FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wu, CP Ohnuma, S Ambudkar, SV AF Wu, Chung-Pu Ohnuma, Shinobu Ambudkar, Suresh V. TI Discovering Natural Product Modulators to Overcome Multidrug Resistance in Cancer Chemotherapy SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE ATP-binding cassette transporters; bioavailability; chemotherapy; modulators; multidrug resistance; natural products ID P-GLYCOPROTEIN FUNCTION; MEDIATED DRUG-RESISTANCE; KAEMPFERIA-PARVIFLORA EXTRACTS; ACUTE MYELOID-LEUKEMIA; MOUSE LYMPHOMA-CELLS; IN-VITRO; ABC TRANSPORTERS; DOXORUBICIN-RESISTANCE; CHEMOPREVENTIVE AGENT; ORAL BIOAVAILABILITY AB Multidrug resistance caused by the overexpression of ABC drug transporters is a major obstacle in clinical cancer chemotherapy. For several years, it appeared that direct inhibition of ABC transporters would be the cheapest and most efficient way to combat this problem. Unfortunately, progress in finding a potent, selective inhibitor to modulate ABC transporters and restore drug sensitivity in multidrug-resistant cancer cells has been slow and challenging. Candidate drugs should ideally be selective, potent and relatively non-toxic. Many researchers in recent years have turned their attention to utilizing natural products as the building blocks for the development of the next generation of inhibitors, especially after the disappointing results obtained from inhibitors of the first three generations at the clinical trial stage. The first step is to discover natural substances (distinct from the first three generation inhibitors) that are potent, selective and relatively non-toxic in order to be used clinically. Here, we present a brief overview of the prospect of using natural products to modulate the function of ABC drug transporters clinically and their impact on human physiology and pharmacology. C1 [Wu, Chung-Pu; Ohnuma, Shinobu; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wu, Chung-Pu] Chang Gung Univ, Dept Physiol & Pharmacol, Tao Yuan, Taiwan. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX We thank George Leiman for editorial assistance in preparation of the manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 163 TC 49 Z9 51 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD APR PY 2011 VL 12 IS 4 BP 609 EP 620 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 753JZ UT WOS:000289770000014 PM 21118092 ER PT J AU Gillet, JP Gottesman, MM AF Gillet, Jean-Pierre Gottesman, Michael M. TI Advances in the Molecular Detection of ABC Transporters Involved in Multidrug Resistance in Cancer SO CURRENT PHARMACEUTICAL BIOTECHNOLOGY LA English DT Review DE ABC transporters; clinical diagnosis; personalized medicine; TaqMan-based qRT-PCR ID BINDING CASSETTE TRANSPORTERS; GENE-EXPRESSION ANALYSIS; DRUG TRANSPORTERS; MYELOID-LEUKEMIA; P-GLYCOPROTEIN; CELL-LINES; PROTEINS; MICROARRAY; PREDICTION; CHEMOSENSITIVITY AB ATP-Binding Cassette (ABC) transporters are important mediators of multidrug resistance (MDR) in patients with cancer. Although their role in MDR has been extensively studied in vitro, their value in predicting response to chemotherapy has yet to be fully determined. Establishing a molecular diagnostic assay dedicated to the quantitation of ABC transporter genes is therefore critical to investigate their involvement in clinical MDR. In this article, we provide an overview of the methodologies that have been applied to analyze the mRNA expression levels of ABC transporters, by describing the technology, its pros and cons, and the experimental protocols that have been followed. We also discuss recent studies performed in our laboratory that assess the ability of the currently available high-throughput gene expression profiling platforms to discriminate between highly homologous genes. This work led to the conclusion that high-throughput TaqMan-based qRT-PCR platforms provide standardized clinical assays for the molecular detection of ABC transporters and other families of highly homologous MDR-linked genes encoding, for example, the uptake transporters (solute carriers-SLCs) and the phase I and II metabolism enzymes. C1 [Gillet, Jean-Pierre; Gottesman, Michael M.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM gottesmanm@mail.nih.gov RI gillet, jean-pierre/A-3714-2012 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX We thank George Leiman for editorial assistance. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 52 TC 33 Z9 34 U1 2 U2 18 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2010 J9 CURR PHARM BIOTECHNO JI Curr. Pharm. Biotechnol. PD APR PY 2011 VL 12 IS 4 BP 686 EP 692 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 753JZ UT WOS:000289770000020 PM 21118086 ER PT J AU Jiang, JK Shen, M Thomas, CJ Boxer, MB AF Jiang, Jian-kang Shen, Min Thomas, Craig J. Boxer, Mathew B. TI Chiral Kinase Inhibitors SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Kinase inhibitors; chirality; P38a; AKT; Erk; Jak3; TrkA ID P38 MAP KINASE; SMALL-MOLECULE INHIBITORS; RESORCYLIC ACID LACTONES; ETHER LIPID ANALOGS; NERVE GROWTH-FACTOR; PROTEIN-KINASES; SELECTIVE INHIBITORS; POTENT INHIBITORS; DRUG DISCOVERY; AKT/PKB FAMILY AB Small molecule kinase inhibitors are important tools for studying cellular signaling pathways, phenotypes and are, occasionally, useful clinical agents. With stereochemistry pervasive throughout the molecules of life it is no surprise that a single stereocenter can bestow a ligand with distinct binding affinities to various protein targets. While the majority of small molecule kinase inhibitors reported to date are achiral, a number of asymmetric compounds show great utility as tools for probing kinase-associated biomolecular events as well as promising therapeutic leads. The mechanism by which chirality is introduced varies but includes screening of chiral libraries, incorporation of chiral centers during optimization efforts and the rational installation of a chiral moiety as guided by structural and modeling efforts. Here we discuss several advanced chiral small molecule kinase inhibitors where stereochemistry plays an important role in terms of potency and selectivity. C1 [Jiang, Jian-kang; Shen, Min; Thomas, Craig J.; Boxer, Mathew B.] NHGRI, NIH Chem Genom Ctr, NIH, Rockville, MD 20850 USA. RP Thomas, CJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr,Bldg B,Room 3005,MSC 3370, Bethesda, MD 20892 USA. EM craigt@nhgri.nih.gov FU Molecular Libraries Initiative of the National Institutes of Health; National Human Genome Research Institute, National Institutes of Health FX The authors would foremost like to acknowledge the talent, work and ingenuity of the researchers whose work is reviewed in this manuscript. We thank Ms. Allison Mandich for critical reading of this manuscript. Research at the NIH Chemical Genomics Center is supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 106 TC 4 Z9 4 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 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD APR PY 2011 VL 11 IS 7 BP 800 EP 809 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 753JR UT WOS:000289768900004 PM 21291394 ER PT J AU Issaq, HJ Waybright, TJ Veenstra, TD AF Issaq, Haleem J. Waybright, Timothy J. Veenstra, Timothy D. TI Cancer biomarker discovery: Opportunities and pitfalls in analytical methods SO ELECTROPHORESIS LA English DT Review DE Biomarker discovery; Cancer; MS; Metabolomics; Proteomics ID HUMAN SERUM PROTEOME; BLADDER-CANCER; MASS-SPECTROMETRY; TUMOR-MARKERS; KIDNEY CANCER; PLASMA; URINE; DIAGNOSIS; METABOLOMICS; SARCOSINE AB Many diseases result in specific and characteristic changes in the chemical and biochemical profiles of biological fluids and tissues prior to development of clinical symptoms. These changes are often useful diagnostic and prognostic biomarkers. Identifying biomarkers that can be used for the early detection of cancer will result in more efficient treatments, reduction in suffering, and lower mortality rates. An ideal screening test should be non-invasive with high sensitivity and specificity. Proteomic and metabolomic analyses of biological samples can reveal changes in abundance levels of metabolites and proteins that when validated and confirmed through clinical trials can function as clinical tests for early detection, diagnosis, monitoring disease progression, and predicting therapeutic response. While the past decade has seen great advancements in proteomics and metabolomics research producing potential biomarkers for cancer, most of the identified biomarkers have failed to replace existing clinical tests. To become a clinically approved test, a potential biomarker should be confirmed and validated using hundreds of specimens and should be reproducible, specific, and sensitive. A search of the scientific and medical literature indicates that many studies report the discovery of potential biomarkers without proper validation and/or they do not meet the above criteria. In this manuscript, we will discuss the successes and the pitfalls of biomarker research and comment on study and experimental design, which in most cases is lacking, resulting in suboptimal biomarkers. C1 [Issaq, Haleem J.; Waybright, Timothy J.; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, 1050 Boyles St,POB B, Frederick, MD 21702 USA. EM issaqh@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts 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 United States Government. NR 48 TC 64 Z9 66 U1 7 U2 62 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD APR PY 2011 VL 32 IS 9 SI SI BP 967 EP 975 DI 10.1002/elps.201000588 PN 1 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 751TB UT WOS:000289639400003 PM 21449066 ER PT J AU Eberle, FC Rodriguez-Canales, J Wei, L Hanson, JC Killian, JK Sun, HW Adams, LG Hewitt, SM Wilson, WH Pittaluga, S Meltzer, PS Staudt, LM Emmert-Buck, MR Jaffe, ES AF Eberle, Franziska C. Rodriguez-Canales, Jaime Wei, Lai Hanson, Jeffrey C. Killian, J. Keith Sun, Hong-Wei Adams, Lisa G. Hewitt, Stephen M. Wilson, Wyndham H. Pittaluga, Stefania Meltzer, Paul S. Staudt, Louis M. Emmert-Buck, Michael R. Jaffe, Elaine S. TI Methylation profiling of mediastinal gray zone lymphoma reveals a distinctive signature with elements shared by classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE mediastinal gray zone lymphoma; classical Hodgkin's lymphoma; primary mediastinal large B-cell lymphoma; epigenetics; microdissection ID FOLLICULAR LYMPHOMA; GENE; FEATURES; AMPLIFICATION; EXPRESSION; INSIGHTS; DISEASE; BIOLOGY; ORIGIN; CANCER AB Background Mediastinal gray zone lymphoma is a newly recognized entity with transitional morphological and immunophenotypic features between the nodular sclerosis subtype of Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. Diagnostic criteria for mediastinal gray zone lymphoma are still challenging, and the optimal therapy is as yet undetermined. Epigenetic changes have been implicated in the loss of the B-cell program in classical Hodgkin's lymphoma, and might provide a basis for the immunophenotypic alterations seen in mediastinal gray zone lymphoma. Design and Methods We performed a large-scale DNA methylation analysis of microdissected tumor cells to investigate the biological underpinnings of mediastinal gray zone lymphoma and its association with the related entities classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma, making comparisons with the presumptively less related diffuse large B-cell lymphoma. Results Principal component analysis demonstrated that mediastinal gray zone lymphoma has a distinct epigenetic profile intermediate between classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma but remarkably different from that of diffuse large B-cell lymphoma. Analysis of common hypo- and hypermethylated CpG targets in mediastinal gray zone lymphoma, classical Hodgkin's lymphoma, primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma was performed and confirmed the findings of the principal component analysis. Based on the epigenetic profiles we were able to establish class prediction models utilizing genes such as HOXA5, NIMP9, EPH47 and DAPK1 which could distinguish between mediastinal gray zone lymphoma, classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma with a final combined prediction of 100%. Conclusions Our data confirm a close relationship between mediastinal gray zone lymphoma and both classical Hodgkin's lymphoma and primary mediastinal large B-cell lymphoma. However, important differences were observed as well, allowing a clear distinction from both parent entities. Thus, mediastinal gray zone lymphoma cannot be assigned to either classical Hodgkin's lymphoma or primary mediastinal large B-cell lymphoma, validating the decision to create an intermediate category in the World Health Organization classification. C1 [Jaffe, Elaine S.] NCI, Hematopathol Sect, Pathol Lab, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. [Killian, J. Keith; Adams, Lisa G.; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Wilson, Wyndham H.; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Wei, Lai] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Sun, Hong-Wei] NIAMSD, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH,Ctr Canc Res, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov RI Wei, Lai/D-1088-2014; OI Hewitt, Stephen/0000-0001-8283-1788; Rodriguez-Canales, Jaime/0000-0002-0885-2377; Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX this work was supported by the intramural research program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 43 TC 48 Z9 56 U1 0 U2 3 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 APR PY 2011 VL 96 IS 4 BP 558 EP 566 DI 10.3324/haematol.2010.033167 PG 9 WC Hematology SC Hematology GA 752AC UT WOS:000289658600014 PM 21454882 ER PT J AU Feng, XM Scheinberg, P Wu, CO Samsel, L Nunez, O Prince, C Ganetzky, RD McCoy, JP Maciejewski, JR Young, NS AF Feng, Xingmin Scheinberg, Phillip Wu, Colin O. Samsel, Leigh Nunez, Olga Prince, Courtney Ganetzky, Rebecca D. McCoy, J. Philip, Jr. Maciejewski, Jaroslaw R. Young, Neal S. TI Cytokine signature profiles in acquired aplastic anemia and myelodysplastic syndromes SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE cytokine; aplastic anemia; myelodysplastic syndromes ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; ANTITHYMOCYTE GLOBULIN; PLASMA THROMBOPOIETIN; PATHOPHYSIOLOGY; ERYTHROPOIETIN; CYCLOSPORINE; EXPRESSION; MARROW AB Although aplastic anemia and myelodysplasia have been extensively investigated, little is known about their circulating cytokine patterns. We compared plasma soluble cytokines in 33 aplastic anemia, 57 myelodysplasia patients, and 48 healthy controls. High levels of thrombopoietin and granulocyte colony-stimulating factor, with low levels of CD40 hgand, chemokine (C-X-C motif) ligand 5, chemokine (C-C motif) ligand 5, chemokine (C-X-C motif) ligand 11, epidermal growth factor, vascular endothelial growth factor, and chemokine (C-C motif) ligand 11 were a signature profile for aplastic anemia. High levels of tumor necrosis factor-a, interleukin-6, chemokine (C-C motif) ligand 3, interleukin-1 receptor antagonist, and hepatocyte growth factor were a cytokine signature for myelodysplasia. Despite similar clinical presentations, distinct cytokine profiles were observed between aplastic anemia and hypocellular myelodysplasia. Future studies focusing on cytokines that better discriminate these two entities such as thrombopoietin and chemokine (C-C motif) ligand 3 may be useful tools in clinical practice. C1 [Feng, Xingmin; Scheinberg, Phillip; Nunez, Olga; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wu, Colin O.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Prince, Courtney; Maciejewski, Jaroslaw R.] Cleveland Clin, Dept Translat Hematol Oncol Res, Taussig Canc Ctr, Cleveland, OH 44106 USA. [Ganetzky, Rebecca D.] Case Western Reserve Univ, Cleveland Clin Lerner Coll Med, Cleveland Clin, Cleveland, OH 44106 USA. RP Feng, XM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Rm 3E-5216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM fengx2@nhlbi.nih.gov RI Scheinberg, Phillip/H-5251-2012; OI Scheinberg, Phillip/0000-0002-9047-4538 FU National Heart, Lung and Blood Institute, National Institutes of Health FX this work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health. NR 16 TC 38 Z9 45 U1 0 U2 3 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 APR PY 2011 VL 96 IS 4 BP 602 EP 606 DI 10.3324/haematol.2010.030536 PG 5 WC Hematology SC Hematology GA 752AC UT WOS:000289658600019 PM 21160069 ER PT J AU Schmuth, M Elentner, A Gonzalez, FJ Dubrac, S AF Schmuth, M. Elentner, A. Gonzalez, F. J. Dubrac, S. TI Pregnane X Receptor ( PXR) links xenobiotic metabolism to the skin immune response SO JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT LA English DT Meeting Abstract C1 [Schmuth, M.; Elentner, A.; Dubrac, S.] Innsbruck Med Univ, Dept Dermatol & Venereol, Innsbruck, Austria. [Gonzalez, F. J.] NCI, Ctr Canc Res, Lab Metab, 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 1610-0379 J9 J DTSCH DERMATOL GES JI J. Dtsch. Dermatol. Ges. PD APR PY 2011 VL 9 SU 1 BP 147 EP 147 PG 1 WC Dermatology SC Dermatology GA 742OY UT WOS:000288955200520 ER PT J AU Holsgaard-Larsen, A Caserotti, P Puggaard, L Aagaard, P AF Holsgaard-Larsen, Anders Caserotti, Paolo Puggaard, Lis Aagaard, Per TI Stair-Ascent Performance in Elderly Women: Effect of Explosive Strength Training SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE antagonist muscle coactivation; muscle power; functional performance; exercise ID GROUND REACTION FORCES; OLDER-ADULTS; MUSCLE FUNCTION; FUNCTIONAL ABILITY; MAXIMAL STRENGTH; POWER; MEN; PEOPLE; EXERCISE; COACTIVATION AB Explosive-type strength training may alter kinetics and neuromuscular activity during stair ascent in elderly women. This may improve functional ability. Nineteen women (69.7 +/- 3.4 yr) were randomly allocated to strength training (TG; twice per wk, 12 wk) or a control group (CO). Stair ascent was assessed at self-chosen (AFV), standardized (ASV), and maximal velocity (AM V) pre- and posttraining. Ground-reaction force (GRF) and EMG quantified kinetics and neuromuscular activity. After training, TO increased AM V and AFV velocity by 8% (p = .02) and 17% (p = .007), respectively (TG vs. CG; p < .05). This was accompanied by elevated rectus femoris EMG (from 21% to 48%, p < .047). At AFV, TO increased GRF first peak force 4% (p = .047), and CO increased second peak force 5% (p = .036). Muscle coactivation remained unaltered in both groups. Explosive-type strength training led to enhanced stair-climbing performance at maximal and self-chosen speed, reflecting an improved functional ability. C1 [Holsgaard-Larsen, Anders; Puggaard, Lis; Aagaard, Per] Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. [Caserotti, Paolo] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Holsgaard-Larsen, A (reprint author), Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark. RI Holsgaard-Larsen, Anders/F-1033-2013; OI Holsgaard-Larsen, Anders/0000-0003-4106-6930 FU Danish Ministry of Social Affairs; National Institutes of Health, National Institute of Aging FX This study was supported by research grants from the Danish Ministry of Social Affairs. Furthermore, it was supported in part by Intramural Research Program of the National Institutes of Health, National Institute of Aging. We like to express our gratitude to all the subjects who volunteered to participate in the study. NR 44 TC 16 Z9 18 U1 1 U2 7 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD APR PY 2011 VL 19 IS 2 BP 117 EP 136 PG 20 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA 748FR UT WOS:000289375900003 PM 21558567 ER PT J AU Horwitz, BN Ganiban, JM Spotts, EL Lichtenstein, P Reiss, D Neiderhiser, JM AF Horwitz, Briana N. Ganiban, Jody M. Spotts, Erica L. Lichtenstein, Paul Reiss, David Neiderhiser, Jenae M. TI The Role of Aggressive Personality and Family Relationships in Explaining Family Conflict SO JOURNAL OF FAMILY PSYCHOLOGY LA English DT Article DE aggression; family conflict; marital quality; negative parenting ID GENETIC-ANALYSIS; ENVIRONMENTAL-INFLUENCES; COGNITIVE APPROACH; MARITAL QUALITY; ADJUSTMENT; SPILLOVER; MARRIAGE; BEHAVIOR; QUESTIONNAIRE; TEMPERAMENT AB This study investigated whether genetic and environmental influences on global family conflict are explained by parents' personality, marital quality, and negative parenting. The sample comprised 876 same-sex pairs of twins, their spouses, and one adolescent child per twin from the Twin and Offspring Study in Sweden. Genetic influences on aggressive personality were correlated with genetic influences on global family conflict. Nonshared environmental influences on marital quality and negative parenting were correlated with nonshared environmental influences on global family conflict. Results suggest that parents' personality and unique experiences within their family relationships are important for understanding genetic and environmental influences on global conflict in the home. C1 [Horwitz, Briana N.; Neiderhiser, Jenae M.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Ganiban, Jody M.] George Washington Univ, Dept Psychol, Washington, DC 20052 USA. [Spotts, Erica L.] NIA, Div Behav & Social Res, Bethesda, MD 20892 USA. [Lichtenstein, Paul] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden. [Reiss, David] Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. RP Neiderhiser, JM (reprint author), Penn State Univ, Dept Psychol, 111 Moore, University Pk, PA 16802 USA. EM bnh2@psu.edu; jenaemn@psu.edu RI Baines, Andrew/B-3491-2014; OI lichtenstein, paul/0000-0003-3037-5287 FU NIMH NIH HHS [R01 MH059014-03, R01 MH054610, R01 MH059014, R01MH54610] NR 59 TC 4 Z9 4 U1 3 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0893-3200 J9 J FAM PSYCHOL JI J. Fam. Psychol. PD APR PY 2011 VL 25 IS 2 BP 174 EP 183 DI 10.1037/a0023049 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 747MS UT WOS:000289324700002 PM 21480697 ER PT J AU Lozama, A Cunningham, CW Caspers, MJ Douglas, JT Dersch, CM Rothman, RB Prisinzano, TE AF Lozama, Anthony Cunningham, Christopher W. Caspers, Michael J. Douglas, Justin T. Dersch, Christina M. Rothman, Richard B. Prisinzano, Thomas E. TI Opioid Receptor Probes Derived from Cycloaddition of the Hallucinogen Natural Product Salvinorin A SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DIELS-ALDER REACTIONS; SALVIA-DIVINORUM; TEUCRIN-A; NEOCLERODANE DITERPENES; FURAN RING; IN-VIVO; AGONIST; POTENT; IDENTIFICATION; BIOACTIVATION AB As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerociane diterpene, salvinorin A, we report the synthesis and biological Characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted Methods Were: developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via; microwave assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization. Of the bent oxanorbornadiene system, possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analognes 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products: C1 [Cunningham, Christopher W.; Caspers, Michael J.; Prisinzano, Thomas E.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Lozama, Anthony] Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. [Douglas, Justin T.] Univ Kansas, Mol Struct Grp, Lawrence, KS 66045 USA. [Dersch, Christina M.; Rothman, Richard B.] NIDA, DHHS, IRP, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Prisinzano, TE (reprint author), Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. EM prisinza@ku.edu FU National Institute on Drug Abuse [DA018151]; National Institute on Drug Abuse, NIH, DHHS FX The authors would like to thank the National Institute on Drug Abuse (DA018151) for financial support of ongoing research. Portions of this work were supported by the Intramural Research Program, National Institute on Drug Abuse, NIH, DHHS. The content is the sole responsibility of the authors and not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. NR 42 TC 15 Z9 15 U1 1 U2 18 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 APR PY 2011 VL 74 IS 4 BP 718 EP 726 DI 10.1021/np1007872 PG 9 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 753CL UT WOS:000289742300028 PM 21338114 ER PT J AU Zhang, L Su, TP Choi, K Maree, W Li, CT Chung, MY Chen, YS Bai, YM Chou, YH Barker, JL Barrette, JE Li, XX Li, H Benedek, DM Ursano, R AF Zhang, Lei Su, Tung-Ping Choi, Kwang Maree, Webster Li, Cheng-Ta Chung, Ming-Yi Chen, Ying-Sheue Bai, Ya-Mei Chou, Yuan-Hwa Barker, Jeffery L. Barrette, James E. Li, Xiao Xia Li, He Benedek, David M. Ursano, Robert TI P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Suicide; Suicide attempt; Post-traumatic stress disorder (PTSD); Major depressive disorder (MDD); P11 ID DEPRESSION; STATES AB Although suicide represents 1.8% of the global burden of disease, there are few objective assays for suicide risk. Being associated with depressive disorders, which have a high risk of suicide, the proteins P11. P2RX7, and S100 beta may be biomarkers for a suicidal disposition. We measured levels of p11 and P2RX7 mRNA in peripheral blood mononuclear cells (PBMCs) of 26 psychiatric patients (11 suicide attempters, 15 suicide non-attempters) with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), and 14 normal controls, using quantitative real-time PCR. We also conducted a meta-analysis of microarray data of p11, P2RX7 and S100 beta from post-mortem prefrontal cortex (PFC) of patients who committed suicide (n = 56) and non-suicide controls (n = 61). We found that PBMC p11 mRNA levels were significantly lower in suicide attempters and higher in suicide non-attempters, when compared to normal controls. The PFC p11 mRNA levels in suicide completers were also lower than non-suicide controls (adjusted p = 0.007). Unlike p11, PBMC P2RX7 mRNA levels were significantly lower than normal controls in all patients including suicide attempters, suicide non-attempters, and suicide completers. In addition, levels of S100 beta in PFC did not differ between suicide completers and non-suicide controls. These results suggest that PBMC p11 mRNA levels may be a potential adjunctive biomarker for the assessment of suicide risk in mental disorders and warrants a larger translational study to determine its clinical utility. Published by Elsevier Ltd. C1 [Zhang, Lei; Li, Xiao Xia; Li, He; Benedek, David M.; Ursano, Robert] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [Su, Tung-Ping; Chen, Ying-Sheue; Bai, Ya-Mei; Chou, Yuan-Hwa] Natl Yang Ming Univ, Fac Med, Div Psychiat, Taipei 112, Taiwan. [Su, Tung-Ping; Chen, Ying-Sheue; Bai, Ya-Mei; Chou, Yuan-Hwa] Taipei Vet Gen Hosp, Dept Psychiat, Taipei, Taiwan. [Li, Cheng-Ta; Chung, Ming-Yi] Natl Yang Ming Univ, Inst Genome Sci, Taipei 112, Taiwan. [Barker, Jeffery L.] Natl Inst Neurol Disorders & Stroke, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. [Barrette, James E.] Drexel Univ, Coll Med, Dept Pharmacol & Physiol, Philadelphia, PA 19102 USA. RP Zhang, L (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. EM Lezhang@USUHS.mil FU Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences FX This research was supported in part by the Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences. NR 24 TC 23 Z9 24 U1 3 U2 5 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 APR PY 2011 VL 45 IS 4 BP 435 EP 441 DI 10.1016/j.jpsychires.2010.08.012 PG 7 WC Psychiatry SC Psychiatry GA 747NE UT WOS:000289325900002 PM 20863517 ER PT J AU Baca-Garcia, E Perez-Rodriguez, MM Keyes, KM Oquendo, MA Hasin, DS Grant, BF Blanco, C AF Baca-Garcia, Enrique Perez-Rodriguez, M. Mercedes Keyes, Katherine M. Oquendo, Maria A. Hasin, Deborah S. Grant, Bridget F. Blanco, Carlos TI Suicidal ideation and suicide attempts among Hispanic subgroups in the United States: 1991-1992 and 2001-2002 SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Attempted suicide; Epidemiology; Prevalence; Health surveys; Ethnic groups; Age groups ID NATIONAL EPIDEMIOLOGIC SURVEY; IV PSYCHIATRIC-DISORDERS; ATAQUE-DE-NERVIOS; MEXICAN-AMERICANS; MAJOR DEPRESSION; LATINO SUBGROUPS; MENTAL-HEALTH; ALCOHOL-ABUSE; ETHNIC-GROUPS; RISK-FACTORS AB Objective: To compare the prevalence of suicidal ideation/attempts among Hispanic subgroups in the US in 1991-1992 and 2001-2002, and identify high-risk groups. Method: Data were drawn from the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (NLAES, n = 42,862) and the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n = 43,093), two nationally representative surveys of individuals aged 18 years and older. Results: 1) Puerto Ricans are the Hispanic ethnic subgroup with the highest rates of suicide attempts; 2) 45- to 64-year-old Puerto Rican women are a high-risk group for suicide attempts; 3) Over the 10 year period between the two surveys, the lifetime prevalence of suicide attempts significantly increased among 18- to 24-year-old Puerto Rican women and Cuban men, and among 45- to 64-year-old Puerto Rican men. Conclusion: Hispanics in the US are not a homogeneous group. We identify high-risk groups among Hispanics. Specific interventions for subgroups of Hispanics at high risk for suicidal behaviors may be required. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Grant, Bridget F.] NIAAA, NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD 20892 USA. [Baca-Garcia, Enrique; Oquendo, Maria A.; Hasin, Deborah S.; Blanco, Carlos] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Baca-Garcia, Enrique; Oquendo, Maria A.; Hasin, Deborah S.; Blanco, Carlos] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA. [Baca-Garcia, Enrique] Univ Autonoma Madrid, CIBERSAM, Fdn Jimenez Diaz Hosp, Madrid, Spain. [Perez-Rodriguez, M. Mercedes] Hosp Ramon & Cajal, CIBERSAM, E-28034 Madrid, Spain. [Perez-Rodriguez, M. Mercedes] Mt Sinai Sch Med, New York, NY 10029 USA. [Keyes, Katherine M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, MS 9304,5635 Fishers Lane,Room 3077, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013; Perez Rodriguez, Maria/B-9410-2013; Baca-Garcia, Enrique/F-4106-2015 OI Blanco, Carlos/0000-0001-6187-3057; Perez Rodriguez, Maria/0000-0001-5137-1993; Baca-Garcia, Enrique/0000-0002-6963-6555 FU National Institute on Alcohol Abuse and Alcoholism; NIAAA, National Institutes of Health; Alicia Koplowitz Foundation; Instituto de Salud Carlos III CIBERSAM; Spanish Ministry of Health; NIH [DA019606, DA020783, DA023200, DA023973, MH076051, MH082773, CA133050, AA014223]; American Foundation for Suicide Prevention; New York State Psychiatric Institute FX The National Longitudinal Alcohol Epidemiologic Survey and the National Epidemiologic Survey on Alcohol and Related Conditions were sponsored by the National Institute on Alcohol Abuse and Alcoholism and funded, in part, by the Intramural Program, NIAAA, National Institutes of Health. The NIH had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Additional support was provided by Alicia Koplowitz Foundation (Dr. Baca-Garcia), Instituto de Salud Carlos III CIBERSAM and the Spanish Ministry of Health (Drs. Baca-Garcia and Perez-Rodriguez), NIH grants DA019606, DA020783, DA023200, DA023973, MH076051, MH082773 and CA133050 (Dr. Blanco) and AA014223 (Dr. Hasin), the American Foundation for Suicide Prevention (Dr. Blanco), and the New York State Psychiatric Institute (Drs. Blanco, Hasin and Oquendo). NR 39 TC 18 Z9 18 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 EI 1879-1379 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD APR PY 2011 VL 45 IS 4 BP 512 EP 518 DI 10.1016/j.jpsychires.2010.09.004 PG 7 WC Psychiatry SC Psychiatry GA 747NE UT WOS:000289325900012 PM 20937507 ER PT J AU Houston, DK Tooze, JA Neiberg, RH Hausman, DB Johnson, MA Cauley, JA Bauer, DC Schwartz, GG Williamson, JD Shorr, RI Simonsick, EM Harris, TB Kritchevsky, SB AF Houston, D. K. Tooze, J. A. Neiberg, R. H. Hausman, D. B. Johnson, M. A. Cauley, J. A. Bauer, D. C. Schwartz, G. G. Williamson, J. D. Shorr, R. I. Simonsick, E. M. Harris, T. B. Kritchevsky, S. B. TI Serum 25-hydroxyvitamin D and Recurrent Falls: the Health ABC Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Houston, D. K.; Tooze, J. A.; Neiberg, R. H.; Schwartz, G. G.; Williamson, J. D.; Kritchevsky, S. B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Hausman, D. B.; Johnson, M. A.] Univ Georgia, Athens, GA 30602 USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, D. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shorr, R. I.] Univ Florida, Gainesville, FL USA. [Simonsick, E. M.; Harris, T. B.] NIA, 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2011 VL 59 SU 1 BP S14 EP S14 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600040 ER PT J AU Kilpatrick, L Houston, D Wilson, V Lovato, J Ayonayon, H Cauley, J Harris, T Simonsick, E Yaffe, K Kritchevsky, S Sink, K AF Kilpatrick, L. Houston, D. Wilson, V. Lovato, J. Ayonayon, H. Cauley, J. Harris, T. Simonsick, E. Yaffe, K. Kritchevsky, S. Sink, K. TI Predicting Cognitive Impairment: Do low vitamin D levels increase risk? The Health ABC Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Kilpatrick, L.; Houston, D.; Lovato, J.; Kritchevsky, S.; Sink, K.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Wilson, V.] Moses Cone Mem Hosp, Greensboro, NC USA. [Ayonayon, H.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cauley, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, T.; Simonsick, E.] NIA, Bethesda, MD 20892 USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2011 VL 59 SU 1 BP S12 EP S12 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600036 ER PT J AU Liu, C Leng, I Kritchevsky, S Ding, J Earnest, C Ferrucci, L Goodpaster, B Guralnik, J Hsu, F Lenchik, L Fielding, RA AF Liu, C. Leng, I. Kritchevsky, S. Ding, J. Earnest, C. Ferrucci, L. Goodpaster, B. Guralnik, J. Hsu, F. Lenchik, L. Fielding, R. A. TI The impact of sarcopenia on the response to a physical activity intervention in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Liu, C.] Boston Univ, Boston, MA 02215 USA. [Leng, I.; Kritchevsky, S.; Ding, J.; Hsu, F.; Lenchik, L.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Earnest, C.] Pennington Biomed Res Ctr, Baton Rouge, LA USA. [Ferrucci, L.; Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Goodpaster, B.] Univ Pittsburgh, Pittsburgh, PA USA. [Fielding, R. A.] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL 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 APR PY 2011 VL 59 SU 1 BP S63 EP S63 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600184 ER PT J AU Philippopoulos, SE Simonsick, EM Ferrucci, L Schrack, JA AF Philippopoulos, S. E. Simonsick, E. M. Ferrucci, L. Schrack, J. A. TI Hemoglobin and Iron Levels and Walking-Related Performance and Energy Expenditure in Late Life. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Philippopoulos, S. E.] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Simonsick, E. M.; Ferrucci, L.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Schrack, J. A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2011 VL 59 SU 1 BP S89 EP S90 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600258 ER PT J AU Sanders, J Boudreau, R Fried, L Walston, J Harris, T Newman, A AF Sanders, J. Boudreau, R. Fried, L. Walston, J. Harris, T. Newman, A. TI Understanding the physiologic basis of frailty is enhanced by multiple noninvasive measurements of organ structure and function. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Sanders, J.; Boudreau, R.; Newman, A.] Univ Pittsburgh, Pittsburgh, PA USA. [Fried, L.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. [Walston, J.] Johns Hopkins Univ, Baltimore, MD USA. [Harris, T.] NIA, Intramural Res Program, Baltimore, MD 21224 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2011 VL 59 SU 1 BP S33 EP S33 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600093 ER PT J AU Williams, J Houston, D Davis, C Cauley, J Rubin, S Tylavsky, F Ayonayon, H Atkinson, H Yaffe, K Simonsick, E Kim, L Kritchevsky, S Sink, K AF Williams, J. Houston, D. Davis, C. Cauley, J. Rubin, S. Tylavsky, F. Ayonayon, H. Atkinson, H. Yaffe, K. Simonsick, E. Kim, L. Kritchevsky, S. Sink, K. TI Vitamin D Status and Depression in Community-Dwelling Older Adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Williams, J.; Houston, D.; Davis, C.; Atkinson, H.; Kritchevsky, S.; Sink, K.] Wake Forest Univ, Greensboro, NC USA. [Cauley, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Rubin, S.; Ayonayon, H.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tylavsky, F.] Univ Tennessee Hlth Sci, Memphis, TN USA. [Simonsick, E.; Kim, L.] NIA, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL 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 APR PY 2011 VL 59 SU 1 BP S105 EP S105 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600302 ER PT J AU Wilson, V Houston, D Kilpatrick, L Lovato, J Ayonayon, H Cauley, J Harris, T Simonsick, EM Yaffe, K Kritchevsky, S Sink, KM AF Wilson, V. Houston, D. Kilpatrick, L. Lovato, J. Ayonayon, H. Cauley, J. Harris, T. Simonsick, E. M. Yaffe, K. Kritchevsky, S. Sink, K. M. TI Relationship between Vitamin D level and Cognitive Function in Older Adults: the Health ABC Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting on the American-Geriatrics-Society CY MAY 11-14, 2011 CL National Harbor, MD SP Amer Geriatr Soc C1 [Wilson, V.] Moses Cone Mem Hosp, Greensboro, NC USA. [Houston, D.; Kilpatrick, L.; Kritchevsky, S.; Sink, K. M.] WFU Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. [Ayonayon, H.; Yaffe, K.] UCSF, San Francisco, CA USA. [Cauley, J.] U Pitt, Pittsburgh, PA USA. [Harris, T.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Simonsick, E. M.] NIA, Clin Res Branch, Baltimore, MD 21224 USA. 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 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2011 VL 59 SU 1 BP S70 EP S70 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 750DJ UT WOS:000289524600204 ER PT J AU Tricoli, JV Seibel, NL Blair, DG Albritton, K Hayes-Lattin, B AF Tricoli, James V. Seibel, Nita L. Blair, Donald G. Albritton, Karen Hayes-Lattin, Brandon TI Unique Characteristics of Adolescent and Young Adult Acute Lymphoblastic Leukemia, Breast Cancer, and Colon Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PHASE-II TRIALS; COLORECTAL-CANCER; GENE-EXPRESSION; BCP-ALL; CARCINOMA; CHILDREN; FEATURES; PROGNOSIS; PROTOCOLS; SURVIVAL AB Each year in the United States, nearly 70 000 individuals between the ages of 15 and 40 years are diagnosed with cancer. Although overall cancer survival rates among pediatric and older adult patients have increased in recent decades, there has been little improvement in survival of adolescent and young adult (AYA) cancer patients since 1975 when collected data became adequate to evaluate this issue. In 2006, the AYA Oncology Progress Review Group made recommendations for addressing the needs of this population that were later implemented by the LIVESTRONG Young Adult Alliance. One of their overriding questions was whether the cancers seen in AYA patients were biologically different than the same cancers in adult and/or pediatric patients. On June 9-10, 2009, the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) convened a workshop in Bethesda, MD, entitled "Unique Characteristics of AYA Cancers: Focus on Acute Lymphocytic Leukemia (ALL), Breast Cancer and Colon Cancer" that aimed to examine the current state of basic and translational research on these cancers and to discuss the next steps to improve their prognosis and treatment. C1 [Tricoli, James V.] NCI, Canc Diag Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. [Blair, Donald G.] NCI, Div Canc Biol, Rockville, MD 20852 USA. [Albritton, Karen] Univ N Texas, Hlth Sci Ctr, Dept Pediat, Adolescent & Young Adult Oncol Program, Ft Worth, TX USA. [Albritton, Karen] Cook Childrens Med Ctr, Ft Worth, TX USA. [Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Hematol & Med Oncol, Portland, OR 97201 USA. RP Tricoli, JV (reprint author), NCI, Canc Diag Program, Div Canc Treatment & Diag, 6130 Execut Blvd,Execut Plaza N, Rockville, MD 20852 USA. EM tricolij@mail.nih.gov NR 51 TC 34 Z9 36 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR PY 2011 VL 103 IS 8 BP 628 EP 635 DI 10.1093/jnci/djr094 PG 8 WC Oncology SC Oncology GA 754FK UT WOS:000289839900006 PM 21436065 ER PT J AU Kirkpatrick, SI Tarasuk, V AF Kirkpatrick, Sharon I. Tarasuk, Valerie TI Housing Circumstances are Associated with Household Food Access among Low-Income Urban Families SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Household food insecurity; Food access; Housing affordability; Social housing; Housing subsidy; Poverty; Urban; Families ID NUTRITION EXAMINATION SURVEY; CHILD HUNGER; TORONTO FAMILIES; NATIONAL-HEALTH; MENTAL-HEALTH; UNITED-STATES; INSECURITY; INSUFFICIENCY; CONSEQUENCES; ADULTS AB Household food insecurity is a pervasive problem in North America with serious health consequences. While affordable housing has been cited as a potential policy approach to improve food insecurity, the relationship between conventional notions of housing affordability and household food security is not well understood. Furthermore, the influence of housing subsidies, a key policy intervention aimed at improving housing affordability in Western countries, on food insecurity is unclear. We undertook a cross-sectional survey of 473 families in market rental (n = 222) and subsidized (n = 251) housing in high-poverty urban neighborhoods to examine the influence of housing circumstances on household food security. Food insecurity, evident among two thirds of families, was inversely associated with income and after-shelter income. Food insecurity prevalence did not differ between families in market and subsidized housing, but families in subsidized housing had lower odds of food insecurity than those on a waiting list for such housing. Market families with housing costs that consumed more than 30% of their income had increased odds of food insecurity. Rent arrears were also positively associated with food insecurity. Compromises in housing quality were evident, perhaps reflecting the impact of financial constraints on multiple basic needs as well as conscious efforts to contain housing costs to free up resources for food and other needs. Our findings raise questions about current housing affordability norms and highlight the need for a review of housing interventions to ensure that they enable families to maintain adequate housing and obtain their other basic needs. C1 [Kirkpatrick, Sharon I.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Tarasuk, Valerie] Univ Toronto, Fac Med, Dept Nutr Sci, Toronto, ON, Canada. RP Kirkpatrick, SI (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM sharon.kirkpatrick@nih.gov OI Kirkpatrick, Sharon/0000-0001-9896-5975 FU Canadian Institutes for Health Research [IGP-74207, MOP-77766]; Social Sciences and Humanities Research Council of Canada; Ontario Graduate Scholarship FX The authors gratefully acknowledge our collaborators at the City of Toronto Shelter, Support and Housing Division, and Toronto Public Health. This study was supported by grants from the Canadian Institutes for Health Research (IGP-74207, MOP-77766) and funding from the Neighbourhood Change & Building Inclusive Communities from Within Community University Research Alliance (CURA) program of the Social Sciences and Humanities Research Council of Canada. Sharon Kirkpatrick was a doctoral candidate at the time that this study was conducted and received financial support from an Ontario Graduate Scholarship and a Social Sciences and Humanities Research Council of Canada Doctoral Scholarship. NR 48 TC 26 Z9 27 U1 2 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD APR PY 2011 VL 88 IS 2 BP 284 EP 296 DI 10.1007/s11524-010-9535-4 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 752KY UT WOS:000289691300009 PM 21286826 ER PT J AU Kaplan, SA Lee, JY Meehan, AG Kusek, JW AF Kaplan, Steven A. Lee, Jeannette Y. Meehan, Alan G. Kusek, John W. CA MTOPS Res Grp TI Long-Term Treatment With Finasteride Improves Clinical Progression of Benign Prostatic Hyperplasia in Men With an Enlarged Versus a Smaller Prostate: Data From the MTOPS Trial SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; urinary tract; finasteride; organ size; prostate ID COMBINATION THERAPY; SYMPTOMS; DOXAZOSIN; VOLUME AB Purpose: This post hoc analysis of the Medical Therapy of Prostatic Symptoms trial examined the effect of finasteride alone compared to placebo on the clinical progression of benign prostatic hyperplasia in men with a baseline prostate volume less than 30 ml, or 30 ml or greater. Materials and Methods: Men were randomized to placebo (737), 4 to 8 mg doxazosin alone (756), 5 mg finasteride alone (768) or doxazosin plus finasteride (786) (average followup was 4.5 years). Approximately 50% of patients had a baseline prostate volume of 30 ml or greater. The present analysis was based on the finasteride alone and placebo arms only, and included patients for whom baseline and end of study data were available. We examined the effect of treatment on the cumulative percentage of men who did not experience clinical progression of benign prostatic hyperplasia by study end. Results: In men with baseline prostate volume 30 ml or greater treatment with finasteride produced a significant (p < 0.001) increase relative to placebo in the cumulative percentage of patients who did not experience clinical progression of benign prostatic hyperplasia (finasteride 88.1% vs placebo 77.8%). There was no significant (p = 0.441) between-group difference in men with baseline prostate volume less than 30 ml (91.4% vs 89.1%, respectively). Conclusions: Long-term treatment with finasteride led to a significant beneficial effect compared to placebo on the clinical progression of benign prostatic hyperplasia in patients with lower urinary tract symptoms with an enlarged prostate (baseline prostate volume 30 ml or greater). Finasteride had no significant effect compared to placebo on the clinical progression of benign prostatic hyperplasia in patients with lower urinary tract symptoms with a smaller prostate (baseline prostate volume less than 30 ml). C1 [Kaplan, Steven A.] Cornell Univ, Inst Bladder & Prostate Hlth, Weill Cornell Med Coll, New York, NY 10021 USA. [Lee, Jeannette Y.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Meehan, Alan G.] Merck & Co Inc, Rahway, NJ 07065 USA. [Kusek, John W.] NIDDK, Bethesda, MD USA. RP Kaplan, SA (reprint author), Cornell Univ, Inst Bladder & Prostate Hlth, Weill Cornell Med Coll, 1300 York Ave,F9 W,Box 261, New York, NY 10021 USA. EM kaplans@med.cornell.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK49977, U01 DK46416, U01 DK41418, U01 DK46429, U01 DK46431, U01 DK46437, U01 DK46468, U01 DK46472, U01 DK49880, U01 DK49912, U01 DK49921, U01 DK49951, U01 DK49954, U01 DK49960, U01 DK49961, U01 DK49963, U01 DK49964, U01 DK49971, U01 DK49980]; National Center on Minority Health and Health Disparities, National Institutes of Health; Merck; Pfizer FX MTOPS was supported by the following cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases: U01 DK49977, U01 DK46416, U01 DK41418, U01 DK46429, U01 DK46431, U01 DK46437, U01 DK46437, U01 DK46468, U01 DK46472, U01 DK49880, U01 DK49912, U01 DK49921, U01 DK49951, U01 DK49954, U01 DK49960, U01 DK49961, U01 DK49963, U01 DK49964, U01 DK49971, U01 DK49980, as well as by the National Center on Minority Health and Health Disparities, National Institutes of Health. Financial support and drug products for MTOPS were also provided by Merck and Pfizer. NR 9 TC 16 Z9 17 U1 0 U2 4 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 APR PY 2011 VL 185 IS 4 BP 1369 EP 1373 DI 10.1016/j.juro.2010.11.060 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 735PU UT WOS:000288430200068 PM 21334655 ER PT J AU Moon, AF Midon, M Meiss, G Pingoud, A London, RE Pedersen, LC AF Moon, Andrea F. Midon, Marika Meiss, Gregor Pingoud, Alfred London, Robert E. Pedersen, Lars C. TI Structural insights into catalytic and substrate binding mechanisms of the strategic EndA nuclease from Streptococcus pneumoniae SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NEUTROPHIL EXTRACELLULAR TRAPS; INVASIVE PNEUMOCOCCAL DISEASE; GENETIC-TRANSFORMATION; DIPLOCOCCUS-PNEUMONIAE; CHEMICAL RESCUE; PROTEIN CRYSTALLIZATION; DEOXYRIBONUCLEASE-I; POLYACRYLAMIDE-GEL; ACTIVE-SITE; ENDONUCLEASE AB EndA is a sequence non-specific endonuclease that serves as a virulence factor during Streptococcus pneumoniae infection. Expression of EndA provides a strategy for evasion of the host's neutrophil extracellular traps, digesting the DNA scaffold structure and allowing further invasion by S. pneumoniae. To define mechanisms of catalysis and substrate binding, we solved the structure of EndA at 1.75 A resolution. The EndA structure reveals a DRGH (Asp-Arg-Gly-His) motif-containing beta beta alpha-metal finger catalytic core augmented by an interesting 'finger-loop' interruption of the active site alpha-helix. Subsequently, we delineated DNA binding versus catalytic functionality using structure-based alanine substitution mutagenesis. Three mutants, H154A, Q186A and Q192A, exhibited decreased nuclease activity that appears to be independent of substrate binding. Glu205 was found to be crucial for catalysis, while residues Arg127/Lys128 and Arg209/Lys210 contribute to substrate binding. The results presented here provide the molecular foundation for development of specific antibiotic inhibitors for EndA. C1 [Moon, Andrea F.; London, Robert E.; Pedersen, Lars C.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Midon, Marika; Meiss, Gregor; Pingoud, Alfred] Univ Giessen, Inst Biochem, D-35392 Giessen, Germany. RP Pedersen, LC (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM pederse2@niehs.nih.gov FU Division of Intramural Research of the National Institute of Environmental Health Sciences, US National Institutes of Health; National Institutes of Health; National Institute of Environmental Health Sciences; US Department of Energy, Office of Science, Office of Basic Energy Sciences, Advanced Photon [W-31-109-Eng-38]; National Institute of Environmental Health Sciences; National Institutes of Health FX This research was funded by the Division of Intramural Research of the National Institute of Environmental Health Sciences, US National Institutes of Health. Intramural Research Program of the National Institutes of Health; National Institute of Environmental Health Sciences; US Department of Energy, Office of Science, Office of Basic Energy Sciences, Advanced Photon (contract no. W-31-109-Eng-38). Funding for open access charge: The Intramural Research Program of the National Institute of Environmental Health Sciences; National Institutes of Health. NR 48 TC 14 Z9 16 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD APR PY 2011 VL 39 IS 7 BP 2943 EP 2953 DI 10.1093/nar/gkq1152 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 751OW UT WOS:000289628400047 PM 21113026 ER PT J AU Low, JSW Tao, Q Ng, KM Goh, HK Shu, XS Woo, WL Ambinder, RF Srivastava, G Shamay, M Chan, ATC Popescu, NC Hsieh, WS AF Low, J. S. W. Tao, Q. Ng, K. M. Goh, H. K. Shu, X-S Woo, W. L. Ambinder, R. F. Srivastava, G. Shamay, M. Chan, A. T. C. Popescu, N. C. Hsieh, W-S TI A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors SO ONCOGENE LA English DT Article DE DLC1; RhoGAP; methylation; tumor suppressor gene; carcinoma; p53 ID GTPASE-ACTIVATING PROTEIN; STRESS-RESPONSIVE GENE; BARR-VIRUS INFECTION; HEPATOCELLULAR-CARCINOMA; CANCER-CELLS; TRANSCRIPTIONAL REGULATION; PROMOTER HYPERMETHYLATION; MITOCHONDRIAL PROTEINS; MORPHOLOGICAL-CHANGES; TARGETING SEQUENCES AB The critical 8p22 tumor suppressor deleted in liver cancer 1 (DLC1) is frequently inactivated by aberrant CpG methylation and/or genetic deletion and implicated in tumorigeneses of multiple tumor types. Here, we report the identification and characterization of its new isoform, DLC1 isoform 4 (DLC1-i4). This novel isoform encodes an 1125-aa (amino acid) protein with distinct N-terminus as compared with other known DLC1 isoforms. Similar to other isoforms, DLC1-i4 is expressed ubiquitously in normal tissues and immortalized normal epithelial cells, suggesting a role as a major DLC1 transcript. However, differential expression of the four DLC1 isoforms is found in tumor cell lines: Isoform 1 (longest) and 3 (short thus probably nonfunctional) share a promoter and are silenced in almost all cancer and immortalized cell lines, whereas isoform 2 and 4 utilize different promoters and are frequently downregulated. DLC1-i4 is significantly downregulated in multiple carcinoma cell lines, including 2/4 nasopharyngeal, 8/16 (50%) esophageal, 4/16 (25%) gastric, 6/9 (67%) breast, 3/4 colorectal, 4/4 cervical and 2/8(25%) lung carcinoma cell lines. The functional DLC1-i4 promoter is within a CpG island and is activated by wild-type p53. CpG methylation of the DLC1-i4 promoter is associated with its silencing in tumor cells and was detected in 38-100% of multiple primary tumors. Treatment with 5-aza-20-deoxycytidine or genetic double knockout of DNMT1 and DNMT3B led to demethylation of the promoter and reactivation of its expression, indicating a predominantly epigenetic mechanism of silencing. Ectopic expression of DLC1-i4 in silenced tumor cells strongly inhibited their growth and colony formation. Thus, we identified a new isoform of DLC1 with tumor suppressive function. The differential expression of various DLC1 isoforms suggests interplay in modulating the complex activities of DLC1 during carcinogenesis. Oncogene (2011) 30, 1923-1935; doi: 10.1038/onc.2010.576; published online 10 January 2011 C1 [Low, J. S. W.; Tao, Q.; Goh, H. K.; Woo, W. L.; Ambinder, R. F.; Shamay, M.; Hsieh, W-S] Johns Hopkins Singapore, Div Biomed Sci, Singapore, Singapore. [Low, J. S. W.; Goh, H. K.; Ambinder, R. F.; Hsieh, W-S] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117456, Singapore. [Tao, Q.; Ambinder, R. F.; Shamay, M.; Hsieh, W-S] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Tao, Q.; Ng, K. M.; Shu, X-S; Chan, A. T. C.] Chinese Univ Hong Kong, Dept Clin Oncol, State Key Lab Oncol S China, Sir YK Pao Ctr Canc,Hong Kong Canc Inst,Canc Epig, Shatin, Hong Kong, Peoples R China. [Tao, Q.] Chinese Univ Hong Kong, PWH, Ctr Canc, Dept Clin Oncol,Li Ka Shing Inst Hlth Sci, Shatin, Hong Kong, Peoples R China. [Srivastava, G.] Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. [Popescu, N. C.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Tao, Q (reprint author), Chinese Univ Hong Kong, PWH, Ctr Canc, Dept Clin Oncol,Li Ka Shing Inst Hlth Sci, Rm 315, Shatin, Hong Kong, Peoples R China. EM qtao@clo.cuhk.edu.hk; whsieh1@jhem.jhmi.edu FU A*STAR; Chinese University of Hong Kong; Singapore National Research Foundation; Ministry of Education FX This project was supported by an A*STAR grant (Johns Hopkins Singapore, QT/WS/RA), a Chinese University of Hong Kong grant (QT) and a grant from Singapore National Research Foundation and the Ministry of Education under the Research Center of Excellence Program (WS/RA). We thank Drs Bert Vogelstein, George Tsao, (Dolly Huang), Michael Obster and Guiyuan Li for some cell lines; and DSMZ (German Collection of Microorganisms & Cell Cultures) for the KYSE cell lines (Shimada et al., Cancer 69: 277-284, 1992). We also thank Drs Wenling Han, Thomas Putti, Luke Tan for some tumor samples. NR 66 TC 32 Z9 36 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2011 VL 30 IS 16 BP 1923 EP 1935 DI 10.1038/onc.2010.576 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 753MA UT WOS:000289777700008 PM 21217778 ER PT J AU Yan, HG Ji, XH AF Yan, Honggao Ji, Xinhua TI Role of Protein Conformational Dynamics in the Catalysis by 6-Hydroxymethyl-7, 8-Dihydropterin Pyrophosphokinase SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE Bisubstrate enzyme; enzymatic catalysis; folate biosynthesis; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase; HPPK; NMR; protein dynamics; X-ray crystallography ID ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ARGININE RESIDUE-82; TERNARY COMPLEX; HPPK; TRANSITIONS; MECHANISM; BINDING; ENZYME; ANALOG AB Enzymatic catalysis has conflicting structural requirements of the enzyme. In order for the enzyme to form a Michaelis complex, the enzyme must be in an open conformation so that the substrate can get into its active center. On the other hand, in order to maximize the stabilization of the transition state of the enzymatic reaction, the enzyme must be in a closed conformation to maximize its interactions with the transition state. The conflicting structural requirements can be resolved by a flexible active center that can sample both open and closed conformational states. For a bisubstrate enzyme, the Michaelis complex consists of two substrates in addition to the enzyme. The enzyme must remain flexible upon the binding of the first substrate so that the second substrate can get into the active center. The active center is fully assembled and stabilized only when both substrates bind to the enzyme. However, the side-chain positions of the catalytic residues in the Michaelis complex are still not optimally aligned for the stabilization of the transition state, which lasts only approximately 10(-13) s. The instantaneous and optimal alignment of catalytic groups for the transition state stabilization requires a dynamic enzyme, not an enzyme which undergoes a large scale of movements but an enzyme which permits at least a small scale of adjustment of catalytic group positions. This review will summarize the structure, catalytic mechanism, and dynamic properties of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase and examine the role of protein conformational dynamics in the catalysis of a bisubstrate enzymatic reaction. C1 [Yan, Honggao] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Ji, Xinhua] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Yan, HG (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM yanh@msu.edu; jix@mail.nih.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIH [GM51901]; National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Our work was supported in part by NIH grant GM51901 (H. Y.) and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. We thank our collaborators, particularly Drs. Yue Li, Jaroslaw Blaszczyk, Genbin Shi, Bing Xiao, Ewen Lescop, and Changwen Jin, for most fruitful collaborations. NR 28 TC 8 Z9 9 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD APR PY 2011 VL 18 IS 4 BP 328 EP 335 DI 10.2174/092986611794654003 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753MO UT WOS:000289780100002 PM 21222642 ER PT J AU Buch, I Tsai, CJ Wolfson, HJ Nussinov, R AF Buch, Idit Tsai, Chung-Jung Wolfson, Haim J. Nussinov, Ruth TI Symmetry-Based Self-assembled Nanotubes Constructed Using Native Protein Structures: The Key Role of Flexible Linkers SO PROTEIN AND PEPTIDE LETTERS LA English DT Article DE Building blocks; molecular dynamics simulations; nanotube design; self-assembly; oligomerization domain; symmetry ID MOLECULAR-DYNAMICS; PEPTIDE NANOTUBES; BUILDING-BLOCKS; POLYPROLINE-II; SIMULATION; DESIGN; NANOSTRUCTURES; NANOSCALE; NANOWIRES; VESICLES AB We construct nanotubes using native protein structures and their native associations from structural databases. The construction is based on a shape-guided symmetric self-assembly concept. Our strategy involves fusing judiciously-selected oligomerization domains via peptide linkers. Linkers are inherently flexible, hence their choice is critical: they should position the domains in three-dimensional space in the desired orientation while retaining their own natural conformational tendencies; however, at the same time, retain the construct stability. Here we outline a design scheme which accounts for linker flexibility considerations, and present two examples. The first is HIV-1 capsid protein, which in vitro self-assembles into nanotubes and conical capsids, and its linker exists as a short flexible loop. The second involves novel nanotubes construction based on antimicrobial homodimer Magainin 2, employing linkers of distinct lengths and flexibility levels. Our strategy utilizes the abundance of unique shapes and sizes of proteins and their building blocks which can assemble into a vast number of combinations, and consequently, nanotubes of distinct morphologies and diameters. Computational design and assessment methodologies can help reduce the number of candidates for experimental validation. This is an invited paper for a special issue on protein dynamics, here focusing on flexibility in nanotube design based on protein building blocks. C1 [Tsai, Chung-Jung; Nussinov, Ruth] NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Buch, Idit; Nussinov, Ruth] Tel Aviv Univ, Sackler Fac Med, Sackler Inst Mol Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. [Wolfson, Haim J.] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM ruthnu@helix.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX We thank Dr. Bernard R Brooks for fruitful discussions and support. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This study utilized the high-performance computational capabilities of the LoBoS supercomputers as well as the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). NR 51 TC 0 Z9 0 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 0929-8665 J9 PROTEIN PEPTIDE LETT JI Protein Pept. Lett. PD APR PY 2011 VL 18 IS 4 BP 362 EP 372 DI 10.2174/092986611794653996 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753MO UT WOS:000289780100006 PM 21222638 ER PT J AU Darney, S Fowler, B Grandjean, P Heindel, J Mattison, D Slikker, W AF Darney, Sally Fowler, Bruce Grandjean, Philippe Heindel, Jerrold Mattison, Donald Slikker, William, Jr. TI Prenatal Programming and Toxicity II (PPTOX II): Role of environmental stressors in the developmental origins of disease SO REPRODUCTIVE TOXICOLOGY LA English DT Editorial Material C1 [Heindel, Jerrold] NIEHS, NIH, HHS, Res Triangle Pk, NC 27709 USA. [Darney, Sally] US EPA, Off Res & Dev, Washington, DC USA. [Fowler, Bruce] Ctr Dis Control, Div Toxicol & Environm Med, ATSDR, Atlanta, GA 30333 USA. [Grandjean, Philippe] Univ So Denmark, Odense, Denmark. [Mattison, Donald] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, HHS, Bethesda, MD USA. [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Heindel, J (reprint author), NIEHS, NIH, HHS, Res Triangle Pk, NC 27709 USA. EM heindelj@niehs.nih.gov RI Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Grandjean, Philippe/0000-0003-4046-9658 NR 0 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2011 VL 31 IS 3 SI SI BP 271 EP 271 DI 10.1016/j.reprotox.2010.10.010 PG 1 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 753EQ UT WOS:000289749100001 PM 21035539 ER PT J AU Jefferson, WN Williams, CJ AF Jefferson, Wendy N. Williams, Carmen J. TI Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE Ovary; Oviduct; Uterus; Fertility ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR-ALPHA; SOY-BASED FORMULA; PHYTOESTROGEN GENISTEIN; POLYOVULAR FOLLICLES; INFANT FORMULA; MAMMARY-GLAND; UDP-GLUCURONOSYLTRANSFERASE; DIETHYLSTILBESTROL DES; UTERINE ADENOCARCINOMA AB Developmental exposure to estrogenic compounds can disrupt sexual differentiation and adult reproductive function in many animals including humans. Phytoestrogens (plant estrogens) in the diet comprise a significant source of estrogenic exposure to humans, particularly in infants who are fed soy-based infant formula. Animal models have been developed to test the effects of phytoestrogen exposure on the developing fetus and neonate. Here we review studies quantifying the amount of phytoestrogen exposure in human adults and infants and discuss the few available epidemiological studies that have addressed long-term consequences of developmental phytoestrogen exposure. We then describe in detail rodent models of developmental exposure to the most prevalent phytoestrogen in soy products, genistein, and the effects of this exposure on female reproductive function. These models have used various dosing strategies to mimic the phytoestrogen levels in human populations. Serum circulating levels of genistein following each of the models and their correlation to reproductive outcomes are also discussed. Taken together, the studies clearly demonstrate that environmentally relevant doses of genistein have significant negative impacts on ovarian differentiation, estrous cyclicity, and fertility in the rodent model. Additional studies of reproductive function in human populations exposed to high levels of phytoestrogens during development are warranted. Published by Elsevier Inc. C1 [Jefferson, Wendy N.; Williams, Carmen J.] NIEHS, Lab Reprod & Dev Toxicol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Jefferson, WN (reprint author), NIEHS, Lab Reprod & Dev Toxicol, NIH, DHHS, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 82 TC 25 Z9 26 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2011 VL 31 IS 3 SI SI BP 272 EP 279 DI 10.1016/j.reprotox.2010.10.001 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 753EQ UT WOS:000289749100002 PM 20955782 ER PT J AU Winans, B Humble, MC Lawrence, BP AF Winans, Bethany Humble, Michael C. Lawrence, B. Paige TI Environmental toxicants and the developing immune system: A missing link in the global battle against infectious disease? SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE Maternal exposure; Pollutants; Fetal basis of adult disease; Infectious disease susceptibility; Immune development ID PRENATAL CHLORDANE EXPOSURE; ARYL-HYDROCARBON RECEPTOR; UTERO ARSENIC EXPOSURE; EPIGENETIC TRANSGENERATIONAL ACTIONS; POLYCYCLIC AROMATIC-HYDROCARBONS; TOBACCO-SMOKE EXPOSURE; CENTRAL-NERVOUS-SYSTEM; PAH-DNA ADDUCTS; BISPHENOL-A; IN-UTERO AB There is now compelling evidence that developmental exposure to chemicals from our environment contributes to disease later in life, with animal models supporting this concept in reproductive, metabolic, and neurodegenerative diseases. In contrast, data regarding how developmental exposures impact the susceptibility of the immune system to functional alterations later in life are surprisingly scant. Given that the immune system forms an integrated network that detects and destroys invading pathogens and cancer cells, it provides the body's first line of defense. Thus, the consequences of early life exposures that reduce immune function are profound. This review summarizes available data for pollutants such as cigarette smoke and dioxin-like compounds, which consistently support the idea that developmental exposures critically impact the immune system. These findings suggest that exposure to common chemicals from our daily environment represent overlooked contributors to the fact that infectious diseases remain among the top five causes of death worldwide. (C) 2010 Elsevier Inc. All rights reserved. C1 [Winans, Bethany; Lawrence, B. Paige] Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. [Winans, Bethany; Lawrence, B. Paige] Univ Rochester, Sch Med & Dent, Toxicol Training Program, Rochester, NY 14642 USA. [Humble, Michael C.] NIEHS, Cellular Organs & Syst Pathobiol Branch, Div Extramural Res & Training, Res Triangle Pk, NC 27560 USA. RP Lawrence, BP (reprint author), Univ Rochester, Sch Med & Dent, Dept Environm Med, 575 Elmwood Ave,Box 850, Rochester, NY 14642 USA. EM paige_lawrence@urmc.rochester.edu FU National Institutes of Health [R01-ES013958, RC2-ES018730, R01-HL097141, T32-ES07026, P30-ES01247] FX On-going research is supported by the following research and training grants from the National Institutes of Health: R01-ES013958 (B.P.L), RC2-ES018730 (B.P.L.), R01-HL097141 (B.P.L.), T32-ES07026 (B.W.), and P30-ES01247. NR 150 TC 28 Z9 30 U1 5 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2011 VL 31 IS 3 SI SI BP 327 EP 336 DI 10.1016/j.reprotox.2010.09.004 PG 10 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 753EQ UT WOS:000289749100009 PM 20851760 ER PT J AU Morris, SE Insel, TR AF Morris, Sarah E. Insel, Thomas R. TI Reconceptualizing Schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Editorial Material ID FUNCTIONAL RECOVERY; FACTS C1 [Morris, Sarah E.; Insel, Thomas R.] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 12 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2011 VL 127 IS 1-3 BP 1 EP 2 DI 10.1016/j.schres.2011.01.027 PG 2 WC Psychiatry SC Psychiatry GA 748MQ UT WOS:000289395100001 PM 21353482 ER PT J AU Averbeck, BB Evans, S Chouhan, V Bristow, E Shergill, SS AF Averbeck, Bruno B. Evans, Simon Chouhan, Viraj Bristow, Eleanor Shergill, Sukhwinder S. TI Probabilistic learning and inference in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Learning; Inference; Decision making ID CONCLUSIONS BIAS; DELUSION-PRONENESS; LIBERAL ACCEPTANCE; DECISION-MAKING; DOPAMINE; CONFIDENCE; PSYCHOSIS; ERRORS; DEFICITS; ACCOUNT AB Patients with schizophrenia make decisions on the basis of less evidence when required to collect information to make an inference, a behavior often called jumping to conclusions. The underlying basis for this behavior remains controversial. We examined the cognitive processes underpinning this finding by testing subjects on the beads task, which has been used previously to elicit jumping to conclusions behavior, and a stochastic sequence learning task, with a similar decision theoretic structure. During the sequence learning task, subjects had to learn a sequence of button presses, while receiving a noisy feedback on their choices. We fit a Bayesian decision making model to the sequence task and compared model parameters to the choice behavior in the beads task in both patients and healthy subjects. We found that patients did show a jumping to conclusions style; and those who picked early in the beads task tended to learn less from positive feedback in the sequence task. This favours the likelihood of patients selecting early because they have a low threshold for making decisions, and that they make choices on the basis of relatively little evidence. Published by Elsevier B.V. C1 [Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. [Averbeck, Bruno B.; Evans, Simon] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England. [Chouhan, Viraj; Bristow, Eleanor; Shergill, Sukhwinder S.] Kings Coll London, Dept Psychosis Studies, Cognit Schizophrenia & Imaging Lab, London, England. RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. EM bruno.averbeck@nih.gov RI Shergill, Sukhi/G-7725-2011 FU National Institute of Mental Health, National Institutes of Health; Wellcome Trust; Medical Research Council; Glaxo Smith Kline FX This work was supported by the Intramural Program of the National Institute of Mental Health, National Institutes of Health (BBA), the Wellcome Trust (BBA, SSS) and the Medical Research Council (SE, SSS).; Over the last 3 years SSS has received study funding from Glaxo Smith Kline. NR 39 TC 40 Z9 42 U1 5 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2011 VL 127 IS 1-3 BP 115 EP 122 DI 10.1016/j.schres.2010.08.009 PG 8 WC Psychiatry SC Psychiatry GA 748MQ UT WOS:000289395100019 PM 20810252 ER PT J AU Lo, S Heishman, SJ Raley, H Wright, K Wehring, HJ Moolchan, ET Feldman, S Liu, F McMahon, RP Richardson, CM Kelly, DL AF Lo, Suzanne Heishman, Stephen J. Raley, Heather Wright, Katherine Wehring, Heidi J. Moolchan, Eric T. Feldman, Stephanie Liu, Fang McMahon, Robert P. Richardson, Charles M. Kelly, Deanna L. TI Tobacco craving in smokers with and without schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Nicotine; Smoking; Craving; Dependency ID NICOTINE DEPENDENCE; SMOKING-CESSATION; CIGARETTE-SMOKING; FAGERSTROM TEST; RECEPTOR; QUESTIONNAIRE; INDIVIDUALS; ABSTINENCE; CUES AB We examined tobacco craving and dependence in current smokers (18-65 years) with schizophrenia (N = 100) and those without a psychiatric disorder (normal controls, N = 100). During the 2-3 h visit participants completed demographic and smoking-related questionnaires and provided a breath CO sample. The Tobacco Craving Questionnaire-Short Form (TCQ-SF) was administered. Immediately after smoking one cigarette, no difference in TCQ-SF total score was noted (46.7 +/- 19.5 schizophrenia, 42.8 +/- 18.2 controls, p = 0.15); however, after 15 min TCQ-SF total score was significantly higher in people with schizophrenia (50.0 +/- 19.6) than in controls (38.6 +/- 19.4) (p = 0.0014). TCQ-SF factors of emotionality (p = 0.0015), compulsivity (p = 0.0003) and purposefulness (p = 0.0174) were significantly greater in the schizophrenia group than the control group. MID scores (5.5 +/- 2.0 vs 5.3 +/- 2.0, p = 0.62) number of cigarettes smoked daily (17.9 +/- 11.6 vs. 17.0 +/- 7.9), expired breath CO (28.0 +/- 14.5 ppm vs. 22.0 +/- 8.0 ppm) and age at smoking initiation (16.2 +/- 5.4 vs. 15.6 +/- 5.5 years, p = 0.44) did not differ in the schizophrenia and control groups respectively. In conclusion, tobacco craving as measured by the TCQ-SF was significantly greater in people with schizophrenia than controls 15 min post-smoking, despite similar scores in dependence and similar smoking histories and current smoking patterns. (C) 2010 Elsevier B.V. All rights reserved. C1 [Raley, Heather; Wright, Katherine; Wehring, Heidi J.; Feldman, Stephanie; Liu, Fang; McMahon, Robert P.; Richardson, Charles M.; Kelly, Deanna L.] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Lo, Suzanne; Heishman, Stephen J.] NIDA, Nicotine Psychopharmacol Sect, NIH, Intramural Res Program, Baltimore, MD 21224 USA. [Moolchan, Eric T.] Alkermes Inc, Cambridge, MA 02139 USA. RP Kelly, DL (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Box 21247, Baltimore, MD 21228 USA. EM dkelly@mprc.umaryland.edu RI McMahon, Robert/C-5462-2009 FU NIH; National Institute on Drug Abuse (NIDA); NIDA Residential Research Support Services [HHSN271200599091CADB] FX Funding for this study was provided by the Intramural Research Program of the NIH, National Institute on Drug Abuse (NIDA), and NIDA Residential Research Support Services Contract HHSN271200599091CADB (PI Kelly). Both NIDA funds and personnel supported the design, study methods and analysis of this study. NR 31 TC 14 Z9 15 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 2011 VL 127 IS 1-3 BP 241 EP 245 DI 10.1016/j.schres.2010.06.017 PG 5 WC Psychiatry SC Psychiatry GA 748MQ UT WOS:000289395100037 PM 20637571 ER PT J AU Gottschall, JL Triulzi, DJ Curtis, B Kakaiya, RM Busch, MP Norris, PJ Glynn, SA Carrick, D Wright, DJ Kleinman, S AF Gottschall, Jerome L. Triulzi, Darrell J. Curtis, Brian Kakaiya, Ram M. Busch, Michael P. Norris, Philip J. Glynn, Simone A. Carrick, Danielle Wright, David J. Kleinman, Steve CA NHLBI Retrovirus Epidemiology Dono TI The frequency and specificity of human neutrophil antigen antibodies in a blood donor population SO TRANSFUSION LA English DT Article ID ACUTE LUNG INJURY; AUTOIMMUNE NEUTROPENIA; TRANSFUSION; PLASMA; ALLOANTIBODIES; PATHOGENESIS; PREGNANCY; WORKSHOP; STRATEGY; BACK AB BACKGROUND: Transfusion-related acute lung injury (TRALI) has been associated with both human leukocyte antigen (HLA) and human neutrophil antigen (HNA) antibodies. HNA antibody frequency, specificity, and demographic associations have not been well defined in the blood donor population. STUDY DESIGN AND METHODS: A subset of 1171 donors (388 nontransfused males, 390 HLA antibody-negative females with three or more pregnancies, and 393 HLA antibody-positive females with three or more pregnancies) from a larger Leukocyte Antibody Prevalence Study was tested for immunoglobulin (Ig)G and IgM HNA antibody using a granulocyte immunofluorescence flow cytometry assay. Additional testing on selected samples included monoclonal antibody immobilization of granulocyte antigen-flow cytometry and granulocyte genotyping. RESULTS: Eight samples were HNA antibody positive (prevalence, 0.7%; 95% confidence interval [CI], 0.3%-1.3%]). Three HNA antibodies (one IgG and two IgM) were found in nontransfused males (prevalence, 0.8%; 95% CI, 0.2%-2.2%); all were panreactive or nonspecific. One HLA antibody-negative previously pregnant female had an IgG HNA antibody with HNA-1a specificity (prevalence, 0.3%; 95% CI, 0.01%-1.4%). Four HLA antibody-positive previously pregnant females demonstrated HNA antibodies, three IgG and one IgM (prevalence, 1%; 95% CI, 0.3%-2.6%). Two of these were HNA-1a specific, one HNA-4a specific, and one nonspecific. CONCLUSIONS: HNA antibodies occur with low frequency in the donor population and are present in both male and female donors. Despite the implementation of TRALI reduction strategies, HNA antibodies are still present in donor blood products. Although our data do not create a case for urgent implementation of donor HNA antibody testing, future new developments for high-throughput HNA antibody screening, including for HNA-3a, may warrant reconsideration. C1 [Gottschall, Jerome L.] Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA. Inst Transfus Med, Pittsburgh, PA USA. Blood Syst Res Inst, San Francisco, CA USA. Blood Ctr Pacific, San Francisco, CA USA. NHLBI, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. RP Gottschall, JL (reprint author), Blood Ctr SE Wisconsin Inc, 638 N 18th St, Milwaukee, WI 53233 USA. EM jerry.gottschall@bcw.edu FU National Heart, Lung and Blood Institute [N01-HB-47168, N01-HB-47169, N01-HB-47170, N01-HB-47171, N01-HB-47172, N01-HB-47174, N01-HB-47175, N01-HB-57181] FX This work was supported by contracts N01-HB-47168, N01-HB-47169, N01-HB-47170, N01-HB-47171, N01-HB-47172, N01-HB-47174, N01-HB-47175 and N01-HB-57181 from the National Heart, Lung and Blood Institute. NR 28 TC 18 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2011 VL 51 IS 4 BP 820 EP 827 DI 10.1111/j.1537-2995.2010.02913.x PG 8 WC Hematology SC Hematology GA 751PH UT WOS:000289629500023 PM 20977484 ER PT J AU Ghosh, AK Martyr, CD Steffey, M Wang, YF Agniswamy, J Amano, M Weber, IT Mitsuya, H AF Ghosh, Arun K. Martyr, Cuthbert D. Steffey, Melinda Wang, Yuan-Fang Agniswamy, Johnson Amano, Masayuki Weber, Irene T. Mitsuya, Hiroaki TI Design, Synthesis, and X-ray Structure of Substituted Bis-tetrahydrofuran (Bis-THF)-Derived Potent HIV-1 Protease Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIV-1 protease inhibitors; Darunavir; bis-THF; drug-resistant; design; synthesis; X-ray structure ID DRUG-RESISTANCE; RESOLUTION; MUTATION AB We investigated substituted bis-THF-derived HIV-1 protease inhibitors in order to enhance liga:nd-binding site interactions in the HIV-1 protease active site. In this context:, we have carried out convenient syntheses of optically active bis-THF and C4-substituted bis-THF ligands using a [2,3]-sigmatropic rearrangement as the key step. The synthesis provided convenient access to a number of substituted bis-THF derivatives. Incorporation of these ligands led to a series of potent HIV-1 protease inhibitors. Inhibitor 23c turned out to be the most potent (K-i = 2.9 pM; IC50 = 2.4 nM) among the inhibitors. An X-ray structure of 23c-bound HIV-1 protease e showed extensive interactions of the inhibitor with the protease active site, including a unique water-mediated hydrogen bond to the Gly-48 amide NH in the S2 site. C1 [Ghosh, Arun K.; Martyr, Cuthbert D.; Steffey, Melinda] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Ghosh, Arun K.; Martyr, Cuthbert D.; Steffey, Melinda] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. [Wang, Yuan-Fang; Agniswamy, Johnson; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA. [Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Hematol, Kumamoto 8608556, Japan. [Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med & Pharmaceut Sci, Dept Infect Dis, Kumamoto 8608556, Japan. [Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. EM akghosh@purdue.edu RI Amano, Masayuki/N-7407-2016 OI Amano, Masayuki/0000-0003-0516-9502 FU National Institutes of Health [GM 53386, GM 062920]; Center for Cancer Research, National Cancer Institute, National Institutes of Health; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Ministry of Health, Welfare, and Labor of Japan; U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX Financial support by the National Institutes of Health (GM 53386, A.K.G.; GM 062920, I.T.W.) is gratefully acknowledged. This work was also supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health, and in part by a Grant-in-aid for Scientific Research (Priority Areas) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho) and a Grant for Promotion of AIDS Research from the Ministry of Health, Welfare, and Labor of Japan.; We thank the staff at the Southeast Regional-Collaborative Access Team (SER-CAT) at the Advanced Photon Source, Argonne National Laboratory, for assistance during X-ray data collection. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. W-31-109-Eng-38. We thank Drs. K. V. Rao and Bruno Chapsal (Purdue University) for helpful discussions. NR 30 TC 13 Z9 13 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD APR PY 2011 VL 2 IS 4 BP 298 EP 302 DI 10.1021/ml100289m PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 751JK UT WOS:000289613200009 PM 22509432 ER PT J AU Britton, KA Aggarwal, V Chen, AY Alexander, KP Amsterdam, E Fraulo, E Muntner, P Thomas, L McGuire, DK Wiviott, SD Roe, MT Schubart, UK Fox, CS AF Britton, Kathryn A. Aggarwal, Vikas Chen, Anita Y. Alexander, Karen P. Amsterdam, Ezra Fraulo, Elizabeth Muntner, Paul Thomas, Laine McGuire, Darren K. Wiviott, Stephen D. Roe, Matthew T. Schubart, Ulrich K. Fox, Caroline S. TI No association between hemoglobin A1c and in-hospital mortality in patients with diabetes and acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ALL-CAUSE MORTALITY; GLYCOSYLATED HEMOGLOBIN; CARDIOVASCULAR-DISEASE; PROGNOSTIC VALUE; HEART-FAILURE; GLUCOSE; HYPOGLYCEMIA; OUTCOMES; EVENTS AB Background Patients with diabetes have increased in-hospital mortality following acute myocardial infarction (AMI), with studies suggesting higher risk with both hypoglycemia and hyperglycemia. We assessed whether a J-shaped relation exists between hemoglobin A1c (A1C) in patients with diabetes and AMI. Methods We assessed the associations between A1C and in-hospital mortality using data from a nationwide sample of AMI patients who had both prior diabetes and measurement of A1C (N = 15,337). Results When evaluated continuously, we observed no evidence of a J-shaped relation between A1C and in-hospital mortality in multivariable analysis (test for linearity P=.89). Patients with lowest (<5.5%) and highest A1C (>= 9.5%) had a crude mortality rate of 4.6% and 2.8%, respectively, compared with 3.8% among those in the referent A1C category (6.5% to <7%). In multivariable regression, we observed no association between low A1C (<5.5%, odds ratio 0.81, 95% CI 0.47-1.39) or high A1C (A1C >= 9.5, odds ratio 1.31, 95% CI 0.94-1.83) and mortality as compared with the referent group. These findings can only be generalized to the subset of patients with diabetes who had A1C assessed during their hospitalization; these patients tended to be healthier than those in whom A1C was not assessed. Conclusion In this large contemporary cohort of patients with diabetes presenting with AMI, we did not observe a J-shaped association between A1C and mortality. (Am Heart J 2011; 161: 657-663.e1.) C1 [Britton, Kathryn A.; Wiviott, Stephen D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Britton, Kathryn A.; Wiviott, Stephen D.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Anita Y.; Alexander, Karen P.; Fraulo, Elizabeth; Thomas, Laine; Roe, Matthew T.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Amsterdam, Ezra] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA 95817 USA. [Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Muntner, Paul] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA. [McGuire, Darren K.] Univ Texas SW Med Ctr Dallas, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75390 USA. [Schubart, Ulrich K.] Albert Einstein Coll Med, Jacobi Med Ctr, Dept Med, Div Endocrinol, Bronx, NY 10467 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU Eli Lilly; Daiichi Sankyo; Schering-Plough; Merck; NovoNordisk; AstraZeneca; F. Hoffmann-LaRoche; Daiichi-Sankyo; Tethys Bioscience; Biosite, Inc; Bristol-Myers Squibb; Sanofi-Aventis; Merck-Schering Plough FX The authors report the following conflicts of interest: Dr Wiviott-research funding: Eli Lilly, Daiichi Sankyo, Schering-Plough, and Merck; consulting or honoraria: Eli Lilly, Daiichi Sankyo, Schering-Plough, Merck, AstraZeneca, Biogen, and Novartis; Dr McGuire-consulting fees: NovoNordisk, AstraZeneca, F. Hoffmann-LaRoche, Daiichi-Sankyo, Tethys Bioscience, and Biosite, Inc; Dr Roe-research funding: Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, and Merck-Schering Plough; consulting or honoraria: Glaxo Smith Kline, Novartis, Eli Lilly, Bristol-Myers Squibb, Sanofi-Aventis, Merck-Schering Plough, and Astra Zeneca. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents. NR 28 TC 17 Z9 17 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD APR PY 2011 VL 161 IS 4 BP 657 EP U1502 AR 663.e1 DI 10.1016/j.ahj.2010.12.004 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 745TW UT WOS:000289190500007 PM 21473963 ER PT J AU Daugherty, SE Pfeiffer, RM Sigurdson, AJ Hayes, RB Leitzmann, M Schatzkin, A Hollenbeck, AR Silverman, DT AF Daugherty, Sarah E. Pfeiffer, Ruth M. Sigurdson, Alice J. Hayes, Richard B. Leitzmann, Michael Schatzkin, Arthur Hollenbeck, Albert R. Silverman, Debra T. TI Nonsteroidal Antiinflammatory Drugs and Bladder Cancer: A Pooled Analysis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE anti-inflammatory agents; non-steroidal; aspirin; meta-analysis; urinary bladder neoplasms ID TRANSITIONAL-CELL CARCINOMA; LOW-DOSE ASPIRIN; URINARY-BLADDER; LARGE COHORT; CYCLOOXYGENASE-2 EXPRESSION; RADIOLOGIC TECHNOLOGISTS; SCREENING TRIAL; RISK; HEALTH; LUNG AB Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (> 2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P-trend = 0.008) (P-interaction = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers. C1 [Daugherty, Sarah E.; Pfeiffer, Ruth M.; Sigurdson, Alice J.; Schatzkin, Arthur; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. [Hayes, Richard B.] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA. [Leitzmann, Michael] Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany. [Hollenbeck, Albert R.] AARP, Res & Strateg Anal Dept, Washington, DC USA. RP Daugherty, SE (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,MSC 7240,EPS 8113, Rockville, MD 20852 USA. EM daughers@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 OI Hayes, Richard/0000-0002-0918-661X; FU NIH, National Cancer Institute, US National Institutes of Health; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; NIH, National Cancer Institute [HHSN261200800001E]; Florida Department of Health (FDOH); Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, US National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services (DHHS), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.; The PLCO research was supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The authors thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute; the Screening Center investigators and staff of the PLCO Cancer Screening Trial; Tom Riley and staff, Information Management Services, Inc.; and Barbara O'Brien and staff, Westat, Inc.; The AARP research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute. Cancer incidence data from the Atlanta, Georgia, metropolitan area were collected by the Georgia Center for Cancer Statistics, Department of Epidemiology, Rollins School of Public Health, Emory University. Cancer incidence data from California were collected by the California Department of Health Services, Cancer Surveillance Section. Cancer incidence data from the Detroit metropolitan area were collected by the Michigan Cancer Surveillance Program, Community Health Administration, State of Michigan. The Florida cancer incidence data used in this report were collected by the Florida Cancer Data System (FCDC) under contract with the Florida Department of Health (FDOH). The views expressed herein are solely those of the authors and do not necessarily reflect those of the FCDC or FDOH. Cancer incidence data from Louisiana were collected by the Louisiana Tumor Registry, Louisiana State University Medical Center in New Orleans. Cancer incidence data from New Jersey were collected by the New Jersey State Cancer Registry, Cancer Epidemiology Services, New Jersey State Department of Health and Senior Services. Cancer incidence data from North Carolina were collected by the North Carolina Central Cancer Registry. Cancer incidence data from Pennsylvania were supplied by the Division of Health Statistics and Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. Cancer incidence data from Arizona were collected by the Arizona Cancer Registry, Division of Public Health Services, Arizona Department of Health Services. Cancer incidence data from Texas were collected by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services. The authors thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcomes ascertainment and management and Leslie Carroll at Information Management Services for data support and analysis.; The USRT research has been funded in part by the National Cancer Institute, NIH, under contract HHSN261200800001E and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The authors are grateful to Jerry Reid of the American Registry of Radiologic Technologists for continued support of this study; Diane Kampa and Allison Iwan of the University of Minnesota for study coordination and data collection, and Laura Bowen of Information Management Systems for data management. NR 39 TC 37 Z9 39 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2011 VL 173 IS 7 BP 721 EP 730 DI 10.1093/aje/kwq437 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 747DT UT WOS:000289301200001 PM 21367875 ER PT J AU Mondul, AM Watters, JL Mannisto, S Weinstein, SJ Snyder, K Virtamo, J Albanes, D AF Mondul, Alison M. Watters, Joanne L. Mannisto, Satu Weinstein, Stephanie J. Snyder, Kirk Virtamo, Jarmo Albanes, Demetrius TI Serum Retinol and Risk of Prostate Cancer SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; prospective studies; prostatic neoplasms; vitamin A ID BETA-CAROTENE SUPPLEMENTATION; NUTRITION EXAMINATION SURVEY; VITAMIN-A; ALPHA-TOCOPHEROL; DIETARY FACTORS; FOLLOW-UP; NATIONAL-HEALTH; SUBSEQUENT RISK; PLASMA LYCOPENE; EFFICACY TRIAL AB Greater exposure to retinol (vitamin A) may prevent prostate cancer, although under some conditions it could promote cell growth and de-differentiation. The authors prospectively examined prostate cancer risk and serum retinol levels, measured by using high-performance liquid chromatography, at baseline (n = 29,104) and after 3 years (n = 22,843) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort. Cox proportional hazards models were used to estimate the relative risk of total (n = 2,041) and aggressive (n = 461) prostate cancer by quintiles of baseline and 3-year serum retinol concentrations and by change in serum retinol levels from baseline to 3 years. Men with higher retinol concentrations at baseline were more likely to develop prostate cancer (quintile 5 vs. quintile 1 hazard ratio = 1.19, 95% confidence interval: 1.03, 1.36; P-trend = 0.009). The results were similar for aggressive disease. Joint categorization based on baseline and 3-year retinol levels showed that men who were in the highest quintile at both time points had the greatest increased risk (baseline/3-year quintile 5/quintile 5 vs. quintile 1/quintile 1 hazard ratio = 1.31, 95% confidence interval: 1.08, 1.59). In this largest study to date of vitamin A status and subsequent risk of prostate cancer, higher serum retinol was associated with elevated risk, with sustained high exposure conferring the greatest risk. Future studies may clarify the underlying biologic mechanisms of the retinol-prostate cancer association. C1 [Mondul, Alison M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Snyder, Kirk] Informat Management Serv Inc, Silver Spring, MD USA. RP Mondul, AM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Rockville, MD 20852 USA. EM mondulam@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Mannisto, Satu/0000-0002-8668-3046; Mondul, Alison/0000-0002-8843-1416 FU National Cancer Institute, Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]; National Cancer Institute FX This work was supported by US Public Health Service contracts from the National Cancer Institute, Department of Health and Human Services (N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C) and by funding from the Intramural Research Program of the National Cancer Institute. NR 54 TC 20 Z9 21 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 2011 VL 173 IS 7 BP 813 EP 821 DI 10.1093/aje/kwq429 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 747DT UT WOS:000289301200013 PM 21389041 ER PT J AU Georgiopoulou, VV Kalogeropoulos, AP Psaty, BM Rodondi, N Bauer, DC Butler, AB Koster, A Smith, AL Harris, TB Newman, AB Kritchevsky, SB Butler, J AF Georgiopoulou, Vasiliki V. Kalogeropoulos, Andreas P. Psaty, Bruce M. Rodondi, Nicolas Bauer, Douglas C. Butler, Abida B. Koster, Annemarie Smith, Andrew L. Harris, Tamara B. Newman, Anne B. Kritchevsky, Stephen B. Butler, Javed TI Lung Function and Risk for Heart Failure Among Older Adults: The Health ABC Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Elderly; Epidemiology; Heart failure; Pulmonary function test ID OBSTRUCTIVE PULMONARY-DISEASE; 3RD NATIONAL-HEALTH; NUTRITION-EXAMINATION; OXIDATIVE STRESS; CARDIOVASCULAR-DISEASE; MULTIPLE IMPUTATION; BODY-COMPOSITION; INFLAMMATION; MORTALITY; COPD AB BACKGROUND: The impact of abnormal spirometric findings on risk for incident heart failure among older adults without clinically apparent lung disease is not well elucidated. METHODS: We evaluated the association of baseline lung function with incident heart failure, defined as first hospitalization for heart failure, in 2125 participants of the community-based Health, Aging, and Body Composition (Health ABC) Study (age, 73.6 +/- 2.9 years; 50.5% men; 62.3% white; 37.7% black) without prevalent lung disease or heart failure. Abnormal lung function was defined either as forced vital capacity (FVC) or forced expiratory volume in 1(st) second (FEV1) to FVC ratio below lower limit of normal. Percent predicted FVC and FEV1 also were assessed as continuous variables. RESULTS: During follow-up (median, 9.4 years), heart failure developed in 68 of 350 (19.4%) participants with abnormal baseline lung function, as compared with 172 of 1775 (9.7%) participants with normal lung function (hazard ratio [HR] 2.31; 95% confidence interval [CI], 1.74-3.07; P <.001). This increased risk persisted after adjusting for previously identified heart failure risk factors in the Health ABC Study, body mass index, incident coronary heart disease, and inflammatory markers (HR 1.83; 95% CI, 1.33-2.50; P <.001). Percent predicted (%) FVC and FEV 1 had a linear association with heart failure risk (HR 1.21; 95% CI, 1.11-1.32 and 1.18; 95% CI, 1.10-1.26, per 10% lower % FVC and % FEV1, respectively; both P <.001 in fully adjusted models). Findings were consistent in sex and race subgroups and for heart failure with preserved or reduced ejection fraction. CONCLUSIONS: Abnormal spirometric findings in older adults without clinical lung disease are associated with increased heart failure risk. (C) 2011 Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, 334-341 C1 [Georgiopoulou, Vasiliki V.; Kalogeropoulos, Andreas P.; Smith, Andrew L.; Butler, Javed] Emory Univ, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rodondi, Nicolas] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland. [Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. [Butler, Abida B.] Louisiana State Univ, Bogalusa Med Ctr, Emergency Dept, Bogalusa, LA USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Dept Geriatr & Gerontol, Winston Salem, NC 27109 USA. RP Georgiopoulou, VV (reprint author), Emory Univ Hosp, Div Cardiol, 1462 Clifton Rd NE,Suite 535A, Atlanta, GA 30322 USA. EM vgeorgi@emory.edu RI Koster, Annemarie/E-7438-2010; Library, Woodruff Health/A-6096-2012; Newman, Anne/C-6408-2013; Kalogeropoulos, Andreas/A-9494-2009; OI Newman, Anne/0000-0002-0106-1150; Kalogeropoulos, Andreas/0000-0002-1284-429X; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute of Aging; National Institutes of Health, Bethesda [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; PHS [UL1 RR025008]; National Heart, Lung, and Blood Institute [R01-HL-7-4104]; Emory University Heart and Vascular Board FX This work was supported in part by the Intramural Research Program of the National Institute of Aging, National Institutes of Health, Bethesda MD (Grants N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106); and by PHS (Grant UL1 RR025008) from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources. Dr. Kritchevsky is also supported by National Heart, Lung, and Blood Institute grant R01-HL-7-4104. This work was also partially funded through an Emory University Heart and Vascular Board grant entitled "Novel Risk Markers and Prognosis Determination in Heart Failure." NR 41 TC 16 Z9 16 U1 2 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD APR PY 2011 VL 124 IS 4 BP 334 EP 341 DI 10.1016/j.amjmed.2010.12.006 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 750QN UT WOS:000289563200016 PM 21435424 ER PT J AU Green, MF Schooler, NR Kern, RS Frese, FJ Granberry, W Harvey, PD Karson, CN Peters, RNN Stewart, M Seidman, LJ Sonnenberg, J Stone, WS Walling, D Stover, E Marder, SR AF Green, Michael F. Schooler, Nina R. Kern, Robert S. Frese, Fred J. Granberry, Wendy Harvey, Philip D. Karson, Craig N. Peters, Nancy R. N. Stewart, Michelle Seidman, Larry J. Sonnenberg, John Stone, William S. Walling, David Stover, Ellen Marder, Stephen R. TI Evaluation of Functionally Meaningful Measures for Clinical Trials of Cognition Enhancement in Schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MATRICS; RELIABILITY; VALIDITY; BATTERY; STANDARDIZATION; SCALE AB Objective: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U. S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. Method: In this four-site validation study, schizophrenia patients were assessed at baseline (N= 166) and 4 weeks later (N= 144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performance-based measures were evaluated. Results: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. Conclusions: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance. C1 Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. VA Desert Pacific Mental Illness Res, Educ & Clin Ctr, Los Angeles, CA USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. VISN 5 Mental Illness Res, Educ & Clin Ctr, Baltimore, MD USA. Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Rootstown, OH 44272 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Emory Univ, Atlanta, GA 30322 USA. Merck, N Wales, PA USA. Sanofi Aventis, Malvern, PA USA. Pfizer Inc, New London, CT USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Uptown Res Inst, Chicago, IL USA. Collaborat Neurosci Network, Garden Grove, CA USA. NIMH, Bethesda, MD 20892 USA. RP Green, MF (reprint author), 300 UCLA Med Plaza,Rm 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu FU NIMH [HHSN 278 2004 41003C, MH042392]; AstraZeneca FX Dr. Green has served as a consultant for Abbott Laboratories, Astellas, Cypress, Dainippon Sumitomo Pharma, GlaxoSmithKline, Lund-beck, Otsuka, Sanofi-Aventis, Takeda, Teva, and Wyeth and has been a speaker for Janssen-Cilag, Otsuka, and Sunovion. Dr. Schooler has received research support or served as a consultant or speaker for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Eli Lilly, Hoffmann-La Roche, Janssen Cilag-Spain, Lundbeck, Merck, OrthoMcNeil Janssen, Pfizer, and Schering Plough. Dr. Kern has served as a consultant for Otsuka. Dr. Granberry is an employee of GlaxoSmithKline. Dr. Harvey has served as a consultant for Abbott, Cypress, Eli Lilly, Merck, Johnson & Johnson, Solvay, Dainippon Sumitomo Pharma America, and Wyeth and has received research support from AstraZeneca. Dr. Karson is an employee of Merck. Ms. Peters is an employee of Sanofi-Aventis. Dr. Stewart is an employee of Pfizer. Dr. Sonnenberg has provided clinical trial or consulting services for Abbott, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo Pharma, Eli Lilly, Enviro, Forest, Johnson & Johnson, Lundbeck, Novartis, Otsuka, Pfizer, Shire, Solvay, Sanofi-Aventis, and Takeda. Dr. Stone has received research support from Ortho-McNeil Janssen Scientific Affairs. Dr. Walling has provided clinical trial or consulting services to Abbott, Alexza, AstraZeneca, BrainCell, Cephalon, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Memory Pharmaceuticals, Novartis, Otsuka, Pfizer, Roche, Sepracor, Shire, Solvay, Sanofi-Aventis, Takeda, Toyama, Vanda, and Wyeth and has served as a consultant or speaker for Abbott, GlaxoSmithKline, Janssen, Novartis, and Otsuka. Dr. Marder has been a consultant for Wyeth, Otsuka, Pfizer, Schering Plough, Lundbeck, and Sanofi-Aventis. The other authors report no financial relationships with commercial interests.; Supported by an extension to contract HHSN 278 2004 41003C from NIMH, with additional support from grant MH042392.; The authors thank the members of the MATRICS-CT (Co-Primary and Translation) Scientific Board, which consisted of representatives from academia, the pharmaceutical industry, NIMH, and the Foundation at NIH. The board provided excellent input and guidance for this study. The authors also thank the members of the MATRICS-CT Rand Panel who are not listed as authors on this paper: Drs. Deanna Barch, John Brekke, Judith Cook, Patrick Corrigan, Michael Egan, Helena Kraemer, William Lawson, Andy Leon, Steve Romano, and Sophia Vinogradov. NR 26 TC 63 Z9 63 U1 1 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2011 VL 168 IS 4 BP 400 EP 407 DI 10.1176/appi.ajp.2010.10030414 PG 8 WC Psychiatry SC Psychiatry GA 746KM UT WOS:000289245500012 PM 21285142 ER PT J AU Mattai, A Hosanagar, A Weisinger, B Greenstein, D Stidd, R Clasen, L Lalonde, F Rapoport, J Gogtay, N AF Mattai, Anand Hosanagar, Avinash Weisinger, Brian Greenstein, Deanna Stidd, Reva Clasen, Liv Lalonde, Francois Rapoport, Judith Gogtay, Nitin TI Hippocampal Volume Development in Healthy Siblings of Childhood-Onset Schizophrenia Patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VOXEL-BASED MORPHOMETRY; OBSTETRIC COMPLICATIONS; BRAIN-DEVELOPMENT; 1ST-EPISODE SCHIZOPHRENIA; GEOMETRICALLY ACCURATE; PERSONALITY-DISORDERS; UNAFFECTED SIBLINGS; MEMORY; RISK; MORPHOLOGY AB Objective: Previous anatomic studies have established a reduction in hippocampal volume in schizophrenia, but few have investigated the progressive course of these changes and whether they are trait markers. In the present study, the authors examined hippocampal volumes in relation to age for patients with childhood-onset schizophrenia, their nonpsychotic healthy siblings, and healthy comparison subjects. Method: Anatomic brain magnetic resonance scans were obtained in childhood-onset schizophrenia probands (N= 89, 198 scans), their nonpsychotic full siblings (N= 78, 172 scans), and matched healthy comparison subjects (N= 79, 198 scans) between the ages of 10 and 29 years. Total, left, and right hippocampal volumes were measured using FreeSurfer software and analyzed using a linear mixed-model regression covarying for sex and intracranial volume. Results: Childhood-onset schizophrenia probands had a fixed reduction in hippocampal volumes (total, left, and right) relative to both nonpsychotic siblings and healthy comparison subjects, whereas there were no significant volumetric or trajectory differences between non-psychotic siblings and healthy comparison subjects. Conclusions: Fixed hippocampal volume loss seen in childhood-onset schizophrenia, which is not shared by healthy siblings, appears to be related to the illness. De-creased hippocampal volume is not strongly genetically related but represents an important intermediate disease phenotype. C1 [Mattai, Anand] NIH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Mattai, A (reprint author), NIH, Child Psychiat Branch, Bldg 10,Rm 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM mattaia@mail.nih.gov RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS [ZIA MH002581-21] NR 85 TC 24 Z9 24 U1 4 U2 10 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2011 VL 168 IS 4 BP 427 EP 435 DI 10.1176/appi.ajp.2010.10050681 PG 9 WC Psychiatry SC Psychiatry GA 746KM UT WOS:000289245500015 PM 21245087 ER PT J AU Parascandola, M AF Parascandola, Mark TI TOBACCO HARM REDUCTION and the Evolution of Nicotine Dependence SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID CANCER-INSTITUTE SMOKING; SMOKELESS TOBACCO; INDUSTRY DOCUMENTS; HEALTH-PROGRAM; UNITED-STATES; CIGARETTE; ADDICTION; PRODUCTS; EXPOSURE; SMOKERS AB In recent years, a renewed debate has developed around the potential for modified tobacco products to play a role in reducing tobacco-related harm. During the 1960s and 1970s medical experts recommended to smokers who could not quit that they switch to cigarettes with lower tar and nicotine content. At the time, survey data suggested that smokers who switched did not compensate for the reduction in nicotine by increasing their intake. However, public health scientists were hindered in their ability to evaluate the population impact of the reduced tar strategy by a limited understanding of nicotine addiction. Smoking dependence was seen as primarily psychological and social, rather than pharmacological or biological, until the late 1970s, when addiction researchers began to apply experimental techniques from other forms of drug abuse to study smoking behavior. This history has important lessons for current discussions about tobacco harm reduction and regulation of nicotine delivery. (Am J Public Health. 2011;101:632-641. doi:10.2105/AJPH.2009.189274) C1 NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4032,MSC 7337, Bethesda, MD 20892 USA. EM paramark@mail.nih.gov NR 86 TC 14 Z9 14 U1 1 U2 10 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2011 VL 101 IS 4 BP 632 EP 641 DI 10.2105/AJPH.2009.189274 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 740UN UT WOS:000288820000016 PM 21330596 ER PT J AU Newgard, CD Schmicker, RH Sopko, G Andrusiek, D Bialkowski, W Minei, JP Brasel, K Bulger, E Fleischman, RJ Kerby, JD Bigham, BL Warden, CR AF Newgard, Craig D. Schmicker, Robert H. Sopko, George Andrusiek, Dug Bialkowski, Walter Minei, Joseph P. Brasel, Karen Bulger, Eileen Fleischman, Ross J. Kerby, Jeffrey D. Bigham, Blair L. Warden, Craig R. CA Resuscitation Outcomes Consortium TI Trauma in the Neighborhood: A Geospatial Analysis and Assessment of Social Determinants of Major Injury in North America SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID TRIAGE CRITERIA; FIELD TRIAGE; EPIDEMIOLOGY; PREVENTION; PATTERNS; COLLEGE; SCIENCE; SYSTEM AB Objectives. We sought to identify and characterize areas with high rates of major trauma events in 9 diverse cities and counties in the United States and Canada. Methods. We analyzed a prospective, population-based cohort of injured individuals evaluated by 163 emergency medical service agencies transporting patients to 177 hospitals across the study sites between December 2005 and April 2007. Locations of injuries were geocoded, aggregated by census tract, assessed for geospatial clustering, and matched to sociodemographic measures. Negative binomial models were used to evaluate population measures. Results. Emergency personnel evaluated 8786 major trauma patients, and data on 7326 of these patients were available for analysis. We identified 529 (13.7%) census tracts with a higher than expected incidence of major trauma events. In multivariable models, trauma events were associated with higher unemployment rates, larger percentages of non-White residents, smaller percentages of foreign-born residents, lower educational levels, smaller household sizes, younger age, and lower income levels. Conclusions. Major trauma events tend to cluster in census tracts with distinct population characteristics, suggesting that social and contextual factors may play a role in the occurrence of significant injury events. (Am J Public Health. 2011;101:669-677. doi:10.2105/AJPH.2010.300063) C1 [Newgard, Craig D.; Fleischman, Ross J.; Warden, Craig R.] Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, Portland, OR 97239 USA. [Schmicker, Robert H.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Andrusiek, Dug] Univ British Columbia, Emergency & Hlth Serv Commiss British Columbia, Vancouver, BC V5Z 1M9, Canada. [Bialkowski, Walter] Med Coll Wisconsin, Dept Emergency Med, Milwaukee, WI 53226 USA. [Minei, Joseph P.] Univ Texas SW Med Ctr Dallas, Dept Surg, Dallas, TX 75390 USA. [Brasel, Karen] Med Coll Wisconsin, Dept Surg, Milwaukee, WI 53226 USA. [Bulger, Eileen] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Kerby, Jeffrey D.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Bigham, Blair L.] Univ Toronto, St Michaels Hosp, Toronto, ON M5B 1W8, Canada. RP Newgard, CD (reprint author), Oregon Hlth & Sci Univ, Dept Emergency Med, Ctr Policy & Res Emergency Med, 3181 SW Sam Jackson Pk Rd,Mailcode CR-114, Portland, OR 97239 USA. EM newgardc@ohsu.edu FU National Heart, Lung, and Blood Institute [5U01 HL077863, HL077881, HL077871, HL077872, HL077866, HL077908, HL077867, HL077885, HL077863]; National Institute of Neurological Disorders and Stroke; US Army Medical Research and Materiel Command; Canadian Institutes of Health Research; Defence Research and Development Canada; Heart and Stroke Foundation of Canada; American Heart Association FX The Resuscitation Outcomes Consortium was supported by a series of cooperative agreements to 10 regional clinical centers and 1 data coordinating center (5U01 HL077863, HL077881, HL077871, HL077872, HL077866, HL077908, HL077867, HL077885, HL077885, and HL077863) from the National Heart, Lung, and Blood Institute in partnership with the National Institute of Neurological Disorders and Stroke, the US Army Medical Research and Materiel Command, the Canadian Institutes of Health Research, Defence Research and Development Canada, the Heart and Stroke Foundation of Canada, and the American Heart Association. Additional details are included in Appendix C (available as a supplement to the online version of this article at http://www.ajph.org). NR 36 TC 8 Z9 9 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2011 VL 101 IS 4 BP 669 EP 677 DI 10.2105/AJPH.2010.300063 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 740UN UT WOS:000288820000022 PM 21389292 ER PT J AU Hasko, G Pacher, P AF Hasko, Gyoergy Pacher, Pal TI Suppression of Tumorigenicity 2 A Janus-faced Player in Sepsis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID INTERLEUKIN-1 RECEPTOR; IL-1 RECEPTOR; ST2; GENE; INFLAMMATION; CYTOKINE; PROTEIN; MICE C1 [Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. [Pacher, Pal] NIAAA, NIH, Bethesda, MD USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA. RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 NR 15 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2011 VL 183 IS 7 BP 841 EP 843 DI 10.1164/rccm.201011-1789ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 747KN UT WOS:000289318800007 PM 21471075 ER PT J AU Jiang, CC Zhao, ML Scearce, RM Diaz, M AF Jiang, Chuancang Zhao, Ming-Lang Scearce, Richard M. Diaz, Marilyn TI Activation-Induced Deaminase-Deficient MRL/lpr Mice Secrete High Levels of Protective Antibodies Against Lupus Nephritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTI-DNA ANTIBODIES; B-CELLS; MURINE LUPUS; LPR MICE; AUTOANTIBODY PRODUCTION; AUTOIMMUNE-DISEASE; SOMATIC MUTATION; DENDRITIC CELLS; PRONE MICE; ERYTHEMATOSUS AB Objective. We previously generated MRL/lpr mice deficient in activation-induced deaminase (AID) that lack isotype switching and immunoglobulin hypermutation. These mice have high levels of unmutated (germline) autoreactive IgM, yet they experienced an increase in survival and an improvement in lupus nephritis that exceeded that of MRL/lpr mice lacking IgG. The purpose of the present study was to test the hypothesis that high levels of germline autoreactive IgM in these mice confer protection against lupus nephritis. Methods. Autoreactive IgM antibodies of various specificities, including antibodies against double-stranded DNA (dsDNA), from AID-deficient MRL/lpr mice were given to asymptomatic MRL/lpr mice, and the levels of cytokines, proteinuria, immune complex deposition in the kidneys, and glomerulonephritis were examined. Novel AID-deficient MRL/lpr mice that lack any antibodies were generated for comparison to AID-deficient MRL/lpr mice that secrete only IgM. Results. Treatment with IgM anti-dsDNA resulted in a dramatic improvement in lupus nephritis. Other autoreactive IgM antibodies, such as antiphospholipid and anti-Sm, did not alter the pathologic changes. Secretion of proinflammatory cytokines by macrophages and the levels of inflammatory cells and apoptotic debris in the kidneys were lower in mice receiving IgM anti-dsDNA. Protective IgM derived from AID-deficient MRL/lpr mice displayed a distinct B cell repertoire, with a bias toward members of the V(H)7183 family. Conclusion. IgM anti-dsDNA protected MRL/lpr mice from lupus nephritis, likely by stopping the inflammatory cascade leading to kidney damage. A distinct repertoire of V-H usage in IgM anti-dsDNA hybridomas from AID-deficient mice suggests that there is enrichment of a dedicated B cell population that secretes unmutated protective IgM in these mice. C1 [Diaz, Marilyn] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. [Scearce, Richard M.] Duke Univ, Med Ctr, Durham, NC USA. RP Diaz, M (reprint author), Natl Inst Environm Hlth Sci, NIH, D3-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM diaz@niehs.nih.gov FU NIH (National Institute of Environmental Health Sciences) [1ZIAES-101603-07] FX Supported by the NIH (grant 1ZIAES-101603-07 from the Intramural Research Program of the National Institute of Environmental Health Sciences). NR 50 TC 28 Z9 28 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD APR PY 2011 VL 63 IS 4 BP 1086 EP 1096 DI 10.1002/art.30230 PG 11 WC Rheumatology SC Rheumatology GA 748VO UT WOS:000289421100027 PM 21225690 ER PT J AU Higham, JP Barr, CS Hoffman, CL Mandalaywala, TM Parker, KJ Maestripieri, D AF Higham, James P. Barr, Christina S. Hoffman, Christy L. Mandalaywala, Tara M. Parker, Karen J. Maestripieri, Dario TI Mu-opioid Receptor (OPRM1) Variation, Oxytocin Levels and Maternal Attachment in Free-Ranging Rhesus Macaques Macaca mulatta SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE mother-infant bond; opioids; oxytocin; functional genetics; attachment ID SINGLE-NUCLEOTIDE POLYMORPHISM; GENE OPRM1; BEHAVIOR; ASSOCIATION; PRIMATES; MONKEYS; SYSTEMS; STRESS AB Understanding the genetic and neuroendocrine basis of the mother-infant bond is critical to understanding mammalian affiliation and attachment. Functionally similar nonsynonymous mu-opioid receptor (OPRM1) SNPs have arisen and been maintained in humans (A118G) and rhesus macaques Macaca mulatta (C77G). In rhesus macaques, variation in OPRM1 predicts individual differences in infant affiliation for mothers. Specifically, infants carrying the G allele show increased distress on separation from their mothers, and spend more time with them upon reunion, than individuals homozygous for the C allele. In humans, individuals possessing the G allele report higher perceptions of emotional pain on receiving rejection by social partners. We studied maternal behavior over the course of a year among free-ranging female rhesus macaques on Cayo Santiago, Puerto Rico. We then trapped females and collected blood samples from which we assessed OPRM1 genotype; we also collected cerebrospinal fluid samples from which we measured oxytocin (OT) levels. We show that females possessing the G allele restrain their infants more (i.e., prevent infants from separating from them by pulling them back) than females homozygous for the C allele. Females possessing the G allele also show higher OT levels when lactating, and lower OT levels when neither lactating nor pregnant, than females homozygous for the C allele. This is the first study to demonstrate an association between OPRM1 genotype and maternal attachment for infants, and is one of the first studies of any free-ranging primate population to link functional genetic variation to behavior via potentially related neuroendocrine mechanisms. C1 [Higham, James P.; Hoffman, Christy L.; Mandalaywala, Tara M.; Maestripieri, Dario] Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA. [Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, Rockville, MD 20852 USA. [Barr, Christina S.] NIAAA, Sect Comparat Behav Genom, Neurogenet Lab, NIH, Rockville, MD 20852 USA. [Hoffman, Christy L.; Mandalaywala, Tara M.; Maestripieri, Dario] Univ Chicago, Dept Comparat Human Dev, Chicago, IL 60637 USA. [Parker, Karen J.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Higham, JP (reprint author), Univ Chicago, Inst Mind & Biol, 940 E 57th St, Chicago, IL 60637 USA. EM jhigham@uchicago.edu RI Parker, Karen/G-1347-2012; OI Hoffman, Christy/0000-0003-3077-6363; Parker, Karen/0000-0002-6836-6338 FU National Institutes of Health (NIH) [R21-AG029862]; NIH National Center for Research Resources (NCRR) [CM-5-P40RR003640] FX We thank Richelle Scales, Geoff Gallice, Bianca Giura, and Jake Reeder for assistance with data collection, and Adaris Mas-Rivera, James Ayala, and the staff of the Caribbean Primate Research Center for logistical support. We also thank Lauren Brent for helpful thoughts on genetic relatedness. This research was supported by National Institutes of Health (NIH) Grant R21-AG029862 to Dario Maestripieri and conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals. The protocol for this study was approved by the Institutional Animal Care and Use Committee, Medical Sciences Department, University of Puerto Rico. This publication was made possible by grant number CM-5-P40RR003640 from the NIH National Center for Research Resources (NCRR) to the Caribbean Primate Research Center of the University of Puerto Rico. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of NCRR or NIH. NR 38 TC 28 Z9 28 U1 2 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD APR PY 2011 VL 125 IS 2 BP 131 EP 136 DI 10.1037/a0022695 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 745QZ UT WOS:000289182000001 PM 21463018 ER PT J AU Moore, HM Kelly, A Jewell, SD McShane, LM Clark, DP Greenspan, R Hainaut, P Hayes, DF Kim, P Mansfield, E Potapova, O Riegman, P Rubinstein, Y Seijo, E Somiari, S Watson, P Weier, HU Zhu, C Vaught, J AF Moore, Helen M. Kelly, Andrea Jewell, Scott D. McShane, Lisa M. Clark, Douglas P. Greenspan, Renata Hainaut, Pierre Hayes, Daniel F. Kim, Paula Mansfield, Elizabeth Potapova, Olga Riegman, Peter Rubinstein, Yaffa Seijo, Edward Somiari, Stella Watson, Peter Weier, Heinz-Ulrich Zhu, Claire Vaught, Jim TI Biospecimen Reporting for Improved Study Quality SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID PARAFFIN-EMBEDDED TISSUES; FLIGHT-MASS-SPECTROMETRY; APPROACHING CLINICAL PROTEOMICS; GENE-EXPRESSION PROFILES; NEEDLE-ASPIRATION BIOPSY; HUMAN POSTMORTEM TISSUES; LONG-TERM STORAGE; MESSENGER-RNA; HUMAN BRAIN; MICROARRAY ANALYSIS AB Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The Biospecimen Reporting for Improved Study Quality guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected. C1 [Moore, Helen M.; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Kelly, Andrea] Rose Li & Associates Inc, Brookeville, MD USA. [Jewell, Scott D.] Van Andel Res Inst, Program Biospecimen Sci, Grand Rapids, MI USA. [McShane, Lisa M.] NCI, Biometr Res Branch, Rockville, MD USA. [Clark, Douglas P.] Johns Hopkins Univ Hosp, Div Cytopathol, Baltimore, MD 21287 USA. [Greenspan, Renata] Walter Reed Army Med Ctr, USMCI, Washington, DC 20307 USA. [Hainaut, Pierre] WHO, Int Agcy Res Canc, Lyon, France. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Breast Canc Res, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Kim, Paula] TRAC Translating Res Communities, Green Cove Springs, FL USA. [Mansfield, Elizabeth] Ctr Devices & Radiol Hlth, CDRH Off Vitro Diagnost Device Evaluat & Safety, Silver Spring, MD USA. [Potapova, Olga] Cureline Inc, San Francisco, CA USA. [Riegman, Peter] Erasmus MC Tissue Bank, Rotterdam, Netherlands. [Rubinstein, Yaffa] NIH, Off Rare Dis Res, Rockville, MD USA. [Seijo, Edward] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somiari, Stella] Windber Res Inst, Windber, PA USA. [Watson, Peter] Univ British Columbia, Dept Pathol & Lab Med, Victoria, BC, Canada. [Weier, Heinz-Ulrich] Lawrence Berkeley Natl Lab, Berkeley, CA USA. [Zhu, Claire] NCI, Canc Prevent Div, Rockville, MD USA. RP Vaught, J (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, 11400 Rockville Pike,Suite 700, Rockville, MD 20852 USA. EM vaughtj@mail.nih.gov RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU NCI, National Institutes of Health [HHSN261200800001E]; NIH [CA136685]; Lawrence Berkeley National Laboratory [DE-AC002-05CH11231] FX This project has been funded in whole or in part with Federal Funds from the NCI, National Institutes of Health, under contract no. HHSN261200800001E and by NIH grant CA136685 (HUW) carried out at the Lawrence Berkeley National Laboratory under contract DE-AC002-05CH11231. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. NR 81 TC 49 Z9 49 U1 2 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD APR PY 2011 VL 9 IS 1 BP 57 EP 70 DI 10.1089/bio.2010.0036 PG 14 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 751KS UT WOS:000289617000010 ER PT J AU Jung, S Silvius, D Nolan, KA Borchert, GL Millet, YH Phang, JM Gunn, TM AF Jung, SeungWoo Silvius, Derek Nolan, Katherine A. Borchert, Gregory L. Millet, Yoann H. Phang, James M. Gunn, Teresa M. TI Developmental Cardiac Hypertrophy in a Mouse Model of Prolidase Deficiency SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE cardiac hypertrophy; peptidase d (Pepd); prolidase deficiency; collagen; pigmentation ID FOCAL ADHESION KINASE; POSTNATAL-DEVELOPMENT; COLLAGEN BIOSYNTHESIS; GENERAL-POPULATION; HEART-DISEASE; CARDIOMYOPATHY; MYOCYTES; PROLINE; MICE; PATHWAY AB BACKGROUND: Hypertrophic cardiomyopathy, characterized by thickened ventricular walls and reduced ventricular chamber volume, is a common cause of sudden cardiac death in young people. Most inherited forms result from mutations in genes encoding sarcomeric proteins. METHODS: Histologic analysis identified embryonic cardiac hypertrophy in dark-like mutant mice. BrdU analysis was performed to measure proliferation and cardiomyocytes were isolated to measure cell size. The dark-like mutation was identified by positional cloning. RESULTS: The dark-like mutation causes cardiomyocyte hypertrophy due to loss-of-function of peptidase d (Pepd), which encodes prolidase, a cytosolic enzyme that recycles proline for collagen re-synthesis. Prolidase deficiency is a rare autosomal recessive disease in humans with a broad phenotypic spectrum not reported to include heart defects, but a conserved role for prolidase in heart development was confirmed by morpholino knockdown in zebrafish. We tested the hypothesis that loss of prolidase function disrupts collagen-mediated integrin signaling and determined that the levels of several key integrin transducers were reduced in the hearts of dark-like mutant embryos. CONCLUSIONS: This work identifies dark-like mice as a model of prolidase deficiency that will be valuable for studying the role of proline metabolism in normal physiology and disease processes, and suggests that integrin signaling may regulate the onset of hypertrophic cardiac growth. Birth Defects Research (Part A) 91:204-217, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Silvius, Derek; Gunn, Teresa M.] McLaughlin Res Inst, Great Falls, MT 59405 USA. [Jung, SeungWoo; Nolan, Katherine A.; Millet, Yoann H.; Gunn, Teresa M.] Cornell Univ, Dept Biomed Sci, Ithaca, NY USA. [Borchert, Gregory L.] Sci Applicat Int Corp, Basic Sci Program, Frederick, MD USA. [Phang, James M.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Gunn, TM (reprint author), McLaughlin Res Inst, 1520 23rd St S, Great Falls, MT 59405 USA. EM tmg@mri.montana.edu OI Gunn, Teresa/0000-0003-2688-6420 FU National Cancer Institute, National Institutes of Health [HHSN26120080001E]; National Institutes of Health, National Cancer Institute, Center for Cancer Research; Montana's Department of Commerce; M. J. Murdock Charitable Trust; Browning-Kimball Foundation; Oakland Family, Sletten Construction, Ian and Nancy Davidson, and others FX The authors thank Dr. Michael Kotlikoff for Tg(aMHC-GCaMP2) mice, Dr. Yvonne N. Tallini for assistance with calcium imaging, Dr. Joseph R. Fetcho and Jamien Shea for providing zebrafish embryos and training for morpholino injections, Dr. Kira Novakofski for assistance with phalloidin staining, and Dr. Marc Antonyak for providing antibodies against integrin pathway transducers. This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN26120080001E, and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States Government. Renovations to the McLaughlin Research Institute Animal Resource Center were funded by Montana's Department of Commerce, the M. J. Murdock Charitable Trust, the Browning-Kimball Foundation, the Oakland Family, Sletten Construction, Ian and Nancy Davidson, and others. NR 55 TC 3 Z9 3 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD APR PY 2011 VL 91 IS 4 BP 204 EP 217 DI 10.1002/bdra.20789 PG 14 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 751SC UT WOS:000289636900002 PM 21472842 ER PT J AU Lateef, T Swanson, S Cui, LH Nelson, K Nakamura, E Merikangas, K AF Lateef, Tarannum Swanson, Sonja Cui, Lihong Nelson, Karin Nakamura, Erin Merikangas, Kathleen TI Headaches and sleep problems among adults in the United States: Findings from the National Comorbidity Survey-Replication Study SO CEPHALALGIA LA English DT Article DE Headache; sleep; NCS-R; migraine ID TENSION-TYPE HEADACHE; GENERAL-POPULATION; AMERICAN MIGRAINE; FAMILY IMPACT; LIFE-STYLE; PREVALENCE; DISABILITY; BURDEN; HEALTH; COSTS AB Background: Several studies have demonstrated an association between headache and disturbed sleep. None have examined this association across the headache spectrum. Our goal was to determine whether migraine and migraine with aura differ from nonmigraine headache in terms of associated insomnia complaints or severity of sleep problems. Methods: A probability sample of US adults was used. A structured interview administered by trained interviewers was used. Diagnostic criteria for migraine and migraine with aura were based on the International Headache Society classification. The presence or absence of four forms of sleep disturbance associated with an insomnia diagnosis was ascertained. Results: There was a significant association between frequent severe headache, including migraine with and without aura, and disordered sleep. Adults with headache reported more frequently difficulty initiating sleep (odds ratio [confidence interval] = 2.0 [1.6-2.5]), difficulty staying asleep (2.5 [2.1-3]), early morning awakening (2.0 [1.7-2.5]) and daytime fatigue (2.6 [2.2-3.2]) and also were more than twice as likely to report three or more of these symptoms( 2.5 [2-3.1]) compared to the individuals without headache. Discussion: Adults with severe headache are at significantly higher risk of also suffering from sleep problems, when compared with the general population, regardless of specific headache type. Optimal treatment of headache must include investigation for sleep disorders and vice versa. C1 [Lateef, Tarannum] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, Washington, DC 20010 USA. [Lateef, Tarannum; Swanson, Sonja; Cui, Lihong; Nakamura, Erin; Merikangas, Kathleen] NIMH, Bethesda, MD 20894 USA. [Nelson, Karin] Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20824 USA. RP Lateef, T (reprint author), George Washington Univ, Childrens Natl Med Ctr, Sch Med, Dept Neurol, 111 Michigan Ave, Washington, DC 20010 USA. EM TLateef@cnmc.org NR 33 TC 23 Z9 23 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0333-1024 EI 1468-2982 J9 CEPHALALGIA JI Cephalalgia PD APR PY 2011 VL 31 IS 6 BP 648 EP 653 DI 10.1177/0333102410390395 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 750EP UT WOS:000289528100003 PM 21220375 ER PT J AU McAllister, DA MacNee, W Duprez, D Hoffman, EA Vogel-Claussen, J Criqui, MH Budoff, M Jiang, R Bluemke, DA Barr, RG AF McAllister, David A. MacNee, William Duprez, Daniel Hoffman, Eric A. Vogel-Claussen, Jens Criqui, Michael H. Budoff, Matthew Jiang, Rui Bluemke, David A. Barr, R. Graham TI Pulmonary Function is Associated with Distal Aortic Calcium, Not Proximal Aortic Distensibility. MESA Lung Study SO COPD-JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE Forced expiratory volume; Pulmonary emphysema; Aorta; Calcification; Compliance ID CARDIOVASCULAR RISK-FACTORS; ATHEROSCLEROSIS MESA; ARTERIAL STIFFNESS; REFERENCE VALUES; CORONARY-ARTERY; CARDIAC CT; DISEASE; CALCIFICATION; POPULATION; MEN AB Forced expiratory volume in one second strongly predicts mortality from cardiovascular disease. FEV(1) has been associated with aortic stiffness a strong independent predictor of cardiovascular mortality. However, the anatomical site and possible mechanisms linking aortic stiffness and lung function are unknown. We therefore examined if FEV(1) and CT percent emphysema were associated with calcification of the abdominal aorta or reduced distensibility of the proximal thoracic aorta. The Multi-Ethnic Study of Atherosclerosis (MESA) measured aortic calcification on cardiac and abdominal CT scans and proximal aortic distensibility using magnetic resonance among participants aged 45-84 years without clinical cardiovascular disease. Spirometry was measured following ATS/ERS guidelines and percent emphysema was measured in the lung fields of cardiac CT scans. Multivariate analyses adjusted for age, sex, race/ethnicity and cardiovascular risk factors. Of 1,917 participants with aortic distensibility measures, 13% were current and 38% were former smokers. Eighteen percent had airflow limitation without asthma. FEV1 was associated with the extent of distal aortic calcification (0.76; 95% CI 0.60-0.97, p = 0.02) but not proximal aortic calcification or proximal aortic distensibility (-0.04 mmHg(-1); 95% CI-0.16-0.09 mmHg(-1), p = 0.60). Percent emphysema was associated with neither measure. FEV1 was associated with severity of distal aortic calcification where it was present independently of smoking and other cardiovascular risk factors but not with distensibility or calcification of the proximal aorta. C1 [Barr, R. Graham] Columbia Univ, Med Ctr, Dept Med, Coll Phys & Surg, New York, NY 10032 USA. [McAllister, David A.; MacNee, William] Univ Edinburgh, MRC ELEGI Colt Labs, Edinburgh, Midlothian, Scotland. [Duprez, Daniel] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Hoffman, Eric A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. [Vogel-Claussen, Jens; Bluemke, David A.] NIH, Bethesda, MD 20892 USA. [Criqui, Michael H.] Univ Calif San Diego, Sch Med, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Budoff, Matthew] Harbor UCLA Med Ctr, Div Cardiol, Torrance, CA 90509 USA. [Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. RP Barr, RG (reprint author), Columbia Univ, Med Ctr, Dept Med, Coll Phys & Surg, PH 9 E Room 105,630 W 168th St, New York, NY 10032 USA. EM rgb9@columbia.edu OI MacNee, William/0000-0002-3692-1448; Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [R01-HL077612, R01-HL075476, N01-HC95159, HC95160, HC95161, HC95162, HC95163, HC95164, HC95165, N01-HC95169]; Chest, Heart and Stroke Scotland [R40329]; NHBLI [N01-HC-95159, N01-HC-95165, N01-HC-95169, R01 HL-077612, R01 HL-075476] FX Funding: National Institutes of Health R01-HL077612, R01-HL075476, N01-HC95159, HC95160, HC95161, HC95162, HC95163, HC95164, HC95165, N01-HC95169; Chest, Heart and Stroke Scotland R40329.; The MESA and MESA-Lung Studies are conducted and supported by the NHBLI (contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 and grants R01 HL-077612 and R01 HL-075476) in collaboration with the MESA and MESA-Lung Investigators. This manuscript has been reviewed by the MESA Investigators for scientific content and consistency of data interpretation with previous MESA publications and significant comments have been incorporated prior to submission for publication. David McAllister is supported by a Fellowship Grant from Chest, Heart and Stroke Scotland. The authors thank the other investigators, staff, and participants of the MESA and MESA-Lung Studies for their valuable contributions. The authors wish to thank Dr Firas Ahmed for his help with coding. A full list of participating MESA Investigators and institutions can be found at http://www.mesa-nhlbi.org. NR 35 TC 14 Z9 14 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1541-2555 J9 COPD JI COPD-J. Chronic Obstr. Pulm. Dis. PD APR PY 2011 VL 8 IS 2 BP 71 EP 78 DI 10.3109/15412555.2011.558543 PG 8 WC Respiratory System SC Respiratory System GA 750VZ UT WOS:000289577400004 PM 21495835 ER PT J AU Kim, W Doyle, ME Liu, Z Lao, QZ Shin, YK Carlson, OD Kim, HS Thomas, S Napora, JK Lee, EK Moaddel, R Wang, Y Maudsley, S Martin, B Kulkarni, RN Egan, JM AF Kim, Wook Doyle, Maire E. Liu, Zhuo Lao, Qizong Shin, Yu-Kyong Carlson, Olga D. Kim, Hee Seung Thomas, Sam Napora, Joshua K. Lee, Eun Kyung Moaddel, Ruin Wang, Yan Maudsley, Stuart Martin, Bronwen Kulkarni, Rohit N. Egan, Josephine M. TI Cannabinoids Inhibit Insulin Receptor Signaling in Pancreatic beta-Cells SO DIABETES LA English DT Article ID CB1 RECEPTORS; ENDOCANNABINOID DYSREGULATION; ENERGY-BALANCE; FOOD-INTAKE; IN-VIVO; MICE; SECRETION; GLUCOSE; RATS; OBESITY AB OBJECTIVE-Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting beta-cells in the islets of Langerhans. Insulin itself positively regulates beta-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway. It is now coining to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate beta-cell proliferation and if they influence insulin action. RESEARCH DESIGN AND METHODS-We measured EC production in isolated human and mouse islets and beta-cell line in response to glucose and KC1. We evaluated human and mouse islets, several beta-cell lines, and CB1R-null (CB1R(-/-)) mice for the presence of a fully functioning EC system. We investigated if ECs influence beta-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice. RESULTS-ECs are generated within beta-cells, which also express CB1Rs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CB1R results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in beta-cells and leads to increased beta-cell proliferation and mass. CB1R antagonism in db/db mice results in reduced blood glucose and increased beta-cell proliferation and mass, coupled with enhanced IR signaling in beta-cells. Furthermore, CB1R activation impedes insulin-stimulated IR autophosphorylation on beta-cells in a G alpha(i)-dependent manner. CONCLUSIONS-These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of beta-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance beta-cell function and proliferation in diabetes. Diabetes 60:1198-1209, 2011 C1 [Kim, Wook; Liu, Zhuo; Lao, Qizong; Shin, Yu-Kyong; Carlson, Olga D.; Kim, Hee Seung; Thomas, Sam; Napora, Joshua K.; Lee, Eun Kyung; Moaddel, Ruin; Wang, Yan; Maudsley, Stuart; Martin, Bronwen; Egan, Josephine M.] NIA, NIH, Baltimore, MD 21224 USA. [Doyle, Maire E.] Johns Hopkins Med Inst, Div Endocrinol, Baltimore, MD 21205 USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Egan, JM (reprint author), NIA, NIH, Baltimore, MD 21224 USA. EM eganj@grc.nia.nih.gov FU National Institute on Aging (NIA)/NIH; NIH [R01-DK-67536, 68721]; JDRF [26-2008-864] FX This work was supported by the Intramural Research Program of the National Institute on Aging (NIA)/NIH. R.N.K. is supported by NIH R01-DK-67536 and 68721. M.E.D. is supported by JDRF 26-2008-864. NR 47 TC 49 Z9 49 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2011 VL 60 IS 4 BP 1198 EP 1209 DI 10.2337/db10-1550 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 749UK UT WOS:000289496100015 PM 21346174 ER PT J AU Kraja, AT Vaidya, D Pankow, JS Goodarzi, MO Assimes, TL Kullo, IJ Sovio, U Mathias, RA Sun, YV Franceschini, N Absher, D Li, G Zhang, QY Feitosa, MF Glazer, NL Haritunians, T Hartikainen, AL Knowles, JW North, KE Iribarren, C Kral, B Yanek, L O'Reilly, PF McCarthy, MI Jaquish, C Couper, DJ Chakravarti, A Psaty, BM Becker, LC Province, MA Boerwinkle, E Quertermous, T Palotie, L Jarvelin, MR Becker, DM Kardia, SLR Rotter, JI Chen, YDI Borecki, IB AF Kraja, Aldi T. Vaidya, Dhananjay Pankow, James S. Goodarzi, Mark O. Assimes, Themistocles L. Kullo, Iftikhar J. Sovio, Ulla Mathias, Rasika A. Sun, Yan V. Franceschini, Nora Absher, Devin Li, Guo Zhang, Qunyuan Feitosa, Mary F. Glazer, Nicole L. Haritunians, Talin Hartikainen, Anna-Liisa Knowles, Joshua W. North, Kari E. Iribarren, Carlos Kral, Brian Yanek, Lisa O'Reilly, Paul F. McCarthy, Mark I. Jaquish, Cashell Couper, David J. Chakravarti, Aravinda Psaty, Bruce M. Becker, Lewis C. Province, Michael A. Boerwinkle, Eric Quertermous, Thomas Palotie, Leena Jarvelin, Marjo-Riitta Becker, Diane M. Kardia, Sharon L. R. Rotter, Jerome I. Chen, Yii-Der Ida Borecki, Ingrid B. TI A Bivariate Genome-Wide Approach to Metabolic Syndrome STAMPEED Consortium SO DIABETES LA English DT Article ID CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; FASTING PLASMA-GLUCOSE; TYPE-2 DIABETES RISK; INSULIN-RESISTANCE; APOLIPOPROTEIN A5; HDL CHOLESTEROL; HEART-DISEASE; MEXICAN-AMERICANS; BLOOD-PRESSURE AB OBJECTIVE-The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS-Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of similar to 2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS-Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from similar to 9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS-Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants. Diabetes 60:1329-1339, 2011 C1 [Kraja, Aldi T.; Zhang, Qunyuan; Feitosa, Mary F.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63101 USA. [Vaidya, Dhananjay; Mathias, Rasika A.; Kral, Brian; Yanek, Lisa; Becker, Lewis C.; Becker, Diane M.] Johns Hopkins Univ, GeneSTAR Res Program, Baltimore, MD USA. [Pankow, James S.] Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. [Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Kullo, Iftikhar J.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [Sovio, Ulla] London Sch Hyg & Trop Med, Dept Med Stat, London WC1, England. [Sun, Yan V.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Li, Guo; Glazer, Nicole L.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Li, Guo; Glazer, Nicole L.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Haritunians, Talin; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Hartikainen, Anna-Liisa] Univ Oulu, Inst Clin Med, Oulu, Finland. [North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Iribarren, Carlos] Kaiser Fdn Res Inst, Oakland, CA USA. [O'Reilly, Paul F.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Biostat & Epidemiol, Sch Publ Hlth, Fac Med, London, England. [McCarthy, Mark I.] Univ Oxford, Churchill Hosp, OCDEM, Oxford, England. [Jaquish, Cashell] NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. [Couper, David J.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Couper, David J.] Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. [Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Seattle, WA USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Palotie, Leena] Wellcome Trust Sanger Inst, Cambridge, England. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland. [Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland. [Chen, Yii-Der Ida] Univ Calif Los Angeles, Los Angeles, CA USA. RP Kraja, AT (reprint author), Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63101 USA. EM aldi@wustl.edu RI Sun, Yan/A-7461-2008; Li, Guo/E-5613-2012; Knowles, Josh/C-9241-2013; Feitosa, Mary/K-8044-2012; OI Feitosa, Mary/0000-0002-0933-2410; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vaidya, Dhananjay/0000-0002-7164-1601 FU National Institutes of Health (NIH) [STAMPEED HL-087700, ADVANCE 5R01-HL-087647, ARIC U01-HL-075572, CHS HL-087652, FHS HL-0877700, GeneSTAR 5R01-HL-087698, GENOA HL-087660, NFBC1RL1-MH-083268-01, HHSN268200625226C, UL1-RR-025005]; NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018]; National Human Genome Research Institute [U01HG004402]; National Institute of Neurologic Disorders and Stroke; National Center for Research Resources [M01RR00425]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-063491]; Academy of Finland, Center of Excellence in Complex Disease Genetics [104781, 120315]; University Hospital Oulu, Biocenter; University of Oulu, Finland; European Commission [QLG1-CT-2000-01643]; NIH/NIMH [5R01-MH-63706:02]; ENGAGE [HEALTH-F4-2007-201413]; Medical Research Council [G0500539]; Academy of Finland and Biocentrum Helsinki FX This collaborative work was supported in part by the National Institutes of Health (NIH) grants STAMPEED HL-087700, ADVANCE 5R01-HL-087647, ARIC U01-HL-075572, CHS HL-087652, FHS HL-0877700, GeneSTAR 5R01-HL-087698, GENOA HL-087660, and NFBC1RL1-MH-083268-01.; The ARIC Study is carried out as a collaborative study supported by NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL-087641, R01-HL-59367, and R01-HL-086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1-RR-025005, a component of the NIH and NIH Roadmap for Medical Research.; The CHS research reported in this article was supported by contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01-HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, grant numbers U01-HL-080295 and R01-HL-087652 from the NHLBI, with additional contribution from the National Institute of Neurologic Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. DNA handling and genotyping was supported in part by National Center for Research Resources Grant M01RR00425 to the Cedars-Sinai General Clinical Research Center Genotyping core and National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-063491 to the Southern California Diabetes Endocrinology Research Center.; The NFBC 1966 study received financial support from the Academy of Finland (project grants 104781, 120315, and Center of Excellence in Complex Disease Genetics); University Hospital Oulu, Biocenter; University of Oulu, Finland; the European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643); NHLBI Grant 5R01-HL-087679-02 through the STAMPEED program (1RL1MH083268-01); NIH/NIMH (5R01-MH-63706:02); ENGAGE project and grant agreement HEALTH-F4-2007-201413; and the Medical Research Council (studentship grant G0500539). The DNA extractions, sample quality controls, biobank upkeeping, and aliquoting were performed in the National Public Health Institute, Biomedicum Helsinki, Finland and supported financially by the Academy of Finland and Biocentrum Helsinki. NR 50 TC 105 Z9 107 U1 1 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2011 VL 60 IS 4 BP 1329 EP 1339 DI 10.2337/db10-1011 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 749UK UT WOS:000289496100029 PM 21386085 ER PT J AU Hivert, MF Jablonski, KA Perreault, L Saxena, R McAteer, JB Franks, PW Hamman, RF Kahn, SE Haffner, S Meigs, JB Altshuler, D Knowler, WC Florez, JC AF Hivert, Marie-France Jablonski, Kathleen A. Perreault, Leigh Saxena, Richa McAteer, Jarred B. Franks, Paul W. Hamman, Richard F. Kahn, Steven E. Haffner, Steven Meigs, James B. Altshuler, David Knowler, William C. Florez, Jose C. CA DIAGRAM Consortium Diabet Prevention Program Res Grp TI Updated Genetic Score Based on 34 Confirmed Type 2 Diabetes Loci Is Associated With Diabetes Incidence and Regression to Normoglycemia in the Diabetes Prevention Program SO DIABETES LA English DT Article ID GENOME-WIDE ASSOCIATION; LIFE-STYLE INTERVENTION; INSULIN-RESISTANCE; COMMON VARIANTS; SUSCEPTIBILITY LOCI; RISK-FACTORS; GLUCOSE; RECLASSIFICATION; POLYMORPHISMS; MELLITUS AB OBJECTIVE Over 30 loci have been associated with risk of type 2 diabetes at genome-wide statistical significance. Genetic risk scores (GRSs) developed from these loci predict diabetes in the general population. We tested if a GRS based on an updated list of 34 type 2 diabetes-associated loci predicted progression to diabetes or regression toward normal glucose regulation (NGR) in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS We genotyped 34 type 2 diabetes-associated variants in 2,843 DPP participants at high risk of type 2 diabetes from five ethnic groups representative of the U.S. population, who had been randomized to placebo, metformin, or lifestyle intervention. We built a GRS by weighting each risk allele by its reported effect size on type 2 diabetes risk and summing these values. We tested its ability to predict diabetes incidence or regression to NGR in models adjusted for age, sex, ethnicity, waist circumference, and treatment assignment. RESULTS lit multivariate-adjusted models, the GRS was significantly associated with increased risk of progression to diabetes (hazard ratio [HR] = 1.02 per risk allele [95% CI 1.00-1.05]; P = 0.03) and a lower probability of regression to NGR (HR = 0.95 per risk allele [95% CI 0.93-0.981; P < 0.0001). At baseline, a higher GRS was associated with a lower insulinogenic index (P < 0.001), confirming an impairment in beta-cell function. We detected no significant interaction between GRS and treatment, but the lifestyle intervention was effective in the highest quartile of ORS (P < 0.0001). CONCLUSIONS A high GRS is associated with increased risk of developing diabetes and lower probability of returning to NGR in high-risk individuals, but a lifestyle intervention attenuates this risk. Diabetes 60:1340-1348, 2011 C1 [Saxena, Richa; McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [Jablonski, Kathleen A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Perreault, Leigh] Univ Colorado Denver Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Aurora, CO USA. [Saxena, Richa; McAteer, Jarred B.; Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Franks, Paul W.] Umea Univ Hosp, Dept Publ Hlth & Clin Med, Div Med, Genet Epidemiol & Clin Res Grp, S-90185 Umea, Sweden. [Franks, Paul W.] Lund Univ, Ctr Diabet, Dept Clin Sci, Malmo, Sweden. [Hamman, Richard F.] Univ Colorado Denver, Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA. [Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA. [Haffner, Steven] Baylor Coll Med, Houston, TX 77030 USA. [Meigs, James B.] Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. [Meigs, James B.; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Knowler, William C.] NIDDKD, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM jcflorez@partners.org RI Altshuler, David/A-4476-2009; Boehm, Bernhard/F-8750-2015; OI Altshuler, David/0000-0002-7250-4107; Griffin, Simon/0000-0002-2157-4797; Franks, Paul/0000-0002-0520-7604; Kahn, Steven/0000-0001-7307-9002 FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK [K24 DK080140]; Indian Health Service; National Center for Research Resources; Department of Veterans Affairs; Massachusetts General Hospital; Doris Duke Charitable Foundation; Swedish Research Council; Novo Nordisk; Swedish Diabetes Association; Swedish Heart-Lung Foundation; GlaxoSmithKline; [R01 DK072041] FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the Coordinating Center for the design and conduct of the study, and the collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women's Health, the Centers for Disease Control and Prevention, and the American Diabetes Association. This research was also supported, in part, by the intramural research program of the NIDDK.; This work was also funded by R01 DK072041 (to D.A., J.C.F., and K.A.J.). J.C.F. is also supported by Massachusetts General Hospital and a Clinical Scientist Development Award by the Doris Duke Charitable Foundation. This work was partially supported by a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award to D.A. J.B.Me. is supported by NIDDK K24 DK080140. P.W.F. was supported by the Swedish Research Council, Novo Nordisk, the Swedish Diabetes Association, and the Swedish Heart-Lung Foundation. J.B.Me. currently has a research grant from GlaxoSmithKline and serves on a consultancy board for Interleukin Genetics. J.C.F. has received consulting honoraria from Daiichi-Sankyo and AstraZeneca. NR 33 TC 77 Z9 78 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD APR PY 2011 VL 60 IS 4 BP 1340 EP 1348 DI 10.2337/db10-1119 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 749UK UT WOS:000289496100030 PM 21378175 ER PT J AU Wilson, PWF D'Agostino, RB Fox, CS Sullivan, LM Meigs, JB AF Wilson, Peter W. F. D'Agostino, Ralph B. Fox, Caroline S. Sullivan, Lisa M. Meigs, James B. TI Type 2 diabetes risk in persons with dysglycemia: The Framingham Offspring Study SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Dysglycemia; Type 2 diabetes mellitus; Prospective cohort study; Risk prediction; Metabolic syndrome ID GLUCOSE-TOLERANCE TEST; INSULIN-RESISTANCE; METABOLIC SYNDROME; FASTING GLUCOSE; LIFE-STYLE; MELLITUS; PREDICTION; ATHEROSCLEROSIS; ADULTS AB Aims: Detection of risk of type 2 diabetes mellitus (T2DM) among adults with dysglycemia. Methods: We used a nested case-cohort prospective design to estimate risk of new diabetes (diabetes treatment or FPG >= 7.0 mmol/L) among 1004 Framingham Heart Study Offspring with baseline dysglycemia [ fasting plasma glucose (FPG) 5.4-6.9 mmol/L and/or 2-h post glucose load level 7.8-11.0 mmol/L]. Using clinical characteristics previously shown to predict incident T2DM, we used logistic regression to estimate odds ratios (OR), p-values for predictors, and assessment of model discrimination. Results: At the end of 7 years follow-up there were 118 incident T2DM cases. In a model that included age, sex, elevated blood pressure or blood pressure treatment, lipid-lowering treatment and elevated triglycerides, we found the following additional characteristics to be independently associated with new T2DM: parental history of diabetes (OR 2.28, p = 0.004); excess adiposity (BMI >= 30 kg/m(2) or waist circumference >= 101.6 cm) (OR 2.04, p = 0.0005), and low HDL-C [<1.0 (men) or <1.3 mmol/L (women)] (OR 2.77, p < 0.0001). The multivariable C-statistic for this model was 0.701, and with glycemic category information included, c = 0.751. Conclusions: The key non-glycemic traits that predicted later T2DM in adults with dysglycemia were parental history of diabetes, excess adiposity and low HDL-C. (C) 2010 Published by Elsevier Ireland Ltd. C1 [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, EPICORE, Atlanta, GA 30322 USA. [Wilson, Peter W. F.] Atlanta VAMC Epidemiol & Genet Sect, Atlanta, GA 30306 USA. [D'Agostino, Ralph B.] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. EM jmeigs@partners.org RI Library, Woodruff Health/A-6096-2012; OI Sullivan, Lisa/0000-0003-0726-7149 FU NIDDK NIH HHS [K24 DK080140-03, K24 DK080140] NR 14 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD APR PY 2011 VL 92 IS 1 BP 124 EP 127 DI 10.1016/j.diabres.2010.12.024 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 750OR UT WOS:000289558300027 PM 21242014 ER PT J AU Fath, T Fischer, RS Dehmelt, L Halpain, S Fowler, VM AF Fath, Thomas Fischer, Robert S. Dehmelt, Leif Halpain, Shelley Fowler, Velia M. TI Tropomodulins are negative regulators of neurite outgrowth SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE Tropomodulin; F-actin; Neurite outgrowth; N2a mouse neuroblastoma cells; Cultured hippocampal neurons ID GROWTH CONE MOTILITY; POINTED ENDS; TROPOMYOSIN ISOFORMS; CARDIAC MYOCYTES; ACTIN-FILAMENTS; BINDING-PROTEIN; SKELETAL-MUSCLE; THIN-FILAMENTS; LIM KINASE; MICE AB Regulation of the actin cytoskeleton is critical for neurite formation. Tropomodulins (Tmods) regulate polymerization at actin filament pointed ends. Previous experiments using a mouse model deficient for the neuron specific isoform Tmod2 suggested a role for Tmods in neuronal function by impacting processes underlying learning and memory. However, the role of Tmods in neuronal function on the cellular level remains unknown. Immunofluorescence localization of the neuronal isoforms Tmod1 and Tmod2 in cultured rat primary hippocampal neurons revealed that Tmod1 is enriched along the proximal part of F-actin bundles in lamellipodia of spreading cells and in growth cones of extending neurites, while Tmod2 appears largely cytoplasmic. Functional analysis of these Tmod isoforms in a mouse neuroblastoma N2a cell line showed that knockdown of Tmod2 resulted in a significant increase in the number of neurite-forming cells and in neurite length. While N2a cells compensated for Tmod2 knockdown by increasing Tmod1 levels, over-expression of exogenous Tmod1 had no effect on neurite outgrowth. Moreover, knockdown of Tmod1 increased the number of neurites formed per cell, without effect on the number of neurite-forming cells or neurite length. Taken together, these results indicate that Tmodl1 and Tmod2 have mechanistically distinct inhibitory roles in neurite formation, likely mediated via different effects on F-actin dynamics and via differential localizations during early neuritogenesis. (C) 2010 Elsevier GmbH. All rights reserved. C1 [Fath, Thomas] Univ New S Wales, Sch Med Sci, Sydney, NSW 2052, Australia. [Fischer, Robert S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Dehmelt, Leif] Max Planck Inst Mol Physiol, Dept Systemat Cell Biol, D-44227 Dortmund, Germany. [Halpain, Shelley] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92037 USA. [Fowler, Velia M.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. RP Fath, T (reprint author), Univ New S Wales, Sch Med Sci, Wallace Wurth Bldg C27,Rm502, Sydney, NSW 2052, Australia. EM t.fath@unsw.edu.au; velia@scripps.edu OI Fath, Thomas/0000-0002-6877-7567 FU NIGMS NIH HHS [R01 GM034225-18, R01 GM034225]; NIMH NIH HHS [R01 MH087823] NR 50 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0171-9335 EI 1618-1298 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD APR PY 2011 VL 90 IS 4 BP 291 EP 300 DI 10.1016/j.ejcb.2010.10.014 PG 10 WC Cell Biology SC Cell Biology GA 748JR UT WOS:000289387400002 PM 21146252 ER PT J AU Milaneschi, Y Bandinelli, S Corsi, AM Lauretani, F Paolisso, G Dominguez, LJ Semba, RD Tanaka, T Abbatecola, AM Talegawkar, SA Guralnik, JM Ferrucci, L AF Milaneschi, Yuri Bandinelli, Stefania Corsi, Anna Maria Lauretani, Fabrizio Paolisso, Giuseppe Dominguez, Ligia J. Semba, Richard D. Tanaka, Toshiko Abbatecola, Angela M. Talegawkar, Sameera A. Guralnik, Jack M. Ferrucci, Luigi TI Mediterranean diet and mobility decline in older persons SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE Mediterranean diet; Mobility; SPPB; Aging ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE; RANDOMIZED-TRIAL; SKELETAL-MUSCLE; STYLE DIET; DISABILITY; INCHIANTI; CAROTENOIDS; ADHERENCE; COHORT AB We examined whether adherence to a Mediterranean-style diet has positive effects on mobility assessed over a 9-year follow-up in a representative sample of older adults. This research is part of the InCHIANTI Study, a prospective population-based study of older persons in Tuscany, Italy. The sample for this analysis included 935 women and men aged 65 years and older. Adherence to the Mediterranean diet was assessed at baseline by the standard 10-unit Mediterranean diet score (MDS). Lower extremity function was measured at baseline, and at the 3-, 6- and 9-year follow-up visits using the short physical performance battery (SPPB). At baseline, higher adherence to Mediterranean diet was associated with better lower body performance. Participants with higher adherence experienced less decline in SPPB score, which was of 0.9 points higher (p<.0001) at the 3-year-follow, 1.1 points higher (p=0.0004) at the 6-year follow-up and 0.9 points higher (p = 0.04) at the 9-year follow-up compared to those with lower adherence. Among participants free of mobility disability at baseline, those with higher adherence had a lower risk (HR = 0.71, 95% CI = 0.51-0.98, p = 0.04) of developing new mobility disability. High adherence to a Mediterranean-style diet is associated with a slower decline of mobility over time in community-dwelling older persons. If replicated, this observation is highly relevant in terms of public health. Published by Elsevier Inc. C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Baltimore, MD 21225 USA. [Bandinelli, Stefania] ASF, Geriatr Unit, Florence, Italy. [Corsi, Anna Maria; Lauretani, Fabrizio] Tuscany Hlth Reg Agcy, Florence, Italy. [Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr Med & Metab Dis, Naples, Italy. [Dominguez, Ligia J.] Univ Palermo, Geriatr Unit, Palermo, Italy. [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Tanaka, Toshiko] Medstar Hlth Res Inst, Baltimore, MD USA. [Abbatecola, Angela M.] INRCA Ancona, Ancona, Italy. [Talegawkar, Sameera A.] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, Harbor Hosp Ctr, Room NM540,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov OI Paolisso, Giuseppe/0000-0002-2137-455X; dominguez, ligia j/0000-0003-1466-8610 FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institute on Aging, National Institutes of Health FX "The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002); supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health. NR 35 TC 31 Z9 31 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 2011 VL 46 IS 4 BP 303 EP 308 DI 10.1016/j.exger.2010.11.030 PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 751GJ UT WOS:000289605200012 PM 21111801 ER PT J AU Gao, B Bertola, A AF Gao, Bin Bertola, Adeline TI Natural Killer Cells Take Two Tolls to Destruct Bile Ducts SO HEPATOLOGY LA English DT Editorial Material ID NK CELLS; CYTOKINE PRODUCTION; LIVER-DISEASE; KUPFFER CELLS; RECEPTOR 4; PIT CELL; HEPATITIS; LIGANDS; INJURY; CYTOTOXICITY C1 [Gao, Bin; Bertola, Adeline] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov OI Bertola, Adeline/0000-0002-4885-8423 FU Intramural NIH HHS [Z99 AA999999, ZIA AA000368-11, ZIA AA000369-11] NR 27 TC 6 Z9 7 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1076 EP 1079 DI 10.1002/hep.24275 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600002 PM 21384404 ER PT J AU Di Bisceglie, AM Stoddard, AM Dienstag, JL Shiffman, ML Seeff, LB Bonkovsky, HL Morishima, C Wright, EC Snow, KK Lee, WM Fontana, RJ Morgan, TR Ghany, MG AF Di Bisceglie, Adrian M. Stoddard, Anne M. Dienstag, Jules L. Shiffman, Mitchell L. Seeff, Leonard B. Bonkovsky, Herbert L. Morishima, Chihiro Wright, Elizabeth C. Snow, Kristin K. Lee, William M. Fontana, Robert J. Morgan, Timothy R. Ghany, Marc G. CA HALT-C Trial Grp TI Excess Mortality in Patients with Advanced Chronic Hepatitis C Treated with Long-Term Peginterferon SO HEPATOLOGY LA English DT Article ID COMPENSATED CIRRHOSIS; CLINICAL-OUTCOMES; NATURAL-HISTORY; VIRUS-INFECTION; PLUS RIBAVIRIN; THERAPY; INTERFERON; MANAGEMENT; MORBIDITY; ALPHA-2B AB Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver-or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (HEPATOLOGY 2011;53:1100-1108) C1 [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, St Louis, MO 63104 USA. [Stoddard, Anne M.; Snow, Kristin K.] New England Res Inst, Watertown, MA 02172 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Seeff, Leonard B.] NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Seeff, Leonard B.; Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. [Wright, Elizabeth C.] NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. RP Di Bisceglie, AM (reprint author), St Louis Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, 1402 S Grand Blvd, St Louis, MO 63104 USA. EM dibiscam@slu.edu FU National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); National Institute of Allergy and Infectious Diseases (NIAID); National Cancer Institute; National Center for Minority Health and Health Disparities; National Center for Research Resources; National Institutes of Health (NIH); Genentech; Novartis; Vertex; Merck FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK contract numbers are listed in the Appendix). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute; the National Center for Minority Health and Health Disparities; by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (NIH grant numbers are listed in the Appendix); and by the Intramural Research Program of the NIH, NIDDK (M. G. Ghany). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc. (now Genentech) through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.; Dr. Bonkovsky consults for and advises Boehringer-Ingelheim and Novartis and received grants from Novartis and Vertex.; Dr. Morgan received grants from Merck, Genentech, and Vertex. He consults for and advises Vertex. NR 23 TC 41 Z9 42 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1100 EP 1108 DI 10.1002/hep.24169 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600005 PM 21480316 ER PT J AU Matsubara, T Tanaka, N Patterson, AD Cho, JY Krausz, KW Gonzalez, FJ AF Matsubara, Tsutomu Tanaka, Naoki Patterson, Andrew D. Cho, Joo-Youn Krausz, Kristopher W. Gonzalez, Frank J. TI Lithocholic Acid Disrupts Phospholipid and Sphingolipid Homeostasis Leading to Cholestasis in Mice SO HEPATOLOGY LA English DT Article ID INDUCED LIVER TOXICITY; NECROSIS-FACTOR-ALPHA; BILE-ACID; HYDROXYSTEROID SULFOTRANSFERASE; ATHEROGENIC LIPOPROTEINS; HEPATOCYTE APOPTOSIS; BILIARY OBSTRUCTION; MASS-SPECTROMETRY; PROTECTIVE ROLE; CELL-DEATH AB Lithocholic acid (LCA) is an endogenous compound associated with hepatic toxicity during cholestasis. LCA exposure in mice resulted in decreased serum lysophosphatidylcholine (LPC) and sphingomyelin levels due to elevated lysophosphatidylcholine acyltransferase (LPCAT) and sphingomyelin phosphodiesterase (SMPD) expression. Global metabolome analysis indicated significant decreases in serum palmitoyl-, stearoyl-, oleoyl-, and linoleoyl-LPC levels after LCA exposure. LCA treatment also resulted in decreased serum sphingomyelin levels and increased hepatic ceramide levels, and induction of LPCAT and SMPD messenger RNAs (mRNAs). Transforming growth factor-beta (TGF-beta) induced Lpcat2/4 and Smpd3 gene expression in primary hepatocytes and the induction was diminished by pretreatment with the SMAD3 inhibitor SIS3. Furthermore, alteration of the LPCs and Lpcat1/2/4 and Smpd3 expression was attenuated in LCA-treated farnesoid X receptor-null mice that are resistant to LCA-induced intrahepatic cholestasis. Conclusion: This study revealed that LCA induced disruption of phospholipid/sphingolipid homeostasis through TGF-beta signaling and that serum LPC is a biomarker for biliary injury. (HEPATOLOGY 2011;53:1282-1293) C1 [Matsubara, Tsutomu; Tanaka, Naoki; Patterson, Andrew D.; Cho, Joo-Youn; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov RI Patterson, Andrew/G-3852-2012; Cho, Joo-Youn/J-5672-2012 OI Patterson, Andrew/0000-0003-2073-0070; FU Center for Cancer Research; Japanese Society for the Promotion of Science FX Supported by the National Cancer Institute Intramural Research Program, Center for Cancer Research. T. M. was supported by a fellowship from the Japanese Society for the Promotion of Science. NR 56 TC 28 Z9 29 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1282 EP 1293 DI 10.1002/hep.24193 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600023 PM 21480330 ER PT J AU Jeong, WI Park, O Suh, YG Byun, JS Park, SY Choi, E Kim, JK Ko, H Wang, H Miller, AM Gao, B AF Jeong, Won-Il Park, Ogyi Suh, Yang-Gun Byun, Jin-Seok Park, So-Young Choi, Earl Kim, Ja-Kyung Ko, Hyojin Wang, Hua Miller, Andrew M. Gao, Bin TI Suppression of Innate Immunity (Natural Killer Cell/Interferon-gamma) in the Advanced Stages of Liver Fibrosis in Mice SO HEPATOLOGY LA English DT Article ID HEPATIC STELLATE CELLS; INTERFERON-GAMMA; RETINOIC ACID; LIPOCYTE ACTIVATION; NK; METABOLISM; INJURY; INHIBITION; INFECTION; CIRRHOSIS AB Activation of innate immunity (natural killer [NK] cell/interferon-gamma [IFN-gamma]) has been shown to play an important role in antiviral and antitumor defenses as well as antifibrogenesis. However, little is known about the regulation of innate immunity during chronic liver injury. Here, we compared the functions of NK cells in early and advanced liver fibrosis induced by a 2-week or a 10-week carbon tetrachloride (CCl4) challenge, respectively. Injection of polyinosinic-polycytidylic acid (poly I:C) or IFN-gamma induced NK cell activation and NK cell killing of hepatic stellate cells (HSCs) in the 2-week CCl4 model. Such activation was diminished in the 10-week CCl4 model. Consistent with these findings, the inhibitory effect of poly I:C and IFN-gamma on liver fibrosis was markedly reduced in the 10-week versus the 2-week CCl4 model. In vitro coculture experiments demonstrated that 4-day cultured (early activated) HSCs induce NK cell activation via an NK group 2 member D/retinoic acid-induced early gene 1-dependent mechanism. Such activation was reduced when cocultured with 8-day cultured (intermediately activated) HSCs due to the production of transforming growth factor-beta (TGF-beta) by HSCs. Moreover, early activated HSCs were sensitive, whereas intermediately activated HSCs were resistant to IFN-gamma-mediated inhibition of cell proliferation, likely due to elevated expression of suppressor of cytokine signaling 1 (SOCS1). Disruption of the SOCS1 gene restored the IFN-gamma inhibition of cell proliferation in intermediately activated HSCs. Production of retinol metabolites by HSCs contributed to SOCS1 induction and subsequently inhibited IFN-c signaling and functioning, whereas production of TGF-beta by HSCs inhibited NK cell function and cytotoxicity against HSCs. Conclusion: The antifibrogenic effects of NK cell/IFN-gamma are suppressed during advanced liver injury, which is likely due to increased production of TGF-beta and expression of SOCS1 in intermediately activated HSCs. (HEPATOLOGY 2011;53:1342-1351) C1 [Jeong, Won-Il] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Liver Res, Taejon 305701, South Korea. [Kim, Ja-Kyung] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Ko, Hyojin] Gwangju Inst Sci & Technol, Kwangju, South Korea. [Jeong, Won-Il; Park, Ogyi; Wang, Hua; Miller, Andrew M.; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. RP Jeong, WI (reprint author), Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Liver Res, Bldg E7,Room 8107,373-1 Guseong Dong, Taejon 305701, South Korea. EM wijeong@kaist.ac.kr RI JEONG, WON IL/B-6615-2011 FU Ministry for Health, Welfare, and Family Affairs, Republic of Korea [A090292]; National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health FX Supported in part by a grant from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare, and Family Affairs, Republic of Korea (A090292), and the intramural program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health. NR 27 TC 44 Z9 47 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD APR PY 2011 VL 53 IS 4 BP 1342 EP 1351 DI 10.1002/hep.24190 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 748VA UT WOS:000289419600029 PM 21480338 ER PT J AU Venkataraman, G Raffeld, M Pittaluga, S Jaffe, ES AF Venkataraman, Girish Raffeld, Mark Pittaluga, Stefania Jaffe, Elaine S. TI CD15-expressing nodular lymphocyte-predominant Hodgkin lymphoma SO HISTOPATHOLOGY LA English DT Letter ID EUROPEAN TASK-FORCE; PROJECT; DISEASE C1 [Venkataraman, Girish; Raffeld, Mark; Pittaluga, Stefania; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Venkataraman, G (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Venkataraman, Girish/0000-0002-8674-2608; Jaffe, Elaine/0000-0003-4632-0301 FU Intramural NIH HHS NR 6 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD APR PY 2011 VL 58 IS 5 BP 803 EP 805 DI 10.1111/j.1365-2559.2011.03829.x PG 3 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 749KQ UT WOS:000289465400020 PM 21457163 ER PT J AU Chandler, RJ Chandrasekaran, S Carrillo-Carrasco, N Senac, JS Hofherr, SE Barry, MA Venditti, CP AF Chandler, Randy J. Chandrasekaran, Suma Carrillo-Carrasco, Nuria Senac, Julien S. Hofherr, Sean E. Barry, Michael A. Venditti, Charles P. TI Adeno-Associated Virus Serotype 8 Gene Transfer Rescues a Neonatal Lethal Murine Model of Propionic Acidemia SO HUMAN GENE THERAPY LA English DT Article ID METHYLMALONIC ACIDEMIA; LIVER-TRANSPLANTATION; MOUSE MODEL; CARDIOMYOPATHY; URINE; SERUM AB Propionic acidemia (PA) is an autosomal recessive disorder of metabolism caused by a deficiency of propionylcoenzyme A carboxylase (PCC). Despite optimal dietary and cofactor therapy, PA patients still suffer from lethal metabolic instability and experience multisystemic complications. A murine model of PA (Pcca(-/-)) of animals that uniformly die within the first 48 hr of life was used to determine the efficacy of adeno-associated viral (AAV) gene transfer as a potential therapy for PA. An AAV serotype 8 (AAV8) vector was engineered to express the human PCCA cDNA and delivered to newborn mice via an intrahepatic injection. Greater than 64% of the Pcca(-/-) mice were rescued after AAV8-mediated gene transfer and survived until day of life 16 or beyond. Western analysis of liver extracts showed that PCC was completely absent from Pcca(-/-) mice but was restored to greater than wild-type levels after AAV gene therapy. The treated Pcca(-/-) mice also exhibited markedly reduced plasma levels of 2-methylcitrate compared with the untreated Pcca(-/-) mice, which indicates significant PCC enzymatic activity was provided by gene transfer. At the time of this report, the oldest treated Pcca(-/-) mice are over 6 months of age. In summary, AAV gene delivery of PCCA effectively rescues Pcca(-/-) mice from neonatal lethality and substantially ameliorates metabolic markers of the disease. These experiments demonstrate a gene transfer approach using AAV8 that might be used as a treatment for PA, a devastating and often lethal disorder desperately in need of new therapeutic options. C1 [Chandler, Randy J.; Chandrasekaran, Suma; Carrillo-Carrasco, Nuria; Senac, Julien S.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Chandler, Randy J.] George Washington Univ, Inst Biomed Sci, Washington, DC 20037 USA. [Hofherr, Sean E.