.6P SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INFECTION; SIV-GAG; MACAQUES; REPLICATION; PROTEIN; PROGRESSION; DISEASE; TRIAL; AIDS AB The effects of the challenge dose and major histocompatibility complex (MHC) class IB alleles were analyzed in 112 Mauritian cynomolgus monkeys vaccinated (n = 67) or not vaccinated (n = 45) with Tat and challenged with simian/human immunodeficiency virus (SHIV) 89.6P(cy243). In the controls, the challenge dose (10 to 20 50% monkey infectious doses [MID50]) or MHC did not affect susceptibility to infection, peak viral load, or acute CD4 T-cell loss, whereas in the chronic phase of infection, the H1 haplotype correlated with a high viral load (P = 0.0280) and CD4 loss (P = 0.0343). Vaccination reduced the rate of infection acquisition at 10 MID50 (P < 0.0001), and contained acute CD4 loss at 15 MID50 (P = 0.0099). Haplotypes H2 and H6 were correlated with increased susceptibility (P = 0.0199) and resistance (P = 0.0087) to infection, respectively. Vaccination also contained CD4 depletion (P = 0.0391) during chronic infection, independently of the challenge dose or haplotype. C1 [Cafaro, Aurelio; Bellino, Stefania; Titti, Fausto; Maggiorella, Maria Teresa; Sernicola, Leonardo; Monini, Paolo; Ensoli, Barbara] Ist Super Sanita, Natl AIDS Ctr, I-00161 Rome, Italy. [Wiseman, Roger W.; Karl, Julie A.; O'Connor, David] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI USA. [Wiseman, Roger W.; Karl, Julie A.; O'Connor, David] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. [Robert-Guroff, Marjorie] NIH, Vaccine Branch, Bethesda, MD 20892 USA. [Robert-Guroff, Marjorie] NCI, NIH, Bethesda, MD 20892 USA. RP Ensoli, B (reprint author), Ist Super Sanita, Natl AIDS Ctr, Viale Regina Elena 299, I-00161 Rome, Italy. EM barbara.ensoli@iss.it RI Ensoli, Barbara/J-9169-2016; Monini, Paolo/K-1429-2016; Cafaro, Aurelio/K-5314-2016; maggiorella, maria teresa/K-4072-2016; OI Ensoli, Barbara/0000-0002-0545-8737; Monini, Paolo/0000-0002-4941-6854; maggiorella, maria teresa/0000-0001-5058-476X; o'connor, david/0000-0003-2139-470X FU Ministry of Health; Italian Concerted Action on Vaccine (ICAV); U.S. National Institute of Allergy and Infectious Diseases [HHSN266200400088C/N01-A1-30061] FX This work was supported in part by the Italian AIDS National Program from the Ministry of Health (to B. E.) and the Italian Concerted Action on Vaccine (ICAV); MHC analyses were supported by U.S. National Institute of Allergy and Infectious Diseases contract HHSN266200400088C/N01-A1-30061. NR 28 TC 18 Z9 18 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2010 VL 84 IS 17 BP 8953 EP 8958 DI 10.1128/JVI.00377-10 PG 6 WC Virology SC Virology GA 634SJ UT WOS:000280605300054 PM 20554774 ER PT J AU Pinn, VW Clayton, JA Begg, L Sass, SE AF Pinn, Vivian W. Clayton, Janine Austin Begg, Lisa Sass, Samantha E. TI Public Partnerships for a Vision for Women's Health Research in 2020 SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material C1 [Pinn, Vivian W.; Clayton, Janine Austin; Begg, Lisa] NIH, Off Res Womens Hlth, DHHS, Bethesda, MD 20892 USA. [Sass, Samantha E.] Off Res Womens Hlth, Wellesley Coll Washington Intern, Bethesda, MD USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, DHHS, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA. EM orwh-research@od.nih.gov NR 9 TC 5 Z9 5 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD SEP PY 2010 VL 19 IS 9 BP 1603 EP 1607 DI 10.1089/jwh.2010.2386 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 646BQ UT WOS:000281510300002 PM 20815755 ER PT J AU Semba, RD Nicklett, EJ Ferrucci, L AF Semba, Richard D. Nicklett, Emily J. Ferrucci, Luigi TI Does Accumulation of Advanced Glycation End Products Contribute to the Aging Phenotype? SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Advanced glycation end products; Aging; Diabetes; Diet; Inflammation; Longevity ID COMMUNITY-DWELLING WOMEN; N-EPSILON-CARBOXYMETHYLLYSINE; CARDIOVASCULAR-DISEASE MORTALITY; CORONARY-ARTERY DISEASE; MAILLARD REACTION; DIABETIC-NEPHROPATHY; CROSS-LINKING; CIRCULATING RECEPTORS; LIQUID-CHROMATOGRAPHY; SERUM-LEVELS AB Aging is a complex multifactorial process characterized by accumulation of deleterious changes in cells and tissues, progressive deterioration of structural integrity and physiological function across multiple organ systems, and increased risk of death. We conducted a review of the scientific literature on the relationship of advanced glycation end products (AGEs) with aging. AGEs are a heterogeneous group of bioactive molecules that are formed by the nonenzymatic glycation of proteins, lipids, and nucleic acids. Humans are exposed to AGEs produced in the body, especially in individuals with abnormal glucose metabolism, and AGEs ingested in foods. AGEs cause widespread damage to tissues through upregulation of inflammation and cross-linking of collagen and other proteins. AGEs have been shown to adversely affect virtually all cells, tissues, and organ systems. Recent epidemiological studies demonstrate that elevated circulating AGEs are associated with increased risk of developing many chronic diseases that disproportionally affect older individuals. Based on these data, we propose that accumulation of AGEs accelerate the multisystem functional decline that occurs with aging, and therefore contribute to the aging phenotype. Exposure to AGEs can be reduced by restriction of dietary intake of AGEs and drug treatment with AGE inhibitors and AGE breakers. Modification of intake and circulating levels of AGEs may be a possible strategy to promote health in old age, especially because most Western foods are processed at high temperature and are rich in AGEs. C1 [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Nicklett, Emily J.] Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Smith Bldg,M015,400 N Broadway, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu RI Nicklett, Emily/A-4281-2012 FU NIH [R01 AG029148, R01 AG027012, R01 HL094507, R37 AG019905]; National Institute on Aging, National Institutes of Health FX This work was supported by NIH R01 AG029148, R01 AG027012, R01 HL094507, R37 AG019905, and the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 108 TC 118 Z9 124 U1 3 U2 32 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2010 VL 65 IS 9 BP 963 EP 975 DI 10.1093/gerona/glq074 PG 13 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 638PD UT WOS:000280906100007 PM 20478906 ER PT J AU Ramakrishnan, M Moisi, JC Etame, MM Klugman, KP Feris, JM Levine, OS AF Ramakrishnan, Meenakshi Moisi, Jennifer C. Etame, Mireille Mpoudi Klugman, Keith P. Feris, Jesus M. Levine, Orin S. TI Invasive infections and sickle-cell disease Reply SO LANCET INFECTIOUS DISEASES LA English DT Letter ID BACTERIAL-INFECTIONS; CHILDREN C1 [Moisi, Jennifer C.; Levine, Orin S.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Etame, Mireille Mpoudi] NIAID, Henry M Jackson Fdn, Div AIDS, NIH, Bethesda, MD 20892 USA. [Klugman, Keith P.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Klugman, Keith P.] MRC, Resp & Meningeal Pathogens Res Unit, Natl Inst Communicable Dis, Johannesburg, South Africa. [Klugman, Keith P.] Univ Witwatersrand, Johannesburg, South Africa. [Feris, Jesus M.] Hosp Infantil Dr Robert Reid Cabral, Bethesda, MD USA. EM meenaramakri@gmail.com NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD SEP PY 2010 VL 10 IS 9 BP 593 EP 594 DI 10.1016/S1473-3099(10)70181-X PG 2 WC Infectious Diseases SC Infectious Diseases GA 645UL UT WOS:000281491600013 ER PT J AU Engels, EA Cho, ER Jee, SH AF Engels, Eric A. Cho, Eo Rin Jee, Sun Ha TI Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study SO LANCET ONCOLOGY LA English DT Article ID C VIRUS; HIGH PREVALENCE; HEPATOCELLULAR-CARCINOMA; SMOKING; CANCERS; HEALTH; WOMEN AB Background Hepatitis B virus (HBV) infection is common throughout Asia and Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma (NHL) is unclear. We aimed to assess the association between chronic HBV infection and subsequent development of NHL in a South Korean cohort. Methods The Korean Cancer Prevention Study is a cohort study of South Korean workers and their dependants enrolled during 1992-95. From this cohort, we excluded individuals who died before Jan 1, 1993, who had cancer at or before the initial visit, who had missing information about weight, height, alanine aminotransferase or aspartate aminotransferase concentrations, or alcohol use, or who had evidence of HIV or HCV infection. Of 1 284 586 eligible participants, 603 585 had baseline data for serum hepatitis B surface antigen (HBsAg) status and were included in our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection. Participants were followed up from baseline until Dec 31, 2006. We used national databases of inpatient and outpatient diagnoses and mortality records to ascertain occurrence of haematological malignancies. We assessed incidence of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox regression to evaluate associations with HBsAg status, adjusting for sex, age, and enrolment year. Findings 53 045 (9%) of 603 585 participants tested positive for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative individuals developed NHL. HBsAg-positive participants had an increased risk of NHL overall compared with those who were HBsAg-negative (incidence 19.4 vs 12.3 per 100 000 person-years; hazard ratio [HR] 1.74, 95% CI 1.45-2.09, adjusted for sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (n=325, incidence 6.86 vs 3.79 per 100 000 person-years; adjusted HR 2.01, 1.48-2.75) and other or unknown subtypes (n=591, incidence 10.5 vs 7.07 per 100 000 person-years; adjusted HR 1.65, 1.29-2.11), compared with HBsAg negativity. Increased risk was also recorded for malignant immunoproliferation (n=14, incidence 0.44 vs 0.15 per 100 000 person-years; adjusted HR 3.79, 1.05-13.7). Risk of these malignancies was consistently raised in HBsAg-positive participants throughout 14 years of follow-up. HBsAg positivity was not associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias. Interpretation During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis. C1 [Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Cho, Eo Rin] Korea Univ, Coll Med, Inst Human Genom Study, Seoul 136705, South Korea. [Jee, Sun Ha] Grad Sch Publ Hlth, Inst Hlth Promot, Dept Epidemiol, Seoul, South Korea. RP Jee, SH (reprint author), Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. EM jsunha@yuhs.ac FU Korean Seoul City Research; Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute FX Korean Seoul City Research and the National Research and Development Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute. NR 37 TC 76 Z9 82 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD SEP PY 2010 VL 11 IS 9 BP 827 EP 834 DI 10.1016/S1470-2045(10)70167-4 PG 8 WC Oncology SC Oncology GA 657KQ UT WOS:000282412000022 PM 20688564 ER PT J AU Dunleavy, K Wilson, WH AF Dunleavy, Kieron Wilson, Wyndham H. TI Targeting CD52 as a novel therapeutic strategy in angioimmunoblastic T-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID EXPRESSION; ALEMTUZUMAB; AITL C1 [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wilson, WH (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 4N115,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wilsonw@mail.nih.gov NR 13 TC 1 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP PY 2010 VL 51 IS 9 BP 1583 EP 1584 DI 10.3109/10428194.2010.508190 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 655FO UT WOS:000282233200001 PM 20795788 ER PT J AU Zhang, ZY Lanza, E Kris-Etherton, PM Colburn, NH Bagshaw, D Rovine, MJ Ulbrecht, JS Bobe, G Chapkin, RS Hartman, TJ AF Zhang, Zhiying Lanza, Elaine Kris-Etherton, Penny M. Colburn, Nancy H. Bagshaw, Deborah Rovine, Michael J. Ulbrecht, Jan S. Bobe, Gerd Chapkin, Robert S. Hartman, Terryl J. TI A High Legume Low Glycemic Index Diet Improves Serum Lipid Profiles in Men SO LIPIDS LA English DT Article DE Legume intake; Lipids; Insulin resistance ID CORONARY-HEART-DISEASE; HOMEOSTASIS MODEL ASSESSMENT; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; VEGETABLE INTAKE; LDL-CHOLESTEROL; BLOOD-LIPIDS; FIBER INTAKE; RISK-FACTORS AB Clinical studies have shown that fiber consumption facilitates weight loss and improves lipid profiles; however, the beneficial effects of high fermentable fiber low glycemic index (GI) diets under conditions of weight maintenance are unclear. In the Legume Inflammation Feeding Experiment, a randomized controlled cross-over feeding study, 64 middle-aged men who had undergone colonoscopies within the previous 2 years received both a healthy American (HA) diet (no legume consumption, fiber consumption = 9 g/1,000 kcal, and GI = 69) and a legume enriched (1.5 servings/1,000 kcal), high fiber (21 g/1,000 kcal), low GI (GI = 38) diet (LG) in random order. Diets were isocaloric and controlled for macronutrients including saturated fat; they were consumed each for 4 weeks with a 2-4 week break separating dietary treatments. Compared to the HA diet, the LG diet led to greater declines in both fasting serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) (P < 0.001 and P < 0.01, respectively). Insulin-resistant (IR) subjects had greater reductions in high density lipoprotein cholesterol (HDL-C; P < 0.01), and triglycerides (TAG)/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. Insulin-sensitive (IS) subjects had greater reductions in TC (P < 0.001), LDL-C (P < 0.01), TC/HDL-C (P < 0.01), and LDL-C/HDL-C (P = 0.02) after the LG diet, compared to the HA diet. In conclusion, a high legume, high fiber, low GI diet improves serum lipid profiles in men, compared to a healthy American diet. However, IR individuals do not achieve the full benefits of the same diet on cardiovascular disease (CVD) lipid risk factors. C1 [Zhang, Zhiying; Kris-Etherton, Penny M.; Bagshaw, Deborah; Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. [Rovine, Michael J.] Penn State Univ, Dept Human Develop & Family Studies, University Pk, PA 16802 USA. [Ulbrecht, Jan S.] Penn State Univ, Dept Biobehav Hlth & Med, University Pk, PA 16802 USA. [Lanza, Elaine; Colburn, Nancy H.; Bobe, Gerd] NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. [Chapkin, Robert S.] Texas A&M Univ, Program Integrat Nutr & Complex Dis, College Stn, TX USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutr Sci, 110 Chandlee Lab, University Pk, PA 16802 USA. EM tjh9@psu.edu OI Chapkin, Robert/0000-0002-6515-3898 FU National Cancer Institute [25XS101]; General Clinical Research Center at Penn State University (NIH) [M01 RR 10732] FX The present study was supported by the National Cancer Institute (subcontract 25XS101) with partial support provided by the General Clinical Research Center at Penn State University (NIH M01 RR 10732). We would like to thank Amy Ciccarella, Sami Heim, and Mary Lou Kiel for their help with menu and food preparation, Diane Mitchell and Linda Phelps for their assistance with the analysis of 24-h dietary recalls, and Dr. Lawrence Demers at Hershey Medical Center for the measurement of lipid profiles. All of the authors have read and approved the final submitted manuscript and there was no conflict of interest with the present paper. The authors' contributions were as follows: ZZ conducted research with participants, data analysis, and write up of manuscript; EL designed the research, contributed to data interpretation and manuscript preparation; PMKE and NHC contributed to data interpretation and manuscript preparation; DB conducted research with participants and and was involved with the write up of the manuscript; MJR contributed to data analysis and the write up of the manuscript; JSU, GB, and RSC contributed to data interpretation and the write up of the manuscript; and TJH designed research, contributed to data interpretation and manuscript preparation, and study oversight. NR 59 TC 23 Z9 23 U1 0 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD SEP PY 2010 VL 45 IS 9 BP 765 EP 775 DI 10.1007/s11745-010-3463-7 PG 11 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 646LV UT WOS:000281543000001 PM 20734238 ER PT J AU Thum, T Batkai, S Malinski, PG Becker, T Mevius, I Klempnauer, J Meyer, HH Frolich, JC Borlak, J Tsikas, D AF Thum, Thomas Batkai, Sandor Malinski, Philipp G. Becker, Thomas Mevius, Iris Klempnauer, Juergen Meyer, Hartmut H. Froelich, Juergen C. Borlak, Juergen Tsikas, Dimitrios TI Measurement and diagnostic use of hepatic cytochrome P450 metabolism of oleic acid in liver disease SO LIVER INTERNATIONAL LA English DT Article DE chronic liver disease; cirrhosis; CYP2C8; 2C9; 1A2; 2C19; 3A4; 3A7; cytochrome P450; epoxidation; hepatitis C; gas chromatography-tandem mass spectrometry; oleic acid ID CHROMATOGRAPHY-MASS-SPECTROMETRY; QUANTITATIVE-DETERMINATION; FATTY-ACIDS; CIS-EODA; IDENTIFICATION; GLUTATHIONE; MICROSOMES; CIRRHOSIS; PLASMA; RAT AB Background Oleic acid is a major systemically circulating fatty acid in humans with atheroprotective and immunomodulatory properties. As of today, the contribution of individual cytochrome P450 (CYP) mono-oxygenases to the epoxidation of this fatty acid is unknown. Furthermore, the extent of the oleic acid oxidation product cis-9,10-epoxyoctadecanoic acid (cis-EODA) in humans and its plasma levels in patients with impaired liver function are not known. Patients and methods We studied cis-EODA in plasma of patients suffering from chronic liver diseases, a condition that often displays impaired liver CYP enzyme activities. Fifteen CYP mono-oxygenases were investigated in vitro as a potential source of cis-EODA. Results Strikingly, plasma levels of cis-EODA were significantly repressed (P < 0.0005) when patients with liver impairment (n=16) were compared with healthy subjects (n=14). Production of cis-EODA was catalysed by CYP in the following order: 2C8, 2C9, 2C19, 3A4, 1A2 and CYP3A7. Conclusion cis-EODA plasma concentrations are decreased in hepatic disease with impaired liver function. Oleic acid is primarily oxidized to oleic acid oxide (cis-EODA) by CYP2C and CYP3A mono-oxygenases. The liver is the major organ responsible for the oxidation of oleic acid to cis-EODA, and thus, cis-EODA may be a suitable biomarker to assess liver function. C1 [Thum, Thomas] Hannover Med Sch, Inst Mol & Translat Therapeut Strategies, D-30625 Hannover, Germany. [Batkai, Sandor; Mevius, Iris; Froelich, Juergen C.; Tsikas, Dimitrios] Hannover Med Sch, Inst Clin Pharmacol, D-30625 Hannover, Germany. [Batkai, Sandor] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. [Malinski, Philipp G.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-30625 Hannover, Germany. [Becker, Thomas; Klempnauer, Juergen] Hannover Med Sch, Dept Visceral & Transplant Surg, D-30625 Hannover, Germany. [Meyer, Hartmut H.] Leibniz Univ Hannover, Inst Organ Chem, Hannover, Germany. [Borlak, Juergen] Fraunhofer Inst Toxicol & Expt Med, Ctr Drug Res & Med Biotechnol, Hannover, Germany. RP Thum, T (reprint author), Hannover Med Sch, Inst Mol & Translat Therapeut Strategies, OE8886,Carl Neuberg Str 1, D-30625 Hannover, Germany. EM thum.thomas@mh-hannover.de RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014; OI Thum, Thomas/0000-0003-4360-1511 FU Alexander von Humboldt Foundation FX The authors thank Anja Mitschke and Maria-Theresia Suchy for excellent laboratory and technical assistance and Frank-Mathias Gutzki for performing GC-tandem MS analyses. Sandor Batkai is a fellowship recipient of the Alexander von Humboldt Foundation. NR 22 TC 3 Z9 3 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1478-3223 J9 LIVER INT JI Liver Int. PD SEP PY 2010 VL 30 IS 8 BP 1181 EP 1188 DI 10.1111/j.1478-3231.2010.02310.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 635PA UT WOS:000280666800015 PM 20629947 ER PT J AU Milenic, DE Wong, KJ Baidoo, KE Nayak, TK Regino, CAS Garmestani, K Brechbiel, MW AF Milenic, Diane E. Wong, Karen J. Baidoo, Kwamena E. Nayak, Tapan K. Regino, Celeste A. S. Garmestani, Kayhan Brechbiel, Martin W. TI Targeting HER2 A report on the in vitro and in vivo pre-clinical data supporting trastuzumab as a radioimmunoconjugate for clinical trials SO MABS LA English DT Article DE monoclonal antibody; HER2; trastuzumab; radioimmunodiagnosis; radioimmunotherapy ID POSITRON-EMISSION-TOMOGRAPHY; DISSEMINATED PERITONEAL DISEASE; BREAST-CANCER XENOGRAFTS; GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; RADIOIMMUNOTHERAPEUTIC APPLICATIONS; BIODISTRIBUTION; EXPRESSION; HER-2/NEU; TUMORS AB The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A"-DTPA yielded a chelate:protein ratio of 3.4 +/- 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 +/- 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of (111)In-trastuzumab by melanoma (A375) s.c. xenografts and (111)In-HulgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected (111)In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of (111)In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 +/- 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by gamma-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected (111)In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimnnunotherapy study at the University of Alabama. C1 [Milenic, Diane E.; Baidoo, Kwamena E.; Nayak, Tapan K.; Garmestani, Kayhan; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Wong, Karen J.; Regino, Celeste A. S.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Milenic, DE (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM dm71q@nih.gov OI Nayak, Tapan/0000-0002-3706-6092 FU NIH, National Cancer Institute, Center for Cancer Research; NCI [R24 CA8630] FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The production of86Y at Washington University School of Medicine is supported by the NCI grant R24 CA86307. NR 69 TC 24 Z9 25 U1 1 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS-AUSTIN JI mAbs PD SEP-OCT PY 2010 VL 2 IS 5 BP 550 EP 564 DI 10.4161/mabs.2.5.13054 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673BV UT WOS:000283634100010 PM 20716957 ER PT J AU Feng, Y Xiao, XD Zhu, ZY Dimitrov, DS AF Feng, Yang Xiao, Xiaodong Zhu, Zhongyu Dimitrov, Dimiter S. TI Identification and characterization of a novel agonistic anti-DR4 human monoclonal antibody SO MABS LA English DT Article DE DR4; TRAIL; lymphoma; therapeutic antibody ID APOPTOSIS-INDUCING LIGAND; FUNCTIONAL-ANALYSIS; RECEPTOR AGONISTS; TUMOR-GROWTH; CELL-DEATH; APO2L/TRAIL; COMBINATION; THERAPY; INHIBIT; DR5 AB The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its functional receptors, DR4 and DR5, have been established as promising targets for cancer treatment. Therapeutics targeting TRAIL and its receptors are not only effective in killing many types of tumors, but they also synergize with traditional therapies and show efficacy against tumors that are otherwise resistant to conventional treatments. We describe here the identification and characterization of two human monoclonal antibodies, m921 and m922, that are specific for human DR4. Both antibodies competed with TRAIL for binding to DR4, but only m921 recognized cell surface-associated DR4 and inhibited the growth of ST486 cells. This antibody may have potential for further development as a candidate therapeutic and research tool. C1 [Feng, Yang; Xiao, Xiaodong; Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21701 USA. [Zhu, Zhongyu] NCI, BRP, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Feng, Y (reprint author), NCI, Prot Interact Grp, CCRNP, NIH, Frederick, MD 21701 USA. EM fengya@mail.nih.gov FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH, National Cancer Institute, Center for Cancer Research FX We thank members of our group for helpful discussions. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. This Research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 21 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1942-0862 J9 MABS-AUSTIN JI mAbs PD SEP-OCT PY 2010 VL 2 IS 5 BP 565 EP 570 DI 10.4161/mabs.2.5.12570 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673BV UT WOS:000283634100011 PM 20581445 ER PT J AU Le, Y Stein, A Berry, C Kellman, P Bennett, EE Taylor, J Lucas, K Kopace, R Chefd'Hotel, C Lorenz, CH Croisille, P Wen, H AF Le, Yuan Stein, Ashley Berry, Colin Kellman, Peter Bennett, Eric E. Taylor, Joni Lucas, Katherine Kopace, Rael Chefd'Hotel, Christophe Lorenz, Christine H. Croisille, Pierre Wen, Han TI Simultaneous Myocardial Strain and Dark-Blood Perfusion Imaging Using a Displacement-Encoded MRI Pulse Sequence SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE ischemia; viability; myocardial perfusion; strain; first pass; DENSE ID CARDIOVASCULAR MAGNETIC-RESONANCE; STATE FREE PRECESSION; CONTRAST ENHANCEMENT; DELAYED-ENHANCEMENT; 1ST-PASS PERFUSION; STIMULATED ECHOES; TISSUE TRACKING; CONSCIOUS DOGS; PHASE-CONTRAST; HUMAN-HEART AB The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in two to three myocardial slices were repeatedly acquired using a single-shot pulse sequence for 3 to 4 min, which covers a bolus infusion of Gadolinium contrast. The magnitudes of the images were T(1) weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n = 9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R(2) = 0.765, Bland-Altman standard deviation = 0.15 mL/min/g). In a group of ST-elevation myocardial infarction patients (n = 11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R(2) = 0.72), and the pixelwise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images. Magn Reson Med 64:787-798, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Le, Yuan; Stein, Ashley; Kellman, Peter; Bennett, Eric E.; Taylor, Joni; Lucas, Katherine; Kopace, Rael; Wen, Han] NHLBI, NIH, Bethesda, MD 20892 USA. [Berry, Colin] Western Infirm & Associated Hosp, Dept Cardiol, Glasgow G11 6NT, Lanark, Scotland. [Chefd'Hotel, Christophe; Lorenz, Christine H.] Siemens Corp Res Inc, Princeton, NJ USA. [Croisille, Pierre] Hop Cardiol & Pneumol, Dept Radiol, Lyon, France. RP Wen, H (reprint author), NHLBI, NIH, Bldg 10,B1D416,10 Ctr Dr, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Le, Yuan/A-8401-2012; Bennett, Eric/A-2551-2013; Croisille, Pierre/H-4928-2014; Wen, Han/G-3081-2010 OI Croisille, Pierre/0000-0003-4019-3460; Wen, Han/0000-0001-6844-2997 FU Chief Scientist Office [SCD/01]; Intramural NIH HHS [ZIA HL004606-13] NR 59 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2010 VL 64 IS 3 BP 787 EP 798 DI 10.1002/mrm.22461 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 644BV UT WOS:000281346300020 PM 20544714 ER PT J AU Hernando, D Liang, ZP Kellman, P AF Hernando, Diego Liang, Zhi-Pei Kellman, Peter TI Chemical Shift-Based Water/Fat Separation: A Comparison of Signal Models SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fat-water imaging; fat quantification; Dixon imaging; multi-peak fat; T(2)* measurement ID FIELD MAP ESTIMATION; FAT DECOMPOSITION; RELAXATION-TIMES; DIXON TECHNIQUE; PROTON MR; IN-VIVO; 3.0 T; QUANTIFICATION; RECONSTRUCTION; T-1 AB Quantitative water/fat separation in MRI requires careful modeling of the acquired signal. Multiple signal models have been proposed in recent years, but their relative performance has not yet been established. This article presents a comparative study of 12 signal models for quantitative water/fat separation. These models were selected according to three main criteria: magnitude or complex fitting, use of single-peak or multipeak fat spectrum, and modeling of T(2)* decay. The models were compared based on an analysis of the bias and standard deviation of their resulting estimates. Results from theoretical analysis, simulation, phantom experiments, and in vivo data were in good agreement. These results show that (a) complex fitting is uniformly superior to magnitude fitting, (b) multipeak fat modeling is able to remove the bias present in single-peak fat modeling, and (c) a single-T(2)* model performs best over a range of clinically relevant signal-to-noise ratios (SNRs) and water/fat ratios. Magn Reson Med 64:811-822, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Hernando, Diego; Liang, Zhi-Pei] Univ Illinois, Beckman Inst Adv Sci & Technol, Urbana, IL 61801 USA. [Hernando, Diego; Liang, Zhi-Pei] Univ Illinois, Dept Elect & Comp Engn, Urbana, IL 61801 USA. [Kellman, Peter] NHLBI, Cardiac Energet Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hernando, D (reprint author), Univ Illinois, Beckman Inst Adv Sci & Technol, 405 N Mathews Ave, Urbana, IL 61801 USA. EM dhernan2@illinois.edu FU NIH [P41-RR023953-01, P41-EB001977-21]; National Heart, Lung, and Blood Institute; Siemens Medical Solutions; NSF [CBET-07-30623] FX This research was supported in part by the Intramural Research Program of the NIH; National Heart, Lung, and Blood Institute; and a Cooperative Research and Development Agreement between the National Heart, Lung, and Blood Institute and Siemens Medical Solutions.; Grant sponsor: NIH; Grant number: P41-RR023953-01, P41-EB001977-21;; Grant sponsor: NSF; Grant number: CBET-07-30623. NR 44 TC 55 Z9 55 U1 1 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD SEP PY 2010 VL 64 IS 3 BP 811 EP 822 DI 10.1002/mrm.22455 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 644BV UT WOS:000281346300022 PM 20593375 ER PT J AU Bothwell, SP Farber, LW Hoagland, A Nussbaum, RL AF Bothwell, Susan P. Farber, Leslie W. Hoagland, Adam Nussbaum, Robert L. TI Species-specific difference in expression and splice-site choice in Inpp5b, an inositol polyphosphate 5-phosphatase paralogous to the enzyme deficient in Lowe Syndrome SO MAMMALIAN GENOME LA English DT Article ID PROTEIN OCRL1 INTERACTS; TRANS-GOLGI NETWORK; OCULOCEREBRORENAL SYNDROME; GENE; MUTATIONS; BINDING; CLATHRIN; DOMAIN; LOCALIZATION; TRAFFICKING AB The oculocerebrorenal syndrome of Lowe (OCRL; MIM #309000) is an X-linked human disorder characterized by congenital cataracts, mental retardation, and renal proximal tubular dysfunction caused by loss-of-function mutations in the OCRL gene that encodes Ocrl, a type II phosphatidylinositol bisphosphate (PtdIns4,5P(2)) 5-phosphatase. In contrast, mice with complete loss-of-function of the highly homologous ortholog Ocrl have no detectable renal, ophthalmological, or central nervous system abnormalities. We inferred that the disparate phenotype between Ocrl-deficient humans and mice was likely due to differences in how the two species compensate for loss of the Ocrl enzyme. We therefore turned our attention to Inpp5b, another type II PtdIns4,5P(2) 5-phosphatase encoded by Inpp5b in mice and INPP5B in humans, as potential compensating genes in the two species, because Inpp5b/INPP5B are the most highly conserved paralogs to Ocrl/OCRL in the respective genomes of both species and Inpp5b demonstrates functional overlap with Ocrl in mice in vivo. We used in silico sequence analysis, reverse-transcription PCR, quantitative PCR, and transient transfection assays of promoter function to define splice-site usage and the function of an internal promoter in mouse Inpp5b versus human INPP5B. We found mouse Inpp5b and human INPP5B differ in their transcription, splicing, and primary amino acid sequence. These observations form the foundation for analyzing the functional basis for the difference in how Inpp5b and INPP5B compensate for loss of Ocrl function and, by providing insight into the cellular roles of Ocrl and Inpp5b, aid in the development of a model system in which to study Lowe syndrome. C1 [Bothwell, Susan P.; Hoagland, Adam; Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. [Nussbaum, Robert L.] Univ Calif San Francisco, Sch Med, Inst Human Genet, San Francisco, CA 94143 USA. [Farber, Leslie W.] NHGRI, Bethesda, MD 20892 USA. [Farber, Leslie W.] George Washington Univ, Sch Biol & Biomed Sci, Washington, DC 20037 USA. RP Nussbaum, RL (reprint author), Univ Calif San Francisco, Dept Med, Sch Med, 513 Parnassus Ave Hse901E,UCSF Box 0794, San Francisco, CA 94143 USA. EM nussbaumr@humgen.ucsf.edu FU Intramural NIH HHS NR 32 TC 14 Z9 14 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP-OCT PY 2010 VL 21 IS 9-10 BP 458 EP 466 DI 10.1007/s00335-010-9281-7 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 679TQ UT WOS:000284184100004 PM 20872266 ER PT J AU Sherman, A AF Sherman, Arthur TI Lessons from models of pancreatic beta cells for engineering glucose-sensing cells SO MATHEMATICAL BIOSCIENCES LA English DT Article DE Calcium; Oscillations; Insulin; Secretion; Diabetes; Cell engineering ID INSULIN-SECRETION; ELECTRICAL-ACTIVITY; CYTOPLASMIC CA2+; IN-VIVO; ENDOPLASMIC-RETICULUM; CALCIUM OSCILLATIONS; COUPLED RECEPTORS; ACTION-POTENTIALS; MINIMAL MODEL; SINGLE-MOUSE AB Mathematical models of pancreatic beta cells suggest design principles that can be applied to engineering cells to sense glucose and secrete insulin. Engineering cells can potentially both contribute to future diabetes therapies and generate new insights into beta-cell function. The focus is on ion channels, Ca(2+) handling, and elements of metabolism that combine to produce the varied oscillatory patterns exhibited by beta cells. (C) 2010 Published by Elsevier Inc. C1 NIDDK, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. RP Sherman, A (reprint author), NIDDK, NIH, Lab Biol Modeling, 12A South Dr,Room 4007, Bethesda, MD 20892 USA. EM asherman@nih.gov FU National Institutes of Health, USA, NIDDK FX The advances in modeling described here would not have been possible without the collaboration on both theory and experiment over more than 15 years with Les Satin and Richard Bertram. I thank Anmar Khadra and Kevin Hall and two anonymous reviewers for helpful comments on the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, USA, NIDDK. NR 75 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD SEP PY 2010 VL 227 IS 1 BP 12 EP 19 DI 10.1016/j.mbs.2010.05.005 PG 8 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 641ZX UT WOS:000281173500002 PM 20580727 ER PT J AU Morens, DM Taubenberger, JK Fauci, AS AF Morens, David M. Taubenberger, Jeffery K. Fauci, Anthony S. TI The 2009 H1N1 Pandemic Influenza Virus: What Next? SO MBIO LA English DT Article ID UNITED-STATES; SEASONAL INFLUENZA; A VIRUS; MORTALITY; REASSORTMENT; EVOLUTION; INFECTION; EPIDEMIC; VACCINES; IMMUNITY AB History suggests that the 2009 pandemic H1N1 influenza virus faces extinction unless it mutates to avoid already high global population immunity. The immune escape mechanisms potentially at its disposal include antigenic drift, antigenic shift via genetic reassortment, and intrasubtypic reassortment. Going back to the late 19th century, the evolutionary histories of past pandemic viruses are examined in an effort to better understand the nature and extent of the immune pressures faced by the 2009 pandemic virus in the immediate future. While human influenza viruses have often surprised us, available evidence leads to the hope that the current pandemic virus will continue to cause low or moderate mortality rates if it does not become extinct. C1 [Morens, David M.; Taubenberger, Jeffery K.