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Barry, Michael A.] Mayo Clin, Div Infect Dis, Dept Internal Med, Dept Immunol,Translat Immunovirol Program, Rochester, MN 55905 USA. [Barry, Michael A.] Mayo Clin, Program Mol Med, Rochester, MN 55905 USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov RI Carrillo-Carrasco, Nuria/B-9034-2009 OI Carrillo-Carrasco, Nuria/0000-0003-0374-0808 FU National Human Genome Research Institute, National Institutes of Health; MMA Research Foundation/Angels for Alyssa Fund; Propionic Acidemia Foundation FX R.J.C., S.C., N.C.C., J.S.S., and C.P.V. were supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health and also graciously acknowledge research support and encouragement from the MMA Research Foundation/Angels for Alyssa Fund. Thanks to the National Human Genome Research Institute mouse core for mouse care and technical assistance. S. H. and M. A. B. were supported, in part, by the Propionic Acidemia Foundation. NR 21 TC 14 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2011 VL 22 IS 4 BP 477 EP 481 DI 10.1089/hum.2010.164 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 748SD UT WOS:000289410600010 PM 20950151 ER PT J AU Fan, BJ Pasquale, LR Rhee, D Li, TS Haines, JL Wiggs, JL AF Fan, Bao Jian Pasquale, Louis R. Rhee, Douglas Li, Tiansen Haines, Jonathan L. Wiggs, Janey L. TI LOXL1 Promoter Haplotypes Are Associated with Exfoliation Syndrome in a US Caucasian Population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID OPEN-ANGLE GLAUCOMA; UNITED-STATES POPULATION; COMMON SEQUENCE VARIANTS; PSEUDOEXFOLIATION SYNDROME; GENE POLYMORPHISMS; JAPANESE POPULATION; PREVALENCE; CHINESE; PEOPLE; SYNDROME/GLAUCOMA AB PURPOSE. LOXL1 is a major genetic risk factor for exfoliation syndrome (ES) and exfoliation glaucoma (EG). Recent evidence documenting reversal of risk alleles for the disease-associated missense variants R141L and G153D suggests that these variants are not causative and that they may be proxies for other unknown functional LOXL1 variants. The purpose of this study was to investigate the disease association of LOXL1 variants spanning the gene region, including the 5' and 3' regulatory regions, in a U.S. Caucasian case-control sample. METHODS. Twenty-five LOXL1 single-nucleotide polymorphisms (SNPs), distributed throughout the gene, were geno-typed in 196 Caucasian patients with ES/EG and 201 matched controls. Genotype data were analyzed for single SNP associations, SNP interactions, and haplotype associations. RESULTS. Promoter region haplotypes that included the risk alleles for rs12914489, a SNP located in the distal promoter region and independently associated with ES, and rs16958477, a SNP previously shown to affect gene transcription, were associated with increased disease risk (P = 0.0008; odds ratio [OR], 2.34; 95% confidence interval [CI], 1.42-3.85) and with protective effects (P = 2.3 x 10(-6); OR, 0.38; 95% CI, 0.25-0.57). Haplotypes containing rs12914489 and rs16958477 risk and protective alleles also significantly influenced the disease risk associated with missense alleles R141L and G153D. CONCLUSIONS. LOXL1 promoter haplotypes were identified that are significantly associated with ES/EG in a U.S. Caucasian population. These results suggest that promoter region SNPs can influence LOXL1 gene expression, potentially causing a reduction of enzyme activity that may predispose to disease. (Invest Ophthalmol Vis Sci. 2011;52:2372-2378) DOI: 10.1167/iovs.10-6268 C1 [Fan, Bao Jian; Pasquale, Louis R.; Rhee, Douglas; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Li, Tiansen] NEI, NIH, Bethesda, MD 20892 USA. [Haines, Jonathan L.] Vanderbilt Univ Sch Med, Ctr Human Genet Res, Nashville, TN USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; OI Fan, Baojian/0000-0002-6851-2737 FU National Institutes of Health (NIH) [EY015882, P30EY014104]; Massachusetts Lions Eye Research Fund; Research to Prevent Blindness FX Supported in part by National Institutes of Health (NIH) Grants EY015882 and P30EY014104, the Massachusetts Lions Eye Research Fund, and Research to Prevent Blindness. NR 38 TC 27 Z9 29 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 APR PY 2011 VL 52 IS 5 BP 2372 EP 2378 DI 10.1167/iovs.10-6268 PG 7 WC Ophthalmology SC Ophthalmology GA 748SJ UT WOS:000289411300004 PM 21212179 ER PT J AU Kristensen, DM Cai, XX Mushegian, A AF Kristensen, David M. Cai, Xixu Mushegian, Arcady TI Evolutionarily Conserved Orthologous Families in Phages Are Relatively Rare in Their Prokaryotic Hosts SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MARINE VIRUSES; GENOME TREES; DOMAIN; LIFE; BACTERIOPHAGES; DATABASE; PREDICTION; ABUNDANCE; ARCHAEAL; REGIONS AB We have identified conserved orthologs in completely sequenced genomes of double-strand DNA phages and arranged them into evolutionary families (phage orthologous groups [POGs]). Using this resource to analyze the collection of known phage genomes, we find that most orthologs are unique in their genomes (having no diverged duplicates [paralogs]), and while many proteins contain multiple domains, the evolutionary recombination of these domains does not appear to be a major factor in evolution of these orthologous families. The number of POGs has been rapidly increasing over the past decade, the percentage of genes in phage genomes that have orthologs in other phages has also been increasing, and the percentage of unknown "ORFans" is decreasing as more proteins find homologs and establish a family. Other properties of phage genomes have remained relatively stable over time, most notably the high fraction of genes that are never or only rarely observed in their cellular hosts. This suggests that despite the renowned ability of phages to transduce cellular genes, these cellular "hitchhiker" genes do not dominate the phage genomic landscape, and a large fraction of the genes in phage genomes maintain an evolutionary trajectory that is distinct from that of the host genes. C1 [Kristensen, David M.; Cai, Xixu; Mushegian, Arcady] Stowers Inst Med Res, Kansas City, MO 64110 USA. [Cai, Xixu; Mushegian, Arcady] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. RP Kristensen, DM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM David.Kristensen@nih.gov OI Mushegian, Arcady/0000-0002-6809-9225 FU Stowers Institute for Medical Research FX This work was supported by the Stowers Institute for Medical Research. NR 65 TC 22 Z9 22 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 8 BP 1806 EP 1814 DI 10.1128/JB.01311-10 PG 9 WC Microbiology SC Microbiology GA 746GA UT WOS:000289229900003 PM 21317336 ER PT J AU Camberg, JL Hoskins, JR Wickner, S AF Camberg, Jodi L. Hoskins, Joel R. Wickner, Sue TI The Interplay of ClpXP with the Cell Division Machinery in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ASSEMBLY DYNAMICS; CYTOSKELETAL PROTEIN; PATTERN-FORMATION; Z-RING; FTSZ; MUTANTS; MIN; ATP; LOCALIZATION; RESISTANCE AB ClpXP is a two-component protease composed of ClpX, an ATP-dependent chaperone that recognizes and unfolds specific substrates, and ClpP, a serine protease. One ClpXP substrate in Escherichia coli is FtsZ, which is essential for cell division. FtsZ polymerizes and forms the FtsZ ring at midcell, where division occurs. To investigate the role of ClpXP in cell division, we examined the effects of clpX and clpP deletions in several strains that are defective for cell division. Together, our results suggested that ClpXP modulates cell division through degradation of FtsZ and possibly other cell division components that function downstream of FtsZ ring assembly. In the ftsZ84 strain, which is temperature sensitive for filamentation due to a mutation in ftsZ, we observed that deletion of clpX or clpP suppresses filamentation and reduces FtsZ84 degradation. These results are consistent with ClpXP playing a role in cell division by modulating the level of FtsZ through degradation. In another division-defective strain, Delta minC, the additional deletion of clpX or clpP delays cell division and exacerbates filamentation. Our results demonstrate that ClpXP modulates division in cells lacking MinC by a mechanism that requires ATP-dependent degradation. However, antibiotic chase experiments in vivo indicate that FtsZ degradation is slower in the Delta minC strain than in the wild type, suggesting there may be another cell division component degraded by ClpXP. Taken together these studies suggest that ClpXP may degrade multiple cell division proteins, thereby modulating the precise balance of the components required for division. C1 [Camberg, Jodi L.; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wickner, S (reprint author), NCI, Mol Biol Lab, NIH, 37 Convent Dr,Room 5144, Bethesda, MD 20892 USA. EM WicknerS@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 40 TC 21 Z9 21 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 8 BP 1911 EP 1918 DI 10.1128/JB.01317-10 PG 8 WC Microbiology SC Microbiology GA 746GA UT WOS:000289229900014 PM 21317324 ER PT J AU Woodcock, HL Miller, BT Hodoscek, M Okur, A Larkin, JD Ponder, JW Brooks, BR AF Woodcock, H. Lee Miller, Benjamin T. Hodoscek, Milan Okur, Asim Larkin, Joseph D. Ponder, Jay W. Brooks, Bernard R. TI MSCALE: A General Utility for Multiscale Modeling SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; PROTEIN CONFORMATIONAL-CHANGES; ELECTRONIC-STRUCTURE PACKAGE; FREE-ENERGY DIFFERENCES; ELASTIC NETWORK MODELS; BIOMOLECULAR SYSTEMS; IMPLEMENTATION; ONIOM; AMBER; STABILIZATION AB The combination of theoretical models of macromolecules that exist at different spatial and temporal scales has become increasingly important for addressing complex biochemical problems. This work describes the extension of concurrent multiscale approaches, introduces a general framework for carrying out calculations, and describes its implementation into the CHARMM macromolecular modeling package. This functionality, termed MSCALE, generalizes both the additive and subtractive multiscale scheme [e.g., quantum mechanical/molecular mechanical (QM/MM) ONIOM-type] and extends its support to classical force fields, coarse grained modeling [e.g., elastic network model (ENM), Gaussian network model (GNM), etc.], and a mixture of them all. The MSC:ALE scheme is completely parallelized with each subsystem running as an independent but connected calculation. One of the most attractive features of MSCALE is the relative ease of implementation using the standard message passing interface communication protocol. This allows external access to the framework and facilitates the combination of functionality previously isolated in separate programs. This new facility is fully integrated with free energy perturbation methods, Hessian-based methods, and the use of periodicity and symmetry, which allows the calculation of accurate pressures. We demonstrate the utility of this new technique with four examples: (1) subtractive QM/MM and QM/QM calculations; (2) multiple force field alchemical free energy perturbation; (3) integration with the SANDER module of AMBER and the TINKER package to gain access to potentials not available in CHARMM; and (4) mixed resolution (i.e., coarse grain/all-atom) normal mode analysis. The potential of this new tool is clearly established, and in conclusion, an interesting mathematical problem is highlighted, and future improvements are proposed. C1 [Woodcock, H. Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA. [Miller, Benjamin T.; Okur, Asim; Larkin, Joseph D.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Hodoscek, Milan] Natl Inst Chem, Ctr Mol Modeling, SI-1000 Ljubljana, Slovenia. [Ponder, Jay W.] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Woodcock, HL (reprint author), Univ S Florida, Dept Chem, 4202 E Fowler Ave,CHE205, Tampa, FL 33620 USA. EM hlw@mail.usf.edu; brb@nih.gov RI Woodc, Henry/D-9275-2011; OI Miller, Benjamin/0000-0003-1647-0122; Woodcock, Henry/0000-0003-3539-273X FU NIH [1K22HL088341-01A1, R01GM58712]; University of South Florida; NSF [0535675]; NIH, National Heart Lung and Blood Institute; NHLBI FX H.L.W. would like to acknowledge NIH (1K22HL088341-01A1) and the University of South Florida (start-up) for funding. J.W.P. acknowledges funding from NIH (R01GM58712) and NSF (Cyberinfrastruaure grant 0535675). This research was supported in part by the Intramural Research Program of the NIH, National Heart Lung and Blood Institute. The NHLBI funding for the LoBoS (http://www.lobos.nih.gov) cluster computing system is also acknowledged and appreciated. NR 74 TC 25 Z9 25 U1 3 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 EI 1549-9626 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD APR PY 2011 VL 7 IS 4 BP 1208 EP 1219 DI 10.1021/ct00738h PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 747JI UT WOS:000289315700042 PM 21691425 ER PT J AU Tumban, E Mitzel, DN Maes, NE Hanson, CT Whitehead, SS Hanley, KA AF Tumban, Ebenezer Mitzel, Dana N. Maes, Nyree E. Hanson, Christopher T. Whitehead, Stephen S. Hanley, Kathryn A. TI Replacement of the 3 ' untranslated variable region of mosquito-borne dengue virus with that of tick-borne Langat virus does not alter vector specificity SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID COMPLETE GENOME SEQUENCE; FUSING AGENT VIRUS; WEST-NILE-VIRUS; NO KNOWN VECTOR; ENCEPHALITIS-VIRUS; FLAVIVIRUS RNA; 3'-UNTRANSLATED REGION; SECONDARY STRUCTURE; VACCINE CANDIDATE; MODOC-VIRUS AB The four major flavivirus clades are transmitted by mosquitoes, ticks, directly between vertebrates or directly between arthropods, respectively, but the molecular determinants of mode of transmission in flaviviruses are unknown. To assess the role of the UTRs in transmission, we generated chimeric genomes in which the 5' UTR, capsid and/or 3' UTR of mosquito-borne dengue virus serotype 4 (rDENV-4) were replaced, separately or in combination, with those of tick-borne Langat virus (rLGTV). None of the chimeric genomes yielded detectable virus following transfection. Replacement of the variable region (VR) in the rDENV-4 3' UTR with that of rLGTV generated virus rDENV-4-rLGTswapVR, which showed lower replication than its wild-type parents in mammalian but not mosquito cells in culture and was able to infect mosquitoes in vivo. Neither rDENV-4 nor rDENV-4-rLGTswapVR could infect larval Ixodes scapularis ticks immersed in virus, while rLGTV was highly infectious via this route. C1 [Tumban, Ebenezer; Maes, Nyree E.; Hanley, Kathryn A.] New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA. [Mitzel, Dana N.] NIAID, Virol Lab, NIH, Hamilton, MT 59840 USA. [Hanson, Christopher T.; Whitehead, Stephen S.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hanley, Kathryn A.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. RP Hanley, KA (reprint author), New Mexico State Univ, Program Mol Biol, Las Cruces, NM 88003 USA. EM khanley@nmsu.edu FU NIH, NIAID; [NIH-K22-A164193]; [NIH-NM-INBRE P20 RR016480-05]; [NSF-NM-AMP HRD-0331446] FX We would like to thank Dr Alexander Pletnev, Ulrike Munderloh and Timothy Kurtti, for providing us with pE5 plasmid and embryonated eggs of I. scapularis, respectively. We would also like to thank Drs Barbara Lyons, Steve Hanson and Jeffrey Arterburn for their suggestions. Two anonymous reviewers greatly improved the quality of the manuscript. This study was supported by intramural Research Program of the NIH, NIAID and in part by NIH-K22-A164193, NIH-NM-INBRE P20 RR016480-05, NSF-NM-AMP HRD-0331446. NR 62 TC 9 Z9 9 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2011 VL 92 BP 841 EP 848 DI 10.1099/vir.0.026997-0 PN 4 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 748KP UT WOS:000289389800012 PM 21216984 ER PT J AU Arumugam, A Weng, Z Kopelovich, L Athar, M AF Arumugam, A. Weng, Z. Kopelovich, L. Athar, M. TI Combined inhibition of sonic hedgehog (shh) and nuclear factor kappa B (NF kappa B) signaling pathways in the prevention of basal cell carcinomas (BCCs) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Arumugam, A.; Weng, Z.; Athar, M.] Univ Alabama, Birmingham, AL USA. [Kopelovich, L.] NCI, Canc Prevent Div, 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 APR PY 2011 VL 131 SU 1 MA 164 BP S28 EP S28 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600166 ER PT J AU Aubert, P Suarez-Farinas, M Mitsui, H Johnson-Huang, LM Pierson, K Dolan, JG Novitskaya, I Coats, I Krueger, JG Estes, J Cowen, E Plass, N Lee, C Sun, H Lowes, MA Goldbach-Mansky, R AF Aubert, P. Suarez-Farinas, M. Mitsui, H. Johnson-Huang, L. M. Pierson, K. Dolan, J. G. Novitskaya, I. Coats, I. Krueger, J. G. Estes, J. Cowen, E. Plass, N. Lee, C. Sun, H. Lowes, M. A. Goldbach-Mansky, R. TI Dissecting the inflammatory skin lesions in NOMID and the resulting homeostatic tissue responses in the context of IL-1 blocking therapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Aubert, P.; Dolan, J. G.; Plass, N.; Lee, C.; Goldbach-Mansky, R.] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA. [Suarez-Farinas, M.; Mitsui, H.; Johnson-Huang, L. M.; Pierson, K.; Novitskaya, I.; Coats, I.; Krueger, J. G.; Lowes, M. A.] Rockefeller Univ, Invest Dermatol Lab, New York, NY 10021 USA. [Suarez-Farinas, M.] Rockefeller Univ, Ctr Clin & Translat Sci, New York, NY 10021 USA. [Estes, J.] SAIC, Frederick, MD USA. [Cowen, E.] NCI, 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 APR PY 2011 VL 131 SU 1 MA 045 BP S8 EP S8 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600045 ER PT J AU Chaudhary, SC Kurundkar, D Singh, T Weng, Z Elmets, CA Kopelovich, L Athar, M AF Chaudhary, S. C. Kurundkar, D. Singh, T. Weng, Z. Elmets, C. A. Kopelovich, L. Athar, M. TI Rapamycin augments the chemopreventive effects of sulindac and suppresses UVB-induced cutaneous photocarcinogenesis in Ptch+/- hairless mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Chaudhary, S. C.; Kurundkar, D.; Singh, T.; Weng, Z.; Elmets, C. A.; Athar, M.] Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. [Kopelovich, L.] NCI, Canc Prevent Div, 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 APR PY 2011 VL 131 SU 1 MA 152 BP S26 EP S26 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600154 ER PT J AU Chellammal, PV Stepp, M Speer, K Dengler, S Edwards, J Coppola, V Tessarollo, L Yuspa, S AF Chellammal, P. Velayuthan Stepp, M. Speer, K. Dengler, S. Edwards, J. Coppola, V. Tessarollo, L. Yuspa, S. TI Compromised TGF-beta signaling, reduced wound healing and spontaneous skin erosions characterize CLIC4-/- mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Chellammal, P. Velayuthan; Speer, K.; Dengler, S.; Yuspa, S.] NCI, Bethesda, MD 20892 USA. [Stepp, M.] GWU Med Sch, Washington, DC USA. [Coppola, V.; Tessarollo, L.] NCI, Frederick, MD 21701 USA. [Edwards, J.] Univ N Carolina, Chapel Hill, NC USA. RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 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 APR PY 2011 VL 131 SU 1 MA 785 BP S131 EP S131 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600782 ER PT J AU Curiel-Lewandrowski, C Swetter, S Einspahr, J Hsu, C Saboda, K Nagle, R LaPresto, L Sagerman, P Lian, F Tangrea, J Parnes, H Chow, H AF Curiel-Lewandrowski, C. Swetter, S. Einspahr, J. Hsu, C. Saboda, K. Nagle, R. LaPresto, L. Sagerman, P. Lian, F. Tangrea, J. Parnes, H. Chow, H. TI Effect of oral sulindac on biomarkers of drug bioavailability and carcinogenesis in melanocytic nevi-A double-blind, randomized, placebo-controlled trial SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Curiel-Lewandrowski, C.; Einspahr, J.; Hsu, C.; Saboda, K.; Nagle, R.; LaPresto, L.; Sagerman, P.; Lian, F.; Chow, H.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. [Tangrea, J.; Parnes, H.] NCI, Bethesda, MD 20892 USA. [Swetter, S.] Stanford Univ, Palo Alto, CA 94304 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 APR PY 2011 VL 131 SU 1 MA 773 BP S129 EP S129 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600770 ER PT J AU Grice, EA Snitkin, ES Yockey, LJ Bermudez, DM Liechty, KW Segre, JA AF Grice, E. A. Snitkin, E. S. Yockey, L. J. Bermudez, D. M. Liechty, K. W. Segre, J. A. TI Microbiome and corresponding cutaneous defense response in chronic diabetic wounds SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Grice, E. A.; Snitkin, E. S.; Yockey, L. J.; Segre, J. A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Bermudez, D. M.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Liechty, K. W.] Univ Mississippi, Med Ctr, Dept Surg, Jackson, MS 39216 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 APR PY 2011 VL 131 SU 1 MA 817 BP S137 EP S137 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600814 ER PT J AU Hwang, I Kita, R Kwon, H Choi, E Lee, S Udey, MC Morasso, MI AF Hwang, I. Kita, R. Kwon, H. Choi, E. Lee, S. Udey, M. C. Morasso, M. I. TI Epidermal ablation of Dlx3 is linked to barrier disruption and a skin inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Hwang, I.; Kita, R.; Morasso, M. I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA. [Kwon, H.; Udey, M. C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Choi, E.] Yonsei Univ, Dept Dermatol, Wonju Coll Med, Wonju, South Korea. [Lee, S.] Yonsei Univ, Coll Med, Dept Dermatol, Seoul, South Korea. 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 APR PY 2011 VL 131 SU 1 MA 010 BP S2 EP S2 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600012 ER PT J AU Inozume, T Hanada, K Rosenberg, SA Shimada, S Yang, JC AF Inozume, T. Hanada, K. Rosenberg, S. A. Shimada, S. Yang, J. C. TI Biosensor system to detect the tumor reactive population in bulk tumor infiltrating T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Inozume, T.; Shimada, S.] Yamanashi Univ, Chuo, Japan. [Inozume, T.; Hanada, K.; Rosenberg, S. A.; Yang, J. C.] NCI, Bethesda, MD 20892 USA. RI Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 NR 0 TC 0 Z9 0 U1 1 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 APR PY 2011 VL 131 SU 1 MA 555 BP S93 EP S93 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600554 ER PT J AU Kong, HH Oh, J Grice, EA Conlan, SP Deming, C Murray, PR Turner, ML Segre, JA AF Kong, H. H. Oh, J. Grice, E. A. Conlan, S. P. Deming, C. Murray, P. R. Turner, M. L. Segre, J. A. TI Reduced skin microbiome diversity is associated with atopic dermatitis severity and disease status SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Kong, H. H.; Turner, M. L.] NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. [Oh, J.; Grice, E. A.; Conlan, S. P.; Deming, C.; Segre, J. A.] NHGRI, GMBB, NIH, Bethesda, MD 20892 USA. [Murray, P. R.] NIH, DLM, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 8 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 APR PY 2011 VL 131 SU 1 MA 638 BP S107 EP S107 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600636 ER PT J AU Koppel, AC Lin, C Burns, C Gribben, E Anders, J Cataisson, C Yuspa, SH Kissling, GE Blumenberg, M Arthur, JC Efimova, T AF Koppel, A. C. Lin, C. Burns, C. Gribben, E. Anders, J. Cataisson, C. Yuspa, S. H. Kissling, G. E. Blumenberg, M. Arthur, J. C. Efimova, T. TI The p38 mitogen-activated protein kinase isoforms p38 beta and p38 delta are essential in vivo regulators of mouse skin carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Koppel, A. C.; Lin, C.; Burns, C.; Gribben, E.; Efimova, T.] Washington Univ, Sch Med, St Louis, MO USA. [Anders, J.; Cataisson, C.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Kissling, G. E.] NIEHS, Res Triangle Pk, NC 27709 USA. [Blumenberg, M.] NYU, Sch Med, New York, NY USA. [Arthur, J. C.] Univ Dundee, Fac Life Sci, MRC Prot Phosphorylat Unit, Dundee, Scotland. 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 APR PY 2011 VL 131 SU 1 MA 123 BP S21 EP S21 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600122 ER PT J AU Liu, F Cataisson, C Zaidi, R Merlino, G Yuspa, SH AF Liu, F. Cataisson, C. Zaidi, R. Merlino, G. Yuspa, S. H. TI HGF transactivates keratinocyte EGFR signaling, potentiates the tumorigenic phenotype of oncogenic rat-transduced keratinocytes in vitro and enhances skin carcinogenesis in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Liu, F.; Cataisson, C.; Zaidi, R.; Merlino, G.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Liu, F.] Howard Hughes Med Inst, HHMI NIH Res Scholar, Chevy Chase, MD 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 APR PY 2011 VL 131 SU 1 BP S17 EP S17 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600100 ER PT J AU Milstone, L Zambrano, H Majumdar, A Alam, R Li, H Thazhathveeti, A Glazer, P Seidman, M AF Milstone, L. Zambrano, H. Majumdar, A. Alam, R. Li, H. Thazhathveeti, A. Glazer, P. Seidman, M. TI Targeting keratin 6a gene sequences using small oligonucleotides and PNAs SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Milstone, L.; Zambrano, H.; Glazer, P.] Yale Univ, New Haven, CT USA. [Majumdar, A.; Alam, R.; Li, H.; Thazhathveeti, A.; Seidman, M.] NIA, Baltimore, MD 21224 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 APR PY 2011 VL 131 SU 1 MA 408 BP S68 EP S68 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600408 ER PT J AU Ming, M Shea, CR Feng, L Soltani, K He, Y AF Ming, M. Shea, C. R. Feng, L. Soltani, K. He, Y. TI UVA induces lesions resembling seborrheic keratoses in mice with keratinocyte-specific PTEN down-regulation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Ming, M.; Shea, C. R.; Soltani, K.; He, Y.] Univ Chicago, Chicago, IL 60637 USA. [Feng, L.] NIEHS, Res Triangle Pk, NC 27709 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 APR PY 2011 VL 131 SU 1 MA 657 BP S110 EP S110 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600655 ER PT J AU Ming, M Shea, C Guo, X Li, X Soltani, K Han, W He, Y AF Ming, M. Shea, Cr Guo, X. Li, X. Soltani, K. Han, W. He, Y. TI The deacetylase SIRT1 regulates global genome nucleotide excision repair SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Ming, M.; Shea, Cr; Soltani, K.; Han, W.; He, Y.] Univ Chicago, Chicago, IL 60637 USA. [Guo, X.; Li, X.] NIEHS, Res Triangle Pk, NC 27709 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 APR PY 2011 VL 131 SU 1 MA 086 BP S15 EP S15 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600088 ER PT J AU Motegi, S Garfield, S Udey, MC AF Motegi, S. Garfield, S. Udey, M. C. TI Regulation of PDGF receptor signaling in pericytes by MFG-E8 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Motegi, S.; Udey, M. C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Garfield, S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, 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 APR PY 2011 VL 131 SU 1 MA 177 BP S30 EP S30 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600176 ER PT J AU Okano, J Lichti, U Aronova, M Zhang, G Yuspa, SH Sakai, Y Morasso, MI AF Okano, J. Lichti, U. Aronova, M. Zhang, G. Yuspa, S. H. Sakai, Y. Morasso, M. I. TI Increased endogenous retinoic acid by the absence of Cyp26b1 impairs peridermal development and skin barrier formation during development SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Okano, J.; Morasso, M. I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA. [Lichti, U.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Aronova, M.; Zhang, G.] NIBIB, Lab Bioengn & Phys Sci, NIH, Bethesda, MD USA. [Sakai, Y.] Osaka Univ, Dept Plast & Reconstruct Surg, Osaka, Japan. 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 APR PY 2011 VL 131 SU 1 MA 266 BP S45 EP S45 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600266 ER PT J AU Purwar, R Xiao, S Takeda, Y Elyaman, A Jiang, X Jetten, A Khoury, S Fuhlbrigge, R Kuchroo, V Kupper, T AF Purwar, R. Xiao, S. Takeda, Y. Elyaman, A. Jiang, X. Jetten, A. Khoury, S. Fuhlbrigge, R. Kuchroo, V. Kupper, T. TI IL-9 is a potent mediator of tumor immunity, and its expression is negatively regulated by the Th17 transcription factor ROR gamma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Purwar, R.; Xiao, S.; Elyaman, A.; Jiang, X.; Khoury, S.; Fuhlbrigge, R.; Kuchroo, V.; Kupper, T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Takeda, Y.; Jetten, A.] NIEHS, NIH, Res Triangle Pk, NC 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 APR PY 2011 VL 131 SU 1 MA 595 BP S100 EP S100 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600594 ER PT J AU Takekoshi, T Fang, L Sells, R Hwang, ST AF Takekoshi, T. Fang, L. Sells, R. Hwang, S. T. TI CCR7-expressing B16 melanoma cells down-regulate interferon (IFN)-gamma-mediated inflammation and increase lymphangiogenesis in the tumor microenvironment SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Takekoshi, T.; Sells, R.; Hwang, S. T.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Fang, L.] NCI, 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 APR PY 2011 VL 131 SU 1 MA 727 BP S122 EP S122 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600725 ER PT J AU Tan, X Anzick, SL Khan, SG Ueda, T Stone, G DiGiovanna, JJ Tamura, D Wattendorf, D Brewer, C Zalewski, C Walker, R Griffith, A Butman, J Meltzer, P Bergstresser, P Kraemer, KH AF Tan, X. Anzick, S. L. Khan, S. G. Ueda, T. Stone, G. DiGiovanna, J. J. Tamura, D. Wattendorf, D. Brewer, C. Zalewski, C. Walker, R. Griffith, A. Butman, J. Meltzer, P. Bergstresser, P. Kraemer, K. H. TI Fusion of the melanoma gene, p14arf on 9p, to a translocation hotspot in a gap in 22q in a patient with melanoma, deafness and DNA repair deficiency, is a negative regulator of p14arf and TBX1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Tan, X.; Anzick, S. L.; Khan, S. G.; Stone, G.; DiGiovanna, J. J.; Tamura, D.; Walker, R.; Meltzer, P.; Kraemer, K. H.] NCI, Bethesda, MD 20892 USA. [Ueda, T.] Pharm Med Dev, Tokyo, Japan. [Brewer, C.; Zalewski, C.; Griffith, A.] NIDCD, Bethesda, MD USA. [Butman, J.] CC, Dept Radiol, Bethesda, MD USA. [Wattendorf, D.] DARPA, Washington, DC USA. [Bergstresser, P.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 1 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 APR PY 2011 VL 131 SU 1 MA 126 BP S21 EP S21 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600126 ER PT J AU Thangapazham, R Li, S Wang, J Rajesh, S Moss, J Darling, TN AF Thangapazham, R. Li, S. Wang, J. Rajesh, S. Moss, J. Darling, T. N. TI TSC2-null fibroblast-like cells recreate multiple niches in grafted skin equivalents including dermal papilla SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Thangapazham, R.; Li, S.; Wang, J.; Rajesh, S.; Darling, T. N.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Moss, J.] NHLBI, Cardiovasc & Pulm Branch, 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 APR PY 2011 VL 131 SU 1 MA 805 BP S135 EP S135 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600802 ER PT J AU Wolf, R Mascia, F Cataisson, C Dharamsi, A Howard, Z Bliskovski, V Winston, J Feigenbaum, L Lichti, U Ruzicka, T Chavakis, T Yuspa, SH AF Wolf, R. Mascia, F. Cataisson, C. Dharamsi, A. Howard, Z. Bliskovski, V. Winston, J. Feigenbaum, L. Lichti, U. Ruzicka, T. Chavakis, T. Yuspa, S. H. TI Small S100 molecules from the psoriasis susceptibility locus (PSORS4) prime the skin for inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Wolf, R.; Mascia, F.; Cataisson, C.; Dharamsi, A.; Bliskovski, V.; Winston, J.; Lichti, U.; Yuspa, S. H.] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Chavakis, T.] NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. [Howard, Z.] NIH, Mol Immunoregulat Lab, Frederick, MD USA. [Feigenbaum, L.] NIH, Lab Anim Sci, Frederick, MD USA. [Ruzicka, T.] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Chavakis, T.] Tech Univ Dresden, Dept Med, D-8027 Dresden, Germany. [Chavakis, T.] Tech Univ Dresden, Inst Physiol, D-8027 Dresden, Germany. 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 APR PY 2011 VL 131 SU 1 MA 002 BP S1 EP S1 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600005 ER PT J AU Seltzman, HH Fix, SE Risbood, P AF Seltzman, Herbert H. Fix, Scott E. Risbood, Prabhakar TI Deuterated batracylin: deuterium-hydrogen exchange during synthesis and mass spectral analysis SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE batracylin; deuterium; ortho exchange; mass spectrum ID GENERAL-METHOD; DERIVATIVES; ANALOGS AB Deuterium-labeled analogs of the topoisomerase inhibitor batracylin were prepared for metabolism studies to further its evaluation as an antitumor agent. Established syntheses of unlabeled batracylin were adapted for the preparation of deuterated batracylin that was trideuterated in the quinazoline ring (d(3)-batracylin 5), tetradeuterated in the isoindolo ring (d(4)-batracylin 11), and heptadeuterated in both rings (d(7)-batracylin 12). Extensive exchange of deuterium or hydrogen in the quinazoline ring was observed from an intermediate in the final concentrated sulfuric acid promoted deblocking/cyclodehydration step of the synthesis. Introduction of deuterated concentrated sulfuric acid in the final step both retained the label in the quinazoline-labeled product and enabled extended labeling of a more exhaustively deuterated analog. Batracylin itself did not readily exchange aromatic protons under the reaction conditions but did loose and scramble deuterium atoms during mass spectral analysis leading to an under calculation of the deuterium content in the quinazoline ring. These results identify a chemical exchange process that can either undo, maintain, or facilitate the labeling process and also mass spectral analyses issues that must be taken into account to characterize and utilize these analogs and, more broadly, that can be recognized as potentially applicable to other classes of compounds. C1 [Seltzman, Herbert H.; Fix, Scott E.] Res Triangle Inst, Ctr Organ & Med Chem, Res Triangle Pk, NC 27709 USA. [Risbood, Prabhakar] NCI, Drug Synth & Chem Branch, Dev Therapeut Program, Div Canc Treatment & Diagnost,NIH, Bethesda, MD 20892 USA. RP Seltzman, HH (reprint author), Res Triangle Inst, Ctr Organ & Med Chem, POB 12194, Res Triangle Pk, NC 27709 USA. EM hhs@rti.org FU National Cancer Institute [N02-CM-62228] FX Informative discussions with Drs James Mathews and Timothy Fennell of RTI International are acknowledged. This work was funded by the National Cancer Institute on Contract No. N02-CM-62228. NR 8 TC 2 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 2011 VL 54 IS 4 BP 206 EP 210 DI 10.1002/jlcr.1847 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 749AH UT WOS:000289434000009 ER PT J AU Basuli, F Wu, HT Griffiths, GL AF Basuli, Falguni Wu, Haitao Griffiths, Gary L. TI Syntheses of meta-[F-18]fluorobenzaldehyde and meta-[F-18]fluorobenzylbromide from phenyl(3-Formylphenyl) iodonium salt precursors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE fluorine-18; iodonium salt precursors; meta-[F-18]fluorobenzaldehyde; meta-[F-18]fluorobenzylbromide ID POSITRON-EMISSION-TOMOGRAPHY; CROSS-COUPLING REACTIONS; NO-CARRIER; DIARYLIODONIUM-SALTS; AROMATIC-COMPOUNDS; ARYLBORONIC ACIDS; ARYL IODIDES; F-18; PET; RADIOPHARMACEUTICALS AB F-18-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho-and para-[F-18]fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[F-18]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of F-18-labeled electron-rich, as well as electron-deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. F-18 radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (similar to 80%) to meta-[F-18]fluorobenzaldehyde was obtained using CsHCO3 base at a reaction temperature of 110 degrees C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[F-18]F/CsHCO3 in DMF at 110 degrees C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs= 1 year survivors) and five excess cancers per 1000 patients treated with radiotherapy by 15 years after diagnosis. Interpretation A relatively small proportion of second cancers are related to radiotherapy in adults, suggesting that most are due to other factors, such as lifestyle or genetics. C1 [de Gonzalez, Amy Berrington; Curtis, Rochelle E.; Gilbert, Ethel; Lamart, Stephanie; Ron, Elaine] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Kry, Stephen F.; Stovall, Marilyn] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. [Berg, Christine D.] NCI, Early Detect Res Grp, Bethesda, MD 20892 USA. RP de Gonzalez, AB (reprint author), NCI, Radiat Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov RI Berg , Christine/K-1047-2014; OI Kry, Stephen/0000-0001-6899-197X FU US National Cancer Institute FX US National Cancer Institute. NR 37 TC 96 Z9 96 U1 1 U2 16 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 APR PY 2011 VL 12 IS 4 BP 353 EP 360 DI 10.1016/S1470-2045(11)70061-4 PG 8 WC Oncology SC Oncology GA 751BZ UT WOS:000289593800017 ER PT J AU Anderson, BO Cazap, E El Saghir, NS Yip, CH Khaled, HM Otero, IV Adebamowo, CA Badwe, RA Harford, JB AF Anderson, Benjamin O. Cazap, Eduardo El Saghir, Nagi S. Yip, Cheng-Har Khaled, Hussein M. Otero, Isabel V. Adebamowo, Clement A. Badwe, Rajendra A. Harford, Joe B. TI Optimisation of breast cancer management in low-resource and middle-resource countries: executive summary of the Breast Health Global Initiative consensus, 2010 SO LANCET ONCOLOGY LA English DT Review ID INCOME COUNTRIES; GUIDELINE IMPLEMENTATION; CERVIX CANCER; UNITED-STATES; CARE; ALLOCATION; SURVIVAL; PROGRAM; COLLABORATION; STATISTICS AB The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health-care systems. C1 [Anderson, Benjamin O.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Anderson, Benjamin O.] Fred Hutchinson Canc Res Ctr, Breast Hlth Global Initiat, Seattle, WA 98104 USA. [Cazap, Eduardo] SLACOM Soc Latinoamer & Caribe Oncol Med, Buenos Aires, DF, Argentina. [El Saghir, Nagi S.] Amer Univ Beirut, NK Basile Canc Inst, Breast Canc Ctr Excellence, Beirut, Lebanon. [Yip, Cheng-Har] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia. [Khaled, Hussein M.] Cairo Univ, Natl Canc Inst, Cairo, Egypt. [Otero, Isabel V.; Harford, Joe B.] NCI, Off Int Affairs, NIH, Bethesda, MD 20892 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Adebamowo, Clement A.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. [Badwe, Rajendra A.] Tata Mem Hosp, Dept Surg, Bombay 400012, Maharashtra, India. RP Anderson, BO (reprint author), Univ Washington, Dept Surg, Box 356410, Seattle, WA 98195 USA. EM banderso@u.washington.edu RI Yip, Cheng-Har/B-1909-2010; OI Adebamowo, Clement/0000-0002-6571-2880 FU BHGI; Bayer Sherling Pharma; Breast Cancer Research Foundation; Poniard Pharmaceuticals; GlaxoSmithKline; Fred Hutchinson Cancer Research Center, Susan G Komen for the Cure [SG09-0605-01-BHGI]; US Office of International Affairs, National Cancer Institute; European School of Oncology; Pan American Health Organization; Sheikh Mohammed Hussein Al-Amoudi Center of Excellence in Breast Cancer; American Society of Clinical Oncology; LIVESTRONG; US Centers for Disease Control and Prevention; US Office of Women's Health, Department of Health and Human Services; US Office of Science Planning and Assessment, National Cancer Institute; US Office of Research on Women's Health; National Institutes of Health; GE Healthcare; Sanofi-Aventis FX BOA received funding from BHGI. EC received consultancy funding from Bayer Sherling Pharma; received grants from Breast Cancer Research Foundation and Poniard Pharmaceuticals; was on the speakers bureaus for Bayer and Bristol-Myers Squibb; and received travel expenses from ASCO, Union for International Cancer Control (UICC), European Society for Medical Oncology, and Breast Cancer Research Foundation. C-HY was on an expert panel and received research funding from GlaxoSmithKline, and was on the speakers bureaus for Sanofi-Aventis and Roche. All other authors declare that they have no conflicts of interest.; BHGI received (2010 global summit) grants and contributions from Fred Hutchinson Cancer Research Center, Susan G Komen for the Cure (grant award SG09-0605-01-BHGI); US Office of International Affairs, National Cancer Institute; European School of Oncology; Pan American Health Organization; Sheikh Mohammed Hussein Al-Amoudi Center of Excellence in Breast Cancer; American Society of Clinical Oncology; LIVESTRONG; US Centers for Disease Control and Prevention; US Office of Women's Health, Department of Health and Human Services; US Office of Science Planning and Assessment, National Cancer Institute; US Office of Research on Women's Health; National Institutes of Health; and unrestricted educational grants from GE Healthcare and Sanofi-Aventis. On behalf of all authors and contributors, BHGI thanks Sandra Ripley Distelhorst for her invaluable services and outstanding contributions as publication editor in the preparation of this consensus report. NR 73 TC 91 Z9 95 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2011 VL 12 IS 4 BP 387 EP 398 PG 12 WC Oncology SC Oncology GA 751BZ UT WOS:000289593800021 PM 21463833 ER PT J AU Yong, ASM Stephens, N Weber, G Li, Y Savani, BN Eniafe, R Keyvanfar, K Kurlander, R Rezvani, K Barrett, AJ AF Yong, A. S. M. Stephens, N. Weber, G. Li, Y. Savani, B. N. Eniafe, R. Keyvanfar, K. Kurlander, R. Rezvani, K. Barrett, A. J. TI Improved outcome following allogeneic stem cell transplantation in chronic myeloid leukemia is associated with higher expression of BMI-1 and immune responses to BMI-1 protein SO LEUKEMIA LA English DT Article DE chronic myeloid leukemia; BMI-1; graft-versus-leukemia effect; leukemia-associated antigens ID CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; TUMOR-ASSOCIATED ANTIGENS; EX-VIVO CHARACTERIZATION; POLYCOMB GROUP PROTEINS; HUMAN CD34(+) CELLS; HEMATOPOIETIC STEM; T-CELLS; PERIPHERAL-BLOOD AB BMI-1 and EZH2 are polycomb group (PcG) proteins that maintain self-renewal of stem cells, and are overexpressed in leukemia. To investigate the potential of PcG proteins as leukemia-associated antigens, and as targets for graft-versus-leukemia (GVL) effects, we studied cells obtained from 86 patients with chronic myeloid leukemia (CML) and 25 human leukocyte antigen (HLA)-A*0201(+) sibling donors collected before allogeneic stem cell transplantation (SCT). Although BMI-1 overexpression in CD34(+) cells of CML patients treated with pharmacotherapy is associated with poor prognosis, we found, conversely, that in CML patients treated with SCT, a higher expression of BMI-1, and correspondingly a lower expression of its target for repression, CDKN2A, is associated with improved leukemia-free survival. Cytotoxic T-lymphocyte (CTL) responses to the BMI-1 peptide were detected in 5 of 25 (20%) donors, and in 8 of 19 (42%) HLA-A*0201(+) CML patients. BMI-1 generated more total and high-avidity immune responses, and was more immunogenic than EZH2. PcG-specific CTLs had a memory phenotype, were readily expanded in short-term cultures and were detected after SCT in recipients of PcG-specific CTL-positive donors. A higher BMI-1 expression in CML CD34(+) progenitors was associated with native BMI-1 immune responses. These immune responses to PcG proteins may target leukemia stem cells and have relevance for disease control by GVL. Leukemia (2011) 25, 629-637; doi:10.1038/leu.2010.325; published online 21 January 2011 C1 [Yong, A. S. M.; Stephens, N.; Weber, G.; Savani, B. N.; Eniafe, R.; Keyvanfar, K.; Rezvani, K.; Barrett, A. J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Li, Y.; Kurlander, R.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Yong, ASM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Hatfield CRC,Room 3-5330,10 Ctr Dr,MSC 12, Bethesda, MD 20892 USA. EM yonga@nhlbi.nih.gov FU National Institutes of Health, at the NHLBI FX This research was supported by the Intramural Research Program of the National Institutes of Health, at the NHLBI. NR 43 TC 18 Z9 18 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2011 VL 25 IS 4 BP 629 EP 637 DI 10.1038/leu.2010.325 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 749NO UT WOS:000289475300009 PM 21252986 ER PT J AU Madani, H Rahimi, Z Manavi-Shad, M Mozafari, H Akramipour, R Vaisi-Raygani, A Rezaei, M Malek-Khosravi, S Shakiba, E Parsian, A AF Madani, Hamid Rahimi, Zohreh Manavi-Shad, Mohammad Mozafari, Hadi Akramipour, Reza Vaisi-Raygani, Asad Rezaei, Mansour Malek-Khosravi, Shohreh Shakiba, Ebrahim Parsian, Abbas TI Plasma lipids and lipoproteins in children and young adults with major beta-thalassemia from western Iran: influence of genotype SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE beta-thalassemia; Mutation; Lipid; Lipoprotein; Western Iran ID SICKLE-CELL-DISEASE; INTERMEDIA PATIENTS; HYPOCHOLESTEROLEMIA; CHOLESTEROL AB To determine the plasma lipid and lipoprotein profiles and their possible association with the type of beta-thalassemia mutation we studied 103 major beta-thalassemia patients including 71 children and 32 young adults compared to 102 healthy subjects consisted of 90 children and 12 young healthy adults. The plasma lipid and lipoprotein levels were measured by conventional methods. Considering all of the patients the levels of total cholesterol (TC), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C) were significantly lower compared to controls. However, the level of TG was significantly higher in cases than controls. Comparing thalassemic patients homozygous for a beta(0) type of mutation with those homozygous for a beta(+) type of mutation (IVSI.110 G:A) indicated that the levels of LDL-C, TC were significantly increased and TG concentration tended to be higher in the latter patients. In conclusion, our study indicates that hemolytic stress results in hypocholesterolemia in major beta-thalassemia patients and the presence of more severe genotype in patients is correlated with more reduction in TG, TC, and LDL-C levels. C1 [Madani, Hamid] Kermanshah Univ Med Sci, Sch Med, Dept Pathol, Kermanshah, Iran. [Rahimi, Zohreh; Mozafari, Hadi] Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Kermanshah, Iran. [Rahimi, Zohreh; Vaisi-Raygani, Asad; Shakiba, Ebrahim] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran. [Manavi-Shad, Mohammad; Akramipour, Reza] Kermanshah Univ Med Sci, Sch Med, Dept Pediat, Kermanshah, Iran. [Rezaei, Mansour; Malek-Khosravi, Shohreh] Kermanshah Univ Med Sci, Rhazes Ctr Res Family Hlth & Sexual Med, Kermanshah, Iran. [Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA. RP Rahimi, Z (reprint author), Kermanshah Univ Med Sci, Sch Med, Med Biol Res Ctr, Daneshgah Ave,POB 67148-69914, Kermanshah, Iran. EM zrahimi@kums.ac.ir NR 21 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD APR PY 2011 VL 38 IS 4 BP 2573 EP 2578 DI 10.1007/s11033-010-0397-3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746OR UT WOS:000289257100045 PM 21086180 ER PT J AU Heo, JI Oh, SJ Kho, YJ Kim, JH Kang, HJ Park, SH Kim, HS Shin, JY Kim, MJ Kim, SC Park, JB Kim, J Lee, JY AF Heo, Jee-In Oh, Soo-Jin Kho, Yoon-Jung Kim, Jeong-Hyeon Kang, Hong-Joon Park, Seong-Hoon Kim, Hyun-Seok Shin, Jong-Yeon Kim, Min-Ju Kim, Sung Chan Park, Jae-Bong Kim, Jaebong Lee, Jae-Yong TI ERK mediates anti-apoptotic effect through phosphorylation and cytoplasmic localization of p21(Waf1/Cip1/Sdi) in response to DNA damage in normal human embryonic fibroblast (HEF) cells SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE p21; ERK; Etoposide; Camptothecin; HEF; Apoptosis ID SIGNAL-REGULATED KINASE; CARCINOMA CELLS; MESSENGER-RNA; P21(CIP1); PATHWAY; DEGRADATION; ACTIVATION; SENESCENCE; INDUCTION; STABILITY AB Since anti-apoptotic effect of ERK has not been elucidated clearly in DNA-damage-induced cell death, the role of ERK was examined in normal HEF cells treated with mild DNA damage using etoposide or camptothecin. ERK was activated by DNA damage in HEF cells. PD98059 increased apoptosis and reduced DNA-damage-induced p21(Waf1/Cip1/Sdi) level. Depletion of p21(Waf1/Cip1/Sdi) induced cell death and PD98059 induced additional cell death. DNA-damage-induced increase in cytoplasmic localization and phosphorylation of threonine residues of p21(Waf1/Cip1/Sdi) was reversed by PD98059. Thus, the results suggest that ERK pathway mediates anti-apoptotic effects through phosphorylation and cytoplasmic localization of p21(Waf1/Cip1/Sdi) in response to mild DNA damage. C1 [Heo, Jee-In; Oh, Soo-Jin; Kim, Jeong-Hyeon; Kang, Hong-Joon; Kim, Sung Chan; Park, Jae-Bong; Kim, Jaebong; Lee, Jae-Yong] Hallym Univ, Dept Biochem, Coll Med, Gangwon Do 200702, South Korea. [Heo, Jee-In; Kho, Yoon-Jung; Lee, Jae-Yong] Hallym Univ, Inst Nat Med, Coll Med, Chunchon 200702, Gangwon Do, South Korea. [Park, Seong-Hoon; Kim, Hyun-Seok] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shin, Jong-Yeon] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul, South Korea. [Kim, Min-Ju] Hallym Univ, Dept Anat & Neurobiol, Coll Med, Chunchon 200702, Gangwon Do, South Korea. RP Lee, JY (reprint author), Hallym Univ, Dept Biochem, Coll Med, 1 Okchon Dong Chuncheon, Gangwon Do 200702, South Korea. EM jyolee@hallym.ac.kr FU Ministry of Education, Science and Technology [2009-0094074] FX This work was supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0094074). NR 23 TC 12 Z9 13 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-4851 EI 1573-4978 J9 MOL BIOL REP JI Mol. Biol. Rep. PD APR PY 2011 VL 38 IS 4 BP 2785 EP 2791 DI 10.1007/s11033-010-0423-5 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 746OR UT WOS:000289257100071 PM 21110119 ER PT J AU Fan, T Jiang, SL Chung, N Alikhan, A Ni, C Lee, CCR Hornyak, TJ AF Fan, Tao Jiang, Shunlin Chung, Nancy Alikhan, Ali Ni, Christina Lee, Chyi-Chia Richard Hornyak, Thomas J. TI EZH2-Dependent Suppression of a Cellular Senescence Phenotype in Melanoma Cells by Inhibition of p21/CDKN1A Expression SO MOLECULAR CANCER RESEARCH LA English DT Article ID GROUP PROTEIN EZH2; HISTONE METHYLTRANSFERASE ACTIVITY; DNA METHYLATION; PROSTATE-CANCER; BRAF MUTATIONS; POLYCOMB; P53; GENE; NEVI; REPRESSION AB Polycomb group (PcG) proteins such as Enhancer of zeste homolog 2 (EZH2) are epigenetic transcriptional repressors that function through recognition and modification of histone methylation and chromatin structure. Targets of PcG include cell cycle regulatory proteins which govern cell cycle progression and cellular senescence. Senescence is a characteristic of melanocytic nevi, benign melanocytic proliferations that can be precursors of malignant melanoma. In this study, we report that EZH2, which we find absent in melanocytic nevi but expressed in many or most metastatic melanoma cells, functionally suppresses the senescent state in human melanoma cells. EZH2 depletion in melanoma cells inhibits cell proliferation, restores features of a cellular senescence phenotype, and inhibits growth of melanoma xenografts in vivo. p21/CDKN1A is activated upon EZH2 knockdown in a p53-independent manner and contributes substantially to cell cycle arrest and induction of a senescence phenotype. EZH2 depletion removes histone deacetylase 1 (HDAC1) from the CDKN1A transcriptional start site and downstream region, enhancing histone 3 acetylation globally and at CDKN1A. This results in recruitment of RNA polymerase II, leading to p21/CDKN1A activation. Depletion of EZH2 synergistically activates p21/CDKN1A expression in combination with the HDAC inhibitor trichostatin A. Since melanomas often retain wild-type p53 function activating p21, our findings describe a novel mechanism whereby EZH2 activation during tumor progression represses p21, leading to suppression of cellular senescence and enhanced tumorigenicity. Mol Cancer Res; 9(4); 418-29. (C) 2011 AACR. C1 [Fan, Tao; Jiang, Shunlin; Chung, Nancy; Alikhan, Ali; Ni, Christina; Hornyak, Thomas J.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hornyak, TJ (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10-12N242,10 Ctr Dr, Bethesda, MD 20892 USA. EM hornyakt@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 53 TC 68 Z9 70 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2011 VL 9 IS 4 BP 418 EP 429 DI 10.1158/1541-7786.MCR-10-0511 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 749ZI UT WOS:000289511600004 PM 21383005 ER PT J AU Lu, XD Yang, CY Yin, CY Van Dyke, T Simin, K AF Lu, Xiangdong Yang, Chunyu Yin, Chaoying Van Dyke, Terry Simin, Karl TI Apoptosis Is the Essential Target of Selective Pressure against p53, whereas Loss of Additional p53 Functions Facilitates Carcinoma Progression SO MOLECULAR CANCER RESEARCH LA English DT Article ID IN-VIVO; P53-DEPENDENT APOPTOSIS; BAX; MICE; TUMORIGENESIS; MUTATIONS; CELLS; LYMPHOMAGENESIS; INACTIVATION; SUPPRESSION AB The high frequency of p53 mutation in human cancers indicates the important role of p53 in suppressing tumorigenesis. It is well established that the p53 regulates multiple, distinct cellular functions such as cell-cycle arrest and apoptosis. Despite intensive studies, little is known about which function is essential, or if multiple pathways are required, for p53-dependent tumor suppression in vivo. Using a mouse brain carcinoma model that shows high selective pressure for p53 inactivation, we found that even partially abolishing p53-dependent apoptosis by Bax inactivation was sufficient to significantly reduce the selective pressure for p53 loss. This finding is consistent with previous reports that apoptosis is the primary p53 function selected against during Em-myc-induced mouse lymphoma progression. However, unlike observed in the Em-myc-induced lymphoma model, attenuation of apoptosis is not sufficient to phenocopy the aggressive tumor progression associated with complete loss of p53 activity. We conclude that apoptosis is the primary tumor suppressive p53 function and the ablation of additional p53 pleiotropic effects further exacerbates tumor progression. Mol Cancer Res; 9( 4); 430-9. (C) 2011 AACR. C1 [Simin, Karl] Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. [Lu, Xiangdong; Yang, Chunyu; Yin, Chaoying] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Van Dyke, Terry] NCI, Frederick, MD 21701 USA. RP Simin, K (reprint author), Univ Massachusetts, Sch Med, Dept Canc Biol, 364 Plantat St,Lazare Res Bldg 413, Worcester, MA 01605 USA. EM karl.simin@umassmed.edu FU NIH [5-RO1CA46283]; ACS [IRG-93-033-15] FX This work was supported by NIH grant 5-RO1CA46283 to T. V. Dyke and ACS grant IRG-93-033-15 to K. Simin. NR 30 TC 2 Z9 2 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 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2011 VL 9 IS 4 BP 430 EP 439 DI 10.1158/1541-7786.MCR-10-0277 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 749ZI UT WOS:000289511600005 PM 21385880 ER PT J AU To, KKW Robey, R Zhan, ZR Bangiolo, L Bates, SE AF To, Kenneth K. W. Robey, Robert Zhan, Zhirong Bangiolo, Lois Bates, Susan E. TI Upregulation of ABCG2 by Romidepsin via the Aryl Hydrocarbon Receptor Pathway SO MOLECULAR CANCER RESEARCH LA English DT Article ID HISTONE-DEACETYLASE INHIBITORS; BREAST-CANCER CELLS; AH-RECEPTOR; CHAPERONE FUNCTION; DEPSIPEPTIDE FR901228; MULTIDRUG-RESISTANCE; INDUCED ACTIVATION; HYDROXAMIC ACID; LIGAND-BINDING; LEUKEMIA-CELLS AB Histone deacetylase inhibitors (HDACI) are promising anticancer agents and their use in combination with conventional anticancer drugs is currently under investigation. We previously reported cell line-specific upregulation of ABCG2, a multidrug resistance transporter shown to control oral bioavailability and CNS penetration, by the HDACI romidepsin, although the precise mechanism in a particular cell line remains to be determined. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that can be activated by numerous environmental contaminants and has been shown to be a client protein of heat shock protein 90 (Hsp90). A xenobiotic response element was defined in the ABCG2 promoter and was shown to mediate AhR signaling. Activated AhR was found to be associated with the ABCG2 promoter only in cell line models that respond to romidepsin with ABCG2 upregulation. Our data suggest that romidepsin acetylated Hsp70 and inhibited the chaperone function of Hsp90, thereby allowing the dissociation of AhR from Hsp90. The dissociation of AhR from Hsp90 may be a prerequisite for the differential upregulation of ABCG2 by romidepsin. Increasing our understanding of the mechanism(s) governing differential upregulation of ABCG2 in response to romidepsin could provide an insight into strategies needed to tackle resistance to HDACIs in cancer therapeutics. Mol Cancer Res; 9(4); 516-27. (C) 2011 AACR. C1 [To, Kenneth K. W.] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China. [To, Kenneth K. W.; Robey, Robert; Zhan, Zhirong; Bangiolo, Lois; Bates, Susan E.] NCI, Mol Therapeut Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP To, KKW (reprint author), Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China. EM kennethto@cuhk.edu.hk RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU NIH, National Cancer Institute, Center for Cancer Research; School of Pharmacy, Chinese University of Hong Kong FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Seed Research Funding provided by the School of Pharmacy, Chinese University of Hong Kong (K.K.W. To). NR 56 TC 20 Z9 21 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 EI 1557-3125 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2011 VL 9 IS 4 BP 516 EP 527 DI 10.1158/1541-7786.MCR-10-0270 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 749ZI UT WOS:000289511600013 PM 21357443 ER PT J AU Woo, HG Park, ES Thorgeirsson, SS Kim, YJ AF Woo, Hyun Goo Park, Eun Sung Thorgeirsson, Snorri S. Kim, Yoon Jun TI Exploring Genomic Profiles of Hepatocellular Carcinoma SO MOLECULAR CARCINOGENESIS LA English DT Article DE signature; microarray; integrative analysis; hepatocellular carcinoma ID GENE-EXPRESSION SIGNATURE; LIVER-CANCER; MOLECULAR CLASSIFICATION; HEPATITIS-B; INTEGRATIVE ANALYSIS; THERAPEUTIC TARGETS; MICRORNA EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; RNA-SEQ AB Gene expression profiling using microarray technologies provides a powerful approach to understand complex biological systems and the pathogenesis of diseases. In the field of liver cancer research, a number of genome-wide profiling studies have been published. These studies have provided gene sets, that is, signature, which could classify tumors and predict clinical outcomes such as survival, recurrence, and metastasis. More recently, the application of genomic profiling has been extended to identify molecular targets, pathways, and the cellular origins of the tumors. Systemic and integrative analyses of multiple data sets and emerging new technologies also accelerate the progress of the cancer genomic studies. Here, we review the genomic signatures identified from the genomic profiling studies of hepatocellular carcinoma (HCC), and categorize and characterize them into prediction, phenotype, function, and molecular target signatures according to their utilities and properties. Our classification of the signatures would be helpful to understand and design studies with extended application of genomic profiles. (C) 2011 Wiley-Liss, Inc. C1 [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 110744, South Korea. [Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul 110744, South Korea. [Woo, Hyun Goo] Ajou Univ, Sch Med, Dept Physiol, Suwon 441749, South Korea. [Park, Eun Sung] Yonsei Univ, Coll Med, Med Convergence Res Inst, Seoul, South Korea. [Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kim, YJ (reprint author), Seoul Natl Univ, Coll Med, Dept Internal Med, 28 Yongon Dong, Seoul 110744, South Korea. RI Kim, Yoon Jun/J-2746-2012 FU Ministry for Health and Welfare, Republic of Korea [0920280]; Ministry of Education, Science and Technology [2010-0001200] FX This project was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (0920280), and the Basic Research Laboratory (BRL) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2010-0001200). NR 74 TC 31 Z9 32 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 EI 1098-2744 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 2011 VL 50 IS 4 SI SI BP 235 EP 243 DI 10.1002/mc.20691 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 748SX UT WOS:000289413200003 PM 21465573 ER PT J AU Gaillard, WD Berl, MM Duke, ES Ritzl, E Miranda, S Liew, C Finegersh, A Martinez, A Dustin, I Sato, S Theodore, WH AF Gaillard, W. D. Berl, M. M. Duke, E. S. Ritzl, E. Miranda, S. Liew, C. Finegersh, A. Martinez, A. Dustin, I. Sato, S. Theodore, W. H. TI fMRI language dominance and FDG-PET hypometabolism SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; COMPLEX PARTIAL EPILEPSY; POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; BLOOD-FLOW; HIPPOCAMPAL SCLEROSIS; GLUCOSE-METABOLISM; RECEPTOR-BINDING; PARTIAL SEIZURES; LATERALIZATION AB Background: Atypical language dominance is common in patients with temporal lobe epilepsy. We examined the association of left temporal hypometabolism with laterality of fMRI activation in a language task in a cross-sectional study. Methods: Thirty patients with temporal lobe epilepsy (mean age 32.4 +/- 11.0 years [range 1855]; epilepsy onset 15.3 +/- 11.3 years [range 0.8-40]; 22 left focus, 8 right focus) had (18)fluorodeoxyglucose (FDG)-PET using noninvasive cardiac input function. After MRI-based partial volume correction, regional glucose metabolism (CMRglc) was measured and asymmetry index, AI = 2(L - R)/(L + R), calculated. fMRI language dominance was assessed with an auditory definition decision paradigm at 3 T. fMRI data were analyzed in SPM2 using regions of interest from Wake Forest PickAtlas (Wernicke area [WA], inferior frontal gyrus [IFG], middle frontal gyrus [MFG]) and bootstrap laterality index, LI = (L - R/L + R). Results: Nineteen patients had ipsilateral temporal hypometabolism; 3 of 4 patients with atypical language had abnormal FDG-PET. Increasing left midtemporal hypometabolism correlated with decreased MFG LI (r = -0.41, p < 0.05) and showed trends with WA LI (r = -0.37, p = 0.055) and IFG LI (r = -0.31, p = 0.099); these relationships became more significant after controlling for age at onset. Increasing hypometabolism was associated with fewer activated voxels in WA ipsilateral to the focus and more activated voxels contralaterally, but overall, activation amount in left WA was similar to subjects without left temporal hypometabolism (t = -1.39, p > 0.10). Conclusions: We did not find evidence of impaired blood oxygenation level-dependent response in hypometabolic cortex. Regional hypometabolism appears to be a marker for the temporal lobe dysfunction that leads to displacement of language function. Neurology (R) 2011;76:1322-1329 C1 [Gaillard, W. D.; Berl, M. M.; Duke, E. S.] George Washington Univ, Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA. [Gaillard, W. D.; Duke, E. S.; Ritzl, E.; Miranda, S.; Liew, C.; Finegersh, A.; Martinez, A.; Dustin, I.; Sato, S.; Theodore, W. H.] Natl Inst Neurol Disorders & Stroke, Clin Epilepsy Sect, NIH, Bethesda, MD USA. [Ritzl, E.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. RP Gaillard, WD (reprint author), George Washington Univ, Childrens Natl Med Ctr, Ctr Neurosci, 111 Michigan Ave NW, Washington, DC 20010 USA. EM wgaillar@cnmc.org FU Clinical Epilepsy Section, NINDS, NIH; Pediatric Research Epilepsy Foundation; Children's Research Institute; Lundbeck Inc.; King Pharmaceuticals; PRA International; Eisai Inc.; Marinus Pharmaceuticals, Inc.; NIH (NINDS, NICHD, NIMH); CDC; NIH; NIH/NINDS DIR FX Supported by the Clinical Epilepsy Section, NINDS, NIH; Partnership for Pediatric Research Epilepsy Foundation (M.M.B.); and the Children's Research Institute Avery Award (M.M.B.). The contents are solely the responsibility of the authors and do not necessarily represent the official views of NIH.; Dr. Gaillard has served on a scientific advisory board for GE Healthcare and educational material advisory panels for Ovation Pharmaceuticals (now Lundbeck Inc.) and Questcor Pharmaceuticals, Inc.; served as an editor of Epilepsia; his department derives income from the clinical evaluation and management of children with epilepsy including performing EEG and vEEG; receives research support from Lundbeck Inc., King Pharmaceuticals, PRA International, Eisai Inc., Marinus Pharmaceuticals, Inc., the NIH (NINDS, NICHD, NIMH), and the CDC; and holds stock in Johnson & Johnson, Eli Lilly and Company, GlaxoSmithKline, and Pfizer Inc. Dr. Berl receives research support from the NIH. E. S. Duke reports no disclosures. Dr. Ritzl's spouse has served on the speakers' bureau for Wyeth. Dr. Miranda, Dr. Liew, A. Finegersh, A. Martinez, and I. Dustin report no disclosures. Dr. Sato receives research support and salary from NIH/NINDS DIR. Dr. Theodore serves as Co-editor-in-Chief of Epilepsy Research; receives research support and salary from the NIH/NINDS DIR; and holds stock in GE Healthcare. NR 35 TC 9 Z9 9 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD APR PY 2011 VL 76 IS 15 BP 1322 EP 1329 DI 10.1212/WNL.0b013e31821527b5 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 748RA UT WOS:000289407100010 PM 21368285 ER PT J AU Harada, T Lopez-Chavez, A Xi, L Raffeld, M Wang, Y Giaccone, G AF Harada, T. Lopez-Chavez, A. Xi, L. Raffeld, M. Wang, Y. Giaccone, G. TI Characterization of epidermal growth factor receptor mutations in non-small-cell lung cancer patients of African-American ancestry SO ONCOGENE LA English DT Article DE EGFR; mutation; African American; EGFR-TKI ID TYROSINE KINASE; GEFITINIB TREATMENT; GENE-MUTATIONS; EGFR MUTANTS; RESISTANCE; ACTIVATION; INHIBITOR; SENSITIVITY; ERLOTINIB; MECHANISM AB Epidermal growth factor receptor (EGFR) mutations are predictive markers for response to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in non-small-cell lung cancer (NSCLC). The most common mutations, exon 19 short deletions and exon 20 point mutation (L858R), activate the tyrosine kinase and confer sensitivity to EGFR-TKIs. However, the function and sensitivity of rare mutations to EGFR-TKIs are unknown. In this study, we found five EGFR mutations out of 16 patients with NSCLC of African-American descent. The frequency of such mutations in this patient population appears to be significantly higher than previously reported. Two of them (N771GY and A767-V769dup) are rare insertion mutations located in exon 20. Using YFP-tagged EGFR mutants, we demonstrated that the mutations confer increased kinase activity, but no sensitivity to erlotinib at clinically available concentrations. In addition, we examined efficacy of PF00299804, an irreversible EGFR-TKI. Although the drug failed to show efficacy to T790M and S768N mutations, the exon 20 insertion mutations were sensitive to PF00299804. These data suggest that rare mutations in exon 20 are resistant to erlotinib but may be sensitive to irreversible inhibitors. Oncogene (2011) 30, 1744-1752; doi:10.1038/onc.2010.545; published online 6 December 2010 C1 [Harada, T.; Lopez-Chavez, A.; Wang, Y.; Giaccone, G.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Xi, L.; Raffeld, M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Giaccone, G (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM giacconeg@mail.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 25 TC 18 Z9 19 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2011 VL 30 IS 15 BP 1744 EP 1752 DI 10.1038/onc.2010.545 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 749ZM UT WOS:000289512200002 PM 21132006 ER PT J AU Hollander, MC Maier, CR Hobbs, EA Ashmore, AR Linnoila, RI Dennis, PA AF Hollander, M. C. Maier, C. R. Hobbs, E. A. Ashmore, A. R. Linnoila, R. I. Dennis, P. A. TI Akt1 deletion prevents lung tumorigenesis by mutant K-ras SO ONCOGENE LA English DT Article DE Akt1; Akt3; K-ras; lung ID PLECKSTRIN HOMOLOGY DOMAIN; GLUCOSE-HOMEOSTASIS; ONCOGENIC MUTATION; THERAPEUTIC TARGET; TUMOR-DEVELOPMENT; MICE LACKING; IN-VIVO; CANCER; ACTIVATION; IDENTIFICATION AB K-ras mutations are associated with smoking-induced lung cancer and poor clinical outcomes. In mice, K-ras mutations are sufficient to induce lung tumors, which require phosphoinoside-3-kinase (PI3K) and further downstream, mammalian target of rapamycin (mTOR) activation. However, the roles of individual Akt isoforms that link PI3K and mTOR are unknown. Here, we show that deletion of Akt1 but not Akt2 or Akt3 prevents lung tumorigenesis in a tobacco carcinogen-induced model and a genetic model. Akt1 deletion prevented tumor initiation as well as tumor progression, coincident with decreased Akt signaling in tumor tissues. In contrast, deletion of Akt3 increased tumor multiplicity in the carcinogen model and increased tumor size in the genetic model. Fibroblasts lacking Akt1 are resistant to transformation by mutant K-ras and stimulation by epidermal growth factor. Human lung cancer cells with mutant K-ras and diminished Akt1 levels fail to grow in vivo. These data suggest that Akt1 is the primary Akt isoform activated by mutant K-ras in lung tumors, and that Akt3 may oppose Akt1 in lung tumorigenesis and lung tumor progression. Given that Akt inhibitors in clinical development as cancer therapeutics are not isoform selective, these studies support specific targeting of Akt1 to mitigate the effects of mutant K-ras in lung cancer. Oncogene (2011) 30, 1812-1821; doi:10.1038/onc.2010.556; published online 17 January 2011 C1 [Hollander, M. C.; Maier, C. R.; Hobbs, E. A.; Ashmore, A. R.; Dennis, P. A.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20889 USA. [Linnoila, R. I.] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, NIH, NNMC8-5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@mail.nih.gov FU NIH FX This project was funded through the NIH intramural research program. NR 49 TC 28 Z9 28 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2011 VL 30 IS 15 BP 1812 EP 1821 DI 10.1038/onc.2010.556 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 749ZM UT WOS:000289512200008 PM 21242979 ER PT J AU Pacher, P Mechoulam, R AF Pacher, P. Mechoulam, R. TI Is lipid signaling through cannabinoid 2 receptors part of a protective system? SO PROGRESS IN LIPID RESEARCH LA English DT Review DE Endocannabinoids; Cannabinoid 1 and 2 receptors; Disease; Inflammation; Immune function; Disease ID ACID AMIDE HYDROLASE; HEPATIC ISCHEMIA/REPERFUSION INJURY; ISCHEMIA-REPERFUSION INJURY; CEREBRAL ISCHEMIC/REPERFUSION INJURY; ACTIVATED ENDOCANNABINOID SYSTEM; AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN MONOCYTE MIGRATION; FOS PROTEIN EXPRESSION; LONG-TERM DEPRESSION; CB2 RECEPTOR AB The mammalian body has a highly developed immune system which guards against continuous invading protein attacks and aims at preventing, attenuating or repairing the inflicted damage. It is conceivable that through evolution analogous biological protective systems have been evolved against non-protein attacks. There is emerging evidence that lipid endocannabinoid signaling through cannabinoid 2 (CB2) receptors may represent an example/part of such a protective system/armamentarium. Inflammation/tissue injury triggers rapid elevations in local endocannabinoid levels, which in turn regulate signaling responses in immune and other cells modulating their critical functions. Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans, ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer, and modulating CB2 receptor activity holds tremendous therapeutic potential in these pathologies. While CB2 receptor activation in general mediates immunosuppressive effects, which limit inflammation and associated tissue injury in large number of pathological conditions, in some disease states activation of the CB2 receptor may enhance or even trigger tissue damage, which will also be discussed alongside the protective actions of the CB2 receptor stimulation with endocannabinoids or synthetic agonists, and the possible biological mechanisms involved in these effects. Published by Elsevier Ltd. C1 [Pacher, P.] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. [Mechoulam, R.] Hebrew Univ Jerusalem, Fac Med, Inst Drug Res, Jerusalem, Israel. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413, Bethesda, MD 20892 USA. EM Pacher@mail.nih.gov; mechou@cc.huji.ac.il RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU NIH/NIAAA; NIDA [9789] FX This study was supported by the Intramural Research Program of NIH/NIAAA (to P.P.) and by NIDA grant #9789 (to R.M.). The authors are indebted to Dr. George Kunos for providing key resources and support and apologize to colleagues whose important work could not be cited because of the size limitations of this review. NR 286 TC 142 Z9 145 U1 0 U2 33 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7827 J9 PROG LIPID RES JI Prog. Lipid Res. PD APR PY 2011 VL 50 IS 2 BP 193 EP 211 DI 10.1016/j.plipres.2011.01.001 PG 19 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 750KA UT WOS:000289543800004 PM 21295074 ER PT J AU Johnson, CH Patterson, AD Krausz, KW Lanz, C Kang, DW Luecke, H Gonzalez, FJ Idle, JR AF Johnson, Caroline H. Patterson, Andrew D. Krausz, Kristopher W. Lanz, Christian Kang, Dong Wook Luecke, Hans Gonzalez, Frank J. Idle, Jeffrey R. TI Radiation Metabolomics. 4. UPLC-ESI-QTOFMS-Based Metabolomics for Urinary Biomarker Discovery in Gamma-Irradiated Rats SO RADIATION RESEARCH LA English DT Article ID IONIZING-RADIATION; MESSENGER-RNA; STRESS GENES; NITRIC-OXIDE; EXCRETION; CANCER; METABOLISM; EXPRESSION; EXPOSURE; TAURINE AB Johnson, C. H, Patterson, A. D., Krausz, K. W., Lanz, C., Kang, D. W., Luecke, H., Gonzalez, F. J. and Idle, J. R. Radiation Metabolomics. 4. UPLC-ESI-QTOFMS-Based Metabolomics for Urinary Biomarker Discovery in Gamma-Irradiated Rats. Radiat. Res. 175, 473-484 (2011). Radiation metabolomics has aided in the identification of a number of biomarkers in cells and mice by ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and in rats by gas chromatography-coupled mass spectrometry (GCMS). These markers have been shown to be both dose- and time-dependent. Here UPLC-ESI-QTOFMS was used to analyze rat urine samples taken from 12 rats over 7 days; they were either sham-irradiated or gamma-irradiated with 3 Gy after 4 days of metabolic cage acclimatization. Using multivariate data analysis, nine urinary biomarkers of gamma radiation in rats were identified, including a novel mammalian metabolite, N-acetyltaurine. These upregulated urinary biomarkers were confirmed through tandem mass spectrometry and comparisons with authentic standards. They include thymidine, 2'-deoxyuridine, 2'deoxyxanthosine, N'-acetylspermidine, N-acetylglucosamine/galactosamine-6-sulfate, N-acetyltaurine, N-hexanoylglyeine, taurine and, tentatively, isethionic acid. Of these metabolites, 2'-deoxyuridine and thymidine were previously identified in the rat by GCMS (observed as uridine and thymine) and in the mouse by UPLC-ESI-QTOFMS. 2'Deoxyxanthosine, taurine and N-hexanoylglycine were also seen in the mouse by UPLC-ESI-QTOFMS. These are now unequivocal cross-species biomarkers for ionizing radiation exposure. Downregulated biomarkers were shown to be related to food deprivation and starvation mechanisms. The UPLC-ESI-QTOFMS approach has aided in the advance for finding common biomarkers of ionizing radiation exposure. (C) 2011 by Radiation Research Society C1 [Lanz, Christian; Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol & Visceral Res, CH-3010 Bern, Switzerland. [Johnson, Caroline H.; Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kang, Dong Wook; Luecke, Hans] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Idle, JR (reprint author), Univ Bern, Inst Clin Pharmacol & Visceral Res, Murtenstr 35, CH-3010 Bern, Switzerland. EM jidle@ikp.unibe.ch RI Patterson, Andrew/G-3852-2012; OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520 FU National Cancer Institute; NIH (NIAID) [U19 AI067773-05/06] FX This work was supported by the National Cancer Institute Intramural Research Program and also performed as part of the Columbia University Center for Medical Countermeasures against Radiation (P.I. David Brenner) funded by NIH (NIAID) grant U19 AI067773-05/06. NR 29 TC 58 Z9 61 U1 0 U2 20 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD APR PY 2011 VL 175 IS 4 BP 473 EP 484 DI 10.1667/RR2437.1 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 747KP UT WOS:000289319000008 PM 21309707 ER PT J AU Singh, NK Fleshman, R AF Singh, Nishith K. Fleshman, Ranleigh TI Extramedullary Hematopoiesis on the Aortic Valve SO TEXAS HEART INSTITUTE JOURNAL LA English DT Editorial Material C1 [Singh, Nishith K.] So Illinois Univ, Sch Med, Dept Internal Med, Springfield, IL 62794 USA. [Fleshman, Ranleigh] So Illinois Univ, Sch Med, Dept Pathol & Lab Med, Springfield, IL 62794 USA. [Fleshman, Ranleigh] Pathol Associates Cent Illinois Ltd, Springfield, IL 62781 USA. RP Singh, NK (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr MSC 1475,Bldg 10,CRC 4-5140, Bethesda, MD 20892 USA. EM nishith.singh@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 EI 1526-6702 J9 TEX HEART I J JI Tex. Heart Inst. J. PD APR PY 2011 VL 38 IS 2 BP 210 EP 211 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 749FM UT WOS:000289449200031 PM 21494542 ER PT J AU Bolukbas, S Eberlein, MH Schirren, J AF Boeluekbas, S. Eberlein, M. H. Schirren, J. TI Pneumonectomy vs. Sleeve Resection for Non-Small Cell Lung Carcinoma in the Elderly: Analysis of Short-term and Long-term Results SO THORACIC AND CARDIOVASCULAR SURGEON LA English DT Article DE pneumonectomy; sleeve resection; NSCLC; elderly ID PULMONARY RESECTION; CANCER; LOBECTOMY; SURVIVAL; OCTOGENARIANS; CARBOPLATIN; PACLITAXEL; CISPLATIN AB Background: Aim of the study was to assess the short-and long-term results of sleeve resections and pneumonectomies for centrally located non-small cell lung cancer (NSCLC) in a cohort of elderly patients. Methods: We retrospectively reviewed our prospective database of all patients aged >= 70 years who underwent sleeve resection (SL group) or pneumonectomy (PN group) for NSCLC between January 1999 and December 2005. Patients' characteristics, morbidity, mortality and survival were analyzed and compared between groups. Results: Sixty patients qualified for the analysis, of whom 31 underwent sleeve resection and 29 had pneumonectomy. Both groups were statistically equivalent with regard to age (73.6 +/- 2.4 vs. 74.2 +/- 3.6 years), sex, comorbidities, histology, completeness of resection and stage. Presurgical FEV1 was higher in the PN group (p = 0.02). There were no statistical differences in the morbidity rate (SL: 41.9%, PN: 44.8%), mortality rate (SL: 6.5%, PN: 10.3%), local recurrence (SL: 3.2%, PN: 0%) or distant metastases (SL: 19.4%, PN: 24.1%). The loss of FEV1 was higher in the PN group (27.3%) compared to the SL group (12.0%; p = 0.001). Overall 5-year survival and mean survival for SL patients was 59% and 51.9 months compared to 0% and 30.1 months for the PN patients (p = 0.038). In patients with stage N2 disease, the type of surgery showed a trend to prolonged long-term survival favoring sleeve resection (p = 0.096). Conclusion: In specialized centers both pneumonectomy and sleeve resection can be performed with acceptable mortality and morbidity rates in elderly patients with centrally located NSCLC. In elderly patients with anatomically suitable NSCLC, sleeve resections offer better functional results and long-term survival irrespective of nodal status. C1 [Boeluekbas, S.; Schirren, J.] Dr Horst Schmidt Klin, Dept Thorac Surg, D-65199 Wiesbaden, Germany. [Eberlein, M. H.] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD USA. [Eberlein, M. H.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Bolukbas, S (reprint author), Dr Horst Schmidt Klin, Dept Thorac Surg, Ludwig Erhard Str 100, D-65199 Wiesbaden, Germany. EM servet_boeluekbas@web.de NR 29 TC 10 Z9 10 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0171-6425 J9 THORAC CARDIOV SURG JI Thorac. Cardiovasc. Surg. PD APR PY 2011 VL 59 IS 3 BP 142 EP 147 DI 10.1055/s-0030-1250426 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 747UA UT WOS:000289344000004 PM 21480133 ER PT J AU Hauth, JC Clifton, RG Roberts, JM Myatt, L Spong, CY Leveno, KJ Varner, MW Wapner, RJ Thorp, JM Mercer, BM Peaceman, AM Ramin, SM Carpenter, MW Samuels, P Sciscione, A Tolosa, JE Saade, G Sorokin, Y Anderson, GD AF Hauth, John C. Clifton, Rebecca G. Roberts, James M. Myatt, Leslie Spong, Catherine Y. Leveno, Kenneth J. Varner, Michael W. Wapner, Ronald J. Thorp, John M., Jr. Mercer, Brian M. Peaceman, Alan M. Ramin, Susan M. Carpenter, Marshall W. Samuels, Philip Sciscione, Anthony Tolosa, Jorge E. Saade, George Sorokin, Yoram Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst TI Maternal insulin resistance and preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 07-12, 2011 CL San Francisco, CA SP Soc Maternal Fetal Med DE insulin resistance; low-risk nulliparous woman; preeclampsia ID HOMEOSTASIS MODEL ASSESSMENT; DIABETES-MELLITUS; PREGNANT-WOMEN; PLASMA-GLUCOSE; SENSITIVITY; METABOLISM; STANDARDIZATION; CARBOHYDRATE; HYPERTENSION; SECRETION AB OBJECTIVE: The purpose of this study was to determine whether mid-trimester insulin resistance is associated with subsequent preeclampsia. STUDY DESIGN: This was a secondary analysis of 10,154 nulliparous women who received vitamin C and E or placebo daily from 9-16 weeks gestation until delivery. Of these, 1187 women had fasting plasma glucose and insulin tested between 22 and 26 weeks gestation. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index. RESULTS: Obese women were twice as likely to have a HOMA-IR result of >= 75th percentile. Hispanic and African American women had a higher percentage at >= 75th percentile for HOMA-IR than white women (42.2%, 27.2%, and 16.9%, respectively; P < .001). A HOMA-IR result of >= 75th percentile was higher among the 85 nulliparous women who subsequently had preeclampsia, compared with women who remained normotensive (40.5% vs 24.8%; adjusted odds ratio, 1.9; 95% confidence interval, 1.1-3.2). Quantitative insulin sensitivity check index results were similar to the HOMA-IR results. CONCLUSION: Midtrimester maternal insulin resistance is associated with subsequent preeclampsia. C1 [Hauth, John C.] Univ Alabama, Dept Obstet & Gynecol, Sch Med, Birmingham, AL 35249 USA. [Clifton, Rebecca G.] George Washington Univ, Ctr Biostat, Washington, DC USA. [Roberts, James M.] Univ Pittsburgh, Pittsburgh, PA USA. [Myatt, Leslie] Univ Cincinnati, Cincinnati, OH USA. [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Varner, Michael W.] Univ Utah, Salt Lake City, UT USA. [Wapner, Ronald J.] Columbia Univ, New York, NY USA. [Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Mercer, Brian M.] Case Western Reserve Univ, MetroHlth Med Ctr, Cleveland, OH 44106 USA. [Peaceman, Alan M.] Northwestern Univ, Chicago, IL 60611 USA. [Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Carpenter, Marshall W.] Brown Univ, Providence, RI 02912 USA. [Samuels, Philip] Ohio State Univ, Columbus, OH 43210 USA. [Sciscione, Anthony] Drexel Univ, Philadelphia, PA 19104 USA. [Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Saade, George] Univ Texas Med Branch, Galveston, TX USA. [Sorokin, Yoram] Wayne State Univ, Detroit, MI USA. [Anderson, Garland D.] Univ Texas Med Ctr, Galveston, TX USA. RP Hauth, JC (reprint author), Univ Alabama, Dept Obstet & Gynecol, Sch Med, 619 19th St S 176F,Suite 10360, Birmingham, AL 35249 USA. EM jchauth@uab.edu RI Samuels, Philip/E-4011-2011; Varner, Michael/K-9890-2013 OI Peaceman, Alan/0000-0002-4515-4850; Varner, Michael/0000-0001-9455-3973 FU NCRR NIH HHS [M01 RR000080, M01 RR00080, UL1 RR024153, UL1 RR024989, UL1RR025777]; NICHD NIH HHS [HD53097, HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, HD53118, R24 HD050924, U01 HD036801, U10 HD021410, U10 HD027860, U10 HD027869, U10 HD027869-23, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, U10 HD040500, U10 HD040512, U10 HD040544, U10 HD040545, U10 HD040560, U10 HD053097, U10 HD053118, UG1 HD027869, UG1 HD027915, UG1 HD034116, UG1 HD034208, UG1 HD040485, UG1 HD040500, UG1 HD040512, UG1 HD040544, UG1 HD040545, UG1 HD040560, UG1 HD053097]; NIDDK NIH HHS [P30-DK56336, P60DK079626] NR 23 TC 5 Z9 9 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2011 VL 204 IS 4 AR 327.e1 DI 10.1016/j.ajog.2011.02.024 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 743ZD UT WOS:000289058800028 PM 21458622 ER PT J AU Sibai, BM Koch, MA Freire, S Silva, JLPE Rudge, MVC Martins-Costa, S Moore, J Santos, CD Cecatti, JG Costa, R Ramos, JG Moss, N Spinnato, JA AF Sibai, Baha M. Koch, Matthew A. Freire, Salvio Pinto e Silva, Joao Luiz Cunha Rudge, Marilza Vieira Martins-Costa, Sergio Moore, Janet Santos, Cleide de Barros Cecatti, Jose Guilherme Costa, Roberto Ramos, Jose Geraldo Moss, Nancy Spinnato, Joseph A., II TI The impact of prior preeclampsia on the risk of superimposed preeclampsia and other adverse pregnancy outcomes in patients with chronic hypertension SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL San Diego, CA SP Soc Maternal-Fetal Med DE adverse pregnancy outcome; chronic hypertension; superimposed preeclampsia ID WOMEN AB OBJECTIVE: We sought to compare the rates of superimposed preeclampsia and adverse outcomes in women with chronic hypertension with or without prior preeclampsia. STUDY DESIGN: We conducted secondary analysis of 369 women with chronic hypertension (104 with prior preeclampsia) enrolled at 12-19 weeks as part of a multisite trial of antioxidants to prevent preeclampsia (no reduction was found). Outcome measures were rates of superimposed preeclampsia and other adverse perinatal outcomes. RESULTS: Prepregnancy body mass index, blood pressure, and smoking status at enrollment were similar between groups. The rates of superimposed preeclampsia (17.3% vs 17.7%), abruptio placentae (1.0% vs 3.1%), perinatal death (6.7% vs 8.7%), and small for gestational age (18.4% vs 14.3%) were similar between groups, but preterm delivery <37 weeks was higher in the prior preeclampsia group (36.9% vs 27.1%; adjusted risk ratio, 1.46; 95% confidence interval, 1.05-2.03; P = .032). CONCLUSION: In women with chronic hypertension, a history of preeclampsia does not increase the rate of superimposed preeclampsia, but is associated with an increased rate of delivery at <37 weeks. C1 [Sibai, Baha M.; Spinnato, Joseph A., II] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Freire, Salvio; Santos, Cleide de Barros] Univ Fed Pernambuco, Hosp Clin, Recife, PE, Brazil. [Pinto e Silva, Joao Luiz; Cecatti, Jose Guilherme] Univ Estadual Campinas, Campinas, SP, Brazil. [Cunha Rudge, Marilza Vieira; Martins-Costa, Sergio] Univ Estadual Paulista, Botucatu, SP, Brazil. [Martins-Costa, Sergio; Ramos, Jose Geraldo] Univ Fed Rio Grande do Sul, Hosp Clin, Porto Alegre, RS, Brazil. [Koch, Matthew A.; Moore, Janet] RTI Int, Res Triangle Pk, NC USA. [Moss, Nancy] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Sibai, BM (reprint author), 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM baha.sibai@uc.edu RI Rudge, Marilza /C-8338-2012 OI Rudge, Marilza /0000-0002-9227-832X FU NICHD NIH HHS [1 U01 HD40565, U01 HD44036] NR 14 TC 5 Z9 6 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2011 VL 204 IS 4 AR 345.e1 DI 10.1016/j.ajog.2010.11.027 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 743ZD UT WOS:000289058800036 PM 21354549 ER PT J AU Gao, B Seki, E Brenner, DA Friedman, S Cohen, JI Nagy, L Szabo, G Zakhari, S AF Gao, Bin Seki, Ekihiro Brenner, David A. Friedman, Scott Cohen, Jessica I. Nagy, Laura Szabo, Gyongyi Zakhari, Samir TI Innate immunity in alcoholic liver disease SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Review DE alcoholic liver injury; complement; NK cells; TLR4 ID NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR-4; HEPATITIS-C VIRUS; ACTIVATED STELLATE CELLS; NECROSIS-FACTOR-ALPHA; KUPFFER CELLS; CHRONIC ETHANOL; FATTY LIVER; NK CELLS; T-CELLS AB Gao B, Seki E, Brenner DA, Friedman S, Cohen JI, Nagy L, Szabo G, Zakhari S. Innate immunity in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 300: G516-G525, 2011. First published January 20, 2011; doi: 10.1152/ajpgi.00537.2010.-Excessive alcohol consumption is a leading cause of chronic liver disease in the Western world. Alcohol-induced hepatotoxicity and oxidative stress are important mechanisms contributing to the pathogenesis of alcoholic liver disease. However, emerging evidence suggests that activation of innate immunity involving TLR4 and complement also plays an important role in initiating alcoholic steatohepatitis and fibrosis, but the role of adaptive immunity in the pathogenesis of alcoholic liver disease remains obscure. Activation of a TLR4-mediated MyD88-independent (TRIF/IRF-3) signaling pathway in Kupffer cells contributes to alcoholic steatohepatitis, whereas activation of TLR4 signaling in hepatic stellate cells promotes liver fibrosis. Alcohol consumption activates the complement system in the liver by yet unidentified mechanisms, leading to alcoholic steatohepatitis. In contrast to activation of TLR4 and complement, alcohol consumption can inhibit natural killer cells, another important innate immunity component, contributing to alcohol-mediated acceleration of viral infection and liver fibrosis in patients with chronic viral hepatitis. Understanding of the role of innate immunity in the pathogenesis of alcoholic liver disease may help us identify novel therapeutic targets to treat this disease. C1 [Gao, Bin] NIAAA, Lab Liver Dis, LPS, NIH, Bethesda, MD 20892 USA. [Zakhari, Samir] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA. [Seki, Ekihiro; Brenner, David A.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. [Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. [Cohen, Jessica I.; Nagy, Laura] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, LPS, NIH, 5625 Fishers Lane,Rm 2S-33, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov RI Seki, Ekihiro/K-2481-2016 FU NIAAA NIH HHS [R01 AA020172, R01 AA020172-01]; NIDDK NIH HHS [R01 DK085252, R01 DK085252-01A1]; NIGMS NIH HHS [R01 GM041804] NR 129 TC 77 Z9 78 U1 3 U2 19 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2011 VL 300 IS 4 BP G516 EP G525 DI 10.1152/ajpgi.00537.2010 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 746VT UT WOS:000289276500002 PM 21252049 ER PT J AU Liou, AP Sei, Y Zhao, XL Feng, JY Lu, XP Thomas, C Pechhold, S Raybould, HE Wank, SA AF Liou, Alice P. Sei, Yoshitatsu Zhao, Xilin Feng, Jianying Lu, Xinping Thomas, Craig Pechhold, Susanne Raybould, Helen E. Wank, Stephen A. TI The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE amino acid sensing; protein sensing; enteroendocrine ID ALTERNATIVELY SPLICED FORM; ANTRAL GASTRIN CELLS; CA2+-SENSING RECEPTOR; STC-1 CELLS; CATION CHANNEL; INSULIN-SECRETION; CA2+ OSCILLATIONS; TASTE RECEPTORS; FOOD-INTAKE; BETA-CELLS AB Liou AP, Sei Y, Zhao X, Feng J, Lu X, Thomas C, Pechhold S, Raybould HE, Wank SA. The extracellular calcium-sensing receptor is required for cholecystokinin secretion in response to L-phenylalanine in acutely isolated intestinal I cells. Am J Physiol Gastrointest Liver Physiol 300: G538-G546, 2011. First published January 20, 2011; doi: 10.1152/ajpgi.00342.2010.-The extracellular calcium-sensing receptor (CaSR) has recently been recognized as an L-amino acid sensor and has been implicated in mediating cholecystokinin (CCK) secretion in response to aromatic amino acids. We investigated whether direct detection of L-phenylalanine (L-Phe) by CaSR results in CCK secretion in the native I cell. Fluorescence-activated cell sorting of duodenal I cells from CCK-enhanced green fluorescent protein (eGFP) transgenic mice demonstrated CaSR gene expression. Immunostaining of fixed and fresh duodenal tissue sections confirmed CaSR protein expression. Intracellular calcium fluxes were CaSR dependent, stereoselective for L-Phe over D-Phe, and responsive to type II calcimimetic cinacalcet in CCK-eGFP cells. Additionally, CCK secretion by an isolated I cell population was increased by 30 and 62% in response to L-Phe in the presence of physiological (1.26 mM) and superphysiological (2.5 mM) extracellular calcium concentrations, respectively. While the deletion of CaSR from CCK-eGFP cells did not affect basal CCK secretion, the effect of L-Phe or cinacalcet on intracellular calcium flux was lost. In fact, both secretagogues, as well as superphysiological Ca(2+), evoked an unexpected 20-30% decrease in CCK secretion compared with basal secretion in CaSR(-/-) CCK-eGFP cells. CCK secretion in response to KCl or tryptone was unaffected by the absence of CaSR. The present data suggest that CaSR is required for hormone secretion in the specific response to L-Phe by the native I cell, and that a receptor-mediated mechanism may inhibit hormone secretion in the absence of a fully functional CaSR. C1 [Liou, Alice P.; Sei, Yoshitatsu; Zhao, Xilin; Feng, Jianying; Lu, Xinping; Wank, Stephen A.] NIDDK, DDB, NIH, Bethesda, MD 20892 USA. [Liou, Alice P.; Raybould, Helen E.] Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. [Pechhold, Susanne] NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Thomas, Craig] NHGRI, Chem Genom Ctr, Bethesda, MD 20892 USA. RP Wank, SA (reprint author), NIDDK, DDB, NIH, 10-9C-101, Bethesda, MD 20892 USA. EM stevew@bdg10.niddk.nih.gov FU University of California, Davis School of Veterinary Medicine; National Institute of Diabetes and Digestive and Kidney Diseases [DK-41004] FX This work was partially supported by the Veterinary Scientists Training Program, University of California, Davis School of Veterinary Medicine (A. P. Liou) and by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK-41004 (H. E. Raybould). NR 47 TC 66 Z9 71 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2011 VL 300 IS 4 BP G538 EP G546 DI 10.1152/ajpgi.00342.2010 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 746VT UT WOS:000289276500005 PM 21252045 ER PT J AU Ogwang, MD Zhao, W Ayers, LW Mbulaiteye, SM AF Ogwang, Martin D. Zhao, Weigiang Ayers, Leona W. Mbulaiteye, Sam M. TI Accuracy of Burkitt Lymphoma Diagnosis in Constrained Pathology Settings Importance to Epidemiology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NON-HODGKIN-LYMPHOMA; EAST-AFRICA; UGANDA; CANCER; INFECTION; CAPACITY AB Context.-Burkitt lymphoma (BL) is endemic in Uganda and because of the high incidence, diagnosis is often presumed during clinical care and epidemiologic studies. Objectives.-To assess the accuracy of the clinical and the local pathology diagnosis of BL as assessed by an outside pathology review diagnosis and to understand the limitations on histopathology practice in a resource-constrained setting at 1 hospital in Uganda. Design.-Clinically presumed pediatric (<15 years) BL cases with biopsies and pathology reports, from 1993 to 2007, were identified at St Mary's Hospital, Lacor (Gulu, Uganda). Local histopathology procedures, hematoxylin-eosin-stained tissue sections, and formalin-fixed paraffin-embedded blocks were reviewed onsite by an outside pathologist, followed by outside study that included tissue microarray immunohistochemistry and in situ hybridization. Results.-Local pathology laboratory procedures were inconsistent and suboptimal, especially for tissue fixation. There were 88 clinically presumed BL cases. Sixty-three could be reviewed by outside pathology (25 cases of lost blocks or no remaining tumor) and showed a clinical diagnostic accuracy of 75% (47 confirmed of 63), with a possible range of 62% to 85%, depending on the actual diagnosis of the 25 nonevaluable cases. There were 64 BL cases diagnosed by local pathology. Forty-five could be reviewed by outside pathology (19 cases of lost blocks or no remaining tumor) and showed a local pathology diagnostic accuracy of 82% (37 confirmed of 45), with a possible range of 58% to 88%, depending on the actual diagnosis of the 19 nonevaluable cases. Non-BL diagnoses included other non-Hodgkin lymphomas, Hodgkin lymphoma, and benign infectious lymphadenopathy. Conclusions.-Accuracy of clinical diagnosis of BL was reduced by inclusion of other diseases with similar clinical presentations. Local pathology, using morphology alone, only marginally improved clinical accuracy and often could not support outside pathology review due to inadequate laboratory procedures. There is an urgent need to improve pathology services in Uganda before conducting high-quality clinical and epidemiologic studies. (Arch Pathol Lab Med. 2011;135:445-450) C1 [Ogwang, Martin D.] St Marys Hosp, Dept Surg, Lacor, Gulu, Uganda. [Zhao, Weigiang; Ayers, Leona W.] Ohio State Univ, Ctr Comprehens Canc, Pathol Core Res Lab, Columbus, OH 43210 USA. [Mbulaiteye, Sam M.] NCI, Infect & Immunoepidemiol Branch, DCEG, Bethesda, MD 20892 USA. RP Mbulaiteye, SM (reprint author), DCEG, Infect & Immunoepidemiol Branch, 6120 Execut Blvd,Execut Plaza S Room 7080, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov RI Zhao, Weiqiang/E-4368-2011 FU Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (Bethesda, Maryland); NCI Infections and Epidemiology Branch (Bethesda, Maryland); Ohio State University FX We thank Mr David Nohle, MS, of The Ohio State University AIDS and Cancer Specimen Resource for comments on the manuscript. We also thank the reviewers for their comments, which greatly improved the clarity of our manuscript. This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services (Bethesda, Maryland) and with an Extramural Research Program grant to NCI Infections and Epidemiology Branch (Bethesda, Maryland) and The Ohio State University Comprehensive Cancer Center Research Enhancement and Assistance Program (REAP 200925). NR 23 TC 11 Z9 11 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2011 VL 135 IS 4 BP 445 EP 450 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 746BS UT WOS:000289217200011 PM 21466360 ER PT J AU Bandiera, FC Richardson, AK Lee, DJ He, JP Merikangas, KR AF Bandiera, Frank C. Richardson, Amanda Kalaydjian Lee, David J. He, Jian-Ping Merikangas, Kathleen R. TI Secondhand Smoke Exposure and Mental Health Among Children and Adolescents SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; ENVIRONMENTAL TOBACCO-SMOKE; ALLOSTATIC LOAD; PASSIVE SMOKING; MATERNAL DEPRESSION; PARENTAL SMOKING; RESPIRATORY SYMPTOMS; NICOTINE METABOLISM; CHILDHOOD ASTHMA; CUMULATIVE RISK AB Objective: To examine a potential association between biologically confirmed secondhand smoke exposure and symptoms of Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) major depressive disorder, generalized anxiety disorder, panic disorder, attention-deficit/hyperactivity disorder, and conduct disorder using a nationally representative sample of US children and adolescents. Design: Nationally representative cross-sectional survey of the United States. Setting: Continental United States. Participants: Children and adolescents aged 8 to 15 years who participated in the National Health and Nutrition Examination Survey from 2001 to 2004. Intervention: Measurement of serum cotinine level to assess secondhand smoke exposure among nonsmokers. Main Outcome Measures: The DSM-IV symptoms were derived from selected modules of the National Institute of Mental Health's Diagnostic Interview Schedule for Children Version IV, a structured diagnostic interview administered by trained lay interviewers. Results: Among nonsmokers, serum cotinine level was positively associated with symptoms of DSM-IV major depressive disorder, generalized anxiety disorder, attention-deficit/hyperactivity disorder, and conduct disorder after adjusting for survey design, age, sex, race/ethnicity, poverty, migraine, asthma, hay fever, maternal smoking during pregnancy, and allostatic load. Associations with serum cotinine level were more apparent for boys and for participants of non-Hispanic white race/ethnicity. Conclusions: Our results are consistent with a growing body of research documenting an association between secondhand smoke exposure and mental health outcomes. Future research is warranted to establish the biological or psychological mechanisms of association. C1 [He, Jian-Ping; Merikangas, Kathleen R.] NIMH, Genet Epidemiol Res Branch, NIH, Bethesda, MD 20892 USA. [Bandiera, Frank C.; Lee, David J.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Richardson, Amanda Kalaydjian] Legacy, Washington, DC USA. RP Merikangas, KR (reprint author), NIMH, Genet Epidemiol Res Branch, NIH, 35 Convent Dr,Room 1A201,Mail Stop Code 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov FU National Institute of Mental Health [1F31MH084567-01A1]; National Hispanic Science Network on Drug Abuse; National Institute on Drug Abuse; Section on Developmental Genetic Epidemiology, National Institute of Mental Health; Flight Attendant Medical Research Institute FX Funding/Support: This study was supported in part by the National Institute of Mental Health, Intramural Research Program (Dr Merikangas). During the course of the study, Mr Bandiera received a summer fellowship through the National Hispanic Science Network on Drug Abuse, which is sponsored by the National Institute on Drug Abuse. Mr Bandiera completed his fellowship at the Section on Developmental Genetic Epidemiology, National Institute of Mental Health under the direction of principal investigator Merikangas. Mr Bandiera is also a recipient of predoctoral grant 1F31MH084567-01A1 from the National Institute of Mental Health. Dr Lee is also funded by a grant from the Flight Attendant Medical Research Institute. NR 51 TC 43 Z9 44 U1 7 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2011 VL 165 IS 4 BP 332 EP 338 PG 7 WC Pediatrics SC Pediatrics GA 745LF UT WOS:000289166200008 PM 21464381 ER PT J AU Wei, S Niu, JG Zhao, H Liu, ZS Wang, LE Han, YH Chen, WV Amos, CI Rafnar, T Sulem, P Stefansson, K Landi, MT Caporaso, NE Albanes, D Thun, MJ McKay, JD Brennan, P Wang, YF Houlston, RS Spitz, MR Wei, QY AF Wei, Sheng Niu, Jiangong Zhao, Hui Liu, Zhensheng Wang, Li-E Han, Younghun Chen, Wei V. Amos, Christopher I. Rafnar, Thorunn Sulem, Patrick Stefansson, Kari Landi, Maria T. Caporaso, Neil E. Albanes, Demetrius Thun, Michael J. McKay, James D. Brennan, Paul Wang, Yufei Houlston, Richard S. Spitz, Margaret R. Wei, Qingyi TI Association of a novel functional promoter variant (rs2075533 C > T) in the apoptosis gene TNFSF8 with risk of lung cancer-a finding from Texas lung cancer genome-wide association study SO CARCINOGENESIS LA English DT Article ID PROGRAMMED CELL-DEATH; SUSCEPTIBILITY LOCUS; MISSING HERITABILITY; POLYMORPHISMS; DISEASES; SELECTION; NICOTINE; PATHWAY; 5P15.33; REPAIR AB Published genome-wide association studies (GWASs) have identified few variants in the known biological pathways involved in lung cancer etiology. To mine the possibly hidden causal single nucleotide polymorphisms (SNPs), we explored all SNPs in the extrinsic apoptosis pathway from our published GWAS dataset for 1154 lung cancer cases and 1137 cancer-free controls. In an initial association analysis of 611 tagSNPs in 41 apoptosis-related genes, we identified only 10 tagSNPs associated with lung cancer risk with a P value < 10(-2), including four tagSNPs in DAPK1 and three tagSNPs in TNFSF8. Unlike DAPK1 SNPs, TNFSF8 rs2181033 tagged other four predicted functional but untyped SNPs (rs776576, rs776577, rs31813148 and rs2075533) in the promoter region. Therefore, we further tested binding affinity of these four SNPs by performing the electrophoretic mobility shift assay. We found that only rs2075533T allele modified levels of nuclear proteins bound to DNA, leading to significantly decreased expression of luciferase reporter constructs by 5- to -10-fold in H1299, HeLa and HCT116 cell lines compared with the C allele. We also performed a replication study of the untyped rs2075533 in an independent Texas population but did not confirm the protective effect. We further performed a mini meta-analysis for SNPs of TNFSF8 obtained from other four published lung cancer GWASs with 12 214 cases and 47 721 controls, and we found that only rs3181366 (r(2) = 0.69 with the untyped rs2075533) was associated to lung cancer risk (P = 0.008). Our findings suggest a possible role of novel TNFSF8 variants in susceptibility to lung cancer. C1 [Wei, Sheng; Niu, Jiangong; Zhao, Hui; Liu, Zhensheng; Wang, Li-E; Han, Younghun; Chen, Wei V.; Amos, Christopher I.; Spitz, Margaret R.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Rafnar, Thorunn; Sulem, Patrick; Stefansson, Kari] DeCODE Genet, IS-101 Reykjavik, Iceland. [Landi, Maria T.; Caporaso, Neil E.; Albanes, Demetrius] NIH, Div Canc Epidemiol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [McKay, James D.; Brennan, Paul] Int Agcy Res Canc, Genet Epidemiol Grp, F-69008 Lyon, France. [Wang, Yufei; Houlston, Richard S.] Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. RP Wei, QY (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. EM qwei@mdanderson.org RI Albanes, Demetrius/B-9749-2015; OI Houlston, Richard/0000-0002-5268-0242 FU National Institutes of Health [R01ES011740, R01CA131274, R01CA055769, R01CA127219, R01CA121197]; Cancer Center [P30 CA016672] FX This study was supported in part by National Institutes of Health grants (R01ES011740 and R01CA131274 to Q. W., R01CA055769 and R01CA127219 to M. R. S. and R01CA121197 to C. I. S.) and Cancer Center Core Grant (P30 CA016672 to MD Anderson Cancer Center). NR 43 TC 4 Z9 4 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2011 VL 32 IS 4 BP 507 EP 515 DI 10.1093/carcin/bgr014 PG 9 WC Oncology SC Oncology GA 745KM UT WOS:000289164300009 PM 21292647 ER PT J AU Li, R Yang, YA An, Y Zhou, Y Liu, YH Yu, Q Lu, DR Wang, HY Jin, L Zhou, WP Qian, J Shugart, YY AF Li, Rui Yang, Yuan An, Yu Zhou, Yun Liu, Yanhong Yu, Qing Lu, Daru Wang, Hongyang Jin, Li Zhou, Weiping Qian, Ji Shugart, Yin Yao TI Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma SO CARCINOGENESIS LA English DT Article ID JOINING PATHWAY GENES; HUMAN SOMATIC-CELLS; CANCER RISK; LIVER-CANCER; CHROMOSOMAL STABILITY; GENOMIC INSTABILITY; TELOMERE LENGTH; MICE; HEPATOCARCINOGENESIS; CARCINOGENESIS AB Environmental risk factors cause DNA damages. Imprecise DNA repair leads to chromosome aberrations, genome destabilization and hepatocarcinogenesis. Ku is a key DNA double-strand break repair protein. We hypothesized that the genetic variants in Ku subunits encoding genes, XRCC5/XRCC6, may contribute to hepatocellular carcinoma (HCC) susceptibility. We genotyped 13 common single nucleotide polymorphisms (SNPs) in XRCC5 and XRCC6 and evaluated their associations with HCC risk in 689 pathologically confirmed cases and 690 cancer-free controls from a Chinese population. We found that a significantly reduced risk for HCC was associated with XRCC5 rs16855458 [odds ratio (OR) = 0.59; 95% confidence interval (CI) = 0.43-0.81; CA + AA versus CC] and a significantly increased risk for HCC was associated with XRCC5 rs9288516 (OR = 2.02; 95% CI = 1.42-2.86; TA + AA versus TT) even after Bonferroni correction (P(corrected) = 0.026 and 0.002, respectively). The effects of rs16855458 (OR = 0.57; 95% CI = 0.37-0.86, P = 0.008) and rs9288516 (OR = 1.86; 95% CI = 1.19-2.90, P = 0.007) were more significant in hepatitis B surface antigen-infected subjects than non-infected subjects. The haplotype-based analysis revealed that in XRCC5, AA in block 1 (OR = 0.63; 95% CI = 0.48-0.83) and CGGTT in block 2 (OR = 0.52; 95% CI = 0.39-0.69) were associated with decreased HCC risk (P(corrected) = 0.013 and < 0.001, respectively). The aforementioned two SNPs exhibited a significant cumulative risk effect (P(trend) < 0.001). Additionally, potential interaction among XRCC5 rs9288516 and rs2267437, rs5751131 in XRCC6 was indicated by the multifactor dimensionality reduction analysis. In conclusion, XRCC5 variants may play a role in determining individual's HCC susceptibility, which warranted validation in larger studies. C1 [Li, Rui; An, Yu; Liu, Yanhong; Lu, Daru; Jin, Li; Qian, Ji] Fudan Univ, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Li, Rui; An, Yu; Liu, Yanhong; Lu, Daru; Jin, Li; Qian, Ji] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 200433, Peoples R China. [Li, Rui; An, Yu; Liu, Yanhong; Lu, Daru; Jin, Li; Qian, Ji] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Yang, Yuan; Zhou, Weiping] Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 3, Shanghai 200438, Peoples R China. [Yang, Yuan; Zhou, Yun; Wang, Hongyang] Eastern Hepatobiliary Surg Inst, Int Cooperat Lab Signal Transduct, Shanghai, Peoples R China. [Liu, Yanhong] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Yu, Qing] Wenzhou Med Coll, Sch Environm Sci & Publ Hlth, Wenzhou 325035, Zhejiang, Peoples R China. [Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Qian, J (reprint author), Fudan Univ, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. EM ehphwp@126.com; jiqian@fudan.edu.cn RI Jin, Li/C-1468-2009 OI Jin, Li/0000-0002-4546-2415 FU National Outstanding Youth Science Foundation of China [30971577]; National Science Foundation of China [30890034, 81071681]; 863 Program [2007AA02Z312]; National Major ST Projects [2008ZX10002-016, 2009ZX10004-104, 2009ZX10004-904, 2008ZX10002-010, 2008ZX10002-015, 2008ZX10002-019]; Shanghai Leading Academic Discipline Project [B111] FX This research was supported by grants from the National Outstanding Youth Science Foundation of China (30971577); National Science Foundation of China (30890034, 81071681); 863 Program (2007AA02Z312); National Major S&T Projects (2008ZX10002-016, 2009ZX10004-104, 2009ZX10004-904, 2008ZX10002-010, 2008ZX10002-015 and 2008ZX10002-019). L.J. is also supported by Shanghai Leading Academic Discipline Project (B111). NR 52 TC 16 Z9 16 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2011 VL 32 IS 4 BP 530 EP 536 DI 10.1093/carcin/bgr018 PG 7 WC Oncology SC Oncology GA 745KM UT WOS:000289164300012 PM 21304054 ER PT J AU Zhang, LP Lan, Q Guo, WH Hubbard, AE Li, GL Rappaport, SM McHale, CM Shen, M Ji, ZY Vermeulen, R Yin, SN Rothman, N Smith, MT AF Zhang, Luoping Lan, Qing Guo, Weihong Hubbard, Alan E. Li, Guilan Rappaport, Stephen M. McHale, Cliona M. Shen, Min Ji, Zhiying Vermeulen, Roel Yin, Songnian Rothman, Nathaniel Smith, Martyn T. TI Chromosome-wide aneuploidy study (CWAS) in workers exposed to an established leukemogen, benzene SO CARCINOGENESIS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; THERAPY-RELATED MYELODYSPLASIA; IN-SITU HYBRIDIZATION; LONG ARM DELETION; CHINESE WORKERS; LYMPHOCYTES; MALIGNANCIES; ABERRATIONS; GENETICS; CANCER AB Evidence suggests that de novo, therapy-related and benzene-induced acute myeloid leukemias (AML) occur via similar cytogenetic and genetic pathways, several of which involve aneuploidy, the loss or gain of chromosomes. Aneuploidy of specific chromosomes has been detected in benzene-related leukemia patients as well as in healthy benzene-exposed workers, suggesting that aneuploidy precedes and may be a potential mechanism underlying benzene-induced leukemia. Here, we analyzed the peripheral blood lymphocytes of 47 exposed workers and 27 unexposed controls using a novel OctoChrome fluorescence in situ hybridization (FISH) technique that simultaneously detects aneuploidy in all 24 chromosomes. Through this chromosome-wide aneuploidy study (CWAS) approach, we found heterogeneity in the monosomy and trisomy rates of the 22 autosomes when plotted against continuous benzene exposure. In addition, statistically significant, chromosome-specific increases in the rates of monosomy [5, 6, 7, 10, 16 and 19] and trisomy [5, 6, 7, 8, 10, 14, 16, 21 and 22] were found to be dose dependently associated with benzene exposure. Furthermore, significantly higher rates of monosomy and trisomy were observed in a priori defined 'susceptible' chromosome sets compared with all other chromosomes. Together, these findings confirm that benzene exposure is associated with specific chromosomal aneuploidies in hematopoietic cells, which suggests that such aneuploidies may play roles in benzene-induced leukemogenesis. C1 [Zhang, Luoping; Guo, Weihong; Hubbard, Alan E.; Rappaport, Stephen M.; McHale, Cliona M.; Ji, Zhiying; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Lan, Qing; Shen, Min; Vermeulen, Roel; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Li, Guilan; Yin, Songnian] Chinese Ctr Dis Control & Prevent, Inst Occupat Hlth & Poison Control, Beijing 100050, Peoples R China. RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. EM luoping@berkeley.edu RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health [R01ES006721]; National Institute of Environmental Health Sciences [P42ES004705]; American Petroleum Institute; American Chemistry Council FX This study was supported in part by the National Institutes of Health (R01ES006721 to M.T.S.) and the National Institute of Environmental Health Sciences (P42ES004705 to M.T.S.).; Dr M.T.S. has received consulting and expert testimony fees from lawyers representing both plaintiffs and defendants in cases involving claims related to exposure to benzene. S.M.R. has received consulting and expert testimony fees from law firms representing plaintiffs' cases involving exposure to benzene and has received research support from the American Petroleum Institute and the American Chemistry Council. G.L. has received funds from the American Petroleum Institute for consulting on benzene-related health research. NR 52 TC 26 Z9 28 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2011 VL 32 IS 4 BP 605 EP 612 DI 10.1093/carcin/bgq286 PG 8 WC Oncology SC Oncology GA 745KM UT WOS:000289164300022 PM 21216845 ER PT J AU Johannessen, L Remsberg, J Gaponenko, V Adams, KM Barchi, JJ Tarasov, SG Jiang, S Tarasova, NI AF Johannessen, Liv Remsberg, Jarrett Gaponenko, Vadim Adams, Kristie M. Barchi, Joseph J., Jr. Tarasov, Sergey G. Jiang, Sheng Tarasova, Nadya I. TI Peptide Structure Stabilization by Membrane Anchoring and its General Applicability to the Development of Potent Cell-Permeable Inhibitors SO CHEMBIOCHEM LA English DT Article DE cancer; insulin-like growth factor receptor; lipopeptides; protein-protein interactions; retro-inverso ID RECEPTOR TYROSINE KINASES; ACTIVATION; CANCER; GROWTH; DISCOVERY; PROTEINS; PALMITOYLATION; PROLIFERATION; STABILITY; SCAFFOLDS AB Isolated protein motifs that are involved in interactions with their binding partners can be used to inhibit these interactions. However, peptides corresponding to protein fragments tend to have no defined secondary or tertiary structure in the absence of scaffolding by the rest of protein molecule. This results in low inhibitor potency. NMR and CD spectroscopy studies of lipopeptide inhibitors of the Hedgehog pathway revealed that membrane anchoring allows the cell membrane to function as a scaffold and facilitate the folding of short peptides. In addition, lipidation enhances cell permeability and increases the concentration of the compounds near the membrane, thus facilitating potent inhibition. The general applicability of this rational approach was further confirmed by the generation of selective antagonists of the insulin-like growth factor 1 receptor with GI(50) values in the nanomolar range. Lipopeptides corresponding to protein fragments were found to serve as potent and selective inhibitors of a number of nondruggable molecular targets. C1 [Johannessen, Liv; Remsberg, Jarrett; Tarasova, Nadya I.] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Gaponenko, Vadim] Univ Illinois, Chicago, IL 60607 USA. [Adams, Kristie M.; Barchi, Joseph J., Jr.] NCI, Biol Chem Lab, Frederick, MD 21702 USA. [Tarasov, Sergey G.; Jiang, Sheng] NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Tarasova, NI (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, POB B, Frederick, MD 21702 USA. EM tarasova@ncifcrf.gov RI Barchi Jr., Joseph/N-3784-2014 FU National Cancer Institute; Drug Development Committee of the National Cancer Institute; NIH, National Cancer Institute; NIH [R01CA135341] FX We are indebted to Dr. Joseph Kalen, Lisa Riffle, and Avrum Leeder (NCI-Frederick Small Animal Imaging Program) for their help with the biodistribution studies, to Carrie J. Saucedo (Molecular Target Development Program, NCI-Frederick) for the kind gift of the recombinant human IGF1R kinase domain, and to Mary Starich (Structural Biophysics Laboratory, NCI-Frederick) for her help in collecting NMR data. L.J. and J.R. were supported by Cancer Research Training Awards for undergraduate students of the National Cancer Institute. The research was sponsored by the Drug Development Committee of the National Cancer Institute. The research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute and by NIH grant R01CA135341 to V.G. NR 44 TC 10 Z9 10 U1 0 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1439-4227 J9 CHEMBIOCHEM JI ChemBioChem PD APR PY 2011 VL 12 IS 6 BP 914 EP 921 DI 10.1002/cbic.201000563 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 746BB UT WOS:000289214900015 PM 21365731 ER PT J AU Crowder, RN Zhao, H Chatham, WW Zhou, T Carter, RH AF Crowder, Roslyn N. Zhao, Hong Chatham, W. Winn Zhou, Tong Carter, Robert H. TI B lymphocytes are resistant to death receptor 5-induced apoptosis SO CLINICAL IMMUNOLOGY LA English DT Article DE Death receptor 5; B lymphocyte; Systemic lupus erythematosus; Cancer ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CYTOTOXIC LIGAND TRAIL; NF-KAPPA-B; RHEUMATOID-ARTHRITIS; T-CELLS; C-FLIP; MEDIATED APOPTOSIS; TUMOR-CELLS; SYNOVIAL FIBROBLASTS; TUMORICIDAL ACTIVITY AB Death Receptor 5 (DR5) induces apoptosis in various types of cells and is a potential therapeutic target. We have investigated whether targeting DR5 could be used to eliminate pathogenic B lymphocytes from systemic lupus erythematosus (SLE) patients. We examined DR5 expression and function on B lymphocytes from healthy controls subjects, SLE patients, and human tonsil. DR5 was expressed similarly on all B cell subpopulations, including resting and activated B cells. Expression of DR5 was equivalent on B cells from SLE patients and healthy subjects. Additionally, DR5 expression was unchanged after B lymphocyte stimulation. However, B cells were resistant to DR5-induced apoptosis, including after in vitro activation. No changes in subsets of B cells were observed in subjects of a trial of CS-1008, an agonist anti-DR5. While DR5 shows promise as a way to selectively eliminate tumor cells and activated synoviocytes, these data suggest DR5 alone cannot be used as a target to remove pathogenic SLE B cells. Published by Elsevier Inc. C1 [Crowder, Roslyn N.] Penn State Coll Med, Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Zhao, Hong; Chatham, W. Winn; Zhou, Tong] Univ Alabama, Dept Med, Birmingham, AL USA. [Carter, Robert H.] Natl Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD USA. RP Carter, RH (reprint author), NIAMS, Bldg 31 Room 4C32,31 Ctr Dr,MSC 2350, Bethesda, MD 20892 USA. EM carterrob@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH [U19 AI056542]; Alliance for Lupus Research FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH grant U19 AI056542 and the Alliance for Lupus Research. NR 67 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2011 VL 139 IS 1 BP 21 EP 31 DI 10.1016/j.clim.2010.12.006 PG 11 WC Immunology SC Immunology GA 745RN UT WOS:000289183500004 PM 21276756 ER PT J AU Heimall, J Davis, J Shaw, PA Hsu, AP Gu, WJ Welch, P Holland, SM Freeman, AF AF Heimall, Jennifer Davis, Joie Shaw, Pamela A. Hsu, Amy P. Gu, Wenjuan Welch, Pam Holland, Steven M. Freeman, Alexandra F. TI Paucity of genotype-phenotype correlations in STAT3 mutation positive Hyper IgE Syndrome (HIES) SO CLINICAL IMMUNOLOGY LA English DT Article DE Autosomal dominant; hyper-IgE syndrome(AD-HIES); Job's syndrome; STAT-3; Genotype phenotype ID RECURRENT INFECTION SYNDROME; CORONARY-ARTERY ANEURYSMS; HYPERIMMUNOGLOBULINEMIA-E; PHOSPHORYLATION AB Autosomal dominant HIES (AD-HIES) is a primary immunodeficiency caused by dominant negative mutations in STAT3 clustered in the DNA binding and SH2 domains. Although in vitro differences in mutational constructs are observed, clinical phenotypic correlates of these genetic changes have not been described. We reviewed the charts of 65 AD-HIES patients (DNA binding n = 35; SH2 n = 30), recorded the components of the NIH HIES clinical scoring system as well as brain and coronary artery abnormalities and analyzed data by mutation region in adults and children. Patients with SH2 domain mutations had increased frequency of high palate, broad inter-alar distance, upper respiratory tract infections and, in the pediatric sub-group, significant scoliosis. There was suggestion of increased mortality for patients with DNA binding mutations. Although subtle differences in phenotype were observed to depend on the STAT3 genotype, overall the clinical phenotypes were similar between individuals with DNA binding and SH2 domain mutations. Published by Elsevier Inc. C1 [Heimall, Jennifer; Hsu, Amy P.; Holland, Steven M.; Freeman, Alexandra F.] NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Davis, Joie] NIAID, NIH, Intramural Clin Management & Operat Branch, Bethesda, MD 20892 USA. [Shaw, Pamela A.] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. [Gu, Wenjuan] SAIC Frederick Inc, NCI, Biostat Res Branch, Frederick, MD 21702 USA. [Welch, Pam] SAIC Frederick Inc, NCI, Lab Clin Infect Dis, Frederick, MD 21702 USA. RP Freeman, AF (reprint author), NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM heimallj@mail.nih.gov FU Division of Intramural Research, NIAID, NIH; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This research was supported by the Division of Intramural Research, NIAID, NIH. The views expressed in this article are those of the authors and do not reflect the official policy of the U.S. Government. This project has been funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services. NR 16 TC 20 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2011 VL 139 IS 1 BP 75 EP 84 DI 10.1016/j.clim.2011.01.001 PG 10 WC Immunology SC Immunology GA 745RN UT WOS:000289183500010 PM 21288777 ER PT J AU Collins, PY von Unger, H Putnins, S Crawford, N Dutt, R Hoffer, M AF Collins, Pamela Y. von Unger, Hella Putnins, Susan Crawford, Natalie Dutt, Ragini Hoffer, Marcela TI Adding the Female Condom to HIV Prevention Interventions for Women with Severe Mental Illness: A Pilot Test SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Severe mental illness; HIV prevention; Women; Female condoms; Pilot test ID SEXUAL RISK BEHAVIOR; SUBSTANCE-ABUSE; PEOPLE; ADULTS; REDUCTION; RELIABILITY; GENDER; SKILLS; ACCEPTABILITY; STRATEGIES AB We evaluated the efficacy of a gender-specific intervention to reduce sexual risk behaviors by introducing female-initiated methods to urban women with severe mental illness. Seventy-nine women received 10 sessions of an HIV prevention intervention or a control intervention. The primary outcome was unprotected oral, anal, or vaginal intercourse, expressed using the Vaginal Episode Equivalent (VEE) score. Knowledge and use of the female condom were also assessed. Women in the HIV prevention intervention showed a three-fold reduction in the VEE score at the 3-month follow-up compared to the control group, but the difference was not significant. These women were significantly more likely to know about female condoms, have inserted one and used it with a sexual partner at the 3-month follow-up and to have inserted it at 6 months compared to controls. The female condom may be a useful addition, for a subset of women with SMI, to comprehensive HIV prevention programs. C1 [Collins, Pamela Y.] NIMH, Bethesda, MD 20892 USA. [Collins, Pamela Y.; Crawford, Natalie; Hoffer, Marcela] Columbia Univ, New York, NY USA. [von Unger, Hella] Social Sci Res Ctr Berlin WZB, Res Grp Publ Hlth, Berlin, Germany. [Putnins, Susan] Mc Lean Hosp, Belmont, MA USA. [Dutt, Ragini] UNICEF Headquarters, New York, NY USA. RP Collins, PY (reprint author), NIMH, 6001 Execut Blvd,Room 8125, Bethesda, MD 20892 USA. EM Pamela.Collins@nih.gov FU NIMH NIH HHS [K01 MH001691-05, K01 MH01691, K01 MH001691] NR 49 TC 2 Z9 2 U1 3 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD APR PY 2011 VL 47 IS 2 BP 143 EP 155 DI 10.1007/s10597-010-9302-8 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 735WQ UT WOS:000288451700003 PM 20336486 ER PT J AU Machado-Vieira, R Zarate, CA AF Machado-Vieira, Rodrigo Zarate, Carlos A., Jr. TI PROOF OF CONCEPT TRIALS IN BIPOLAR DISORDER AND MAJOR DEPRESSIVE DISORDER: A TRANSLATIONAL PERSPECTIVE IN THE SEARCH FOR IMPROVED TREATMENTS SO DEPRESSION AND ANXIETY LA English DT Review DE cholinergic; depression; glutamate; mood disorders; novel treatments; pathophysiology ID PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3; D-ASPARTATE ANTAGONIST; FORCED-SWIM TEST; METABOTROPIC GLUTAMATE RECEPTORS; DELTA-OPIOID RECEPTORS; RAPID ANTIDEPRESSANT RESPONSE; LEARNED HELPLESSNESS MODEL; MESSENGER-RNA EXPRESSION; PLACEBO-CONTROLLED TRIAL AB A better understanding of the neurobiology of mood disorders, informed by preclinical research and bi-directionally translated to clinical research, is critical for the future development of new and effective treatments. Recently, diverse new targets/compounds have been specifically tested in preclinical models and in proof-of-concept studies, with potential relevance as treatments for mood disorders. Most of the evidence comes from case reports, case series, or controlled proof-of-concept studies, some with small sample sizes. These include (1) the opioid neuropeptide system, (2) the purinergic system, (3) the glutamatergic system, (4) the tachykinin neuropeptide system, (5) the cholinergic system (muscarinic system), and (6) intracellular signaling pathways. These targets may be of substantial interest in defining future directions in drug development, as well as in developing the next generation of therapeutic agents for the treatment of mood disorders. Overall, further study of these and similar drugs may lead to a better understanding of relevant and clinically useful drug targets in the treatment of these devastating illnesses. Depression and Anxiety 28:267-281, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Machado-Vieira, Rodrigo] Univ Sao Paulo, Sch Med, Inst Psychiat, BR-09500900 Sao Paulo, Brazil. [Machado-Vieira, Rodrigo] Univ Sao Paulo, Sch Med, Dept Psychiat, BR-09500900 Sao Paulo, Brazil. [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), Mark O Hatfield Clin Res Ctr, Unit SE 7, 10 Ctr Dr,Rm 7-3465, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov RI MACHADO-VIEIRA, RODRIGO/D-8293-2012 OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190 FU National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS) FX Contract grant sponsor: Intramural Research Program of the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services (IRP-NIMH-NIH-DHHS). Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression. Dr. Zarate has assigned his patent rights on ketamine to the US government. NR 204 TC 14 Z9 15 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 EI 1520-6394 J9 DEPRESS ANXIETY JI Depress. Anxiety PD APR PY 2011 VL 28 IS 4 BP 267 EP 281 DI 10.1002/da.20800 PG 15 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 744UT UT WOS:000289121000002 PM 21456037 ER PT J AU Wei, GS Coady, SA Goff, DC Brancati, FL Levy, D Selvin, E Vasan, RS Fox, CS AF Wei, Gina S. Coady, Sean A. Goff, David C., Jr. Brancati, Frederick L. Levy, Daniel Selvin, Elizabeth Vasan, Ramachandran S. Fox, Caroline S. TI Blood Pressure and the Risk of Developing Diabetes in African Americans and Whites ARIC, CARDIA, and the Framingham Heart Study SO DIABETES CARE LA English DT Article ID ATHEROSCLEROSIS RISK; CARDIOVASCULAR-DISEASE; RECEPTOR BLOCKERS; OLDER-ADULTS; MELLITUS; HYPERTENSION; COMMUNITIES; INSULIN; HEALTH; PREVENTION AB OBJECTIVE-We examined the association between high blood pressure and incident type 2 diabetes in African Americans and whites aged 35-54 years at baseline. RESEARCH DESIGN AND METHODS-We combined data from the Atherosclerosis Risk in Communities (ARIC) study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, and the Framingham Heart Study offspring cohort. Overall, 10,893 participants (57% women; 23% African American) were categorized by baseline blood pressure (normal, pie hypertension. hypertension) and examined for incident diabetes (median follow-up 8.9 years). RESULTS-Overall, 14.6% of African Americans and 7.9% of whites developed diabetes. Age-adjusted incidence was increasingly higher across increasing blood pressure groups (P values for I rend: <0.05 for African American men; <0.001 for other race-sex groups). After adjustment for age, sex, BMI, fasting glucose, HDL cholesterol, and triglycerides, prehypertension or hypertension (compared with normal blood pressure) was associated with greater risks of diabetes in whites (hazard ratio [HR] for prehypertension: 1.32[95% CI 1.09-1.61]; for hypertension: 1.25 [1.03-1.53]), but not African Americans (HR for prehypertension: 0.86 [0.63-1.17]; for hypertension: 0.92 [0.70-1.21]). HRs for developing diabetes among normotensive, prehypenensive, and hypertensive African Americans versus normotensive whites were: 2.75, 2.28, and 2.36, respectively (P values <0.001). CONCLUSIONS-In African Americans, higher diabetes incidence among hypertensive individuals may be explained by BMI, fasting glucose, triglyceride, and HDL. cholesterol. In whites, prehypertension and hypertension are associated with greater risk of diabetes, beyond that explained by other risk factors. African Americans, regardless of blood pressure, have greater risks of developing diabetes than whites. Diabetes Care 34:873-879, 2011. C1 [Wei, Gina S.; Coady, Sean A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Goff, David C., Jr.] Wake Forest Univ, Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27109 USA. [Brancati, Frederick L.; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Brancati, Frederick L.; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Brancati, Frederick L.; Selvin, Elizabeth] Johns Hopkins Univ, Dept Med, Div Gen Internal Med, Baltimore, MD USA. [Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. RP Wei, GS (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. EM weig@nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095, N01-HC-25195]; National Institute of Diabetes and Digestive and Kidney Disease [P60]; National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK076595] FX The Atherosclerosis Risk in Communities (ARIC) Study is supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is supported NHLBI contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095. The Framingham Heart Study is supported by NHLBI contract N01-HC-25195. F.L.B. was supported by a Diabetes Research and Training Center (P60) grant from the National Institute of Diabetes and Digestive and Kidney Diseases. E.S. was supported by grant K01 DK076595 from National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. NR 25 TC 19 Z9 20 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2011 VL 34 IS 4 BP 873 EP 879 DI 10.2337/dc10-1786 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746DE UT WOS:000289221800016 PM 21346180 ER PT J AU Xu, Q Park, Y Huang, XM Hollenbeck, A Blair, A Schatzkin, A Chen, HL AF Xu, Qun Park, Yikyung Huang, Xuemei Hollenbeck, Albert Blair, Aaron Schatzkin, Arthur Chen, Honglei TI Diabetes and Risk of Parkinson's Disease SO DIABETES CARE LA English DT Article ID HYPERTENSION; DISORDERS; MELLITUS; GLUCOSE; COHORT; STROKE; HEALTH AB OBJECTIVE-To investigate the relationship between diabetes and future risk of Parkinson's disease (PD) among older U.S. adults. RESEARCH DESIGN AND METHODS-A prospective study of self-reported diabetes in 1995 and 1996 in relation to PD diagnosed after 1995 among 288,662 participants of the National Institutes of Health-AARP Diet and Health Study. Multivariate odds ratio (OR) and 95% CI were derived from logistic regression models. RESULTS-A total of 1,565 participants with PD diagnosed after 1995 were included in the analysis. After adjustment for potential confounders, PD risk was similar to 40% higher (OR = 1.41 [95% CI 1.20-1.66]) among diabetic patients than among participants without diabetes. Further analysis showed that the risk elevation was largely limited to individuals who had diabetes for more than 10 years at the time of baseline survey (1.75 [1.36-2.25]). The association with diabetes was seen for both participants with PD diagnosed between 1995 and 1999 and participants with PD diagnosed after 2000. In addition, similar results were obtained after excluding participants with stroke, heart disease, cancers, or poor or fair health status and in subgroup analyses by age, sex, smoking status, and coffee consumption. CONCLUSIONS-This large study showed that diabetes was associated with a higher future risk of PD and the nature of this association warrants further investigation. Diabetes Care 34:910-915, 2011 C1 [Xu, Qun; Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Rockville, MD USA. [Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurol, Hershey, PA 17033 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. [Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Rockville, MD USA. RP Chen, HL (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. EM chenh2@niehs.nih.gov OI Chen, Honglei/0000-0003-3446-7779; Park, Yikyung/0000-0002-6281-489X FU NIH; National Institute of Environmental Health Sciences [Z01-ES-101986]; National Cancer Institute [Z01-CP-010196-02] FX This study was supported by the intramural research program of the NIH, the National Institute of Environmental Health Sciences (Z01-ES-101986), and the National Cancer Institute (Z01-CP-010196-02). NR 25 TC 66 Z9 69 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2011 VL 34 IS 4 BP 910 EP 915 DI 10.2337/dc10-1922 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746DE UT WOS:000289221800022 PM 21378214 ER PT J AU Tamerius, J Nelson, MI Zhou, SZ Viboud, C Miller, MA Alonso, WJ AF Tamerius, James Nelson, Martha I. Zhou, Steven Z. Viboud, Cecile Miller, Mark A. Alonso, Wladimir J. TI Global Influenza Seasonality: Reconciling Patterns across Temperate and Tropical Regions SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE contact rates; immunity; influenza; seasonality; virus survival ID RESPIRATORY-TRACT INFECTIONS; VITAMIN-E SUPPLEMENTATION; VIRAL-INFECTIONS; HONG-KONG; DEFICIENCY INCREASES; AMBIENT-TEMPERATURE; PANDEMIC INFLUENZA; RELATIVE-HUMIDITY; ABSOLUTE-HUMIDITY; SCHOOL CLOSURE AB BACKGROUND: Despite the significant disease burden of the influenza virus in humans, our understanding of the basis for its pronounced seasonality remains incomplete. Past observations that influenza epidemics occur in the winter across temperate climates, combined with insufficient knowledge about the epidemiology of influenza in the tropics, led to the perception that cool and dry conditions were a necessary, and possibly sufficient, driver of influenza epidemics. Recent reports of substantial levels of influenza virus activity and well-defined seasonality in tropical regions, where warm and humid conditions often persist year-round, have rendered previous hypotheses insufficient for explaining global patterns of influenza. OBJECTIVE: In this review, we examined the scientific evidence for the seasonal mechanisms that potentially explain the complex seasonal patterns of influenza disease activity observed globally. METHODS: In this review we assessed the strength of a range of hypotheses that attempt to explain observations of influenza seasonality across different latitudes and how they relate to each other. We reviewed studies describing population-scale observations, mathematical models, and ecological, laboratory, and clinical experiments pertaining to influenza seasonality. The literature review includes studies that directly mention the topic of influenza seasonality, as well as other topics we believed to be relevant. We also developed an analytical framework that highlights the complex interactions among environmental stimuli, mediating mechanisms, and the seasonal timing of influenza epidemics and identify critical areas for further research. CONCLUSIONS: The central questions in influenza seasonality remain unresolved. Future research is particularly needed in tropical localities, where our understanding of seasonality remains poor, and will require a combination of experimental and observational studies. Further understanding of the environmental factors that drive influenza circulation also may be useful to predict how dynamics will be affected at regional levels by global climate change. C1 [Tamerius, James; Nelson, Martha I.; Viboud, Cecile; Miller, Mark A.; Alonso, Wladimir J.] NIH, Fogarty Int Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tamerius, James] Univ Arizona, Sch Geog & Dev, Tucson, AZ USA. [Zhou, Steven Z.] London Sch Hyg & Trop Med, London WC1, England. [Zhou, Steven Z.] British Columbia Inst Technol, Burnaby, BC, Canada. RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, Dept Hlth & Human Serv, 16 Ctr Dr, Bethesda, MD 20892 USA. EM alonsow@mail.nih.gov FU Fogarty International, National Institutes of Health FX This research was funded by Fogarty International, National Institutes of Health. We thank the anonymous reviewers that provided valuable feedback. NR 103 TC 118 Z9 119 U1 1 U2 39 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 APR PY 2011 VL 119 IS 4 BP 439 EP 445 DI 10.1289/ehp.1002383 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 744BA UT WOS:000289065900022 PM 21097384 ER PT J AU Finegersh, A Avedissian, C Shamim, S Dustin, I Thompson, PM Theodore, WH AF Finegersh, Andrey Avedissian, Christina Shamim, Sadat Dustin, Irene Thompson, Paul M. Theodore, William H. TI Bilateral hippocampal atrophy in temporal lobe epilepsy: Effect of depressive symptoms and febrile seizures SO EPILEPSIA LA English DT Article DE Radial mapping; Hippocampus; Febrile seizures; Depression; Temporal lobe epilepsy ID VOXEL-BASED MORPHOMETRY; HIGH-RESOLUTION MRI; MAGNETIC-RESONANCE; SURGICAL OUTCOMES; SCLEROSIS; VOLUME; ABNORMALITIES; CONVULSIONS; DURATION; ONSET AB Purpose: Neuroimaging studies suggest a history of febrile seizures, and depression, are associated with hippocampal volume reductions in patients with temporal lobe epilepsy (TLE). Methods: We used radial atrophy mapping (RAM), a three-dimensional (3D) surface modeling tool, to measure hippocampal atrophy in 40 patients with unilateral TLE, with or without a history of febrile seizures and symptoms of depression. Multiple linear regression was used to single out the effects of covariates on local atrophy. Key Findings: Subjects with a history of febrile seizures (n = 15) had atrophy in regions corresponding to the CA1 and CA3 subfields of the hippocampus contralateral to seizure focus (CHC) compared to those without a history of febrile seizures (n = 25). Subjects with Beck Depression Inventory II (BDI-II) score 14 (n = 11) had atrophy in the superoanterior portion of the CHC compared to subjects with BDI-II <14 (n = 29). Significance: Contralateral hippocampal atrophy in TLE may be related to febrile seizures or depression. C1 [Finegersh, Andrey; Shamim, Sadat; Dustin, Irene; Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Avedissian, Christina; Thompson, Paul M.] Univ Calif Los Angeles, Lab Neuroimaging, Los Angeles, CA USA. RP Theodore, WH (reprint author), Bldg 10,Rm 5N-250,9000 Rockville Pike MSC 1408, Bethesda, MD 20892 USA. EM theodorew@ninds.nih.gov FU NINDS Division of Intramural Research. FX We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. None of the authors has anything to disclose. Supported by the NINDS Division of Intramural Research. NR 47 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD APR PY 2011 VL 52 IS 4 BP 689 EP 697 DI 10.1111/j.1528-1167.2010.02928.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 745HO UT WOS:000289156700007 PM 21269286 ER PT J AU Freire, JM Domingues, MM Matos, J Melo, MN Veiga, AS Santos, NC Castanho, MARB AF Freire, Joao M. Domingues, Marco M. Matos, Joana Melo, Manuel N. Veiga, Ana Salome Santos, Nuno C. Castanho, Miguel A. R. B. TI Using zeta-potential measurements to quantify peptide partition to lipid membranes SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article; Proceedings Paper CT 455th Seminar on Biophysics of Membrane Active Peptides CY APR 11-14, 2010 CL Bad Honnef, GERMANY DE Partition constant; Zeta-potential; Fluorescence; Membrane; Antimicrobial peptides ID ANTIMICROBIAL PEPTIDES; LIGHT-SCATTERING; SPECTROSCOPIC METHODS; PHASE-ANALYSIS; FLUORESCENCE; BILAYERS; BP100; MODEL AB Many cellular phenomena occur on the biomembranes. There are plenty of molecules (natural or xenobiotics) that interact directly or partially with the cell membrane. Biomolecules, such as several peptides (e.g., antimicrobial peptides) and proteins, exert their effects at the cell membrane level. This feature makes necessary investigating their interactions with lipids to clarify their mechanisms of action and side effects necessary. The determination of molecular lipid/water partition constants (K (p) ) is frequently used to quantify the extension of the interaction. The determination of this parameter has been achieved by using different methodologies, such as UV-Vis absorption spectrophotometry, fluorescence spectroscopy and zeta-potential measurements. In this work, we derived and tested a mathematical model to determine the K (p) from zeta-potential data. The values obtained with this method were compared with those obtained by fluorescence spectroscopy, which is a regular technique used to quantify the interaction of intrinsically fluorescent peptides with selected biomembrane model systems. Two antimicrobial peptides (BP100 and pepR) were evaluated by this new method. The results obtained by this new methodology show that zeta-potential is a powerful technique to quantify peptide/lipid interactions of a wide variety of charged molecules, overcoming some of the limitations inherent to other techniques, such as the need for fluorescent labeling. C1 [Freire, Joao M.; Domingues, Marco M.; Matos, Joana; Melo, Manuel N.; Veiga, Ana Salome; Santos, Nuno C.; Castanho, Miguel A. R. B.] Univ Lisbon, Inst Mol Med, Fac Med, P-1649028 Lisbon, Portugal. [Veiga, Ana Salome] NCI, Biol Chem Lab, Frederick, MD 21702 USA. RP Castanho, MARB (reprint author), Univ Lisbon, Inst Mol Med, Fac Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal. EM macastanho@fm.ul.pt RI Santos, Nuno/N-7248-2013; Miguel Freire, Joao/J-4881-2015; OI Santos, Nuno/0000-0002-0580-0475; Miguel Freire, Joao/0000-0002-8674-0813; Veiga, Ana Salome/0000-0002-9892-2243; Melo, Manuel Nuno/0000-0001-6567-0513; Castanho, Miguel/0000-0001-7891-7562 NR 26 TC 21 Z9 21 U1 2 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD APR PY 2011 VL 40 IS 4 SI SI BP 481 EP 487 DI 10.1007/s00249-010-0661-4 PG 7 WC Biophysics SC Biophysics GA 744UI UT WOS:000289119700012 PM 21229352 ER PT J AU Lusso, P Vangelista, L Cimbro, R Secchi, M Sironi, F Longhi, R Faiella, M Maglio, O Pavone, V AF Lusso, Paolo Vangelista, Luca Cimbro, Raffaello Secchi, Massimiliano Sironi, Francesca Longhi, Renato Faiella, Marina Maglio, Ornella Pavone, Vincenzo TI Molecular engineering of RANTES peptide mimetics with potent anti-HIV-1 activity SO FASEB JOURNAL LA English DT Article DE chemokines; viral receptors; CCR5; AIDS; antivirals; rational design ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-STRUCTURE PREDICTION; NUCLEIC-ACIDS; HIV-1 INFECTION; FORCE-FIELD; CELL FUSION; CHEMOKINE; CCR5; SPECTROSCOPY; ANTAGONIST AB The chemokine receptor CCR5 is utilized as a critical coreceptor by most primary HIV-1 strains. While the lack of structural information on CCR5 has hampered the rational design of specific inhibitors, mimetics of the chemokines that naturally bind CCR5 can be molecularly engineered. We used a structure-guided approach to design peptide mimetics of the N-loop and beta 1-strand regions of regulated on activation normal T-cell-expressed and secreted (RANTES)/CCL5, which contain the primary molecular determinants of HIV-1 blockade. Rational modifications were sequentially introduced into the N-loop/beta 1-strand sequence, leading to the generation of mimetics with potent activity against a broad spectrum of CCR5-specific HIV-1 isolates (IC(50) range: 104-640 nM) but lacking activity against CXCR4-specific HIV-1 isolates. Functional enhancement was initially achieved with the stabilization of the N loop in the beta-extended conformation adopted in full-length RANTES, as confirmed by nuclear magnetic resonance (NMR) analysis. However, the most dramatic increase in antiviral potency resulted from the engraftment of an in silico-optimized linker segment designed using de novo structure-prediction algorithms to stabilize the C-terminal alpha-helix and experimentally validated by NMR. Our mimetics exerted CCR5-antagonistic effects, demonstrating that the antiviral and proinflammatory functions of RANTES can be uncoupled. RANTES peptide mimetics provide new leads for the development of safe and effective HIV-1 entry inhibitors.-Lusso, P., Vangelista, L., Cimbro, R., Secchi, M., Sironi, F., Longhi, R., Faiella, M., Maglio, O., Pavone, V. Molecular engineering of RANTES peptide mimetics with potent anti-HIV-1 activity. FASEB J. 25, 1230-1243 (2011). www.fasebj.org C1 [Lusso, Paolo; Vangelista, Luca; Cimbro, Raffaello; Secchi, Massimiliano; Sironi, Francesca] Ist Sci San Raffaele, Dept Biol & Technol Res DIBIT, Unit Human Virol, I-20132 Milan, Italy. [Lusso, Paolo] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy. [Longhi, Renato] CNR, ICRM, I-20133 Milan, Italy. [Faiella, Marina; Maglio, Ornella; Pavone, Vincenzo] Univ Naples Federico 2, Dept Chem, Naples, Italy. RP Lusso, P (reprint author), NIAID, Immunoregulat Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM plusso@niaid.nih.gov RI Pavone, Vincenzo/D-1688-2011; Maglio, Ornella/F-1162-2016; OI Pavone, Vincenzo/0000-0001-6432-0802; Maglio, Ornella/0000-0002-7829-1907; Cimbro, Raffaello/0000-0002-6251-5160 FU Istituto Superiore di Sanita (ISS)-AIDS Project, Rome; European Microbicides Project (EMPRO); EU, Brussels FX The authors thank Paolo Sarmientos for helpful discussion and peptide synthesis, Luca DeGioia and Stephan Grzesiek for critical reading of the manuscript, Gabriella Scarlatti (DIBIT-HSR, Milan, Italy) for providing pediatric HIV-1 isolates, Monica Tolazzi for performing virologic assays, and the NIH AIDS Research and Reference Reagent Program (Rockville, MD, USA) for providing primary HIV-1 isolates. This work was supported in part by the Istituto Superiore di Sanita (ISS)-AIDS Project, Rome; the European Microbicides Project (EMPRO); and Combined Highly Active Anti-Retroviral Microbicides (CHAARM), EU, Brussels. The authors declare no competing financial interests. NR 40 TC 13 Z9 14 U1 0 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 IS 4 BP 1230 EP 1243 DI 10.1096/fj.10-167627 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 742ZA UT WOS:000288982800012 PM 21199933 ER PT J AU Rautenberg, M Joo, HS Otto, M Peschel, A AF Rautenberg, Maren Joo, Hwang-Soo Otto, Michael Peschel, Andreas TI Neutrophil responses to staphylococcal pathogens and commensals via the formyl peptide receptor 2 relates to phenol-soluble modulin release and virulence SO FASEB JOURNAL LA English DT Article DE pathogen-associated molecular patterns; coagulase-negative staphylococci; skin microbiota; neutrophil chemotaxis ID LIPOXIN A(4) RECEPTOR; COAGULASE-NEGATIVE STAPHYLOCOCCI; ACTIVATES NEUTROPHILS; MOLECULAR-PATTERNS; IMMUNE EVASION; AUREUS; LUGDUNENSIS; EPIDERMIDIS; RECOGNITION; CHEMOTAXIS AB The mechanisms used by the immune system to discriminate between pathogenic and commensal bacteria have remained largely unclear. Recently, we have shown that virulence of Staphylococcus aureus depends on secretion of phenol-soluble modulin (PSM) peptides that disrupt neutrophils at micromolar concentrations. Moreover, all S. aureus PSMs stimulate and attract neutrophils at nanomolar concentrations via interaction with the formyl-peptide receptor 2 (FPR2). Here, we demonstrate that FPR2 allows neutrophils to adjust their responses in relation to the aggressiveness of staphylococcal species, which differ largely in their capacity to infect or colonize humans and animals. PSM-related peptides were detected in all human and animal pathogenic staphylococci, but were absent from most commensal species. Three PSM beta-like peptides produced by the serious human pathogen Staphylococcus lugdunensis were identified as the previously described S. lugdunensis-synergistic hemolysins (SLUSHs). SLUSHs attracted and stimulated human leukocytes in a FPR2-dependent manner, indicating that FPR2 is a general receptor for all PSM-like peptide toxins. Remarkably, the release of PSMs correlated closely with the apparent capacity of staphylococcal species to cause invasive infections and with their ability to activate FPR2. These findings suggest that the innate immune system may be able to respond in different ways to pathogenic or innocuous staphylococci by monitoring the presence of PSMs via FPR2.-Rautenberg, M., Joo, H. S., Otto, M., Peschel, A. Neutrophil responses to staphylococcal pathogens and commensals via the formyl peptide receptor 2 relates to phenol-soluble modulin release and virulence. FASEB J. 25, 1254-1263 (2011). www.fasebj.org C1 [Rautenberg, Maren; Peschel, Andreas] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Cellular & Mol Microbiol Div, D-72076 Tubingen, Germany. [Joo, Hwang-Soo; Otto, Michael] NIAID, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Peschel, A (reprint author), Univ Tubingen, Interfac Inst Microbiol & Infect Med, Cellular & Mol Microbiol Div, Elfriede Aulhorn Str 6, D-72076 Tubingen, Germany. EM motto@niaid.nih.gov; andreas.peschel@uni-tuebingen.de OI JOO, HWANG-SOO/0000-0003-4668-3225; Otto, Michael/0000-0002-2222-4115 FU German Research Foundation [SFB685, GRK685, TR34]; German Ministry of Education and Research; Medical Faculty, University of Tubingen; National Institutes of Allergy and Infectious Diseases, U.S. National Institutes of Health FX The authors thank Nele Nikola for excellent technical help, Jos van Strijp (Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands) for CHIPS, Francois Boulay (Universite Joseph Fourier, Grenoble, France) for FPR1 and FPR2-transfected cell lines, and Bernhard Krismer (Interfaculty Institute of Microbiology and Infection Medicine, University of Tuebingen, Tuebingen, Germany) for staphylococcal strains. This research is supported by grants from the German Research Foundation (SFB685, GRK685, TR34), the German Ministry of Education and Research (SkinStaph Menage), and the IZKF program of the Medical Faculty, University of Tubingen, to A. P. and from the Intramural Program of the National Institutes of Allergy and Infectious Diseases, U.S. National Institutes of Health, to M.O. NR 44 TC 42 Z9 45 U1 2 U2 12 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 IS 4 BP 1254 EP 1263 DI 10.1096/fj.10-175208 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 742ZA UT WOS:000288982800014 PM 21183593 ER PT J AU Good, CH Hoffman, AF Hoffer, BJ Chefer, VI Shippenberg, TS Backman, CM Larsson, NG Olson, L Gellhaar, S Galter, D Lupica, CR AF Good, Cameron H. Hoffman, Alexander F. Hoffer, Barry J. Chefer, Vladimir I. Shippenberg, Toni S. Baeckman, Cristina M. Larsson, Nils-Goeran Olson, Lars Gellhaar, Sandra Galter, Dagmar Lupica, Carl R. TI Impaired nigrostriatal function precedes behavioral deficits in a genetic mitochondrial model of Parkinson's disease SO FASEB JOURNAL LA English DT Article DE dopamine; patch clamp; striatum; substantia nigra pars compacta ID ACTIVATED CATION CURRENT; SUBSTANTIA-NIGRA NEURONS; MIDBRAIN DOPAMINERGIC-NEURONS; CURRENT I-H; NUCLEUS-ACCUMBENS; PHYSIOLOGICAL-FUNCTION; DNA DELETIONS; HCN CHANNELS; RAT; MICRODIALYSIS AB Parkinson's disease (PD) involves progressive loss of nigrostriatal dopamine (DA) neurons over an extended period of time. Mitochondrial damage may lead to PD, and neurotoxins affecting mitochondria are widely used to produce degeneration of the nigrostriatal circuitry. Deletion of the mitochondrial transcription factor A gene (Tfam) in C57BL6 mouse DA neurons leads to a slowly progressing parkinsonian phenotype in which motor impairment is first observed at similar to 12 wk of age. L-DOPA treatment improves motor dysfunction in these "MitoPark" mice, but this declines when DA neuron loss is more complete. To investigate early neurobiological events potentially contributing to PD, we compared the neurochemical and electrophysiological properties of the nigrostriatal circuit in behaviorally asymptomatic 6- to 8-wk-old MitoPark mice and age-matched control littermates. Release, but not uptake of DA, was impaired in MitoPark mouse striatal brain slices, and nigral DA neurons lacked characteristic pacemaker activity compared with control mice. Also, hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel function was reduced in MitoPark DA neurons, although HCN messenger RNA was unchanged. This study demonstrates altered nigrostriatal function that precedes behavioral parkinsonian symptoms in this genetic PD model. A full understanding of these presymptomatic cellular properties may lead to more effective early treatments of PD.-Good, C. H., Hoffman, A. F., Hoffer, B. J., Chefer, V. I., Shippenberg, T. S., Backman, C. M., Larsson, N.-G., Olson, L., Gellhaar, S., Galter, D., Lupica, C. R. Impaired nigrostriatal function precedes behavioral deficits in a genetic mitochondrial model of Parkinson's disease. FASEB J. 25, 1333-1344 (2011). www.fasebj.org C1 [Good, Cameron H.; Hoffman, Alexander F.; Lupica, Carl R.] NIDA, NIH, IRP, Electrophys Res Sect,US Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Good, Cameron H.; Hoffman, Alexander F.; Hoffer, Barry J.; Baeckman, Cristina M.; Lupica, Carl R.] NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,US Dept Hlth & Human Serv, Baltimore, MD 21224 USA. [Chefer, Vladimir I.; Shippenberg, Toni S.] NIDA, Behav Neurosci Res Branch, Integrat Neurosci Sect, Intramural Res Program,NIH,US Dept Hlth & Human, Baltimore, MD 21224 USA. [Larsson, Nils-Goeran] Max Planck Inst Biol Ageing, Cologne, Germany. [Olson, Lars; Gellhaar, Sandra; Galter, Dagmar] Karolinska Inst Stockholm, Dept Neurosci, Stockholm, Sweden. RP Lupica, CR (reprint author), NIDA, NIH, IRP, Electrophys Res Sect,US Dept Hlth & Human Serv, 333 Cassell Dr, Baltimore, MD 21224 USA. EM clupica@mail.nih.gov RI Galter, Dagmar/C-4826-2011; Hoffman, Alexander/H-3035-2012; backman, cristina/C-1276-2013 OI Galter, Dagmar/0000-0001-6485-6244; Hoffman, Alexander/0000-0002-2676-0628; FU U.S. National Institutes of Health, the National Institute on Drug Abuse; Swedish Research Council; Swedish Brain Foundation; Hallsten's Foundation; Swedish Parkinson's Foundation; Swedish Brain Power; Michael J. Fox Foundation; Karolinska Institute FX This work supported by the U.S. National Institutes of Health, the National Institute on Drug Abuse Intramural Research Program, the Swedish Research Council, the Swedish Brain Foundation, Hallsten's Foundation, the Swedish Parkinson's Foundation, Swedish Brain Power, the Michael J. Fox Foundation, and the Karolinska Institute. N.-G. L. and L.O. are co-owners of a company owning commercial rights to the MitoPark mice. NR 57 TC 44 Z9 45 U1 2 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 IS 4 BP 1333 EP 1344 DI 10.1096/fj.10-173625 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 742ZA UT WOS:000288982800022 PM 21233488 ER PT J AU Cao, XM Pobezinskaya, YL Morgan, MJ Liu, ZG AF Cao, Xiumei Pobezinskaya, Yelena L. Morgan, Michael J. Liu, Zheng-gang TI The role of TRADD in TRAIL-induced apoptosis and signaling SO FASEB JOURNAL LA English DT Article DE MEF; FADD; RIP1; DR5 ID NF-KAPPA-B; FADD-DEPENDENT APOPTOSIS; DEATH-DOMAIN KINASE; INDUCED ACTIVATION; RECEPTORS 1; PATHWAY; CASPASE-8; LIGAND; CELLS; RIP AB Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL is promising for anticancer therapy because it induces apoptosis in cancer cells with little or no toxicity to normal cells; hence, TRAIL-receptor agonists are currently undergoing clinical trials for cancer treatment. However, many molecular signaling mechanisms in TRAIL signaling are not completely characterized. The functions of adaptor proteins, including TNF-receptor-associated death domain protein (TRADD) and receptor-interacting protein-1 (RIP1) in TRAIL signaling have been controversial. We demonstrate that while wild-type mouse embryonic fibroblasts (MEFs) are completely resistant to TRAIL-induced apoptosis, MEFs derived from Tradd(-/-) mice are hypersensitive to TRAIL (IC(50)similar to 0.5 nM rmTRAIL, 24 h), an effect also seen in primary keratinocytes treated with TRAIL/CHX. Restoration of TRADD in Tradd(-/-) MEFs restores TRAIL resistance, indicating that TRADD plays a survival role in TRAIL signaling. We show that TRADD is recruited to the TRAIL-receptor complex, and RIP1 recruitment is mediated by TRADD. While early activation of the MAP kinase ERK is deficient in Tradd(-/-) cells, the main mechanism for enhanced TRAIL sensitivity is likely due to increased recruitment of FADD to the receptor complex, indicating that TRADD may limit FADD binding within the receptor complex and also mediate RIP1-dependent nonapoptotic signaling events, thus reducing caspase activation and subsequent apoptosis. These novel findings have potential implications for cancer therapy using TRAIL-receptor agonists.-Cao, X., Pobezinskaya, Y. L., Morgan, M. J., Liu, Z. The role of TRADD in TRAIL-induced apoptosis and signaling. FASEB J. 25, 1353-1358 (2011). www.fasebj.org C1 [Cao, Xiumei; Pobezinskaya, Yelena L.; Morgan, Michael J.; Liu, Zheng-gang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, 37 Convent Dr,Rm 1130, Bethesda, MD 20892 USA. EM zgliu@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, NIH FX The authors thank S. Lipkowitz (U.S. NIH, Bethesda, MD, USA) for GST-rhTRAIL and Jianke Zhang (Thomas Jefferson University, Philadelphia, PA, USA) for the mouse FADD antibody. This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 23 TC 17 Z9 18 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 IS 4 BP 1353 EP 1358 DI 10.1096/fj.10-170480 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 742ZA UT WOS:000288982800024 PM 21187341 ER PT J AU Manipalviratn, S Tong, ZB Stegmann, B Widra, E Carter, J DeCherney, A AF Manipalviratn, Somjate Tong, Zhi-Bin Stegmann, Barbara Widra, Eric Carter, Jennifer DeCherney, Alan TI Effect of vitrification and thawing on human oocyte ATP concentration SO FERTILITY AND STERILITY LA English DT Editorial Material DE Human oocytes; ATP; vitrification; thawing ID DEVELOPMENTAL COMPETENCE AB Vitrification/thawing has a significant negative impact on oocyte ATP concentration. However, incubating oocytes up to 180 minutes after thawing allowed oocytes to regain some ATP level. (Fertil Steril (R) 2011;95:1839-41. (C)2011 by American Society for Reproductive Medicine.) C1 [Manipalviratn, Somjate; Tong, Zhi-Bin; Stegmann, Barbara; DeCherney, Alan] NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. [Widra, Eric] Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. [Widra, Eric; Carter, Jennifer] Shady Grove Reprod Sci Ctr, Rockville, MD USA. RP Manipalviratn, S (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,Room 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM somjate@thaisuperiorart.com FU Intramural NIH HHS NR 8 TC 17 Z9 20 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 APR PY 2011 VL 95 IS 5 BP 1839 EP 1841 DI 10.1016/j.fertnstert.2010.10.040 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 738OA UT WOS:000288648000080 PM 21071026 ER PT J AU Potty, ASR Kourentzi, K Fang, H Schuck, P Willson, RC AF Potty, Ajish S. R. Kourentzi, Katerina Fang, Han Schuck, Peter Willson, Richard C. TI Biophysical characterization of DNA and RNA aptamer interactions with hen egg lysozyme SO INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES LA English DT Article DE Aptamers; Hen egg white lysozyme; Fluorescence anisotropy; Isothermal titration calorimetry ID SINGLE-STRANDED-DNA; ANTIBODY HYHEL-5; PROTEIN; BINDING; ASSOCIATION; AFFINITY; CHROMATOGRAPHY; SELECTION; PURIFICATION; MOLECULES AB This work characterized the binding of an RNA aptamer recognizing hen egg white lysozyme, as well as a literature-reported single-stranded DNA analog of sequence identical to the original RNA aptamer, using fluorescence anisotropy, isothermal titration calorimetry (ITC) and analytical ultracentrifugation. The polyanionic DNA aptamer analog is selective for lysozyme even over cationic cytochrome c and has been reported to be successfully used in biosensing applications. The association however, is predominantly of electrostatic character, strongly salt-sensitive and entropically-driven, in contrast to previously described enthalpically-driven antibody-lysozyme and DNA aptamer-VEGF interactions. With a moderate selectivity for their target, high salt-sensitivity along with fast association and dissociation behavior, these molecules might serve as pseudo-affinity ligands for biomolecular separations. (C) 2011 Elsevier B.V. All rights reserved. C1 [Potty, Ajish S. R.; Kourentzi, Katerina; Willson, Richard C.] Univ Houston, Dept Chem & Biomol Engn, Houston, TX 77204 USA. [Fang, Han] Univ Houston, Dept Chem, Houston, TX 77204 USA. [Schuck, Peter] NIBIB, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20893 USA. RP Willson, RC (reprint author), Univ Houston, Dept Chem & Biomol Engn, 4800 Calhoun Rd, Houston, TX 77204 USA. EM willson@uh.edu OI Schuck, Peter/0000-0002-8859-6966 FU NASA [NNJ04HF43G]; NSF [CTS-0004544]; Welch Foundation [E-1264]; NIH, NIBIB FX This research was funded in part by grants from NASA (Grant NNJ04HF43G), NSF (Grant CTS-0004544) and the Welch Foundation (Grant E-1264). This work was also supported in part by the Intramural Research Program of the NIH, NIBIB. NR 40 TC 20 Z9 20 U1 3 U2 43 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0141-8130 J9 INT J BIOL MACROMOL JI Int. J. Biol. Macromol. PD APR 1 PY 2011 VL 48 IS 3 BP 392 EP 397 DI 10.1016/j.ijbiomac.2010.12.007 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Polymer Science SC Biochemistry & Molecular Biology; Chemistry; Polymer Science GA 743MC UT WOS:000289021400003 PM 21167858 ER PT J AU Eisenberg, ML Park, Y Brinton, LA Hollenbeck, AR Schatzkin, A AF Eisenberg, Michael L. Park, Yikyung Brinton, Louise A. Hollenbeck, Albert R. Schatzkin, Arthur TI Fatherhood and incident prostate cancer in a prospective US cohort SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Fertility; prostatic neoplasms; fathers; sex ratio; family size ID HUMAN SEX-RATIO; RISK; MEN; MORTALITY; HEALTH; ASSOCIATION; PROGRESSION; CHILDLESS; HORMONES; RECALL AB Background Fatherhood status has been hypothesized to affect prostate cancer risk but the current evidence is limited and contradictory. Methods We prospectively evaluated the relationship between offspring number and the risk of prostate cancer in 161 823 men enrolled in the National Institues of Health - American Association of Retired Persons Diet and Health Study. Participants were aged 50-71 years without a cancer diagnosis at baseline in 1995. Analysing 8134 cases of prostate cancer, Cox regression was used to estimate the association between offspring number and prostate cancer incidence while accounting for socio-demographic and lifestyle characteristics. Results When examining the entire cohort, there was no relationship between fatherhood and incident prostate cancer [hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.86-1.02]. However, after stratifying for prostate cancer screening, prostate-specific antigen (PSA) unscreened childless men had a lower risk of prostate cancer (HR 0.73, 95% CI 0.58-0.91) compared with fathers due to the interaction between PSA screening and fatherhood (P for interaction < 0.01). A trend for the lower risk of prostate cancer among unscreened fathers compared with childless men was seen for low-grade prostate cancer (HR 0.78, 95% CI 0.61-1.01), high-grade prostate cancer (HR 0.62, 95% CI 0.37-1.04) and even fatal prostate cancer (HR 0.28, 95% CI 0.07-1.12). The number of children fathered was not related to prostate cancer (P-trend = 0.17). In addition, men's inability to sire female offspring showed a weak positive association with prostate cancer in the PSA unscreened study subjects. Conclusions Our findings suggest fatherhood status and offspring gender is associated with a man's prostate cancer risk. C1 [Eisenberg, Michael L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. [Park, Yikyung; Brinton, Louise A.; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RP Eisenberg, ML (reprint author), Univ Calif San Francisco, Dept Urol, 400 Parnassus Ave,UC Clin,A-631, San Francisco, CA 94143 USA. EM michael.eisenberg@gmail.com RI Brinton, Louise/G-7486-2015; OI Brinton, Louise/0000-0003-3853-8562; Eisenberg, Michael/0000-0001-5482-0141; Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS NR 37 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2011 VL 40 IS 2 BP 480 EP 487 DI 10.1093/ije/dyq163 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 745LB UT WOS:000289165800028 PM 20959354 ER PT J AU Kolenbrander, PE AF Kolenbrander, Paul E. TI Multispecies communities: interspecies interactions influence growth on saliva as sole nutritional source SO INTERNATIONAL JOURNAL OF ORAL SCIENCE LA English DT Review DE growth on saliva; multispecies communities; biofilm; flow cell; interspecies interactions ID ORAL MICROBIAL COMMUNITIES; FUSOBACTERIUM-NUCLEATUM; DENTAL PLAQUE; STREPTOCOCCUS-ORALIS; BIOFILM COMMUNITIES; VEILLONELLA SP; FLOW CHAMBER; CO-ADHESION; COAGGREGATION; MUCIN AB Human oral bacteria live in multispecies communities in the biofilm called dental plaque. This review focuses on the interactions of seven species and the ability of each species individually and together with other species to grow on saliva as the sole source of nutrient. Community formation in biofilms in flow cells is monitored using species-specific fluorophore-conjugated immunoglobulin G, and images are captured by confocal microscopy. Early colonizing veillonellae emerge from this review of interspecies interactions in saliva as a critical genus that guides the development of multispecies communities. Highly selective interspecies recognition is evident as initial colonizers pair with early and middle colonizers to form multispecies communities that grow on saliva. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nider.nih.gov FU National Institute of Dental and Craniofacial Research, National Institutes of Health FX I thank S. Periasamy for the confocal images of three-species biofilm communities. I am grateful to the Intramural Research Program of the National Institute of Dental and Craniofacial Research, National Institutes of Health for supporting my research program. NR 28 TC 45 Z9 51 U1 3 U2 35 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 APR PY 2011 VL 3 IS 2 BP 49 EP 54 DI 10.4248/IJOS11025 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 744WK UT WOS:000289125700002 PM 21485308 ER PT J AU Wood, RA Bloomberg, GR Kattan, M Conroy, K Sandel, MT Dresen, A Gergen, PJ Gold, DR Schwarz, JC Visness, CM Gern, JE AF Wood, Robert A. Bloomberg, Gordon R. Kattan, Meyer Conroy, Kathleen Sandel, Megan T. Dresen, Amy Gergen, Peter J. Gold, Diane R. Schwarz, John C. Visness, Cynthia M. Gern, James E. TI Relationships among environmental exposures, cord blood cytokine responses, allergy, and wheeze at 1 year of age in an inner-city birth cohort (Urban Environment and Childhood Asthma study) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Immune development; birth cohort; atopy; asthma; cytokines; allergen exposure; inner city ID INTERFERON-GAMMA PRODUCTION; PRENATAL MATERNAL STRESS; NEW-YORK-CITY; ATOPIC-DERMATITIS; MOUSE ALLERGEN; SUBSEQUENT DEVELOPMENT; MONONUCLEAR-CELLS; IL-13 PRODUCTION; CONTROLLED-TRIAL; NATURAL COURSE AB Background: The Urban Environment and Childhood Asthma study was established to investigate the immunologic and environmental causes of asthma in inner-city children. Objective: We sought to evaluate potential atopic outcomes in the first 12 months and their relationships to environmental exposures and immune development. Methods: A birth cohort of 560 children with at least 1 parent with allergy or asthma was established in Baltimore, Boston, New York, and St Louis. Wheezing is assessed every 3 months, allergen-specific IgE yearly, and mononuclear cell cytokine responses at birth and yearly; environmental assessments include dust allergen and endotoxin, maternal stress, and indoor nicotine and nitrogen dioxide levels. Results: Key outcomes in the first year include wheeze in 49%, 2 or more episodes of wheeze in 23%, eczema in 30%, and detectable IgE to milk, egg, and/or peanut in 32% and to cockroach in 4%. Household dust revealed levels of greater than 2 mu g/g to cockroach in 40%, mite in 19%, cat in 25%, and mouse in 29%, and 66% of homes housed at least 1 smoker. Positive associations were detected between multiple wheeze and cotinine levels, maternal stress, and maternal depression, whereas cytokine responses to a variety of innate, adaptive, and mitogenic stimuli were inversely related to eczema. Conclusions: This high-risk cohort of inner-city infants is exhibiting high rates of wheeze, eczema, and allergic sensitization. Low cytokine responses at birth might be a risk factor for eczema, whereas a variety of adverse environmental exposures contribute to the risk of wheezing in infancy. These findings provide evidence of specificity in the interactions between immune development, environmental exposures, and the development of early features that might predict future asthma. (J Allergy Clin Immunol 2011;127:913-9.) C1 [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO USA. [Kattan, Meyer] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Conroy, Kathleen; Sandel, Megan T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Dresen, Amy; Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Gergen, Peter J.] NIH, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Schwarz, John C.; Visness, Cynthia M.] Rho Fed Syst Div Inc, Chapel Hill, NC USA. RP Wood, RA (reprint author), Johns Hopkins Univ, Sch Med, 600 N Wolfe St,CMSC 1102, Baltimore, MD 21287 USA. EM rwood@jhmi.edu FU National Institute of Allergy and Infectious Diseases/National Institutes of Health [NO1-AI-25496, NO1-AI-25482]; National Center for Research Resources/National Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02]; National Institutes of Health (NIH); Medical Advisory Board for the Food Allergy and Anaphylaxis Network; NIH/National Institute of Allergy and Infectious Diseases (NIAID); NIH; Environmental Protection Agency; AstraZeneca and Merck FX Supported in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases/National Institutes of Health under contracts NO1-AI-25496 and NO1-AI-25482. Additional funds were provided by the National Center for Research Resources/National Institutes of Health under grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02.; Disclosure of potential conflict of interest: R. A. Wood has received research support from the National Institutes of Health (NIH) and is on the Medical Advisory Board for the Food Allergy and Anaphylaxis Network. G. R. Bloomberg has received research support from the NIH/National Institute of Allergy and Infectious Diseases (NIAID). M. Kattan and C. M. Visness have received research support from the NIH. D. R. Gold has received research support from the NIH and the Environmental Protection Agency. J. E. Gern is on the Scientific Advisory Board and has stock options with 3V Biosciences; is a consultant and has stock options with EraGen Biosciences; is a consultant for Synairgen, Centocor, Boehringer Ingelheim, Pulmatrix, GlaxoSmithKline, and Biota; and has received research support from AstraZeneca and Merck. The rest of the authors have declared that they have no conflict of interest. NR 50 TC 25 Z9 25 U1 3 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2011 VL 127 IS 4 BP 913 EP U136 DI 10.1016/j.jaci.2010.12.1122 PG 13 WC Allergy; Immunology SC Allergy; Immunology GA 743YL UT WOS:000289055800012 PM 21333343 ER PT J AU Rariy, CM Ratcliffe, SJ Weinstein, R Bhasin, S Blackman, MR Cauley, JA Robbins, J Zmuda, JM Harris, TB Cappola, AR AF Rariy, Chevon M. Ratcliffe, Sarah J. Weinstein, Rachel Bhasin, Shalender Blackman, Marc R. Cauley, Jane A. Robbins, John Zmuda, Joseph M. Harris, Tamara B. Cappola, Anne R. TI Higher Serum Free Testosterone Concentration in Older Women Is Associated with Greater Bone Mineral Density, Lean Body Mass, and Total Fat Mass: The Cardiovascular Health Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING GLOBULIN; HUMAN-IMMUNODEFICIENCY-VIRUS; CLINICAL-PRACTICE GUIDELINE; ENDOGENOUS SEX STEROIDS; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES; MUSCLE STRENGTH; BIOCHEMICAL MARKERS; ESTROGEN-ANDROGEN; CONTROLLED TRIAL AB Context: The physiological importance of endogenous testosterone (T) in older women is poorly understood. Objective: The aim of the study was to determine the association of higher total and free T levels with bone mineral density (BMD), lean body mass, and fat mass in elderly women. Design: Total and free T were measured using sensitive assays in 232 community-dwelling women aged 67-94 yr who were enrolled in the Cardiovascular Health Study and had dual-energy x-ray absorptiometry scans. Cross-sectional analyses were performed to examine associations between total and free T and BMD and body composition. Results: In adjusted models, total T was directly associated with BMD at the lumbar spine (P = 0.04) and hip (P = 0.001), but not body composition outcomes, in all women, and after excluding estrogen users and adjusting for estradiol (P = 0.04 and 0.01, respectively). Free T was positively related to hip BMD, lean body mass, and body fat (all P < 0.05), with more than 10% differences in each outcome between women at the highest and lowest ends of the free T range, with attenuation after excluding estrogen users and adjusting for estradiol. Conclusions: In the setting of the low estradiol levels found in older women, circulating T levels were associated with bone density. Women with higher free T levels had greater lean body mass, consistent with the anabolic effect of T, and, in contrast to men, greater fat mass. Mechanistic studies are required to determine whether a causal relationship exists between T, bone, and body composition in this population and the degree to which any T effects are estrogen-independent. (J Clin Endocrinol Metab 96: 989-996, 2011) C1 [Rariy, Chevon M.; Cappola, Anne R.] Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Ratcliffe, Sarah J.; Weinstein, Rachel] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Bhasin, Shalender] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02118 USA. [Blackman, Marc R.] Washington DC Vet Affairs Med Ctr, Res Serv, Washington, DC 20422 USA. [Cauley, Jane A.; Zmuda, Joseph M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Robbins, John] Univ Calif Davis, Div Gen Internal Med, Sacramento, CA 95817 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Cappola, AR (reprint author), Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, 764 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. EM acappola@mail.med.upenn.edu OI Ratcliffe, Sarah/0000-0002-6644-8284; Cauley, Jane A/0000-0003-0752-4408 FU National Institute on Aging [K23 AG19161]; American Federation for Aging Research/Pfizer [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133]; National Heart, Lung, and Blood Institute [U01 HL080295] FX This work was supported by National Institute on Aging Grant K23 AG19161; an American Federation for Aging Research/Pfizer Research grant; contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-HC-45133, and Grant U01 HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke; and the Intramural Research Program of the National Institute on Aging. A full list of principal Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. NR 44 TC 15 Z9 16 U1 0 U2 7 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 APR PY 2011 VL 96 IS 4 BP 989 EP 996 DI 10.1210/jc.2010-0926 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746JO UT WOS:000289242800040 PM 21289255 ER PT J AU Hong, DS Cabanillas, ME Wheler, J Naing, A Tsimberidou, AM Ye, L Waguespack, SG Hernandez, M El Naggar, AK Bidyasar, S Wright, J Sherman, SI Kurzrock, R AF Hong, David S. Cabanillas, Maria E. Wheler, Jennifer Naing, Aung Tsimberidou, Apostolia M. Ye, Lei Waguespack, Steven G. Hernandez, Mike El Naggar, Alder K. Bidyasar, Savita Wright, John Sherman, Steven I. Kurzrock, Razelle TI Inhibition of the Ras/Raf/MEK/ERK and RET Kinase Pathways with the Combination of the Multikinase Inhibitor Sorafenib and the Farnesyltransferase Inhibitor Tipifarnib in Medullary and Differentiated Thyroid Malignancies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PHASE-II TRIAL; MYELODYSPLASTIC SYNDROME; BREAST-CANCER; CARCINOMA; R115777; TUMORS; FARNESYLATION; CHEMOTHERAPY; DOXORUBICIN; ACTIVATION AB Purpose: Ras/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins. Patients and Methods: We treated 35 patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in a phase I trial. Sorafenib and tipifarnib were given for 21 d with 7 d rest in each 28-d cycle. Results: We enrolled 22 patients with metastatic DTC (16 papillary, five follicular, and one poorly differentiated) and 13 patients with MTC, of whom 15 with DTC and 10 with MTC reached first restaging. When tissue was available, eight of 15 DTC patients (53%) had B-Raf mutations; eight of 13 MTC (61.5%) patients had RET mutations. MTC partial response rate was 38% (five of 13) (duration = 9+, 12, 13, 16+, and 34+ months), stable disease of at least 6 months was 31% (four of 13). The DTC partial response rate was 4.5% (one of 22), and stable disease of at least 6 months was 36% (eight of 22). Median progression-free survival for all 35 patients was 18 months (95% confidence interval, 14.6 to not reached months). Median overall survival has not been reached, with a median follow-up of 24 months with 80% overall survival. Grade 1-2 toxicities were mainly rash, fatigue, and diarrhea. The most common grade 3-4 toxicities were rash, rise in amylase/lipase, and fatigue. Conclusions: Inhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer. (J Clin Endocrinol Metab 96: 997-1005, 2011) C1 [Hong, David S.] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Div Canc Med,Unit 455, Houston, TX 77030 USA. [Cabanillas, Maria E.; Ye, Lei; Waguespack, Steven G.; Hernandez, Mike; Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA. [El Naggar, Alder K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wright, John] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Hong, DS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Phase Clin Trials Program 1, Div Canc Med,Unit 455, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dshong@mdanderson.org OI Sherman, Steven/0000-0002-3079-5153 FU National Institutes of Health [5 U01 CA062461]; Translational Initiative Grant [25XS0688]; Bayer; Plexxikon; Exelixis; Eisai; Semafore; Oxigene; Celgene; AstroZeneca; Johnson Johnson FX This work was supported by National Institutes of Health Grant 5 U01 CA062461 (to R. K.) and Translational Initiative Grant 25XS0688 (to D.S.H.).; Disclosure Summary: D. S. H. received a translational initiative grant (25XS0688). M. E. C., J.W., A.N., A. M. T., L.Y., S. G. W., M. H., A. K. E., S. B., and J.W., have nothing to declare. S. I. S. received fees, served as a paid board member, and serves on advisory boards for Bayer, Plexxikon, Exelixis, Eisai, Semafore, Oxigene, Celgene, and AstroZeneca. R. K. served on an advisory board and received consulting fees for Johnson & Johnson. NR 40 TC 53 Z9 54 U1 0 U2 4 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 APR PY 2011 VL 96 IS 4 BP 997 EP 1005 DI 10.1210/jc.2010-1899 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746JO UT WOS:000289242800041 PM 21289252 ER PT J AU Maggio, M Ceda, GP Lauretani, F Bandinelli, S Corsi, AM Giallauria, F Guralnik, JM Zuliani, G Cattabiani, C Parrino, S Ablondi, F Dall'Aglio, E Ceresini, G Basaria, S Ferrucci, L AF Maggio, Marcello Ceda, Gian Paolo Lauretani, Fulvio Bandinelli, Stefania Corsi, Anna Maria Giallauria, Francesco Guralnik, Jack M. Zuliani, Giovanni Cattabiani, Chiara Parrino, Stefano Ablondi, Fabrizio Dall'Aglio, Elisabetta Ceresini, Graziano Basaria, Shehzad Ferrucci, Luigi TI SHBG, Sex Hormones, and Inflammatory Markers in Older Women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID C-REACTIVE PROTEIN; ADULT LIFE-SPAN; POSTMENOPAUSAL WOMEN; BINDING GLOBULIN; CARDIOVASCULAR RISK; METABOLIC SYNDROME; TESTOSTERONE; INCHIANTI; ASSOCIATION; DISEASE AB Context: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. Objective: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. Design and Patients: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-alpha. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. Results: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-alpha (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 +/- 0.08; P = 0.006) and E2 (0.21 +/- 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state. (J Clin Endocrinol Metab 96: 1053-1059, 2011) C1 [Maggio, Marcello; Ceda, Gian Paolo; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'Aglio, Elisabetta; Ceresini, Graziano] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. [Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Ceresini, Graziano] Univ Hosp Parma, Geriatr Rehabil Dept, I-43100 Parma, Italy. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, I-50125 Florence, Italy. [Corsi, Anna Maria] Tuscany Hlth Reg Agcy, I-50134 Florence, Italy. [Giallauria, Francesco; Ferrucci, Luigi] Univ Naples Federico 2, Cardiac Rehabil Unit, Dept Clin Med, I-80138 Naples, Italy. [Giallauria, Francesco] NIA, Longitudinal Studies Sect, Clin Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Zuliani, Giovanni] Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, I-44121 Ferrara, Italy. [Basaria, Shehzad] Boston Univ, Sch Med, Endocrinol Sect, Boston, MA 02118 USA. [Basaria, Shehzad] Boston Univ, Sch Med, Sect Diabet, Boston, MA 02118 USA. [Basaria, Shehzad] Boston Univ, Sch Med, Sect Nutr, Boston, MA 02118 USA. RP Maggio, M (reprint author), Harbor Hosp, NIA, NIH, Adv Studies Translat Res Aging Unit, 3001 S Hanover St, Baltimore, MD 21225 USA. EM marcellomaggio2001@yahoo.it RI Perez , Claudio Alejandro/F-8310-2010; Giallauria, Francesco/B-5681-2013; Lauretani, Fulvio/K-5115-2016; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Giallauria, Francesco/0000-0003-4119-9397; Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Italian Ministry of Health [ICS 110.1/RS97.71]; U.S. National Institute on Aging (NIA) [N01-AG-916413, N01-AG-821336, 263 MD 9164 13, 263 MD 821336] FX The InCHIANTI Study was supported as a "targeted project" (ICS 110.1/RS97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (NIA) (contracts N01-AG-916413 and N01-AG-821336), and by the Intramural Research Program of the U.S. NIA (contracts 263 MD 9164 13 and 263 MD 821336). None of the sponsoring institutions interfered with the collection, analysis, presentation, or interpretation of the data reported here. NR 32 TC 25 Z9 26 U1 1 U2 4 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 APR PY 2011 VL 96 IS 4 BP 1053 EP 1059 DI 10.1210/jc.2010-1902 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746JO UT WOS:000289242800048 PM 21239514 ER PT J AU Almeida, MQ Harran, M Bimpaki, EI Hsiao, HP Horvath, A Cheadle, C Watkins, T Nesterova, M Stratakis, CA AF Almeida, Madson Q. Harran, Michelle Bimpaki, Eirini I. Hsiao, Hui-Pin Horvath, Anelia Cheadle, Chris Watkins, Tonya Nesterova, Maria Stratakis, Constantine A. TI Integrated Genomic Analysis of Nodular Tissue in Macronodular Adrenocortical Hyperplasia: Progression of Tumorigenesis in a Disorder Associated with Multiple Benign Lesions SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INDEPENDENT CUSHINGS-SYNDROME; ADRENAL-HYPERPLASIA; HYBRIDIZATION ANALYSIS; MOLECULAR PATHWAYS; HORMONE-RECEPTORS; SOMATIC MUTATIONS; GENE-EXPRESSION; TUMORS; KINASE; SUBUNIT AB Context: Massive macronodular adrenocortical disease or ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a clinically and genetically heterogeneous disorder. Objective and Design: Whole-genome expression profiling and oligonucleotide array comparative genomic hybridization changes were analyzed in samples of different nodules from the same patients with AIMAH. Quantitative RT-PCR and staining were employed to validate them RNA array data. Results: Chromosomal gains were more frequent in larger nodules when compared with smaller nodules from the same patients. Among the 50 most overexpressed genes, 50% had a chromosomal locus that was amplified in the comparative genomic hybridization data. Although the list of most over-and under expressed genes was similar between the nodules of different size, the gene set enrichment analysis identified different pathways associated with AIMAH that corresponded to the size; the smaller nodules were mainly enriched for metabolic pathways, whereas p53 signaling and cancer genes were enriched in larger nodules. Confirmatory studies demonstrated that BCL2, E2F1, EGF, c-KIT, MYB, PRKCA, and CTNNB1 were overexpressed in the larger nodules at messenger and/or protein levels. Chromosomal enrichment analysis showed that chromosomes 20q13 and 14q23 might be involved in progression of AIMAH from smaller to larger tumors. Conclusion: Integrated transcriptomic and genomic data for AIMAH provides supporting evidence to the hypothesis that larger adrenal lesions, in the context of this chronic, polyclonal hyperplasia, accumulate an increased number of genomic and, subsequently, transcript abnormalities. The latter shows that the disease appears to start with mainly tissue metabolic derangements, as suggested by the study of the smaller nodules, but larger lesions showed aberrant expression of oncogenic pathways. (J Clin Endocrinol Metab 96: E728-E738, 2011) C1 [Almeida, Madson Q.; Harran, Michelle; Bimpaki, Eirini I.; Hsiao, Hui-Pin; Horvath, Anelia; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA. [Cheadle, Chris; Watkins, Tonya] Johns Hopkins Univ, Sch Med, Div Allergy & Clin Immunol, Baltimore, MD 21224 USA. RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov FU U.S. National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [Z01-HD-000642-04] FX This work was supported by U.S. National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural project Z01-HD-000642-04 (to C.A.S.). NR 46 TC 19 Z9 20 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2011 VL 96 IS 4 BP E728 EP E738 DI 10.1210/jc.2010-2420 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746JO UT WOS:000289242800022 PM 21252250 ER PT J AU Allik, J Realo, A Mottus, R Pullmann, H Trifonova, A McCrae, RR Yurina, AA Shebanets, EY Fadina, AG Tikhonova, EV Troitskaya, IY Fatyhova, RM Petrova, IF Tudupova, TT Tsiring, DA Panfilov, AN L'dokova, GM Aristova, IL Mescheryakov, BG Zorina, J Yuschenkova, DV Fotekova, TA Osmina, EV Vavilkina, NG Skhorohodova, NY Zernova, TI Dostovalov, SG Kadykova, SA Korepanova, IA Saharova, A Naumov, ND Snegireva, TV Kuznetsov, IY Kuznetsova, SA Rubtsova, MO Filatova, AF Nechaeva, TM Borisova, SN Postnikova, MI Gluhanyuk, NS Dyachenko, EV Fomina, NA Eromasova, AA Myshkina, SV Rulina, TK Yavkina, EV Knyazev, GG Ryabichenko, TI Demidova, IF Uvarov, EA Lopukhova, OG Vasyagina, NN Leonenko, NO Arinin, EI Lyapina, AA Dulina, NV Poyarova, TA Gaidar, KM Baranov, AA Kozhevnikova, OV Kalinichenko, OV Korneeva, EE AF Allik, Jueri Realo, Anu Mottus, Rene Pullmann, Helle Trifonova, Anastasia McCrae, Robert R. Yurina, Alla A. Shebanets, Elena Y. Fadina, Anelina G. Tikhonova, Elenora V. Troitskaya, Irina Y. Fatyhova, Rimma M. Petrova, Irina F. Tudupova, Tuyana T. Tsiring, Diana A. Panfilov, Aleksey N. L'dokova, Galya M. Aristova, Irina L. Mescheryakov, Boris G. Zorina, Julia Yuschenkova, Darya V. Fotekova, Tatiana A. Osmina, Elena V. Vavilkina, Natalya G. Skhorohodova, Nina Y. Zernova, Tatyana I. Dostovalov, Sergey G. Kadykova, Svetlana A. Korepanova, Inna A. Saharova, Anna Naumov, Nikolai D. Snegireva, Tatyana V. Kuznetsov, Igor Y. Kuznetsova, Snezhana A. Rubtsova, Maria O. Filatova, Aleksandra F. Nechaeva, Tatyana M. Borisova, Svetlana N. Postnikova, Margarita I. Gluhanyuk, Natalya S. Dyachenko, Elena V. Fomina, Natalya A. Eromasova, Aleksandra A. Myshkina, Svetlana V. Rulina, Tatyana K. Yavkina, Elena V. Knyazev, Gennady G. Ryabichenko, Tatyana I. Demidova, Irina F. Uvarov, Evgeni A. Lopukhova, Olga G. Vasyagina, Natalya N. Leonenko, Natalya O. Arinin, Evgeni I. Lyapina, Anna A. Dulina, Nadezhda V. Poyarova, Tatyana A. Gaidar, Karina M. Baranov, Aleksandr A. Kozhevnikova, Oksana V. Kalinichenko, Olga V. Korneeva, Ekaterina E. TI Personality Profiles and the "Russian Soul": Literary and Scholarly Views Evaluated SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article DE Personality; Russian soul; Russian national character: NEO PI-R; Big Five; Cross-cultural comparison; Personality ratings ID NATIONAL CHARACTER; 5-FACTOR MODEL; CULTURES; STEREOTYPE; RELIGION AB Many domestic and foreign observers have claimed that Russians have a unique constellation of personality traits that mirrors their distinctive historical and cultural experience. To examine the hypothesized uniqueness of Russian personality, members of the Russian Character and Personality Survey collected data from 39 samples in 33 administrative areas of the Russian Federation. Respondents (N = 7,065) identified an ethnically Russian adult or college-aged man or woman whom they knew well and rated the target using the Russian observer-rating version of the Revised NEO Personality Inventory. The mean personality profile of Russians was very similar to the international average based on 50 different countries, debunking the myth of a unique Russian soul. The small variations from world norms did not converge with depictions of Russian national character in fiction and the scholarly literature. New items intended to capture distinctive, emic aspects of Russian personality provided no new information beyond the familiar Big Five dimensions. Religion, ethnicity, and beliefs about the uniqueness of the Russian character and the malleability of personality traits had little effect on personality ratings. Perceptions of the Russian soul do not seem to be based on the personality traits of Russians. C1 [Allik, Jueri; Realo, Anu; Mottus, Rene; Pullmann, Helle; Trifonova, Anastasia] Univ Tartu, Dept Psychol, Estonian Ctr Behav & Hlth Sci, EE-50410 Tartu, Estonia. [McCrae, Robert R.] NIA, NIH, Baltimore, MD 21224 USA. [Yurina, Alla A.; Shebanets, Elena Y.] Adyghe State Univ, Maykop, Adygea Republic, Russia. [Fadina, Anelina G.] Astrakhan State Univ, Astrakhan, Russia. [Tikhonova, Elenora V.; Troitskaya, Irina Y.] Arzamas State Pedag Univ, Arzamas, Nizhny Novgorod, Russia. [Fatyhova, Rimma M.; Petrova, Irina F.] Bashkir State Pedag Univ, Ufa, Republ Bashkort, Russia. [Tudupova, Tuyana T.] Buryat State Univ, Ulan Ude, Buryat Republic, Russia. [Tsiring, Diana A.] Chelyabinsk State Univ, Chelyabinsk, Russia. [Panfilov, Aleksey N.; L'dokova, Galya M.] Elabuga State Pedag Univ, Yelabuga, Tatarstan Repub, Russia. [Aristova, Irina L.] Far Eastern Natl Univ, Vladivostok, Primorsky Krai, Russia. [Mescheryakov, Boris G.; Zorina, Julia; Yuschenkova, Darya V.] Int Univ Nat Soc & Man Dubna, Dubna, Moscow Oblast, Russia. [Fotekova, Tatiana A.] Katanov State Univ, Abakan, Republic Khakas, Russia. [Osmina, Elena V.; Vavilkina, Natalya G.] Izhevsk State Techonl Univ, Izhevsk, Republic Udmuri, Russia. [Skhorohodova, Nina Y.] Karelian State Pedag Univ, Petrozavodsk, Republic Kareli, Russia. [Zernova, Tatyana I.] Kuban State Univ Phys Educ Sport & Tourism, Krasnodar, Krasnodar Krai, Russia. [Dostovalov, Sergey G.] Kurgan State Univ, Kurgan, Russia. [Kadykova, Svetlana A.] Mari State Univ, Yoshkar Ola, Mari El Republi, Russia. [Korepanova, Inna A.; Saharova, Anna] Moscow City Univ Psychol & Educ, Moscow, Russia. [Naumov, Nikolai D.; Snegireva, Tatyana V.] Nizhnevartovsk State Humanitarian Univ, Nizhnevartovsk, Khanty Mansi Au, Russia. [Kuznetsov, Igor Y.; Kuznetsova, Snezhana A.] NE State Univ, Magadan, Russia. [Rubtsova, Maria O.] Novosibirsk State Pedag Univ, Novosibirsk, Russia. [Filatova, Aleksandra F.] Omsk State Pedag Univ, Omsk, Russia. [Nechaeva, Tatyana M.] Orel State Univ, Oryol, Russia. [Borisova, Svetlana N.] Perm State Univ, Perm, Perm Krai, Russia. [Postnikova, Margarita I.] Pomor State Univ, Arkhangelsk, Russia. [Gluhanyuk, Natalya S.; Dyachenko, Elena V.] Russia State Profess Pedag Univ, Ekaterinburg, Sverdlovsk Obla, Russia. [Fomina, Natalya A.] Ryazan State Univ, Ryazan, Russia. [Eromasova, Aleksandra A.; Myshkina, Svetlana V.] Sakhalin State Univ, Yuzhno Sakhalinsk, Sakhalin Oblast, Russia. [Rulina, Tatyana K.; Yavkina, Elena V.] Samara State Pedag Univ, Samara, Russia. [Knyazev, Gennady G.; Ryabichenko, Tatyana I.] Russian Acad Med Sci Novosibirsk, Siberian Branch, Novosibirsk, Russia. [Demidova, Irina F.] Taganrog Inst Management & Econ, Taganrog, Rostov Oblast, Russia. [Uvarov, Evgeni A.] Tambov State Univ, Tambov, Russia. [Lopukhova, Olga G.] Tatar State Humanitarian Pedag Univ, Kazan, Republic Tatars, Russia. [Vasyagina, Natalya N.; Leonenko, Natalya O.] Ural State Pedag Univ, Ekaterinburg, Sverdlovsk Obla, Russia. [Arinin, Evgeni I.] Vladimir State Univ, Vladimir, Russia. [Lyapina, Anna A.] Volgograd Acad Publ Adm, Volgograd, Russia. [Dulina, Nadezhda V.] Volgograd State Tech Univ, Volgograd, Russia. [Gaidar, Karina M.] Voronezh State Univ, Voronezh 394693, Russia. [Baranov, Aleksandr A.; Kozhevnikova, Oksana V.] Udmurt State Univ, Izhevsk, Republic Udmurt, Russia. [Kalinichenko, Olga V.] Ussuriysk State Pedag Inst, Ussuriysk, Primorsky Krai, Russia. [Korneeva, Ekaterina E.] Yaroslavl Demidov State Univ, Yaroslavl, Yaroslavl Oblas, Russia. [Poyarova, Tatyana A.] Vologda State Pedag Univ, Vologda, Russia. RP Allik, J (reprint author), Univ Tartu, Dept Psychol, Estonian Ctr Behav & Hlth Sci, EE-50410 Tartu, Estonia. EM juri.allik@ut.ee RI Allik, Juri/D-5609-2009; Knyazev, Gennady/F-6095-2010; Fadina, Angelina/D-8005-2014; Lopukhova, Olga/M-8997-2013; Okatova, Svetlana/P-3375-2015; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; Knyazev, Gennady/0000-0002-8628-4678; Lopukhova, Olga/0000-0003-1243-3594; NR 39 TC 3 Z9 3 U1 1 U2 33 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD APR PY 2011 VL 42 IS 3 BP 372 EP 389 DI 10.1177/0022022110362751 PG 18 WC Psychology, Social SC Psychology GA 741FP UT WOS:000288849200004 ER PT J AU Taverna, L Bornstein, MH Putnick, DL Axia, G AF Taverna, Livia Bornstein, Marc H. Putnick, Diane L. Axia, Giovanna TI Adaptive Behaviors in Young Children: A Unique Cultural Comparison in Italy SO JOURNAL OF CROSS-CULTURAL PSYCHOLOGY LA English DT Article ID QUALITY-OF-LIFE; GERMAN; PSYCHOLOGY; UNIVERSAL; ROUTINES; MOTHER; MATTER; SLEEP; GOALS; POWER AB On account of a series of unique historical events, the present-day denizens of South Tyrol inhabit a cultural, political, and linguistic autonomous region that intercalates Italians and Austrian/German Italians. The authors compared contemporary Italian and Austrian/German Italian girls' and boys' adaptive behaviors in everyday activities in this region. Using the Vineland Adaptive Behavior Scales, the authors first interviewed mothers about their children's communication, daily living, socialization, and motor skills. Main effects of local culture (and no interactions with gender) emerged: Austrian/German Italian children were rated higher than Italian children in both adaptive daily living and socialization skills. Next, the authors explored ethnic differences in childrearing. Austrian/German Italians reported fostering greater autonomy in their children than Italians, and children's autonomy was associated with their adaptive behavior. Children living in neighboring Italian and Austrian/German Italian cultural niches appear to experience subtle but consequentially different conditions of development that express themselves in terms of differing levels of adaptive behaviors. C1 [Taverna, Livia] Free Univ Bozen Bolzano, Fac Educ, I-1639042 Brixen, Italy. [Taverna, Livia] Libera Univ Bolzano, Fac Sci Formaz, Bolzano, Italy. [Bornstein, Marc H.; Putnick, Diane L.] NICHHD, Eunice Kennedy Shriver NICHHD, Bethesda, MD USA. [Axia, Giovanna] Univ Padua, Dipartimento Psicol Sviluppo & Proc Socializzaz, Padua, Italy. RP Taverna, L (reprint author), Free Univ Bozen Bolzano, Fac Educ, Viale Stn 16, I-1639042 Brixen, Italy. EM livia.taverna@unibz.it; Marc_H_Bornstein@nih.gov OI Putnick, Diane/0000-0002-6323-749X FU Intramural NIH HHS [Z99 HD999999, Z01 HD001119-20] NR 79 TC 5 Z9 5 U1 2 U2 12 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0221 J9 J CROSS CULT PSYCHOL JI J. Cross-Cult. Psychol. PD APR PY 2011 VL 42 IS 3 BP 445 EP 465 DI 10.1177/0022022110362748 PG 21 WC Psychology, Social SC Psychology GA 741FP UT WOS:000288849200008 PM 21532914 ER PT J AU Whitaker, TM Bada, HS Bann, CM Shankaran, S LaGasse, L Lester, BM Bauer, CR Hammond, J Higgins, R AF Whitaker, Toni M. Bada, Henrietta S. Bann, Carla M. Shankaran, Seetha LaGasse, Linda Lester, Barry M. Bauer, Charles R. Hammond, Jane Higgins, Rosemary TI Serial Pediatric Symptom Checklist Screening in Children With Prenatal Drug Exposure SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE behavior disorder; child behavior; mental health; screening; prenatal cocaine exposure; Pediatric Symptom Checklist ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; PSYCHOSOCIAL DYSFUNCTION; BEHAVIOR PROBLEMS; PSYCHIATRIC MORBIDITY; PRIMARY-CARE; SCHOOL-AGE; CHILDHOOD; OUTCOMES; SMOKING AB Objective: To examine screening results obtained by serial annual behavioral assessment of children with prenatal drug exposure. Method: The Maternal Lifestyle Study enrolled children with prenatal cocaine exposure (PCE) at birth for longitudinal assessments of developmental, behavioral, and health outcomes. At 8, 9, 10, 11, and 12 years of age, caregivers rated participants on the Pediatric Symptom Checklist (PSC). Serial PSC results were compared with an established broad-based behavioral measure at 9, 11, and 13 years. PSC results were analyzed for 1081 children who had at least 2 annual screens during the 5-year time span. Most subjects (87%) had 4 or more annual screens rated by the same caregiver (80%). PSC scores (and Positive screens) over time were compared at different time points for those with and without PCE. Covariates, including demographic factors and exposures to certain other substances, were controlled. Results: Children with PCE had significantly higher scores overall, with more Positive screens for behavior problems than children without PCE. Children with PCE had more externalizing behavior problems. Children exposed to tobacco prenatally and postnatally also showed higher PSC scores. Over time, PSC scores differed slightly from the 8-year scores, without clear directional trend. Earlier PSC results predicted later behavioral outcomes. Conclusion: Findings of increased total PSC scores and Positive PSC screens for behavioral concerns in this group of children with prenatal substance exposure support the growing body of evidence that additional attention to identification of mental health problems may be warranted in this high-risk group. (J Dev Behav Pediatr 32:206-215, 2011) C1 [Whitaker, Toni M.] Univ Tennessee, Boling Ctr Dev Disabil, Hlth Sci Ctr, Dept Pediat,Coll Med, Memphis, TN 38105 USA. [Bada, Henrietta S.] Univ Kentucky, Coll Med, Stat & Epidemiol Unit, Dept Pediat, Lexington, KY USA. [Bann, Carla M.; Hammond, Jane] Res Triangle Inst Int, Res Triangle Pk, NC USA. [Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA. [LaGasse, Linda; Lester, Barry M.] Brown Univ, Sch Med, Dept Pediat, Providence, RI 02912 USA. [Bauer, Charles R.] Univ Miami, Dept Pediat, Sch Med, Miami, FL 33152 USA. [Higgins, Rosemary] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA. RP Whitaker, TM (reprint author), Univ Tennessee, Boling Ctr Dev Disabil, Hlth Sci Ctr, Dept Pediat,Coll Med, 711 Jefferson Ave, Memphis, TN 38105 USA. EM twhitaker@uthsc.edu FU National Institute on Drug Abuse (NIDA); National Institute of Mental Health (NIMH); National Institutes of Health (NIH); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Brown University Warren Alpert Medical School, Women & Infants Hospital of Rhode Island [U10 DA24119, U10 HD27904, N01 HD23159]; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute on Drug Abuse; RTI International [U10 HD36790]; University of Miami Holtz Children's Hospital [U10 DA24118, U10 HD21397]; University of Tennessee [U10 DA24128, U10 HD21415, U10 HD42638]; Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan [U10 DA24117, U10 HD21385] FX This investigation was supported by the National Institute on Drug Abuse (NIDA), the National Institute of Mental Health (NIMH), the National Institutes of Health (NIH), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).; The following individuals, in addition to those listed as authors, and federal funding grants contributed to this study:; Brown University Warren Alpert Medical School, Women & Infants Hospital of Rhode Island (U10 DA24119, U10 HD27904, N01 HD23159)-Katherine Halloran, MA; Seamus Hearne, BA; Melissa Hooks, BA; Jing Liu, PhD; Cynthia Miller-Loncar, PhD; Geidy Nolasco, BS; Lia O'Brien, BA; Sonia Tobon; Jean Twomey, PhD.; Eunice Kennedy Shriver National Institute of Child Health and Human Development-Rosemary D. Higgins, MD.; National Institute on Drug Abuse-Nicolette Borek, PhD.; RTI International (U10 HD36790)-W. Kenneth Poole, PhD; Abhik Das, PhD; Debra Fleischmann, BS; Susan McRitchie, MS.; University of Miami Holtz Children's Hospital (U10 DA24118, U10 HD21397)-Carmel Azemar, MSW; Miriam Borges, BS; Khania Contreras, BA; Susan Gauthier, BA; Ann L. Graziotti, MSN; Rafael Guzman, MSW; Michelle Lugo, BA; Mary Triolo, RN, ARNP.; University of Tennessee (U10 DA24128, U10 HD21415, U10 HD42638)-Ashley Bayne, BS; Charlotte C. Bursi, MSSW, LCSW; Daneen Deptula, MS; Claudia Duncan, MSN, RNSC, PNP; Tina Hudson, RN, BSN; Lillie Hughey, MSSW, LCSW; Sheldon B. Korones, MD; Deloris Lee, MSSW; Pamela LeNoue, RN; Sue Meewes, RN; Laura Murphy, PhD; Sidney Ornduff, PhD; Mario C. Petersen, MD; Leanne Plumlee Pollard, BS; Jonathan Rowland, BS; Michelle Silcox Miller, BS; Andrea Simmons, RNC, MSN, PNP; Toni Whitaker, MD.; Wayne State University Hutzel Women's Hospital and Children's Hospital of Michigan (U10 DA24117, U10 HD21385)-Eunice Woldt, MSN; Jay Ann Nelson, BSN; Kathleen Abramczyk, BS; Tovonne Lucas BS. NR 38 TC 9 Z9 9 U1 2 U2 7 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 APR PY 2011 VL 32 IS 3 BP 206 EP 215 DI 10.1097/DBP.0b013e318208ee3c PG 10 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 743AL UT WOS:000288987200005 PM 21200328 ER PT J AU Emani, S Young, JB Acker, M Mangi, A Cleveland, JC Miller, MA Naftel, DC Kirklin, JK Cannon, A Hasan, AK Sai-Sudhaker, CB Sun, B AF Emani, S. Young, J. B. Acker, M. Mangi, A. Cleveland, J. C. Miller, M. A. Naftel, D. C. Kirklin, J. K. Cannon, A. Hasan, A. K. Sai-Sudhaker, C. B. Sun, B. TI Bridge to Candidacy: A Fulfilled Promise? SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 31st Annual Meeting and Scientific Sessions on International-Society-for-Heart-and-Lung-Transplantation CY APR 13-16, 2011 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Emani, S.; Hasan, A. K.; Sai-Sudhaker, C. B.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Acker, M.] Univ Penn, Philadelphia, PA 19104 USA. [Mangi, A.] Temple Univ, Philadelphia, PA 19122 USA. [Cleveland, J. C.] Univ Colorado, Aurora, CO USA. [Naftel, D. C.; Kirklin, J. K.] Univ Alabama, Birmingham, AL USA. [Sun, B.] Minneapolis Heart Inst, Minneapolis, MN USA. [Miller, M. A.] NHLBI, Adv Technol & Surg Branch, NIH, Bethesda, MD 20892 USA. [Cannon, A.] Univ Colorado Hosp, Cardiac & Vasc Serv, Aurora, CO USA. RI Hasan, Ayesha/E-3214-2011 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2011 VL 30 IS 4 SU S MA 362 BP S125 EP S125 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 742EO UT WOS:000288924300361 ER PT J AU Goldstein, DJ Milano, CA Su, KN Iribarne, A Woo, JY Ailawadi, G Thourani, VA Miller, MA Goldsmith, L Swayze, R Chen, Y Ascheim, DD Argenziano, M AF Goldstein, D. J. Milano, C. A. Su, K. N. Iribarne, A. Woo, J. Y. Ailawadi, G. Thourani, V. A. Miller, M. A. Goldsmith, L. Swayze, R. Chen, Y. Ascheim, D. D. Argenziano, M. TI Infections after Surgery for Advanced Heart Failure: Experience of the NIH CT Surgical Trials Network SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 31st Annual Meeting and Scientific Sessions on International-Society-for-Heart-and-Lung-Transplantation CY APR 13-16, 2011 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Su, K. N.; Chen, Y.; Ascheim, D. D.] Mt Sinai Sch Med, Dept Hlth Evidence & Policy, New York, NY USA. [Iribarne, A.; Goldsmith, L.; Argenziano, M.] Columbia Univ, Dept Surg, Med Ctr, New York, NY USA. [Goldstein, D. J.; Swayze, R.] Montefiore Einstein Heart Ctr, Dept Surg, Bronx, NY USA. [Miller, M. A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Ailawadi, G.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA. [Thourani, V. A.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. [Milano, C. A.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Woo, J. Y.] Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2011 VL 30 IS 4 SU S MA 101 BP S41 EP S42 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 742EO UT WOS:000288924300102 ER PT J AU Jessup, ML Goldstein, D Ascheim, DD Teuteberg, JJ Park, SJ Naftel, DC Gonzales-Stawirski, GV Ulisney, KL Kirklin, JK Kormos, RL AF Jessup, M. L. Goldstein, D. Ascheim, D. D. Teuteberg, J. J. Park, S. J. Naftel, D. C. Gonzales-Stawirski, G. V. Ulisney, K. L. Kirklin, J. K. Kormos, R. L. TI Risk for Bleeding after MCSD Implant: An Analysis of 2358 Patients in INTERMACS SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 31st Annual Meeting and Scientific Sessions on International-Society-for-Heart-and-Lung-Transplantation CY APR 13-16, 2011 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Jessup, M. L.] Univ Penn, Philadelphia, PA 19104 USA. [Goldstein, D.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Ascheim, D. D.] Mt Sinai Sch Med, Dept Hlth Evidence Policy, Cardiovasc Inst, New York, NY USA. [Teuteberg, J. J.; Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA USA. [Park, S. J.] Mayo Clin, Rochester, MN USA. [Naftel, D. C.; Kirklin, J. K.] Univ Alabama, Birmingham, AL USA. [Gonzales-Stawirski, G. V.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ulisney, K. L.] NIH, Div Cardiovasc Sci, Heart Lung & Blood Inst, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2011 VL 30 IS 4 SU S MA 5 BP S9 EP S9 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 742EO UT WOS:000288924300006 ER PT J AU Starling, RC Stehlik, J Nicholls, S Ikle, D Chandraker, A Teresa, F Baran, D Wolski, K Mfarrej, B Ahmad, U Sayegh, M Heeger, P AF Starling, R. C. Stehlik, J. Nicholls, S. Ikle, D. Chandraker, A. Teresa, F. Baran, D. Wolski, K. Mfarrej, B. Ahmad, U. Sayegh, M. Heeger, P. TI Incidence of Coronary Artery Vasculopathy Has Decreased with Modern Immunosuppression: Insights from Clinical Trials in Organ Transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 31st Annual Meeting and Scientific Sessions on International-Society-for-Heart-and-Lung-Transplantation CY APR 13-16, 2011 CL San Diego, CA SP Int Soc Heart & Lung Transplantat C1 [Starling, R. C.; Stehlik, J.; Nicholls, S.; Ikle, D.; Chandraker, A.; Teresa, F.; Baran, D.; Wolski, K.; Mfarrej, B.; Ahmad, U.; Sayegh, M.; Heeger, P.] Cleveland Clin, Cleveland, OH 44106 USA. [Heeger, P.] Mt Sinai Sch Med, New York, NY USA. [Stehlik, J.] Univ Utah, Salt Lake City, UT USA. [Ikle, D.] NIH, Rho Fed Syst Div, Chapel Hill, NC USA. [Starling, R. C.; Stehlik, J.; Nicholls, S.; Ikle, D.; Chandraker, A.; Teresa, F.; Baran, D.; Wolski, K.; Mfarrej, B.; Ahmad, U.; Sayegh, M.; Heeger, P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Baran, D.] New Jersy Med Sch, Newark, NJ 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 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD APR PY 2011 VL 30 IS 4 SU S MA 542 BP S182 EP S182 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 742EO UT WOS:000288924300538 ER PT J AU Bomboi, G Ikonomidou, VN Pellegrini, S Stern, SK Gallo, A Auh, S Evangelou, IE Agarwal, J Pellicano, C Ohayon, JM Cantor, FK Ehrmantraut, M McFarland, HF Kane, RL Bagnato, F AF Bomboi, Giuseppe Ikonomidou, Vasiliki N. Pellegrini, Stefano Stern, Susan K. Gallo, Antonio Auh, Sungyoung Evangelou, Iordanis E. Agarwal, Jhalak Pellicano, Clelia Ohayon, Joan M. Cantor, Fredric K. Ehrmantraut, Mary McFarland, Henry F. Kane, Robert L. Bagnato, Francesca TI Quality and Quantity of Diffuse and Focal White Matter Disease and Cognitive Disability of Patients with Multiple Sclerosis SO JOURNAL OF NEUROIMAGING LA English DT Article DE Multiple sclerosis; MACFIMS; cognitive functions; magnetization transfer ratio; high-field MRI; normal-appearing white matter ID FUNCTIONAL COMPOSITE; COORDINATE SYSTEM; CORTICAL SURFACE; IMPAIRMENT; BRAIN; DYSFUNCTION; MRI; SEGMENTATION; REGISTRATION; SENSITIVITY AB BACKGROUND AND PURPOSE Using high-field magnetic resonance imaging (MRI), we investigated the relationships between white matter (WM) lesion volume (LV), normal-appearing WM (NAWM) normalized volume, WM-lesion and NAWM magnetization transfer ratios (MTRs), brain parenchyma fraction (BPF), and cognitive impairment (CI) in multiple sclerosis (MS). METHODS Twenty-four patients and 24 healthy volunteers (age, sex, and years of education-matched) underwent a 3.0 Tesla (3T) scan and evaluation of depression, fatigue, and CI using the Minimal Assessment of Cognitive Function in MS (MACFIMS) battery. RESULTS In this clinically relatively well-preserved cohort of patients (median score on the Expanded Disability Status Scale = 1.5), CI was detected on Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and Controlled Oral Word Association Test. MT data were available in 19 pairs on whom correlation analyses were performed. Associations were seen between SDMT and normalized NAWM volume (P = .034, r = .502), CVLT-II long delay and normalized NAWM volume (P = .012, r = .563), WM-LV (P = .024, r = .514), and BPF (P = .002, r = .666). CONCLUSIONS The use of 3T MRI in a sample of clinically stable MS patients shows the importance of WM disease in hampering processing speed and word retrieval. C1 [Bomboi, Giuseppe; Ikonomidou, Vasiliki N.; Pellegrini, Stefano; Stern, Susan K.; Gallo, Antonio; Evangelou, Iordanis E.; Agarwal, Jhalak; Pellicano, Clelia; Ohayon, Joan M.; Cantor, Fredric K.; Ehrmantraut, Mary; McFarland, Henry F.; Bagnato, Francesca] NINDS, NIB, NIH, Bethesda, MD 20892 USA. [Auh, Sungyoung] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Kane, Robert L.] VA Maryland Healthcare Syst, Bethesda, MD USA. RP Bagnato, F (reprint author), NINDS, NIB, NIH, Bldg 10,Room 5C103 10 Ctr Drive,1400 MSC, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov RI Pellicano, Clelia/K-1062-2016 OI Pellicano, Clelia/0000-0002-3272-1094 FU NINDS, NIH; University of Rome (Italy); La Sapienza; Bayer-Schering Pharmaceuticals Group FX This research was supported by the Intramural Research Program of the NINDS, NIH. Dr Giuseppe Bomboi's contribution was sustained by a public-private partnership supported jointly by the University of Rome (Italy), La Sapienza and a grant from Bayer-Schering Pharmaceuticals Group. NR 48 TC 8 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2011 VL 21 IS 2 BP e57 EP e63 DI 10.1111/j.1552-6569.2010.00488.x PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 739YX UT WOS:000288759300006 PM 20626570 ER PT J AU Dasenbrock, HH Smith, SA Ozturk, A Farrell, SK Calabresi, PA Reich, DS AF Dasenbrock, Hormuzdiyar H. Smith, Seth A. Ozturk, Arzu Farrell, Sheena K. Calabresi, Peter A. Reich, Daniel S. TI Diffusion Tensor Imaging of the Optic Tracts in Multiple Sclerosis: Association with Retinal Thinning and Visual Disability SO JOURNAL OF NEUROIMAGING LA English DT Article DE Multiple sclerosis; optic neuritis; magnetic resonance imaging; diffusion tensor imaging; optic tract; optical coherence tomography ID NERVE-FIBER LAYER; CONTRAST LETTER ACUITY; COHERENCE TOMOGRAPHY; CORTICOSPINAL TRACT; AXONAL LOSS; FUNCTIONAL COMPOSITE; BRAIN MRI; NEURITIS; DAMAGE; DYSFUNCTION AB BACKGROUND AND PURPOSE Visual disability is common in multiple sclerosis, but its relationship to abnormalities of the optic tracts remains unknown. Because they are only rarely affected by lesions, the optic tracts may represent a good model for assessing the imaging properties of normal-appearing white matter in multiple sclerosis. METHODS Whole-brain diffusion tensor imaging was performed on 34 individuals with multiple sclerosis and 26 healthy volunteers. The optic tracts were reconstructed by tractography, and tract-specific diffusion indices were quantified. In the multiple-sclerosis group, peripapillary retinal nerve-fiber-layer thickness and total macular volume were measured by optical coherence tomography, and visual acuity at 100%, 2.5%, and 1.25% contrast was examined. RESULTS After adjusting for age and sex, optic-tract mean and perpendicular diffusivity were higher (P = .002) in multiple sclerosis. Lower optic-tract fractional anisotropy was correlated with retinal nerve-fiber-layer thinning (r = .51, P = .003) and total-macular-volume reduction (r = .59, P = .002). However, optic-tract diffusion indices were not specifically correlated with visual acuity or with their counterparts in the optic radiation. CONCLUSIONS Optic-tract diffusion abnormalities are associated with retinal damage, suggesting that both may be related to optic-nerve injury, but do not appear to contribute strongly to visual disability in multiple sclerosis. C1 [Dasenbrock, Hormuzdiyar H.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Smith, Seth A.; Ozturk, Arzu; Reich, Daniel S.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA. [Farrell, Sheena K.; Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. [Smith, Seth A.; Reich, Daniel S.] Kennedy Krieger Inst, FM Kirby Res Ctr Funct Brain Imaging, Baltimore, MD USA. RP Reich, DS (reprint author), NIH, Translat Neuroradiol Unit, 10 Ctr Dr,Bldg 10-5C103, Bethesda, MD 20892 USA. EM reichds@ninds.nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU National Multiple Sclerosis Society [CA1029A2, TR3760A3]; NIH [K99NS064098, P41RR015241, R01AG020012, K01EB009120]; Nancy Davis Center without Walls FX The authors thank Terri Brawner, Brian Caffo, Deanna Cettomai, Jonathan Farrell, Eliza Gordon-Lipkin, Kathleen Kahl, Ivana Kusevic, Bennett Landman, Susumu Mori, Mathew Pulicken, and Peter van Zijl for useful discussions and for assistance with data collection. The study was supported by National Multiple Sclerosis Society grants CA1029A2 and TR3760A3; NIH grants K99NS064098, P41RR015241, R01AG020012, and K01EB009120; and the Nancy Davis Center without Walls. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 60 TC 14 Z9 14 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1051-2284 J9 J NEUROIMAGING JI J. Neuroimaging PD APR PY 2011 VL 21 IS 2 BP e41 EP e49 DI 10.1111/j.1552-6569.2010.00468.x PG 9 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 739YX UT WOS:000288759300004 PM 20331501 ER PT J AU Pearson, JP Williams, NM Majounie, E Waite, A Stott, J Newsway, V Murray, A Hernandez, D Guerreiro, R Singleton, AB Neal, J Morris, HR AF Pearson, Justin P. Williams, Nigel M. Majounie, Elisa Waite, Adrian Stott, Jennifer Newsway, Victoria Murray, Alex Hernandez, Dena Guerreiro, Rita Singleton, Andrew B. Neal, James Morris, Huw R. TI Familial frontotemporal dementia with amyotrophic lateral sclerosis and a shared haplotype on chromosome 9p SO JOURNAL OF NEUROLOGY LA English DT Article DE Frontotemporal dementia; Amyotrophic lateral sclerosis; Mendelian; Chromosome 9 ID MOTOR-NEURON DISEASE; LOBAR DEGENERATION; COGNITIVE IMPAIRMENT; TDP-43; ALS; PREVALENCE; MUTATIONS; PATHOLOGY; LINKAGE; LOCUS AB Families with autosomal dominant frontotemporal dementia and amyotrophic lateral sclerosis (FTD/ALS) have previously been linked to a locus on chromosome 9p21. We describe the clinical phenotype and pathology of a large family with autosomal dominant FTD/ALS with nine affected members originating from Gwent in South Wales, UK. We also further refine the locus on chromosome 9p21 using a haplotype sharing approach and assess heterogeneity in 9p21 linked families. Within this family, affected individuals present with either FTD or ALS or both diseases simultaneously. In addition there was marked phenotypic variation including ataxia, Parkinsonism, psychosis and visuo-spatial cognitive deficits. The pathological features of the three cases described were consistent with type 2 FTD pathology, as previously reported in similar families. However, we also report distinctive cerebellar and glial pathology and a significant proportion of TDP-43 negative inclusions. No mutations in known genes for FTD or ALS were found. We identified a large 4.8-megabase haplotype on chromosome 9p21, which was shared by all affected family members. This haplotype overlaps and limits the previously reported FTD/ALS linkage region on chromosome 9p21. Sequencing of this region did not identify any evidence of a pathogenic exonic mutation. This suggests that the pathogenic change affects non-coding DNA and that the disease is caused by variation in gene or protein expression. C1 [Morris, Huw R.] Univ Wales Hosp, Cardiff CF14 4XN, S Glam, Wales. [Pearson, Justin P.; Williams, Nigel M.; Majounie, Elisa; Waite, Adrian; Newsway, Victoria; Morris, Huw R.] Cardiff Univ, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF14 4XN, S Glam, Wales. [Murray, Alex] Univ Wales Hosp, Inst Med Genet, Cardiff CF14 4XN, S Glam, Wales. [Hernandez, Dena; Guerreiro, Rita; Singleton, Andrew B.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. [Stott, Jennifer; Neal, James] Cardiff Univ, Sch Med, Dept Pathol, Cardiff CF14 4XN, S Glam, Wales. [Morris, Huw R.] Royal Gwent Hosp, Dept Neurol, Aneurin Bevan Local Hlth Board, Cardiff, Gwent, Wales. RP Morris, HR (reprint author), Univ Wales Hosp, Cardiff CF14 4XN, S Glam, Wales. EM morrishr@cf.ac.uk RI Morris, Huw/B-8527-2008; Singleton, Andrew/C-3010-2009; Guerreiro, Rita/A-1327-2011 OI Morris, Huw/0000-0002-5473-3774; FU Motor Neuron Disease Assocaition (UK); Medical Research Council (UK) [G0700943]; National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000951-06] FX We are grateful to members of this family for participating in this research. We are grateful for the opportunity to review clinical notes made by Prof. P. Harper, Prof. A. Compston and Dr. T. Pickersgill and to Dr A. Liu (Consultant Neuroradiologist, University Hospital of Wales) for reviewing the radiology. This work was supported by the Motor Neuron Disease Assocaition (UK), the Medical Research Council (UK) Grant G0700943 and the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services; project Z01 AG000951-06. NR 24 TC 57 Z9 57 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD APR PY 2011 VL 258 IS 4 BP 647 EP 655 DI 10.1007/s00415-010-5815-x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 741ZB UT WOS:000288906300017 PM 21072532 ER PT J AU Marion, DW Curley, KC Schwab, K Hicks, RR AF Marion, Donald W. Curley, Kenneth C. Schwab, Karen Hicks, Ramona R. CA mTBI Diagnostics Workgrp TI Proceedings of the Military mTBI Diagnostics Workshop, St. Pete Beach, August 2010 SO JOURNAL OF NEUROTRAUMA LA English DT Article DE concussion; diagnosis; mild traumatic brain injury; Neurocognitive Assessment Tool (NCAT); Military Acute Concussion Evaluation (MACE); Operation Iraqi Freedom (OIF); Operation Enduring Freedom (OEF); military mild traumatic brain injury ID TRAUMATIC BRAIN-INJURY; COLLEGIATE FOOTBALL PLAYERS; BIOCHEMICAL MARKERS; HEAD-INJURY; CONCUSSION; SERUM; S-100B; DAMAGE; S100B; BIOMARKERS AB Approximately 28,000 service members (SMs) sustain a traumatic brain injury (TBI) each year in the U. S. military. The majority of the injuries result either in a brief or no loss of consciousness, and are classified as a mild TBI (mTBI or concussion). Current evaluation guidelines of SMs suspected of having a mTBI rely heavily on self-reports. However, there is concern that SMs typically minimize or do not report their symptoms of mTBI for fear that doing so will result in being removed from the battlefield. Because mTBI often results in headaches, cognitive dysfunction, attention difficulties, and balance problems, returning to the battlefield before resolution of their symptoms can be dangerous for the SM and for their unit. Sustaining a second concussion before resolution of a previous mTBI also may make long-term neuronal injury more likely. The mTBI Diagnostics Workshop was designed as a forum where civilian and military experts from a variety of TBI-related clinical and basic science disciplines could meet to define the diagnostic tools, alone or in combination, that were most likely to result in an acute, objective diagnosis of mTBI. The premise of the meeting was that a small number of well-focused research projects conducted over the next 2-3 years could be done to validate the optimal test, or more likely combination of tests, that would be practical and reliable for the acute diagnosis of mTBI within 2-3 h of injury in theater. The recommendations of the Workshop are provided in this report. C1 [Marion, Donald W.; Schwab, Karen] Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Washington, DC 20307 USA. [Curley, Kenneth C.] USA, Combat Casualty Care Directorate, Med Res & Mat Command, Ft Detrick, MD USA. [Hicks, Ramona R.] NINDS, Bethesda, MD 20892 USA. RP Marion, DW (reprint author), Walter Reed Army Med Ctr, Def & Vet Brain Injury Ctr, Bldg 1,Room B209 6900 Georgia Ave NW, Washington, DC 20307 USA. EM Donald.Marion@us.army.mil FU mTBI Diagnostics Workshop FX Support for the mTBI Diagnostics Workshop was provided by Col. Dallas Hack, Director of the Combat Casualty Care Directorate, U.S. Army Medical Research and Materiel Command, and by Col. Jamie Grimes, National Director of the Defense and Veterans Brain Injury Center. Marithea Goberville, Ph.D., provided a transcript of the report-out session of the conference. NR 36 TC 19 Z9 21 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD APR PY 2011 VL 28 IS 4 BP 517 EP 526 DI 10.1089/neu.2010.1638 PG 10 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 746IW UT WOS:000289240200003 PM 21265587 ER PT J AU Mullins, LL Wolfe-Christensen, C Chaney, JM Elkin, TD Wiener, L Hullmann, SE Fedele, DA Junghans, A AF Mullins, Larry L. Wolfe-Christensen, Cortney Chaney, John M. Elkin, T. David Wiener, Lori Hullmann, Stephanie E. Fedele, David A. Junghans, Ashley TI The Relationship Between Single-Parent Status and Parenting Capacities in Mothers of Youth with Chronic Health Conditions: The Mediating Role of Income SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE adjustment; chronic illness; parent stress; psychosocial functioning ID PERCEIVED CHILD VULNERABILITY; QUALITY-OF-LIFE; CHRONIC ILLNESS; SOCIAL SUPPORT; OVERPROTECTION; CANCER; STRESS; ADJUSTMENT; PERCEPTIONS; LEUKEMIA AB Objective To retrospectively examine the relationship of single-parent status to parenting capacity variables in mothers of youth with a chronic health condition. Methods Parental overprotection, perceived vulnerability, and parenting stress were assessed in 383 mothers (308 married and 75 single parents) of youth with one of six chronic health conditions (i.e., type 1 diabetes, asthma, cancer, cystic fibrosis, hemophilia, or sickle cell disease). Results Single mothers evidenced higher levels of both perceived vulnerability and parenting stress, but not overprotection, than married parents. These differences disappeared in the presence of income as a predictor. Conclusions Single parents appear to evidence differences in parenting capacity; however, low income appears to account in large part for the higher level of risk associated with single-parent status. C1 [Mullins, Larry L.; Chaney, John M.; Hullmann, Stephanie E.; Fedele, David A.; Junghans, Ashley] Oklahoma State Univ, Dept Psychol, Stillwater, OK 74078 USA. [Wolfe-Christensen, Cortney] Childrens Hosp Michigan, Dept Pediat Neurol, Detroit, MI USA. [Elkin, T. David] Univ Mississippi, Dept Psychiat & Human Behav, Med Ctr, University, MS 38677 USA. [Wiener, Lori] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Mullins, LL (reprint author), Oklahoma State Univ, Dept Psychol, 116 N Murray Hall, Stillwater, OK 74078 USA. EM larry.mullins@okstate.edu NR 36 TC 12 Z9 12 U1 1 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD APR PY 2011 VL 36 IS 3 BP 249 EP 257 DI 10.1093/jpepsy/jsq080 PG 9 WC Psychology, Developmental SC Psychology GA 740NA UT WOS:000288800300001 PM 20817713 ER PT J AU Curtis, J Kim, G Wehr, NB Levine, RL AF Curtis, J. Kim, G. Wehr, N. B. Levine, R. L. TI Group B Streptococcus, phospholipids and pulmonary hypertension SO JOURNAL OF PERINATOLOGY LA English DT Article DE Group B Streptococcus; persistent pulmonary hypertension of the newborn; phospholipids; cardiolipin ID TREATED CORYNEBACTERIUM-ALKANOLYTICUM; MEMBRANE-PERMEABILITY BARRIER; BETA-HEMOLYTIC STREPTOCOCCUS; L-GLUTAMIC ACID; MUTANS BHT; EXTRACELLULAR ACCUMULATION; ESCHERICHIA-COLI; POLAR LIPIDS; PENICILLIN; EXCRETION AB Objective: Group B Streptococcus is the most common cause of bacterial infection in the newborn. Our aim was to purify and identify molecules produced by the bacterium, which cause pulmonary hypertension. Study Design: Guided by bioassays performed in neonatal lambs, we utilized standard biochemical techniques for the purification of these bioactive compounds. The compounds were identified by mass spectrometry. Fully synthetic compounds were then tested using the bioassay to confirm their ability to induce pulmonary hypertension. Result: The purified bacterial components causing pulmonary hypertension were the phospholipids cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. Conclusion: Bacterial phospholipids are capable of causing pulmonary hypertension. This finding opens new avenues for therapeutic intervention in persistent pulmonary hypertension of the newborn and generates hypotheses regarding the etiology of respiratory distress in the newborn and the possible effect of antibiotic therapy. Journal of Perinatology (2011) 31, S24-S28; doi: 10.1038/jp.2010.168 C1 [Levine, R. L.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Curtis, J.] Uniformed Serv Univ Hlth Sci, Off Grad Med Educ, Bethesda, MD 20814 USA. [Curtis, J.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU National Heart, Lung and Blood Institute; National Naval Medical Center; Navy Bureau of Medicine and Surgery, Washington, District of Columbia, Clinical Investigation Program [B00-022] FX This work was supported by the Intramural Research Program of the National Heart, Lung and Blood Institute and by grants to JC from the National Naval Medical Center and The Chief, Navy Bureau of Medicine and Surgery, Washington, District of Columbia, Clinical Investigation Program (no. B00-022). The views expressed are those of the author (JC) and do not reflect the official policy or position of the USUHS, the Department of Defense, or the United States Government. NR 34 TC 2 Z9 2 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0743-8346 J9 J PERINATOL JI J. Perinatol. PD APR PY 2011 VL 31 SU 1 BP S24 EP S28 DI 10.1038/jp.2010.168 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 746IB UT WOS:000289236900004 PM 21448200 ER PT J AU Kan, H Folsom, AR Cushman, M Rose, KM Rosamond, WD Liao, D Lurmann, F London, SJ AF Kan, H. Folsom, A. R. Cushman, M. Rose, K. M. Rosamond, W. D. Liao, D. Lurmann, F. London, S. J. TI Traffic exposure and incident venous thromboembolism in the Atherosclerosis Risk in Communities (ARIC) Study SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE air pollution; cohort; traffic exposure; VTE ID DEEP-VEIN THROMBOSIS; AMERICAN-HEART-ASSOCIATION; PARTICULATE AIR-POLLUTION; CARDIOVASCULAR-DISEASE; MORTALITY; STATEMENT; ETIOLOGY; CHILDREN; COHORT; MATTER AB Background: Two recent case-control studies in Italy reported that long-term exposure to particulate air pollution or living near major traffic roads was associated with an increased risk of deep vein thrombosis (DVT). No prospective evidence exists on the possible association between long-term traffic-related air pollution and incident venous thromboembolism (VTE). Objectives: To examine the association between long-term traffic exposure and incident VTE in a population-based prospective cohort study. Methods: We studied 13 143 middle-aged men and women in the Atherosclerosis Risk in Communities Study without a history of DVT or pulmonary embolism at baseline examination (1987-1989). The Geographical Information System-mapped traffic density and distance to major roads in the four study communities served as measures of traffic exposure. We examined the association between traffic exposure and incident VTE with proportional hazards regression models. Results: A total of 405 subjects developed VTE in 2005. Traffic density was not significantly associated with VTE. Relative to those in the lowest quartile of traffic density, the adjusted hazard ratios across increasing quartiles were 1.18 (95% confidence interval [CI] 0.88-1.57), 0.99 (95% CI 0.74-1.34) and 1.14 (95% CI 0.86-1.51) (P-value for trend across quartiles = 0.64). For residents living within 150 m of major roads, as compared with subjects living further away, the adjusted hazard ratio was 1.16 (95% CI 0.95-1.42, P = 0.14). Conclusions: This first prospective study in the general population does not support an association between air pollution exposure or traffic proximity and risk of DVT. More data may be needed to clarify whether traffic or air pollution influences the risk of VTE. C1 [London, S. J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Kan, H.] Fudan Univ, Sch Publ Hlth, Key Lab Publ Hlth Safety, Minist Educ,Inst Global Environm Change Res, Shanghai 200433, Peoples R China. [Folsom, A. R.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Cushman, M.] Univ Vermont, Dept Med, Burlington, VT USA. [Rose, K. M.; Rosamond, W. D.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [Liao, D.] Penn State Univ, Dept Hlth Evaluat Sci, Hershey, PA USA. [Lurmann, F.] Sonoma Technol Inc, Petaluma, CA USA. RP London, SJ (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 london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL59367]; National Institute of Environmental Health Sciences, National Institutes of Health, DHHS [ZO1 ES043012]; National Basic Research Program (973 program) of China [2011CB503802] FX The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, and N01-HC-55022. This work was also supported by NHLBI grant R01-HL59367 and the Intramural Research Program, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS ZO1 ES043012. H. Kan was supported by the National Basic Research Program (973 program) of China (2011CB503802). NR 25 TC 15 Z9 15 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD APR PY 2011 VL 9 IS 4 BP 672 EP 678 DI 10.1111/j.1538-7836.2011.04210.x PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 745HP UT WOS:000289156800007 PM 21255249 ER PT J AU Mitchell, SJ Huizer-Pajkos, A Cogger, VC McLachlan, AJ Le Couteur, DG Jones, B de Cabo, R Hilmer, SN AF Mitchell, Sarah J. Huizer-Pajkos, Aniko Cogger, Victoria C. McLachlan, Andrew J. Le Couteur, David G. Jones, Brett de Cabo, Rafael Hilmer, Sarah N. TI Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Acetaminophen; Pseudocapillarization; Aging; Isolated liver perfusion; Extraction ID HYPOXIA-REOXYGENATION INJURY; MULTIPLE-INDICATOR DILUTION; GLUCOSE-TRANSPORT; DRUG CLEARANCE; CIRRHOSIS; PHARMACOKINETICS; METABOLISM; EXTRACTION; BLOOD; HEPATOTOXICITY AB We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer (14)C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 +/- 0.04, old; 0.59 +/- 0.05, young; p < .05). In old age, there was significant reduction of the intercompartmental rate constant k(1) (0.34 +/- 0.10s(-1) old; 0.61 +/- 0.38s(-1) young; p < .05) and the permeability-surface area product for the transfer of acetaminophen across the sinusoidal endothelium (0.034 +/- 0.006 mL/s/g. old: 0.048 +/- 0.014 mL/s/g, young; p < .005). There was no difference in k(3). the measure of sequestration of acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. C1 [Mitchell, Sarah J.; Huizer-Pajkos, Aniko; Jones, Brett; Hilmer, Sarah N.] Royal N Shore Hosp, Kolling Inst Med Res, Sydney, NSW, Australia. [Mitchell, Sarah J.; Huizer-Pajkos, Aniko; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Aged Care, Sydney, NSW, Australia. [Mitchell, Sarah J.; Cogger, Victoria C.; Le Couteur, David G.; Hilmer, Sarah N.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [McLachlan, Andrew J.] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia. [Jones, Brett] Royal N Shore Hosp, Dept Gastroenterol & Hepatol, Sydney, NSW, Australia. [de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. RP Mitchell, SJ (reprint author), Royal N Shore Hosp, Kolling Inst Med Res, Lab Ageing & Pharmacol, Level 12 Kolling Bldg,Pacific Highway, St Leonards, NSW 2065, Australia. EM sarah.mitchell@sydney.edu.au RI de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Hilmer, Sarah/0000-0002-5970-1501; , rafael/0000-0003-2830-5693; McLachlan, Andrew/0000-0003-4674-0242 FU Geoff and Elaine Penney Aging Research Unit, Royal North Shore Hospital; National Health and Medical Research Council of Australia [570968, 570937]; Ageing and Alzheimers Research Foundation; National Institute on Aging of the National Institutes of Health, USA FX This study was funded by the Geoff and Elaine Penney Aging Research Unit, Royal North Shore Hospital, by the National Health and Medical Research Council of Australia project grants #570968 and #570937, the Ageing and Alzheimers Research Foundation and was supported in part by the Intramural Research Program of the National Institute on Aging of the National Institutes of Health, USA. NR 46 TC 12 Z9 16 U1 0 U2 2 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 APR PY 2011 VL 66 IS 4 BP 400 EP 408 DI 10.1093/gerona/glq221 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 741AX UT WOS:000288836600005 PM 21300741 ER PT J AU Crasto, CL Semba, RD Sun, K Dalal, M Corsi, AM Bandinelli, S Guralnik, JM Ferrucci, L AF Crasto, Candace L. Semba, Richard D. Sun, Kai Dalal, Mansi Corsi, Anna Maria Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Endogenous Secretory Receptor for Advanced Glycation End Products Is Associated With Low Serum Interleukin-1 Receptor Antagonist and Elevated IL-6 in Older Community-Dwelling Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Advanced glycation end products; C-reactive protein; Endogenous secretory receptor for advanced glycation end products; Interleukin-1 receptor antagonist; Interleukin-6 ID TYPE-1 DIABETIC-PATIENTS; INFLAMMATORY MARKERS; CIRCULATING RECEPTORS; MORTALITY; DISEASE; WOMEN; NONAGENARIANS; INCHIANTI; DECLINE; ESRAGE AB Background. Advanced glycation end products (AGEs) are thought to cause inflammation through interaction with the receptor for AGEs (RAGE), therefore contributing to adverse aging-related processes. The relationship between AGEs. RAGE, and inflammation has not been well characterized. Methods. We examined the relationship of plasma endogenous secretory RAGE (esRAGE); carboxymethyl-lysine (CML), a circulating AGE; and inflammatory mediators in 1,298 adults, 20-97 years, who participated in the InCHIANTI study in Tuscany, Italy. Blood levels of esRAGE, CM L, interleukin-1 receptor antagonist (IL-IRA), 1L-1 beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-6 receptor (IL-6R), IL-18, C-reactive protein (CRP), transforming growth factor-beta (TGF-beta), and fibrinogen were measured. Results. Log plasma esRAGE was associated with log IL-IRA (beta = -0.069, SE = 0.036, p = .05) and log IL-6 (beta = 0.077, SE = 0.035, p = .03), respectively, in separate multivariable linear regression models, adjusting for potential confounders. Log plasma esRAGE was also negatively associated with log TGF-beta but did not reach statistical significance (beta = -0.091, SE = 0.053, p =.09). Log plasma esRAGE was not significantly associated with log IL-1 beta, log TNF-alpha, IL-6R, log IL-18, or CRP. Log plasma CML was not associated with any of the inflammatory mediators except for IL-6R (beta = -14.10, SE = 5.94, p = .02) and fibrinogen (beta = 13.95, SE =7.21, p = .05) in separate multivariable models, adjusting for potential confounders. Conclusions. Plasma esRAGE is correlated with higher IL-6 and lower IL-IRA. These findings suggest that plasma esRAGE plays a role in modulating inflammation, although the exact mechanisms remain to be elucidated. C1 [Crasto, Candace L.; Semba, Richard D.; Sun, Kai; Dalal, Mansi] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. [Corsi, Anna Maria; Bandinelli, Stefania] Azienda Sanit Firenze, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 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 FU National Institute on Aging [R01 AG027012, R01 AG029148, R01 HL094507]; Italian Ministry of Health [ICS110.1/RF97.71]; NIA [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institute on Aging, National Institutes of Health FX This work was supported by National Institute on Aging Grants R01 AG027012, R01 AG029148, R01 HL094507; the Italian Ministry of Health (ICS110.1/RF97.71), NIA contracts 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, and N01-AG-5-0002; and the Intramural Research Program, National Institute on Aging, National Institutes of Health. NR 28 TC 5 Z9 5 U1 0 U2 2 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 APR PY 2011 VL 66 IS 4 BP 437 EP 443 DI 10.1093/gerona/glq225 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 741AX UT WOS:000288836600009 PM 21357189 ER PT J AU Cook, NL Orav, EJ Liang, CL Guadagnoli, E Hicks, LS AF Cook, Nakela L. Orav, E. John Liang, Catherine L. Guadagnoli, Edward Hicks, LeRoi S. TI Racial and Gender Disparities in Implantable Cardioverter-Defibrillator Placement: Are They Due to Overuse or Underuse? SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article DE Disparities; Race/Ethnicity; Sex; Implantable-Cardioverter Defibrillator; Ventricular Arrhythmia ID QUALITY-OF-CARE; HEART-FAILURE; VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; UNITED-STATES; SEX; MANAGEMENT; OUTCOMES; RACE AB Previous studies documented racial and gender disparities in implantable cardioverter-defibrillator (ICD) placement. The authors examined whether racial and gender disparities in ICD placement are due to underutilization or overutilization. Among 1,054 adults hospitalized from 2001 to 2004 with ventricular arrhythmias in a large academic hospital, the study found that 17% of patients had clinical indicators concordant with ICD placement criteria. Among those, Blacks were less likely than Whites to receive an ICD (adjusted odds ratio [OR] = 0.24; 95% CI = 0.08-0.71). Among the 83% who were discordant with ICD placement criteria, Blacks (adjusted OR = 0.30; 95% CI = 0.18-0.52) and Hispanics (adjusted OR = 0.24, 95% CI = 0.10-0.57) were less likely than Whites, and women less likely than men, to receive an ICD (adjusted OR = 0.48; 95% CI = 0.34-0.67). In this cohort, these differences appear related to overutilization among men and Whites who are discordant with ICD placement criteria in addition to underutilization among Blacks concordant with placement criteria. C1 [Cook, Nakela L.] NHLBI, Bethesda, MD 20892 USA. [Orav, E. John; Liang, Catherine L.; Hicks, LeRoi S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Guadagnoli, Edward; Hicks, LeRoi S.] Harvard Univ, Sch Med, Boston, MA USA. RP Cook, NL (reprint author), NHLBI, 6701 Rockledge Dr,Rockledge 2,Suite 10018, Bethesda, MD 20892 USA. EM cookn2@nhlbi.nih.gov FU Agency for Healthcare Research and Quality [5 T32 HS000020-21]; Harvard Medical School Center of Excellence in Minority Health and Health Disparities FX This study received grant funding from the Harvard Medical School Center of Excellence in Minority Health and Health Disparities. Nakela L. Cook was supported by an institutional National Research Service Award from the Agency for Healthcare Research and Quality (5 T32 HS000020-21) during the conduct of this research. LeRoi S. Hicks received grant funding from the Harvard Medical School Center of Excellence in Minority Health and Health Disparities." To "This study received grant funding from the Harvard Medical School Center of Excellence in Minority Health and Health Disparities. Nakela L. Cook was supported by an institutional National Research Service Award from the Agency for Healthcare Research and Quality (5 T32 HS000020-21) during the conduct of this research. NR 36 TC 9 Z9 9 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD APR PY 2011 VL 68 IS 2 BP 226 EP 246 DI 10.1177/1077558710379421 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 738OG UT WOS:000288648900005 PM 20829236 ER PT J AU Habermann, JK Brucker, CA Freitag-Wolf, S Heselmeyer-Haddad, K Kruger, S Barenboim, L Downing, T Bruch, HP Auer, G Roblick, UJ Ried, T AF Habermann, Jens K. Brucker, Constanze A. Freitag-Wolf, Sandra Heselmeyer-Haddad, Kerstin Krueger, Stefan Barenboim, Linda Downing, Tricia Bruch, Hans-Peter Auer, Gert Roblick, Uwe J. Ried, Thomas TI Genomic instability and oncogene amplifications in colorectal adenomas predict recurrence and synchronous carcinoma SO MODERN PATHOLOGY LA English DT Article DE amplifications; colorectal adenomas; colorectal carcinogenesis; deletions; genomic instability ID RECEPTOR COACTIVATOR GENE; CYCLIN-A; CHROMOSOMAL INSTABILITY; ULCERATIVE-COLITIS; EPITHELIAL-CELLS; GAMMA-2 CHAIN; RAB PROTEINS; S-PHASE; CANCER; AIB1 AB Individual colorectal adenomas have different propensities to progress to invasive disease. In this study, we explored whether these differences could be explained by gene copy number alterations. We evaluated 18 adenomas of patients without synchronous or subsequent carcinoma (6.5 years follow-up), 23 adenomas of carcinoma patients, and 6 related carcinomas. All samples were measured for their DNA ploidy status. Centromere probes for chromosomes 17 and 18, as well as gene-specific probes for SMAD7, EGFR, NCOA3, TP53, MYC, and RAB20 were assessed by multicolor fluorescence in situ hybridization. An increased genomic instability index of CEP17, SMAD7, and EGFR, as well as TP53 deletions and MYC amplifications defined adenomas of patients with synchronous carcinoma (P<0.05). Diploid NCOA3 signal counts were associated with longer adenoma recurrence-free surveillance (P=0.042). In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (P<0.05). Furthermore, aberrations of NCOA3, MYC, and RAB20 were associated with histopathologically defined high-risk adenomas (P<0.05). RAB20 amplifications were also correlated with high-grade dysplastic adenomas (P=0.002). We conclude that genomic instability in colorectal adenomas is reflected by EGFR, MYC, NCOA3, and RAB20 amplifications that do correlate with histomorphological features and are indicative for adenoma recurrence and the presence of synchronous carcinomas. Modern Pathology (2011) 24, 542-555; doi: 10.1038/modpathol.2010.217; published online 19 November 2010 C1 [Habermann, Jens K.] Univ Clin Schleswig Holstein, Dept Surg, Surg Res Lab, D-23538 Lubeck, Germany. [Habermann, Jens K.; Auer, Gert; Roblick, Uwe J.] Karolinska Inst, Karolinska Biom Ctr, Unit Canc Prote, Stockholm, Sweden. [Habermann, Jens K.; Brucker, Constanze A.; Heselmeyer-Haddad, Kerstin; Barenboim, Linda; Downing, Tricia; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Freitag-Wolf, Sandra] Univ Clin Schleswig Holstein, Inst Med Informat & Stat, Kiel, Germany. [Krueger, Stefan] Univ Clin Schleswig Holstein, Inst Pathol, D-23538 Lubeck, Germany. RP Habermann, JK (reprint author), Univ Clin Schleswig Holstein, Dept Surg, Surg Res Lab, Campus Lubeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM Jens.Habermann@gmail.com RI Habermann, Jens/E-2968-2010 FU NIH, National Cancer Institute; Werner und Klara Kreitz-Foundation, Schleswig-Holstein, Germany; DAAD (Deutscher Akademischer Austauschdienst); Boehringer Ingelheim Fond (BIF), Germany FX We express our gratitude to Timo Gemoll, Buddy Chen and Joseph Cheng for IT support, to Ulla Aspenblad and Inga Maurin for excellent assistance with immunohistochemistry, to Marco Gerling and Gisela Grosser-Pape for excellent assistance with image cytometry, and to Elke Gheribi and Regina Kaatz for clinical sample and data collection. This project was supported by the Intramural Research Program of the NIH, National Cancer Institute and by the Werner und Klara Kreitz-Foundation, Schleswig-Holstein, Germany. CAB received a stipend by the DAAD (Deutscher Akademischer Austauschdienst) and a travel grant by the Boehringer Ingelheim Fond (BIF), Germany. This study was performed in collaboration with the North German Tumorbank Colorectal Cancer (DKH no. 108446) and the Surgical Center for Translational Oncology-Lubeck (SCTO-L). NR 38 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 2011 VL 24 IS 4 BP 542 EP 555 DI 10.1038/modpathol.2010.217 PG 14 WC Pathology SC Pathology GA 744CT UT WOS:000289072100008 PM 21102417 ER PT J AU Burnette, DT Manley, S Sengupta, P Sougrat, R Davidson, MW Kachar, B Lippincott-Schwartz, J AF Burnette, Dylan T. Manley, Suliana Sengupta, Prabuddha Sougrat, Rachid Davidson, Michael W. Kachar, Bechara Lippincott-Schwartz, Jennifer TI A role for actin arcs in the leading-edge advance of migrating cells SO NATURE CELL BIOLOGY LA English DT Article ID NEURONAL GROWTH CONE; FOCAL ADHESIONS; NASCENT ADHESIONS; MOTILE CELLS; DYNAMICS; FILAMENTS; MICROTUBULE; PROTRUSION; NETWORKS; BUNDLES AB Epithelial cell migration requires coordination of two actin modules at the leading edge: one in the lamellipodium and one in the lamella. How the two modules connect mechanistically to regulate directed edge motion is not understood. Using live-cell imaging and photoactivation approaches, we demonstrate that the actin network of the lamellipodium evolves spatio-temporally into the lamella. This occurs during the retraction phase of edge motion, when myosin II redistributes to the lamellipodial actin and condenses it into an actin arc parallel to the edge. The new actin arc moves rearward, slowing down at focal adhesions in the lamella. We propose that net edge extension occurs by nascent focal adhesions advancing the site at which new actin arcs slow down and form the base of the next protrusion event. The actin arc there by serves as a structural element underlying the temporal and spatial connection between the lamellipodium and the lamella during directed cell motion. C1 [Burnette, Dylan T.; Manley, Suliana; Sengupta, Prabuddha; Sougrat, Rachid; Lippincott-Schwartz, Jennifer] NICHHD, NIH, Bethesda, MD 20892 USA. [Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32310 USA. [Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. [Kachar, Bechara] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM lippincj@mail.nih.gov RI Manley, Suliana/D-3818-2012; OI Manley, Suliana/0000-0002-4755-4778; Sougrat, Rachid/0000-0001-6476-1886; Sengupta, Prabuddha/0000-0001-7094-6967 FU NIGMS, NIH FX We thank the members of the Lippincott-Schwartz Laboratory for helpful comments and suggestions. D.T.B. was supported by a Pharmacology Research Associate Fellowship from NIGMS, NIH during the course of these studies. NR 40 TC 144 Z9 145 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2011 VL 13 IS 4 BP 371 EP U88 DI 10.1038/ncb2205 PG 17 WC Cell Biology SC Cell Biology GA 744CK UT WOS:000289070900009 PM 21423177 ER PT J AU Kuo, JC Han, XM Hsiao, CT Yates, JR Waterman, CM AF Kuo, Jean-Cheng Han, Xuemei Hsiao, Cheng-Te Yates, John R., III Waterman, Clare M. TI Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for beta-Pix in negative regulation of focal adhesion maturation SO NATURE CELL BIOLOGY LA English DT Article ID MIGRATING CELLS; EXCHANGE FACTOR; ALPHA-ACTININ; PAXILLIN PHOSPHORYLATION; INTEGRIN ACTIVATION; SHOTGUN PROTEOMICS; LEADING-EDGE; F-ACTIN; DYNAMICS; RHO AB Focal adhesions undergo myosin-II-mediated maturation wherein they grow and change composition to modulate integrin signalling for cell migration, growth and differentiation. To determine how focal adhesion composition is affected by myosin II activity, we performed proteomic analysis of isolated focal adhesions and compared protein abundance in focal adhesions from cells with and without myosin II inhibition. We identified 905 focal adhesion proteins, 459 of which changed in abundance with myosin II inhibition, defining the myosin-II-responsive focal adhesion proteome. The abundance of 73% of the proteins in the myosin-II-responsive focal adhesion proteome was enhanced by contractility, including proteins involved in Rho-mediated focal adhesion maturation and endocytosis-and calpain-dependent focal adhesion disassembly. During myosin II inhibition, 27% of proteins in the myosin-II-responsive focal adhesion proteome, including proteins involved in Rac-mediated lamellipodial protrusion, were enriched in focal adhesions, establishing that focal adhesion protein recruitment is also negatively regulated by contractility. We focused on the Rac guanine nucleotide exchange factor beta-Pix, documenting its role in the negative regulation of focal adhesion maturation and the promotion of lamellipodial protrusion and focal adhesion turnover to drive cell migration. C1 [Kuo, Jean-Cheng; Waterman, Clare M.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Han, Xuemei; Yates, John R., III] Scripps Res Inst, La Jolla, CA 92037 USA. [Hsiao, Cheng-Te] NIA, Prote & Analyt Biochem Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Waterman, CM (reprint author), NHLBI, Cell Biol & Physiol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM jyates@scripps.edu; watermancm@nhlbi.nih.gov OI Waterman, Clare/0000-0001-6142-6775 FU NHLBI; NIH [P41 RR011823] FX We thank J. Hildebrand (University of Pittsburgh), J. Peterson (Fox Chase Cancer Centre), M. Davidson (Florida State), R.H. Chen (Academia Sinica) and M. Beckerle (University of Utah) for reagents, the NHLBI proteomics and flow cytometry facilities, W. Shin and I. Schneider for help with imaging and analysis, and A. Aslanian. C.M.W. is supported by NHLBI, J.R.Y. by NIH P41 RR011823. NR 75 TC 222 Z9 225 U1 1 U2 30 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2011 VL 13 IS 4 BP 383 EP U109 DI 10.1038/ncb2216 PG 21 WC Cell Biology SC Cell Biology GA 744CK UT WOS:000289070900010 PM 21423176 ER PT J AU Vickers, KC Palmisano, BT Shoucri, BM Shamburek, RD Remaley, AT AF Vickers, Kasey C. Palmisano, Brian T. Shoucri, Bassem M. Shamburek, Robert D. Remaley, Alan T. TI MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins SO NATURE CELL BIOLOGY LA English DT Article ID APOLIPOPROTEIN-A-I; HEPATOCELLULAR-CARCINOMA; DIVALENT-CATIONS; MESSENGER-RNAS; EXPRESSION; MECHANISM; BINDING; GENES; DNA; ATHEROSCLEROSIS AB Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. Reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of messenger RNA reporters. Furthermore, HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be dependent on scavenger receptor class B type I. The human HDL-miRNA profile of normal subjects is significantly different from that of familial hypercholesterolemia subjects. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations indicate that HDL participates in a mechanism of intercellular communication involving the transport and delivery of miRNAs. C1 [Vickers, Kasey C.; Palmisano, Brian T.; Shoucri, Bassem M.; Shamburek, Robert D.; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Vickers, KC (reprint author), NHLBI, NIH, 10 Ctr Dr,Bldg 10 8N222, Bethesda, MD 20892 USA. EM vickerskc@nhlbi.nih.gov OI Palmisano, Brian T./0000-0002-2140-1060 FU NIH, NHLBI DIR FX This study was helped by the NHLBI Electron Microscopy Core, Genomics Core and Proteomics Core Facilities. Special thanks are extended to P. Sethupathy, PhD, for target prediction and discussion, M. Sampson for her work on patient lipid profiles and A. Loncarich for statistical analysis. This research was supported in total by the Intramural Research Program of the NIH, NHLBI DIR. NR 62 TC 872 Z9 924 U1 13 U2 115 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2011 VL 13 IS 4 BP 423 EP U182 DI 10.1038/ncb2210 PG 19 WC Cell Biology SC Cell Biology GA 744CK UT WOS:000289070900014 PM 21423178 ER PT J AU Spellman, P Gray, J AF Spellman, Paul Gray, Joe TI A new treasure in the breast cancer gene hunt SO NATURE MEDICINE LA English DT Editorial Material ID THERAPEUTIC TARGET C1 [Spellman, Paul] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. [Spellman, Paul] US Natl Canc Inst, Bethesda, MD USA. [Gray, Joe] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Spellman, P (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. EM grayjo@ohsu.edu NR 9 TC 9 Z9 9 U1 0 U2 2 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 APR PY 2011 VL 17 IS 4 BP 422 EP 423 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 746KI UT WOS:000289245100027 PM 21475233 ER PT J AU Wang, TJ Larson, MG Vasan, RS Cheng, S Rhee, EP McCabe, E Lewis, GD Fox, CS Jacques, PF Fernandez, C O'Donnell, CJ Carr, SA Mootha, VK Florez, JC Souza, A Melander, O Clish, CB Gerszten, RE AF Wang, Thomas J. Larson, Martin G. Vasan, Ramachandran S. Cheng, Susan Rhee, Eugene P. McCabe, Elizabeth Lewis, Gregory D. Fox, Caroline S. Jacques, Paul F. Fernandez, Celine O'Donnell, Christopher J. Carr, Stephen A. Mootha, Vamsi K. Florez, Jose C. Souza, Amanda Melander, Olle Clish, Clary B. Gerszten, Robert E. TI Metabolite profiles and the risk of developing diabetes SO NATURE MEDICINE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; AMINO-ACID; INSULIN-RESISTANCE; LIFE-STYLE; SECRETION; PROTEIN; PREDICTION; MIXTURES; MELLITUS; OBESITY AB Emerging technologies allow the high-throughput profiling of metabolic status from a blood specimen (metabolomics). We investigated whether metabolite profiles could predict the development of diabetes. Among 2,422 normoglycemic individuals followed for 12 years, 201 developed diabetes. Amino acids, amines and other polar metabolites were profiled in baseline specimens by liquid chromatography-tandem mass spectrometry (LC-MS). Cases and controls were matched for age, body mass index and fasting glucose. Five branched-chain and aromatic amino acids had highly significant associations with future diabetes: isoleucine, leucine, valine, tyrosine and phenylalanine. A combination of three amino acids predicted future diabetes (with a more than fivefold higher risk for individuals in top quartile). The results were replicated in an independent, prospective cohort. These findings underscore the potential key role of amino acid metabolism early in the pathogenesis of diabetes and suggest that amino acid profiles could aid in diabetes risk assessment. C1 [Wang, Thomas J.; Rhee, Eugene P.; Lewis, Gregory D.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. [Wang, Thomas J.; Cheng, Susan; McCabe, Elizabeth; Lewis, Gregory D.; O'Donnell, Christopher J.; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Wang, Thomas J.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; McCabe, Elizabeth; Fox, Caroline S.; O'Donnell, Christopher J.] Boston Univ, Sch Med, Framingham, MA USA. [Wang, Thomas J.; Larson, Martin G.; Vasan, Ramachandran S.; Cheng, Susan; McCabe, Elizabeth; Fox, Caroline S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. [Cheng, Susan] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol, Boston, MA USA. [Rhee, Eugene P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Renal, Boston, MA USA. [Rhee, Eugene P.; Lewis, Gregory D.; O'Donnell, Christopher J.; Carr, Stephen A.; Mootha, Vamsi K.; Florez, Jose C.; Souza, Amanda; Clish, Clary B.; Gerszten, Robert E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol, Boston, MA USA. [Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept, Agr Human Nutr Res Ctr, Boston, MA 02111 USA. [Fernandez, Celine] Lund Univ, Dept Expt Med Sci, Malmo, Sweden. [Mootha, Vamsi K.; Florez, Jose C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA USA. [Mootha, Vamsi K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Melander, Olle] Lund Univ, Dept Clin Sci, Malmo, Sweden. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. EM tjwang@partners.org; rgerszten@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU US National Institutes of Health [NO1-HC-25195, R01-DK-HL081572]; Donald W. Reynolds Foundation; Leducq Foundation; American Heart Association; Ellison Foundation; Massachusetts General Hospital; Doris Duke Charitable Foundation FX This work was supported by US National Institutes of Health contract NO1-HC-25195, R01-DK-HL081572, the Donald W. Reynolds Foundation, the Leducq Foundation and the American Heart Association. S. C. is also supported by an award from the Ellison Foundation. J.C.F. is also supported by the Massachusetts General Hospital and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. NR 31 TC 801 Z9 827 U1 50 U2 276 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 APR PY 2011 VL 17 IS 4 BP 448 EP U83 DI 10.1038/nm.2307 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 746KI UT WOS:000289245100035 PM 21423183 ER PT J AU Hanson, JC Tangrea, MA Kim, S Armani, MD Pohida, TJ Bonner, RF Rodriguez-Canales, J Emmert-Buck, MR AF Hanson, Jeffrey C. Tangrea, Michael A. Kim, Skye Armani, Michael D. Pohida, Thomas J. Bonner, Robert F. Rodriguez-Canales, Jaime Emmert-Buck, Michael R. TI Expression microdissection adapted to commercial laser dissection instruments SO NATURE PROTOCOLS LA English DT Article ID QUANTITATIVE RT-PCR; CAPTURE MICRODISSECTION; IN-SITU; PROMOTER METHYLATION; TISSUE SPECIMENS; PROSTATE-CANCER; IMMUNO-LCM; CELLS; MICROENVIRONMENT; VALIDATION AB Laser-based microdissection facilitates the isolation of specific cell populations from clinical or animal model tissue specimens for molecular analysis. Expression microdissection (xMD) is a second-generation technology that offers considerable advantages in dissection capabilities; however, until recently the method has not been accessible to investigators. This protocol describes the adaptation of xMD to commonly used laser microdissection instruments and to a commercially available handheld laser device in order to make the technique widely available to the biomedical research community. The method improves dissection speed for many applications by using a targeting probe for cell procurement in place of an operator-based, cell-by-cell selection process. Moreover, xMD can provide improved dissection precision because of the unique characteristics of film activation. The time to complete the protocol is highly dependent on the target cell population and the number of cells needed for subsequent molecular analysis. C1 [Hanson, Jeffrey C.; Rodriguez-Canales, Jaime; Emmert-Buck, Michael R.] NCI, Laser Microdissect Core, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Tangrea, Michael A.; Kim, Skye; Armani, Michael D.; Emmert-Buck, Michael R.] NCI, Pathogenet Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Pohida, Thomas J.] NIH, Signal Proc & Instrumentat Sect, Ctr Informat Technol, Bethesda, MD 20892 USA. [Bonner, Robert F.] NICHHD, Lab Med Biophys, NIH, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Laser Microdissect Core, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM buckm@mail.nih.gov RI Bonner, Robert/C-6783-2015; OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU NIH National Cancer Institute, Center for Cancer Research FX This research was supported, in part, by the intramural program of the NIH National Cancer Institute, Center for Cancer Research. NR 27 TC 11 Z9 11 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD APR PY 2011 VL 6 IS 4 BP 457 EP 467 DI 10.1038/nprot.2010.202 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 743CF UT WOS:000288993200005 PM 21412274 ER PT J AU Kopp, JB AF Kopp, Jeffrey B. TI BIOMARKERS Kidney markers predict mortality in patients with HIV disease SO NATURE REVIEWS NEPHROLOGY LA English DT News Item ID INFECTED PERSONS; CYSTATIN-C; ANTIRETROVIRAL THERAPY; ALL-CAUSE; ALBUMINURIA; ASSOCIATION; OUTCOMES; WOMEN; RISK C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10 Ctr Dr,Room 3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS NR 10 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 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD APR PY 2011 VL 7 IS 4 BP 186 EP 188 DI 10.1038/nrneph.2011.27 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 741VN UT WOS:000288893700002 PM 21441967 ER PT J AU Smirnovas, V Baron, GS Offerdahl, DK Raymond, GJ Caughey, B Surewicz, WK AF Smirnovas, Vytautas Baron, Gerald S. Offerdahl, Danielle K. Raymond, Gregory J. Caughey, Byron Surewicz, Witold K. TI Structural organization of brain-derived mammalian prions examined by hydrogen-deuterium exchange SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID SECONDARY STRUCTURE; IN-VITRO; PROTEIN; SCRAPIE; SPECTROSCOPY; INFECTIVITY; PARALLEL AB One of the mysteries in prion research is the structure of the infectious form of mammalian prion protein PrP(Sc). Here we used mass spectrometry analysis of hydrogen-deuterium exchange to examine brain-derived PrP(Sc). Our data indicate that, contrary to popular models, prion-protein conversion involves refolding of the entire region from residue similar to 80-90 to the C-terminus, which in PrP(Sc) consists of beta-strands and relatively short turns and/or loops, with no native alpha-helices present. C1 [Smirnovas, Vytautas; Surewicz, Witold K.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Baron, Gerald S.; Offerdahl, Danielle K.; Raymond, Gregory J.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Surewicz, WK (reprint author), Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. EM witold.surewicz@case.edu RI Smirnovas, Vytautas/C-5583-2009; OI Smirnovas, Vytautas/0000-0002-1829-5455 FU US National Institutes of Health [NS44158, NS38604, AG14359]; National Institute of Allergy and Infectious Diseases FX This study was supported by US National Institutes of Health grants NS44158, NS38604 and AG14359, and by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases. NR 20 TC 108 Z9 108 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2011 VL 18 IS 4 BP 504 EP 506 DI 10.1038/nsmb.2035 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 745UZ UT WOS:000289195000017 PM 21441913 ER PT J AU Tolstorukov, MY Volfovsky, N Stephens, RM Park, PJ AF Tolstorukov, Michael Y. Volfovsky, Natalia Stephens, Robert M. Park, Peter J. TI Impact of chromatin structure on sequence variability in the human genome SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID NUCLEOSOME ORGANIZATION; HIGH-RESOLUTION; DNA-SEQUENCE; START SITES; IN-VIVO; YEAST; POSITIONS; ELEMENTS; REPAIR; TRANSCRIPTION AB DNA sequence variations in individual genomes give rise to different phenotypes within the same species. One mechanism in this process is the alteration of chromatin structure due to sequence variation that influences gene regulation. We composed a high-confidence collection of human single-nucleotide polymorphisms and indels based on analysis of publicly available sequencing data and investigated whether the DNA loci associated with stable nucleosome positions are protected against mutations. We addressed how the sequence variation reflects the occupancy profiles of nucleosomes bearing different epigenetic modifications on genome scale. We found that indels are depleted around nucleosome positions of all considered types, whereas single-nucleotide polymorphisms are enriched around the positions of bulk nucleosomes but depleted around the positions of epigenetically modified nucleosomes. These findings indicate an increased level of conservation for the sequences associated with epigenetically modified nucleosomes, highlighting complex organization of the human chromatin. C1 [Tolstorukov, Michael Y.; Park, Peter J.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. [Tolstorukov, Michael Y.; Park, Peter J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Volfovsky, Natalia; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Informat Syst Program, SAIC Frederick, Frederick, MD 21701 USA. [Park, Peter J.] Childrens Hosp Boston, HST Informat Program, Boston, MA USA. RP Park, PJ (reprint author), Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA 02115 USA. EM peter_park@harvard.edu FU US National Institutes of Health [GM082798, U01HG004258, HHSN261200800001E] FX We thank S. Sunyaev, I. Adzhubei and G. Kryukov for the helpful discussions. This project has been funded in part with federal funds from the US National Institutes of Health (GM082798 and U01HG004258 to P.J.P.; contract no. HHSN261200800001E to R. M. S.