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM dmorens@niaid.nih.gov NR 40 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD SEP-OCT PY 2010 VL 1 IS 4 AR e00211-10 DI 10.1128/mBio.00211-10 PG 5 WC Microbiology SC Microbiology GA 686TG UT WOS:000284718000001 ER PT J AU Jun, SB Smith, KL Shain, W Dowell-Mesfin, NM Kim, SJ Hynd, MR AF Jun, Sang Beom Smith, Karen L. Shain, William Dowell-Mesfin, Natalie M. Kim, Sung June Hynd, Matthew R. TI Optical monitoring of neural networks evoked by focal electrical stimulation on microelectrode arrays using FM dyes SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Neural network; FM dye; Focal stimulation; Microelectrode array AB Patch-clamping or microelectrode arrays (MEA) are conventional methods to monitor the electrical activity in biological neural networks in vitro. Despite the effectiveness of these techniques, there are disadvantages including the limited number of electrodes and the predetermined location of electrodes in MEAs. In particular, these drawbacks raise a difficulty in monitoring a number of neurons outnumbering the electrodes. Here, we propose an optical technique to determine the effective range of focal electrical stimulation using FM dyes in neural networks grown on planar-type MEAs. After 3 weeks in culture, electrical stimulation was delivered to neural networks via an underlying electrode in the presence of FM dyes. The stimulation induced the internalization of the dye into the neurons around the stimulating electrodes. Fluorescent images of dye distribution successfully showed the effects of focal stimulation. A range of stimulus amplitudes and frequencies were examined to collect fluorescence images. FM-dye uptake after electrical stimulation resulted in the labeling of cells up to approximately 300 mu m away from the stimulating electrode. Fluorescence intensity increased proportionally to stimulation amplitude. Tetrodotoxin was shown to inhibit the labeling of neurons except those located immediately adjacent (within 40 mu m) from the stimulating electrode. In the presence of AMPA and NMDA receptors antagonists, the FM-dye labeling appeared within 80 mu m from the electrode, indicating directly evoked neural networks via blocking of glutamatergic synaptic transmission. These results showed that FM dyes can be a useful tool for monitoring activity-dependent synaptic events and determining the effect of focal stimulation in cultured neural networks. C1 [Jun, Sang Beom; Kim, Sung June] Seoul Natl Univ, Nanobioelect & Syst Res Ctr, Seoul 151742, South Korea. [Jun, Sang Beom; Kim, Sung June] Seoul Natl Univ, Sch Elect Engn & Comp Sci, Seoul 151742, South Korea. [Smith, Karen L.; Shain, William] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. [Dowell-Mesfin, Natalie M.] SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12203 USA. [Hynd, Matthew R.] SUNY Albany, Coll Nanoscale Sci & Engn, Albany, NY 12203 USA. RP Jun, SB (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD USA. EM tonijun@gmail.com FU International Collaboration Program NBS-ERC/KOSEF; NIBIB [R21-EB 007782, P41-EB002003]; NINDS [R01-NS0044287] FX This study was supported by the International Collaboration Program NBS-ERC/KOSEF (SJK), NIBIB R21-EB 007782 (MRH), P41-EB002003 (WS), and NINDS R01-NS0044287 (WS). Wide-field microscopy was performed in the Wadsworth Center Advanced microscopy and Image Analysis Core. The authors thank Dr. Stephen R. Ikeda in NIAAA/NIH and J. W. Kim in Seoul National University for the technical guidance for image analysis and the fabrication of microelectrode arrays, respectively. NR 13 TC 0 Z9 0 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 2010 VL 48 IS 9 BP 933 EP 940 DI 10.1007/s11517-010-0628-8 PG 8 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 642XQ UT WOS:000281255600011 PM 20490941 ER PT J AU Strech, D Hurst, S Danis, M AF Strech, Daniel Hurst, Samia Danis, Marion TI The Role of Ethics Committees and Ethics Consultation in Allocation Decisions A 4-Stage Process SO MEDICAL CARE LA English DT Article DE rationing; prioritization; ethics committees; ethics consultation; hospital management ID HEALTH-CARE; CLINICAL-PRACTICE; MEDICAL LITERATURE; SCARCE RESOURCES; GENERAL-PRACTICE; USERS GUIDES; PHYSICIANS; COST; BEDSIDE; PERCEPTIONS AB Background: Decisions about the allocation and rationing of medical interventions likely occur in all health care systems worldwide. So far very little attention has been given to the question of what role ethics consultation and ethics committees could or should play in questions of allocation at the hospital level. Objectives and Methods: This article argues for the need for ethics consultation in rationing decisions using empirical data about the status quo and the inherent nature of bedside rationing. Subsequently, it introduces a 4-stage process for establishing and conducting ethics consultation in rationing questions with systematic reference to core elements of procedural justice. Results: Qualitative and quantitative findings show a significant demand for ethics consultation expressed directly by doctors, as well as additional indirect evidence of such a need as indicated by ethically challenging circumstances of inconsistent and structurally disadvantaging rationing decisions. To address this need, we suggest 4 stages for establishing and conducting ethics consultation in rationing questions we recommend: (1) training, (2) identifying actual scarcity-related problems at clinics, (3) supporting decision-making, and (4) evaluation. Conclusion: This process of ethics consultation regarding rationing decisions would facilitate the achievement of several practical goals: (i) encouragement of an awareness and understanding of ethical problems in bedside rationing, (ii) encouragement of achieving efficiency along with rationing, (iii) reinforcement of consistency in inter-and intraindvidual decision-making, (iv) encouragement of explicit reflection and justification of the prioritization criteria taken into consideration, (v) improvement in internal (in-house) and external transparency, and (vi) prevention of the misuse of the corresponding consulting structures. C1 [Strech, Daniel] Hannover Med Sch, Inst Hist Eth & Philosophy Med, Ctr Publ Hlth & Healthcare, D-3000 Hannover, Germany. [Hurst, Samia] Univ Geneva, Sch Med, Inst Biomed Eth, CH-1211 Geneva, Switzerland. [Danis, Marion] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Strech, D (reprint author), Inst Geschichte Eth & Philosophie Med, Carl Neuberg St 1, D-30625 Hannover, Germany. EM strech.daniel@mh-hannover.de RI Hurst, Samia/A-9661-2008; OI Hurst, Samia/0000-0002-1980-5226; Strech, Daniel/0000-0002-9153-079X FU Intramural NIH HHS [Z99 CL999999] NR 42 TC 5 Z9 5 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2010 VL 48 IS 9 BP 821 EP 826 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 641JZ UT WOS:000281122800009 PM 20706163 ER PT J AU Rothney, MP Brychta, RJ Meade, NN Chen, KY Buchowski, MS AF Rothney, Megan P. Brychta, Robert J. Meade, Natalie N. Chen, Kong Y. Buchowski, Maciej S. TI Validation of the ActiGraph Two-Regression Model for Predicting Energy Expenditure SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ACCELEROMETRY; INDIRECT CALORIMETRY; DOUBLY LABELED WATER; LOW-PASS FILTER ID DOUBLY-LABELED-WATER; ARTIFICIAL NEURAL-NETWORK; PHYSICAL-ACTIVITY; COMPUTER-SCIENCE; UNITED-STATES; TIME SPENT; ACCELEROMETER; CALIBRATION; ADULTS; INC. AB ROTHNEY, M. P., R. J. BRYCHTA, N. N. MEADE, K. Y. CHEN, and M. S. BUCHOWSKI. Validation of the ActiGraph Two-Regression Model for Predicting Energy Expenditure. Med. Sci. Sports Exerc., Vol. 42, No. 9, pp. 1785-1792, 2010. Purpose: The purpose of this study was to validate a two-regression model for predicting energy expenditure (EE) from ActiGraph GT1M accelerometer-generated activity counts using a whole-room indirect calorimeter and the doubly labeled water (DLW) technique. We also investigated if a low-pass filter (LPF) approach would improve the model's accuracy in the minute-to-minute EE prediction. Methods: Thirty-four healthy volunteers (age = 20-67 yr, body mass index = 19.3-52.1 kg.m(-2)) spent approximately 24 h in a room calorimeter while wearing a GT1M monitor and performed structured and self-selected activities followed by overnight sleep. The EE predicted by the models and expressed in metabolic equivalents (MET-minutes) during waking times was compared with the room calorimeter-measured EE. A subset of volunteers (n = 22) completed a 14-d DLW protocol in free living while wearing an ActiGraph. The average daily EE predicted by the models (MET-minutes) was compared with the DLW. Results: Compared with the room calorimeter, the two-regression model overpredicted EE by 10.2% +/- 11.4% (1282 +/- 125 and 1174 +/- 152 MET.min, P < 0.001) and time spent in moderate physical activity (PA) by 36.9 perpendicular to 46.0 min while underestimating the time spent in light PA by -48.3 perpendicular to 55.0 min (P < 0.05). The LPF reduced the squared and mean absolute error in the EE prediction (P < 0.05) but not the prediction error in time spent in moderate or light PA (both P > 0.05). The EE measured by DLW (2108 +/- 358 MET.min.d(-1)) and predicted by both filtered and unfiltered models (2104 +/- 218 and 2192 +/- 228 MET.min.d(-1), respectively) were similar (P > 0.05). Conclusions: The two-regression model with LPF showed good agreement with total EE measured using room calorimeter and DLW. However, the individual variability in assessing time spent in sedentary, low, and moderate PA intensities and related EE remains significant. C1 [Rothney, Megan P.; Brychta, Robert J.; Chen, Kong Y.] NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. [Meade, Natalie N.; Chen, Kong Y.; Buchowski, Maciej S.] Vanderbilt Univ, Med Ctr, Dept Med, Energy Balance Lab,Div Gastroenterol Hepatol & Nu, Nashville, TN USA. RP Brychta, RJ (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 6-3940, Bethesda, MD 20892 USA. EM brychtar@niddk.nih.gov RI Buchowski, Maciej/A-2683-2008; OI Buchowski, Maciej/0000-0002-0566-1743; Chen, Kong/0000-0002-0306-1904 FU NIH/NIDDK [R01 DK69465]; NCRR/NIH [1UL1 RR024975]; Vanderbilt Diabetes Research and Training Center [DK20593]; NIH/NHLB [R01 HL082988]; NIDDK/NIH [Z01-DK071044] FX This study was supported in part by grant No. R01 DK69465 from NIH/NIDDK, the Vanderbilt Institute for Clinical and Translational Research (VICTR) grant No. 1UL1 RR024975 from NCRR/NIH, and the Vanderbilt Diabetes Research and Training Center grant No. DK20593. MSB was also supported by R01 HL082988 from NIH/NHLB. MPR, RJB, and KYC were supported by Intramural Research Program of the NIDDK/NIH (Z01-DK071044). NR 29 TC 23 Z9 23 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 2010 VL 42 IS 9 BP 1785 EP 1792 DI 10.1249/MSS.0b013e3181d5a984 PG 8 WC Sport Sciences SC Sport Sciences GA 641JE UT WOS:000281120500022 PM 20142778 ER PT J AU McHone, B Jarrett, TW Pinto, PA AF McHone, B. Jarrett, T. W. Pinto, P. A. TI Tips and tricks of laparoscopic partial nephrectomy SO MINERVA UROLOGICA E NEFROLOGICA LA English DT Review DE Nephrectomy; Laparoscopy; Surgical procedures, operative; Robotics; Kidney neoplasms AB The field of urology has embraced minimally invasive surgical procedures, from endoscopic to laparoscopic to robotic assisted surgery. As these surgical techniques are applied to renal cancer, the oncological outcomes need to be compared to more traditional open surgery. Laparoscopic partial nephrectomy emulates the open surgical technique and has become an alternative to open surgery at many academic centers. Still its wide spread adoption has been limited by the challenges of renal mass extirpation and renal reconstruction in a timely fashion to limit renal ischemia. The following review is designed to assist the urologic surgeon in performing a successful laparoscopic partial nephrectomy by detailing the "tips and tricks" of the procedure. C1 [McHone, B.; Pinto, P. A.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jarrett, T. W.] George Washington Univ, Dept Urol, Washington, DC 20052 USA. RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM pintop@mail.nih.gov NR 25 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0393-2249 J9 MINERVA UROL NEFROL JI Minerva Urol. Nefrol. PD SEP PY 2010 VL 62 IS 3 BP 273 EP 281 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA V28DM UT WOS:000208661500008 PM 20940696 ER PT J AU Schellmann, N Deckert, PM Bachran, D Fuchs, H Bachran, C AF Schellmann, N. Deckert, P. M. Bachran, D. Fuchs, H. Bachran, C. TI Targeted Enzyme Prodrug Therapies SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review DE ADEPT; GDEPT; cancer; gene therapy; antibody ID SUICIDE GENE-THERAPY; PURINE NUCLEOSIDE PHOSPHORYLASE; MONOCLONAL-ANTIBODY A33; ADVANCED COLORECTAL-CARCINOMA; RECOMBINANT FUSION PROTEIN; ADVANCED COLON-CANCER; I CLINICAL-TRIAL; PHASE-I; CYTOSINE DEAMINASE; PROSTATE-CANCER AB The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview of the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial - (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs. C1 [Schellmann, N.; Bachran, D.; Fuchs, H.] Charite, Zent Inst Lab Med & Pathobiochem, D-12200 Berlin, Germany. [Deckert, P. M.] Stadt Klinikum Brandenburg GmbH, Innere Med Gastroenterol Onkol 2, D-14770 Brandenburg, Germany. [Bachran, C.] NIAID, NIH, Bethesda, MD 20892 USA. RP Fuchs, H (reprint author), Charite, Zent Inst Lab Med & Pathobiochem, Campus Benjamin Franklin,Hindenburgdamm 30, D-12200 Berlin, Germany. EM hendrik.fuchs@charite.de FU Deutsche Krebshilfe [108492]; Deutsche Forschungsgemeinschaft [FU 408/3-1]; Sonnenfeld-Stiftung; Berliner Krebsgesellschaft [FUFF200801] FX We are grateful to Athulaprabha Murthi for carefully proofreading the manuscript. We acknowledge the generous financial support of the Deutsche Krebshilfe (108492), the Deutsche Forschungsgemeinschaft (FU 408/3-1), the Sonnenfeld-Stiftung via a scholarship for D. B. and the Berliner Krebsgesellschaft (FUFF200801). NR 149 TC 31 Z9 32 U1 5 U2 66 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD SEP PY 2010 VL 10 IS 10 BP 887 EP 904 PG 18 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 653LN UT WOS:000282093000001 PM 20560876 ER PT J AU Abdelmohsen, K Hutchison, ER Lee, EK Kuwano, Y Kim, MM Masuda, K Srikantan, S Subaran, SS Marasa, BS Mattson, MP Gorospe, M AF Abdelmohsen, Kotb Hutchison, Emmette R. Lee, Eun Kyung Kuwano, Yuki Kim, Mihee M. Masuda, Kiyoshi Srikantan, Subramanya Subaran, Sarah S. Marasa, Bernard S. Mattson, Mark P. Gorospe, Myriam TI miR-375 Inhibits Differentiation of Neurites by Lowering HuD Levels SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING PROTEIN HUD; GAP-43 MESSENGER-RNA; NEURONAL ELAV PROTEINS; DEPENDENT EXPRESSION; CELL-PROLIFERATION; ANIMAL DEVELOPMENT; UP-REGULATION; PC12 CELLS; MICRORNAS; ASSOCIATION AB Neuronal development and plasticity are maintained by tightly regulated gene expression programs. Here, we report that the developmentally regulated microRNA miR-375 affects dendrite formation and maintenance. miR-375 overexpression in mouse hippocampus potently reduced dendrite density. We identified the predominantly neuronal RNA-binding protein HuD as a key effector of miR-375 influence on dendrite maintenance. Heterologous reporter analysis verified that miR-375 repressed HuD expression through a specific, evolutionarily conserved site on the HuD 3' untranslated region. miR-375 overexpression lowered both HuD mRNA stability and translation and recapitulated the effects of HuD silencing, which reduced the levels of target proteins with key functions in neuronal signaling and cytoskeleton organization (N-cadherin, PSD-95, RhoA, NCAM1, and integrin alpha 1). Moreover, the increase in neurite outgrowth after brain-derived neurotrophic factor (BDNF) treatment was diminished by miR-375 overexpression; this effect was rescued by reexpression of miR-375-refractory HuD. Our findings indicate that miR-375 modulates neuronal HuD expression and function, in turn affecting dendrite abundance. C1 [Abdelmohsen, Kotb; Lee, Eun Kyung; Kuwano, Yuki; Kim, Mihee M.; Masuda, Kiyoshi; Srikantan, Subramanya; Marasa, Bernard S.; Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. [Hutchison, Emmette R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Hutchison, Emmette R.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Subaran, Sarah S.] NIA, Confocal Imaging Facil, Res Resources Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Abdelmohsen, K (reprint author), NIA, LCMB, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM abdelmohsenk@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU National Institute on Aging; National Institutes of Health [Z01-AG000518-5] FX This research was supported entirely by the National Institute on Aging-Intramural Research Program, National Institutes of Health, Z01-AG000518-5. NR 50 TC 65 Z9 70 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2010 VL 30 IS 17 BP 4197 EP 4210 DI 10.1128/MCB.00316-10 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 636TF UT WOS:000280762900009 PM 20584986 ER PT J AU Lee, RCH Gill, EE Roy, SW Fast, NM AF Lee, Renny C. H. Gill, Erin E. Roy, Scott W. Fast, Naomi M. TI Constrained Intron Structures in a Microsporidian SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE intron; Encephalitozoon cuniculi; genome reduction; microsporidia; intron loss; splice site selection ID SPLICEOSOMAL INTRONS; ENCEPHALITOZOON-CUNICULI; SACCHAROMYCES-CEREVISIAE; GENOME; EVOLUTION; TRANSCRIPT; SEQUENCE; NUCLEUS; SIGNALS; GENES AB The 2.9-Mbp genome of the microsporidian Encephalitozoon cuniculi is severely reduced and compacted, possessing only 16 known tiny spliceosomal introns. Based on motif and expression data, intron profiles were constructed to screen the genome. Twenty additional introns were predicted and verified, doubling the previous estimate. We further predict that accurate 3' splice site (3'SS) selection is accomplished via a scanning mechanism with specificity achieved by maintaining a constrained variable length between the branch point motif and 3'SS. Only introns in ribosomal protein genes exhibit positional bias, and we hypothesize that splicing could be regulating expression of these genes. The large set of new introns in non-ribosomal protein genes suggests that current models of intron loss are unlikely sufficient to explain the distribution of introns. Together, these results extend our understanding of the role of intron loss in genome evolution and contribute to a novel model for splice site selection. C1 [Lee, Renny C. H.; Gill, Erin E.; Fast, Naomi M.] Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Lee, Renny C. H.; Gill, Erin E.; Fast, Naomi M.] Univ British Columbia, Dept Bot, Vancouver, BC V5Z 1M9, Canada. [Roy, Scott W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Fast, NM (reprint author), Univ British Columbia, Biodivers Res Ctr, Vancouver, BC V5Z 1M9, Canada. EM nfast@interchange.ubc.ca FU Natural Sciences and Engineering Research Council of Canada [262988] FX We thank Lisa Bowers and Elizabeth Didier for generous gifts of material. This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (262988 to N.M.F.). NR 21 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD SEP PY 2010 VL 27 IS 9 BP 1979 EP 1982 DI 10.1093/molbev/msq087 PG 4 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 642DO UT WOS:000281184100001 PM 20360213 ER PT J AU Firth, C Kitchen, A Shapiro, B Suchard, MA Holmes, EC Rambaut, A AF Firth, Cadhla Kitchen, Andrew Shapiro, Beth Suchard, Marc A. Holmes, Edward C. Rambaut, Andrew TI Using Time-Structured Data to Estimate Evolutionary Rates of Double-Stranded DNA Viruses SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE double-stranded DNA viruses; nucleotide substitution rates; evolution; codivergence; variola virus ID VARICELLA-ZOSTER-VIRUS; PHYLOGENETIC ANALYSIS; MOLECULAR EVOLUTION; HUMAN-POPULATIONS; SPONTANEOUS MUTATION; SEQUENCES; GENOME; SUBSTITUTION; DIVERSITY; INFERENCE AB Double-stranded (ds) DNA viruses are often described as evolving through long-term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution. However, the hypothesis of codivergence between dsDNA viruses and their hosts has rarely been rigorously tested, even though the vast majority of nucleotide substitution rate estimates for dsDNA viruses are based upon this assumption. It is therefore important to estimate the evolutionary rates of dsDNA viruses independent of the assumption of host-virus codivergence. Here, we explore the use of temporally structured sequence data within a Bayesian framework to estimate the evolutionary rates for seven human dsDNA viruses, including variola virus (VARV) (the causative agent of smallpox) and herpes simplex virus-1. Our analyses reveal that although the VARV genome is likely to evolve at a rate of approximately 1 x 10(-5) substitutions/site/year and hence approaching that of many RNA viruses, the evolutionary rates of many other dsDNA viruses remain problematic to estimate. Synthetic data sets were constructed to inform our interpretation of the substitution rates estimated for these dsDNA viruses and the analysis of these demonstrated that given a sequence data set of appropriate length and sampling depth, it is possible to use time-structured analyses to estimate the substitution rates of many dsDNA viruses independently from the assumption of host-virus codivergence. Finally, the discovery that some dsDNA viruses may evolve at rates approaching those of RNA viruses has important implications for our understanding of the long-term evolutionary history and emergence potential of this major group of viruses. C1 [Firth, Cadhla; Kitchen, Andrew; Shapiro, Beth; Holmes, Edward C.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. [Suchard, Marc A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Holmes, Edward C.; Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland. RP Firth, C (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA. EM cbf2118@columbia.edu OI Rambaut, Andrew/0000-0003-4337-3707; Shapiro, Beth/0000-0002-2733-7776; Holmes, Edward/0000-0001-9596-3552 FU Natural Sciences and Engineering Research Council of Canada; United States Public Health Service [GM086887] FX C. F. received funding from the Natural Sciences and Engineering Research Council of Canada. M. A. S. is supported by United States Public Health Service grant GM086887. We thank the National Evolutionary Synthesis Center for hosting the working group "Software for BEAST,'' from which this project profited. NR 78 TC 90 Z9 92 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD SEP PY 2010 VL 27 IS 9 BP 2038 EP 2051 DI 10.1093/molbev/msq088 PG 14 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 642DO UT WOS:000281184100007 PM 20363828 ER PT J AU Sekine, Y Demosky, SJ Stonik, JA Furuya, Y Koike, H Suzuki, K Remaley, AT AF Sekine, Yoshitaka Demosky, Steve J. Stonik, John A. Furuya, Yosuke Koike, Hidekazu Suzuki, Kazuhiro Remaley, Alan T. TI High-Density Lipoprotein Induces Proliferation and Migration of Human Prostate Androgen-Independent Cancer Cells by an ABCA1-Dependent Mechanism SO MOLECULAR CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; CHOLESTEROL EFFLUX; SPHINGOSINE 1-PHOSPHATE; PLASMA-LIPOPROTEINS; SIGNAL-TRANSDUCTION; SCAVENGER RECEPTOR; ENDOTHELIAL-CELLS; STATINS; AKT; MACROPHAGES AB Androgen deprivation therapy for prostate cancer leads to a significant increase of high-density lipoprotein (HDL), which is generally viewed as beneficial, particularly for cardiovascular disease, but the effect of HDL on prostate cancer is unknown. In this study, we investigated the effect of HDL on prostate cancer cell proliferation, migration, intracellular cholesterol levels, and the role of cholesterol transporters, namely ABCA1, ABCG1, and SR-BI in these processes. HDL induced cell proliferation and migration of the androgen-independent PC-3 and DU145 cells by a mechanism involving extracellular signal-regulated kinase (ERK) 1/2 and Akt, but had no effect on the androgen-dependent LNCaP cell, which did not express ABCA1 unlike the other cell lines. Treatment with HDL did not significantly alter the cholesterol content of the cell lines. Knockdown of ABCA1 but not ABCG1 or SR-BI by small interfering RNA (siRNA) inhibited HDL-induced cell proliferation, migration, and ERK1/2 and Akt signal transduction in PC-3 cells. Moreover, after treatment of LNCaP cells with charcoal-stripped fetal bovine serum, ABCA1 was induced similar to 10-fold, enabling HDL to induce ERK1/2 activation, whereas small interfering RNA knockdown of ABCA1 inhibited HDL-induced ERK1/2 activation. Simvastatin, which inhibited ABCA1 expression in PC-3 and DU145 cells, attenuated HDL-induced PC-3 and DU145 cell proliferation, migration, and ERK1/2 and Akt phosphorylation. In human prostate biopsy samples, ABCA1 mRNA expression was similar to 2-fold higher in the androgen deprivation therapy group than in subjects with benign prostatic hyperplasia or pretreatment prostate cancer groups. In summary, these results suggest that HDL by an ABCA1-dependent mechanism can mediate signal transduction, leading to increased proliferation and migration of prostate cancer cells. Mol Cancer Res; 8(9); 1284-94. (C)2010 AACR. C1 [Sekine, Yoshitaka; Demosky, Steve J.; Stonik, John A.; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Sekine, Yoshitaka; Furuya, Yosuke; Koike, Hidekazu; Suzuki, Kazuhiro] Gunma Univ, Grad Sch Med, Dept Urol, Gunma, Japan. RP Sekine, Y (reprint author), NHLBI, Lipoprot Metab Sect, Pulm & Vasc Med Branch, NIH, Bldg 10,Room 8N224,9000 Rockville Pike, Bethesda, MD 20892 USA. EM ysekine@showa.gunma-u.ac.jp FU NHBLI FX Research by A. T. Remaley and Y. Sekine was supported by intramural NHBLI funding. NR 43 TC 29 Z9 29 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2010 VL 8 IS 9 BP 1284 EP 1294 DI 10.1158/1541-7786.MCR-10-0008 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 650RI UT WOS:000281868700011 PM 20671065 ER PT J AU Yasuda, M Schmid, T Rubsamen, D Colburn, NH Irie, K Murakami, A AF Yasuda, Michiko Schmid, Tobias Ruebsamen, Daniela Colburn, Nancy H. Irie, Kazuhiro Murakami, Akira TI Downregulation of Programmed Cell Death 4 by Inflammatory Conditions Contributes to the Generation of the Tumor Promoting Microenvironment SO MOLECULAR CARCINOGENESIS LA English DT Article DE Pdcd4; TNF-alpha; inflammation ID COLON-CARCINOMA CELLS; PDCD4; EXPRESSION; CANCER; MACROPHAGES; SUPPRESSOR; INHIBITOR; INDUCTION; RECEPTOR; PROTEIN AB Ample evidence has shown key roles of inflammation in tumor promotion and carcinogenesis, and tumor-associated macrophages are known to promote tumor growth and dissemination. Programmed cell death 4 (Pdcd4) is a novel tumor suppressor, and although various studies have revealed that the functions and expression mechanisms of Pdcd4 in tumor promotion, those in regard to inflammation remain unclear. In the present study, we examined whether inflammatory stimuli regulate Pdcd4 expression. 12-O-tetradecanoylphorbol 13-acetate (TPA) suppressed expression of pdcd4 mRNA in human monocytic cell lines (U937, THP-1). Similarly, the bacterial endotoxin lipopolysaccharide (LPS) downregulated pdcd4 level in mouse RAW264.7 and peritoneal macrophages. Furthermore, conditioned medium from LPS-stimulated RAW264.7 macrophages suppressed pdcd4 mRNA in RAW264.7 macrophages, and findings obtained with recombinant tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha-specific siRNA suggested that TNF-alpha partly mediates [PS-triggered Pdcd4 downregulation via an autocrine mechanism. Specific inhibitors of phosphoinositide-3-kinase (PI3K) and c-jun N-terminus kinase (JNK) restored LPS-abolished pdcd4 mRNA. Consistently, in MCF7 mammary carcinoma cells, conditioned medium from TPA-differentiated/activated U937 cells suppressed pdcd4 mRNA. Additionally, knockdown of pdcd4 in RAW264.7 macrophages using siRNA significantly enhanced [PS-induced TNF-alpha protein production, and interferon-gamma, CC chemokine ligand (Ccl) 1, Ccl20, and interleukin-10 mRNA expression. These results suggest that Pdcd4 suppresses the induction of these inflammatory mediators. Taken together, loss of Pdcd4 in macrophages may be a critical step in establishing the inflammatory environment while that in tumor cells contributes to tumor progression. (C) 2010 Wiley-Liss, Inc. C1 [Murakami, Akira] Kyoto Univ, Div Food Sci & Biotechnol, Grad Sch Agr, Sakyo Ku, Kyoto 6068502, Japan. [Schmid, Tobias; Ruebsamen, Daniela] Goethe Univ Frankfurt, Sch Med, Inst Biochem 1, Frankfurt, Germany. [Colburn, Nancy H.] NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21701 USA. RP Murakami, A (reprint author), Kyoto Univ, Div Food Sci & Biotechnol, Grad Sch Agr, Sakyo Ku, Oiwake Cho, Kyoto 6068502, Japan. RI Irie, Kazuhiro/A-6121-2014; OI Irie, Kazuhiro/0000-0001-7109-8568; Yasuda, Michiko/0000-0002-8984-6138 FU Ministry of Health, Labor and Welfare of Japan; Hessian Ministry of Higher Education, Research and the Arts [III L 4-518/55.004] FX This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (A.M.) and the LOEWE Schwerpunkt OSF (III L 4-518/55.004 (2009)) funded by the Hessian Ministry of Higher Education, Research and the Arts (T.S.). NR 39 TC 19 Z9 20 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 2010 VL 49 IS 9 BP 837 EP 848 DI 10.1002/mc.20660 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 639ZI UT WOS:000281015800007 PM 20607724 ER PT J AU Biek, R Real, LA AF Biek, Roman Real, Leslie A. TI The landscape genetics of infectious disease emergence and spread SO MOLECULAR ECOLOGY LA English DT Review DE emerging infectious diseases; gene flow; heterogeneity; invasion; molecular epidemiology; parasite ID HANTAVIRUS PULMONARY SYNDROME; RABBIT ORYCTOLAGUS-CUNICULUS; RABIES VIRUS; MOLECULAR EVOLUTION; AVIAN INFLUENZA; PEROMYSCUS-MANICULATUS; EPIDEMIOLOGIC DYNAMICS; IMMUNODEFICIENCY-VIRUS; HEMORRHAGIC-DISEASE; POPULATION-GENETICS AB The spread of parasites is inherently a spatial process often embedded in physically complex landscapes. It is therefore not surprising that infectious disease researchers are increasingly taking a landscape genetics perspective to elucidate mechanisms underlying basic ecological processes driving infectious disease dynamics and to understand the linkage between spatially dependent population processes and the geographic distribution of genetic variation within both hosts and parasites. The increasing availability of genetic information on hosts and parasites when coupled to their ecological interactions can lead to insights for predicting patterns of disease emergence, spread and control. Here, we review research progress in this area based on four different motivations for the application of landscape genetics approaches: (i) assessing the spatial organization of genetic variation in parasites as a function of environmental variability, (ii) using host population genetic structure as a means to parameterize ecological dynamics that indirectly influence parasite populations, for example, gene flow and movement pathways across heterogeneous landscapes and the concurrent transport of infectious agents, (iii) elucidating the temporal and spatial scales of disease processes and (iv) reconstructing and understanding infectious disease invasion. Throughout this review, we emphasize that landscape genetic principles are relevant to infection dynamics across a range of scales from within host dynamics to global geographic patterns and that they can also be applied to unconventional 'landscapes' such as heterogeneous contact networks underlying the spread of human and livestock diseases. We conclude by discussing some general considerations and problems for inferring epidemiological processes from genetic data and try to identify possible future directions and applications for this rapidly expanding field. C1 [Biek, Roman] Univ Glasgow, Div Ecol & Evolutionary Biol, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland. [Real, Leslie A.] Emory Univ, Dept Biol, Ctr Dis Ecol, Atlanta, GA 30322 USA. [Real, Leslie A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Biek, R (reprint author), Univ Glasgow, Div Ecol & Evolutionary Biol, Boyd Orr Ctr Populat & Ecosyst Hlth, Glasgow G12 8QQ, Lanark, Scotland. EM r.biek@bio.gla.ac.uk OI Biek, Roman/0000-0003-3471-5357 FU University of Glasgow; National Institutes of Health [RO1 AI047498]; Science and Technology Directorate, Department of Homeland Security; Fogarty International Center, National Institutes of Health FX This research was supported by the University of Glasgow Kelvin-Smith Fellowship to RB, National Institutes of Health grant RO1 AI047498 to LAR and by the RAPIDD Program of the Science and Technology Directorate, Department of Homeland Security and the Fogarty International Center, National Institutes of Health. We thank several reviewers for their helpful comments on an earlier draft of this manuscript and the authors whose work we reproduced for sharing their graphic material. NR 105 TC 68 Z9 68 U1 9 U2 75 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD SEP PY 2010 VL 19 IS 17 SI SI BP 3515 EP 3531 DI 10.1111/j.1365-294X.2010.04679.x PG 17 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 643HC UT WOS:000281285200003 PM 20618897 ER PT J AU Margolis, R Smith, P AF Margolis, Ronald Smith, Philip TI Commentary: Parallel Evolution of Molecular Endocrinology as a Journal and a Discipline: Convergence of Interests with the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK/NIH) SO MOLECULAR ENDOCRINOLOGY LA English DT Editorial Material ID NUCLEAR RECEPTOR SUPERFAMILY; THYROID-HORMONE RECEPTOR; FIBROBLAST-GROWTH-FACTOR; BINDING-SITES; CO-REPRESSOR; COACTIVATOR; ATLAS; EXPRESSION; ENHANCER; OBESITY AB The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) celebrates in 2010 its 60(th) year as an institute of the National Institutes of Health. NIDDK has been fundamental in providing support for research in endocrinology, fostering research to elucidate basic principles of endocrine signaling leading to understanding of diseases and disorders of hormone action. Over this time span, a move to a more molecular level in understanding of the basis of hormone action has emerged and been supported by NIDDK, with many advances finding their way into a new journal, Molecular Endocrinology. The merging of disciplines that has made this possible constitutes a major force for further progress as NIDDK moves forward over the next 60 yr. Together, NIDDK and Molecular Endocrinology have served as catalysts for advancing knowledge in the field, energizing new paradigms that have led to advances in the clinic. (Molecular Endocrinology 24: 1697-1702, 2010) C1 [Margolis, Ronald] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Margolis, R (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd,Room 693, Bethesda, MD 20892 USA. EM margolisr@mail.nih.gov OI Margolis, Ronald/0000-0002-8956-0455 NR 34 TC 0 Z9 0 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2010 VL 24 IS 9 BP 1697 EP 1702 DI 10.1210/me.2010-0168 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644OE UT WOS:000281387300001 PM 20660301 ER PT J AU Nader, N Ng, SSM Lambrou, GI Pervanidou, P Wang, YH Chrousos, GP Kino, T AF Nader, Nancy Ng, Sinnie Sin Man Lambrou, George I. Pervanidou, Panagiota Wang, Yonghong Chrousos, George P. Kino, Tomoshige TI AMPK Regulates Metabolic Actions of Glucocorticoids by Phosphorylating the Glucocorticoid Receptor through p38 MAPK SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; CELL-PERMEABLE ACTIVATOR; N-TERMINAL KINASE; TRANSCRIPTIONAL ACTIVITY; INDUCED APOPTOSIS; SKELETAL-MUSCLE; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE; CLINICAL-IMPLICATIONS; GENE-TRANSCRIPTION; INSULIN-RESISTANCE AB Glucocorticoids play central roles in the regulation of energy metabolism by shifting it toward catabolism, whereas AMP-activated protein kinase (AMPK) is the master regulator of energy homeostasis, sensing energy depletion and stimulating pathways of increasing fuel uptake and saving on peripheral supplies. We showed here that AMPK regulates glucocorticoid actions on carbohydrate metabolism by targeting the glucocorticoid receptor (GR) and modifying transcription of glucocorticoid-responsive genes in a tissue- and promoter-specific fashion. Activation of AMPK in rats reversed glucocorticoid-induced hepatic steatosis and suppressed glucocorticoid-mediated stimulation of glucose metabolism. Transcriptomic analysis in the liver suggested marked overlaps between the AMPK and glucocorticoid signaling pathways directed mostly from AMPK to glucocorticoid actions. AMPK accomplishes this by phosphorylating serine 211 of the human GR indirectly through phosphorylation and consequent activation of p38 MAPK and by altering attraction of transcriptional coregulators to DNA-bound GR. In human peripheral mononuclear cells, AMPK mRNA expression positively correlated with that of glucocorticoid-responsive glucocorticoid-inducible leucine zipper protein, which correlated also positively with the body mass index of subjects. These results indicate that the AMPK-mediated energy control system modulates glucocorticoid action at target tissues. Because increased action of glucocorticoids is associated with the development of metabolic disorders, activation of AMPK could be a promising target for developing pharmacological interventions to these pathologies. (Molecular Endocrinology 24: 1748-1764, 2010) C1 [Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Natl Inst Hlth,Clin Res Ctr, Bethesda, MD 20892 USA. [Wang, Yonghong] NCI, Adv Technol Ctr, NIH, Bethesda, MD 20892 USA. [Ng, Sinnie Sin Man] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. [Lambrou, George I.; Pervanidou, Panagiota; Chrousos, George P.] Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, Natl Inst Hlth,Clin Res Ctr, Bldg 10,Room 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov OI Lambrou, George/0000-0001-8389-1360 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Cancer Institute, National Institutes of Health; University of Athens FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Cancer Institute, National Institutes of Health, and the University of Athens. NR 66 TC 27 Z9 28 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2010 VL 24 IS 9 BP 1748 EP 1764 DI 10.1210/me.2010-0192 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 644OE UT WOS:000281387300006 PM 20660302 ER PT J AU Vincent, LM Gilbert, F DiPace, JI Ciccone, C Markello, TC Jeong, A Dorward, H Westbroek, W Gahl, WA Bussel, JB Huizing, M AF Vincent, Lisa M. Gilbert, Fred DiPace, Jennifer I. Ciccone, Carla Markello, Thomas C. Jeong, Andrew Dorward, Heidi Westbroek, Wendy Gahl, William A. Bussel, James B. Huizing, Marjan TI Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2 SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE GTPase; Hypopigmentation; Immunodeficiency; Lytic granule; Melanosome; SNP-array ID PARTIAL ALBINISM; GENE; MUTATIONS; DISEASE; MELANOCYTES; MYOSIN; IMMUNODEFICIENCY; CYTOTOXICITY; MECHANISM; ORGANELLE AB Griscelli syndrome (GS), a rare autosomal recessive disorder characterized by partial albinism and immunological impairment and/or severe neurological impairment, results from mutations in the MYO5A (GS1), RAB27A (GS2), or MLPH (GS3) genes. We identified a Hispanic patient born of a consanguineous union who presented with immunodeficiency, partial albinism, hepatic dysfunction, hemophagocytosis, neurological impairment, nystagmus, and silvery hair indicative of Griscelli Syndrome Type 2 (GS2). We screened for point mutations, but only exons 2-6 of the patient's DNA could be PCR-amplified. Whole genome analysis using the Illumina (R) 1M-Duo DNA Analysis BeadChip identified a homozygous deletion in the patient's DNA. The exact breakpoints of the 47.5-kb deletion were identified as chr15q15-q21.1:g.53332432_53379990del (NCBI Build 37.1); the patient lacks the promoter and 5'UTR regions of RAB27A, thus confirming the diagnosis of GS2. Published by Elsevier Inc. C1 [Vincent, Lisa M.; Ciccone, Carla; Markello, Thomas C.; Jeong, Andrew; Dorward, Heidi; Westbroek, Wendy; Gahl, William A.; Huizing, Marjan] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gilbert, Fred] Weill Cornell Med Coll, Div Human Genet, Dept Pediat, New York, NY 10021 USA. [Gilbert, Fred; DiPace, Jennifer I.; Bussel, James B.] New York Presbyterian Weill Cornell Med Ctr, New York, NY 10021 USA. [Gahl, William A.] NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. [DiPace, Jennifer I.; Bussel, James B.] Weill Cornell Med Coll, Dept Pediat, Div Hematol Oncol, New York, NY 10021 USA. RP Huizing, M (reprint author), 10 Ctr Dr,Bldg 10,Rm 10C103,MSC1851, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov FU National Human Genome Research Institute, National Institutes of Health, Bethesda, MD FX We thank the patient's family for participating in our protocol. We thank Jennifer Parkes for excellent laboratory assistance. This study was supported by the Intramural Research program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD. NR 34 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP PY 2010 VL 101 IS 1 BP 62 EP 65 DI 10.1016/j.ymgme.2010.05.015 PG 4 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 644BX UT WOS:000281346500009 PM 20591709 ER PT J AU Chen, Q Decker, KB Boucher, PE Hinton, D Stibitz, S AF Chen, Qing Decker, Kimberly Baxter Boucher, Philip E. Hinton, Deborah Stibitz, Scott TI Novel architectural features of Bordetella pertussis fimbrial subunit promoters and their activation by the global virulence regulator BvgA SO MOLECULAR MICROBIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; MUTATIONAL ANALYSIS; FHA PROMOTER; TRANSCRIPTIONAL ACTIVATION; SEQUENCE SIMILARITIES; RESPONSE REGULATOR; ACCESSORY GENES; BACTERIOPHAGE-T4; DNA; MOTA AB P>A prominent feature of the promoters of Bordetella pertussis fimbrial subunit genes fim2, fim3 and fimX is the presence of a 'C-stretch', a monotonic run of C residues. The C-stretch renders these genes capable of phase variation, through spontaneous variations in its length. For each of these we determined the length of the C-stretch that gave maximal transcriptional activity, and found that the three optimized promoters align perfectly, with identical distances between conserved upstream sequences and the downstream -10 elements and transcriptional start sites. We also demonstrated, for Pfim3, that the conserved sequence corresponds to BvgA binding sites. The more upstream of the two binding sites is predicted to be high affinity, by comparison to a functionally derived consensus BvgA-binding sequence. The other binding site is a fairly poor match to this consensus, with 10 of 14 bp belonging to the C-stretch. Interestingly, the centre of this downstream site of BvgA binding coincides exactly with the centre of the expected typical location of a -35 sequence. However, the lack of a recognizable -35 element (CCCCCC versus TTGACA), and the occupation of this site by BvgA similar to P suggest that activation of the fim promoters involves unusual interactions among BvgA, RNA polymerase and promoter DNA. C1 [Chen, Qing; Boucher, Philip E.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Decker, Kimberly Baxter; Hinton, Deborah] NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Chen, Q (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM qing.chen@fda.hhs.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX The authors would like to thank M. Schmitt, C. Jones, R. Bonocora, L. Knipling, T. James and M. Hsieh for helpful discussions. K. Decker is a graduate student in the Graduate Partnership Program, Johns Hopkins University-National Institutes of Health. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 46 TC 17 Z9 17 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2010 VL 77 IS 5 BP 1326 EP 1340 DI 10.1111/j.1365-2958.2010.07293.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 643HW UT WOS:000281287200020 PM 20662776 ER PT J AU Wang, XQ Sykes, DB Miller, DS AF Wang, Xueqian Sykes, Destiny B. Miller, David S. TI Constitutive Androstane Receptor-Mediated Up-Regulation of ATP-Driven Xenobiotic Efflux Transporters at the Blood-Brain Barrier SO MOLECULAR PHARMACOLOGY LA English DT Article ID PREGNANE-X-RECEPTOR; NUCLEAR RECEPTORS; P-GLYCOPROTEIN; MOUSE-LIVER; SENSING RECEPTORS; DRUG TRANSPORTER; CAR; EXPRESSION; INDUCTION; RESISTANCE AB ATP-driven efflux transporters at the blood-brain barrier both protect against neurotoxicants and limit drug delivery to the brain. In other barrier and excretory tissues, efflux transporter expression is regulated by certain ligand-activated nuclear receptors. Here we identified constitutive androstane receptor (CAR) as a positive regulator of P-glycoprotein, multidrug resistance-associated protein 2 (Mrp2), and breast cancer resistance protein (BCRP) expression in rat and mouse brain capillaries. Exposing rat brain capillaries to the CAR activator, phenobarbital (PB), increased the transport activity and protein expression (Western blots) of P-glycoprotein, Mrp2, and BCRP. Induction of transport was abolished by the protein phosphatase 2A inhibitor, OA. Similar effects on transporter activity and expression were found when mouse brain capillaries were exposed to the mouse-specific CAR ligand, 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). In brain capillaries from CAR-null mice, TCPOBOP did not increase transporter activity. Finally, treating mice with 0.33 mg/kg TCPOBOP or rats with 80 mg/kg PB increased P-glycoprotein-, Mrp2-, and BCRP-mediated transport and protein expression in brain capillaries assayed ex vivo. Thus, CAR activation selectively tightens the blood-brain barrier by increasing transport activity and protein expression of three xenobiotic efflux pumps. C1 [Wang, Xueqian; Sykes, Destiny B.; Miller, David S.] Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. RP Miller, DS (reprint author), Natl Inst Environm Hlth Sci, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov FU National Institute of Environmental Health Sciences, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences, National Institutes of Health. NR 35 TC 52 Z9 53 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2010 VL 78 IS 3 BP 376 EP 383 DI 10.1124/mol.110.063685 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641DK UT WOS:000281104700007 PM 20547735 ER PT J AU Palkar, PS Borland, MG Naruhn, S Ferry, CH Lee, C Sk, UH Sharma, AK Amin, S Murray, IA Anderson, CR Perdew, GH Gonzalez, FJ Muller, R Peters, JM AF Palkar, Prajakta S. Borland, Michael G. Naruhn, Simone Ferry, Christina H. Lee, Christina Sk, Ugir H. Sharma, Arun K. Amin, Shantu Murray, Iain A. Anderson, Cherie R. Perdew, Gary H. Gonzalez, Frank J. Mueller, Rolf Peters, Jeffrey M. TI Cellular and Pharmacological Selectivity of the Peroxisome Proliferator-Activated Receptor-beta/delta Antagonist GSK3787 SO MOLECULAR PHARMACOLOGY LA English DT Article ID DELTA PPAR-DELTA; LIGAND ACTIVATION; CANCER; GROWTH; EXPRESSION; AGONISTS; CELLS; LINES; DIFFERENTIATION; IDENTIFICATION AB The availability of high-affinity agonists for peroxisome proliferator-activated receptor-beta/delta (PPAR beta/delta) has led to significant advances in our understanding of the functional role of PPAR beta/delta. In this study, a new PPAR beta/delta antagonist, 4-chloro-N-(2-{[5-trifluoromethyl)-2-pyridyl]sulfonyl}ethyl)benzamide (GSK3787), was characterized using in vivo and in vitro models. Orally administered GSK3787 caused antagonism of 4-[2-(3-fluoro-4-trifluoromethyl-phenyl)-4-methyl-thiazol-5-ylmethylsulfanyl]-2-methylphenoxy}-acetic acid (GW0742)-induced up-regulation of Angptl4 and Adrp mRNA expression in wild-type mouse colon but not in Ppar beta/delta-null mouse colon. Chromatin immunoprecipitation (ChIP) analysis indicates that this correlated with reduced promoter occupancy of PPAR beta/delta on the Angptl4 and Adrp genes. Reporter assays demonstrated antagonism of PPAR beta/delta activity and weak antagonism and agonism of PPAR gamma activity but no effect on PPAR alpha activity. Time-resolved fluorescence resonance energy transfer assays confirmed the ability of GSK3787 to modulate the association of both PPAR beta/delta and PPAR gamma coregulator peptides in response to ligand activation, consistent with reporter assays. In vivo and in vitro analysis indicates that the efficacy of GSK3787 to modulate PPAR gamma activity is markedly lower than the efficacy of GSK3787 to act as a PPAR beta/delta antagonist. GSK3787 antagonized GW0742-induced expression of Angptl4 in mouse fibroblasts, mouse keratinocytes, and human cancer cell lines. Cell proliferation was unchanged in response to either GW0742 or GSK3787 in human cancer cell lines. Results from these studies demonstrate that GSK3787 can antagonize PPAR beta/delta in vivo, thus providing a new strategy to delineate the functional role of a receptor with great potential as a therapeutic target for the treatment and prevention of disease. C1 [Palkar, Prajakta S.; Borland, Michael G.; Ferry, Christina H.; Lee, Christina; Murray, Iain A.; Anderson, Cherie R.; Perdew, Gary H.; Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Palkar, Prajakta S.; Borland, Michael G.; Ferry, Christina H.; Lee, Christina; Murray, Iain A.; Anderson, Cherie R.; Perdew, Gary H.; Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. [Naruhn, Simone; Mueller, Rolf] Univ Marburg, Inst Mol Biol & Tumor Res, Marburg, Germany. [Sk, Ugir H.; Sharma, Arun K.; Amin, Shantu] Penn State Univ, Milton S Hershey Med Ctr, Dept Pharmacol, Penn State Hershey Canc Inst, Hershey, PA 17033 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; Muller, Rolf/L-4997-2016 OI Muller, Rolf/0000-0003-3339-4248 FU National Institutes of Health National Cancer Institute [CA124533, CA126826, CA141029]; Deutsche Forschungsgemeinschaft [SFB-TR17/A3] FX This work was supported by the National Institutes of Health National Cancer Institute [Grants CA124533, CA126826, CA141029]; the Deutsche Forschungsgemeinschaft [Grant SFB-TR17/A3]; and in part by the Intramural Research Program of the National Institutes of Health National Cancer Institute. NR 37 TC 31 Z9 31 U1 2 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2010 VL 78 IS 3 BP 419 EP 430 DI 10.1124/mol.110.065508 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641DK UT WOS:000281104700012 PM 20516370 ER PT J AU Zhang, F Shi, JS Zhou, H Wilson, B Hong, JS Gao, HM AF Zhang, Feng Shi, Jing-Shan Zhou, Hui Wilson, Belinda Hong, Jau-Shyong Gao, Hui-Ming TI Resveratrol Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity through Its Anti-Inflammatory Actions SO MOLECULAR PHARMACOLOGY LA English DT Article ID NADPH OXIDASE ACTIVITY; NECROSIS-FACTOR-ALPHA; PARKINSONS-DISEASE; GENE-EXPRESSION; MICROGLIAL ACTIVATION; NITRIC-OXIDE; IN-VITRO; DEGENERATION; RESPONSES; PHOSPHORYLATION AB Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by a progressive loss of dopamine (DA) neurons in the substantia nigra. Accumulating evidence indicates that inhibition of microglia-mediated neuroinflammation may become a reliable protective strategy for PD. Resveratrol, a nonflavonoid polyphenol naturally found in red wine and grapes, has been known to possess antioxidant, anticancer, and anti-inflammatory properties. Although recent studies have shown that resveratrol provided neuroprotective effects against ischemia, seizure, and neurodegenerative disorders, the mechanisms underlying its beneficial effects on dopaminergic neurodegeneration are poorly defined. In this study, rat primary midbrain neuron-glia cultures were used to elucidate the molecular mechanisms underlying resveratrol-mediated neuroprotection. The results clearly demonstrated that resveratrol protected DA neurons against lipopolysaccharide (LPS)-induced neurotoxicity in concentration-and time-dependent manners through the inhibition of microglial activation and the subsequent reduction of proinflammatory factor release. Mechanistically, resveratrol-mediated neuroprotection was attributed to the inhibition of NADPH oxidase. This conclusion is supported by the following observations. First, resveratrol reduced NADPH oxidase-mediated generation of reactive oxygen species. Second, LPS-induced translocation of NADPH oxidase cytosolic subunit p47 to the cell membrane was significantly attenuated by resveratrol. Third and most importantly, resveratrol failed to exhibit neuroprotection in cultures from NADPH oxidase-deficient mice. Furthermore, this neuroprotection was also related to an attenuation of the activation of mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways in microglia. These findings suggest that resveratrol exerts neuroprotection against LPS-induced dopaminergic neurodegeneration, and NADPH oxidase may be a major player in resveratrol-mediated neuroprotection. C1 [Zhang, Feng; Zhou, Hui; Wilson, Belinda; Hong, Jau-Shyong; Gao, Hui-Ming] Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Zhang, Feng; Shi, Jing-Shan] Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China. [Zhang, Feng; Shi, Jing-Shan] Zunyi Med Coll, Dept Pharmacol, Zunyi, Peoples R China. [Zhang, Feng; Shi, Jing-Shan] Zunyi Med Coll, Key Lab Basic Pharmacol Guizhou, Zunyi, Peoples R China. RP Gao, HM (reprint author), Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM gao2@niehs.nih.gov RI gao, huiming/C-8454-2012 FU National Institutes of Health National Institute of Environmental Health Sciences [XXX]; National Natural Science Foundation of China [30960447]; Science and Technology Foundation of Guizhou Province of China [20107030] FX This work was supported by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences [Grant XXX]; the National Natural Science Foundation of China [Grant 30960447]; and the Science and Technology Foundation of Guizhou Province of China [Grant 20107030]. NR 38 TC 62 Z9 65 U1 1 U2 14 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 2010 VL 78 IS 3 BP 466 EP 477 DI 10.1124/mol.110.064535 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 641DK UT WOS:000281104700017 PM 20554604 ER PT J AU Chen, G Henter, ID Manji, HK AF Chen, G. Henter, I. D. Manji, H. K. TI Translational research in bipolar disorder: emerging insights from genetically based models SO MOLECULAR PSYCHIATRY LA English DT Review DE mania; depression; bipolar disorder; animal model; lithium ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISM; GLUCOCORTICOID-RECEPTOR GENE; FORCED SWIMMING TEST; ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION; SUSCEPTIBILITY LOCUS; MITOCHONDRIAL-DNA; MOOD DISORDERS; ANIMAL-MODELS AB Bipolar disorder (BPD) is characterized by vulnerability to episodic depression and mania and spontaneous cycling. Because of marked advances in candidate-gene and genome-wide association studies, the list of risk genes for BPD is growing rapidly, creating an unprecedented opportunity to understand the pathophysiology of BPD and to develop novel therapeutics for its treatment. However, genetic findings are associated with major unresolved issues, including whether and how risk variance leads to behavioral abnormalities. Although animal studies are key to resolving these issues, consensus is needed regarding how to define and monitor phenotypes related to mania, depression and mood swing vulnerability in genetically manipulated rodents. In this study we discuss multiple facets of this challenging area, including theoretical considerations, available tests, limitations associated with rodent behavioral modeling and promising molecular-behavioral findings. These include CLOCK, glycogen synthase kinase 3 beta (GSK-3 beta), glutamate receptor 6 (GluR6), extracellular signal-regulated kinase-1 (ERK1), p11 (or S100A10), vesicular monoamine transporter 2 (VMAT2 or SLC18A2), glucocorticoid receptors (GRs), Bcl-2-associated athanogene-1 (BAG1) and mitochondrial DNA polymerase-c (POLG). Some mutant rodent strains show behavioral clusters or activity patterns that cross-species phenocopy objective/observable facets of mood syndromes, and changes in these clustered behaviors can be used as outcome measures in genetic-behavioral research in BPD. Molecular Psychiatry (2010) 15, 883-895; doi:10.1038/mp.2010.3; published online 9 February 2010 C1 [Chen, G.; Henter, I. D.; Manji, H. K.] NIMH, MAP, NIH, IRP,MSC 3711,Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. [Manji, H. K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. RP Chen, G (reprint author), NIMH, MAP, NIH, IRP,MSC 3711,Mood & Anxiety Disorders Program, Bldg 35,Room 1C 912 Main off & 1BC 108,35 Convent, Bethesda, MD 20892 USA. EM guangchen@mail.nih.gov RI Chen, Guang/A-2570-2017 FU Intramural NIH HHS [Z99 MH999999] NR 80 TC 33 Z9 33 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2010 VL 15 IS 9 BP 883 EP 895 DI 10.1038/mp.2010.3 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 648EB UT WOS:000281672100004 PM 20142820 ER PT J AU Wakschlag, LS Kistner, EO Pine, DS Biesecker, G Pickett, KE Skol, AD Dukic, V Blair, RJR Leventhal, BL Cox, NJ Burns, JL Kasza, KE Wright, RJ Cook, EH AF Wakschlag, L. S. Kistner, E. O. Pine, D. S. Biesecker, G. Pickett, K. E. Skol, A. D. Dukic, V. Blair, R. J. R. Leventhal, B. L. Cox, N. J. Burns, J. L. Kasza, K. E. Wright, R. J. Cook, E. H., Jr. TI Interaction of prenatal exposure to cigarettes and MAOA genotype in pathways to youth antisocial behavior SO MOLECULAR PSYCHIATRY LA English DT Article DE prenatal smoking; MAOA; gene x environment interaction; developmental psychopathology ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENOTYPE; GENE-ENVIRONMENT INTERACTION; MATERNAL SMOKING; MONOAMINE-OXIDASE; DEVELOPMENTAL PSYCHOPATHOLOGY; FUNCTIONAL POLYMORPHISM; EXTERNALIZING PROBLEMS; INDIVIDUAL-DIFFERENCES; LUNG-FUNCTION AB Genetic susceptibility to antisocial behavior may increase fetal sensitivity to prenatal exposure to cigarette smoke. Testing putative gene x exposure mechanisms requires precise measurement of exposure and outcomes. We tested whether a functional polymorphism in the gene encoding the enzyme monoamine oxidase A (MAOA) interacts with exposure to predict pathways to adolescent antisocial behavior. We assessed both clinical and information-processing outcomes. One hundred seventy-six adolescents and their mothers participated in a follow-up of a pregnancy cohort with well-characterized exposure. A sex-specific pattern of gene x exposure interaction was detected. Exposed boys with the low-activity MAOA 5' uVNTR (untranslated region variable number of tandem repeats) genotype were at increased risk for conduct disorder (CD) symptoms. In contrast, exposed girls with the high-activity MAOA uVNTR genotype were at increased risk for both CD symptoms and hostile attribution bias on a face-processing task. There was no evidence of a gene-environment correlation (rGE). Findings suggest that the MAOA uVNTR genotype, prenatal exposure to cigarettes and sex interact to predict antisocial behavior and related information-processing patterns. Future research to replicate and extend these findings should focus on elucidating how gene x exposure interactions may shape behavior through associated changes in brain function. Molecular Psychiatry (2010) 15, 928-937; doi:10.1038/mp.2009.22; published online 3 March 2009 C1 [Wakschlag, L. S.; Biesecker, G.; Leventhal, B. L.; Burns, J. L.; Cook, E. H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60608 USA. [Kistner, E. O.; Dukic, V.; Kasza, K. E.