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. NR 46 TC 36 Z9 37 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2011 VL 18 IS 4 BP 510 EP U152 DI 10.1038/nsmb.2012 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 745UZ UT WOS:000289195000019 PM 21399641 ER PT J AU Kanaya, AM Wassel, CL Stoddard, PJ Harris, TB Cummings, SR Kritchevsky, SB Goodpaster, BH Green, C Satterfield, S Gross, MD AF Kanaya, Alka M. Wassel, Christina L. Stoddard, Pamela J. Harris, Tamara B. Cummings, Steven R. Kritchevsky, Stephen B. Goodpaster, Bret H. Green, Christie Satterfield, Suzanne Gross, Myron D. CA Hlth ABC Study TI F-2-Isoprostanes and Adiposity in Older Adults SO OBESITY LA English DT Article ID SYSTEMIC OXIDATIVE STRESS; CORONARY-HEART-DISEASE; IN-VIVO FORMATION; INSULIN-RESISTANCE; DIABETES-MELLITUS; INFLAMMATORY MARKERS; OXIDANT STRESS; LEPTIN; ADIPONECTIN; ASSOCIATION AB We examined whether a systemic marker of oxidative stress, F-2-isoprostanes (F-2-IPs), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition (Health ABC) study, F-2-IPs and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole-body dual-energy X-ray absorptiometry and regional adiposity by abdominal and thigh computed tomography scans at baseline and 5-year follow-up. ANOVA models were estimated to examine associations between F-2-IP tertiles and baseline adiposity and changes in body composition. Median F-2-IPs was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, P < 0.001). F-2-IPs were associated with higher levels of adiponectin, leptin, and tumor necrosis factor-alpha (TNF-alpha). Positive associations were found between F-2-IPs and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow-up, women in the highest vs. lowest F-2-IP tertile exhibited significant loss of weight (lowest tertile: -1.1 kg, highest tertile: -2.7 kg, P < 0.05). In conclusion, F-2-IPs were associated with measures of total and regional adiposity in women alone and these associations were partially explained by adipocytokines. F-2-IPs predicted loss of total adiposity over time among women. C1 [Kanaya, Alka M.; Stoddard, Pamela J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wassel, Christina L.] Univ Calif San Diego, San Diego, CA 92103 USA. [Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, San Francisco, CA USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Pittsburgh, PA USA. [Green, Christie; Satterfield, Suzanne] Univ Tennessee, Memphis, TN USA. [Gross, Myron D.] Univ Minnesota, Minneapolis, MN USA. RP Kanaya, AM (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. EM alka.kanaya@ucsf.edu OI Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH, National Institute on Aging; [R21DK068608]; [K23HL080026] FX A.M.K. was funded by R21DK068608 and K23HL080026. The Health ABC study was funded via contracts with the National Institute on Aging contract nos: N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging and included substantial involvement of NIA staff in data collection, analysis, interpretation, review, and approval of the manuscript. NR 34 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD APR PY 2011 VL 19 IS 4 BP 861 EP 867 DI 10.1038/oby.2010.243 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 741XV UT WOS:000288901400030 PM 20948516 ER PT J AU Ozdemir, V Smith, C Bongiovanni, K Cullen, D Knoppers, BM Lowe, A Peters, M Robbins, R Stewart, E Yee, GN Yu, YK Kolker, E AF Ozdemir, Vural Smith, Charles Bongiovanni, Kathleen Cullen, David Knoppers, Bartha M. Lowe, Andrew Peters, Mette Robbins, Robert Stewart, Elizabeth Yee, Gene Yu, Yi-Kuo Kolker, Eugene TI Policy and Data-Intensive Scientific Discovery in the Beginning of the 21st Century SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article AB Recent developments in our ability to capture, curate, and analyze data, the field of data-intensive science (DIS), have indeed made these interesting and challenging times for scientific practice as well as policy making in real time. We are confronted with immense datasets that challenge our ability to pool, transfer, analyze, or interpret scientific observations. We have more data available than ever before, yet more questions to be answered as well, and no clear path to answer them. We are excited by the potential for science-based solutions to humankind's problems, yet stymied by the limitations of our current cyberinfrastructure and existing public policies. Importantly, DIS signals a transformation of the hypothesis-driven tradition of science ("first hypothesize, then experiment'') to one that is typified by "first experiment, then hypothesize'' mode of discovery. Another hallmark of DIS is that it amasses data that are public goods (i.e., creates a "commons'') that can further be creatively mined for various applications in different sectors. As such, this calls for a science policy vision that is long term. We herein reflect on how best to approach to policy making at this critical inflection point when DIS applications are being diversified in agriculture, ecology, marine biology, and environmental research internationally. This article outlines the key policy issues and gaps that emerged from the multidisciplinary discussions at the NSF-funded DIS workshop held at the Seattle Children's Research Institute in Seattle, on September 19-20, 2010. C1 [Ozdemir, Vural] McGill Univ, Fac Med, Ctr Genom & Policy, Dept Human Genet, Montreal, PQ, Canada. [Smith, Charles; Bongiovanni, Kathleen; Cullen, David; Lowe, Andrew; Stewart, Elizabeth; Kolker, Eugene] Seattle Childrens Res Inst, Seattle, WA 98101 USA. [Smith, Charles; Peters, Mette; Kolker, Eugene] Univ Washington, Seattle, WA 98195 USA. [Robbins, Robert] Elect Scholarly Publishing Project, Woodinville, WA USA. [Yee, Gene] Fenwick & West, Seattle, WA USA. [Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. RP Ozdemir, V (reprint author), McGill Univ, Fac Med, Ctr Genom & Policy, Dept Human Genet, Montreal, PQ, Canada. EM vural.ozdemir@mcgill.ca; eugene.kolker@seattlechildrens.org RI Kolker, Eugene/C-6711-2008 FU SCRI; NSF [DBI-0969929] FX This policy report and DIS workshop were supported by SCRI and NSF Grant DBI-0969929 to E. Kolker ( Principal investigator). V. Ozdemir is supported by an investigator salary award for science-in-society research on omics technology applications from FRSQ ( Montreal, Canada). The views expressed in this article are entirely personal opinions of the authors and do not necessarily represent positions of their affiliated institutions or NSF. NR 13 TC 10 Z9 13 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD APR PY 2011 VL 15 IS 4 BP 221 EP 225 DI 10.1089/omi.2011.0007 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 746XC UT WOS:000289281300007 PM 21476845 ER PT J AU Moses, W Weng, J Kebebew, E AF Moses, Willieford Weng, Julie Kebebew, Electron TI Prevalence, Clinicopathologic Features, and Somatic Genetic Mutation Profile in Familial Versus Sporadic Nonmedullary Thyroid Cancer SO THYROID LA English DT Article ID CARCINOMA; ENTITY; SERIES; BRAF AB Background: Although hereditary nonmedullary thyroid cancer is recognized as a distinct and isolated familial syndrome, the precise prevalence and genetic basis are poorly understood. Moreover, whether familial nonmedullary thyroid cancer (FNMTC) has a more aggressive clinical behavior is controversial. The objectives of this study were to determine the prevalence of FNMTC, and compare the extent of disease and tumor somatic genetic alteration in patients with familial and sporadic papillary thyroid cancer. Methods: The main study entry criterion was patients who had a thyroid nodule that required a clinical evaluation with fine-needle aspiration biopsy and or thyroidectomy. A family history questionnaire was used to determine the presence of familial and sporadic thyroid cancer. Thyroid nodule fine-needle aspiration biopsy samples and tumor tissue at the time of thyroidectomy were used to test for somatic genetic mutations (BRAF V600E, NRAS, KRAS, NTRK1, RET/PTC1, and RET/PTC3). Results: There were 402 patients with 509 thyroid nodules enrolled in the study. The prevalence of FNMTC was 8.8% in all patients with thyroid cancer and 9.4% in patients with only papillary thyroid cancer. None of the patients with FNMTC had another familial cancer syndrome. There was no significant difference in gender, tumor size, lymph node metastasis, and overall stage between sporadic and familial cases of thyroid cancer. Patients with FNMTC were younger at diagnosis than patients with sporadic papillary thyroid cancer (p<0.002). Seventy-nine of the 504 thyroid nodules had somatic genetic mutations (29 BRAF V600E, 29 NRAS, 8 KRAS, 1 NTRK1, 4 RET/PTC1, and 8 RET/PTC3). There was no significant difference in the number or type of somatic mutations between sporadic and hereditary cases of papillary thyroid cancer. Conclusions: We found a higher prevalence of FNMTC in patients with papillary thyroid cancer than previously reported. Patients with FNMTC present at a younger age. Somatic mutations and extent of disease are similar in sporadic and FNMTC cases. C1 [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. [Moses, Willieford; Weng, Julie] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, CRC Room 4-5952,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM kebebewe@mail.nih.gov NR 18 TC 38 Z9 44 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2011 VL 21 IS 4 BP 367 EP 371 DI 10.1089/thy.2010.0256 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745TV UT WOS:000289190400006 PM 21190444 ER PT J AU Hatch, M Polyanskaya, O McConnell, R Gong, ZH Drozdovitch, V Rozhko, A Prokopovich, A Petrenko, S Brenner, A Zablotska, L AF Hatch, Maureen Polyanskaya, Olga McConnell, Robert Gong, Zhihong Drozdovitch, Vladimir Rozhko, Alexander Prokopovich, Alexander Petrenko, Sergey Brenner, Alina Zablotska, Lydia TI Urinary Iodine and Goiter Prevalence in Belarus: Experience of the Belarus-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Nuclear Accident SO THYROID LA English DT Article ID REFERENCE VALUES; DEFICIENCY; CHILDREN; VOLUME; ULTRASOUND; NUTRITION; EXCRETION; RISK; SCHOOLCHILDREN; RADIATION AB Background: Because iodine deficiency can influence background rates of thyroid disease or modify radiation dose-response relationships, we compiled descriptive data on iodine status among participants in a Belarusian-American screening study who were exposed in childhood to radioiodine fallout from the Chornobyl nuclear accident. We have used the data from two consecutive screening cycles to examine whether indicators of iodine status changed before and after documented government initiatives to improve iodine intake. Methods: Urinary iodine concentrations in spot samples and prevalence of diffuse goiter by palpation were assessed in 11,676 exposed subjects who were 18 years or younger at the time of the accident on April 26, 1986, and were screened beginning 11 years later in connection with the Belarus-American Thyroid Study. Data for the first (January 1997-March 2001) and second (April 2001-December 2004) screening cycles, which largely correspond to time periods before and after official iodination efforts in 2000/2001, were compared for the cohort overall as well as by oblast of residence (i.e., state) and type of residency (urban/rural). Results: Median urine iodine levels among cohort members increased significantly in the later period (111.5 mu g/L) compared to the earlier (65.3 mu g/L), with the cycle 2 level in the range defined as adequate iodine intake by the World Health Organization. During the same period, a significant decline in diffuse goiter prevalence was also observed. In both cycles, urinary iodine levels were lower in rural than in urban residents. Urinary iodine levels, but not rates of goiter, varied by oblast of residence. In both periods, adjusted median urine iodine concentrations were similar in Gomel and Minsk oblasts, where similar to 89% of cohort members resided, and were lowest in Mogilev oblast. Yet Mogilev oblast and rural areas showed the most marked increases over time. Conclusions: Trends in urinary iodine concentrations and prevalence of diffuse goiter by palpation suggest that iodination efforts in Belarus were successful, with benefits extending to the most iodine-deficient populations. Iodine status should be considered when evaluating thyroid disease risk in radioiodine-exposed populations since it can change over time and may influence rates of disease and, possibly, dose-response relationships. C1 [Hatch, Maureen] NCI, Chornobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Polyanskaya, Olga; Rozhko, Alexander; Prokopovich, Alexander] Republican Ctr Radiat Med & Human Ecol, Gomel, Byelarus. [McConnell, Robert] Columbia Univ, Coll Phys & Surg, Dept Med, Thyroid Ctr, New York, NY USA. [Gong, Zhihong; Zablotska, Lydia] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Petrenko, Sergey] Int Sakharov Environm Univ, Dept Anthropoecol & Epidemiol, Minsk, Byelarus. RP Hatch, M (reprint author), NCI, Chornobyl Res Unit, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7098, Rockville, MD 20852 USA. EM hatchm@mail.nih.gov; drozdovv@mail.nih.gov; brennera@mail.nih.gov FU U.S. National Cancer Institute; NIH; DHHS; Department of Energy; U.S. Nuclear Regulatory Commission FX This research was supported by the Intramural Research Program of the U.S. National Cancer Institute, NIH, DHHS, and the Department of Energy, with the U.S. Nuclear Regulatory Commission providing initial funds for purchase of equipment. The study team owes a special debt of gratitude to our eminent collaborator, the late Dr. Jacob Robbins, who gathered experts in the field for a workshop devoted to discussion of the measurement and role of iodine nutrition in a study population exposed to radioiodines. We are grateful as well to the late Dr. Daniel Fink, who provided guidance, oversight, and quality assurance of laboratory testing for iodine content in the urine samples collected from our study subjects. We also thank Miriam Ishak for her contributions to work on this topic during a summer internship in 2006. NR 27 TC 5 Z9 5 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2011 VL 21 IS 4 BP 429 EP 437 DI 10.1089/thy.2010.0143 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745TV UT WOS:000289190400013 PM 21323597 ER PT J AU Boris, RS Gupta, G Linehan, WM Pinto, PA Bratslavsky, G AF Boris, Ronald S. Gupta, Gopal Linehan, W. Marston Pinto, Peter A. Bratslavsky, Gennady TI Robot-assisted Laparoscopic Partial Adrenalectomy: Initial Experience SO UROLOGY LA English DT Article ID ALDOSTERONE-PRODUCING ADENOMAS; SPARING SURGERY; PHEOCHROMOCYTOMA; NEOPLASIA; RESECTION AB OBJECTIVES To evaluate the feasibility of performing robot-assisted laparoscopic partial adrenalectomy (RALPA) in patients seen at the National Cancer Institute and report the results of our initial experience. METHODS We reviewed the records of patients with adrenal masses who underwent attempted RALPA from July of 2008 until January of 2010. Demographic, perioperative, and pathologic data were collected. The functional and early oncological outcomes were examined by the need for steroid replacement and development of recurrent disease, respectively. RESULTS Ten patients underwent a total of 13 attempted RALPAs for removal of 19 adrenal tumors. There was one open conversion with successful completion of partial adrenalectomy. Of the patients, 80% had a known hereditary syndrome predisposing them to adrenal tumors. One patient had bilateral multifocal adrenal masses with unknown germ line genetic alteration and 1 patient had a sporadic adrenal mass. Of the 19 tumors removed, 17 were pheochromocytoma and 2 were adrenal-cortical hyperplasia. Two patients underwent partial adrenalectomy on a solitary adrenal gland, with one subsequently requiring steroid replacement postoperatively. On postoperative imaging, all but one operated adrenal gland demonstrated contrast enhancement. No patient developed local recurrence at a median follow-up of 16.2 months (range, 2-29). CONCLUSIONS RALPA appears safe and feasible in our early experience. Only 1 patient in our series required steroid replacement. Local recurrence rates are low but will require longer follow-up. UROLOGY 77: 775-780, 2011. Published by Elsevier Inc. C1 [Boris, Ronald S.; Gupta, Gopal; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM bratslag@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 27 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2011 VL 77 IS 4 BP 775 EP 780 DI 10.1016/j.urology.2010.07.501 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 746IX UT WOS:000289240300016 PM 21122898 ER PT J AU Khot, S Park, BS Longstreth, WT AF Khot, Sandeep Park, Buhm Soon Longstreth, W. T., Jr. TI The Vietnam War and Medical Research: Untold Legacy of the US Doctor Draft and the NIH "Yellow Berets" SO ACADEMIC MEDICINE LA English DT Article ID ACADEMIC MEDICINE AB Purpose From the outbreak of the Korean War in 1950 through the end of the Vietnam War in 1973, many American physicians were inducted into military service through the Doctor Draft. Some fulfilled their obligations by conducting clinical research in the National Institutes of Health (NIH) Associate Training Program (ATP) and later labeled themselves "Yellow Berets." The authors examined the history of the ATP and its influence on NIH associates' future careers. Method Via interviews with former associates and archival research, the authors explored the training and collaboration in the ATP during 1953-1973. Using databases, they compared later academic positions of associates with those of nonassociate peers who also entered academia and identified associates with prestigious awards or honorary society memberships. Results The physician-scientists trained in the selective ATP were highly qualified individuals who received training and networking opportunities not available to others. They were approximately 1.5 times as likely as nonassociates to become a full professor, twice as likely to become chair of a department, and three times as likely to become a dean. Associates were also more likely to hold positions at top-ranked medical schools, to fill leadership roles in the NIH, and to win prestigious awards and honorary society memberships. Conclusions The cadre of physician-scientists trained in the ATP during the Doctor Draft rose through the academic ranks to leadership roles and continued their productive scientific collaborations. Their legacy continues to have implications for medical research today, particularly for training programs in clinical research. C1 [Khot, Sandeep; Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Park, Buhm Soon] Korea Adv Inst Sci & Technol, Grad Program Sci & Technol Policy, Taejon 305701, South Korea. [Park, Buhm Soon] NIH, Off NIH Hist, Bethesda, MD 20892 USA. RP Khot, S (reprint author), Harborview Med Ctr, Dept Neurol, 325 9th Ave,Box 359775, Seattle, WA 98104 USA. EM skhot@uw.edu RI Park, Buhm Soon/C-1681-2011 FU Office of NIH History, National Institutes of Health FX Office of NIH History, National Institutes of Health, under a John J. Pisano Travel Grant awarded to Dr. Khot in 2001. NR 33 TC 0 Z9 0 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2011 VL 86 IS 4 BP 502 EP 508 DI 10.1097/ACM.0b013e31820f1ed7 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 742TA UT WOS:000288966200024 PM 21346494 ER PT J AU Carpenter, MA Bostom, A Kusek, JW Adey, D Cole, E House, A Weir, M AF Carpenter, Myra A. Bostom, Andrew Kusek, John W. Adey, Deborah Cole, Edward House, Andrew Weir, Matthew CA FAVORIT Trial Investigators TI PREVALENCE OF CVD RISK FACTORS AND THEIR TREATMENT IN CHRONIC, STABLE KIDNEY TRANSPLANT RECIPIENTS IN THE FOLIC ACID FOR VASCULAR OUTCOME REDUCTION IN TRANSPLANTATION (FAVORIT) TRIAL SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT 2011 Spring Clinical Meeting on National Kidney Foundation CY APR 26-30, 2011 CL Las Vegas, NV SP Natl Kidney Fdn C1 [Carpenter, Myra A.] Univ N Carolina, Chapel Hill, NC USA. [Bostom, Andrew] Rhode Isl Hosp, Providence, RI USA. [Kusek, John W.] NIDDK, NIH, Bethesda, MD USA. [Adey, Deborah] UVM Fletcher Allen Hlth Care, Burlington, VT USA. [Cole, Edward] Univ Toronto, Toronto, ON, Canada. [House, Andrew] London Hlth Sci Ctr, London, ON, Canada. [Weir, Matthew] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2011 VL 57 IS 4 MA 52 BP A29 EP A29 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 738QN UT WOS:000288657100053 ER PT J AU Hamadeh, Z Ahuja, TS Kopp, J AF Hamadeh, Zaher Ahuja, Tejinder S. Kopp, Jeffrey TI ACUTE KIDNEY INJURY SECONDARY TO KIDNEY CRYSTALLIZATION ATTRIBUTABLE TO NELFINAVIR. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT 2011 Spring Clinical Meeting on National Kidney Foundation CY APR 26-30, 2011 CL Las Vegas, NV SP Natl Kidney Fdn C1 [Hamadeh, Zaher] Jacobi Med Ctr, New York, NY USA. [Ahuja, Tejinder S.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. [Kopp, Jeffrey] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2011 VL 57 IS 4 MA 113 BP A45 EP A45 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 738QN UT WOS:000288657100114 ER PT J AU Feric, M Zhao, B Hoffert, JD Pisitkun, T Knepper, MA AF Feric, Marina Zhao, Boyang Hoffert, Jason D. Pisitkun, Trairak Knepper, Mark A. TI Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE mass spectrometry; kidney; thiazide; sodium-chloride cotransporter ID SHORT-TERM STIMULATION; COLLECTING DUCT CELLS; THICK ASCENDING LIMB; NA+-CL-COTRANSPORTER; TANDEM MASS-SPECTRA; QUANTITATIVE PHOSPHOPROTEOMICS; REGULATED PHOSPHORYLATION; SIGNALING PATHWAYS; PROTEOMIC ANALYSIS; RAT-KIDNEY AB Feric M, Zhao B, Hoffert JD, Pisitkun T, Knepper MA. Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule. Am J Physiol Cell Physiol 300: C755-C770, 2011. First published January 5, 2011; doi:10.1152/ajpcell.00360.2010.-Recent advances in mass spectrometry (MS) have provided means for large-scale phosphoproteomic profiling of specific tissues. Here, we report results from large-scale tandem MS [liquid chromatography (LC)-MS/MS]-based phosphoproteomic profiling of biochemically isolated membranes from the renal cortex, with focus on transporters and regulatory proteins. Data sets were filtered (by target-decoy analysis) to limit false-positive identifications to <2%. A total of 7,125 unique nonphosphorylated and 743 unique phosphorylated peptides were identified. Among the phosphopeptides identified were sites on transporter proteins, i.e., solute carrier (Slc, n = 63), ATP-binding cassette (Abc, n = 4), and aquaporin (Aqp, n = 3) family proteins. Database searches reveal that a majority of the phosphorylation sites identified in transporter proteins were previously unreported. Most of the Slc family proteins are apical or basolateral transporters expressed in proximal tubule cells, including proteins known to mediate transport of glucose, amino acids, organic ions, and inorganic ions. In addition, we identified potentially important phosphorylation sites for transport proteins from distal nephron segments, including the bumetanide-sensitive Na-K-2Cl cotransporter (Slc12a1 or NKCC2) at Ser(87), Thr(101), and Ser(126) and the thiazide-sensitive Na-Cl cotransporter (Slc12a3 or NCC) at Ser(71) and Ser(124). A subset of phosphorylation sites in regulatory proteins coincided with known functional motifs, suggesting specific regulatory roles. An online database from this study (http://dir.nhlbi.nih.gov/papers/lkem/rcmpd/) provides a resource for future studies of transporter regulation. C1 [Feric, Marina; Zhao, Boyang; Hoffert, Jason D.; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, 10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU NHLBI [Z01-HL-001285]; National Institute of Biomedical Imaging and Bioengineering FX This study was supported by the Intramural Budget of the NHLBI (Project Z01-HL-001285). Mass spectrometry was done in the NHLBI Proteomics Core Facility (Marjan Gucek, Director). M. Feric was a student intern from the University of Maryland Department of Chemical Engineering (e-mail: mferic@princeton.edu). B. Zhao was a student intern from the University of Michigan in the National Institutes of Health Biomedical Engineering Summer Internship Program, funded by the National Institute of Biomedical Imaging and Bioengineering (e-mail: zhaob@umich.edu). NR 53 TC 18 Z9 19 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 APR PY 2011 VL 300 IS 4 BP C755 EP C770 DI 10.1152/ajpcell.00360.2010 PG 16 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 741VS UT WOS:000288894200004 PM 21209370 ER PT J AU Kohr, MJ Aponte, AM Sun, JH Wang, GH Murphy, E Gucek, M Steenbergen, C AF Kohr, Mark J. Aponte, Angel M. Sun, Junhui Wang, Guanghui Murphy, Elizabeth Gucek, Marjan Steenbergen, Charles TI Characterization of potential S-nitrosylation sites in the myocardium SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardioprotection; ischemic preconditioning ID NITRIC-OXIDE; RYANODINE RECEPTOR; MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; ENDOTHELIAL-CELLS; INDUCED APOPTOSIS; IDENTIFICATION; NITROSATION; PROTEINS; INJURY AB Kohr MJ, Aponte AM, Sun J, Wang G, Murphy E, Gucek M, Steenbergen C. Characterization of potential S-nitrosylation sites in the myocardium. Am J Physiol Heart Circ Physiol 300: H1327-H1335, 2011. First published January 28, 2011; doi:10.1152/ajpheart.00997.2010.-S-nitrosylation (SNO) is a reversible protein modification that has the ability to alter the activity of target proteins. However, only a small number of SNO proteins have been found in the myocardium, and even fewer specific sites of SNO have been identified. Therefore, this study aims to characterize potential SNO sites in the myocardium. We utilized a modified version of the SNO-resin-assisted capture technique in tandem with mass spectrometry. In brief, a modified biotin switch was performed using perfused mouse heart homogenates incubated with or without the S-nitrosylating agent S-nitrosoglutathione. Our modified SNO-resin-assisted capture protocol identified 116 unique SNO-modified proteins under basal conditions, and these represent the constitutive SNO proteome. These constitutive SNO proteins are likely to be physiologically relevant targets, since nitric oxide has been shown to play an important role in the regulation of normal cardiovascular physiology. Following S-nitrosoglutathione treatment, we identified 951 unique SNO proteins, many of which contained multiple SNO sites. These proteins show the potential for SNO. This study provides novel information regarding the constitutive SNO proteome of the myocardium, as well as potential myocardial SNO sites, and yields additional information on the SNO sites for many key proteins involved in myocardial contraction, metabolism, and cellular signaling. C1 [Kohr, Mark J.; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21257 USA. [Kohr, Mark J.; Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Aponte, Angel M.; Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. RP Steenbergen, C (reprint author), Johns Hopkins Med Inst, Dept Pathol, 632N Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21257 USA. EM csteenb1@jhmi.edu RI Sun, Junhui/C-3499-2011; OI Kohr, Mark/0000-0002-6034-5962 FU NHLBI [1F32HL096142, 5R01HL039752]; NHLBI/NIH FX This work was supported by NHLBI Grants 1F32HL096142 (M. J. Kohr) and 5R01HL039752 (C. Steenbergen), and the NHLBI/NIH Intramural Program (A. M. Aponte, E. Murphy, G. Wang, J. Sun, and M. Gucek). NR 37 TC 60 Z9 61 U1 1 U2 9 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 APR PY 2011 VL 300 IS 4 BP H1327 EP H1335 DI 10.1152/ajpheart.00997.2010 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 742KR UT WOS:000288942300020 PM 21278135 ER PT J AU Ungvari, Z Bailey-Downs, L Gautam, T Jimenez, R Losonczy, G Zhang, CH Ballabh, P Recchia, FA Wilkerson, DC Sonntag, WE Pearson, K de Cabo, R Csiszar, A AF Ungvari, Zoltan Bailey-Downs, Lora Gautam, Tripti Jimenez, Rosario Losonczy, Gyorgy Zhang, Cuihua Ballabh, Praveen Recchia, Fabio A. Wilkerson, Donald C. Sonntag, William E. Pearson, Kevin de Cabo, Rafael Csiszar, Anna TI Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE diabetes; oxidative stress; endothelial dysfunction ID TRANSCRIPTION FACTOR NRF2; INDUCED OXIDATIVE STRESS; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; KAPPA-B ACTIVATION; HIGH-FAT DIET; MITOCHONDRIAL SUPEROXIDE; HYDROGEN-PEROXIDE; PHASE-2 ENZYMES; UP-REGULATION AB Ungvari Z, Bailey-Downs L, Gautam T, Jimenez R, Losonczy G, Zhang C, Ballabh P, Recchia FA, Wilkerson DC, Sonntag WE, Pearson K, de Cabo R, Csiszar A. Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am J Physiol Heart Circ Physiol 300: H1133-H1140, 2011. First published January 7, 2011; doi:10.1152/ajpheart.00402.2010.-Hyperglycemia in diabetes mellitus promotes oxidative stress in endothelial cells, which contributes to development of cardiovascular diseases. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a transcription factor activated by oxidative stress that regulates expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes. This study was designed to elucidate the homeostatic role of adaptive induction of Nrf2-driven free radical detoxification mechanisms in endothelial protection under diabetic conditions. Using a Nrf2/antioxidant response element (ARE)-driven luciferase reporter gene assay we found that in a cultured coronary arterial endothelial cell model hyperglycemia (10-30 mmol/l glucose) significantly increases transcriptional activity of Nrf2 and upregulates the expression of the Nrf2 target genes NQO1, GCLC, and HMOX1. These effects of high glucose were significantly attenuated by small interfering RNA (siRNA) downregulation of Nrf2 or overexpression of Keap-1, which inactivates Nrf2. High-glucose-induced upregulation of NQO1, GCLC, and HMOX1 was also prevented by pretreatment with polyethylene glycol (PEG)-catalase or N-acetylcysteine, whereas administration of H(2)O(2) mimicked the effect of high glucose. To test the effects of metabolic stress in vivo, Nrf2(+/+) and Nrf2(-/-) mice were fed a high-fat diet (HFD). HFD elicited significant increases in mRNA expression of Gclc and Hmox1 in aortas of Nrf2(+/+) mice, but not Nrf2(-/-) mice, compared with respective standard diet-fed control mice. Additionally, HFD-induced increases in vascular ROS levels were significantly greater in Nrf2(-/-) than Nrf2(+/+) mice. HFD-induced endothelial dysfunction was more severe in Nrf2(-/-) mice, as shown by the significantly diminished acetylcholine-induced relaxation of aorta of these animals compared with HFD-fed Nrf2(+/+) mice. Our results suggest that adaptive activation of the Nrf2/ARE pathway confers endothelial protection under diabetic conditions. C1 [Ungvari, Zoltan; Bailey-Downs, Lora; Gautam, Tripti; Sonntag, William E.; Csiszar, Anna] Univ Oklahoma, HSC, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Oklahoma City, OK 73104 USA. [Jimenez, Rosario] Univ Granada, Sch Pharm, Dept Pharmacol, Granada, Spain. [Losonczy, Gyorgy] Semmelweis Univ, Dept Pulmonol, Budapest, Hungary. [Zhang, Cuihua] Univ Missouri, Dept Internal Med, Columbia, MO USA. [Zhang, Cuihua] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO USA. [Zhang, Cuihua] Univ Missouri, Dept Nutr Sci, Columbia, MO USA. [Ballabh, Praveen; Recchia, Fabio A.] New York Med Coll, Dept Pediat, Westchester Med Ctr, Valhalla, NY 10595 USA. [Ballabh, Praveen; Recchia, Fabio A.] New York Med Coll, Dept Cell Biol, Westchester Med Ctr, Valhalla, NY 10595 USA. [Ballabh, Praveen; Recchia, Fabio A.] New York Med Coll, Dept Physiol, Westchester Med Ctr, Valhalla, NY 10595 USA. [Wilkerson, Donald C.; Pearson, Kevin] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA. [Pearson, Kevin; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. RP Csiszar, A (reprint author), Univ Oklahoma, HSC, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, 975 NE 10th St,BRC 1303, Oklahoma City, OK 73104 USA. EM zoltan-ungvari@ouhsc.edu; anna-csiszar@ouhsc.edu RI JIMENEZ, ROSARIO/K-9701-2014; de Cabo, Rafael/J-5230-2016; OI JIMENEZ, ROSARIO/0000-0003-3872-2669; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 FU American Diabetes Association; American Federation for Aging Research; University of Oklahoma College of Medicine Alumni Association; National Institutes of Health (NIH) [AG-031085, AT-006526, HL-077256, P01-AG-11370] FX This work was supported by grants from the American Diabetes Association (to Z. Ungvari), the American Federation for Aging Research (to A. Csiszar), the University of Oklahoma College of Medicine Alumni Association (to A. Csiszar), the National Institutes of Health (NIH) (AG-031085 to A. Csiszar; AT-006526 and HL-077256 to Z. Ungvari; P01-AG-11370 to W. E. Sonntag), and the Intramural Research Program of NIH (to R. de Cabo). NR 41 TC 63 Z9 64 U1 1 U2 14 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 APR PY 2011 VL 300 IS 4 BP H1133 EP H1140 DI 10.1152/ajpheart.00402.2010 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 742KR UT WOS:000288942300001 PM 21217061 ER PT J AU Rioth, M Beauharnais, CA Noel, F Ikizler, MR Mehta, S Zhu, YW Long, CA Pape, JW Wright, PF AF Rioth, Meghan Beauharnais, Carole Anne Noel, Francine Ikizler, Mine R. Mehta, Sapna Zhu, Yuwei Long, Carole A. Pape, Jean W. Wright, Peter F. TI Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID TYPE-4 VACCINE CANDIDATE; HEMORRHAGIC-FEVER; ANTIBODIES; TRANSMISSION; TRIAL; ASSAY AB Dengue is endemic to Haiti but not recognized as an important illness in the autochthonous population. To evaluate the prevalence of antibodies to dengue virus (DENV), serum samples from infants and young children 7-36 months of age (n = 166) were assayed by plaque reduction neutralization assays to each DENV serotype. Dengue virus serotype 1 had infected 40% of this study population, followed by serotype 2 (12%), serotype 3 (11%), and serotype 4 (2%). Fifty-three percent of infants and young children less than 12 months of age had already experienced DENV infection, and the seroprevalence of antibody to DEN V increased to 65% by 36 months. Heterotypic antibody responses were an important component of the total dengue immunity profile. C1 [Rioth, Meghan; Zhu, Yuwei] Vanderbilt Univ, Dept Biostat, Nashville, TN 37232 USA. [Beauharnais, Carole Anne; Noel, Francine; Pape, Jean W.] GHESKIO Ctr, Port Au Prince, Haiti. [Ikizler, Mine R.] Pediat Infect Dis, Nashville, TN USA. [Long, Carole A.] NIAID, Malaria Immunol Sect, NIH, Bethesda, MD 20892 USA. Dartmouth Med Sch, Div Infect Dis & Int Hlth, Lebanon, NH USA. Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Weill Cornell Med Coll, Div Infect Dis & Int Med, New York, NY USA. RP Rioth, M (reprint author), Vanderbilt Univ, Dept Biostat, 2200 Childrens Way, Nashville, TN 37232 USA. EM meghan.rioth@vanderbilt.edu; caroleanne26@hotmail.com; fsevere@gheskio.org; mine.ikizler@vanderbilt.edu; mehta_sapna@hotmail.com; yuwei.zhu@vanderbilt.edu; clong@niaid.nih.gov; jwpape@gheskio.org; peter.f.wright@dartmouth.edu FU Infectious Disease Society of America; Vanderbilt Emphasis Program FX The study was supported by an Infectious Disease Society of America summer fellowship to Meghan Rioth, a supplement to the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet), and the Vanderbilt Emphasis Program. NR 28 TC 8 Z9 8 U1 0 U2 2 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 APR PY 2011 VL 84 IS 4 BP 630 EP 636 DI 10.4269/ajtmh.2011.10-0323 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 743MY UT WOS:000289023600022 PM 21460022 ER PT J AU Geraldo, DA Duran-Lara, EF Aguayo, D Cachau, RE Tapia, J Esparza, R Yacaman, MJ Gonzalez-Nilo, FD Santos, LS AF Geraldo, Daniela A. Duran-Lara, Esteban F. Aguayo, Daniel Cachau, Raul E. Tapia, Jaime Esparza, Rodrigo Yacaman, Miguel J. Gonzalez-Nilo, Fernando Danilo Santos, Leonardo S. TI Supramolecular complexes of quantum dots and a polyamidoamine (PAMAM)-folate derivative for molecular imaging of cancer cells SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Quantum dots; PAMAM dendrimers; Supramolecular complexes; Transmission electron microscopy (TEM); Molecular dynamics (MD) simulations; Gastric cancer cells ID RESPONSIVE CONFORMATIONAL-CHANGES; PAMAM DENDRIMERS; CDTE NANOCRYSTALS; SEMICONDUCTOR NANOCRYSTALS; BIOMEDICAL APPLICATIONS; AQUEOUS-SOLUTIONS; DRUG-DELIVERY; FOLATE; NANOPARTICLES; CDSE AB Polyamidoamine (PAMAM) dendrimers and water-soluble 3-mercaptopropionic acid (MPA)-capped CdSe quantum dots (QDs) were combined to produce a new gel containing supramolecular complexes of QDs/PAMAM dendrimers. The formation of the QDs/PAMAM supramolecular complexes was confirmed by high resolution electron microscopy and Fourier transform infrared (FTIR) analyses. Molecular dynamics simulations corroborated the structure of the new QDs/PAMAM-based supramolecular compound. Finally, on the basis of the prominent fluorescent properties of the supramolecular complexes, PAMAM dendrimer was functionalized with folic acid to produce a new QDs/PAMAM-folate derivative that showed an efficient and selective performance as a marker for gastric cancer cells. C1 [Geraldo, Daniela A.; Duran-Lara, Esteban F.; Tapia, Jaime; Santos, Leonardo S.] Univ Talca, Lab Asymmetr Synth, Chem Inst Nat Resources, Talca, Chile. [Geraldo, Daniela A.; Gonzalez-Nilo, Fernando Danilo] Univ Talca, Ctr Bioinformat & Mol Simulat, Talca, Chile. [Cachau, Raul E.] NCI, Sci Applicat Int Corp SAIC Frederick Inc, Frederick, MD 21702 USA. [Esparza, Rodrigo; Yacaman, Miguel J.] Univ Texas San Antonio, Dept Phys & Astron, San Antonio, TX 78249 USA. RP Santos, LS (reprint author), Univ Talca, Lab Asymmetr Synth, Chem Inst Nat Resources, POB 747, Talca, Chile. EM lssantos@utalca.cl RI Santos, Leonardo/A-7953-2008; jose yacaman, miguel/B-5622-2009; Gonzalez-Nilo, Fernando/M-5671-2016 OI Santos, Leonardo/0000-0003-0908-0134; Gonzalez-Nilo, Fernando/0000-0001-6857-3575 FU FONDECYT [3100037]; Proyecto Anillo Cientifico [ACT/24]; University of Texas at San Antonio; NCI-NIH [HHSN261200800001E] FX D.A.G. and L. S. S. thank FONDECYT (Post-doctoral Grant 3100037), Proyecto Anillo Cientifico ACT/24 (F.D.G. N.), and University of Texas at San Antonio (M.J.Y.) for supporting the research activity. This work has been funded in part with funds from the NCI-NIH (Contract No. HHSN261200800001E). The contents of this publication do not necessarily reflect the views or policies of the DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 39 TC 18 Z9 19 U1 5 U2 63 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD APR PY 2011 VL 400 IS 2 BP 483 EP 492 DI 10.1007/s00216-011-4756-2 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 743EM UT WOS:000289000300021 PM 21373833 ER PT J AU Zhou, YF Wang, SN Yu, ZX Hoyt, RF Qu, XA Horvath, KA AF Zhou, Yifu Wang, Suna Yu, Zuxi Hoyt, Robert F., Jr. Qu, Xuan Horvath, Keith A. TI Marrow Stromal Cells Differentiate Into Vasculature After Allogeneic Transplantation Into Ischemic Myocardium SO ANNALS OF THORACIC SURGERY LA English DT Article ID COLONY-STIMULATING FACTOR; MESENCHYMAL STEM-CELLS; LEFT-VENTRICULAR FUNCTION; CORONARY-ARTERY-DISEASE; HEART-FAILURE; TOPCARE-AMI; INFARCTION; TRIAL; REGENERATION; MOBILIZATION AB Background. Marrow stromal cells (MSCs) are reportedly able to improve ventricular function after myocardial infarction through the paracrine effect or regenerating myocytes. However, the evidence to prove that is scant. In this animal study, we employed MSCs isolated from transgenic pigs designed to express enhanced green fluorescent proteins as the donor to study the fate of the cells after allogeneic transplantation. Methods. Green MSCs prepared from transgenic pigs were allogeneically transplanted into chronic ischemic myocardium of 8 Yorkshire pigs by direct intramyocardial injection (total 1.2 x 10(8) cells in 2.5 mL saline, with 25 injection sites). Cohorts of 2 animals were sacrificed at 1, 2, 4, and 6 weeks, and 3 months after injection to study the fate of the injected cells. Results. Allogeneic injection of the green MSCs is safe; no observable side effects or signs of graft versus host disease were observed. By 4',6-diamidino-2-phenylindole (DAPI) counterstained frozen sections, the green cells were found migrating from the injected area into deeper layers of myocardium over the course of 1 to 6 weeks. By immunofluorescent staining, the green cells were associated with smooth muscle actin or von Willebrand factor positive cells, suggesting that the transplanted cells were contributing to the formation of new vessels. We found no evidence that these cells were associated with the new generation of cardiac myocytes. Three months after injection, clusters of MSCs still can be found in the middle layer of ischemic myocardium; however, no unlimited cell growth was found. Conclusions. Allogeneic transplantation of green MSCs can be safely used to elucidate the mechanisms of cell-based therapy. The benefits of this therapy appear mainly due to the angiogenesis, not the regeneration, of cardiac myocytes. C1 [Zhou, Yifu] NHLBI, Cellular Biol Sect, CSRP, NIH, Bethesda, MD 20892 USA. RP Zhou, YF (reprint author), NHLBI, Cellular Biol Sect, CSRP, NIH, 10 Ctr Dr,MSC 1550,Bldg 10,Rm B1D47, Bethesda, MD 20892 USA. EM zhouyifu@mail.nih.gov FU Intramural NIH HHS [Z99 HL999999] NR 26 TC 12 Z9 12 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2011 VL 91 IS 4 BP 1206 EP 1212 DI 10.1016/j.athoracsur.2011.01.021 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 740IL UT WOS:000288785800058 PM 21353199 ER PT J AU Zocca, JM Shomaker, LB Tanofsky-Kraff, M Columbo, KM Raciti, GR Brady, SM Crocker, MK Ali, AH Matheson, BE Yanovski, SZ Yanovski, JA AF Zocca, Jaclyn M. Shomaker, Lauren B. Tanofsky-Kraff, Marian Columbo, Kelli M. Raciti, Gina R. Brady, Sheila M. Crocker, Melissa K. Ali, Asem H. Matheson, Brittany E. Yanovski, Susan Z. Yanovski, Jack A. TI Links between mothers' and children's disinhibited eating and children's adiposity SO APPETITE LA English DT Article DE Disinhibited eating; Eating in the absence of hunger; Loss of control eating; Binge eating; Obesity ID BODY-MASS INDEX; DIETARY RESTRAINT; ENVIRONMENTAL-INFLUENCES; DISORDER EXAMINATION; WEIGHT PATTERNS; OVERWEIGHT; ADOLESCENTS; BEHAVIORS; OBESITY; HUNGER AB Few studies have examined relationships between parents' and children's specific disinhibited eating behaviors. We investigated links among mothers' and children's binge/loss of control eating, eating in the absence of hunger, and children's adiposity in 305 non-treatment-seeking youth, aged 8-17 years (13.62 +/- 2.65 years; 49.8% female) and their mothers. Youths' loss of control eating and eating in the absence of hunger were assessed by interview and self-report questionnaire. Children's adiposity was assessed with BMI-z and air displacement plethysmography. Maternal binge eating, eating in the absence of hunger and highest, non-pregnant BMI were self-reported. In structural equation models controlling for mothers' BMI, mothers' binge eating related to children's loss of control eating, and mothers' eating in the absence of hunger related to children's eating in the absence of hunger. Mothers' binge eating and children's eating in the absence of hunger were unrelated, as were mothers' eating in the absence of hunger and children's loss of control. Further, mothers' binge eating was indirectly related to children's adiposity through children's loss of control eating. Likewise, mothers' eating in the absence of hunger indirectly related to children's adiposity through children's eating in the absence of hunger. Mothers and children share similar, specific disinhibited eating styles. Published by Elsevier Ltd. C1 [Zocca, Jaclyn M.; Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Columbo, Kelli M.; Brady, Sheila M.; Crocker, Melissa K.; Ali, Asem H.; Matheson, Brittany E.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Columbo, Kelli M.; Raciti, Gina R.; Matheson, Brittany E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Ali, Asem H.; Yanovski, Susan Z.] NIDDK, Div Digest Dis & Nutr, NIH, DHHS, Bethesda, MD 20892 USA. RP Shomaker, LB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, CRC Rm 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM shomakel@mail.nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU NIH, NICHD [Z01-HD-00641]; NCMHD; OBSSR; USUHS [R072IC]; NIDDK [1R01DK080906]; NICHD National Research Service [1F32HD056762] FX Intramural Research Program, NIH, grant Z01-HD-00641 (to J.A. Yanovski) from the NICHD, supplemental funding from NCMHD and OBSSR (to J.A. Yanovski), USUHS grant R072IC (to M. Tanofsky-Kraff), NIDDK grant 1R01DK080906 (to M. Tanofsky-Kraff), and NICHD National Research Service Award 1F32HD056762 (to L.B. Shomaker). NR 62 TC 19 Z9 19 U1 4 U2 13 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 J9 APPETITE JI Appetite PD APR PY 2011 VL 56 IS 2 BP 324 EP 331 DI 10.1016/j.appet.2010.12.014 PG 8 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 745SK UT WOS:000289186000016 PM 21182882 ER PT J AU Volpato, S Ferrucci, L Secchiero, P Corallini, F Zuliani, G Fellin, R Guralnik, JM Bandinelli, S Zauli, G AF Volpato, Stefano Ferrucci, Luigi Secchiero, Paola Corallini, Federica Zuliani, Giovanni Fellin, Renato Guralnik, Jack M. Bandinelli, Stefania Zauli, Giorgio TI Association of tumor necrosis factor-related apoptosis-inducing ligand with total and cardiovascular mortality in older adults SO ATHEROSCLEROSIS LA English DT Article DE Cardiovascular disease; TRAIL; Mortality; Epidemiology; Aging ID HUMAN ENDOTHELIAL-CELLS; TRAIL PROMOTES; WOMENS HEALTH; DISEASE; RISK; ATHEROSCLEROSIS; INFLAMMATION; PROLIFERATION; PATHOGENESIS; EXPRESSION AB Objective: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exhibits biological activity on vascular cells in vitro. Rapid variation of circulating TRAIL levels occurs during acute coronary ischemia, suggesting that biological pathways involving TRAIL may be activated during ischemic heart disease. However, whether differential levels of soluble TRAIL in normal individuals are associated with adverse health outcomes has not been investigated. We tested the hypothesis that TRAIL levels predict mortality in a population based sample of community dwelling men and women. Methods: Plasma TRAIL level was measured by ELISA at baseline in 1282 adults (mean age 68 years) enrolled in the InCHIANTI study. Vital status was ascertained over the six-year follow-up. Results: In multivariable Cox regression analysis adjusted for potential confounders including prevalent cardiovascular diseases (CVD), ankle-brachial index, electrocardiogram abnormalities, and inflammatory markers, baseline TRAIL levels were inversely related to all-cause mortality (p = 0.008). In stratified analyses, the prognostic effect of TRAIL level was strong and highly significant in participants with prevalent CVD (N = 321), (lowest versus highest quartile: HR 3.1; 95% CI 1.5-6.5) while it was negligible in those free of CVD (p value for the interaction term between CVD status and TRAIL levels = 0.038). Similar findings were obtained when CVD mortality was considered as the outcome of interest. Conclusions: In older patients with CVD, low levels of TRAIL were associated with increased risk of death over a period of 6 years. Lower concentration of circulating TRAIL may be related to the clinical evolution of older adults with CVD. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Volpato, Stefano; Zuliani, Giovanni; Fellin, Renato] Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, I-44100 Ferrara, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. [Secchiero, Paola; Corallini, Federica; Zauli, Giorgio] Univ Ferrara, Dept Morphol & Embryol, I-44100 Ferrara, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Rehabil Unit, Florence, Italy. RP Volpato, S (reprint author), Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt Med, Via Savonarola 9, I-44100 Ferrara, Italy. EM vlt@unife.it RI secchiero, paola/G-9689-2015; VOLPATO, STEFANO/H-2977-2014; OI secchiero, paola/0000-0003-4101-7987; VOLPATO, STEFANO/0000-0003-4335-6034; Zauli, Giorgio/0000-0002-3750-8698 FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01 AG-5-0002]; National Institute on Aging, National Institutes of Health, Baltimore, Maryland FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the InCHIANTI Follow-ups 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01 AG-5-0002); supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. NR 34 TC 45 Z9 46 U1 0 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2011 VL 215 IS 2 BP 452 EP 458 DI 10.1016/j.atherosclerusis.2010.11.004 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 742KC UT WOS:000288940000029 PM 21122855 ER PT J AU Scuteri, A Orru, M Morrell, C Piras, MG Taub, D Schlessinger, D Uda, M Lakatta, EG AF Scuteri, Angelo Orru, Marco Morrell, Christopher Piras, Maria Grazia Taub, Dennis Schlessinger, David Uda, Manuela Lakatta, Edward G. TI Independent and additive effects of cytokine patterns and the metabolic syndrome on arterial aging in the SardiNIA Study SO ATHEROSCLEROSIS LA English DT Article DE Cytokines; Metabolic syndrome; Aging; Large artery properties; Arterial stiffness; Carotid intima media thickness ID PLASMA ADIPONECTIN LEVELS; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; CARDIOVASCULAR HEALTH; INFLAMMATION; STIFFNESS; ATHEROSCLEROSIS; MARKERS; OBESITY; WOMEN AB Objective: Metabolic syndrome (MetS) and its components accelerate age-associated increases in arterial stiffness and thickness. We investigated whether specific proinflammatory cytokines contribute to arterial aging, independent of age, sex, MetS, and other traditional CV risk factors. Research design and methods: MetS components (ATP III criteria) and arterial properties were assessed in 6148 subjects, aged 14-102 in Sardinia, Italy. Common carotid artery (CCA) diameter, intima-media thickness (IMT), and aortic pulse wave velocity (PWV), adiponectin, leptin, high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein 1 (MCP1), and interleukin 6 (IL6) were measured. Results: While cytokine levels - except for MCP1 - were significantly higher (lower for adiponectin) in MetS than in control subjects, and the increased PWV and CCA IMT with aging were associated with MetS, this association was independent of cytokine levels (p < 0.001 for both PWV and CCA IMT). Specific cytokines, however, were significantly associated with arterial stiffness (higher leptin, p < 0.001, and higher hsCRP,p < 0.001) or thickness (lower adiponectin, p < 0.05, and higher IL6, p < 0.001) - independent of age, sex, MetS and other traditional CV risk factors. The co-occurrence of both MetS and higher cytokines levels was associated with greater increases in arterial stiffness and thickness. Conclusion: While MetS and specific cytokine patterns associated with arterial aging, the increases in arterial stiffness and thickness are greater when both MetS and higher cytokine levels are present, suggesting a possible synergistic effect of MetS and inflammation on the arterial wall. Published by Elsevier Ireland Ltd. C1 [Scuteri, Angelo; Morrell, Christopher; Taub, Dennis; Schlessinger, David; Lakatta, Edward G.] NIA, Intramural Res Program, NIA, Baltimore, MD 21224 USA. [Orru, Marco; Piras, Maria Grazia; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy. RP Scuteri, A (reprint author), INRCA IRCCS, UOC Geriatria, Via Cassia 1167, I-00189 Rome, Italy. EM angeloelefante@interfree.it OI piras, maria grazia/0000-0001-9004-0900 FU NIA [NO1-AG-1-2109]; NIH, National Institute on Aging (USA) FX The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA.; This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging (USA). NR 29 TC 29 Z9 29 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2011 VL 215 IS 2 BP 459 EP 464 DI 10.1016/j.athrrosclerosis.2010.12.023 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 742KC UT WOS:000288940000030 PM 21241986 ER PT J AU Cai, QA Sheng, ZH AF Cai, Qian Sheng, Zu-Hang TI Uncovering the role of Snapin in regulating autophagy-lysosomal function SO AUTOPHAGY LA English DT Editorial Material DE autophagy; dynein; late endosomes; lysosomes; retrograde transport C1 [Cai, Qian; Sheng, Zu-Hang] Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, NIH, Bethesda, MD 20824 USA. RP Sheng, ZH (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Funct Sect, NIH, Bethesda, MD 20824 USA. EM shengz@ninds.nih.gov FU Intramural NIH HHS NR 0 TC 8 Z9 8 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR PY 2011 VL 7 IS 4 BP 445 EP 447 DI 10.4161/auto.7.4.14682 PG 3 WC Cell Biology SC Cell Biology GA 744DW UT WOS:000289075600015 PM 21233602 ER PT J AU Zhang, B Tian, Y Jin, L Li, HA Shih, IM Madhavan, S Clarke, R Hoffman, EP Xuan, JH Hilakivi-Clarke, L Wang, Y AF Zhang, Bai Tian, Ye Jin, Lu Li, Huai Shih, Ie-Ming Madhavan, Subha Clarke, Robert Hoffman, Eric P. Xuan, Jianhua Hilakivi-Clarke, Leena Wang, Yue TI DDN: a caBIG (R) analytical tool for differential network analysis SO BIOINFORMATICS LA English DT Article ID GENE; MUTATIONS; ARID1A AB Differential dependency network (DDN) is a caBIG(R) (cancer Biomedical Informatics Grid) analytical tool for detecting and visualizing statistically significant topological changes in transcriptional networks representing two biological conditions. Developed under caBIG(R)'s In Silico Research Centers of Excellence (ISRCE) Program, DDN enables differential network analysis and provides an alternative way for defining network biomarkers predictive of phenotypes. DDN also serves as a useful systems biology tool for users across biomedical research communities to infer how genetic, epigenetic or environment variables may affect biological networks and clinical phenotypes. Besides the standalone Java application, we have also developed a Cytoscape plug-in, CytoDDN, to integrate network analysis and visualization seamlessly. C1 [Zhang, Bai; Tian, Ye; Jin, Lu; Xuan, Jianhua; Wang, Yue] Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA. [Li, Huai] NIA, Bioinformat Unit, RRB, NIH, Baltimore, MD 21224 USA. [Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Obstet Gynecol, Baltimore, MD 21231 USA. [Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. [Shih, Ie-Ming] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. [Madhavan, Subha; Clarke, Robert; Hilakivi-Clarke, Leena] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. [Madhavan, Subha; Clarke, Robert; Hilakivi-Clarke, Leena] Georgetown Univ, Dept Oncol, Washington, DC 20057 USA. [Hoffman, Eric P.] Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. RP Wang, Y (reprint author), Virginia Polytech Inst & State Univ, Bradley Dept Elect & Comp Engn, Arlington, VA 22203 USA. EM yuewang@vt.edu RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 FU National Institutes of Health [HHSN261200800001E, CA109872, CA149147, NS029525, GM085665]; National Institutes of Health, National Institute on Aging FX National Institutes of Health, under Contract No. HHSN261200800001E and Grants CA109872, CA149147, NS029525, GM085665 (in parts); Intramural Research Program of the National Institutes of Health, National Institute on Aging (in parts). NR 13 TC 23 Z9 23 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 1 PY 2011 VL 27 IS 7 BP 1036 EP 1038 DI 10.1093/bioinformatics/btr052 PG 3 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 745JP UT WOS:000289162000031 PM 21296752 ER PT J AU Bishop, MR Alyea, EP Cairo, MS Falkenburg, JHF June, CH Kroger, N Little, RF Miller, JS Pavletic, SZ Porter, DL Riddell, SR van Besien, K Wayne, AS Weisdorf, DJ Wu, RS Giralt, S AF Bishop, Michael R. Alyea, Edwin P., III Cairo, Mitchell S. Falkenburg, J. H. Frederik June, Carl H. Kroeger, Nicolaus Little, Richard F. Miller, Jeffrey S. Pavletic, Steven Z. Porter, David L. Riddell, Stanley R. van Besien, Koen Wayne, Alan S. Weisdorf, Daniel J. Wu, Roy S. Giralt, Sergio TI National Cancer Institute's First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Summary and Recommendations from the Organizing Committee SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Graft-versus-tumor; Minimal residual disease; Donor lymphocyte infusion ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; DONOR LEUKOCYTE TRANSFUSIONS; CHRONIC MYELOID-LEUKEMIA; DISEASE-SPECIFIC METHODS; GRAFT-VERSUS-LEUKEMIA; HOST DISEASE; IMMUNOTHERAPY; CYCLOPHOSPHAMIDE; CHEMOTHERAPY AB The National Cancer Institute's First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation was organized and convened to identify, prioritize, and coordinate future research activities related to relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Each of the Workshop's 6 Working Committees has published individual reports of ongoing basic, translational, and clinical research and recommended areas for future research related to the areas of relapse biology, epidemiology, prevention, and treatment. This document summarizes each committee's recommendations and suggests 3 major initiatives for a coordinated research effort to address the problem of relapse after allo-HSCT: (1) to establish multicenter correlative and clinical trial networks for basic/translational, epidemiologic, and clinical research; (2) to establish a network of biorepositories for the collection of samples before and after allo-HSCT to aid in laboratory and clinical studies; and (3) to further refine, implement, and study the Workshop-proposed definitions for disease-specific response and relapse and recommendations for monitoring of minimal residual disease. These recommendations, in coordination with ongoing research initiatives and transplantation organizations, provide a research framework to rapidly and efficiently address the significant problem of relapse after allo-HSCT. Biol Blood Marrow Transplant 17: 443-454 (2011) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Bishop, Michael R.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. [Bishop, Michael R.; Alyea, Edwin P., III; Cairo, Mitchell S.; Falkenburg, J. H. Frederik; June, Carl H.; Kroeger, Nicolaus; Little, Richard F.; Miller, Jeffrey S.; Pavletic, Steven Z.; Porter, David L.; Riddell, Stanley R.; van Besien, Koen; Wayne, Alan S.; Weisdorf, Daniel J.; Wu, Roy S.; Giralt, Sergio] NCI, Organizing Comm, Bethesda, MD 20892 USA. [Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Cairo, Mitchell S.] Columbia Univ, Dept Pediat, Morgan Stanley Childrens Hosp New York Presbyteri, New York, NY 10027 USA. [Falkenburg, J. H. Frederik] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands. [June, Carl H.; Porter, David L.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Kroeger, Nicolaus] Univ Hosp Hamburg Eppendorf, Ctr Stem Cell Transplantat, D-52425 Hamburg, Germany. [Little, Richard F.; Wu, Roy S.] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. [Miller, Jeffrey S.; Weisdorf, Daniel J.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Riddell, Stanley R.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [van Besien, Koen] Univ Chicago, Sch Med, Dept Med, Chicago, IL 60637 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Giralt, Sergio] Mem Sloan Kettering Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapies, New York, NY 10021 USA. RP Bishop, MR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,CRC Room 4-3152, Bethesda, MD 20892 USA. EM mbishop@mail.nih.gov RI van Besien, Koen/G-4221-2012; OI van Besien, Koen/0000-0002-8164-6211; Miller, Jeffrey S/0000-0002-0339-4944 FU Center for Cancer Research, National Cancer Institute FX This work was supported by the Center for Cancer Research, National Cancer Institute, Intramural Research Program. NR 34 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD APR PY 2011 VL 17 IS 4 BP 443 EP 454 DI 10.1016/j.bbmt.2010.12.713 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 742DJ UT WOS:000288920000001 PM 21224011 ER PT J AU Carpenter, RD Sigurdsson, S Zhao, S Lu, Y Eiriksdottir, G Sigurdsson, G Jonsson, BY Prevrhal, S Harris, TB Siggeirsdottir, K Guonason, V Lang, TF AF Carpenter, R. D. Sigurdsson, S. Zhao, S. Lu, Y. Eiriksdottir, G. Sigurdsson, G. Jonsson, B. Y. Prevrhal, S. Harris, T. B. Siggeirsdottir, K. Guonason, V. Lang, T. F. TI Effects of age and sex on the strength and cortical thickness of the femoral neck SO BONE LA English DT Article DE Bone QCT; Biomechanics; Bone geometry; Aging; Osteoporosis ID PROXIMAL FEMUR; MECHANICAL-PROPERTIES; STRUCTURAL-ANALYSIS; GENDER-DIFFERENCES; ADOLESCENT GROWTH; TRABECULAR BONE; OLD-AGE; HIP; GEOMETRY; DENSITY AB A group of 48 men (22 aged 65-75 years, 26 aged 80-90 years) and 59 women (32 aged 65-75 years, 27 aged 80-90 years) were enrolled in the Age, Gene/Environment Susceptibility-Reykjavik study and imaged with in vivo volumetric Quantitative Computed Tomography (QCT) to investigate the effects of age and sex on femoral neck structure and strength. Femoral neck cross-sectional moment of inertia for bending directions near those of standing and walking (I(AP)), bending strength (M(y)), and axial compressive strength (F(y)) were computed at the location of minimum cross-sectional area (minCSA). Local cortical thickness was computed in the inferior femoral neck based on density profiles extending through the cortex of the minCSA femoral neck section. Multivariate models accounting for height, weight, and age group (younger or older) showed that men had a 46% higher M(y) and a 23% higher F(y) than women, while women had a 13% thicker inferior cortex than men. Cortical thickness in the inferoposterior region of the femoral neck was significantly related to bending and axial strength after adjusting for overall volumetric bone mineral density. Both minCSA and I(AP) were higher in the older, gender-pooled age group, but F(y) and M(y) did not differ between the two age groups. The results suggest that age-related expansion of the femoral neck primarily occurs in the superior and inferior directions and helps maintain homeostasis of femoral neck stiffness and strength. The higher bending strength of the male femoral neck may partly explain why elderly men have a lower risk of hip fracture than elderly women. (C) 2010 Elsevier Inc. All rights reserved. C1 [Carpenter, R. D.; Zhao, S.; Lang, T. F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Sigurdsson, S.; Eiriksdottir, G.; Sigurdsson, G.; Siggeirsdottir, K.; Guonason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Lu, Y.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Sigurdsson, G.] Landspitali Univ Hosp, Reykjavik, Iceland. [Eiriksdottir, G.; Guonason, V.] Univ Iceland, Reykjavik, Iceland. [Jonsson, B. Y.] Malmo Univ Hosp, Malmo, Sweden. [Prevrhal, S.] Philips Med Syst Inc, San Jose, CA USA. [Harris, T. B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. RP Carpenter, RD (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St, San Francisco, CA 94143 USA. EM dana.carpenter@radiology.ucsf.edu RI Lang, Thomas/B-2685-2012; Gudnason, Vilmundur/K-6885-2015 OI Lang, Thomas/0000-0002-3720-8038; Gudnason, Vilmundur/0000-0001-5696-0084 FU National Institute on Aging [5R01AG028832, N01-AG-1-2100]; National Institute on Aging, Hjartavernd (the Icelandic Heart Association); Althingi (the Icelandic Parliament) FX The authors would like to thank A. Gudmundsdottir, A. Reynisdottir, A. Sigmardsottir, B. Oskarsdottir, D. Vilmundarson, G. Karlsdottir, and G. Johannsdottir for their aid in acquiring and processing QCT images. Thanks to Gary S. Beaupre for the use of his femoral neck phantom for accuracy analysis. This study was funded by the National Institute on Aging (grant 5R01AG028832 and contract N01-AG-1-2100), in part by the Intramural Research Program of the National Institute on Aging, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). NR 31 TC 11 Z9 11 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR 1 PY 2011 VL 48 IS 4 BP 741 EP 747 DI 10.1016/j.bone.2010.12.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 742DQ UT WOS:000288920900008 PM 21168538 ER PT J AU Nagata, M Nuckolls, GH Wang, XB Shum, L Seki, Y Kawase, T Takahashi, K Nonaka, K Takahashi, I Noman, AA Suzuki, K Slavkin, HC AF Nagata, Masaki Nuckolls, Glen H. Wang, Xibin Shum, Lillian Seki, Yukie Kawase, Tomoyuki Takahashi, Katsu Nonaka, Kazuaki Takahashi, Ichiro Noman, Arhab A. Suzuki, Kenji Slavkin, Harold C. TI The primary site of the acrocephalic feature in Apert syndrome is a dwarf cranial base with accelerated chondrocytic differentiation due to aberrant activation of the FGFR2 signaling SO BONE LA English DT Article DE Apert syndrome; Fgfr2IIIcP253R transgenic mouse; Accelerated endochondral ossification; Dwarf cranial base; Aberrant ligand specificity ID GROWTH-FACTOR RECEPTOR-2; LIGAND-BINDING SPECIFICITY; SYNDROME-LIKE PHENOTYPES; OF-FUNCTION MUTATION; CROUZON-SYNDROME; BONE-DEVELOPMENT; INDIAN-HEDGEHOG; TRANSCRIPTION FACTOR; MOUSE; OSTEOGENESIS AB Activation of osteoblastic bone anabolism in the calvarial sutures is considered to be the essential pathologic condition underlying mutant FGFR2-related craniofacial dysostosis. However, early clinical investigations indicated that abnormal cartilage development in the cranial base was rather a primary site of abnormal feature in Apert Syndrome (AS). To examine the significance of cartilaginous growth of the cranial base in AS, we generated a transgenic mouse bearing AS-type mutant Fgfr2IIIc under the control of the Col2a1 promoter-enhancer (Fgfr2IIIc(P253R) mouse). Despite the lacking expression of Fgfr2IIIc(P253R) in osteoblasts, exclusive disruption of chondrocytic differentiation and growth reproduced AS-like acrocephaly accompanied by short anterior cranial base with fusion of the cranial base synchondroses, maxillary hypoplasia and synostosis of the calvarial sutures with no significant abnormalities in the trunk and extremities. Gene expression analyses demonstrated upregulation of p21, Ihh and Mmp-13 accompanied by modest increase in expression of Sox9 and Runx2, indicating acceleration of chondrocytic maturation and hypertrophy in the cranial base of the Fgfr2IIIc(P253R) mice. Furthermore, an acquired affinity and specificity of mutant FGFR2IIIc(P253R) receptor with FGF2 and FGF10 is suggested as a mechanism of activation of FGFR2 signaling selectively in the cranial base. In this report, we strongly suggest that the acrocephalic feature of AS is not alone a result of the coronal suture synostosis, but is a result of the primary disturbance in growth of the cranial base with precocious endochondral ossification. (C) 2010 Elsevier Inc. All rights reserved. C1 [Nagata, Masaki; Seki, Yukie; Noman, Arhab A.] Niigata Univ, Dept Oral & Maxillofacial Surg, Grad Sch Med & Dent Sci, Niigata 9518514, Japan. [Nuckolls, Glen H.; Wang, Xibin] NIAMSD, NIH, Bethesda, MD 20892 USA. [Shum, Lillian] Natl Inst Dent & Craniofacial Res, Integrat Biol & Infect Dis Branch, Div Extramural Res, Bethesda, MD 20892 USA. [Kawase, Tomoyuki] Niigata Univ, Div Oral Bioengn, Dept Tissue Regenerat & Reconstitut, Grad Sch Med & Dent Sci, Niigata 9518514, Japan. [Takahashi, Katsu] Kyoto Univ, Grad Sch Med, Dept Oral & Maxillofacial Surg, Sakyo Ku, Kyoto 6068507, Japan. [Nonaka, Kazuaki] Kyushu Univ, Fac Dent Sci, Div Oral Hlth Growth & Dev, Sect Pediat Dent,Higashi Ku, Fukuoka 8128582, Japan. [Takahashi, Ichiro] Kyushu Univ, Sect Orthodont & Dentofacial Orthoped, Fac Dent Sci, Higashi Ku, Fukuoka 8128582, Japan. [Suzuki, Kenji] Niigata Univ, Grad Sch Med & Dent Sci, Dept Gastroenterol & Hepatol, Niigata 9518514, Japan. [Slavkin, Harold C.] Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. RP Nagata, M (reprint author), Niigata Univ, Dept Oral & Maxillofacial Surg, Grad Sch Med & Dent Sci, Gakkocho Dori 2-5274, Niigata 9518514, Japan. EM nagata@dent.niigata-u.ac.jp; nuckollg@mail.nih.gov; wangx1@mail.nih.gov; Lillian.Shum@nih.gov; yukie-s@ymail.plala.or.jp; kawase@dent.niigata-u.ac.jp; takahask@kuhp.kyoto-u.ac.jp; nonaka@dent.kyushu-u.ac.jp; takahashi@dent.kyushu-u.ac.jp; arhabn@dent.niigata-u.ac.jp; kjsuzuki@med.niigata-u.ac.jp; slavkin@usc.edu FU NIH [Z01-AR41114]; NIDCR-DIR; Japan Society for the Promotion of Science [14571883, 16591986] FX We thank Y. Yamada for the Col2a1 promoter and enhancer construct. This work was supported by NIH funding Z01-AR41114 to H.C.S., partly by NIDCR-DIR, and by the Japan Society for the Promotion of Science (Project Nos. 14571883 and 16591986). NR 40 TC 10 Z9 10 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR 1 PY 2011 VL 48 IS 4 BP 847 EP 856 DI 10.1016/j.bone.2010.11.014 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 742DQ UT WOS:000288920900022 PM 21129456 ER PT J AU Horner, MJ Altekruse, SF Zou, ZH Wideroff, L Katki, HA Stinchcomb, DG AF Horner, Marie-Josephe Altekruse, Sean F. Zou, Zhaohui Wideroff, Louise Katki, Hormuzd A. Stinchcomb, David G. TI U.S. Geographic Distribution of Prevaccine Era Cervical Cancer Screening, Incidence, Stage, and Mortality SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNITED-STATES; SOCIOECONOMIC-STATUS; RISK-FACTORS; DISPARITIES; LEVEL; SURVEILLANCE; VACCINATION; PREVENTION; QUALITY; IMPACT AB Background: Cervical cancer prevention programs are being reconfigured to incorporate human papillomavirus (HPV) testing and vaccination. To define priority areas for prevention efforts, we examined the geographic distribution of cervical cancer screening, incidence, stage, and mortality in the United States, prior to the introduction of HPV-based prevention technologies. Methods: County-level cervical cancer incidence data from 37 central registries were obtained from Surveillance, Epidemiology, and End Results and North American Association of Central Cancer Registries. A spatial-temporal model that accounted for demographic and behavioral attributes was used to generate a complete view of county-level incidence from 1995 to 2004, including counties with missing data. Distribution of stage at diagnosis was examined by registry. Counties with high mortality and infrequent screening were identified using vital statistics and newly available county-level screening estimates. Results: Compared with non-Hispanic whites and Asian and Pacific Islanders, incidence rates were higher among non-Hispanic black, American Indian and Alaska Native, and Hispanic women. Counties with infrequent screening often experienced elevated incidence and mortality rates and were located in states with suboptimal stage at diagnosis profiles. Affected areas included Appalachia, the southeastern Atlantic states, and the lower Mississippi Valley. Elevated death rates were experienced in central counties of large metropolitan areas. Conclusions: Geographic and racial/ethnic variability were evident in cervical cancer incidence and mortality. Women living in areas with endemic poverty would benefit from access to HPV-based prevention technologies. Impact: These findings provide a baseline for monitoring progress in cervical cancer control in the era of HPV-based prevention. Cancer Epidemiol Biomarkers Prev; 20(4); 591-9. (C) 2011 AACR. C1 [Horner, Marie-Josephe] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Horner, Marie-Josephe; Altekruse, Sean F.; Stinchcomb, David G.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Zou, Zhaohui] Informat Management Serv Inc, Silver Spring, MD USA. [Wideroff, Louise] NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Horner, MJ (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM hornerm@mail.nih.gov RI Hernandez, Jessica/G-6527-2011; Katki, Hormuzd/B-4003-2015 FU Division of Cancer Control and Population Sciences; Surveillance Research Program; National Cancer Institute; NIH [HHSN261200900022C]; Information Management Services, Inc., Silver Spring, MD FX Division of Cancer Control and Population Sciences, Surveillance Research Program, National Cancer Institute, NIH Contract HHSN261200900022C with Information Management Services, Inc., Silver Spring, MD (for Biomedical Computing Support). NR 40 TC 34 Z9 34 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2011 VL 20 IS 4 BP 591 EP 599 DI 10.1158/1055-9965.EPI-10-1183 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 743CE UT WOS:000288993000009 PM 21266522 ER PT J AU Wright, JL Kwon, EM Ostrander, EA Montgomery, RB Lin, DW Vessella, R Stanford, JL Mostaghel, EA AF Wright, Jonathan L. Kwon, Erika M. Ostrander, Elaine A. Montgomery, R. Bruce Lin, Daniel W. Vessella, Robert Stanford, Janet L. Mostaghel, Elahe A. TI Expression of SLCO Transport Genes in Castration-Resistant Prostate Cancer and Impact of Genetic Variation in SLCO1B3 and SLCO2B1 on Prostate Cancer Outcomes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; TESTOSTERONE; IDENTIFICATION; ANDROGENS; SUPPRESSION; CARCINOMA; RECEPTOR; THERAPY; PROGRAM; CELLS AB Background: Metastases from men with castration-resistant prostate cancer (CRPC) harbor increased tumoral androgens versus untreated prostate cancers. This may reflect steroid uptake by OATP (organic anion transporting polypeptide)/SLCO transporters. We evaluated SLCO gene expression in CRPC metastases and determined whether prostate cancer outcomes are associated with single nucleotide polymorphisms (SNP) in SLCO2B1 and SLCO1B3, transporters previously shown to mediate androgen uptake. Methods: Transcripts encoding eleven SLCO genes were analyzed in untreated prostate cancer and in metastatic CRPC tumors obtained by rapid autopsy. SNPs in SLCO2B1 and SLCO1B3 were genotyped in a population-based cohort of 1,309 Caucasian prostate cancer patients. Median survival follow-up was 7.0 years (0.77-16.4). The risk of prostate cancer recurrence/progression and prostate cancer-specific mortality (PCSM) was estimated with Cox proportional hazards analysis. Results: Six SLCO genes were highly expressed in CRPC metastases versus untreated prostate cancer, including SLCO1B3 (3.6-fold; P = 0.0517) and SLCO2B1 (5.5-fold; P = 0.0034). Carriers of the variant alleles SLCO2B1 SNP rs12422149 (HR: 1.99; 95% CI: 1.11-3.55) or SLCO1B3 SNP rs4149117 (HR: 1.76; 95% CI: 1.00-3.08) had an increased risk of PCSM. Conclusions: CRPC metastases show increased expression of SLCO genes versus primary prostate cancer. Genetic variants of SLCO1B3 and SLCO2B1 are associated with PCSM. Expression and genetic variation of SLCO genes which alter androgen uptake may be important in prostate cancer outcomes. Impact: OATP/SLCO genes may be potential biomarkers for assessing risk of PCSM. Expression and genetic variation in these genes may allow stratification of patients to more aggressive hormonal therapy or earlier incorporation of nonhormonal-based treatment strategies. Cancer Epidemiol Biomarkers Prev; 20(4); 619-27. (C) 2011 AACR. C1 [Wright, Jonathan L.; Lin, Daniel W.; Vessella, Robert] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Wright, Jonathan L.; Lin, Daniel W.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Kwon, Erika M.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. [Montgomery, R. Bruce; Mostaghel, Elahe A.] Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Mostaghel, Elahe A.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Mostaghel, EA (reprint author), 1100 Fairview Ave N,D4-100, Seattle, WA 98109 USA. EM emostagh@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU Prostate Cancer Foundation; Damon Runyon Cancer Research Foundation [CI-40-08]; NIH [SPORE P50 CA97186, R01 CA056678, R01 CA082664, R01 CA092579, T32 CA009168-30] FX Prostate Cancer Foundation (Career Development Award to E. A. Mostaghel and Synergy Award to R. B. Montgomery); Damon Runyon Cancer Research Foundation (Damon Runyon-Genentech Clinical Investigator Award CI-40-08 to E. A. Mostaghel); NIH (Pacific Northwest Prostate Cancer SPORE P50 CA97186 (J.L. Stanford, Career Development Award to J.L. Wright, and Pilot Project Award to E. A. Mostaghel); R01 CA056678 (J.L. Stanford); R01 CA082664 (J.L. Stanford); R01 CA092579 (J.L. Stanford); T32 CA009168-30 (J.L. Wright); with additional support from the Fred Hutchinson Cancer Research Center and the Intramural Program of the National Human Genome Research Institute (E.M. Kwon and E.A. Ostrander). NR 34 TC 53 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2011 VL 20 IS 4 BP 619 EP 627 DI 10.1158/1055-9965.EPI-10-1023 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 743CE UT WOS:000288993000012 PM 21266523 ER PT J AU Lai, GY Rohrmann, S Agurs-Collins, T Sutcliffe, CG Bradwin, G Rifai, N Bienstock, JL Platz, EA AF Lai, Gabriel Y. Rohrmann, Sabine Agurs-Collins, Tanya Sutcliffe, Catherine G. Bradwin, Gary Rifai, Nader Bienstock, Jessica L. Platz, Elizabeth A. TI Racial Variation in Umbilical Cord Blood Leptin Concentration in Male Babies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROSTATE-CANCER RISK; CATCH-UP GROWTH; PLASMA LEPTIN; BIRTH-WEIGHT; AFRICAN-AMERICAN; C-PEPTIDE; POPULATION; CHILDREN; INSULIN; AGE AB Background: We hypothesize that racial differences in utero contribute to the racial disparity in prostate cancer risk. Leptin is a candidate for evaluating this hypothesis because it influences fetal development and newborn growth. Methods: We measured leptin concentration by ELISA in venous cord blood collected from 70 African-American and 37 white male full-term babies. We measured sex steroid hormones and insulin-like growth factor (IGF) axis concentrations previously. Separately by race, we calculated the geometric mean leptin concentration and estimated the geometric mean adjusted for birth and placental weights, mother's age and parity, time of day and season of birth, and sex steroid hormone and IGF axis concentrations by linear regression. Results: Leptin was positively correlated with birth (r = 0.34) and placental (r = 0.25) weights, IGF-1 (r = 0.21), and IGF binding protein-3 (r = 0.29) adjusting for race. Unadjusted geometric mean leptin did not differ (P = 0.92) between African Americans (5,280 pg/mL; 95% CI: 4,322-6,451) and whites (5,187 pg/mL; 95% CI: 3,938-6,832). Adjusted geometric mean leptin was nonstatistically significantly higher (P = 0.15) in African Americans (5,954 pg/mL; 95% CI: 4,725-7,502) than in whites (4,133 pg/mL; 95% CI: 2,890-5,910). Conclusion: We observed a nonsignificantly higher adjusted cord blood leptin concentration in African-American male babies than in white male babies, although unadjusted levels were similar. Impact: These findings do not support the hypothesis that leptin level in utero contributes to the racial disparity in prostate cancer risk in adulthood. Cancer Epidemiol Biomarkers Prev; 20(4); 665-71. (C) 2011 AACR. C1 [Lai, Gabriel Y.; Sutcliffe, Catherine G.; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Rohrmann, Sabine] Univ Zurich, Inst Social & Prevent Med, Div Canc Epidemiol & Prevent, CH-8006 Zurich, Switzerland. [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Bradwin, Gary; Rifai, Nader] Harvard Univ, Sch Med, Dept Lab Med, Boston, MA USA. [Bradwin, Gary; Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Bienstock, Jessica L.] Johns Hopkins Univ, Sch Med, Dept Gynecol, Baltimore, MD USA. [Bienstock, Jessica L.] Johns Hopkins Univ, Sch Med, Dept Obstet, Baltimore, MD USA. [Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Rm E6132,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu RI Rohrmann, Sabine/D-2113-2012 FU NCI [CA091409, CA091431]; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; National Cancer Institute, NIH [T32 CA009314] FX This work was supported by NCI grant U54 (Hopkins CA091409) and U54 (Howard CA091431). Support was also provided by the doctoral research fund from the Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health. G. Lai was supported by a National Research Service Award T32 CA009314 from the National Cancer Institute, NIH. NR 43 TC 5 Z9 5 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2011 VL 20 IS 4 BP 665 EP 671 DI 10.1158/1055-9965.EPI-10-0283 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 743CE UT WOS:000288993000017 PM 21307303 ER PT J AU Shiels, MS Albanes, D Virtamo, J Engels, EA AF Shiels, Meredith S. Albanes, Demetrius Virtamo, Jarmo Engels, Eric A. TI Increased Risk of Lung Cancer in Men with Tuberculosis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EPIDEMIOLOGIC EVIDENCE; MALE SMOKERS; DISEASE; WOMEN; SMOKING; XUANWEI; TRIAL; CHINA AB Background: Lung cancer and tuberculosis cause significant morbidity and mortality worldwide. Tuberculosis may increase lung cancer risk through substantial and prolonged pulmonary inflammation. However, prospective data on tuberculosis and lung cancer risk are limited. Methods: Our study included 29,133 Finnish male smokers followed prospectively in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1985-2005). Lung cancers were identified through linkage with the Finnish Cancer Registry, and hospital-treated tuberculosis cases were ascertained from the National Hospital Discharge Register. We assessed the association between tuberculosis and lung cancer risk with proportional hazards regression models, adjusting for age and cigarette smoking. Results: Forty-four lung cancer cases occurred among 273 men with tuberculosis (incidence rate 1,786 per 100,000 person-years). Tuberculosis was associated with a two-fold elevation in lung cancer risk (HR = 1.97; 95% CI = 1.46-2.65) with significant associations observed for both incident (HR = 2.05; 95% CI = 1.42-2.96) and prevalent tuberculosis (HR = 1.82; 95% CI = 1.09-3.02). Lung cancer risk was greatest in the 2-year window after tuberculosis diagnosis (HR = 5.01; 95% CI = 2.96-8.48) but remained elevated at longer latencies (HR = 1.53; 95% CI = 1.07-2.20). Though tuberculosis was associated with an increased risk of squamous cell carcinoma (HR = 3.71), adenocarcinoma (HR = 1.71), small cell carcinoma (HR = 1.72), and lung cancer of other (HR = 1.23) and unknown histologies (HR = 1.35), only the association for squamous cell carcinoma was statistically significant. Conclusions: Tuberculosis is associated with increased lung cancer risk in male smokers. Impact: Our results add to the growing body of evidence implicating chronic inflammation and pulmonary scarring in the etiology of lung cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 672-8. (C) 2011 AACR. C1 [Shiels, Meredith S.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Shiels, MS (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7059, Rockville, MD 20852 USA. EM shielsms@mail.nih.gov RI Albanes, Demetrius/B-9749-2015 FU National Cancer Institute; U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]; NIH FX The ATBC Study was supported by the Intramural Research Program of the National Cancer Institute, NIH, and U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services. NR 23 TC 21 Z9 23 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2011 VL 20 IS 4 BP 672 EP 678 DI 10.1158/1055-9965.EPI-10-1166 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 743CE UT WOS:000288993000018 PM 21335509 ER PT J AU Lipkin, S Lee, J Imagawa, D Hewitt, SM Tucker, C Zell, JA Wong, V Garcia, A Gonzalez, R Della Zanna, G Richmond, E Rodriguez, LM Bigg, M Schnoll-Sussmans, F Meyskens, F AF Lipkin, Steven Lee, John Imagawa, David Hewitt, Stephen M. Tucker, Chris Zell, Jason A. Wong, Vanessa Garcia, Angela Gonzalez, Rachel Della Zanna, Gary Richmond, Ellen Rodriguez, L. M. Bigg, M. Schnoll-Sussmans, F. Meyskens, Frank TI Phase IIA Trial Testing Erlotinib as an Intervention against Intraductal Pancreatic Mucinous Neoplasms SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID INTRAEPITHELIAL NEOPLASIA; UPDATED EXPERIENCE; PAPILLARY; CLASSIFICATION; CANCER C1 [Lipkin, Steven; Lee, John; Imagawa, David; Zell, Jason A.; Wong, Vanessa; Garcia, Angela; Gonzalez, Rachel; Meyskens, Frank] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [Lipkin, Steven; Lee, John; Imagawa, David; Zell, Jason A.; Wong, Vanessa; Garcia, Angela; Gonzalez, Rachel; Meyskens, Frank] Univ Calif Irvine, Chao Family NCI Designated Comprehens Canc Ctr, Irvine, CA USA. [Hewitt, Stephen M.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Tucker, Chris] OSI Pharmaceut, Boulder, CO USA. [Della Zanna, Gary; Richmond, Ellen; Rodriguez, L. M.] NCI, Canc Prevent Div, Rockville, MD USA. [Lipkin, Steven; Bigg, M.; Schnoll-Sussmans, F.] Weill Cornell Med Coll, Dept Med, Div Gastroenterol Hepatol, New York, NY 10021 USA. RP Lipkin, S (reprint author), Weill Cornell Med Coll, Dept Med, Div Gastroenterol Hepatol, 718 Caspary,541 E 71st St, New York, NY 10021 USA. EM stl2012@med.cornell.edu OI Hewitt, Stephen/0000-0001-8283-1788 FU NCI NIH HHS [N01 CN043302, P30 CA062203] NR 16 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2011 VL 4 IS 4 BP 512 EP 513 DI 10.1158/1940-6207.CAPR-10-0373 PG 2 WC Oncology SC Oncology GA 744DG UT WOS:000289073700006 PM 21464031 ER PT J AU Protiva, P Mason, JB Liu, ZH Hopkins, ME Nelson, C Marshall, JR Lambrecht, RW Pendyala, S Kopelovich, L Kim, M Kleinstein, SH Laird, PW Lipkin, M Holt, PR AF Protiva, Petr Mason, Joel B. Liu, Zhenhua Hopkins, Michael E. Nelson, Celeste Marshall, James R. Lambrecht, Richard W. Pendyala, Swaroop Kopelovich, Levy Kim, Myungjin Kleinstein, Steven H. Laird, Peter W. Lipkin, Martin Holt, Peter R. TI Altered Folate Availability Modifies the Molecular Environment of the Human Colorectum: Implications for Colorectal Carcinogenesis SO CANCER PREVENTION RESEARCH LA English DT Article ID FOLIC-ACID SUPPLEMENTATION; COLONIC MUCOSAL CONCENTRATIONS; GENOMIC DNA METHYLATION; UNIVERSAL BEAD ARRAYS; DIETARY-FOLATE; BLOOD MEASUREMENTS; P53 EXPRESSION; STRAND BREAKS; CANCER-RISK; RAT COLON AB Low folate status increases colorectal cancer risk. Paradoxically, overly abundant folate supplementation, which is not uncommon in the United States, may increase risk. The mechanisms of these effects are unknown. We conducted two translational studies to define molecular pathways in the human colon altered either by folate supplementation or by dietary folate depletion (followed by repletion). In the first study, 10 healthy, at-risk volunteers (with documented stable/normal folate intake) received supplemental folic acid (1 mg/d) for 8 weeks. In the second study, 10 similar subjects were admitted to a hospital as inpatients for 12 weeks to study folate depletion induced by a low folate diet. A repletion regimen of folic acid (1 mg/d) was provided for the last 4 of these weeks. Both studies included an 8-week run-in period to ensure stabilized folate levels prior to intervention. We obtained 12 rectosigmoid biopsies (from 4 quadrants of normal-appearing mucosa 10-15 cm from the anal verge) at baseline and at measured intervals in both studies for assessing the primary endpoints: genome-wide gene expression, genomic DNA methylation, promoter methylation (depletion/repletion study only), and p53 DNA strand breaks. Serum and rectosigmoid folate concentrations accurately tracked all changes in folate delivery (P < 0.05). In the first study, gene array analysis revealed that supplementation upregulated multiple inflammation-and immune-related pathways in addition to altering several 1-carbon-related enzymes (P < 0.001). In the second study, folate depletion downregulated genes involved in immune response, inflammation, the cell cycle, and mitochondrial/energy pathways; repletion reversed most of these changes. However, changes in gene expression after repletion in the second study (involving immune response and inflammation) did not reach the levels seen after supplementation in the first study. Neither genomic nor promoter-specific DNA methylation changed during the course of the depletion/repletion protocol, and genomic methylation did not change with supplementation in the first study. p53 DNA strand breaks increased with depletion after 12 weeks. In sum, depletion downregulates, whereas repletion or supplementation upregulates pathways related to inflammation and immune response. These findings provide novel support to the concept that excessive folate supplementation might promote colorectal carcinogenesis by enhancing proinflammatory and immune response pathways. These results indicate that modest changes in folate delivery create substantial changes in the molecular milieu of the human colon. Cancer Prev Res; 4(4); 530-43. (C) 2011 AACR. C1 [Protiva, Petr] Yale Univ, Sch Med, Dept Med, Sect Digest Dis, New Haven, CT 06520 USA. [Protiva, Petr; Hopkins, Michael E.; Nelson, Celeste; Pendyala, Swaroop; Holt, Peter R.] Rockefeller Univ, New York, NY 10021 USA. [Protiva, Petr] VA Connecticut Healthcare Syst, New Haven, CT USA. [Protiva, Petr; Lambrecht, Richard W.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Mason, Joel B.; Liu, Zhenhua] Tufts Univ, USDA, Human Nutr Res Ctr, Boston, MA 02111 USA. [Marshall, James R.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Rockville, MD USA. [Kim, Myungjin; Laird, Peter W.] Univ So Calif, Keck Sch Med, USC Epigenome Ctr, Los Angeles, CA 90033 USA. [Kleinstein, Steven H.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Kleinstein, Steven H.] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Lipkin, Martin] Weill Cornell Med Coll, New York, NY USA. RP Protiva, P (reprint author), Yale Univ, Sch Med, Dept Med, Sect Digest Dis, 333 Cedar St,LMP1080, New Haven, CT 06520 USA. EM petr.protiva@yale.edu RI Laird, Peter/G-8683-2012 FU GCRC; NCRR [5UL1RR024143]; NIH Roadmap for Medical Research; NIH [NO1-CN35111, CA-29502-24]; University of Connecticut Health Center; [K05 CA100048] FX The study was supported by the GCRC and 5UL1RR024143 from the NCRR and the NIH Roadmap for Medical Research to Rockefeller University, NIH grant NO1-CN35111 (PI: JM), CA-29502-24 (PI: PP), Carol and Ray Neag Colon Cancer Prevention Program research funds at University of Connecticut Health Center to P. Protiva, and K05 CA100048 (J.B. Mason). NR 38 TC 26 Z9 26 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD APR PY 2011 VL 4 IS 4 BP 530 EP 543 DI 10.1158/1940-6207.CAPR-10-0143 PG 14 WC Oncology SC Oncology GA 744DG UT WOS:000289073700009 PM 21321062 ER PT J AU Stauffer, JK Scarzello, AJ Andersen, JB De Kluyver, RL Back, TC Weiss, JM Thorgeirsson, SS Wiltrout, RH AF Stauffer, Jimmy K. Scarzello, Anthony J. Andersen, Jesper B. De Kluyver, Rachel L. Back, Timothy C. Weiss, Jonathan M. Thorgeirsson, Snorri S. Wiltrout, Robert H. TI Coactivation of AKT and beta-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors SO CANCER RESEARCH LA English DT Article ID HEPATOCELLULAR-CARCINOMA; POOR-PROGNOSIS; WNT/BETA-CATENIN; MOUSE MODEL; CANCER; EXPRESSION; GENE; OVARIAN; METABOLISM; PTEN AB Obesity is a risk factor for development of certain cancers but the basis for this risk is unclear. In this study, we developed a novel mouse model that demonstrates directly how lipogenic phenotypes commonly associated with diet-induced metabolic syndromes can influence hepatic cancer development. Activated AKT and beta-catenin (AKT/CAT) genes were hydrodynamically codelivered using the Sleeping Beauty transposon to initiate liver tumorigenesis. AKT/CAT and MET/CAT combination induced microscopic tumor foci by 4 weeks, whereas no tumorigenesis resulted from delivery of AKT, MET, or CAT alone. Primary AKT/CAT tumor cells were steatotic (fatty) hepatocellular adenomas which progressed to hepatocellular carcinomas (HCC) upon in vivo passage, whereas primary MET/CAT tumors emerged directly as frank HCC. Conversion of AKT/CAT tumor cells to frank HCC during passage was associated with induction of the human HCC marker alpha-fetoprotein and the stem cell marker CD133. Using hierarchical clustering and gene set enrichment analysis, we compared the primary murine AKT/CAT and MET/CAT tumors to a panel of 53 human HCCs and determined that these two mouse models could be stratified as distinct subtypes associated in humans with poor clinical prognosis. The chief molecular networks identified in primary and passaged AKT/CAT tumors were steatosis and lipid metabolic pathways, respectively. Our findings show how coactivation of the AKT and CAT pathways in hepatocytes can efficiently model development of a lipogenic tumor phenotype. Furthermore, we believe that our approach could speed the dissection of microenvironmental factors responsible for driving steatotic-neoplastic transformation to frank carcinoma, through genetic modification of existing immunodefined transgenic models. Cancer Res; 71(7); 2718-27. (C)2011 AACR. C1 [Wiltrout, Robert H.] NCI Frederick, LEI NCI Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Wiltrout, RH (reprint author), NCI Frederick, LEI NCI Ctr Canc Res, Canc & Inflammat Program, Bldg 428,Room 48A, Frederick, MD 21702 USA. EM wiltrour@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [HHSN261200800001E] FX This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract no. HHSN261200800001E. NR 39 TC 28 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 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2011 VL 71 IS 7 BP 2718 EP 2727 DI 10.1158/0008-5472.CAN-10-2705 PG 10 WC Oncology SC Oncology GA 743YW UT WOS:000289057600032 PM 21324921 ER PT J AU Edlich, F Banerjee, S Suzuki, M Cleland, MM Arnoult, D Wang, CX Neutzner, A Tjandra, N Youle, RJ AF Edlich, Frank Banerjee, Soojay Suzuki, Motoshi Cleland, Megan M. Arnoult, Damien Wang, Chunxin Neutzner, Albert Tjandra, Nico Youle, Richard J. TI Bcl-x(L) Retrotranslocates Bax from the Mitochondria into the Cytosol SO CELL LA English DT Article ID PROSURVIVAL BCL-2 PROTEINS; CELL-DEATH; MEMBRANE PERMEABILIZATION; CYTOCHROME-C; APOPTOTIC FUNCTION; BH3-ONLY PROTEINS; PROAPOPTOTIC BAX; DISULFIDE BONDS; BH3 DOMAINS; FAMILY AB The Bcl-2 family member Bax translocates from the cytosol to mitochondria, where it oligomerizes and permeabilizes the mitochondrial outer membrane to promote apoptosis. Bax activity is counteracted by prosurvival Bcl-2 proteins, but how they inhibit Bax remains controversial because they neither colocalize nor form stable complexes with Bax. We constrained Bax in its native cytosolic conformation within cells using intramolecular disulfide tethers. Bax tethers disrupt interaction with Bcl-x(L) in detergents and cell-free MOMP activity but unexpectedly induce Bax accumulation on mitochondria. Fluorescence loss in photobleaching (FLIP) reveals constant retrotranslocation of WT Bax, but not tethered Bax, from the mitochondria into the cytoplasm of healthy cells. Bax retrotranslocation depends on prosurvival Bcl-2 family proteins, and inhibition of retrotranslocation correlates with Bax accumulation on the mitochondria. We propose that Bcl-x(L) inhibits and maintains Bax in the cytosol by constant retrotranslocation of mitochondrial Bax. C1 [Edlich, Frank; Banerjee, Soojay; Cleland, Megan M.; Wang, Chunxin; Youle, Richard J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Neutzner, Albert] Univ Spital Basel, Augenklin, CH-4031 Basel, Switzerland. [Arnoult, Damien] Hop Paul Brousse, INSERM, U1014, F-94807 Villejuif, France. RP Youle, RJ (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youle@helix.nih.gov RI Wang, Chunxin/B-9312-2016; OI Wang, Chunxin/0000-0001-6015-6806; Neutzner, Albert/0000-0001-9254-5558 FU Leopoldina, National Academy of Sciences, Germany; La Ligue contre le Cancer; NHLBI; NINDS FX We thank Dr. D. W. Andrews and Dr. J.-C. Martinou for helpful discussions and comments. We also thank Dr. D. R. Green for the Omi-mCherry construct. This work is supported by the Leopoldina, National Academy of Sciences, Germany (F. E.); La Ligue contre le Cancer (D. A.); the NHLBI (M. S. and N.T.); and the NINDS intramural programs. NR 41 TC 172 Z9 180 U1 1 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD APR 1 PY 2011 VL 145 IS 1 BP 104 EP 116 DI 10.1016/j.cell.2011.02.034 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 743XW UT WOS:000289053900013 PM 21458670 ER PT J AU Burch, LH Yang, Y Sterling, JF Roberts, SA Chao, FG Xu, H Zhang, LL Walsh, J Resnick, MA Mieczkowski, PA Gordenin, DA AF Burch, Lauranell H. Yang, Yong Sterling, Joan F. Roberts, Steven A. Chao, Frank G. Xu, Hong Zhang, Leilei Walsh, Jesse Resnick, Michael A. Mieczkowski, Piotr A. Gordenin, Dmitry A. TI Damage-induced localized hypermutability SO CELL CYCLE LA English DT Article DE hypermutability; evolution; DNA damage and repair; single-strand DNA; double-strand breaks ID STRAND-BREAK-REPAIR; DNA-REPLICATION FORK; SACCHAROMYCES-CEREVISIAE; SOMATIC HYPERMUTATION; ULTRAVIOLET-LIGHT; MUTATION-RATE; PROTEIN EVOLUTION; ADAPTIVE MUTATION; GENE CONVERSION; SEQUENCE SPACE AB Genome instability continuously presents perils of cancer, genetic disease and death of a cell or an organism. At the same time, it provides for genome plasticity that is essential for development and evolution. We address here the genome instability confined to a small fraction of DNA adjacent to free DNA ends at uncapped telomeres and double-strand breaks. We found that budding yeast cells can tolerate nearly 20 kilobase regions of subtelomeric single-strand DNA that contain multiple UV-damaged nucleotides. During restoration to the double-strand state, multiple mutations are generated by error-prone translesion synthesis. Genome-wide sequencing demonstrated that multiple regions of damage-induced localized hypermutability can be tolerated, which leads to the simultaneous appearance of multiple mutation clusters in the genomes of UV-irradiated cells. High multiplicity and density of mutations suggest that this novel form of genome instability may play significant roles in generating new alleles for evolutionary selection as well as in the incidence of cancer and genetic disease. C1 [Burch, Lauranell H.; Yang, Yong; Sterling, Joan F.; Roberts, Steven A.; Chao, Frank G.; Xu, Hong; Zhang, Leilei; Resnick, Michael A.; Gordenin, Dmitry A.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. [Walsh, Jesse; Mieczkowski, Piotr A.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC USA. RP Gordenin, DA (reprint author), NIEHS, Mol Genet Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM miecz001@med.unc.edu; Gordenin@niehs.nih.gov OI Gordenin, Dmitry/0000-0002-8399-1836 FU NIH, National Institute of Environmental Health Sciences [ES065073]; National Institute of Environmental Health Sciences [P30ES010126]; NIH [RC1 ESO18091]; University Cancer Research Fund (UCRF) FX We are thankful to Drs. Jan Drake, Jana Stone and Kin Chan for critical reading of the manuscript. The work was supported by funds the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Project ES065073, P.I.-M.A.R.) and by grants from the National Institute of Environmental Health Sciences (P30ES010126), NIH (RC1 ESO18091) and the University Cancer Research Fund (UCRF) to P.A.M. NR 85 TC 20 Z9 21 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2011 VL 10 IS 7 BP 1073 EP 1085 DI 10.4161/cc.10.7.15319 PG 13 WC Cell Biology SC Cell Biology GA 744JF UT WOS:000289090000017 PM 21406975 ER PT J AU Singh, R Zeng, XK Zheng, ZY Hou, SX AF Singh, Ram Zeng, Xiankun Zheng, Zhiyu Hou, Steven X. TI The adult Drosophila gastric and stomach organs are maintained by a multipotent stem cell pool at the foregut/midgut junction in the cardia (proventriculus) SO CELL CYCLE LA English DT Article DE Gastric stem cells; foregut/midgut junction; cardia; proventriculus; stomach; Drosophila ID CONTROLS SELF-RENEWAL; JAK-STAT; CUBITUS INTERRUPTUS; MALPIGHIAN TUBULES; REPRESSOR FORMS; SMALL-INTESTINE; IN-VIVO; GENE; PROTEIN; PATHWAY AB Stomach cancer is the second most frequent cause of cancer-related death worldwide. Thus, it is important to elucidate the properties of gastric stem cells, including their regulation and transformation. To date, such stem cells have not been identified in Drosophila. Here, using clonal analysis and molecular marker labeling, we identify a multipotent stem-cell pool at the foregut/midgut junction in the cardia (proventriculus). We found that daughter cells migrate upward either to anterior midgut or downward to esophagus and crop. The cardia functions as a gastric valve and the anterior midgut and crop together function as a stomach in Drosophila; therefore, we named the foregut/midgut stem cells as gastric stem cells (GaSC). We further found that JAK-STAT signaling regulates GaSCs' proliferation, Wingless signaling regulates GaSCs' self-renewal, and hedgehog signaling regulates GaSCs' differentiation. The differentiation pattern and genetic control of the Drosophila GaSCs suggest the possible similarity to mouse gastric stem cells. The identification of the multipotent stem cell pool in the gastric gland in Drosophila will facilitate studies of gastric stem cell regulation and transformation in mammal. C1 [Singh, Ram; Zeng, Xiankun; Zheng, Zhiyu; Hou, Steven X.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. RP Singh, R (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. EM singhshr@mail.nih.gov; hous@mail.nih.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU National Cancer Institute of the National Institutes of Health FX We thank G. Baeg, K. Basler, J.P. Vincent, V. Hartenstein, S. Hyashi, J. Merriam, M. Pankratz, J. Skeath, T. Xie, S. DiNardo, and the Bloomington stock center for fly stocks; J. Skeath, F. Matszaki, and B. Patterson for antibodies; Dr. Stephen Lockett and Optical Microscopy and Analysis Laboratory (OMAL) staff for help with the confocal microscopy; Dr. David King for help in identifying cell types in the cardia; and Maritta Perry Grau for editing the manuscript. This research was supported by the Intramural Research Program, National Cancer Institute of the National Institutes of Health. NR 72 TC 5 Z9 5 U1 0 U2 8 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2011 VL 10 IS 7 BP 1109 EP 1120 DI 10.4161/cc.10.7.14830 PG 12 WC Cell Biology SC Cell Biology GA 744JF UT WOS:000289090000021 PM 21403464 ER PT J AU Ferris, RL Xi, LQ Seethala, RR Chan, J Desai, S Hoch, B Gooding, W Godfrey, TE AF Ferris, Robert L. Xi, Liqiang Seethala, Raja R. Chan, Jon Desai, Shaun Hoch, Benjamin Gooding, William Godfrey, Tony E. TI Intraoperative qRT-PCR for Detection of Lymph Node Metastasis in Head and Neck Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; POLYMERASE CHAIN-REACTION; CLINICALLY NEGATIVE NECK; ORAL TONGUE CARCINOMA; SENTINEL NODE; MOLECULAR-DETECTION; SELECTIVE NECK; MESSENGER-RNA; TUMOR-CELLS; BIOPSY AB Purpose: Sentinel node biopsy (SNB) has been shown to accurately stage the regional lymphatics in oral carcinoma. However, intraoperative pathology is only moderately sensitive and final pathology takes several days to complete. The purpose of this study was to develop a rapid, automated, and quantitative real-time PCR (qRT-PCR) assay that can match final pathology in an intraoperative time frame. Experimental Design: Four hundred forty-eight grossly tumor-negative lymph nodes were evaluated for expression of 3 markers [PVA (pemphigus vulgaris antigen), PTHrP (parathyroid hormone-related protein), and TACSTD1 (tumor-associated calcium signal transducer 1)]. Conformity of metastasis detection by qRT-PCR was determined using hematoxylin and eosin and immunohistochemistry staining as the gold standard. PVA and TACSTD1 were then multiplexed with beta-glucuronidase to develop a rapid, automated single-tube qRT-PCR assay using the Cepheid GeneXpert system. This assay was used to analyze 103 lymph nodes in an intraoperative time frame. Results: Four hundred forty-two nodes produced an informative result for both qRT-PCR and pathologic examination. Concordance of qRT-PCR for individual markers with final pathology ranged from 93% to 98%. The best marker combination was TACSTD1 and PVA. A rapid, multiplex assay for TACSTD1 and PVA was developed on the Cepheid GeneXpert and demonstrated an excellent reproducibility and linearity. Analysis of 103 lymph nodes demonstrated 94.2% accuracy of this assay for identifying positive and negative nodes. The average time for each assay to yield results was 35 minutes. Conclusions: A rapid, automated qRT-PCR assay can detect lymph node metastasis in head and neck cancer with high accuracy compared to pathologic analysis and may be more accurate than intraoperative pathology. Combined, SNB and rapid qRT-PCR could more appropriately guide surgical treatment of patients with head and neck cancer. Clin Cancer Res; 17(7); 1858-66. (C) 2011 AACR. C1 [Godfrey, Tony E.] Univ Rochester, James P Wilmot Canc Ctr, Med Ctr, Dept Surg, Rochester, NY 14642 USA. [Ferris, Robert L.; Chan, Jon] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Ferris, Robert L.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA. [Seethala, Raja R.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Ferris, Robert L.] Univ Pittsburgh, Inst Canc, Canc Immunol Program, Pittsburgh, PA USA. [Gooding, William] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA. [Xi, Liqiang] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Desai, Shaun] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Hoch, Benjamin] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Godfrey, TE (reprint author), Univ Rochester, James P Wilmot Canc Ctr, Med Ctr, Dept Surg, Box 704,601 Elmwood Ave, Rochester, NY 14642 USA. EM ferrisrl@upmc.edu; tony_godfrey@urmc.rochester.edu RI Godfrey, Tony/A-5572-2013; OI Godfrey, Tony/0000-0002-3283-6983; Ferris, Robert/0000-0001-6605-2071 FU NCI NIH HHS [P50 CA097190] NR 48 TC 32 Z9 32 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2011 VL 17 IS 7 BP 1858 EP 1866 DI 10.1158/1078-0432.CCR-10-3110 PG 9 WC Oncology SC Oncology GA 743XY UT WOS:000289054100023 PM 21355082 ER PT J AU Saito, M Schetter, AJ Mollerup, S Kohno, T Skaug, V Bowman, ED Mathe, EA Takenoshita, S Yokota, J Haugen, A Harris, CC AF Saito, Motonobu Schetter, Aaron J. Mollerup, Steen Kohno, Takashi Skaug, Vidar Bowman, Elise D. Mathe, Ewy A. Takenoshita, Seiichi Yokota, Jun Haugen, Aage Harris, Curtis C. TI The Association of MicroRNA Expression with Prognosis and Progression in Early-Stage, Non-Small Cell Lung Adenocarcinoma: A Retrospective Analysis of Three Cohorts SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; PREDICTS SURVIVAL; POOR-PROGNOSIS; HUMAN CANCERS; MIR-21; METASTASIS; PROMOTES; TARGETS; OVEREXPRESSION; SIGNATURE AB Purpose: There is increasing evidence that altered microRNA expression is associated with tumor progression and survival in cancer patients. We tested if the expression of specific microRNAs was associated with prognosis and disease progression in early-stage lung adenocarcinoma. Experimental Design: The expression of miR-21, miR-17, and miR-155 was measured by quantitative RT-PCR in tissues from 317 non-small cell lung cancer (NSCLC) patients that originated from Maryland, Norway, and Japan. Kaplan-Meier and Cox regression analysis evaluated associations of microRNA expression with cancer-specific mortality and disease-free survival. Results: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and miR-155 (HR 2.37, 1.27-4.42) was associated with worse cancer-specific mortality in the Maryland cohort. These were evaluated in two additional cohorts and only miR-21 was associated with worse cancer-specific mortality in the Norwegian cohort (HR 2.78, 1.22-6.31) and worse relapse-free survival in the Japanese cohort (HR 2.82, 1.57-5.07). More advanced stage tumors expressed significantly higher levels of miR-21 compared with TNM stage I tumors. TNM stage I patients were evaluated separately and high levels of miR-21 was associated with worse cancer-specific mortality (HR 2.16, 1.11-4.21) and relapse-free survival (3.40, 1.57-7.36) independent of other clinical factors. Conclusions: This is the first study to report that increased miR-21 expression is associated with disease progression and survival in stage I lung cancer. This suggests that expression of miR-21 may contribute to lung carcinogenesis and serve as a therapeutic target or early-stage prognostic biomarker for lung adenocarcinoma. Clin Cancer Res; 17(7); 1875-82. (C) 2011 AACR. C1 [Saito, Motonobu; Schetter, Aaron J.; Bowman, Elise D.; Mathe, Ewy A.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mollerup, Steen; Skaug, Vidar; Haugen, Aage] Natl Inst Occupat Hlth, Sect Toxicol, Dept Chem & Biol Working Environm, Oslo, Norway. [Saito, Motonobu; Takenoshita, Seiichi] Fukushima Med Univ, Dept Organ Regulatory Surg, Sch Med, Fukushima, Japan. [Kohno, Takashi; Yokota, Jun] Natl Canc Ctr, Res Inst, Div Biol, Tokyo 104, Japan. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov FU National Cancer Institute, National Institutes of Health, Department of Defense [PR093793]; Norwegian Cancer Society; Ministry of Health, Labor and Welfare FX This research was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Department of Defense Congressionally Directed Medical Research Program Grant PR093793, the Norwegian Cancer Society, and a Grant-in-Aid from the Ministry of Health, Labor and Welfare for the 3rd-term Comprehensive 10-year Strategy for Cancer Control, Japan. NR 50 TC 90 Z9 98 U1 1 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2011 VL 17 IS 7 BP 1875 EP 1882 DI 10.1158/1078-0432.CCR-10-2961 PG 8 WC Oncology SC Oncology GA 743XY UT WOS:000289054100025 PM 21350005 ER PT J AU Yu, KJ Hsu, WL Pfeiffer, RM Chiang, CJ Wang, CP Lou, PJ Cheng, YJ Gravitt, P Diehl, SR Goldstein, AM Chen, CJ Hildesheim, A AF Yu, Kelly J. Hsu, Wan-Lun Pfeiffer, Ruth M. Chiang, Chun-Ju Wang, Cheng-Ping Lou, Pei-Jen Cheng, Yu-Juen Gravitt, Patti Diehl, Scott R. Goldstein, Alisa M. Chen, Chien-Jen Hildesheim, Allan TI Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families SO CLINICAL CANCER RESEARCH LA English DT Article ID EPSTEIN-BARR-VIRUS; NASOPHARYNGEAL CARCINOMA; CAPSID ANTIGEN; DIAGNOSIS; RESPONSES; PROTEIN; SERUM; DEOXYRIBONUCLEASE; MALIGNANCIES; INFECTION AB Purpose: Epstein-Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families. Experimental Design: We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated. Results: A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4-16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5-61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker. Conclusions: Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. Clin Cancer Res; 17(7); 1906-14. (C)2011 AACR. C1 [Yu, Kelly J.] NCI, Infect & Immunoepidemiol Branch, DCEG, NIH,DHHS, Bethesda, MD 20852 USA. [Hsu, Wan-Lun; Chiang, Chun-Ju; Cheng, Yu-Juen; Chen, Chien-Jen] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Hsu, Wan-Lun; Chiang, Chun-Ju; Chen, Chien-Jen] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Wang, Cheng-Ping; Lou, Pei-Jen] Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. [Wang, Cheng-Ping; Lou, Pei-Jen] Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. [Gravitt, Patti] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol & Mol Microbiol & Immunol, Baltimore, MD USA. [Diehl, Scott R.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Ctr Pharmacogen & Complex Dis Res, Newark, NJ 07103 USA. RP Yu, KJ (reprint author), NCI, Infect & Immunoepidemiol Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,Room 7057, Bethesda, MD 20852 USA. EM yuke@mail.nih.gov RI Chen, Chien-Jen/C-6976-2008; Pfeiffer, Ruth /F-4748-2011; Hildesheim, Allan/B-9760-2015; OI Hildesheim, Allan/0000-0003-0257-2363; WANG, CHENG-PING/0000-0001-7872-1463; LOU, PEI-JEN/0000-0002-3383-8593 FU National Cancer Institute FX This project was supported by funds from the Intramural Research Program of the National Cancer Institute. NR 29 TC 26 Z9 30 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2011 VL 17 IS 7 BP 1906 EP 1914 DI 10.1158/1078-0432.CCR-10-1681 PG 9 WC Oncology SC Oncology GA 743XY UT WOS:000289054100028 PM 21447725 ER PT J AU Gronowski, AM Moye, J Wendler, DS Caplan, AL Christman, M AF Gronowski, Ann M. Moye, Jack, Jr. Wendler, David S. Caplan, Arthur L. Christman, Michael TI The Use of Human Tissues in Research: What Do We Owe the Research Subjects? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Gronowski, Ann M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Gronowski, Ann M.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Moye, Jack, Jr.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Childrens Study, NIH, Bethesda, MD USA. [Wendler, David S.] NIH, Unit Vulnerable Populat, Bethesda, MD 20892 USA. [Caplan, Arthur L.] Univ Penn, Dept Med Eth, Philadelphia, PA 19104 USA. [Christman, Michael] Coriell Inst Med Res, Camden, NJ USA. RP Gronowski, AM (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM gronowski@pathology.wustl.edu OI moye, john/0000-0001-9976-8586 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2011 VL 57 IS 4 BP 540 EP 544 DI 10.1373/clinchem.2010.154989 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 741HE UT WOS:000288854000002 PM 21205881 ER PT J AU Boja, ES Jortani, SA Ritchie, J Hoofnagle, AN Tezak, Z Mansfield, E Keller, P Rivers, RC Rahbar, A Anderson, NL Srinivas, P Rodriguez, H AF Boja, Emily S. Jortani, Saeed A. Ritchie, James Hoofnagle, Andrew N. Tezak, Zivana Mansfield, Elizabeth Keller, Penny Rivers, Robert C. Rahbar, Amir Anderson, N. Leigh Srinivas, Pothur Rodriguez, Henry TI The Journey to Regulation of Protein-Based Multiplex Quantitative Assays SO CLINICAL CHEMISTRY LA English DT Article ID BIOMARKER DISCOVERY; MASS-SPECTROMETRY; VALIDATION; QUANTIFICATION; ACTIVATION; ENRICHMENT; MODELS; PLASMA; SERUM AB BACKGROUND: Clinical proteomics presents great promise in biology and medicine because of its potential for improving our understanding of diseases at the molecular level and for detecting disease-related biomarkers for diagnosis, prognosis, and prediction of therapeutic responses. To realize its full potential to improve clinical outcome for patients, proteomic studies have to be well designed, from biosample cohorts to data and statistical analyses. One key component in the biomarker development pipeline is the understanding of the regulatory science that evaluates diagnostic assay performance through rigorous analytical and clinical review criteria. CONTENT: The National Cancer Institute's Clinical Proteomic Technologies for Cancer (CPTC) initiative has proposed an intermediate preclinical "verification" step to close the gap between protein-based biomarker discovery and clinical qualification. In collaboration with the US Food and Drug Administration (FDA), the CPTC network investigators recently published 2 mock submission review documents, first-of-their-kind educational materials that may help the scientific community interested in developing products for the clinic in understanding the likely analytical evaluation requirements for multiplex protein technology-based diagnostic tests. CONCLUSIONS: Building on this momentum, the CPTC continues with this report its collaboration with the FDA, as well as its interactions with the AACC and the Centers for Medicare and Medicaid Services, to further the understanding of regulatory requirements for approving multiplex proteomic platform-based tests and analytically validating multiple analytes.(C) 2011 American Association for Clinical Chemistry C1 [Boja, Emily S.; Rivers, Robert C.; Rahbar, Amir; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. [Jortani, Saeed A.] Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. [Ritchie, James] Emory Univ, Sch Med, Atlanta, GA USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Tezak, Zivana; Mansfield, Elizabeth] US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Keller, Penny] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC USA. [Srinivas, Pothur] NHLBI, NIH, Bethesda, MD 20892 USA. RP Boja, ES (reprint author), NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. EM bojae@mail.nih.gov FU Waters FX A.N. Hoofnagle, Waters. NR 21 TC 25 Z9 26 U1 0 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2011 VL 57 IS 4 BP 560 EP 567 DI 10.1373/clinchem.2010.156034 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 741HE UT WOS:000288854000008 PM 21300740 ER PT J AU Morgan, TR O'Brien, TR AF Morgan, Timothy R. O'Brien, Thomas R. TI IL28B-Genotype Testing Now and in the Era of Direct-Acting Antiviral Agents SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID HEPATITIS-C; GENETIC-VARIATION; INTERFERON-ALPHA; RIBAVIRIN; LAMBDA; IL28B C1 [Morgan, Timothy R.] Calif State Univ Long Beach, Gastroenterol Serv, VA Long Beach Healthcare Syst, Long Beach, CA 90840 USA. [Morgan, Timothy R.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Morgan, TR (reprint author), Calif State Univ Long Beach, Gastroenterol Serv, VA Long Beach Healthcare Syst, Long Beach, CA 90840 USA. FU Intramural NIH HHS; NIDDK NIH HHS [N01 DK092320] NR 11 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD APR PY 2011 VL 9 IS 4 BP 293 EP 294 DI 10.1016/j.cgh.2010.12.014 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 745ED UT WOS:000289147400011 PM 21185399 ER PT J AU Moitra, K Lou, H Dean, M AF Moitra, K. Lou, H. Dean, M. TI Multidrug Efflux Pumps and Cancer Stem Cells: Insights Into Multidrug Resistance and Therapeutic Development SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID BINDING CASSETTE TRANSPORTER; SIDE POPULATION CELLS; ABCG2 EXPRESSION; DRUG-RESISTANCE; P-GLYCOPROTEIN; MESSENGER-RNA; MDR1 PROMOTER; UNTRANSLATED REGION; PROTEIN; GENE AB Stem cells possess the dual properties of self-renewal and pluripotency. Self-renewal affords these populations the luxury of self-propagation, whereas pluripotency allows them to produce the multitude of cell types found in the body. Protection of the stem cell population from damage or death is critical because these cells need to remain intact throughout the life of an organism. The principal mechanism of protection is through expression of multifunctional efflux transporters-the adenosine triphosphate-binding cassette (ABC) transporters that are the "guardians" of the stem cell population. Ironically, it has been shown that these ABC efflux pumps also afford protection to cancer stem cells (CSCs), shielding them from the adverse effects of chemotherapeutic insult. It is therefore imperative to gain a better understanding of the mechanisms involved in the resistance of stem cells to chemotherapy, which could lead to the discovery of new therapeutic targets and improvement of current anticancer strategies. C1 [Moitra, K.; Dean, M.] NCI, Expt Immunol Lab, Human Genet Sect, Canc & Inflammat Program, Frederick, MD 21701 USA. [Lou, H.] SAIC Frederick, Human Genet Sect, Basic Sci Program, Frederick, MD USA. RP Dean, M (reprint author), NCI, Expt Immunol Lab, Human Genet Sect, Canc & Inflammat Program, Frederick, MD 21701 USA. EM deanm@mail.nih.gov OI Dean, Michael/0000-0003-2234-0631 FU National Institutes of Health; National Cancer Institute; SAIC-Frederick [NO1-CO-12400] FX We acknowledge the researchers who have contributed to the advancements in stem cell and ABC transporter research and whose works have not been cited here because of space limitations. This research was supported in part by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, and SAIC-Frederick under contract NO1-CO-12400. NR 50 TC 106 Z9 116 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2011 VL 89 IS 4 BP 491 EP 502 DI 10.1038/clpt.2011.14 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738OK UT WOS:000288649600016 PM 21368752 ER PT J AU Kulich, M Rericha, V Rericha, R Shore, DL Sandler, DP AF Kulich, M. Rericha, V. Rericha, R. Shore, D. L. Sandler, D. P. TI Incidence of non-lung solid cancers in Czech uranium miners: A case-cohort study SO ENVIRONMENTAL RESEARCH LA English DT Article DE Environmental carcinogens; Ionizing radiation; Neoplasms; Occupational exposure; Radon; Smoking ID EXTENDED FOLLOW-UP; RADON EXPOSURE; FRENCH COHORT; MORTALITY; RISK AB Objectives: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Pribram region, Czech Republic. Methods: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. Results: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% Cl 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% Cl 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% Cl 0.52-10.98, n=13), 0.79 for larynx cancer (95% Cl 0.38-1.64, n=62), 2.92 for malignant melanoma (95% Cl 0.91-9.42, n=23), 0.84 for bladder cancer (95% Cl 0.43-1.65, n=73), and 1.13 for kidney cancer (95% Cl 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. Conclusions: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. (C) 2011 Elsevier Inc. All rights reserved. C1 [Kulich, M.] Charles Univ Prague, Fac Math & Phys, Dept Stat, CZ-18675 Prague 8, Czech Republic. [Rericha, V.] Reg Hosp Pribram, Pribram, Czech Republic. [Rericha, R.] Ctr Epidemiol Studies, Pribram, Czech Republic. [Shore, D. L.] Westat Corp, Durham, NC USA. [Sandler, D. P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC USA. RP Kulich, M (reprint author), Charles Univ Prague, Fac Math & Phys, Dept Stat, Sokolovska 83, CZ-18675 Prague 8, Czech Republic. EM kulich@karlin.mff.cuni.cz RI Kulich, Michal/B-1483-2013; OI Kulich, Michal/0000-0002-2812-8968; Sandler, Dale/0000-0002-6776-0018 FU NIH; National Institute of Environmental Health Sciences [Z01-ES-049029]; Regional Hospital in Pribram FX This study was financed by research contracts and additional support from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES-049029) and by the Regional Hospital in Pribram. NR 18 TC 11 Z9 12 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD APR PY 2011 VL 111 IS 3 BP 400 EP 405 DI 10.1016/j.envres.2011.01.008 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 743OC UT WOS:000289026700011 PM 21256480 ER PT J AU Wells, EM Jarrett, JM Lin, YH Caldwell, KL Hibbeln, JR Apelberg, BJ Herbstman, J Halden, RU Witter, FR Goldman, LR AF Wells, Ellen M. Jarrett, Jeffery M. Lin, Yu Hong Caldwell, Kathleen L. Hibbeln, Joseph R. Apelberg, Benjamin J. Herbstman, Julie Halden, Rolf U. Witter, Frank R. Goldman, Lynn R. TI Body burdens of mercury, lead, selenium and copper among Baltimore newborns SO ENVIRONMENTAL RESEARCH LA English DT Article DE Mercury; Lead; Selenium; Copper; Umbilical cord ID UMBILICAL-CORD BLOOD; FISH CONSUMPTION; SEAFOOD CONSUMPTION; INORGANIC MERCURY; CHILD-DEVELOPMENT; NATIONAL-HEALTH; SERUM SELENIUM; MATERNAL BLOOD; PREGNANT-WOMEN; METHYL MERCURY AB Umbilical cord blood or serum concentrations of mercury, lead, selenium and copper were measured with inductively coupled plasma mass spectrometry in a population of 300 infants born in Baltimore, Maryland. Geometric mean values were 1.37 mu g/L (95% confidence interval: 1.27, 1.48) for mercury; 0.66 mu g/dL (95% Cl; 0.61, 0.71) for lead; and 38.62 mu g/dL (95% Cl: 36.73, 40.61) for copper. Mean selenium was 70.10 mu g/L (95% Cl: 68.69, 70.52). Mercury, selenium and copper levels were within exposure ranges reported among similar populations, whereas the distribution of lead levels was lower than prior reports; only one infant had a cord blood lead above 10 mu g/dL. Levels of selenium were significantly correlated with concentrations of lead (Spearman's p=0.20) and copper (Spearman's p=0.51). Multivariable analyses identified a number of factors associated with one of more of these exposures. These included: increase in maternal age (increased lead); Asian mothers (increased mercury and lead, decreased selenium and copper); higher umbilical cord serum n-3 fatty acids (increased mercury, selenium and copper), mothers using Medicaid (increased lead); increasing gestational age (increased copper); increasing birthweight (increased selenium); older neighborhood housing stock (increased lead and selenium); and maternal smoking (increased lead). This work provides additional information about contemporary prenatal element exposures and can help identify groups at risk of atypical exposures. (C) 2011 Elsevier Inc. All rights reserved. C1 [Wells, Ellen M.; Halden, Rolf U.; Goldman, Lynn R.] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. [Wells, Ellen M.] Case Western Reserve Univ Sch Med, Dept Environm Hlth Sci, Cleveland, OH 44106 USA. [Jarrett, Jeffery M.; Caldwell, Kathleen L.] Ctr Dis Control & Prevent, Inorgan & Radiat Analyt Toxicol Branch, Atlanta, GA 30333 USA. [Lin, Yu Hong; Hibbeln, Joseph R.] NIAAA, NIH, Bethesda, MD 20892 USA. [Apelberg, Benjamin J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Herbstman, Julie] Columbia Univ Mailman Sch Publ Hlth, Columbia Ctr Childrens Environm Hlth, New York, NY 10032 USA. [Halden, Rolf U.] Arizona State Univ, Biodesign Inst, Ctr Environm Biotechnol, Tempe, AZ 85287 USA. [Witter, Frank R.] Johns Hopkins Univ Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. [Goldman, Lynn R.] George Washington Univ Sch Publ Hlth & Hlth Serv, Washington, DC 20037 USA. RP Goldman, LR (reprint author), Washington Univ Sch Publ Hlth & Hlth Serv, 2300 Eye St NW,Suite 106, Washington, DC 20039 USA. EM lynn.goldman@gwumc.edu RI Schneider, Larissa/C-9863-2012; Goldman, Lynn/D-5372-2012; Halden, Rolf/F-9562-2010; OI Wells, Ellen/0000-0002-7293-1395; Halden, Rolf/0000-0001-5232-7361; Jarrett, Jeffery/0000-0001-5755-3552 FU United States Environmental Protection Agency (EPA); Science to Achieve Results Fellowship Program (STAR); National Institute of Environmental Health Sciences (NIEHS) [1R01ES015445]; US Centers for Disease Control and Prevention (CDC); Maryland Cigarette Restitution Program Research Grant; Johns Hopkins Bloomberg School of Public Health; Johns Hopkins School of Medicine Department of Gynecology and Obstetrics FX This study received support from the United States Environmental Protection Agency (EPA) Science to Achieve Results Fellowship Program (STAR), the National Institute of Environmental Health Sciences (NIEHS) grant 1R01ES015445, the US Centers for Disease Control and Prevention (CDC) and the Maryland Cigarette Restitution Program Research Grant given to the Johns Hopkins Medical Institutions, the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins School of Medicine Department of Gynecology and Obstetrics. The content and views presented in this work are solely the responsibility of the authors and do not necessarily represent those of US EPA, CDC, NIEHS, or any of the other institutes or centers at the National Institutes of Health. NR 56 TC 22 Z9 22 U1 2 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD APR PY 2011 VL 111 IS 3 BP 411 EP 417 DI 10.1016/j.envres.2010.12.009 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 743OC UT WOS:000289026700013 PM 21277575 ER PT J AU Schwitter, J Arai, AE AF Schwitter, Juerg Arai, Andrew E. TI Assessment of cardiac ischaemia and viability: role of cardiovascular magnetic resonance SO EUROPEAN HEART JOURNAL LA English DT Review DE Cardiovascular magnetic resonance; Coronary artery disease; Myocardial infarction; Acute coronary syndrome; Congestive heart failure; Computed tomography; Single-photon emission computed tomography; Echocardiography ID ACUTE-MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; ST-SEGMENT ELEVATION; EMISSION-COMPUTED-TOMOGRAPHY; ACUTE CHEST-PAIN; INCREMENTAL PROGNOSTIC VALUE; WALL-MOTION ABNORMALITIES; EMERGENCY-DEPARTMENT PATIENTS; RANDOMIZED CONTROLLED-TRIAL; ADENOSINE STRESS PERFUSION AB Over the past years, cardiovascular magnetic resonance (CMR) has proven its efficacy in large clinical trials, and consequently, the assessment of function, viability, and ischaemia by CMR is now an integrated part of the diagnostic armamentarium in cardiology. By combining these CMR applications, coronary artery disease ( CAD) can be detected in its early stages and this allows for interventions with the goal to reduce complications of CAD such as infarcts and subsequently chronic heart failure (CHF). As the CMR examinations are robust and reproducible and do not expose patients to radiation, they are ideally suited for repetitive studies without harm to the patients. Since CAD is a chronic disease, the option to monitor CAD regularly by CMR over many decades is highly valuable. Cardiovascular magnetic resonance also progressed recently in the setting of acute coronary syndromes. In this situation, CMR allows for important differential diagnoses. Cardiovascular magnetic resonance also delineates precisely the different tissue components in acute myocardial infarction such as necrosis, microvascular obstruction (MVO), haemorrhage, and oedema, i.e. area at risk. With these features, CMR might also become the preferred tool to investigate novel treatment strategies in clinical research. Finally, in CHF patients, the versatility of CMR to assess function, flow, perfusion, and viability and to characterize tissue is helpful to narrow the differential diagnosis and to monitor treatment. C1 [Schwitter, Juerg] Univ Hosp Lausanne CHUV, Dept Cardiol, CH-1011 Lausanne, Switzerland. [Arai, Andrew E.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Schwitter, J (reprint author), Univ Hosp Lausanne CHUV, Dept Cardiol, Rue Bugnon 46, CH-1011 Lausanne, Switzerland. EM jurg.schwitter@chuv.ch FU CMR Center of the University Hospital Lausanne (CRMC) FX Funding to pay the Open Access publication charge was provided by the CMR Center of the University Hospital Lausanne (CRMC). NR 149 TC 30 Z9 32 U1 2 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD APR PY 2011 VL 32 IS 7 BP 799 EP U162 DI 10.1093/eurheartj/ehq481 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 745JS UT WOS:000289162300010 PM 21398645 ER PT J AU Malech, HL Kang, EM Choi, U De Ravin, SS Sweeney, C AF Malech, H. L. Kang, E. M. Choi, U. De Ravin, S. S. Sweeney, C. TI Plenary Lectures SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Malech, H. L.; Kang, E. M.; Choi, U.; De Ravin, S. S.; Sweeney, C.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2011 VL 41 SU 1 BP 1 EP 2 DI 10.1111/j.1365-2362.2011.02506.x PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 742AD UT WOS:000288909500004 ER PT J AU Kino, T AF Kino, T. TI Circadian rhythm transcription factor CLOCK-mediated regulation of glucocorticoid action at local target tissues: physiologic and pathophysiologic implications SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Meeting Abstract C1 [Kino, T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2011 VL 41 SU 1 BP 59 EP 59 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 742AD UT WOS:000288909500163 ER PT J AU Kumar, P Shrivastava, B Pandeya, SN Stables, JP AF Kumar, Praveen Shrivastava, Birendra Pandeya, Surendra N. Stables, James P. TI Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Quinazolin-4(3H)-one; 6 Hz psychomotor seizure test activity; Neurotoxicity; Computational study ID ANTICONVULSANT ACTIVITY; 4(3H)-QUINAZOLINONES; DISCOVERY AB Thirty new 2-(substituted)-3-{[substituted]amino}quinazolin-4(3H)-one were designed and synthesized keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant activity and neurotoxicity. The anticonvulsant activity of the titled compounds was assessed using the 6 Hz psychomotor seizure test. The most active compound of the series was 3-({(E)-[3-(4-chloro-3-methylphenoxy)phenyl]methylidene}amino)-2-phenylquinazolin-4(3H)-one PhQZ 7, which showed 100% protection (4/4, 0.5 h) and 75% protection (3/4, 0.25 h) at a dose of 100 mg/kg in mice. A computational study was carried out for calculation of pharmacophore pattern and prediction of pharmacokinetic properties. Titled compounds have also exhibited good binding properties with epilepsy molecular targets such as glutamate, GABA (A) delta and GABA (A) alpha-1 receptors, in Lamarckian genetic algorithm based flexible docking studies. (C) 2011 Elsevier Masson SAS. All rights reserved. C1 [Kumar, Praveen; Shrivastava, Birendra] Jaipur Natl Univ, Sch Pharmaceut Sci, Jaipur 302025, Rajasthan, India. [Pandeya, Surendra N.] Saroj Inst Technol & Management, Lucknow 226002, Uttar Pradesh, India. [Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Kumar, P (reprint author), Jaipur Natl Univ, Sch Pharmaceut Sci, Jaipur 302025, Rajasthan, India. EM praveensha1977@rediffmail.com NR 17 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD APR PY 2011 VL 46 IS 4 BP 1006 EP 1018 DI 10.1016/j.ejmech.2011.01.009 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 743WB UT WOS:000289048400003 PM 21306800 ER PT J AU Beck, S Hallett, M AF Beck, Sandra Hallett, Mark TI Surround inhibition in the motor system SO EXPERIMENTAL BRAIN RESEARCH LA English DT Review DE Human; Transcranial magnetic stimulation; Contrast ID FOCAL HAND DYSTONIA; INDIVIDUATED FINGER MOVEMENTS; WRITERS CRAMP; INTRACORTICAL INHIBITION; BASAL GANGLIA; INTERHEMISPHERIC INHIBITION; ASSOCIATIVE PLASTICITY; AFFERENT INHIBITION; PARKINSONS-DISEASE; BABOONS HAND AB Surround inhibition is a physiological mechanism to focus neuronal activity in the central nervous system. This so-called center-surround organization is well known in sensory systems, where central signals are facilitated and eccentric signals are inhibited in order to sharpen the contrast between them. There is evidence that this mechanism is relevant to skilled motor behavior, and it is deficient, for example, in the affected primary motor cortex of patients with focal hand dystonia (FHD). While it is still not fully elucidated how surround inhibition is generated in healthy subjects, the process is enhanced with handedness and task difficulty indicating that it may be an important mechanism for the performance of individuated finger movements. In FHD, where involuntary overactivation of muscles interferes with precise finger movements, a loss of intracortical inhibition likely contributes to the loss of surround inhibition. Several intracortical inhibitory networks are modulated differently in FHD compared with healthy subjects, and these may contribute to the loss of surround inhibition. Surround inhibition can be observed and assessed in the primary motor cortex. It remains unclear, however, if the effects are created in the cortex or if they are derived from, or supported by, motor signals that come from the basal ganglia. C1 [Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Beck, Sandra] Univ Freiburg, Dept Neurol & Clin Neurophysiol, Freiburg, Germany. RP Hallett, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU NINDS FX Work supported by the NINDS Intramural Program. NR 53 TC 41 Z9 41 U1 2 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2011 VL 210 IS 2 BP 165 EP 172 DI 10.1007/s00221-011-2610-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 742QJ UT WOS:000288959200001 PM 21424259 ER PT J AU Corthout, E Hallett, M Cowey, A AF Corthout, Erik Hallett, Mark Cowey, Alan TI TMS-induced blinking assessed with high-speed video: optical disruption of visual perception SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Blinking; Video recording; Kinematics; Pupil; Transcranial magnetic stimulation (TMS) ID TRANSCRANIAL MAGNETIC STIMULATION; OCCIPITAL CORTEX; EYELID MOVEMENTS; FACIAL-NERVE; SUPPRESSION; HUMANS; LIGHT; TRANSMISSION; CLOSURE; VISION AB It is known that TMS can induce blinking, but it is unknown to what extent and at what time TMS-induced blinking can cover the pupil. We applied single-pulse TMS with a leftward and rightward monophasic current through a round coil over the occipital pole in 8 healthy subjects, using high-speed video to monitor left or right eye with a spatial resolution of 0.1 mm and a temporal resolution of 2 ms. We plotted eyelid position relative to upper and lower pupil borders as a function of time after TMS for each subject and current direction. We found 2 blinks in every subject, an isolated late blink with one current direction and a superimposed early and late blink with the other current direction, in accordance with our previously reported association between a leftward and rightward lower coil rim current and an early blink in right and left eye, respectively. Blink extent varied, but 4 subjects showed total pupil covering with both current directions. Blink timing varied, but pupil covering was initiated as early as 32 ms after TMS and pupil uncovering was completed as late as 200 ms after TMS. We found no saccades. We conclude that TMS can cause an important optical disruption of visual perception. C1 [Corthout, Erik; Cowey, Alan] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. [Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Corthout, E (reprint author), Katholieke Univ Leuven, Expt Psychol Lab, Tiensestr 102, B-3000 Louvain, Belgium. EM erik.corthout@psy.kuleuven.be FU Medical Research Council [G7103979] FX This work was supported by Medical Research Council Programme Grant G7103979 to Alan Cowey. The Kodak Ektapro EM was borrowed from the EPSRC Engineering Instrument Pool in 2000, which was then managed and run by the CLRC Rutherford Appleton Laboratory. NR 34 TC 5 Z9 5 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2011 VL 210 IS 2 BP 243 EP 250 DI 10.1007/s00221-011-2626-y PG 8 WC Neurosciences SC Neurosciences & Neurology GA 742QJ UT WOS:000288959200008 PM 21431430 ER PT J AU Leach, CR Schoenberg, NE Hatcher, J AF Leach, Corinne R. Schoenberg, Nancy E. Hatcher, Jennifer TI Factors Associated With Participation in Cancer Prevention and Control Studies Among Rural Appalachian Women SO FAMILY & COMMUNITY HEALTH LA English DT Article DE Appalachian region; early detection of cancer; research subject recruitment; rural health; women's health ID RETENTION STRATEGIES; AFRICAN-AMERICANS; HEALTH-PROMOTION; RECRUITMENT; COMMUNITY AB Rural Appalachian women bear a disproportionate burden from many types of cancer yet often are underrepresented in cancer research. This article uses 2 case studies to illustrate barriers faced and strategies used when recruiting hard-to-reach rural participants. Recruitment barriers include the population's competing demands and lack of trust of outsiders. Strategies employed include involving insider advocates, highlighting the positive experiences of early participants, spending extensive time in the community, and emphasizing potential community benefits of the study. We suggest recruitment strategies to better involve rural women and others who, by virtue of being "hard-to-reach," often are overlooked. C1 [Leach, Corinne R.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Schoenberg, Nancy E.] Univ Kentucky, Dept Behav Sci, Lexington, KY USA. [Hatcher, Jennifer] Univ Kentucky, Coll Nursing, Lexington, KY USA. RP Leach, CR (reprint author), NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. EM leachcr@mail.nih.gov OI Schoenberg, Nancy/0000-0002-4227-6326 FU AHRQ HHS [1 R36 HS016347, R36 HS016347]; NCI NIH HHS [R01 CA108696, R01 CA108696-01] NR 17 TC 8 Z9 8 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD APR-JUN PY 2011 VL 34 IS 2 BP 119 EP 125 DI 10.1097/FCH.0b013e31820de9bf PG 7 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA 730BO UT WOS:000288004200006 PM 21378508 ER PT J AU Ito, W Chehab, M Thakur, S Li, J Morozov, A AF Ito, W. Chehab, M. Thakur, S. Li, J. Morozov, A. TI BDNF-restricted knockout mice as an animal model for aggression SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Aggression; animal model; BDNF; Cre recombinase; knockout ID LONG-TERM-MEMORY; NEUROTROPHIC FACTOR; SOCIAL RECOGNITION; BEHAVIORAL-MODELS; MEDIAL AMYGDALA; MUTANT MICE; DEPRESSION; RATS; HIPPOCAMPUS; OXYTOCIN AB Mice with global deletion of one brain-derived neurotrophic factor (BDNF) allele or with forebrain-restricted deletion of both alleles show elevated aggression, but this phenotype is accompanied by other behavioral changes, including increases in anxiety and deficits in cognition. Here we performed behavioral characterization of conditional BDNF knockout mice generated using a Cre recombinase driver line, KA1-Cre, which expresses Cre in few areas of brain: highly at hippocampal area CA3 and moderately in dentate gyrus, cerebellum and facial nerve nucleus. The mutant animals exhibited elevated conspecific aggression and social dominance, but did not show changes in anxiety-like behaviors assessed using the elevated plus maze and open field test. There were no changes in depression-like behaviors tested in the forced swim test, but small increase in immobility in the tail suspension test. In cognitive tasks, mutants showed normal social recognition and normal spatial and fear memory, but exhibited a deficit in object recognition. Thus, this knockout can serve as a robust model for BDNF-dependent aggression and object recognition deficiency. C1 [Ito, W.; Chehab, M.; Thakur, S.; Li, J.; Morozov, A.] NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Ito, W (reprint author), NIMH, Unit Behav Genet, Mol Pathophysiol Lab, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM itow@mail.nih.gov; morozova@mail.nih.gov FU NIMH FX This research was supported by the NIMH Intramural Research Program. We thank Kazu Nakazawa and Susumu Tonegawa for KA1-Cre transgenic line and Daniel Sukato and Chao Yang for the editorial work. NR 64 TC 22 Z9 25 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD APR PY 2011 VL 10 IS 3 BP 365 EP 374 DI 10.1111/j.1601-183X.2010.00676.x PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 745FV UT WOS:000289152200012 PM 21255268 ER PT J AU Wu, H D'Alessio, AC Ito, S Wang, ZB Cui, KR Zhao, KJ Sun, YE Zhang, Y AF Wu, Hao D'Alessio, Ana C. Ito, Shinsuke Wang, Zhibin Cui, Kairong Zhao, Keji Sun, Yi Eve Zhang, Yi TI Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells SO GENES & DEVELOPMENT LA English DT Article DE Tet1; 5-methylcytosine (5mC); 5-hydroxymethylcytosine (5hmC); mouse embryonic stem cells; genome-wide 5hmC distribution; Polycomb repression ID DNA METHYLATION; PLURIPOTENT; CONVERSION; MAPS AB Recent studies have demonstrated that the Ten-eleven translocation (Tet) family proteins can enzymatically convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). While 5mC has been studied extensively, little is known about the distribution and function of 5hmC. Here we present a genome-wide profile of 5hmC in mouse embryonic stem (ES) cells. A combined analysis of global 5hmC distribution and gene expression profile in wild-type and Tet1-depleted ES cells suggests that 5hmC is enriched at both gene bodies of actively transcribed genes and extended promoter regions of Polycomb-repressed developmental regulators. Thus, our study reveals the first genome-wide 5hmC distribution in pluripotent stem cells, and supports its dual function in regulating gene expression. C1 [D'Alessio, Ana C.; Ito, Shinsuke; Zhang, Yi] Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Wu, Hao; Sun, Yi Eve] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Intellectual Dev & Disabil Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [D'Alessio, Ana C.; Ito, Shinsuke; Zhang, Yi] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. [Wang, Zhibin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Lab Human Environm Epigenomes, Baltimore, MD 21025 USA. [Cui, Kairong; Zhao, Keji] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Zhang, Y (reprint author), Univ N Carolina, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA. EM yi_zhang@med.unc.edu RI Wu, Hao/G-4145-2013 OI Wu, Hao/0000-0002-1256-6891 FU NIH [GM68804] FX We thank Brian Abraham and Iouri Chepelev for help with data transfer, Jinzhao Wang for FACS sorting, and Susan Wu for critical reading of the manuscript. This work was supported by NIH grant GM68804 (to Y.Z.), and support to the Division of Intramural Research Program of National Heart, Lung, and Blood Institute from the NIH (to K.Z). S.I. is a research fellow of the Japan Society for the Promotion of Science. Y.Z. is an Investigator of the Howard Hughes Medical Institute. NR 26 TC 270 Z9 278 U1 7 U2 39 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2011 VL 25 IS 7 BP 679 EP 684 DI 10.1101/gad.2036011 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 744AD UT WOS:000289062700003 PM 21460036 ER PT J AU Lamb, MM Beers, L Reed-Gillette, D McDowell, MA AF Lamb, Molly M. Beers, Lee Reed-Gillette, Debra McDowell, Margaret A. TI Feasibility of an Audio Computer-Assisted Self-Interview Method to Self-Assess Sexual Maturation SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Sexual maturation; Self-assessment; Feasibility; Children; Adolescents ID NUTRITION EXAMINATION SURVEY; PUBERTAL MATURATION; EARLY ADOLESCENTS; NATIONAL-HEALTH; VALIDITY; GIRLS; RELIABILITY; CHILDREN; STAGE; BOYS AB Purpose: Sexual maturation assessment using physical examination may no longer be feasible in some large epidemiologic surveys, such as National Health and Nutrition Examination Survey, because of the sensitivity of the examination and privacy concerns. This study tested the feasibility of a new automated audio computer-assisted self-interview (ACASI) module for children and adolescents for self-assessment of sexual maturation. Methods: A cross-sectional feasibility study was conducted at a large urban children/adolescent clinic in Washington D. C. Self-assessed sexual maturation (Tanner stages) was reported by 234 youths (119 boys and 115 girls) aged 8-18 years by using the ACASI module. Girls assessed their breast and pubic hair development, and boys assessed their genital and pubic hair development. Self-assessments were compared with Tanner stages recorded by clinical examiners during routine well-child physical examinations conducted on the same day. Results: There was good/excellent agreement between boy's self-assessment and the examiner's assessment of their genital stage (weighted kappa: .65, 95% confidence interval [CI]: .55-.75) and pubic hair stage (weighted kappa: .78, CI: .70-.86). There was excellent agreement between girl's self-assessment and the examiner's assessment of their breast stage (weighted kappa: .81, CI: .74-.87) and pubic hair stage (weighted kappa: .78, CI: .71-.86). Conclusion: The ACASI method is a feasible method of pubertal self-assessment for participants as young as 8 years in large epidemiologic surveys. However, additional testing is needed to determine the validity of this ACASI module. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [McDowell, Margaret A.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Lamb, Molly M.; Reed-Gillette, Debra] Ctr Dis Control & Prevent, Div Hlth & Nutr Examinat Surveys, Natl Ctr Hlth Stat, Hyattsville, MD USA. [Lamb, Molly M.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA. [Reed-Gillette, Debra] Childrens Natl Med Ctr, Washington, DC 20010 USA. RP McDowell, MA (reprint author), NIH, Div Nutr Res Coordinat, 2 Democracy Plaza,Rm 629,6707 Democracy BLVD,MSC, Bethesda, MD 20892 USA. EM margaret.mcdowell@nih.gov NR 36 TC 11 Z9 11 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 2011 VL 48 IS 4 BP 325 EP 330 DI 10.1016/j.jadohealth.2010.09.020 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 733ED UT WOS:000288243800002 PM 21402259 ER PT J AU Wang, J Nansel, TR Iannotti, RJ AF Wang, Jing Nansel, Tonja R. Iannotti, Ronald J. TI Cyber and Traditional Bullying: Differential Association With Depression SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Cyber bullying; Traditional bullying; Depression ID SCHOOL AB Purpose: The study compared levels of depression among bullies, victims, and bully-victims of traditional (physical, verbal, and relational) and cyber bullying that is a relatively new form of bullying. The study also examined the association between depression and frequency of involvement in each form of bullying. Methods: A U. S. nationally representative sample of students in grades 6-10 (N = 7,313) completed the bullying and depression items in the Health Behavior in School-Aged Children 2005 Survey. Results: Depression was associated with each of the four forms of bullying. Cyber victims reported higher depression than bullies or bully-victims, a result not observed in other forms of bullying. For physical, verbal, and relational bullies, the frequently-involved group of victims and bully victims reported a significantly higher level of depression than the corresponding occasionally involved group. For cyber bullying, differences were found only between the occasional and frequent victims. Conclusion: Results indicated the importance of further study of cyber bullying because its association with depression was distinct from traditional forms of bullying. Published by Elsevier Inc. on behalf of Society for Adolescent Health and Medicine. C1 [Wang, Jing; Nansel, Tonja R.; Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, NIH, Bethesda, MD 20892 USA. RP Wang, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, NIH, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20892 USA. EM wangji2@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; Maternal and Child Health Bureau of the Health Resources and Services Administration FX This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Maternal and Child Health Bureau of the Health Resources and Services Administration. NR 10 TC 96 Z9 102 U1 4 U2 54 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD APR PY 2011 VL 48 IS 4 BP 415 EP 417 DI 10.1016/j.jadohealth.2010.07.012 PG 3 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 733ED UT WOS:000288243800016 PM 21402273 ER PT J AU Pietrzak, RH Goldstein, RB Southwick, SM Grant, BF AF Pietrzak, Robert H. Goldstein, Rise B. Southwick, Steven M. Grant, Bridget F. TI Prevalence and Axis I comorbidity of full and partial posttraumatic stress disorder in the United States: Results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE Posttraumatic stress disorder; Epidemiology; Comorbidity; Mood disorders; Anxiety disorders; Substance use disorders ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; ANXIETY DISORDERS; COMMUNITY SAMPLE; MENTAL-HEALTH; YOUNG-ADULTS; PARTIAL PTSD; ENVIRONMENTAL-INFLUENCES; PSYCHIATRIC-DISORDERS; PERSONALITY-DISORDERS AB The present study used data from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653) to examine lifetime Axis I psychiatric comorbidity of posttraumatic stress disorder (PTSD) in a nationally representative sample of U.S. adults. Lifetime prevalences +/- standard errors of PTSD and partial FTSD were 6.4% +/- 0.18 and 6.6% +/- 0.18, respectively. Rates of PTSD and partial PTSD were higher among women (8.6% +/- 0.26 and 8.6% +/- 0.26) than men (4.1% +/- 0.19 and 4.5% +/- 0.21). Respondents with both PTSD and partial PTSD most commonly reported unexpected death of someone close, serious illness or injury to someone close, and sexual assault as their worst stressful experiences. PTSD and partial PTSD were associated with elevated lifetime rates of mood, anxiety, and substance use disorders, and suicide attempts. Respondents with partial PTSD generally had intermediate odds of comorbid Axis I disorders and psychosocial impairment relative to trauma controls and full PTSD. Published by Elsevier Ltd. C1 [Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, Natl Ctr Posttraumat Stress Disorder,VA Connectic, West Haven, CT 06516 USA. [Pietrzak, Robert H.; Southwick, Steven M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Goldstein, Rise B.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Pietrzak, RH (reprint author), Yale Univ, Sch Med, Dept Psychiat, Natl Ctr Posttraumat Stress Disorder,VA Connectic, 950 Campbell Ave 151-E, West Haven, CT 06516 USA. EM robert.pietrzak@yale.edu OI Goldstein, Rise/0000-0002-9603-9473 FU Intramural NIH HHS [Z01 AA000449-05] NR 88 TC 161 Z9 162 U1 5 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD APR PY 2011 VL 25 IS 3 BP 456 EP 465 DI 10.1016/j.janxdis.2010.11.010 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 736VL UT WOS:000288523000021 PM 21168991 ER PT J AU Oliveira, CJF Sa-Nunes, A Francischetti, IMB Carregaro, V Anatriello, E Silva, JS Santos, IKFD Ribeiro, JMC Ferreira, BR AF Oliveira, Carlo Jose F. Sa-Nunes, Anderson Francischetti, Ivo M. B. Carregaro, Vanessa Anatriello, Elen Silva, Joao S. de Miranda Santos, Isabel K. F. Ribeiro, Jose M. C. Ferreira, Beatriz R. TI Deconstructing Tick Saliva NON-PROTEIN MOLECULES WITH POTENT IMMUNOMODULATORY PROPERTIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENDRITIC CELL-FUNCTION; TOLL-LIKE RECEPTOR-2; LONE STAR TICK; RHIPICEPHALUS-SANGUINEUS; PROSTAGLANDIN E-2; IXODES-SCAPULARIS; BOOPHILUS-MICROPLUS; AMBLYOMMA-AMERICANUM; MONOCYTE DIFFERENTIATION; BIOLOGICAL SIGNIFICANCE AB Dendritic cells (DCs) are powerful initiators of innate and adaptive immune responses. Ticks are blood-sucking ectoparasite arthropods that suppress host immunity by secreting immunomodulatory molecules in their saliva. Here, compounds present in Rhipicephalus sanguineus tick saliva with immunomodulatory effects on DC differentiation, cytokine production, and costimulatory molecule expression were identified. R. sanguineus tick saliva inhibited IL-12p40 and TNF-alpha while potentiating IL-10 cytokine production by bone marrow-derived DCs stimulated by Toll-like receptor-2, -4, and -9 agonists. To identify the molecules responsible for these effects, we fractionated the saliva through microcon filtration and reversed-phase HPLC and tested each fraction for DC maturation. Fractions with proven effects were analyzed by micro-HPLC tandem mass spectrometry or competition ELISA. Thus, we identified for the first time in tick saliva the purine nucleoside adenosine (concentration of similar to 110pmol/mu l) as a potent anti-inflammatory salivary inhibitor of DC cytokine production. We also found prostaglandin E-2 (PGE(2) similar to 100 nM) with comparable effects in modulating cytokine production by DCs. Both Ado and PGE(2) inhibited cytokine production by inducing cAMP-PKA signaling in DCs. Additionally, both Ado and PGE(2) were able to inhibit expression of CD40 in mature DCs. Finally, flow cytometry analysis revealed that PGE(2), but not Ado, is the differentiation inhibitor of bone marrow-derived DCs. The presence of non-protein molecules adenosine and PGE(2) in tick saliva indicates an important evolutionary mechanism used by ticks to subvert host immune cells and allow them to successfully complete their blood meal and life cycle. C1 [Ferreira, Beatriz R.] Univ Sao Paulo, Sch Nursing Ribeirao Preto, Dept Maternal Child Nursing & Publ Hlth, BR-14040902 Ribeirao Preto, SP, Brazil. [Oliveira, Carlo Jose F.; Carregaro, Vanessa; Anatriello, Elen; Silva, Joao S.; de Miranda Santos, Isabel K. F.; Ferreira, Beatriz R.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil. [Sa-Nunes, Anderson] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo, Brazil. [Francischetti, Ivo M. B.; Ribeiro, Jose M. C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Ferreira, BR (reprint author), Univ Sao Paulo, Sch Nursing Ribeirao Preto, Dept Maternal Child Nursing & Publ Hlth, Av Bandeirantes 3900, BR-14040902 Ribeirao Preto, SP, Brazil. EM brferrei@usp.br RI Silva, Joao/A-4484-2008; Carregaro, Vanessa/D-2913-2012; Sa-Nunes, Anderson/D-8667-2012; Ferreira, Beatriz/C-2003-2012; de Miranda Santos, Isabel/B-7597-2012; Anatriello, Elen/N-1429-2015; de Miranda Santos, Isabel/D-5261-2016; OI Sa-Nunes, Anderson/0000-0002-1859-4973; Ferreira, Beatriz/0000-0002-6781-2236; de Miranda Santos, Isabel/0000-0002-0438-4430; Ribeiro, Jose/0000-0002-9107-0818 FU National Institutes of Health of the Division of Intramural Research, NIAID; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [06/54985-4, 07/00035-8]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior; Millennium Institute for Vaccine Development and Technology (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) [CNPq-420067/2005-1] FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program of the Division of Intramural Research, NIAID. This work was supported in part by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Grants 06/54985-4 and 07/00035-8, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Millennium Institute for Vaccine Development and Technology (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico) Grant CNPq-420067/2005-1. NR 75 TC 45 Z9 45 U1 1 U2 18 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2011 VL 286 IS 13 BP 10960 EP 10969 DI 10.1074/jbc.M110.205047 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 740LW UT WOS:000288797100008 PM 21270122 ER PT J AU Yang, Z Cooper, PR Damera, G Mukhopadhyay, I Cho, H Kehrl, JH Panettieri, RA Druey, KM AF Yang, Zhao Cooper, Philip R. Damera, Gautam Mukhopadhyay, Indranil Cho, Hyeseon Kehrl, John H. Panettieri, Reynold A., Jr. Druey, Kirk M. TI beta-Agonist-associated Reduction in RGS5 Expression Promotes Airway Smooth Muscle Hyper-responsiveness SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PULMONARY BETA(2)-ADRENOCEPTOR DESENSITIZATION; DOWN-REGULATION; PROTEIN-KINASE; BLOOD-PRESSURE; RECEPTOR; ASTHMA; CELLS; G(I); REGULATOR; CONTRACTILITY AB Although short-acting and long-acting inhaled beta(2)-adrenergic receptor agonists (SABA and LABA, respectively) relieve asthma symptoms, use of either agent alone without concomitant anti-inflammatory drugs (corticosteroids) may increase the risk of disease exacerbation in some patients. We found previously that pretreatment of human precision-cut lung slices (PCLS) with SABA impaired subsequent beta(2)-agonist-induced bronchodilation, which occurred independently of changes in receptor quantities. Here we provide evidence that prolonged exposure of cultured human airway smooth muscle (HuASM) cells to beta(2)-agonists directly augments procontractile signaling pathways elicited by several compounds including thrombin, bradykinin, and histamine. Such treatment did not increase surface receptor amounts or expression of G proteins and downstream effectors (phospholipase C beta and myosin light chain). In contrast, beta-agonists decreased expression of regulator of G protein signaling 5 (RGS5), which is an inhibitor of G-protein-coupled receptor (GPCR) activity. RGS5 knockdown in HuASM increased agonist-evoked intracellular calcium flux and myosin light chain (MLC) phosphorylation, which are prerequisites for contraction. PCLS from Rgs5(-/-) mice contracted more to carbachol than those from WT mice, indicating that RGS5 negatively regulates bronchial smooth muscle contraction. Repetitive beta(2)-agonist use may not only lead to reduced bronchoprotection but also to sensitization of excitation-contraction signaling pathways as a result of reduced RGS5 expression. C1 [Yang, Zhao; Mukhopadhyay, Indranil; Druey, Kirk M.] NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Cho, Hyeseon; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Cooper, Philip R.; Damera, Gautam; Panettieri, Reynold A., Jr.] Univ Penn, Pulm Allergy & Crit Care Div, Airways Biol Initiat, Philadelphia, PA 19104 USA. RP Druey, KM (reprint author), 10 Ctr Dr,Rm 11N242, Bethesda, MD 20892 USA. EM kdruey@niaid.nih.gov FU National Institutes of Health, NIAID [AI000939]; [HL5452235]; [HL543102]; [HL544157] FX This work was supported, in whole or in part, by the Intramural Research Program of the National Institutes of Health, NIAID (Grant No. AI000939 L. A. D., to K. M. D.) and by Grants HL5452235, HL543102, and HL544157 (to R. A. P.). NR 54 TC 13 Z9 14 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 1 PY 2011 VL 286 IS 13 BP 11444 EP 11455 DI 10.1074/jbc.M110.212480 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 740LW UT WOS:000288797100056 PM 21278382 ER PT J AU Cao, YG Liu, FF Simpson, P Antieau, L Bennett, A Cimino, JJ Ely, J Yu, H AF Cao, YongGang Liu, Feifan Simpson, Pippa Antieau, Lamont Bennett, Andrew Cimino, James J. Ely, John Yu, Hong TI AskHERMES: An online question answering system for complex clinical questions SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE Clinical question answering; Question analysis; Passage retrieval; Summarization; Answer presentation ID INFORMATION NEEDS; HEALTH INFORMATION; BIOMEDICAL TEXT; MEDICAL LITERATURE; QUERY EXPANSION; INTERNET; KNOWLEDGE; QUALITY; PHYSICIANS; SEARCH AB Objective: Clinical questions are often long and complex and take many forms. We have built a clinical question answering system named AskHERMES to perform robust semantic analysis on complex clinical questions and output question-focused extractive summaries as answers. Design: This paper describes the system architecture and a preliminary evaluation of AskHERMES, which implements innovative approaches in question analysis, summarization, and answer presentation. Five types of resources were indexed in this system: MEDLINE abstracts, PubMed Central full-text articles, eMedicine documents, clinical guidelines and Wikipedia articles. Measurement: We compared the AskHERMES system with Google (Google and Google Scholar) and UpToDate and asked physicians to score the three systems by ease of use, quality of answer, time spent, and overall performance. Results: AskHERMES allows physicians to enter a question in a natural way with minimal query formulation and allows physicians to efficiently navigate among all the answer sentences to quickly meet their information needs. In contrast, physicians need to formulate queries to search for information in Google and UpToDate. The development of the AskHERMES system is still at an early stage, and the knowledge resource is limited compared with Google or UpToDate. Nevertheless, the evaluation results show that AskHERMES' performance is comparable to the other systems. In particular, when answering complex clinical questions, it demonstrates the potential to outperform both Google and UpToDate systems. Conclusions: AskHERMES, available at http://www.AskHERMES.org, has the potential to help physicians practice evidence-based medicine and improve the quality of patient care. (C) 2011 Elsevier Inc. All rights reserved. C1 [Cao, YongGang; Liu, Feifan; Antieau, Lamont; Yu, Hong] Univ Wisconsin, Dept Hlth Sci, Milwaukee, WI 53201 USA. [Simpson, Pippa] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA. [Bennett, Andrew] Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA. [Bennett, Andrew] Vet Affairs Hosp, Milwaukee, WI USA. [Cimino, James J.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Ely, John] Univ Iowa Hosp & Clin, Dept Family Med, Iowa City, IA 52242 USA. [Yu, Hong] Univ Wisconsin, Dept Elect Engn & Comp Sci, Milwaukee, WI 53201 USA. RP Yu, H (reprint author), 2400 E Hartford Ave,Room 939, Milwaukee, WI 53211 USA. EM hongyu@uwm.edu OI Cimino, James/0000-0003-4101-1622 FU National Institute of Health (NIH) [2R01LM009836] FX The authors acknowledge support from the National Institute of Health (NIH), Grant Number 2R01LM009836. Any opinions, findings, or recommendations are those of the authors and do not necessarily reflect the views of the NIH. NR 106 TC 31 Z9 31 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2011 VL 44 IS 2 SI SI BP 277 EP 288 DI 10.1016/j.jbi.2011.01.004 PG 12 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 743PF UT WOS:000289030100009 PM 21256977 ER PT J AU Neveol, A Dogan, RI Lu, ZY AF Neveol, Aurelie Dogan, Rezarta Islamaj Lu, Zhiyong TI Semi-automatic semantic annotation of PubMed queries: A study on quality, efficiency, satisfaction SO JOURNAL OF BIOMEDICAL INFORMATICS LA English DT Article DE PubMed queries; Biomedical entities; Annotation standards; Annotation methods ID CONSISTENCY; TEXT; LIFE AB Information processing algorithms require significant amounts of annotated data for training and testing. The availability of such data is often hindered by the complexity and high cost of production. In this paper, we investigate the benefits of a state-of-the-art tool to help with the semantic annotation of a large set of biomedical queries. Seven annotators were recruited to annotate a set of 10,000 PubMed (R) queries with 16 biomedical and bibliographic categories. About half of the queries were annotated from scratch, while the other half were automatically pre-annotated and manually corrected. The impact of the automatic pre-annotations was assessed on several aspects of the task: time, number of actions, annotator satisfaction, inter-annotator agreement, quality and number of the resulting annotations. The analysis of annotation results showed that the number of required hand annotations is 28.9% less when using pre-annotated results from automatic tools. As a result, the overall annotation time was substantially lower when pre-annotations were used, while inter-annotator agreement was significantly higher. In addition, there was no statistically significant difference in the semantic distribution or number of annotations produced when pre-annotations were used. The annotated query corpus is freely available to the research community. This study shows that automatic pre-annotations are found helpful by most annotators. Our experience suggests using an automatic tool to assist large-scale manual annotation projects. This helps speed-up the annotation time and improve annotation consistency while maintaining high quality of the final annotations. Published by Elsevier Inc. C1 [Neveol, Aurelie; Dogan, Rezarta Islamaj; Lu, Zhiyong] US Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Lu, ZY (reprint author), Natl Lib Med, Bldg 38A,10N-003A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM zhiyong.lu@nih.gov OI Islamaj Dogan, Rezarta/0000-0001-5651-1860 FU NIH, National Library of Medicine FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. The authors would like to thank G. Jiang, S. Shooshan, T. Tao and W.J. Wilbur for their contribution to the annotation of the query corpus, colleagues in the NCBI engineering branch for their valuable feedback on the categorization scheme, D. Comeau for his editorial assistance, and P. Chappert at NIAID for his help using PRISM. NR 30 TC 33 Z9 33 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1532-0464 J9 J BIOMED INFORM JI J. Biomed. Inform. PD APR PY 2011 VL 44 IS 2 SI SI BP 310 EP 318 DI 10.1016/j.jbi.2010.11.001 PG 9 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 743PF UT WOS:000289030100012 PM 21094696 ER PT J AU Watkins, SK Zhu, ZQ Riboldi, E Shafer-Weaver, KA Stagliano, KER Sklavos, MM Ambs, S Yagita, H Hurwitz, AA AF Watkins, Stephanie K. Zhu, Ziqiang Riboldi, Elena Shafer-Weaver, Kim A. Stagliano, Katherine E. R. Sklavos, Martha M. Ambs, Stefan Yagita, Hideo Hurwitz, Arthur A. TI FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer (Retracted article. See vol. 125, pg. 2179, 2015) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Retracted Publication ID PLASMACYTOID DENDRITIC CELLS; ANTIGEN-PRESENTING CELLS; REGULATORY T-CELLS; DRAINING LYMPH-NODES; INDOLEAMINE 2,3-DIOXYGENASE; IN-VITRO; ANTITUMOR RESPONSES; SUPPRESSOR-CELLS; IMMUNE-RESPONSES; BREAST-CANCER AB The limited success of cancer immunotherapy is often attributed to the loss of antigen-specific T cell function in situ. However, the mechanism for this loss of function is unknown. In this study, we describe a population of tumor-associated DCs (TADCs) in both human and mouse prostate cancer that tolerizes and induces suppressive activity in tumor-specific T cells. In tumors from human prostate cancer patients and transgenic adenocarcinoma of the mouse prostate (TRAMP) mice, TADCs expressed elevated levels of FOXO3 and Foxo3, respectively, which correlated with expression of suppressive genes that negatively regulate T cell function. Silencing FOXO3 and Foxo3 with siRNAs abrogated the ability of human and mouse TADCs, respectively, to tolerize and induce suppressive activity by T cells. Silencing Foxo3 in mouse TADCs was also associated with diminished expression of tolerogenic mediators, such as indoleamine-2,3-dioxygenase, arginase, and TGF-beta, and upregulated expression of costimulatory molecules and proinflammatory cytokines. Importantly, transfer of tumor-specific CD4(+) Th cells into TRAMP mice abrogated TADC tolerogenicity, which was associated with reduced Foxo3 expression. These findings demonstrate that FOXO3 may play a critical role in mediating TADC-induced immune suppression. Moreover, our results identify what we believe to be a novel target for preventing CTL tolerance and enhancing immune responses to cancer by modulating the immunosuppressive activity of TADCs found in the tumor microenvironment. C1 [Riboldi, Elena] NCI, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA. [Watkins, Stephanie K.; Zhu, Ziqiang; Shafer-Weaver, Kim A.; Stagliano, Katherine E. R.; Sklavos, Martha M.; Hurwitz, Arthur A.] NCI, Tumor Immun & Tolerance Sect, Mol Immunoregulat Lab, Frederick, MD 21702 USA. [Shafer-Weaver, Kim A.] SAIC Frederick Inc, Frederick, MD USA. [Ambs, Stefan] NCI, Breast & Prostate Canc Unit, Human Carcinogenesis Lab, Frederick, MD 21702 USA. [Yagita, Hideo] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. RP Hurwitz, AA (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, 211 Bldg 567, Frederick, MD 21702 USA. EM hurwitza@mail.nih.gov FU NCI [Z01 BC 010954]; Center for Cancer Research; Office of Science and Technology Partnerships; Department of Defense FX The authors would like to thank Joost Oppenheim, Giorgio Trinchieri, Jose Conejo-Garcia, Jay Berzofsky, Bill Murphy, and Nicholas Restifo for their helpful discussions and critical review of this manuscript and Scott Hudson for his assistance in uploading microarray data to GEO. This work was supported by the Intramural Research Program of the NCI under award Z01 BC 010954. Additional support was provided by the Center for Cancer Research, Office of Science and Technology Partnerships, and the Department of Defense Prostate Cancer Research Program. NR 54 TC 89 Z9 90 U1 1 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2011 VL 121 IS 4 BP 1361 EP 1372 DI 10.1172/JCI44325 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 745OK UT WOS:000289174600020 PM 21436588 ER PT J AU Rhee, EP Cheng, S Larson, MG Walford, GA Lewis, GD McCabe, E Yang, E Farrell, L Fox, CS O'Donnell, CJ Carr, SA Vasan, RS Florez, JC Clish, CB Wang, TJ Gerszten, RE AF Rhee, Eugene P. Cheng, Susan Larson, Martin G. Walford, Geoffrey A. Lewis, Gregory D. McCabe, Elizabeth Yang, Elaine Farrell, Laurie Fox, Caroline S. O'Donnell, Christopher J. Carr, Steven A. Vasan, Ramachandran S. Florez, Jose C. Clish, Clary B. Wang, Thomas J. Gerszten, Robert E. TI Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FATTY-ACID-COMPOSITION; CORONARY-HEART-DISEASE; MIDDLE-AGED ADULTS; RISK; DESATURASES; MELLITUS; GLUCOSE; ATHEROSCLEROSIS; EXERCISE; DELTA-5 AB Dyslipidemia is an independent risk factor for type 2 diabetes, although exactly which of the many plasma lipids contribute to this remains unclear. We therefore investigated whether lipid profiling can inform diabetes prediction by performing liquid chromatography/mass spectrometry-based lipid profiling in 189 individuals who developed type 2 diabetes and 189 matched disease-free individuals, with over 12 years of follow up in the Framingham Heart Study. We found that lipids of lower carbon number and double bond content were associated with an increased risk of diabetes, whereas lipids of higher carbon number and double bond content were associated with decreased risk. This pattern was strongest for triacylglycerols (TAGs) and persisted after multivariable adjustment for age, sex, BMI, fasting glucose, fasting insulin, total triglycerides, and HDL cholesterol. A combination of 2 TAGs further improved diabetes prediction. To explore potential mechanisms that modulate the distribution of plasma lipids, we performed lipid profiling during oral glucose tolerance testing, pharmacologic interventions, and acute exercise testing. Levels of TAGs associated with increased risk for diabetes decreased in response to insulin action and were elevated in the setting of insulin resistance. Conversely, levels of TAGs associated with decreased diabetes risk rose in response to insulin and were poorly correlated with insulin resistance. These studies identify a relationship between lipid acyl chain content and diabetes risk and demonstrate how lipid profiling could aid in clinical risk assessment. C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Rhee, Eugene P.; Lewis, Gregory D.; Yang, Elaine; Carr, Steven A.; Florez, Jose C.; Clish, Clary B.; Gerszten, Robert E.] Broad Inst, Cambridge, MA 02142 USA. [Cheng, Susan; Larson, Martin G.; McCabe, Elizabeth; Fox, Caroline S.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Study Natl Heart Lung & Blood In, Framingham, MA USA. [Cheng, Susan; Larson, Martin G.; McCabe, Elizabeth; Fox, Caroline S.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Wang, Thomas J.] Boston Univ, Sch Med, Framingham, MA USA. [Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Cheng, Susan; Lewis, Gregory D.; McCabe, Elizabeth; Farrell, Laurie; O'Donnell, Christopher J.; Wang, Thomas J.; Gerszten, Robert E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Walford, Geoffrey A.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Walford, Geoffrey A.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Fox, Caroline S.; O'Donnell, Christopher J.] Boston Univ, Sch Med, Boston Med Ctr, NHLBI Div Intramural Res, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. [Wang, Thomas J.; Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp E, Div Cardiol, 149 13th St,8th Floor, Charlestown, MA 02129 USA. EM clary@broadinstitute.org; tjwang@partners.org; rgerszten@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NIH [N01-HC-25195, R01-DK-HL081572, T32-DK-00754023]; Donald W. Reynolds Foundation; Leducq Foundation; American Heart Association; Endocrine Fellows Foundation; MGH; Doris Duke Charitable Foundation FX This work was supported by NIH contracts N01-HC-25195 and R01-DK-HL081572, the Donald W. Reynolds Foundation, the Leducq Foundation, and the American Heart Association. E.P. Rhee received support from the NIH grant T32-DK-00754023. G.A. Walford is supported by the Endocrine Fellows Foundation. J.C. Florez is also supported by the MGH and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. We also acknowledge David Altshuler for his support. NR 31 TC 160 Z9 161 U1 5 U2 27 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 APR PY 2011 VL 121 IS 4 BP 1402 EP 1411 DI 10.1172/JCI44442 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 745OK UT WOS:000289174600024 PM 21403394 ER PT J AU Arora, NK Reeve, BB Hays, RD Clauser, SB Oakley-Girvan, I AF Arora, Neeraj K. Reeve, Bryce B. Hays, Ron D. Clauser, Steven B. Oakley-Girvan, Ingrid TI Assessment of Quality of Cancer-Related Follow-Up Care From the Cancer Survivor's Perspective SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLORECTAL-CANCER; BREAST-CANCER; PSYCHOMETRIC PROPERTIES; PATIENTS EXPERIENCES; CONSUMER ASSESSMENT; HEALTH PLANS; OF-CARE; PATIENT SATISFACTION; AMERICAN-SOCIETY; RANDOMIZED-TRIAL AB Purpose We assessed cancer survivors' perceptions of the quality of their follow-up care. Methods We surveyed a population-based cohort of leukemia, bladder, and colorectal cancer survivors diagnosed 2 to 5 years previously in northern California (N = 623; participation rate, 69.2%; overall response rate, 49.2%). Data were collected between April 2003 and November 2004. Ten scales assessed survivors' perceptions of different aspects of care in the last 12 months, and an eleventh scale measured their overall ratings of care. Results On nine of the 11 scales, mean scores ranged from 88 to 97 on a 0 to 100 response format, indicating very positive experiences. The two areas where quality perceptions were lower were discussions about health promotion and the physician's knowledge of the whole patient. In adjusted analyses, those without private health insurance (P = .02) and Hispanic and Asian survivors compared with whites (P < .001) reported worse timeliness of care. Survivors who had multiple comorbidities reported better scores on timeliness of care (P < .01) and physicians' knowledge (P = .05) than survivors without any comorbidity. Length of the patient-physician relationship was the variable most consistently found to be significantly associated with survivors' quality assessments. Physicians' information exchange had the strongest relationship with overall ratings of care, followed by physicians' affective behavior, their knowledge of the survivor, and survivors' perceptions of coordination of care (P < .001 for all). Conclusion Delivery of quality follow-up care to cancer survivors may require efforts to improve patient-centered communication and coordination. Special emphasis may need to be placed on health promotion discussions and adoption of a whole-person orientation. C1 [Arora, Neeraj K.