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Pine, D. S.; Blair, R. J. R.] NIMH, Lab Affect & Dev Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. [Pickett, K. E.] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England. [Skol, A. D.; Cox, N. J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Wright, R. J.] Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Wakschlag, LS (reprint author), Univ Illinois, Dept Psychiat, Inst Juvenile Res, 1747 W Roosevelt Rd,MC747, Chicago, IL 60608 USA. EM lwakschlag@psych.uic.edu OI Dukic, Vanja/0000-0002-0348-0834 FU NIDA [DA15223] FX This work was supported by NIDA Grant DA15223 to Dr Wakschlag, including support to Drs Pickett, Cook, Dukic, Wright and Leventhal. Drs Wakschlag, Leventhal and Cook were also supported by the Walden & Jean Young Shaw and Children's Brain Research Foundations, and Dr Pickett was supported by a UK National Institute for Health Research Career Scientist Award. Very special thanks to our colleagues, Margaret Briggs-Gowan, Kimberly Espy, David Henry, Brian Mustanski and Patrick Tolan, whose ongoing critical feedback and consultation on this work has been invaluable. We thank Ira Tager, the founder of MISSEB, for his enthusiasm about the EBFS follow-up and for facilitating access to this cohort. We gratefully acknowledge Neal Benowitz's contribution to exposure measurement. Vincent Smeriglio's steadfast commitment to this program of research is deeply appreciated. We thank Nora Volkow for guidance on the scientific approach taken in this study. Finally, we thank the EBFS research staff, whose thoughtful efforts were vital to study completion, particularly Marian Parker's work on reascertainment, Phil Schumm and Ted Pollari's work on electronic data transmission, and Kathy Hennessy and Greg Moy of the IJR Laboratory of Developmental Neuroscience for their work on genotyping. Portions of this paper were presented at the Meetings of the American College of Neuropsychopharmacology, the Society for the Study of Addiction and the Society for Research in Child Development. NR 68 TC 19 Z9 19 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2010 VL 15 IS 9 BP 928 EP 937 DI 10.1038/mp.2009.22 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 648EB UT WOS:000281672100008 ER PT J AU Grinshpun, A Condiotti, R Waddington, SN Peer, M Zeig, E Peretz, S Simerzin, A Chou, J Pann, CJ Giladi, H Galun, E AF Grinshpun, Albert Condiotti, Reba Waddington, Simon N. Peer, Michael Zeig, Eli Peretz, Sima Simerzin, Alina Chou, Janice Pann, Chi-Jiunn Giladi, Hilla Galun, Eithan TI Neonatal Gene Therapy of Glycogen Storage Disease Type Ia Using a Feline Immunodeficiency Virus-based Vector SO MOLECULAR THERAPY LA English DT Article ID NONPRIMATE LENTIVIRAL VECTOR; LONG-TERM CORRECTION; MOUSE MODEL; RETROVIRAL VECTORS; IMMUNE-RESPONSES; VIRAL VECTORS; FACTOR-IX; LIVER; EXPRESSION; HEMOPHILIA AB Glycogen storage disease type Ia (GSD-Ia), also known as von Gierke disease, is caused by a deficiency of glucose-6-phosphatase-alpha (G6Pase), a key enzyme in glucose homeostasis. From birth, affected individuals cannot maintain normal blood glucose levels and suffer from a variety of metabolic disorders, leading to life-threatening complications. Gene therapy has been proposed as a possible option for treatment of this illness. Vectors have been constructed from feline immunodeficiency virus (FIV), a nonprimate lentivirus, because the wild-type virus does not cause disease in humans. Previously, we have shown that these vectors are capable of integrating stably into hepatocyte cell lines and adult murine livers and lead to long-term transgene expression. In the current work, we have assessed the ability to attenuate disease symptoms in a murine model of GSD-Ia. Single administration of FIV vectors containing the human G6Pase gene to G6Pase-alpha(-/-) mice did not change the biochemical and pathological phenotype. However, a double neonatal administration protocol led to normalized blood glucose levels, significantly extended survival, improved body weight, and decreased accumulation of liver glycogen associated with the disease. This approach shows a promising paradigm for treating GSD-Ia patients early in life thereby avoiding long-term consequences. C1 [Grinshpun, Albert; Condiotti, Reba; Peer, Michael; Zeig, Eli; Simerzin, Alina; Giladi, Hilla; Galun, Eithan] Hadassah Hebrew Univ, Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel. [Waddington, Simon N.] UCL, Inst Womens Hlth, London, England. [Peretz, Sima] Harlan Biotech Ltd, Rehovot, Israel. [Chou, Janice; Pann, Chi-Jiunn] NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. RP Condiotti, R (reprint author), Hadassah Univ Hosp, Goldyne Savad Inst Gene Therapy, POB 12000, IL-91120 Jerusalem, Israel. EM reba@hadassah.org.il RI Waddington, Simon/G-3778-2011 OI Waddington, Simon/0000-0003-4970-4730 FU Children's Fund for Glycogen Storage Disease Research; Alfy and Lilyan Nathan FX We thank the Children's Fund for Glycogen Storage Disease Research, and Alfy and Lilyan Nathan for financially supporting this work. NR 41 TC 10 Z9 10 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2010 VL 18 IS 9 BP 1592 EP 1598 DI 10.1038/mt.2010.119 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 645YO UT WOS:000281502300004 PM 20571544 ER PT J AU Sellers, S Gomes, TJ Larochelle, A Lopez, R Adler, R Krouse, A Donahue, RE Childs, RW Dunbar, CE AF Sellers, Stephanie Gomes, Theotonius J. Larochelle, Andre Lopez, Rebecca Adler, Rima Krouse, Allen Donahue, Robert E. Childs, Richard W. Dunbar, Cynthia E. TI Ex Vivo Expansion of Retrovirally Transduced Primate CD34+Cells Results in Overrepresentation of Clones With MDS1/EVI1 Insertion Sites in the Myeloid Lineage After Transplantation SO MOLECULAR THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CHRONIC GRANULOMATOUS-DISEASE; GENE-THERAPY; NONHUMAN-PRIMATES; VECTOR INTEGRATION; EXPRESSION; LEUKEMIA; PROLIFERATION; GENOTOXICITY; MUTAGENESIS AB Activation of proto-oncogenes by retroviral insertion is an important issue delaying clinical development of gene therapy. We have reported the nonrandom persistence of hematopoietic clones with vector insertions within the MDS1/EVI1 locus following transplantation of rhesus macaques. We now ask whether prolonged culture of transduced CD34(+) cells before transplantation selects for clones with insertions in the MDS1/EVI11 or other proto-oncogene loci. CD34(+) cells were transduced with standard retroviral vectors for 4 days and then continued in culture for an additional 6 days before transplantation. A 15% of insertions identified in granulocytes 6 months post-transplant were in MDS1/EVI11, significantly increased compared to the frequency in animals transplanted with cells immediately following transduction. MDS1/EVI1 clones became more dominant over time post-transplantation in one animal that was followed long term, accompanied by an increased overall copy number of vector-containing granulocytes, with one MDS1/EVI1 clone eventually accounting for 100% of transduced granulocytes and marrow colony-forming unit (CFU). This vector insertion increased the expression of Evi1 mRNA. There was no overrepresentation of MDS1/EVI1 insertions contributing to lymphoid lineages. Strategies involving prolonged ex vivo expansion of transduced cells may increase the risk of genotoxicity. C1 [Dunbar, Cynthia E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 4E-5132,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute FX These studies were supported by the intramural research program of the National Heart, Lung, and Blood Institute. We thank the staff of the 5 Research Court primate center for excellent animal care. T.J.G.: collection and analysis of data, wrote manuscript; S. S.: collection and analysis of data; R. L.: collection and analysis of data; A. L.: data analysis and interpretation; R. A.: collection and analysis of data; A. K.: collection and analysis of data; R. E. D.: data analysis and interpretation; R. W. C.: data analysis and interpretation; C. E. D.: conception, wrote, and approved the final version of the manuscript. NR 36 TC 13 Z9 14 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2010 VL 18 IS 9 BP 1633 EP 1639 DI 10.1038/mt.2010.117 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 645YO UT WOS:000281502300009 PM 20571542 ER PT J AU Graham, BS Kines, RC Corbett, KS Nicewonger, J Johnson, TR Chen, M LaVigne, D Roberts, JN Cuburu, N Schiller, JT Buck, CB AF Graham, B. S. Kines, R. C. Corbett, K. S. Nicewonger, J. Johnson, T. R. Chen, M. LaVigne, D. Roberts, J. N. Cuburu, N. Schiller, J. T. Buck, C. B. TI Mucosal delivery of human papillomavirus pseudovirus-encapsidated plasmids improves the potency of DNA vaccination SO MUCOSAL IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; T-LYMPHOCYTE RESPONSES; IN-VITRO; DENDRITIC CELLS; NEUTRALIZING ANTIBODIES; ORAL IMMUNIZATION; PARTICLE VACCINE; HEPARAN-SULFATE; CHIMERIC VIRUS; YOUNG-WOMEN AB Mucosal immunization may be important for protection against pathogens whose transmission and pathogenesis target the mucosal tissue. The capsid proteins of human papillomavirus (HPV) confer tropism for the basal epithelium and can encapsidate DNA during self-assembly to form pseudovirions (PsVs). Therefore, we produced mucosal vaccine vectors by HPV PsV encapsidation of DNA plasmids expressing an experimental antigen derived from the M and M2 proteins of respiratory syncytial virus (RSV). Intravaginal (IVag) delivery elicited local and systemic M/M2-specific CD8 + T-cell and antibody responses in mice that were comparable to an similar to 10,000-fold higher dose of naked DNA. A single HPV PsV IVag immunization primed for M/M2-specific-IgA in nasal and vaginal secretions. Based on light emission and immunofluorescent microscopy, immunization with HPV PsV-encapsidated luciferase-and red fluorescent protein (RFP)-expressing plasmids resulted in transient antigen expression (< 5 days), which was restricted to the vaginal epithelium. HPV PsV encapsidation of plasmid DNA is a novel strategy for mucosal immunization that could provide new vaccine options for selected mucosal pathogens. C1 [Graham, B. S.; Corbett, K. S.; Nicewonger, J.; Johnson, T. R.; Chen, M.; LaVigne, D.] NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Kines, R. C.; Cuburu, N.; Schiller, J. T.; Buck, C. B.] NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. [Roberts, J. N.] US FDA, Bethesda, MD 20014 USA. RP Graham, BS (reprint author), NIAID, Viral Pathogenesis Lab, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bgraham@nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU National Institute of Allergy and Infectious Diseases; National Cancer Institute FX This work was supported by intramural funding from the National Institute of Allergy and Infectious Diseases and the National Cancer Institute. NR 50 TC 18 Z9 21 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2010 VL 3 IS 5 BP 475 EP 486 DI 10.1038/mi.2010.31 PG 12 WC Immunology SC Immunology GA 641HM UT WOS:000281115400007 PM 20555315 ER PT J AU Butts, CL Candando, KM Warfel, J Belyavskaya, E D'Agnillo, F Sternberg, EM AF Butts, C. L. Candando, K. M. Warfel, J. Belyavskaya, E. D'Agnillo, F. Sternberg, E. M. TI Progesterone regulation of uterine dendritic cell function in rodents is dependent on the stage of estrous cycle SO MUCOSAL IMMUNOLOGY LA English DT Article ID HOST-PATHOGEN INTERFACE; FEMALE GENITAL-TRACT; HUMAN ENDOMETRIUM; IMMUNE-RESPONSES; HORMONAL CONTRACEPTION; REPRODUCTIVE-TRACT; STEROID-HORMONES; EPITHELIAL-CELLS; CUTTING EDGE; SEX-HORMONES AB Steroid hormones, such as progesterone, are able to modify immunity and influence disease outcome. Dendritic cells (DCs) drive potent immune responses, express receptors for steroid hormones, and may be a primary target of steroid hormone actions during infection of the genital tract, including uterine tissue. Here, we report that progesterone limited DC-associated activation marker expression and inhibited cytokine secretion by uterine DCs, which was associated with changes in signal transducer and activator of transcription 1 (STAT1) activity. We also found that DCs from mice at stages with higher progesterone concentrations (diestrus, metaestrus) were more sensitive to progesterone than those in stages with lower progesterone concentrations (proestrus, estrus), both in vitro and in vivo. This difference correlated with the levels of progesterone receptor expressed by DCs. These data suggest that progesterone regulates DC function and could contribute to the susceptibility of females to uterine and other genital tract infections at selected time periods throughout the life cycle. C1 [Butts, C. L.; Candando, K. M.; Belyavskaya, E.; Sternberg, E. M.] NIMH, Sect Neuroendocrine Immunol, Bethesda, MD 20892 USA. [Warfel, J.; D'Agnillo, F.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol, Bethesda, MD 20892 USA. EM sternbee@mail.nih.gov RI Warfel, Jason/D-2557-2011 FU National Institute of Mental Health (NIMH)/NIH; National Institute of Allergy & Infectious Diseases (NIAID)/NIH FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH)/NIH and by a biodefense grant from the National Institute of Allergy & Infectious Diseases (NIAID)/NIH Intramural Research Program. We thank Dr Cecilia Tami for careful manuscript review and technical assistance. NR 68 TC 8 Z9 10 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD SEP PY 2010 VL 3 IS 5 BP 496 EP 505 DI 10.1038/mi.2010.28 PG 10 WC Immunology SC Immunology GA 641HM UT WOS:000281115400009 PM 20505661 ER PT J AU Savage, KJ McPherron, AC AF Savage, Kathleen J. McPherron, Alexandra C. TI ENDURANCE EXERCISE TRAINING IN MYOSTATIN NULL MICE SO MUSCLE & NERVE LA English DT Article DE endurance training; exercise capacity; glycolytic fiber type; hypertrophy; myostatin; skeletal muscle ID SKELETAL-MUSCLE MASS; FIBER CONTRACTILE PROPERTIES; GIRDLE MUSCULAR-DYSTROPHY; DEFICIENT MICE; IMPROVES FUNCTION; MURINE MODEL; FAT MASS; MDX MICE; INHIBITION; BLOCKADE AB The growth factor myostatin (Mstn) is a negative regulator of skeletal muscle mass. Mstn(-/-) muscles are hypertrophied, stronger, and more glycolytic than Mstn(+/+) muscles, suggesting that they might not perform endurance exercise as well as Mstn(+/+) mice. Indeed, it has previously been shown that treadmill exercise training reduces triceps weight in Mste(-/-) mice. To analyze the response of Mstn-/- muscle to endurance exercise in detail, we carried out endurance training over 4 weeks to examine muscle mass, histology, and oxidative enzyme activity. We found that muscle mass was reduced with training in several muscles from both genotypes, with no evidence of muscle damage. Citrate synthase activity was increased with training in control and mutant mice. Non-trained Mstn(-/-) mice did, however, have lower maximal exercise capacity compared with Mstn(+/+) mice. These results show that Mstn(-/-) muscle retains the metabolic plasticity necessary to adapt normally to endurance training. Muscle Nerve 42: 355-362, 2010 C1 [Savage, Kathleen J.; McPherron, Alexandra C.] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP McPherron, AC (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 8D12A, Bethesda, MD 20892 USA. EM mcpherrona@niddk.nih.gov OI McPherron, Alexandra/0000-0002-5875-9154 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. The authors thank Jennifer Portas for assistance with treadmill running and genotyping. NR 52 TC 17 Z9 18 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2010 VL 42 IS 3 BP 355 EP 362 DI 10.1002/mus.21688 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 647OI UT WOS:000281627400007 PM 20544938 ER PT J AU Walker, FO Alter, KE Boon, AJ Cartwright, MS Flores, VH Hobson-Webb, LD Hunt, CH Primack, SJ Shook, SJ AF Walker, Francis O. Alter, Katharine E. Boon, Andrea J. Cartwright, Michael S. Flores, Victor H. Hobson-Webb, Lisa D. Hunt, Christopher H. Primack, Scott J. Shook, Steven J. TI QUALIFICATIONS FOR PRACTITIONERS OF NEUROMUSCULAR ULTRASOUND: POSITION STATEMENT OF THE AMERICAN ASSOCIATION OF NEUROMUSCULAR AND ELECTRODIAGNOSTIC MEDICINE SO MUSCLE & NERVE LA English DT Article DE ultrasound; neuromuscular ultrasound; musculoskeletal ultrasound; ultrasound qualifications; ultrasound indications ID CARPAL-TUNNEL-SYNDROME; BRACHIAL-PLEXUS BLOCK; QUANTITATIVE MUSCLE ULTRASONOGRAPHY; CROSS-SECTIONAL AREA; ULNAR NEUROPATHY; MEDIAN NERVE; DIAGNOSTIC ULTRASOUND; CHILDREN; DISEASE; BIOPSY C1 [Walker, Francis O.; Cartwright, Michael S.] Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27103 USA. [Alter, Katharine E.] NICHD, NIH, Bethesda, MD USA. [Boon, Andrea J.] Mayo Clin, Grad Sch Med, Dept Phys Med & Rehabil, Rochester, MN USA. [Flores, Victor H.] Phys Med Associates, Ft Worth, TX USA. [Hobson-Webb, Lisa D.] Duke Univ, Med Ctr, Div Neurol, Dept Med, Durham, NC 27710 USA. [Hunt, Christopher H.] Mayo Clin, Grad Sch Med, Dept Radiol, Rochester, MN USA. [Primack, Scott J.] Colorado Rehabil & Occupat Med, Aurora, CO USA. [Shook, Steven J.] Cleveland Clin, Neurol Inst, Neuromuscular Ctr, Cleveland, OH 44106 USA. RP Walker, FO (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27103 USA. RI Hunt, Christopher/I-7690-2012; OI Hunt, Christopher/0000-0003-0301-0493 NR 46 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 2010 VL 42 IS 3 BP 442 EP 444 DI 10.1002/mus.21760 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 647OI UT WOS:000281627400020 PM 20806399 ER PT J AU Mouquet, H Scheid, JF Zoller, MJ Krogsgaard, M Ott, RG Shukair, S Artyomov, MN Pietzsch, J Connors, M Pereyra, F Walker, BD Ho, DD Wilson, PC Seaman, MS Eisen, HN Chakraborty, AK Hope, TJ Ravetch, JV Wardemann, H Nussenzweig, MC AF Mouquet, Hugo Scheid, Johannes F. Zoller, Markus J. Krogsgaard, Michelle Ott, Rene G. Shukair, Shetha Artyomov, Maxim N. Pietzsch, John Connors, Mark Pereyra, Florencia Walker, Bruce D. Ho, David D. Wilson, Patrick C. Seaman, Michael S. Eisen, Herman N. Chakraborty, Arup K. Hope, Thomas J. Ravetch, Jeffrey V. Wardemann, Hedda Nussenzweig, Michel C. TI Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; TYPE-1; AUTOREACTIVITY; INDIVIDUALS; MODULATION; GENERATION AB During immune responses, antibodies are selected for their ability to bind to foreign antigens with high affinity, in part by their ability to undergo homotypic bivalent binding. However, this type of binding is not always possible. For example, the small number of gp140 glycoprotein spikes displayed on the surface of the human immunodeficiency virus (HIV) disfavours homotypic bivalent antibody binding(1-3). Here we show that during the human antibody response to HIV, somatic mutations that increase antibody affinity also increase breadth and neutralizing potency. Surprisingly, the responding naive and memory B cells produce polyreactive antibodies, which are capable of bivalent heteroligation between one high-affinity anti-HIV-gp140 combining site and a second low-affinity site on another molecular structure on HIV. Although cross-reactivity to self-antigens or polyreactivity is strongly selected against during B-cell development(4), it is a common serologic feature of certain infections in humans, including HIV, Epstein-Barr virus and hepatitis C virus. Seventy-five per cent of the 134 monoclonal anti-HIV-gp140 antibodies cloned from six patients(5) with high titres of neutralizing antibodies are polyreactive. Despite the low affinity of the polyreactive combining site, heteroligation demonstrably increases the apparent affinity of polyreactive antibodies to HIV. C1 [Mouquet, Hugo; Scheid, Johannes F.; Pietzsch, John; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Scheid, Johannes F.] Charite, D-10117 Berlin, Germany. [Zoller, Markus J.; Wardemann, Hedda] Max Planck Inst Infect Biol, D-10117 Berlin, Germany. [Krogsgaard, Michelle] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Krogsgaard, Michelle] NYU, Sch Med, Inst Canc, New York, NY 10016 USA. [Ott, Rene G.; Ravetch, Jeffrey V.] Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10065 USA. [Shukair, Shetha; Hope, Thomas J.] Northwestern Univ, Dept Cell & Mol Biol, Chicago, IL 60611 USA. [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Artyomov, Maxim N.; Eisen, Herman N.; Chakraborty, Arup K.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Pietzsch, John] Free Univ Berlin, Inst Chem & Biochem, D-14195 Berlin, Germany. [Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Connors, Mark] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Pereyra, Florencia; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA 02114 USA. [Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ho, David D.] Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. [Wilson, Patrick C.] Univ Chicago, Dept Med, Rheumatol Sect, Chicago, IL 60637 USA. [Seaman, Michael S.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM nussenzweig@rockefeller.edu RI Mouquet, Hugo/M-2750-2014 FU Rockefeller University; National Institutes of Health [NIH 1 PO1 AI081677, R01 AI047770]; International AIDS Vaccine Initiative; Bill and Melinda Gates Foundation; German Research Foundation [GRK1121] FX We thank J. R. Mascola and R. T. Wyatt for discussion and supplying gp140 and gp120 proteins. This research was supported by the Rockefeller University, the National Institutes of Health (NIH 1 PO1 AI081677), the International AIDS Vaccine Initiative and the Bill and Melinda Gates Foundation. T.J.H. was supported by the National Institutes of Health (R01 AI047770). M.J.Z. and H.W. were supported by the German Research Foundation (GRK1121). B.D.W. and M.C.N. are Howard Hughes Medical Institute investigators. NR 31 TC 203 Z9 204 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP PY 2010 VL 467 IS 7315 BP 591 EP U117 DI 10.1038/nature09385 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 655TT UT WOS:000282273100039 PM 20882016 ER PT J AU Schreiber, SL Shamji, AF Clemons, PA Hon, C Koehler, AN Munoz, B Palmer, M Stern, AM Wagner, BK Powers, S Lowe, SW Guo, XC Krasnitz, A Sawey, ET Sordella, R Stein, L Trotman, LC Califano, A Dalla-Favera, R Ferrando, A Iavarone, A Pasqualucci, L Silva, J Stockwell, BR Hahn, WC Chin, L DePinho, RA Boehm, JS Gopal, S Huang, A Root, DE Weir, BA Gerhard, DS Zenklusen, JC Roth, MG White, MA Minna, JD MacMillan, JB Posner, BA AF Schreiber, Stuart L. Shamji, Alykhan F. Clemons, Paul A. Hon, Cindy Koehler, Angela N. Munoz, Benito Palmer, Michelle Stern, Andrew M. Wagner, Bridget K. Powers, Scott Lowe, Scott W. Guo, Xuecui Krasnitz, Alex Sawey, Eric T. Sordella, Raffaella Stein, Lincoln Trotman, Lloyd C. Califano, Andrea Dalla-Favera, Riccardo Ferrando, Adolfo Iavarone, Antonio Pasqualucci, Laura Silva, Jose Stockwell, Brent R. Hahn, William C. Chin, Lynda DePinho, Ronald A. Boehm, Jesse S. Gopal, Shuba Huang, Alan Root, David E. Weir, Barbara A. Gerhard, Daniela S. Zenklusen, Jean Claude Roth, Michael G. White, Michael A. Minna, John D. MacMillan, John B. Posner, Bruce A. CA Canc Target Discovery Dev Network TI Towards patient-based cancer therapeutics SO NATURE BIOTECHNOLOGY LA English DT Article ID ONCOGENE ADDICTION; LIVER-CANCER; CELL-LINES; STEM-CELLS; IDENTIFICATION; GENOTYPE; THERAPY; MODELS; TUMORS C1 [Schreiber, Stuart L.; Shamji, Alykhan F.; Clemons, Paul A.; Hon, Cindy; Koehler, Angela N.; Munoz, Benito; Palmer, Michelle; Stern, Andrew M.; Wagner, Bridget K.; Canc Target Discovery Dev Network] Harvard & MIT, Broad Inst, Cambridge, MA USA. [Powers, Scott; Lowe, Scott W.; Guo, Xuecui; Krasnitz, Alex; Sawey, Eric T.; Sordella, Raffaella; Stein, Lincoln; Trotman, Lloyd C.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Califano, Andrea; Dalla-Favera, Riccardo; Ferrando, Adolfo; Iavarone, Antonio; Pasqualucci, Laura; Silva, Jose; Stockwell, Brent R.] Columbia Univ, New York, NY USA. [Hahn, William C.; Chin, Lynda; DePinho, Ronald A.; Boehm, Jesse S.; Gopal, Shuba; Huang, Alan; Root, David E.; Weir, Barbara A.] Dana Farber Canc Inst, Cambridge, MA USA. [Gerhard, Daniela S.; Zenklusen, Jean Claude] US Natl Canc Inst, Bethesda, MD USA. [Roth, Michael G.; White, Michael A.; Minna, John D.; MacMillan, John B.; Posner, Bruce A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Schreiber, SL (reprint author), Harvard & MIT, Broad Inst, Cambridge, MA USA. EM stuart_schreiber@harvard.edu RI Califano, Andrea/F-7239-2012; OI Boehm, Jesse/0000-0002-6795-6336; Roth, Michael/0000-0002-9056-332X; MacMillan, John/0000-0003-1430-1077 NR 22 TC 42 Z9 42 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2010 VL 28 IS 9 BP 904 EP 906 DI 10.1038/nbt0910-904 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 648UF UT WOS:000281719100011 ER PT J AU Demir, E Cary, MP Paley, S Fukuda, K Lemer, C Vastrik, I Wu, GN D'Eustachio, P Schaefer, C Luciano, J Schacherer, F Martinez-Flores, I Hu, ZJ Jimenez-Jacinto, V Joshi-Tope, G Kandasamy, K Lopez-Fuentes, AC Mi, HY Pichler, E Rodchenkov, I Splendiani, A Tkachev, S Zucker, J Gopinath, G Rajasimha, H Ramakrishnan, R Shah, I Syed, M Anwar, N Babur, O Blinov, M Brauner, E Corwin, D Donaldson, S Gibbons, F Goldberg, R Hornbeck, P Luna, A Murray-Rust, P Neumann, E Reubenacker, O Samwald, M van Iersel, M Wimalaratne, S Allen, K Braun, B Whirl-Carrillo, M Cheung, KH Dahlquist, K Finney, A Gillespie, M Glass, E Gong, L Haw, R Honig, M Hubaut, O Kane, D Krupa, S Kutmon, M Leonard, J Marks, D Merberg, D Petri, V Pico, A Ravenscroft, D Ren, LY Shah, N Sunshine, M Tang, R Whaley, R Letovksy, S Buetow, KH Rzhetsky, A Schachter, V Sobral, BS Dogrusoz, U McWeeney, S Aladjem, M Birney, E Collado-Vides, J Goto, S Hucka, M Le Novere, N Maltsev, N Pandey, A Thomas, P Wingender, E Karp, PD Sander, C Bader, GD AF Demir, Emek Cary, Michael P. Paley, Suzanne Fukuda, Ken Lemer, Christian Vastrik, Imre Wu, Guanming D'Eustachio, Peter Schaefer, Carl Luciano, Joanne Schacherer, Frank Martinez-Flores, Irma Hu, Zhenjun Jimenez-Jacinto, Veronica Joshi-Tope, Geeta Kandasamy, Kumaran Lopez-Fuentes, Alejandra C. Mi, Huaiyu Pichler, Elgar Rodchenkov, Igor Splendiani, Andrea Tkachev, Sasha Zucker, Jeremy Gopinath, Gopal Rajasimha, Harsha Ramakrishnan, Ranjani Shah, Imran Syed, Mustafa Anwar, Nadia Babur, Oezguen Blinov, Michael Brauner, Erik Corwin, Dan Donaldson, Sylva Gibbons, Frank Goldberg, Robert Hornbeck, Peter Luna, Augustin Murray-Rust, Peter Neumann, Eric Reubenacker, Oliver Samwald, Matthias van Iersel, Martijn Wimalaratne, Sarala Allen, Keith Braun, Burk Whirl-Carrillo, Michelle Cheung, Kei-Hoi Dahlquist, Kam Finney, Andrew Gillespie, Marc Glass, Elizabeth Gong, Li Haw, Robin Honig, Michael Hubaut, Olivier Kane, David Krupa, Shiva Kutmon, Martina Leonard, Julie Marks, Debbie Merberg, David Petri, Victoria Pico, Alex Ravenscroft, Dean Ren, Liya Shah, Nigam Sunshine, Margot Tang, Rebecca Whaley, Ryan Letovksy, Stan Buetow, Kenneth H. Rzhetsky, Andrey Schachter, Vincent Sobral, Bruno S. Dogrusoz, Ugur McWeeney, Shannon Aladjem, Mirit Birney, Ewan Collado-Vides, Julio Goto, Susumu Hucka, Michael Le Novere, Nicolas Maltsev, Natalia Pandey, Akhilesh Thomas, Paul Wingender, Edgar Karp, Peter D. Sander, Chris Bader, Gary D. TI The BioPAX community standard for pathway data sharing SO NATURE BIOTECHNOLOGY LA English DT Article ID SYSTEMS BIOLOGY; COLLABORATIVE CONSTRUCTION; SOFTWARE ENVIRONMENT; INTERACTION NETWORK; CELLULAR PATHWAYS; REPRESENTATION; ONTOLOGY; INFORMATION; CANCER; KNOWLEDGEBASE AB Biological Pathway Exchange (BioPAX) is a standard language to represent biological pathways at the molecular and cellular level and to facilitate the exchange of pathway data. The rapid growth of the volume of pathway data has spurred the development of databases and computational tools to aid interpretation; however, use of these data is hampered by the current fragmentation of pathway information across many databases with incompatible formats. BioPAX, which was created through a community process, solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. Using BioPAX, millions of interactions, organized into thousands of pathways, from many organisms are available from a growing number of databases. This large amount of pathway data in a computable form will support visualization, analysis and biological discovery. (C) 2010 Nature America, Inc. All rights reserved. C1 [Rodchenkov, Igor; Donaldson, Sylva; Bader, Gary D.] Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. [Demir, Emek; Cary, Michael P.; Anwar, Nadia; Babur, Oezguen; Sander, Chris] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Demir, Emek; Babur, Oezguen; Dogrusoz, Ugur] Bilkent Univ, Ctr Bioinformat, Ankara, Turkey. [Demir, Emek; Babur, Oezguen; Dogrusoz, Ugur] Bilkent Univ, Dept Comp Engn, Ankara, Turkey. [Mi, Huaiyu; Thomas, Paul] SRI Int, Ctr Artificial Intelligence, Menlo Pk, CA 94025 USA. [Fukuda, Ken] Japan Sci & Technol Agcy, Inst Bioinformat Res & Dev, Tokyo, Japan. [Lemer, Christian; Hubaut, Olivier] Univ Libre Bruxelles, Brussels, Belgium. [Vastrik, Imre; Birney, Ewan; Le Novere, Nicolas] European Bioinformat Inst, Cambridge, England. [Wu, Guanming; Haw, Robin] Ontario Inst Canc Res, Toronto, ON, Canada. [D'Eustachio, Peter] NYU, Sch Med, New York, NY USA. [Schaefer, Carl] NCI, Ctr Biomed Informat & Informat Technol, Rockville, MD USA. [Luciano, Joanne] Predict Med, Belmont, MA USA. [Schacherer, Frank; Braun, Burk] BIOBASE Corp, Beverly, MA USA. [Martinez-Flores, Irma; Jimenez-Jacinto, Veronica; Collado-Vides, Julio] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca 62191, Morelos, Mexico. [Hu, Zhenjun] Boston Univ, Biomol Syst Lab, Boston, MA 02215 USA. [Joshi-Tope, Geeta; Ren, Liya] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Kandasamy, Kumaran; Pandey, Akhilesh] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Splendiani, Andrea] Univ Rennes 1, Fac Med, Rennes, France. [Splendiani, Andrea] Rothamsted Res, Harpenden, Herts, England. [Tkachev, Sasha; Hornbeck, Peter] Cell Signaling Technol Inc, Danvers, MA USA. [Zucker, Jeremy] Broad Inst, Cambridge, MA USA. [Gopinath, Gopal] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Rajasimha, Harsha; Sobral, Bruno S.] Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. [Rajasimha, Harsha] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Ramakrishnan, Ranjani; McWeeney, Shannon] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Shah, Imran] US Environm Protect Agcy Durham, Durham, NC USA. [Syed, Mustafa; Glass, Elizabeth; Maltsev, Natalia] Argonne Natl Lab, Math & Comp Sci Div, Argonne, IL 60439 USA. [Blinov, Michael] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Brauner, Erik; Gibbons, Frank] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Corwin, Dan] Lexikos Corp, Boston, MA USA. [Goldberg, Robert] Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. [Luna, Augustin; Sunshine, Margot; Aladjem, Mirit] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Murray-Rust, Peter] Univ Cambridge, Dept Chem, Unilever Ctr Mol Sci Informat, Cambridge CB2 1EW, England. [Neumann, Eric] Clin Semant Grp, Lexington, MA USA. [Reubenacker, Oliver] Univ Connecticut, Ctr Hlth, Ctr Cell Anal & Modeling, Storrs, CT USA. [Samwald, Matthias] Natl Univ Ireland, Digital Enterprise Res Inst, Galway, Ireland. [Samwald, Matthias] Konrad Lorenz Inst Evolut & Cognit Res, Altenberg, Austria. [van Iersel, Martijn] Maastricht Univ, Dept Bioinformat, Maastricht, Netherlands. [Wimalaratne, Sarala] Univ Auckland, Auckland 1, New Zealand. [Allen, Keith; Leonard, Julie] Syngenta Biotech Inc, Res Triangle Pk, NC USA. [Whirl-Carrillo, Michelle; Gong, Li; Tang, Rebecca; Whaley, Ryan] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Cheung, Kei-Hoi] Yale Univ, Yale Ctr Med Informat, New Haven, CT USA. [Dahlquist, Kam] Loyola Marymount Univ, Los Angeles, CA 90045 USA. [Finney, Andrew] Physiomics PLC, Magdalen Ctr, Oxford, England. [Gillespie, Marc] St Johns Univ, Jamaica, NY 11439 USA. [Honig, Michael] Columbia Univ, New York, NY USA. [Kane, David] SRA Int, Fairfax, VA USA. [Krupa, Shiva] Novartis Knowledge Ctr, Cambridge, MA USA. [Kutmon, Martina] Univ Ottawa, Ottawa, ON, Canada. [Marks, Debbie] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Merberg, David] Vertex Pharmaceut, Cambridge, MA USA. [Petri, Victoria] Med Coll Wisconsin, Human & Mol Genet Ctr, Milwaukee, WI 53226 USA. [Pico, Alex] Gladstone Inst Cardiovasc Dis, San Francisco, CA USA. [Ravenscroft, Dean] Cornell Univ, Dept Genet & Plant Breeding, Ithaca, NY USA. [Shah, Nigam] Stanford Univ, Sch Med, Ctr Biomed Informat, Stanford, CA 94305 USA. [Letovksy, Stan] Millennium Pharmaceut Inc, Computat Sci Informat, Cambridge, MA USA. [Buetow, Kenneth H.] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA. [Rzhetsky, Andrey] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA. [Rzhetsky, Andrey] Argonne Natl Lab, Chicago, IL USA. [Schachter, Vincent] Total Gas & Power, Paris, France. [Goto, Susumu] Kyoto Univ, Inst Chem Res, Bioinformat Ctr, Kyoto 606, Japan. [Hucka, Michael] CALTECH, Biol Network Modeling Ctr, Pasadena, CA 91125 USA. [Wingender, Edgar] Dept Bioinformat, Gottingen, Germany. RP Bader, GD (reprint author), Univ Toronto, Banting & Best Dept Med Res, Donnelly Ctr Cellular & Biomol Res, Toronto, ON, Canada. EM biopax-paper@biopax.org RI Haw, Robin/D-1393-2009; van Iersel, Martijn/E-9105-2010; Syed, Mustafa/A-5252-2011; Bader, Gary/C-1176-2009; Le Novere, Nicolas/F-9973-2010; sander, chris/H-1452-2011; Hucka, Michael/B-1896-2012; rzhetsky, andrey/B-6118-2012; Pandey, Akhilesh/B-4127-2009; Vastrik, Imre/C-2690-2009; Zucker, Jeremy/M-3643-2016; OI Birney, Ewan/0000-0001-8314-8497; Fukuda, Ken/0000-0001-7366-1094; D'Eustachio, Peter/0000-0002-5494-626X; Wingender, Edgar/0000-0002-7729-8453; Pico, Alexander/0000-0001-5706-2163; Gillespie, Marc/0000-0002-5766-1702; Haw, Robin/0000-0002-2013-7835; Kutmon, Martina/0000-0002-7699-8191; Wimalaratne, Sarala/0000-0002-5355-2576; Karp, Peter/0000-0002-5876-6418; van Iersel, Martijn/0000-0002-5877-4338; Bader, Gary/0000-0003-0185-8861; Le Novere, Nicolas/0000-0002-6309-7327; Pandey, Akhilesh/0000-0001-9943-6127; Zucker, Jeremy/0000-0002-7276-9009; Murray-Rust, Peter/0000-0003-3386-3972; McWeeney, Shannon/0000-0001-8333-6607; BABUR, OZGUN/0000-0002-0239-5259; Demir, Emek/0000-0002-3663-7113 FU US Department of Energy [DE-FG02-04ER63931]; caBIG program; US National Institute of General Medical Sciences workshop [1R13GM076939, P41HG004118]; US National Human Genome Research Institute and Genome Canada through the Ontario Genomics Institute [2007-OGI-TD-05]; US National Institutes of Health [R01GM071962-07] FX Funded by the US Department of Energy workshop grant DE-FG02-04ER63931, the caBIG program, the US National Institute of General Medical Sciences workshop grant 1R13GM076939, grant P41HG004118 from the US National Human Genome Research Institute and Genome Canada through the Ontario Genomics Institute (2007-OGI-TD-05) and US National Institutes of Health grant R01GM071962-07. Thanks to many people who contributed to discussions on BioPAX mailing lists, at conferences and at BioPAX workshops, especially A. Ruttenberg and J. Rees. NR 65 TC 251 Z9 253 U1 6 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 2010 VL 28 IS 9 BP 935 EP 942 DI 10.1038/nbt.1666 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 648UF UT WOS:000281719100019 PM 20829833 ER PT J AU Walker, A Su, H Conti, MA Harb, N Adelstein, RS Sato, N AF Walker, Andrea Su, Hua Conti, Mary Anne Harb, Nicole Adelstein, Robert S. Sato, Noboru TI Non-muscle myosin II regulates survival threshold of pluripotent stem cells SO NATURE COMMUNICATIONS LA English DT Article ID SELF-RENEWAL; CULTURE; INHIBITOR; MOUSE; DIFFERENTIATION; CYTOKINESIS; MAINTENANCE; MICE AB Human pluripotent stem (hPS) cells such as human embryonic stem (hES) and induced pluripotent stem (hiPS) cells are vulnerable under single cell conditions, which hampers practical applications; yet, the mechanisms underlying this cell death remain elusive. In this paper, we demonstrate that treatment with a specific inhibitor of non-muscle myosin II (NMII), blebbistatin, enhances the survival of hPS cells under clonal density and suspension conditions, and, in combination with a synthetic matrix, supports a fully defined environment for self-renewal. Consistent with this, genetically engineered mouse embryonic stem cells lacking an isoform of NMII heavy chain (NMHCII), or hES cells expressing a short hairpin RNA to knock down NMHCII, show greater viability than controls. Moreover, NMII inhibition increases the expression of self-renewal regulators Oct3/4 and Nanog, suggesting a mechanistic connection between NMII and self-renewal. These results underscore the importance of the molecular motor, NMII, as a novel target for chemically engineering the survival and self-renewal of hPS cells. C1 [Walker, Andrea; Su, Hua; Harb, Nicole; Sato, Noboru] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. [Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Sato, N (reprint author), Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. EM saton@ucr.edu OI Adelstein, Robert/0000-0002-8683-2144 FU UCR FX We acknowledge Hiroko Akuzawa for technical assistance and staff in the animal facility for SCID/beige mice maintenance. We also thank Susan Newbigging, Colin McKerlie and Lily Morikawa for teratoma pathology reports and Rebecca Gaulin for karyotyping analysis and reports. We are indebted to Ali Brivanlou, Ronald G. Crystal and Lorenz Studer for valuable scientific advice. N.S. is supported by UCR. NR 41 TC 34 Z9 36 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD SEP PY 2010 VL 1 AR 71 DI 10.1038/ncomms1074 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673GE UT WOS:000283646500010 PM 20842192 ER PT J AU Abnet, CC Freedman, ND Hu, N Wang, ZM Yu, K Shu, XO Yuan, JM Zheng, W Dawsey, SM Dong, LM Lee, MP Ding, T Qiao, YL Gao, YT Koh, WP Xiang, YB Tang, ZZ Fan, JH Wang, CY Wheeler, W Gail, MH Yeager, M Yuenger, J Hutchinson, A Jacobs, KB Giffen, CA Burdett, L Fraumeni, JF Tucker, MA Chow, WH Goldstein, AM Chanock, SJ Taylor, PR AF Abnet, Christian C. Freedman, Neal D. Hu, Nan Wang, Zhaoming Yu, Kai Shu, Xiao-Ou Yuan, Jian-Min Zheng, Wei Dawsey, Sanford M. Dong, Linda M. Lee, Maxwell P. Ding, Ti Qiao, You-Lin Gao, Yu-Tang Koh, Woon-Puay Xiang, Yong-Bing Tang, Ze-Zhong Fan, Jin-Hu Wang, Chaoyu Wheeler, William Gail, Mitchell H. Yeager, Meredith Yuenger, Jeff Hutchinson, Amy Jacobs, Kevin B. Giffen, Carol A. Burdett, Laurie Fraumeni, Joseph F., Jr. Tucker, Margaret A. Chow, Wong-Ho Goldstein, Alisa M. Chanock, Stephen J. Taylor, Philip R. TI A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CANCER; CHINA; RISK; MUTATIONS; VARIANT; TRACT; CHEK2 AB We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 x 10(-9); per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 x 10(-9); OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 x 10(-15); OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China. C1 [Abnet, Christian C.; Freedman, Neal D.; Hu, Nan; Wang, Zhaoming; Yu, Kai; Dawsey, Sanford M.; Dong, Linda M.; Wang, Chaoyu; Gail, Mitchell H.; Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Jacobs, Kevin B.; Burdett, Laurie; Fraumeni, Joseph F., Jr.; Tucker, Margaret A.; Chow, Wong-Ho; Goldstein, Alisa M.; Chanock, Stephen J.; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Wang, Zhaoming; Yeager, Meredith; Yuenger, Jeff; Hutchinson, Amy; Jacobs, Kevin B.; Burdett, Laurie] SAIC Frederick Inc, NCI Frederick, Core Genotyping Facil, Frederick, MD USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Dept Med, Nashville, TN USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Yuan, Jian-Min] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Lee, Maxwell P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Ding, Ti; Tang, Ze-Zhong] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. [Qiao, You-Lin; Fan, Jin-Hu] Chinese Acad Med Sci, Dept Epidemiol, Canc Inst Hosp, Beijing 100037, Peoples R China. [Gao, Yu-Tang; Xiang, Yong-Bing] Shanghai Canc Inst, Shanghai, Peoples R China. [Koh, Woon-Puay] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Epidemiol & Publ Hlth, Singapore 117595, Singapore. [Wheeler, William; Giffen, Carol A.] Informat Management Serv Inc, Silver Spring, MD USA. RP Abnet, CC (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov RI Liao, Linda/B-3960-2011; Qiao, You-Lin/B-4139-2012; Tucker, Margaret/B-4297-2015; Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015; OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098; Yuan, Jian-Min/0000-0002-4620-3108 FU National Cancer Institute [SMHS: R01 CA82729, SWHS: R37 CA70837, NO2-CP-11010, SCHS: R01 CA55069, R35 CA53890, R01 CA80205, R01 CA144034, NO2-SC-66211, NO1-SC-91030, HHSN261200477001C]; Shanxi Cancer Hospital and Institute; Cancer Institute of the Chinese Academy of Medical Sciences; NIH, National Cancer Institute; Division of Cancer Epidemiology and Genetics; Center for Cancer Research FX We thank the study participants and staff of the Shanghai Men's Health Study (SMHS), Shanghai Women's Health Study (SWHS) and Singapore Chinese Health Study (SCHS). Supported by the National Cancer Institute (SMHS: R01 CA82729; SWHS: R37 CA70837 and contract NO2-CP-11010 with Vanderbilt University; SCHS: R01 CA55069, R35 CA53890, R01 CA80205 and R01 CA144034). We thank M. C. Yu and H.-P. Lee for establishing this cohort. Cancer cases were identified through database linkage by the Ministry of Health in Singapore. The Shanxi Upper Gastrointestinal Cancer Genetics Project was supported by the National Cancer Institute contract NO2-SC-66211 with the Shanxi Cancer Hospital and Institute. The Nutrition Intervention Trials (NIT) were supported by National Cancer Institute contracts NO1-SC-91030 and HHSN261200477001C with the Cancer Institute of the Chinese Academy of Medical Sciences. The current analysis was supported by the Intramural Research Program of the NIH, National Cancer Institute, the Division of Cancer Epidemiology and Genetics, and the Center for Cancer Research. NR 28 TC 229 Z9 244 U1 0 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2010 VL 42 IS 9 BP 764 EP U51 DI 10.1038/ng.649 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 644OM UT WOS:000281388400011 PM 20729852 ER PT J AU Hamza, TH Zabetian, CP Tenesa, A Laederach, A Montimurro, J Yearout, D Kay, DM Doheny, KF Paschall, J Pugh, E Kusel, VI Collura, R Roberts, J Griffith, A Samii, A Scott, WK Nutt, J Factor, SA Payami, H AF Hamza, Taye H. Zabetian, Cyrus P. Tenesa, Albert Laederach, Alain Montimurro, Jennifer Yearout, Dora Kay, Denise M. Doheny, Kimberly F. Paschall, Justin Pugh, Elizabeth Kusel, Victoria I. Collura, Randall Roberts, John Griffith, Alida Samii, Ali Scott, William K. Nutt, John Factor, Stewart A. Payami, Haydeh TI Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUBSTANTIA-NIGRA; RISK-FACTORS; REACTIVE MICROGLIA; ALPHA-SYNUCLEIN; T-CELLS; POPULATION; PATHOGENESIS; METAANALYSIS; EXPRESSION AB Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC)(1-5). We confirmed associations with SNCA(2,6-8) and MAPT(3,7-9), replicated an association with GAK9 (using data from the NGRC and a previous study(9), P = 3.2 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 10(-8)) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ(10,11). The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia(12), and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk(4,13). The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development. C1 [Hamza, Taye H.; Laederach, Alain; Montimurro, Jennifer; Yearout, Dora; Kay, Denise M.; Kusel, Victoria I.; Collura, Randall; Payami, Haydeh] Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA. [Zabetian, Cyrus P.; Yearout, Dora; Samii, Ali] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Zabetian, Cyrus P.; Yearout, Dora; Samii, Ali] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Tenesa, Albert] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Doheny, Kimberly F.; Pugh, Elizabeth] Johns Hopkins Univ, Sch Med, CIDR, Baltimore, MD USA. [Paschall, Justin] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Roberts, John] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Griffith, Alida] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Washington, DC USA. [Scott, William K.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. [Scott, William K.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Nutt, John] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Factor, Stewart A.] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Payami, H (reprint author), Wadsworth Ctr, New York State Dept Hlth, Albany, NY USA. EM hpayami@wadsworth.org OI Kay, Denise/0000-0002-9928-2698; Zabetian, Cyrus/0000-0002-7739-4306; Laederach, Alain/0000-0002-5088-9907 FU National Institute of Neurological Disorders and Stroke [R01NS36960]; Michael J. Fox Foundation for Parkinson's Disease Research; Department of Veterans Affairs [1I01BX000531]; National Institutes of Aging [P30AG08017]; National Institute of Mental Health [R21MH087336]; Office of Research and Development, Clinical Sciences Research and Development Service, Department of Veteran Affairs; US National Institutes of Health (NIH) at the National Library of Medicine; NIH [HHSN268200782096C, AG027944, NS039764] FX We would like to acknowledge the individuals with Parkinson's disease, their families and the healthy volunteers who participated in this study. We thank T. L. Edwards, J.M. Vance, E. R. Martin, J.L. Haines and M. A. Pericak-Vance for sharing their GWAS data with us; R. H. Myers, J.F. Gusella, T. Foroud and N. Pankratz for making their data public via dbGaP; and J. Degner for assistance with the eQTL data repository website at University of Chicago. We acknowledge M. Adams, M. Zilka and the staff of CIDR for excellent genotyping service, M. Palumbo, C. S. Carmack and the staff of the Computational Biology and Statistics Core of Wadsworth Center for computing support and C. Lambert and G. L. Peterson for developing the randomized plate layout. This project was supported by Award Number R01NS36960 from the National Institute of Neurological Disorders and Stroke. Additional support was provided by an Edmond J. Safra Global Genetic Consortium Grant from the Michael J. Fox Foundation for Parkinson's Disease Research, Merit Review Award from the Department of Veterans Affairs (1I01BX000531), National Institutes of Aging (P30AG08017), National Institute of Mental Health (R21MH087336), Office of Research and Development, Clinical Sciences Research and Development Service, Department of Veteran Affairs, The Intramural Research Program of the US National Institutes of Health (NIH) at the National Library of Medicine and the Close to the Cure Foundation. Genotyping services were provided by CIDR, which is fully funded through a federal contract from the NIH to Johns Hopkins University, contract number HHSN268200782096C. The work described in ref. 8, whose data were used for replication, was funded by NIH grants AG027944 and NS039764. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 35 TC 271 Z9 276 U1 4 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2010 VL 42 IS 9 BP 781 EP U75 DI 10.1038/ng.642 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 644OM UT WOS:000281388400015 PM 20711177 ER PT J AU Li, T Morgan, MJ Choksi, S Zhang, Y Kim, YS Liu, ZG AF Li, Tao Morgan, Michael J. Choksi, Swati Zhang, Yan Kim, You-Sun Liu, Zheng-gang TI MicroRNAs modulate the noncanonical transcription factor NF-kappa B pathway by regulating expression of the kinase IKK alpha during macrophage differentiation SO NATURE IMMUNOLOGY LA English DT Article ID CONTROLS PROSTATE-CANCER; GENE-EXPRESSION; ACTIVATION; P100; INFLAMMATION; RECOGNITION; NF-KAPPA-B2; GENERATION; SURVIVAL; BIOLOGY AB MicroRNAs are key regulators of many biological processes including cell differentiation. Here we show that during human monocyte-macrophage differentiation expression of the microRNAs miR-223 miR-15a and miR-16 decreased considerably which led to higher expression of the serine-threonine kinase IKK alpha in macrophages. In macrophages higher IKK alpha expression in conjunction with stabilization of the kinase NIK induced larger amounts of p52. Because of low expression of the transcription factor ReIB in untreated macrophages high p52 expression repressed basal transcription of both canonical and noncanonical NF-kappa B target genes. However proinflammatory stimuli in macrophages resulted in greater induction of noncanonical NF-kappa B target genes. Thus a decrease in certain microRNAs probably prevents macrophage hyperactivation yet primes the macrophage for certain responses to proinflammatory stimuli. C1 [Kim, You-Sun] Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. [Li, Tao; Morgan, Michael J.; Choksi, Swati; Zhang, Yan; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kim, YS (reprint author), Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. EM yousunkim@ajou.ac.kr; zgliu@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX We thank the Preclinical Repository of the National Cancer Institute for the antibody to the p100 C terminus and the National Institutes of Health Blood Bank for elutriated monocytes. Supported by the Intramural Research Program of The Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 40 TC 137 Z9 157 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2010 VL 11 IS 9 BP 799 EP U48 DI 10.1038/ni.1918 PG 8 WC Immunology SC Immunology GA 641HN UT WOS:000281115500007 PM 20711193 ER PT J AU Van Dyke, T AF Van Dyke, Terry TI Approximating a human cancer SO NATURE MEDICINE LA English DT Editorial Material ID PANCREATIC-CANCER; CHEMOTHERAPY C1 [Van Dyke, Terry] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. [Van Dyke, Terry] NCI, Ctr Adv Preclin Res, Frederick, MD 21701 USA. RP Van Dyke, T (reprint author), NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. EM vandyket@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 8 TC 10 Z9 10 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2010 VL 16 IS 9 BP 976 EP 977 DI 10.1038/nm0910-976 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 647MP UT WOS:000281622900024 PM 20823881 ER PT J AU Berkley, S Bertram, K Delfraissy, JF Draghia-Akli, R Fauci, A Hallenbeck, C Kagame, MJ Kim, P Mafubelu, D Makgoba, MW Piot, P Walport, M Warren, M Yamada, T Esparza, J Hankins, C Johnston, MI Levy, Y Romaris, M Ahmed, R Bernstein, A AF Berkley, Seth Bertram, Kenneth Delfraissy, Jean-Francois Draghia-Akli, Ruxandra Fauci, Anthony Hallenbeck, Cynthia Kagame, Madame Jeannette Kim, Peter Mafubelu, Daisy Makgoba, Malegapuru W. Piot, Peter Walport, Mark Warren, Mitchell Yamada, Tadataka Esparza, Jose Hankins, Catherine Johnston, Margaret I. Levy, Yves Romaris, Manuel Ahmed, Rafi Bernstein, Alan CA Council Global HIV Vaccine Enterpr TI The 2010 scientific strategic plan of the Global HIV Vaccine Enterprise SO NATURE MEDICINE LA English DT Article ID YELLOW-FEVER VACCINE; T-CELL RESPONSES; MONOCLONAL-ANTIBODIES; ELITE CONTROLLERS; SYSTEMS BIOLOGY; VIRUS; INFECTION; IMMUNOLOGY; CHALLENGE; TRANSMISSION C1 [Berkley, Seth] IAVI, New York, NY USA. [Bertram, Kenneth] MHRP, Rockville, MD USA. [Delfraissy, Jean-Francois; Levy, Yves] ANRS, Paris, France. [Draghia-Akli, Ruxandra; Romaris, Manuel] European Commiss, Brussels, Belgium. [Fauci, Anthony; Johnston, Margaret I.] NIAID, NIH, Bethesda, MD 20892 USA. [Hallenbeck, Cynthia] Enterprise Secretary Treasurer, New York, NY USA. [Kagame, Madame Jeannette] First Lady Rwanda, Kigali, Rwanda. [Kim, Peter] Merck Res Labs, Rahway, NJ USA. [Mafubelu, Daisy; Hankins, Catherine] WHO UNAIDS, Geneva, Switzerland. [Makgoba, Malegapuru W.] Univ KwaZulu Natal, Durban, South Africa. [Piot, Peter] London Sch Hyg & Trop Med, London WC1, England. [Walport, Mark] Wellcome Trust Res Labs, London, England. [Warren, Mitchell] AVAC Global Advocacy HIV Prevent, New York, NY USA. [Yamada, Tadataka; Esparza, Jose] Bill & Melinda Gates Fdn, Seattle, WA USA. [Bernstein, Alan] Global HIV Vaccine Enterprise, New York, NY USA. [Ahmed, Rafi] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. [Ahmed, Rafi] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. RP Berkley, S (reprint author), IAVI, New York, NY USA. EM abernstein@vaccineenterprise.org OI Walport, Mark/0000-0001-7220-5273; Hankins, Catherine/0000-0002-1642-8592 NR 46 TC 21 Z9 23 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD SEP PY 2010 VL 16 IS 9 BP 981 EP 989 DI 10.1038/nm0910-981 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 647MP UT WOS:000281622900025 ER PT J AU Yao, LN Fan, PD Arolfo, M Jiang, Z Olive, MF Zablocki, J Sun, HL Chu, N Lee, J Kim, HY Leung, K Shryock, J Blackburn, B Diamond, I AF Yao, Lina Fan, Peidong Arolfo, Maria Jiang, Zhang Olive, M. Foster Zablocki, Jeff Sun, Hai-Ling Chu, Nancy Lee, Jeongrim Kim, Hee-Yong Leung, Kwan Shryock, John Blackburn, Brent Diamond, Ivan TI Inhibition of aldehyde dehydrogenase-2 suppresses cocaine seeking by generating THP, a cocaine use-dependent inhibitor of dopamine synthesis SO NATURE MEDICINE LA English DT Article ID VENTRAL TEGMENTAL AREA; PROTEIN-KINASE-A; NUCLEUS-ACCUMBENS; TYROSINE-HYDROXYLASE; DRUG-ADDICTION; NEUROBIOLOGY; BRAIN; METABOLISM; CIRCUITRY; ASSAY AB There is no effective treatment for cocaine addiction despite extensive knowledge of the neurobiology of drug addiction(1-4). Here we show that a selective aldehyde dehydrogenase-2 (ALDH-2) inhibitor, ALDH2i, suppresses cocaine self-administration in rats and prevents cocaine-or cue-induced reinstatement in a rat model of cocaine relapse-like behavior. We also identify a molecular mechanism by which ALDH-2 inhibition reduces cocaine-seeking behavior: increases in tetrahydropapaveroline (THP) formation due to inhibition of ALDH-2 decrease cocaine-stimulated dopamine production and release in vitro and in vivo. Cocaine increases extracellular dopamine concentration, which activates dopamine D2 autoreceptors to stimulate cAMP-dependent protein kinase A (PKA) and protein kinase C (PKC) in primary ventral tegmental area (VTA) neurons. PKA and PKC phosphorylate and activate tyrosine hydroxylase, further increasing dopamine synthesis in a positive-feedback loop. Monoamine oxidase converts dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL), a substrate for ALDH-2. Inhibition of ALDH-2 enables DOPAL to condense with dopamine to form THP in VTA neurons. THP selectively inhibits phosphorylated (activated) tyrosine hydroxylase to reduce dopamine production via negative-feedback signaling. Reducing cocaine-and craving-associated increases in dopamine release seems to account for the effectiveness of ALDH2i in suppressing cocaine-seeking behavior. Selective inhibition of ALDH-2 may have therapeutic potential for treating human cocaine addiction and preventing relapse. C1 [Yao, Lina; Fan, Peidong; Arolfo, Maria; Jiang, Zhang; Zablocki, Jeff; Sun, Hai-Ling; Chu, Nancy; Leung, Kwan; Shryock, John; Blackburn, Brent; Diamond, Ivan] Gilead Sci Inc, Palo Alto, CA USA. [Olive, M. Foster] Med Univ S Carolina, Dept Psychiat, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Olive, M. Foster] Med Univ S Carolina, Dept Neurosci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [Lee, Jeongrim; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD USA. RP Yao, LN (reprint author), Gilead Sci Inc, Palo Alto, CA USA. EM lina.yao@gilead.com OI Olive, Foster/0000-0002-2517-0351 FU Intramural NIH HHS [Z01 AA000500-05] NR 41 TC 50 Z9 50 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 2010 VL 16 IS 9 BP 1024 EP U120 DI 10.1038/nm.2200 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 647MP UT WOS:000281622900032 PM 20729865 ER EF