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ N Carolina, Lineberger Canc Ctr, Chapel Hill, NC USA. Univ Calif Los Angeles, Los Angeles, CA USA. Canc Prevent Inst Calif, Fremont, CA USA. RP Arora, NK (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Executive Blvd,MSC 7344,EPN 4092, Bethesda, MD 20892 USA. EM aroran@mail.nih.gov RI Hays, Ronald/D-5629-2013 FU National Cancer Institute [N01-PC-35136]; University of California, Los Angeles (UCLA) Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly, National Institutes of Health (NIH)/National Institute on Aging (NIA) [P30-AG021684]; UCLA/Drew Project Centers of Excellence; National Center on Minority Health and Health Disparities [2P20MD000182]; UCLA Older Americans Independence Center (NIH/NIA) [P30-AG028748] FX Support for data collection was provided by the National Cancer Institute (Contract No. N01-PC-35136) as a contract to the Cancer Prevention Institute of California (formerly known as the Northern California Cancer Center). R. D. H. was also supported in part by the University of California, Los Angeles (UCLA) Resource Center for Minority Aging Research/Center for Health Improvement in Minority Elderly, National Institutes of Health (NIH)/National Institute on Aging (NIA) Grant No. P30-AG021684, the UCLA/Drew Project Centers of Excellence in Partnerships for Community Outreach and Research on Disparities in Health and Training, National Center on Minority Health and Health Disparities Grant No. 2P20MD000182, and the UCLA Older Americans Independence Center (NIH/NIA Grant No. P30-AG028748). NR 40 TC 47 Z9 47 U1 0 U2 9 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 APR 1 PY 2011 VL 29 IS 10 BP 1280 EP 1289 DI 10.1200/JCO.2010.32.1554 PG 10 WC Oncology SC Oncology GA 743BI UT WOS:000288990100024 PM 21357781 ER PT J AU Sheridan, MB Hefferon, TW Wang, NL Merlo, C Milla, C Borowitz, D Green, ED Mogayzel, PJ Cutting, GR AF Sheridan, Molly B. Hefferon, Timothy W. Wang, Nulang Merlo, Christian Milla, Carlos Borowitz, Drucy Green, Eric D. Mogayzel, Peter J., Jr. Cutting, Garry R. TI CFTR transcription defects in pancreatic sufficient cystic fibrosis patients with only one mutation in the coding region of CFTR SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; NASAL POTENTIAL DIFFERENCE; MESSENGER-RNA; EPITHELIAL-CELLS; SPLICING MUTATIONS; PARTIAL PENETRANCE; PULMONARY-DISEASE; MELTING ANALYSIS; GENE; IDENTIFICATION AB Background Patients with cystic fibrosis (CF) manifest a multisystem disease due to deleterious mutations in each gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). However, the role of dysfunctional CFTR is uncertain in individuals with mild forms of CF (ie, pancreatic sufficiency) and mutation in only one CFTR gene. Methods Eleven pancreatic sufficient (PS) CF patients with only one CFTR mutation identified after mutation screening (three patients), mutation scanning (four patients) or DNA sequencing (four patients) were studied. Bi-directional sequencing of the coding region of CFTR was performed in patients who had mutation screening or scanning. If a second CFTR mutation was not identified, CFTR mRNA transcripts from nasal epithelial cells were analysed to determine if any PS-CF patients harboured a second CFTR mutation that altered RNA expression. Results Sequencing of the coding regions of CFTR identified a second deleterious mutation in five of the seven patients who previously had mutation screening or mutation scanning. Five of the remaining six patients with only one deleterious mutation identified in the coding region of one CFTR gene had a pathologic reduction in the amount of RNA transcribed from their other CFTR gene (8.4-16% of wild type). Conclusions These results show that sequencing of the coding region of CFTR followed by analysis of CFTR transcription could be a useful diagnostic approach to confirm that patients with mild forms of CF harbour deleterious alterations in both CFTR genes. C1 [Sheridan, Molly B.; Wang, Nulang; Cutting, Garry R.] Johns Hopkins Med Inst, McKusicke Nathans Inst Genet Med, Baltimore, MD 21205 USA. [Sheridan, Molly B.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Hefferon, Timothy W.; Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Merlo, Christian] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. [Milla, Carlos] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. [Milla, Carlos] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. [Borowitz, Drucy] SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. [Green, Eric D.] NHGRI, NIH Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. [Mogayzel, Peter J., Jr.] Johns Hopkins Med Inst, Eudowood Div Pediat Resp Sci, Baltimore, MD 21205 USA. RP Cutting, GR (reprint author), Johns Hopkins Med Inst, McKusicke Nathans Inst Genet Med, BRB 559,733 N Broadway, Baltimore, MD 21205 USA. EM gcutting@jhmi.edu OI Milla, Carlos/0000-0001-5515-3053 FU National Institutes of Health [NIDDK R37 99003]; Cystic Fibrosis Foundation FX This work was supported by grants from the National Institutes of Health (NIDDK R37 99003 to GRC) and the Cystic Fibrosis Foundation. NR 51 TC 8 Z9 9 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2011 VL 48 IS 4 BP 235 EP 241 DI 10.1136/jmg.2010.083287 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 740IA UT WOS:000288784300004 PM 21097845 ER PT J AU Savage, SA Giri, N Jessop, L Pike, K Plona, T Burdett, L Alter, BP AF Savage, Sharon A. Giri, Neelam Jessop, Lea Pike, Kristen Plona, Teri Burdett, Laurie Alter, Blanche P. TI Sequence analysis of the shelterin telomere protection complex genes in dyskeratosis congenita SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MARROW FAILURE SYNDROMES; MUTATIONS; DIVERSITY; CANCER; LENGTH; COHORT; TINF2 AB Background Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterised by dystrophic nails, abnormal skin pigmentation and oral leukoplakia. Patients are at very high risk of cancer and other medical problems. They have exceedingly short telomeres for their age and approximately 60% have a germline mutation in a gene important in telomere biology (DKC1, TERC, TERT, TINF2, NOP10, or NHP2). The shelterin complex consists of six proteins encoded by TINF2, ACD, POT1, TERF1, TERF2 and TERF2IP, which are essential for telomeric stability. TINF2 mutations are present in 11-25% of patients with DC. Methods Bi-directional sequence analysis was conducted of all exons, intron-exon boundaries and the proximal promoter of the other five shelterin genes to determine whether mutations in these genes were associated with DC. Sixteen mutation-negative patients, nine with DC and seven patients with short telomeres and bone marrow failure, were evaluated. Results Two variants were identified, ACD Ex1+189 G -> A and TERF1 Ex9+59 G -> A, which were each present in one patient and a healthy parent but absent in 364 controls. Three other variants were rare (<1%) but present in both patients and controls. Discussion These data suggest that except for TINF2, mutations in shelterin genes are not a common cause of DC. C1 [Savage, Sharon A.; Giri, Neelam; Alter, Blanche P.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Jessop, Lea] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Pike, Kristen; Plona, Teri] NCI, Adv Technol Program, SAIC Frederick, Frederick, MD 21701 USA. [Burdett, Laurie] NCI Frederick, Core Genotyping Facil, SAIC Frederick Inc, Gaithersburg, MD USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7018, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 FU NIH [N02-CP-11019, N02-CP-65504, N02-CP-65501]; Lisa Leathwood, RN, Westat, Inc; National Cancer Institute, National Institutes of Health FX The authors are very grateful to the patients, their families and referring clinicians for their generous contributions to this study. Lisa Leathwood, RN, Westat, Inc (NIH contracts N02-CP-11019, N02-CP-65504 and N02-CP-65501) provided outstanding study support. The authors also wish to thank Drs Mark H Greene and Stephen J Chanock, National Cancer Institute, for helpful advice and laboratory support.; This work was supported by the intramural research programme of the National Cancer Institute, National Institutes of Health. NR 20 TC 7 Z9 8 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2011 VL 48 IS 4 BP 285 EP 288 DI 10.1136/jmg.2010.082727 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 740IA UT WOS:000288784300013 PM 21209122 ER PT J AU Asthagiri, AR Mehta, GU Butman, JA Baggenstos, M Oldfield, EH Lonser, RR AF Asthagiri, Ashok R. Mehta, Gautam U. Butman, John A. Baggenstos, Martin Oldfield, Edward H. Lonser, Russell R. TI Long-term stability after multilevel cervical laminectomy for spinal cord tumor resection in von Hippel-Lindau disease Clinical article SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE cervical laminectomy; instability; neck disability index; spinal cord tumor; spinal deformity; von Hippel-Lindau disease ID POSTLAMINECTOMY KYPHOSIS; NATURAL-HISTORY; INSTABILITY; ARTIFACTS; DEFORMITY; SYSTEM; HEMANGIOBLASTOMAS; LAMINOPLASTY; DECOMPRESSION; MYELOPATHY AB Object. Despite the frequent multiplicity and development of new spinal cord hemangioblastomas that require multiple resections in patients with von Hippel-Lindau (VHL) disease, the long-term effects of spinal surgery on spinal column stability in this neoplasia disorder are not known. To determine the effect of multilevel cervical laminectomy for spinal cord tumor resection in VHL, the authors analyzed long-term clinical and radiographic outcomes. Methods. The authors included consecutive patients enrolled in a prospective VHL disease natural history study who underwent cervical laminectomy(s) for spinal cord hemangioblastoma resection. Serial clinical examinations, neck disability indices, and radiographs (static and dynamic), as well as operative records, were analyzed. Results. Twenty-five adult patients (16 female, 9 male) with VHL disease underwent 34 operations (mean 1.4 +/- 0.7 [+/-SD]/patient) for the resection of cervical spinal cord hemangioblastomas (mean number of lamina removed/surgery 3.0 +/- 1.3). The mean age at surgery was 33.9 +/- 11.9 years (range 18-61 years), and the mean follow-up duration was 9.1 +/- 5.6 years. At last follow-up, radiographic criteria indicated that 9 patients (36%) had spinal column instability, 13 patients (52%) developed a cervical spinal deformity, 4 patients (16%) developed moderate to severe neck disability, and 3 patients (12%) met the criteria for clinical instability. Removal of the C-2 lamina was associated with the development of clinical instability (p = 0,02, Fisher exact test); older age at surgery was associated with the development of cervical deformity (p = 0.05, logistic regression); and a greater number of operations (suboccipital T4) were associated with increased neck disability indices (p = 0.01, linear regression). Conclusions. Whereas patients with VHL disease will often require multiple laminectomies for cervical spinal cord hemangioblastoma resection, a limited number of patients (12%) will develop clinical instability. Because prophylactic cervical instrumentation confers limited benefit at the time of spinal cord tumor resection for most patients, and because these patients need life-long MR imaging of the spinal cord, the quality of which may be affected by instrumentation, longitudinal clinical and radiological evaluation may be used to determine which patients will require stabilization. (DOI:10.3171/2010.11.SPINE10429) C1 [Asthagiri, Ashok R.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Asthagiri, AR (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA. EM asthagiria@ninds.nih.gov RI Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU National Institute of Neurological Disorders and Stroke at the NIH FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the NIH. NR 46 TC 4 Z9 6 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 EI 1547-5646 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD APR PY 2011 VL 14 IS 4 BP 444 EP 452 DI 10.3171/2010.11.SPINE10429 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 739NZ UT WOS:000288726200003 PM 21275550 ER PT J AU Abdelmegeed, MA Yoo, SH Henderson, LE Gonzalez, FJ Woodcroft, KJ Song, BJ AF Abdelmegeed, Mohamed A. Yoo, Seong-Ho Henderson, Lauren E. Gonzalez, Frank J. Woodcroft, Kimberley J. Song, Byoung-Joon TI PPAR alpha Expression Protects Male Mice from High Fat-Induced Nonalcoholic Fatty Liver SO JOURNAL OF NUTRITION LA English DT Article ID KINASE ACTIVATION; CHOLINE-DEFICIENT; OXIDATIVE STRESS; HEPATOMA-CELLS; MOUSE-LIVER; KAPPA-B; STEATOHEPATITIS; DISEASE; DIET; MODEL AB Emerging evidence suggests that the lack of PPAR alpha enhances hepatic steatosis and inflammation in Ppara-null mice when fed a high-fat diet (HFD). Thus, the aim of this study was to determine whether Ppara-null mice are more susceptible to nonalcoholic steatohepatitis (NASH) than their wild-type (WT) counterparts following short-term feeding with a HFD. Age-matched male WT and Ppara-null mice were randomly assigned to consume ad libitum a standard Lieber-DeCarli liquid diet (STD) (35% energy from fat) or a HFD (71% energy from fat) for 3 wk. Liver histology, plasma transaminase levels, and indicators of oxidative/nitrosative stress and inflammatory cytokines were evaluated in all groups. Levels of lobular inflammation and the NASH activity score were greater in HFD-exposed Ppara-null mice than in the other 3 groups. Biochemical analysis revealed elevated levels of ethanol-inducible cytochrome P450 2E1 and TNF alpha accompanied by increased levels of malondialdehyde as well as oxidized and nitrated proteins in Ppara-null mice. Elevated oxidative stress and inflammation were associated with activation of c-Jun-N-terminal kinase and p38 kinase, resulting in increased hepatocyte apoptosis in Ppara-null mice fed a HFD. These results, with increased steatosis, oxidative stress, and inflammation observed in Ppara-null mice fed a HFD, demonstrate that inhibition of PPAR alpha functions may increase susceptibility to high fat induced NASH. J. Nutr. 141: 603-610, 2011. C1 [Abdelmegeed, Mohamed A.; Yoo, Seong-Ho; Henderson, Lauren E.; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Woodcroft, Kimberley J.] Henry Ford Hlth Syst, Biostat & Res Epidemiol, Detroit, MI 48202 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. EM bj.song@nih.gov FU National Institute on Alcohol Abuse and Alcoholism FX Supported by the Intramural Research Fund of the National Institute on Alcohol Abuse and Alcoholism. NR 43 TC 94 Z9 98 U1 0 U2 10 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 APR PY 2011 VL 141 IS 4 BP 603 EP 610 DI 10.3945/jn.110.135210 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 741PU UT WOS:000288876800010 PM 21346097 ER PT J AU Wastney, ME Combs, GF Canfield, WK Taylor, PR Patterson, KY Hill, AD Moler, JE Patterson, BH AF Wastney, Meryl E. Combs, Gerald F., Jr. Canfield, Wesley K. Taylor, Philip R. Patterson, Kristine Y. Hill, A. David Moler, James E. Patterson, Blossom H. TI A Human Model of Selenium that Integrates Metabolism from Selenite and Selenomethionine SO JOURNAL OF NUTRITION LA English DT Article ID HUMAN-BODY FLUIDS; SELENOPROTEIN-P; CONTAINING PROTEINS; MASS-SPECTROMETRY; KINETIC-MODEL; RED-CELL; PLASMA; SPECIATION; WOMEN; CHROMATOGRAPHY AB Selenium (Se) metabolism is affected by its chemical form in foods and by its incorporatior (specific vs nonspecific) into multiple proteins. Moor:lino Se kinetics may clarify the impact of form or metabolism. Although the kinetics of Se forms have been compared in different participants, or the same participants at different times, direct comparisons of their respective metabolism in :he same participants have rot been made. The aim of this study was to simultaneous y compare kinetics of absorbed Se from inorganic selerite (Sol) and organic selenomethionine (SeMet) in healthy participants (n= 31). After oral administration of staple solopic trace's of each form, urine and feces were collected for 12 d and blood was sampled over 4 mo. Tracer enrichment was determined by isotope-dilutior-GC-MS. Using WinSAAM, a compartmental model was fited to the data Within 30 mn of ingest on, Se from both forms entered a common poo., and metabolism was similar for severa days before diverging. Slow y turning-over pools were required in tissues and plasma for Se derived from SeMet to account for its 3-times-higher incorporation into RBC compared with Se from Sal; these presumably represent nonspecific incorporation of SeMet into proteins. Pool sizes and transport rates were determined and comparea by form and gender. The final model consisted of 11 plasma pools, 2 pools and a delay in RBC, and extravascular pools for recycling of Se back into plasma. This model will be used to evaluate charges in Se metabolism following long-term (2 y) Se supplementation. J. Nutr. 141: 708-717. 2011. C1 [Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wastney, Meryl E.] Metab Modeling Serv Ltd, Blenheim 7201, New Zealand. [Combs, Gerald F., Jr.; Canfield, Wesley K.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Combs, Gerald F., Jr.; Canfield, Wesley K.] USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. [Patterson, Blossom H.] NCI, Canc Prevent Div, Biometry Res Grp, Bethesda, MD 20892 USA. [Patterson, Kristine Y.; Hill, A. David] USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Moler, James E.] Informat Management Serv Inc, Rockville, MD 20852 USA. RP Taylor, PR (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. OI Moler, James/0000-0001-8738-6898 FU National Cancer Institute [Y1-SC-0023]; USDA; NIH, the National Cancer Institute; The Division of Cancer Epidemiology and Genetics FX Supported by Interagency Agreement Y1-SC-0023 between the National Cancer Institute and USDA This research was supported in part by the Intramural Research Program of the NIH, the National Cancer Institute, and The Division of Cancer Epidemiology and Genetics. NR 50 TC 18 Z9 18 U1 0 U2 17 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2011 VL 141 IS 4 BP 708 EP 717 DI 10.3945/jn.110129049 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 741PU UT WOS:000288876800026 PM 21289202 ER PT J AU Baumann, MH Clark, RD Woolverton, WL Wee, SM Blough, BE Rothman, RB AF Baumann, Michael H. Clark, Robert D. Woolverton, William L. Wee, Sunmee Blough, Bruce E. Rothman, Richard B. TI In Vivo Effects of Amphetamine Analogs Reveal Evidence for Serotonergic Inhibition of Mesolimbic Dopamine Transmission in the Rat SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RHESUS-MONKEYS; LOCOMOTOR-ACTIVITY; DIALYSATE LEVELS; AGONIST-LIKE; RELEASE; PHARMACOTHERAPY; TRANSPORTERS; DEPENDENCE; BRAIN; DRUGS AB Evidence suggests that elevations in extracellular serotonin (5-HT) in the brain can diminish stimulant effects of dopamine (DA). To assess this proposal, we evaluated the pharmacology of amphetamine analogs (m-fluoroamphetamine, p-fluoroamphetamine, m-methylamphetamine, p-methylamphetamine), which display similar in vitro potency as DA releasers (EC(50) = 24-52 nM) but differ in potency as 5-HT releasers (EC(50) = 53-1937 nM). In vivo microdialysis was used to assess the effects of drugs on extracellular DA and 5-HT in rat nucleus accumbens, while simultaneously measuring ambulation (i.e., forward locomotion) and stereotypy (i.e., repetitive movements). Rats received two intravenous injections of drug, 1 mg/kg at time 0 followed by 3 mg/kg 60 min later. All analogs produced dose-related increases in dialysate DA and 5-HT, but the effects on DA did not agree with in vitro predictions. Maximal elevation of dialysate DA ranged from 5- to 14-fold above baseline and varied inversely with 5-HT response, which ranged from 6- to 24-fold above baseline. All analogs increased ambulation and stereotypy, but drugs causing greater 5-HT release (e. g., p-methylamphetamine) were associated with significantly less forward locomotion. The magnitude of ambulation was positively correlated with extracellular DA (p < 0.001) and less so with the ratio of DA release to 5-HT release (i.e., percentage DA increase divided by percentage 5-HT increase) (p < 0.029). Collectively, our findings are consistent with the hypothesis that 5-HT release dampens stimulant effects of amphetamine-type drugs, but further studies are required to address the precise mechanisms underlying this phenomenon. C1 [Baumann, Michael H.; Rothman, Richard B.] NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Clark, Robert D.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Woolverton, William L.; Wee, Sunmee] Univ Mississippi, Med Ctr, Dept Psychiat & Pharmacol & Toxicol, Jackson, MS 39216 USA. [Blough, Bruce E.] Res Triangle Inst Int, Life Sci Grp, Res Triangle Pk, NC USA. RP Rothman, RB (reprint author), NIDA, Translat Pharmacol Sect, Intramural Res Program, NIH, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU National Institutes of Health, National Institute on Drug Abuse [5R01DA012970-10] FX This work was supported by in part by the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse; and the National Institutes of Health National Institute on Drug Abuse [Grant 5R01DA012970-10]. NR 47 TC 45 Z9 45 U1 2 U2 5 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 APR PY 2011 VL 337 IS 1 BP 218 EP 225 DI 10.1124/jpet.110.176271 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738OL UT WOS:000288649700026 PM 21228061 ER PT J AU Baler, RD Volkow, ND AF Baler, Ruben D. Volkow, Nora D. TI Addiction as a Systems Failure: Focus on Adolescence and Smoking SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE drug abuse; addiction; dopamine; adolescence; systems biology ID COCAINE-INDUCED PLASTICITY; GENOME-WIDE ASSOCIATION; ILLICIT DRUG-USE; SUBSTANCE USE; NICOTINE DEPENDENCE; ENVIRONMENTAL-INFLUENCES; EPIGENETIC MECHANISMS; NATIONAL COMORBIDITY; DEPRESSIVE SYMPTOMS; EUROPEAN-AMERICANS AB Objective: Scientific advances in the field of addiction have forever debunked the notion that addiction reflects a character flaw under voluntary control, demonstrating instead that it is a bona fide disease of the brain. The aim of this review is to go beyond this consensus understanding and explore the most current evidence regarding the vast number of genetic, developmental, and environmental factors whose complex interactions modulate addiction risk and trajectory. Method: Focusing on childhood and adolescent smoking as a paradigm, we review the important risk factors for the development of addictions, starting at the level of genetics and closing with a focus on sociocultural and policy factors. Results: A critical review of the pertinent literature provides a detailed view of the cumulative power of risk and protection factors across different phenomenological levels to modulate the risk of undesirable outcomes, particularly for young people. The result represents a compelling argument for the need to engage in comprehensive, multilevel approaches to promoting health. Conclusions: Today, the field of medicine understands more about disease than about health; however it need not be that way. The view of drug addiction as a systems failure should help refocus our general approach to developing dynamic models and early comprehensive interventions that optimize the ways in which we prevent and treat a complex, developmental disorder such as drug addiction. J. Am. Acad. Child Adolesc. Psychiatry, 2011;50(4): 329-339. C1 [Baler, Ruben D.; Volkow, Nora D.] NIDA, NIH, Bethesda, MD 20892 USA. RP Baler, RD (reprint author), 6001 Execut Blvd,Room 5241, Bethesda, MD 20892 USA. EM balerr@mail.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 115 TC 13 Z9 13 U1 1 U2 43 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 APR PY 2011 VL 50 IS 4 BP 329 EP 339 DI 10.1016/j.jaac.2010.12.008 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 742EV UT WOS:000288925000005 PM 21421173 ER PT J AU Markey, SP Milne, B Hess, S Koenig, S Pannell, L Ferretti, J Balaban, B Gottesman, M AF Markey, Sanford P. Milne, Bill Hess, Sonja Koenig, Simone Pannell, Lewis Ferretti, Jim Balaban, Bob Gottesman, Michael TI Henry M. Fales, February 12, 1927-October 28, 2010 OBITUARY SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Biographical-Item C1 [Markey, Sanford P.; Milne, Bill; Hess, Sonja; Koenig, Simone; Pannell, Lewis; Ferretti, Jim; Balaban, Bob; Gottesman, Michael] NIH, Bethesda, MD 20892 USA. RP Markey, SP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM markeys@mail.nih.gov RI Konig, Simone/B-6504-2008 OI Konig, Simone/0000-0003-0672-7246 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 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD APR PY 2011 VL 22 IS 4 BP 789 EP 790 DI 10.1007/s13361-011-0078-z PG 2 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 739JQ UT WOS:000288713600018 PM 21472616 ER PT J AU Cho, YG Cao, XG Shen, DF Tuo, JS Parver, LM Rickles, FR Chan, CC AF Cho, Youngeun Cao, Xiaoguang Shen, DeFen Tuo, Jingsheng Parver, Leonard M. Rickles, Frederick R. Chan, Chi-Chao TI Evidence for enhanced tissue factor expression in age-related macular degeneration SO LABORATORY INVESTIGATION LA English DT Article DE age-related macular degeneration; inflammation; oxidative stress; retina; retinal pigment epithelium; tissue factor ID CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL-CELLS; MOUSE MODEL; FACTOR GENE; ANGIOGENESIS; THROMBOSIS; DRUSEN; INFLAMMATION; DISEASE; IMMUNOTHERAPY AB Tissue factor (TF) is the primary initiator of blood coagulation. In addition to hemostasis, TF can initiate intracellular signaling and promote inflammation and angiogenesis, the key processes underlying the pathogenesis of age-related macular degeneration (AMD). AMD, the leading cause of irreversible blindness among the elderly, involves many genetic and environmental risk factors, including oxidative stress and inflammation. In this study, TF expression was examined in human AMD tissue and in the eyes of a model of AMD, the Ccl2(-/-)/Cx3cr1(-/-) (DKO) mouse, as well as in the ARPE-19 cell line after lipopolysaccharide (LPS) and H(2)O(2) stimulation. Total RNA was extracted from tissue samples and further analyzed by real-time RT-PCR. Immunohistochemistry was performed to evaluate TF protein expression. In the human retina, a 32-fold increase of TF mRNA expression was detected in AMD macular lesions compared with normal maculae. TF protein expression was also enhanced in human AMD maculae. Similarly, TF transcript and protein expression were moderately increased in retinal lesions, neuroretinal tissue, and cultured RPE cells of DKO mice compared with age-matched wild-type mice. TF expression level correlated with age in both wild-type and DKO mice. In order to better understand how AMD might lead to enhanced TF expression, 1, 5, and 10 mu g/ml LPS as well as 100 and 200 mu M H(2)O(2) were used to stimulate ARPE-19 cells for 24 and 2 h, respectively. LPS treatment consistently increased TF transcript and protein expression. H(2)O(2) alone or in combination with LPS also moderately enhanced TF expression. These results indicate that upregulated TF expression may be associated with AMD, and inflammatory and oxidative stress may contribute to TF expression in AMD eyes. Laboratory Investigation (2011) 91, 519-526; doi:10.1038/labinvest.2010.184; published online 1 November 2010 C1 [Cho, Youngeun; Cao, Xiaoguang; Shen, DeFen; Tuo, Jingsheng; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Cao, Xiaoguang] Peking Univ, Dept Ophthalmol, Peoples Hosp, Beijing 100871, Peoples R China. [Parver, Leonard M.] Georgetown Univ, Sch Med, Dept Ophthalmol, Washington, DC USA. [Rickles, Frederick R.] George Washington Univ, Sch Med & Hlth Sci, Dept Med, Washington, DC 20052 USA. [Rickles, Frederick R.] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. [Rickles, Frederick R.] George Washington Univ, Sch Med & Hlth Sci, Dept Physiol & Pharmacol, Washington, DC 20052 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov OI Tuo, Jingsheng/0000-0002-1372-7810 FU National Eye Institute, National Institutes of Health FX This study was supported by the Intramural Research Program of the National Eye Institute, National Institutes of Health. NR 40 TC 14 Z9 14 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2011 VL 91 IS 4 BP 519 EP 526 DI 10.1038/labinvest.2010.184 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 742JE UT WOS:000288937400004 PM 21042291 ER PT J AU Trotter, JF Gillespie, BW Terrault, NA Abecassis, MM Merion, RM Brown, RS Olthoff, KM Hayashi, PH Berg, CL Fisher, RA Everhart, JE AF Trotter, James F. Gillespie, Brenda W. Terrault, Norah A. Abecassis, Michael M. Merion, Robert M. Brown, Robert S., Jr. Olthoff, Kim M. Hayashi, Paul H. Berg, Carl L. Fisher, Robert A. Everhart, James E. CA Adult-to-Adult Living Donor Liver TI Laboratory Test Results After Living Liver Donation in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study SO LIVER TRANSPLANTATION LA English DT Article ID RIGHT HEPATECTOMY; PLATELET COUNT; COMPLICATIONS; REGENERATION; MORBIDITY; SAFETY; VOLUME AB Information on the long-term health of living liver donors is incomplete. Because changes in standard laboratory tests may reflect the underlying health of donors, results before and after donation were examined in the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). A2ALL followed 487 living liver donors who donated at 9 US transplant centers between 1998 and 2009. The aminotransferase [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and alkaline phosphatase (AP) activities, bilirubin, international normalized ratio (INR), albumin, white blood cell count (WBC), hemoglobin (HGB), platelet count, ferritin, serum creatinine (SCR), and blood urea nitrogen (BUN) were measured at the evaluation and after donation (1 week, 1 month, 3 months, 1 year, and yearly thereafter). Repeated measures models were used to estimate median laboratory values at each time point and to test for differences between values at the evaluation (baseline) and postdonation time points. Platelet counts were significantly decreased at every time point in comparison with the baseline, and at 3 years, they were 19% lower. Approximately 10% of donors had a platelet count < 150 x 1000/mm(3) 2 to 3 years post-donation. Donors with a platelet count <= 150 x 1000/mm(3) at 1 year had significantly lower mean platelet counts (189 +/- 32 x 1000/mm(3)) versus the remainder of the cohort (267 +/- 56 x 1000/mm(3), P < 0.0001) at the evaluation. Statistically significant differences compared to the evaluation values were noted for AST, AP, INR, and albumin through the first year, although most measurements were in the normal range. The median values for WBC, HGB, ferritin, albumin, SCR, BUN, and INR were not substantially outside the normal range at any time point. In conclusion, after 3 months, most laboratory values return to normal among right hepatic lobe liver donors, with a slower return to baseline levels for AST, AP, INR, and albumin. Persistently decreased platelet counts warrant further investigation. Liver Transpl 17:409-417, 2011. (C) 2011 AASLD. C1 [Trotter, James F.] Univ Colorado, Dept Surg, Aurora, CO USA. [Gillespie, Brenda W.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Merion, Robert M.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Terrault, Norah A.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Abecassis, Michael M.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Brown, Robert S., Jr.] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Olthoff, Kim M.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Hayashi, Paul H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Berg, Carl L.] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA USA. [Fisher, Robert A.] Virginia Commonwealth Univ, Coll Med, Virginia Hosp, Dept Surg, Richmond, VA USA. [Everhart, James E.] NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Trotter, JF (reprint author), Baylor Univ, Med Ctr, 3500 Gaston Ave, Dallas, TX 75246 USA. EM james.trotter@baylorhealth.edu RI Abecassis, Michael/F-7977-2011 FU National Institute of Diabetes and Digestive and Kidney Diseases FX This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases through cooperative agreements (listed in parentheses). Additional support was provided by the Health Resources and Services Administration and the American Society of Transplant Surgeons. The following individuals were instrumental in the planning, conduct, and/or care of patients enrolled in this study at each of the participating institutions: NR 19 TC 27 Z9 27 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD APR PY 2011 VL 17 IS 4 BP 409 EP 417 DI 10.1002/lt.22246 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 743FV UT WOS:000289004000008 PM 21445924 ER PT J AU Ranguelova, K Mason, RP AF Ranguelova, Kalina Mason, Ronald P. TI The fidelity of spin trapping with DMPO in biological systems SO MAGNETIC RESONANCE IN CHEMISTRY LA English DT Article DE ESR; spin trap; DMPO; sulfite radicals ID TRIOXIDE RADICAL-ANION; N-TERT-BUTYLNITRONE; HORSERADISH-PEROXIDASE; CATALYZED OXIDATION; AQUEOUS-SOLUTION; NUCLEOPHILIC-ADDITION; NONRADICAL ADDITION; CAUTIONARY NOTE; SULFUR-DIOXIDE; RATE CONSTANTS AB Unlike direct ESR, spin trap methodology depends on the absolute fidelity of the spin trap reaction. Two alternative reactions of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) leading to radical adduct artifacts have been discovered and investigated: inverted spin trapping and the Forrester-Hepburn nucleophilic mechanism. These two alternate pathways to radical adducts are a combination of one-electron oxidation and nucleophilic addition, in either order. In biological systems, serious artifacts have been reported due to the Forrester-Hepburn mechanism, which is initiated by the addition of a nucleophile to DMPO. It has recently been demonstrated that (bi) sulfite (hydrated sulfur dioxide) can react with DMPO via a nonradical, nucleophilic reaction, ;and it has been further proposed that DMPO/(center dot)SO(3)(-) formation in biological systems is an artifact and not the result of spin trapping of sulfur trioxide anion radical ((center dot)SO3(-)). The one-electron oxidation of (bi) sulfite catalyzed by horseradish peroxidase (HRP)/hydrogen peroxide (H(2)O(2)) has been reinvestigated by ESR spin trapping with DMPO and oxygen uptake studies to obtain further evidence for the radical reaction mechanism. In the absence of DMPO, the initial rate of (bi) sulfite-dependent oxygen and H(2)O(2) consumption was determined to be half of the initial rate of DMPO/(center dot)SO(3)(-) radical adduct formation as determined by ESR, demonstrating that, under our experimental conditions, DMPO exclusively forms the radical adduct by trapping the (center dot)SO(3)(-). Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, NIH, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. RP Mason, RP (reprint author), NIEHS, NIH, Lab Toxicol & Pharmacol, MD F0-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM mason4@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences FX We would like to acknowledge Mrs Mary Mason, Dr Ann Motten, and Ms Jean Corbett for editing this manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. NR 48 TC 30 Z9 30 U1 1 U2 29 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0749-1581 J9 MAGN RESON CHEM JI Magn. Reson. Chem. PD APR PY 2011 VL 49 IS 4 BP 152 EP 158 DI 10.1002/mrc.2709 PG 7 WC Chemistry, Multidisciplinary; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 741IN UT WOS:000288857500002 PM 21246623 ER PT J AU Zhang, L Kerkar, SP Yu, ZY Zheng, ZL Yang, SC Restifo, NP Rosenberg, SA Morgan, RA AF Zhang, Ling Kerkar, Sid P. Yu, Zhiya Zheng, Zhili Yang, Shicheng Restifo, Nicholas P. Rosenberg, Steven A. Morgan, Richard A. TI Improving Adoptive T Cell Therapy by Targeting and Controlling IL-12 Expression to the Tumor Environment SO MOLECULAR THERAPY LA English DT Article ID METASTATIC MELANOMA; GENE-THERAPY; PHASE-I; ENGINEERED LYMPHOCYTES; HUMAN INTERLEUKIN-12; ANTITUMOR-ACTIVITY; CANCER REGRESSION; IMMUNE-RESPONSES; INTERFERON-GAMMA; ANTIGEN AB Interleukin-12 (IL-12) is an important immunostimulatory cytokine, yet its clinical application has been limited by the systemic toxicity associated with its administration. In this work, we developed a strategy to selectively deliver IL-12 to the tumor environment using genetically engineered lymphocytes. However, peripheral blood lymphocytes (PBLs) transduced with a.-retroviral vector, which constitutively expressed IL-12, failed to expand in culture due to apoptosis. To circumvent this problem, a vector was designed where IL-12 expression was directed by a composite promoter-containing binding motifs for nuclear factor of activated T-cells (NFAT.hIL12.PA2). The NFAT-responsive promoter was activated to drive IL-12 expression upon the recognition of tumor-specific antigen mediated by a T cell receptor (TCR) that was engineered into the same lymphocytes. We tested the efficacy of the inducible IL-12 vector in vivo in a murine melanoma model. Adoptive transfer of pmel-1 T cells genetically engineered with NFAT-murineIL12 (NFAT. mIL12.PA2) significantly enhanced regression of large established B16 melanoma. Notably, this targeted and controlled IL-12 treatment was without toxicity. Taken together, our results suggest that using the NFAT.hIL12. PA2 vector might be a promising approach to enhance adoptive cancer immunotherapy. C1 [Zhang, Ling; Kerkar, Sid P.; Yu, Zhiya; Zheng, Zhili; Yang, Shicheng; Restifo, Nicholas P.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10-CRC,Room 3W-3-5940,10 Ctr Dr, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The authors thank Arnold Mixon and Shawn Farid for their assistance in flow cytometry, Dana Chinnasamy for discussion on mice data, David Jones, Lindsay Garvin, and Douglas C. Palmer for help in mice experiments. The authors declared no conflict of interest. NR 50 TC 79 Z9 81 U1 3 U2 18 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 APR PY 2011 VL 19 IS 4 BP 751 EP 759 DI 10.1038/mt.2010.313 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 744FC UT WOS:000289079300018 PM 21285960 ER PT J AU Fuchs, BB Bishop, LR Kovacs, JA Mylonakis, E AF Fuchs, Beth Burgwyn Bishop, Lisa R. Kovacs, Joseph A. Mylonakis, Eleftherios TI Galleria mellonella are Resistant to Pneumocystis murina Infection SO MYCOPATHOLOGIA LA English DT Article DE Galleria mellonella; Infection model; Pneumocystis murina ID IMMUNE-RESPONSE; CARINII; VIRULENCE; LARVAE; MODEL; MICE; PATHOGENICITY; EXPRESSION AB Studying Pneumocystis has proven to be a challenge from the perspective of propagating a significant amount of the pathogen in a facile manner. The study of several fungal pathogens has been aided by the use of invertebrate model hosts. Our efforts to infect the invertebrate larvae Galleria mellonella with Pneumocystis proved futile since P. murina neither caused disease nor was able to proliferate within G. mellonella. It did, however, show that the pathogen could be rapidly cleared from the host. C1 [Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bishop, Lisa R.; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Fuchs, BB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM hfuchs@partners.org; emylonakis@partners.org FU Intramural NIH HHS [ZIA CL000146-19] NR 18 TC 6 Z9 6 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0301-486X J9 MYCOPATHOLOGIA JI Mycopathologia PD APR PY 2011 VL 171 IS 4 BP 273 EP 277 DI 10.1007/s11046-010-9368-4 PG 5 WC Mycology SC Mycology GA 738TJ UT WOS:000288664900006 PM 20922567 ER PT J AU Giardine, B Borg, J Higgs, DR Peterson, KR Philipsen, S Maglott, D Singleton, BK Anstee, DJ Basak, AN Clark, B Costa, FC Faustino, P Fedosyuk, H Felice, AE Francina, A Galanello, R Gallivan, MVE Georgitsi, M Gibbons, RJ Giordano, PC Harteveld, CL Hoyer, JD Jarvis, M Joly, P Kanavakis, E Kollia, P Menzel, S Miller, W Moradkhani, K Old, J Papachatzopoulou, A Papadakis, MN Papadopoulos, P Pavlovic, S Perseu, L Radmilovic, M Riemer, C Satta, S Schrijver, I Stojiljkovic, M Thein, SL Traeger-Synodinos, J Tully, R Wada, T Waye, JS Wiemann, C Zukic, B Chui, DHK Wajcman, H Hardison, RC Patrinos, GP AF Giardine, Belinda Borg, Joseph Higgs, Douglas R. Peterson, Kenneth R. Philipsen, Sjaak Maglott, Donna Singleton, Belinda K. Anstee, David J. Basak, A. Nazli Clark, Barnaby Costa, Flavia C. Faustino, Paula Fedosyuk, Halyna Felice, Alex E. Francina, Alain Galanello, Renzo Gallivan, Monica V. E. Georgitsi, Marianthi Gibbons, Richard J. Giordano, Piero C. Harteveld, Cornelis L. Hoyer, James D. Jarvis, Martin Joly, Philippe Kanavakis, Emmanuel Kollia, Panagoula Menzel, Stephan Miller, Webb Moradkhani, Kamran Old, John Papachatzopoulou, Adamantia Papadakis, Manoussos N. Papadopoulos, Petros Pavlovic, Sonja Perseu, Lucia Radmilovic, Milena Riemer, Cathy Satta, Stefania Schrijver, Iris Stojiljkovic, Maja Thein, Swee Lay Traeger-Synodinos, Jan Tully, Ray Wada, Takahito Waye, John S. Wiemann, Claudia Zukic, Branka Chui, David H. K. Wajcman, Henri Hardison, Ross C. Patrinos, George P. TI Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach SO NATURE GENETICS LA English DT Article ID SICKLE-CELL-ANEMIA; FACTOR KLF1 CAUSES; FETAL-HEMOGLOBIN; ALPHA-THALASSEMIA; DYSERYTHROPOIETIC ANEMIA; SEQUENCE VARIATION; BETA-THALASSEMIA; MUTATIONS; GLOBIN; VARIANTS AB We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories. A total of 1,941 unique genetic variants in 37 genes, encoding globins and other erythroid proteins, are currently documented in these databases, with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants, leading to a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The principles established here will serve as a model for other systems and for the analysis of other common and/or complex human genetic diseases. C1 [Georgitsi, Marianthi; Patrinos, George P.] Univ Patras, Dept Pharm, Sch Hlth Sci, Patras, Greece. [Giardine, Belinda; Miller, Webb; Riemer, Cathy; Hardison, Ross C.] Penn State Univ, Ctr Comparat Genom & Bioinformat, Philadelphia, PA USA. [Borg, Joseph] Univ Malta, Dept Appl Biomed Sci, Msida, Malta. [Borg, Joseph; Felice, Alex E.] Univ Malta, Dept Physiol & Biochem, Lab Mol Genet, Msida, Malta. [Borg, Joseph; Felice, Alex E.] Mater Dei Hosp, Sect Pathol, Thalassemia Clin, Msida, Malta. [Higgs, Douglas R.; Gibbons, Richard J.] Weatherall Inst Mol Med, MRC, Mol Haematol Unit, Oxford, England. [Peterson, Kenneth R.; Costa, Flavia C.; Fedosyuk, Halyna] Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS USA. [Philipsen, Sjaak; Papadopoulos, Petros] Erasmus Univ, Fac Med & Hlth Sci, Med Ctr, Dept Cell Biol, NL-3000 DR Rotterdam, Netherlands. [Maglott, Donna; Tully, Ray] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Singleton, Belinda K.; Anstee, David J.] Bristol Inst Transfus Sci BITS, Natl Hlth Serv NHS Blood & Transplant, Bristol, Avon, England. [Basak, A. Nazli] Bogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey. [Clark, Barnaby; Menzel, Stephan; Thein, Swee Lay] Kings Coll London, London WC2R 2LS, England. [Faustino, Paula] Inst Nacl Saude Dr Ricardo Jorge, Unidade Invest & Desenvolvimento, Dept Genet, Lisbon, Portugal. [Francina, Alain; Joly, Philippe] Edouard Herriot Univ Hosp, Dept Biochem, Lyon, France. [Galanello, Renzo; Satta, Stefania] Univ Cagliari, Dipartimento Sci Biomed & Biotecnol, Cagliari, Sardinia, Italy. [Gallivan, Monica V. E.] Quest Diagnost Nichols Inst, Chantilly, VA USA. [Giordano, Piero C.; Harteveld, Cornelis L.] Leiden Univ, Hemoglobinopathies Lab, Human & Clin Genet Dept, Med Ctr, Leiden, Netherlands. [Hoyer, James D.] Mayo Clin, Div Hematopathol, Rochester, MN USA. [Jarvis, Martin] N Middlesex Univ Hosp, London, England. [Kanavakis, Emmanuel; Traeger-Synodinos, Jan] Univ Athens, Sch Med, St Sophias Childrens Hosp, Athens 11528, Greece. [Kollia, Panagoula] Univ Athens, Dept Biol, Sch Phys Sci, Athens 11528, Greece. [Moradkhani, Kamran; Wajcman, Henri] Hosp Henri Mondor, Creteil, France. [Moradkhani, Kamran; Wajcman, Henri] Albert Chenevier Grp, Dept Biochem & Genet, Cretile, France. [Old, John] Churchill Hosp, Natl Haemoglobinopathy Reference Lab, Oxford Haemophilia Ctr, Oxford OX3 7LJ, England. [Papachatzopoulou, Adamantia] Univ Patras, Fac Med, Lab Gen Biol, Patras, Greece. [Papadakis, Manoussos N.] Laikon Gen Hosp, Unit Prenatal Diag, Ctr Thalassemia, Athens, Greece. [Pavlovic, Sonja; Radmilovic, Milena; Stojiljkovic, Maja; Zukic, Branka] Univ Belgrade, Inst Mol Genet & Genet Engn, Belgrade, Serbia. [Perseu, Lucia] Ist Neurogenet & Neurofarmacol, Natl Res Council, Cagliari, Sardinia, Italy. [Schrijver, Iris] Stanford Univ, Sch Med, Dept Pathol & Pediat, Stanford, CA 94305 USA. [Wada, Takahito] Kanagawa Childrens Med Ctr, Div Neurol, Kanagawa, Japan. [Waye, John S.] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Waye, John S.] Hamilton Reg Lab Program, Hamilton, ON, Canada. [Wiemann, Claudia] Med Versorgungszentrum MVZ, Lab Prof Seelig, Karlsruhe, Germany. [Chui, David H. K.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Chui, David H. K.] Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. [Wajcman, Henri] Hop Henri Mondor, INSERM, U955, F-94010 Creteil, France. [Hardison, Ross C.] Penn State Univ, Dept Biochem & Mol Biol, Philadelphia, PA USA. RP Patrinos, GP (reprint author), Univ Patras, Dept Pharm, Sch Hlth Sci, Patras, Greece. EM gpatrinos@upatras.gr RI Stojiljkovic, Maja/A-4888-2013; Wiemann, Claudia/B-1746-2010; Papadopoulos, Petros/B-1913-2015; Faustino, Paula/E-4546-2010; Hardison, Ross/G-1142-2010; OI Papadopoulos, Petros/0000-0002-8342-329X; Faustino, Paula/0000-0002-6269-4867; Borg, Joseph/0000-0002-2220-5651; Hardison, Ross/0000-0003-4084-7516; Traeger-Synodinos, Jan/0000-0002-1860-5628 FU Netherlands Genomics Initiative (NGI), Erasmus MC (MRace) [296088]; Landsteiner Foundation for Blood Transfusion Research (LSBR) [1040]; US National Institutes of Health (NIH) [R01-HL073455]; Netherlands Scientific Organization [NWO DN 82-301, 912-07-019]; NIH [R01 DK065806, RC HG005573, U01 HG004695]; National Institutes for Health Research Biomedical Research Centre (Oxford); European Commission [FP6-026539, FP7-200754] FX This work was supported by the Netherlands Genomics Initiative (NGI), Erasmus MC (MRace; 296088), the Landsteiner Foundation for Blood Transfusion Research (LSBR; 1040), US National Institutes of Health (NIH) (R01-HL073455) and the Netherlands Scientific Organization (NWO DN 82-301 and 912-07-019) to S.P., the NIH grants R01 DK065806, RC HG005573 and U01 HG004695 to R.C.H., the National Institutes for Health Research Biomedical Research Centre (Oxford) to D.R.H. and European Commission grants (FP6-026539 (ITHANET), FP7-200754 (GEN2PHEN)) to G.P.P. NR 33 TC 67 Z9 68 U1 1 U2 12 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 APR PY 2011 VL 43 IS 4 BP 295 EP 302 DI 10.1038/ng.785 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 741YL UT WOS:000288903700006 PM 21423179 ER PT J AU Schunkert, H Konig, IR Kathiresan, S Reilly, MP Assimes, TL Holm, H Preuss, M Stewart, AFR Barbalic, M Gieger, C Absher, D Aherrahrou, Z Allayee, H Altshuler, D Anand, SS Andersen, K Anderson, JL Ardissino, D Ball, SG Balmforth, AJ Barnes, TA Becker, DM Becker, LC Berger, K Bis, JC Boekholdt, SM Boerwinkle, E Braund, PS Brown, MJ Burnett, MS Buysschaert, I Carlquist, JF Chen, L Cichon, S Codd, V Davies, RW Dedoussis, G Dehghan, A Demissie, S Devaney, JM Diemert, P Do, R Doering, A Eifert, S El Mokhtari, NE Ellis, SG Elosua, R Engert, JC Epstein, SE de Faire, U Fischer, M Folsom, AR Freyer, J Gigante, B Girelli, D Gretarsdottir, S Gudnason, V Gulcher, JR Halperin, E Hammond, N Hazen, SL Hofman, A Horne, BD Illig, T Iribarren, C Jones, GT Jukema, JW Kaiser, MA Kaplan, LM Kastelein, JJP Khaw, KT Knowles, JW Kolovou, G Kong, A Laaksonen, R Lambrechts, D Leander, K Lettre, G Li, MY Lieb, W Loley, C Lotery, AJ Mannucci, PM Maouche, S Martinelli, N McKeown, PP Meisinger, C Meitinger, T Melander, O Merlini, PA Mooser, V Morgan, T Muhleisen, TW Muhlestein, JB Munzel, T Musunuru, K Nahrstaedt, J Nelson, CP Nothen, MM Olivieri, O Patel, RS Patterson, CC Peters, A Peyvandi, F Qu, L Quyyumi, AA Rader, DJ Rallidis, LS Rice, C Rosendaal, FR Rubin, D Salomaa, V Sampietro, ML Sandhu, MS Schadt, E Schafer, A Schillert, A Schreiber, S Schrezenmeir, J Schwartz, SM Siscovick, DS Sivananthan, M Sivapalaratnam, S Smith, A Smith, TB Snoep, JD Soranzo, N Spertus, JA Stark, K Stirrups, K Stoll, M Tang, WHW Tennstedt, S Thorgeirsson, G Thorleifsson, G Tomaszewski, M Uitterlinden, AG van Rij, AM Voight, BF Wareham, NJ Wells, GA Wichmann, HE Wild, PS Willenborg, C Witteman, JCM Wright, BJ Ye, S Zeller, T Ziegler, A Cambien, F Goodall, AH Cupples, LA Quertermous, T Marz, W Hengstenberg, C Blankenberg, S Ouwehand, WH Hall, AS Deloukas, P Thompson, JR Stefansson, K Roberts, R Thorsteinsdottir, U O'Donnell, CJ McPherson, R Erdmann, J Samani, NJ AF Schunkert, Heribert Koenig, Inke R. Kathiresan, Sekar Reilly, Muredach P. Assimes, Themistocles L. Holm, Hilma Preuss, Michael Stewart, Alexandre F. R. Barbalic, Maja Gieger, Christian Absher, Devin Aherrahrou, Zouhair Allayee, Hooman Altshuler, David Anand, Sonia S. Andersen, Karl Anderson, Jeffrey L. Ardissino, Diego Ball, Stephen G. Balmforth, Anthony J. Barnes, Timothy A. Becker, Diane M. Becker, Lewis C. Berger, Klaus Bis, Joshua C. Boekholdt, S. Matthijs Boerwinkle, Eric Braund, Peter S. Brown, Morris J. Burnett, Mary Susan Buysschaert, Ian Carlquist, John F. Chen, Li Cichon, Sven Codd, Veryan Davies, Robert W. Dedoussis, George Dehghan, Abbas Demissie, Serkalem Devaney, Joseph M. Diemert, Patrick Do, Ron Doering, Angela Eifert, Sandra El Mokhtari, Nour Eddine Ellis, Stephen G. Elosua, Roberto Engert, James C. Epstein, Stephen E. de Faire, Ulf Fischer, Marcus Folsom, Aaron R. Freyer, Jennifer Gigante, Bruna Girelli, Domenico Gretarsdottir, Solveig Gudnason, Vilmundur Gulcher, Jeffrey R. Halperin, Eran Hammond, Naomi Hazen, Stanley L. Hofman, Albert Horne, Benjamin D. Illig, Thomas Iribarren, Carlos Jones, Gregory T. Jukema, J. Wouter Kaiser, Michael A. Kaplan, Lee M. Kastelein, John J. P. Khaw, Kay-Tee Knowles, Joshua W. Kolovou, Genovefa Kong, Augustine Laaksonen, Reijo Lambrechts, Diether Leander, Karin Lettre, Guillaume Li, Mingyao Lieb, Wolfgang Loley, Christina Lotery, Andrew J. Mannucci, Pier M. Maouche, Seraya Martinelli, Nicola McKeown, Pascal P. Meisinger, Christa Meitinger, Thomas Melander, Olle Merlini, Pier Angelica Mooser, Vincent Morgan, Thomas Muehleisen, Thomas W. Muhlestein, Joseph B. Muenzel, Thomas Musunuru, Kiran nahrstaedt, Janja Nelson, Christopher P. Noethen, Markus M. Olivieri, Oliviero Patel, Riyaz S. Patterson, Chris C. Peters, Annette Peyvandi, Flora Qu, Liming Quyyumi, Arshed A. Rader, Daniel J. Rallidis, Loukianos S. Rice, Catherine Rosendaal, Frits R. Rubin, Diana Salomaa, Veikko Sampietro, M. Lourdes Sandhu, Manj S. Schadt, Eric Schaefer, Arne Schillert, Arne Schreiber, Stefan Schrezenmeir, Juergen Schwartz, Stephen M. Siscovick, David S. Sivananthan, Mohan Sivapalaratnam, Suthesh Smith, Albert Smith, Tamara B. Snoep, Jaapjan D. Soranzo, Nicole Spertus, John A. Stark, Klaus Stirrups, Kathy Stoll, Monika Tang, W. H. Wilson Tennstedt, Stephanie Thorgeirsson, Gudmundur Thorleifsson, Gudmar Tomaszewski, Maciej Uitterlinden, Andre G. van Rij, Andre M. Voight, Benjamin F. Wareham, Nick J. Wells, George A. Wichmann, H-Erich Wild, Philipp S. Willenborg, Christina Witteman, Jaqueline C. M. Wright, Benjamin J. Ye, Shu Zeller, Tanja Ziegler, Andreas Cambien, Francois Goodall, Alison H. Cupples, L. Adrienne Quertermous, Thomas Maerz, Winfried Hengstenberg, Christian Blankenberg, Stefan Ouwehand, Willem H. Hall, Alistair S. Deloukas, Panos Thompson, John R. Stefansson, Kari Roberts, Robert Thorsteinsdottir, Unnur O'Donnell, Christopher J. McPherson, Ruth Erdmann, Jeanette Samani, Nilesh J. CA CARDIoGRAM Consortium TI Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; HEART-DISEASE; VARIANTS; DESIGN; RISK; EXPRESSION; GENETICS; ATHEROSCLEROSIS; POLYMORPHISMS AB We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. C1 [Schunkert, Heribert; Preuss, Michael; Aherrahrou, Zouhair; Diemert, Patrick; Freyer, Jennifer; Lieb, Wolfgang; Loley, Christina; Maouche, Seraya; nahrstaedt, Janja; Tennstedt, Stephanie; Willenborg, Christina; Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Koenig, Inke R.; Preuss, Michael; Loley, Christina; nahrstaedt, Janja; Schillert, Arne; Willenborg, Christina; Ziegler, Andreas] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany. [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; Musunuru, Kiran; Voight, Benjamin F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; Altshuler, David; Musunuru, Kiran; Voight, Benjamin F.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Reilly, Muredach P.; Rader, Daniel J.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Assimes, Themistocles L.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Holm, Hilma; Gretarsdottir, Solveig; Gulcher, Jeffrey R.; Kong, Augustine; Thorleifsson, Gudmar; Stefansson, Kari; Thorsteinsdottir, Unnur] DeCODE Genet, Reykjavik, Iceland. [Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Gieger, Christian; Doering, Angela; Illig, Thomas; Meisinger, Christa; Peters, Annette; Wichmann, H-Erich] German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Absher, Devin] Hudson Alpha Inst, Huntsville, TX USA. [Allayee, Hooman] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Altshuler, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Anand, Sonia S.] McMaster Univ, Hamilton, ON, Canada. [Anand, Sonia S.] Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada. [Andersen, Karl; Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. [Andersen, Karl; Gudnason, Vilmundur; Smith, Albert; Thorgeirsson, Gudmundur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Anderson, Jeffrey L.; Carlquist, John F.; Horne, Benjamin D.; Muhlestein, Joseph B.] Univ Utah, Div Cardiol, Cardiovasc Dept, Intermt Med Ctr, Salt Lake City, UT 84112 USA. [Ardissino, Diego] Univ Parma, Div Cardiol, Azienda Osped, I-43100 Parma, Italy. [Ball, Stephen G.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England. [Ball, Stephen G.; Hall, Alistair S.] Univ Leeds, Div Cardiovasc & Neuronal Remodelling, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Balmforth, Anthony J.; Nelson, Christopher P.] Univ Leeds, Div Cardiovasc & Diabet Res, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Barnes, Timothy A.; Braund, Peter S.; Codd, Veryan; Kaiser, Michael A.; Tomaszewski, Maciej; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. [Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. [Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. [Bis, Joshua C.; Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Resarch Unit, Seattle, WA 98195 USA. [Bis, Joshua C.; Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Boekholdt, S. Matthijs; Kastelein, John J. P.; Sivapalaratnam, Suthesh] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Boekholdt, S. Matthijs] Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands. [Brown, Morris J.] Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. [Burnett, Mary Susan; Devaney, Joseph M.; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, Medstar Hlth Res Inst, Washington, DC 20010 USA. [Buysschaert, Ian] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. [Buysschaert, Ian; Lambrechts, Diether] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium. [Chen, Li] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Cichon, Sven; Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Muehleisen, Thomas W.; Noethen, Markus M.] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Cichon, Sven] Inst Neurosci & Med INM 1, Res Ctr Juelich, Julich, Germany. [Dedoussis, George] Harokopio Univ, Dept Dietetics Nutr, Athens, Greece. [Dehghan, Abbas; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jaqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Demissie, Serkalem; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Do, Ron; Engert, James C.] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Eifert, Sandra; Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [El Mokhtari, Nour Eddine] Kreiskrankenhaus Rendsburg, Innere Med Klin, Rendsburg, Germany. [Ellis, Stephen G.; Tang, W. H. Wilson] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Elosua, Roberto] Ciber Epidemiol & Salud Publ CIBERSP, Cardiovasc Epidemiol & Genet Grp, Inst Municipal Invest Med, Barcelona, Spain. [Engert, James C.] McGill Univ, Dept Med, Montreal, PQ, Canada. [de Faire, Ulf; Gigante, Bruna; Leander, Karin] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [de Faire, Ulf; Gigante, Bruna] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden. [Fischer, Marcus; Stark, Klaus; Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany. [Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth ARF, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Girelli, Domenico; Martinelli, Nicola; Olivieri, Oliviero] Univ Verona, Dept Med, I-37100 Verona, Italy. [Gudnason, Vilmundur; Smith, Albert] Iceland Heart Assoc, Kopavogur, Iceland. [Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Hammond, Naomi; Rice, Catherine; Soranzo, Nicole; Stirrups, Kathy; Ouwehand, Willem H.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, S Cambs, England. [Hazen, Stanley L.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Jones, Gregory T.; van Rij, Andre M.] Univ Otago, Dunedin Sch Med, Dept Surg, Dunedin, New Zealand. [Jukema, J. Wouter] Leiden Univ, Dept Cardiol C5 P, Med Ctr, Leiden, Netherlands. [Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands. [Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England. [Kolovou, Genovefa] Onassis Cardiac Surg Ctr, Cardiol Dept 1, Athens, Greece. [Laaksonen, Reijo] Tampere Univ Hosp, Sci Ctr, Tampere, Finland. [Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Lettre, Guillaume] Univ Montreal, Dept Med, Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada. [Lotery, Andrew J.] Univ Southampton, Clin Neurosci Div, Sch Med, Southampton, Hants, England. [Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England. [Mannucci, Pier M.] Osped Maggiore Policlin, Sci Direct, IRCCS, Fdn Ca Granda, Milan, Italy. [McKeown, Pascal P.; Patterson, Chris C.] Queens Univ Belfast, Ctr Publ Hlth, Inst Clin Sci, Belfast, Ireland. [Meitinger, Thomas] Deutsch Forschungszentrum Umwelt & Gesundheit, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Melander, Olle] Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Scania Univ Hosp, Malmo, Sweden. [Merlini, Pier Angelica] Azienda Osped Niguarda CaGranda, Div Cardiol, Milan, Italy. [Mooser, Vincent] GlaxoSmithKline Inc, Genet Div, King Of Prussia, PA USA. [Mooser, Vincent] GlaxoSmithKline Inc, Drug Discovery, King Of Prussia, PA USA. [Morgan, Thomas] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Muenzel, Thomas; Wild, Philipp S.; Zeller, Tanja; Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Univ Med Mainz, Mainz, Germany. [Patel, Riyaz S.; Quyyumi, Arshed A.] Emory Univ, Sch Med, Atlanta, GA USA. [Patel, Riyaz S.] Cardiff Univ, Cardiff, S Glam, Wales. [Peyvandi, Flora] Univ Milan, Osped Maggiore Policlin, A Bianchi Bonomi Hemophilia & Thrombosis Ctr, Dept Med & Med Specialties,Fdn IRCCS Ca Granda, Milan, Italy. [Peyvandi, Flora] Luigi Villa Fdn, Milan, Italy. [Rader, Daniel J.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Rallidis, Loukianos S.] Univ Athens, Sch Med, Attikon Hosp, Dept Cardiol 2, GR-11527 Athens, Greece. [Rosendaal, Frits R.; Snoep, Jaapjan D.] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands. [Rosendaal, Frits R.] Leiden Univ, Dept Thrombosis & Haemostasis, Med Ctr, Leiden, Netherlands. [Rosendaal, Frits R.] Leiden Univ, Einthoven Lab Expt Vasc Med, Med Ctr, Leiden, Netherlands. [Rubin, Diana] Univ Klinikum Schleswig Holstein, Med Klin 1, Kiel, Germany. [Salomaa, Veikko] Natl Inst Hlth & Welf, Chron Dis Epidemiol & Prevent Unit, Dept Chron Dis Prevent, Helsinki, Finland. [Sampietro, M. Lourdes] Leiden Univ, Dept Human Genet & Cardiol, Med Ctr, Leiden, Netherlands. [Sandhu, Manj S.] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Cambridge, England. [Sandhu, Manj S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Cambridge, England. [Schadt, Eric] Pacific Biosci, Menlo Pk, CA USA. [Schadt, Eric] Sage Bionetworks, Palo Alto, CA USA. [Schaefer, Arne; Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Schrezenmeir, Juergen] Max Rubner Inst, Inst Physiol & Biochem Nutr, Kiel, Germany. [Schrezenmeir, Juergen] Kiel Innovat & Technol Ctr, Clin Res Ctr Kiel, Kiel, Germany. [Sivananthan, Mohan] Leeds Teaching Hosp Natl Hlth Serv Trust, Cardiol Div, Leeds, W Yorkshire, England. [Smith, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Spertus, John A.] Mid Amer Heart Inst, Kansas City, KS USA. [Stoll, Monika] Univ Munster, Leibniz Inst Arteriosclerosis Res, Munster, Germany. [Tomaszewski, Maciej; Goodall, Alison H.; Samani, Nilesh J.] Glenfield Gen Hosp, Leicester Natl Inst Hlth Res, Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England. [Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Voight, Benjamin F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Wareham, Nick J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Wichmann, H-Erich] Univ Munich, Inst Med Informat Sci Biometry & Epidemiol, Munich, Germany. [Wright, Benjamin J.] Univ Leicester, Dept Cardiovasc Surg, Leicester, Leics, England. [Altshuler, David] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA. [Ye, Shu] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. [Cambien, Francois] Univ Paris 06, INSERM, UMRS 937, Fac Med Pierre & Marie Curie, Paris, France. [Maerz, Winfried] Synlab Ctr Lab Diagnost Heidelberg, Heidelberg, Germany. [Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Univ Heidelberg, Inst Publ Hlth Social & Prevent Med, Med Fac Manneim, Heidelberg, Germany. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] NHS Blood Transplant, Cambridge, England. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [McPherson, Ruth] Univ Ottawa, Inst Heart, Atherogen Lab, Ottawa, ON, Canada. RP Schunkert, H (reprint author), Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. EM heribert.schunkert@uk-sh.de; njs@le.ac.uk RI Leander, Karin/C-7261-2017; Erdmann, Jeanette/P-7513-2014; Cichon, Sven/B-9618-2014; Mannucci, Pier/C-3102-2014; Meisinger, Christine/B-5358-2014; Laaksonen, Reijo/D-6323-2014; Boekholdt, Matthijs/G-7562-2014; Peters, Annette/A-6117-2011; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Meitinger, Thomas/O-1318-2015; Smith, Albert/K-5150-2015; Martinelli, Nicola/J-5622-2016; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Schreiber, Stefan/B-6748-2008; Voight, Benjamin/F-1775-2011; Morgan, Tom/C-3478-2012; Stewart, Alexandre/A-5677-2011; Stark, Klaus/D-3813-2009; Willenborg, Christina/D-2668-2012; Verdrengh, Evelien/H-4571-2012; Gigante, Bruna/I-9252-2012; Deloukas, Panos/B-2922-2013; Tang, Wai Hong/I-1238-2013; Altshuler, David/A-4476-2009; Library, Woodruff Health/A-6096-2012; Lieb, Wolfgang/C-1990-2012; Cichon, Sven/H-8803-2013 OI Peyvandi, Flora/0000-0001-7423-9864; Gieger, Christian/0000-0001-6986-9554; Ziegler, Andreas/0000-0002-8386-5397; Nothen, Markus/0000-0002-8770-2464; Jones, Gregory T/0000-0002-6950-4210; Ouwehand, Willem/0000-0002-7744-1790; Dehghan, Abbas/0000-0001-6403-016X; Maouche, Seraya/0000-0001-8186-1635; Leander, Karin/0000-0002-1404-9222; Cupples, L. Adrienne/0000-0003-0273-7965; Soranzo, Nicole/0000-0003-1095-3852; Stewart, Alexandre/0000-0003-2673-9164; Meisinger, Christa/0000-0002-9026-6544; ELOSUA, ROBERTO/0000-0001-8235-0095; Erdmann, Jeanette/0000-0002-4486-6231; Cichon, Sven/0000-0002-9475-086X; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Martinelli, Nicola/0000-0001-6465-5119; Schreiber, Stefan/0000-0003-2254-7771; Stark, Klaus/0000-0002-7832-1942; Willenborg, Christina/0000-0001-5217-6882; Deloukas, Panos/0000-0001-9251-070X; Altshuler, David/0000-0002-7250-4107; Cichon, Sven/0000-0002-9475-086X FU British Heart Foundation [PG/08/094/26019, RG/09/012/28096]; Medical Research Council [G0401527, G0801566, G1000143, MC_U106179471]; NHLBI NIH HHS [HL087647, N01 HC025195, R01 HL087647, R01HL089650-02] NR 39 TC 734 Z9 742 U1 8 U2 97 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 APR PY 2011 VL 43 IS 4 BP 333 EP U153 DI 10.1038/ng.784 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 741YL UT WOS:000288903700013 PM 21378990 ER PT J AU York, AG Ghitani, A Vaziri, A Davidson, MW Shroff, H AF York, Andrew G. Ghitani, Alireza Vaziri, Alipasha Davidson, Michael W. Shroff, Hari TI Confined activation and subdiffractive localization enables whole-cell PALM with genetically expressed probes SO NATURE METHODS LA English DT Article ID OPTICAL RECONSTRUCTION MICROSCOPY; PLANE ILLUMINATION MICROSCOPY; SINGLE-MOLECULE LOCALIZATION; FLUORESCENCE MICROSCOPY; SUPERRESOLUTION MICROSCOPY; STRUCTURED ILLUMINATION; DIFFRACTION-LIMIT; PARTICLE-TRACKING; SCALE RESOLUTION; REGISTRATION AB We demonstrate three-dimensional (3D) super-resolution microscopy in whole fixed cells using photoactivated localization microscopy (PALM). The use of the bright, genetically expressed fluorescent marker photoactivatable monomeric (m) Cherry (PA-mCherry1) in combination with near diffraction-limited confinement of photoactivation using two-photon illumination and 3D localization methods allowed us to investigate a variety of cellular structures at < 50 nm lateral and < 100 nm axial resolution. Compared to existing methods, we have substantially reduced excitation and bleaching of unlocalized markers, which allows us to use 3D PALM imaging with high localization density in thick structures. Our 3D localization algorithms, which are based on cross-correlation, do not rely on idealized noise models or specific optical configurations. This allows instrument design to be flexible. By generating appropriate fusion constructs and expressing them in Cos7 cells, we could image invaginations of the nuclear membrane, vimentin fibrils, the mitochondrial network and the endoplasmic reticulum at depths of greater than 8 mu m. C1 [York, Andrew G.; Ghitani, Alireza; Shroff, Hari] Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. [Vaziri, Alipasha] Howard Hughes Med Inst, Ashburn, VA USA. [Davidson, Michael W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. [Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. RP York, AG (reprint author), Natl Inst Biomed Imaging & Bioengn, Sect High Resolut Opt Imaging, NIH, Bethesda, MD USA. EM andrew.g.york+naturemethods@gmail.com RI Shroff, Hari/E-7247-2016 OI Shroff, Hari/0000-0003-3613-8215 FU National Institute of Biomedical Imaging and Bioengineering FX We thank N. Morgan and A. Gillespie for training and use of their spin coater; G. Patterson (National Institute of Biomedical Imaging and Bioengineering) for the gift of purified PA-mCherry1 and mEos2 and for the use of his cell culture facilities; A. Jin for measuring the thickness of our quantum dot films; E. Ramko for help with preparing the PA-mCherry1 fusion vectors; K. Kilborn (Intelligent Imaging Innovations) for loaning us the Vector Point Scanning 2P system; and S. Parekh and H. Eden for feedback and suggestions on the manuscript. This work was supported by the Intramural Research Programs of the National Institute of Biomedical Imaging and Bioengineering. NR 36 TC 95 Z9 98 U1 0 U2 39 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2011 VL 8 IS 4 BP 327 EP U73 DI 10.1038/NMETH.1571 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 742KE UT WOS:000288940300020 PM 21317909 ER PT J AU Komlodi-Pasztor, E Sackett, D Wilkerson, J Fojo, T AF Komlodi-Pasztor, Edina Sackett, Dan Wilkerson, Julia Fojo, Tito TI OPINION Mitosis is not a key target of microtubule agents in patient tumors SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Article ID SOLID TUMORS; CELL-DEATH; AURORA KINASES; PERIPHERAL NEUROPATHY; ANTICANCER AGENTS; DRUG DEVELOPMENT; MOTOR PROTEINS; MITOTIC ARREST; IN-VIVO; CANCER AB Mitosis-specific agents have, to date, not been clinically successful. By contrast, microtubule-targeting agents (MTAs) have a long record of success, usually attributed to the induction of mitotic arrest. Indeed, it was this success that led to the search for mitosis-specific inhibitors. We believe the clinical disappointment of mitosis-specific inhibitors stands as evidence that MTAs have been successful not only by interfering with mitosis but, more importantly, by disrupting essential interphase cellular mechanisms. In this Perspective we will review literature that supports a paradigm shift in how we think about one of our most widely used classes of chemotherapeutics-MTAs. We believe that the steady presence and constant physiological role of microtubules are responsible for the overall success of MTAs. While mitosis-specific inhibitors are effective on only a small fraction of the tumor mass (dividing cells), MTAs target tubulin, a protein that has crucial roles in both mitotic and non-mitotic cells. C1 [Komlodi-Pasztor, Edina; Wilkerson, Julia; Fojo, Tito] NCI, NIH, Bethesda, MD 20892 USA. [Sackett, Dan] NICHHD, NIH, Bethesda, MD 20892 USA. RP Komlodi-Pasztor, E (reprint author), NCI, NIH, Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM komlodie@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The authors would like to thank S. X. Yung for immunohistochemical staining of breast cancer samples. This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 68 TC 97 Z9 98 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD APR PY 2011 VL 8 IS 4 BP 244 EP 250 DI 10.1038/nrclinonc.2010.228 PG 7 WC Oncology SC Oncology GA 742JG UT WOS:000288937600009 PM 21283127 ER PT J AU Popescu, BFG Lennon, VA Parisi, JE Howe, CL Weigand, SD Cabrera-Gomez, JA Newell, K Mandler, RN Pittock, SJ Weinshenker, BG Lucchinetti, CF AF Popescu, B. F. Gh. Lennon, V. A. Parisi, J. E. Howe, C. L. Weigand, S. D. Cabrera-Gomez, J. A. Newell, K. Mandler, R. N. Pittock, S. J. Weinshenker, B. G. Lucchinetti, C. F. TI Neuromyelitis optica unique area postrema lesions Nausea, vomiting, and pathogenic implications SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; WATER CHANNEL; ANTI-AQUAPORIN-4 ANTIBODY; CIRCUMVENTRICULAR ORGANS; INTRACTABLE HICCUP; BRAIN; AQUAPORIN-4; RAT; EXPRESSION; TRANSPORT AB Objective: To characterize the neuropathologic features of neuromyelitis optica (NMO) at the medullary floor of the fourth ventricle and area postrema. Aquaporin-4 (AQP4) autoimmunity targets this region, resulting in intractable nausea associated with vomiting or hiccups in NMO. Methods: This neuropathologic study was performed on archival brainstem tissue from 15 patients with NMO, 5 patients with multiple sclerosis (MS), and 8 neurologically normal subjects. Logistic regression was used to evaluate whether the presence of lesions at this level increased the odds of a patient with NMO having an episode of nausea/vomiting. Results: Six patients with NMO (40%), but no patients with MS or normal controls, exhibited unilateral or bilateral lesions involving the area postrema and the medullary floor of the fourth ventricle. These lesions were characterized by tissue rarefaction, blood vessel thickening, no obvious neuronal or axonal pathology, and preservation of myelin in the subependymal medullary tegmentum. AQP4 immunoreactivity was lost or markedly reduced in all 6 cases, with moderate to marked perivascular and parenchymal lymphocytic inflammatory infiltrates, prominent microglial activation, and in 3 cases, eosinophils. Complement deposition in astrocytes, macrophages, and/or perivascularly, and a prominent astroglial reaction were also present. The odds of nausea/vomiting being documented clinically was 16-fold greater in NMO cases with area postrema lesions (95% confidence interval 1.43-437, p = 0.02). Conclusions: These neuropathologic findings suggest the area postrema may be a selective target of the disease process in NMO, and are compatible with clinical reports of nausea and vomiting preceding episodes of optic neuritis and transverse myelitis or being the heralding symptom of NMO. Neurology (R) 2011;76:1229-1237 C1 [Lucchinetti, C. F.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN 55905 USA. [Lennon, V. A.; Parisi, J. E.; Pittock, S. J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Lennon, V. A.; Howe, C. L.] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. [Weigand, S. D.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Cabrera-Gomez, J. A.] Int Neurol Ctr, Cuban Multiple Sclerosis Soc, Havana, Cuba. [Cabrera-Gomez, J. A.] Int Neurol Ctr, Multiple Sclerosis Clin, Havana, Cuba. [Cabrera-Gomez, J. A.] Int Ctr Neurol Restorat CIREN, Havana, Cuba. [Newell, K.] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, MO USA. [Mandler, R. N.] NIH, Bethesda, MD 20892 USA. RP Lucchinetti, CF (reprint author), Mayo Clin, Coll Med, Dept Neurol, 200 1st St SW, Rochester, MN 55905 USA. EM lucchinetti.claudia@mayo.edu OI Howe, Charles/0000-0002-3889-8739 FU NIH [RO1-NS049577-01-A2]; National Multiple Sclerosis Society [RG 3185-B-3]; Guthy Jackson Foundation; Guthy Jackson Charitable Foundation; Alexion Pharmaceuticals, Inc.; Genzyme Corporation; RSR Ltd.; National MS Society FX Supported by the NIH (RO1-NS049577-01-A2 to C. F. L.), the National Multiple Sclerosis Society (RG 3185-B-3 to C. F. L.), and the Guthy Jackson Foundation (to C.F.L.).; Dr. Popescu reports no disclosures. Dr. Lennon is a named investor on a patent application filed by the Mayo Foundation for Medical Education and Research that relates to the NMO antigen and its application to the diagnosis of NMO; may accrue revenue for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica; and receives research support from the NIH and the Guthy Jackson Charitable Foundation. Dr. Parisi serves on scientific advisory boards for the US Government Defense Health Board and the Subcommittee for Laboratory Services and Pathology; serves as a Section Editor for Neurology (R); receives royalties from the publication of Principles & Practice of Neuropathology, 2nd ed. (Oxford University Press, 2003); and receives research support from the NIH. Dr. Howe, S. D. Weigand, and Dr. Cabrera-Gomez report no disclosures. Dr. Newell receives/has received research support from the NIH. Dr. Mandler reports no disclosures. Dr. Pittock may accrue revenue for patents re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica and aquaporin-4 autoantibody as a cancer marker; and has received research support from Alexion Pharmaceuticals, Inc. and the Guthy Jackson Charitable Foundation. Dr. Weinshenker serves on data safety monitoring boards for Novartis and Biogen Idec; serves on the editorial boards of the Canadian Journal of Neurological Sciences and the Turkish Journal of Neurology; has received research support from Genzyme Corporation and the Guthy-Jackson Charitable Foundation; and receives license royalties from RSR Ltd. for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica. Dr. Lucchinetti may accrue revenue for a patent re: Aquaporin-4 associated antibodies for diagnosis of neuromyelitis optica; receives royalties from the publication of Blue Books of Neurology: Multiple Sclerosis 3 (Saunders Elsevier, 2010); and receives research support from the NIH, the Guthy Jackson Charitable Foundation (PI), and the National MS Society. NR 37 TC 90 Z9 98 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 2011 VL 76 IS 14 BP 1229 EP 1237 DI 10.1212/WNL.0b013e318214332c PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 745CV UT WOS:000289142500009 PM 21368286 ER PT J AU Fields, RD AF Fields, R. Douglas TI Imaging Learning: The Search for a Memory Trace SO NEUROSCIENTIST LA English DT Review DE white matter; gray matter; learning and memory; MRI; DTI; brain imaging; myelin; NG2; activity-dependent plasticity; neuron-glia interactions; oligodendrocytes; enriched environment ID WHITE-MATTER ARCHITECTURE; BRAIN STRUCTURE CHANGES; DIFFUSION TENSOR MRI; ACTION-POTENTIALS; ENVIRONMENTAL COMPLEXITY; MULTIPLE-SCLEROSIS; NEURAL IMPULSES; NERVOUS-SYSTEM; SPEECH SOUNDS; NON-MUSICIANS AB Learning is associated with structural changes in the human brain that can be seen and studied by MRI. These changes are observed in gray matter and surprisingly also in white matter tissue. Learning a wide range of skills, from sports, computer games, music, and reading, to abstract intellectual learning, including classroom study, is associated with structural changes in appropriate cortical regions or fiber tracts. The cellular changes underlying modifications of brain tissue during learning include changes in neuronal and glial morphology as well as vascular changes. Both alterations in axon morphology and myelination are thought to contribute to white matter plasticity during learning but to varying degrees depending on age. Structural changes in white matter could promote learning by improving the speed or synchrony of impulse transmission between cortical regions mediating the behavior. Action potentials can stimulate oligodendrocyte development and myelination by at least three known mechanisms that involve signaling molecules between axons and oligodendrocytes, which do not require neurotransmitter release from synapses. Integrating information from cellular/molecular and systems-level research on normal cognitive function, development, and learning is providing new insights into the biological mechanisms of learning and the structural changes produced in the brain. C1 NICHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU NIH FX The author(s) disclosed receipt of the following financial support for the research and/or authorship of this article: supported by the NIH intramural program. NR 74 TC 29 Z9 29 U1 1 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD APR PY 2011 VL 17 IS 2 BP 185 EP 196 DI 10.1177/1073858410383696 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 742UF UT WOS:000288969800011 PM 21403182 ER PT J AU Simonyan, K Horwitz, B AF Simonyan, Kristina Horwitz, Barry TI Laryngeal Motor Cortex and Control of Speech in Humans SO NEUROSCIENTIST LA English DT Review DE motor control; voice; speech; human; nonhuman primate ID TRANSCRANIAL MAGNETIC STIMULATION; SQUIRREL-MONKEY; RHESUS-MONKEY; BRAIN-STEM; HEMISPHERIC LATERALIZATION; NEURONAL-ACTIVITY; NERVOUS-SYSTEM; BROCAS AREA; PROJECTIONS; VOCALIZATION AB Speech production is one of the most complex and rapid motor behaviors, and it involves a precise coordination of more than 100 laryngeal, orofacial, and respiratory muscles. Yet we lack a complete understanding of laryngeal motor cortical control during production of speech and other voluntary laryngeal behaviors. In recent years, a number of studies have confirmed the laryngeal motor cortical representation in humans and have provided some information about its interactions with other cortical and subcortical regions that are principally involved in vocal motor control of speech production. In this review, the authors discuss the organization of the peripheral and central laryngeal control based on neuroimaging and electrical stimulation studies in humans and neuroanatomical tracing studies in nonhuman primates. It is hypothesized that the location of the laryngeal motor cortex in the primary motor cortex and its direct connections with the brain stem laryngeal motoneurons in humans, as opposed to its location in the premotor cortex with only indirect connections to the laryngeal motoneurons in nonhuman primates, may represent one of the major evolutionary developments in humans toward the ability to speak and vocalize voluntarily. C1 [Simonyan, Kristina] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Simonyan, Kristina] Mt Sinai Sch Med, Dept Otolaryngol, New York, NY 10029 USA. [Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Simonyan, K (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM kristina.simonyan@mssm.edu OI Simonyan, Kristina/0000-0001-7444-0437 FU National Institute on Deafness and Other Communication Disorders, National Institutes of Health [R00DC009620] FX This work was supported by the Extramural and Intramural Programs of the National Institute on Deafness and Other Communication Disorders, National Institutes of Health (R00DC009620 to K.S.). NR 75 TC 54 Z9 56 U1 4 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD APR PY 2011 VL 17 IS 2 BP 197 EP 208 DI 10.1177/1073858410386727 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 742UF UT WOS:000288969800012 PM 21362688 ER PT J AU Elman, MJ Bressler, NM Qin, HJ Beck, RW Ferris, FL Friedman, SM Glassman, AR Scott, IU Stockdale, CR Sun, JK AF Elman, Michael J. Bressler, Neil M. Qin, Haijing Beck, Roy W. Ferris, Frederick L., III Friedman, Scott M. Glassman, Adam R. Scott, Ingrid U. Stockdale, Cynthia R. Sun, Jennifer K. TI Expanded 2-Year Follow-up of Ranibizumab Plus Prompt or Deferred Laser or Triamcinolone Plus Prompt Laser for Diabetic Macular Edema SO OPHTHALMOLOGY LA English DT Article AB Objective: To report expanded 2-year follow-up of a previously reported randomized trial evaluating intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Design: Multicenter, randomized clinical trial. Participants: A total of 854 study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Methods: Continuation of procedures previously reported for the randomized trial. Main Outcome Measures: Best-corrected visual acuity and safety at the 2-year visit. Results: At the 2-year visit, compared with the sham + prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab + prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI], -0.4 to +7.7), 5.8 letters greater in the ranibizumab + deferred laser group (95% aCI, +1.9 to +9.8), and 1.5 letters worse in the triamcinolone + prompt laser group (95% aCI, -5.5 to +2.4). After the 1- to 2-year visit in the ranibizumab + prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness >= 250 mu m were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Conclusions: The expanded 2-year results reported are similar to results published previously and reinforce the conclusions originally reported: Ranibizumab should be considered for patients with DME and characteristics similar to those of the cohort in this clinical trial, including vision impairment with DME involving the center of the macula. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:609-614 (C) 2011 by the American Academy of Ophthalmology. C1 [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Stockdale, Cynthia R.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Elman, Michael J.] PA, Elman Retina Grp, Baltimore, MD USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Ferris, Frederick L., III] NEI, Bethesda, MD 20892 USA. [Ferris, Frederick L., III] NIH, Bethesda, MD 20892 USA. [Friedman, Scott M.] Florida Retina Consultants, Lakeland, FL USA. [Scott, Ingrid U.] Penn State Univ, Coll Med, Hershey, PA USA. [Sun, Jennifer K.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat3@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health; Department of Health and Human Services [EY-14231, EY-14229, EY-18817]; Genentech; Allergan, Inc.; Pfizer; Alcon; Allergan; Office of Research Administration; Bausch Lomb; Carl Zeiss Meditec; EMMES Corporation; Lumenis; Notal Vision; Novartis; QLT; Regeneron; Steba Biotech; Abbott Medical Optics; ForSight Labs; LLC; Genzyme Corporation FX Supported through cooperative agreements from the National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, and Department of Health and Human Services EY-14231, EY-14229, EY-18817; The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the article but not directly in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; or in the preparation of the article. Genentech provided the ranibizumab for the study, and Allergan, Inc., provided the triamcinolone for the study. In addition, Genentech and Allergan, Inc., provided funds to DRCR.net to defray the study's clinical site costs. As described in the DRCR.net Industry Collaboration Guidelines (available at www.drcr.net), the DRCR.net had complete control over the design of the protocol, ownership of the data, and all editorial content of presentations and publications related to the protocol. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net. Writing Committee financial disclosures: Michael J. Elman: Genentech (consultant); Scott M. Friedman: Pfizer (financial support); Alcon (financial support); Allergan (financial support); Genentech (financial support); Ingrid U. Scott: Genentech (consultant); Eyetech (consultant); Jennifer K. Sun: Novartis (lecturer); Neil M. Bressler: Grants to investigators at The Johns Hopkins University are negotiated and administered by the institution (e.g., the School of Medicine) that receives the grants, typically through the Office of Research Administration. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the projects(s). Dr. Neil Bressler is Principal Investigator of grants at The Johns Hopkins University sponsored by the following entities (not including the National Institutes of Health): Allergan, Bausch & Lomb, Carl Zeiss Meditec, EMMES Corporation, Genentech, Lumenis, Notal Vision, Novartis, QLT, Regeneron, Steba Biotech, Abbott Medical Optics, ForSight Labs, LLC, and Genzyme Corporation. A complete list of all DRCR. net investigator financial disclosures can be found at www.drcr.net. NR 3 TC 202 Z9 209 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2011 VL 118 IS 4 BP 609 EP 614 DI 10.1016/j.ophtha.2010.12.033 PG 6 WC Ophthalmology SC Ophthalmology GA 744DS UT WOS:000289075200002 PM 21459214 ER PT J AU Ojaimi, E Nguyen, TT Klein, R Islam, FMA Cotch, MF Klein, BEK Wang, JJ Wong, TY AF Ojaimi, Elvis Nguyen, Thanh T. Klein, Ronald Islam, F. M. Amirul Cotch, Mary Frances Klein, Barbara E. K. Wang, Jie-Jin Wong, Tien Yin TI Retinopathy Signs in People without Diabetes The Multi-Ethnic Study of Atherosclerosis SO OPHTHALMOLOGY LA English DT Article ID RETINAL MICROVASCULAR ABNORMALITIES; CARDIOVASCULAR RISK-FACTORS; HYPERTENSIVE RETINOPATHY; ELDERLY POPULATION; VASCULAR CALIBER; BLOOD-PRESSURE; OLDER PERSONS; PREVALENCE; COMMUNITIES; DISEASE AB Objective: To describe the prevalence of retinopathy and associations with cardiovascular risk factors in persons without diabetes in 4 racial/ethnic groups (white, black, Hispanic, and Chinese). Design: Population-based, cross-sectional study. Participants: We included 6176 subjects aged 45-84 years without diabetes, selected from 6 United States communities. Methods: Fundus images were taken using 45 digital camera through dark-adapted pupils and were graded for retinopathy as defined by the Early Treatment Diabetic Retinopathy Study severity scale: microaneurysms, hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading, and new vessels. Main Outcome Measures: Retinopathy and the association with cardiovascular risk factors. Results: Prevalence rates of retinopathy in persons without diabetes were 12.5% overall, varying from 11.9% (white), 13.9% (black), 12.6% (Hispanic), to 17.2% (Chinese). Hypertension was strongly associated with retinopathy (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.23-1.75). After adjusting for age, gender, race, and other parameters, smoking (OR, 1.50; 95% CI, 1.09-2.06) and increased internal carotid intima media thickness (OR, 1.22; 95% CI, 1.05-1.41) were associated with retinopathy. A range of serum inflammatory factors were examined, but none were found to be significant. Conclusions: Retinopathy in persons without diabetes is common, varies with race/ethnicity, and associated with cardiovascular risk factors, including hypertension, smoking, and carotid artery intima media thickness. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2011; 118: 656-662 (C) 2011 by the American Academy of Ophthalmology. C1 [Wong, Tien Yin] Natl Univ Singapore, Singapore Eye Res Inst, Singapore Natl Eye Ctr, Singapore 117548, Singapore. [Ojaimi, Elvis; Nguyen, Thanh T.; Islam, F. M. Amirul; Wang, Jie-Jin; Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia. [Ojaimi, Elvis; Wong, Tien Yin] Royal Victorian Eye & Ear Hosp, Melbourne, Vic, Australia. [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Islam, F. M. Amirul] Univ So Queensland, Dept Math & Comp, Toowoomba, Qld 4350, Australia. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Wong, TY (reprint author), Natl Univ Singapore, Singapore Eye Res Inst, Singapore Natl Eye Ctr, 11 3rd Hosp Ave, Singapore 117548, Singapore. EM ophwty@nus.edu.sg RI Wang, Jie Jin/P-1499-2014; OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95169]; National Institutes of Health [HL69979-03] FX Supported by contracts N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute. Additional support was provided by National Institutes of Health grants HL69979-03 (Klein R and Wong TY). The funding agencies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 40 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2011 VL 118 IS 4 BP 656 EP 662 DI 10.1016/j.ophtha.2010.08.007 PG 7 WC Ophthalmology SC Ophthalmology GA 744DS UT WOS:000289075200008 PM 21055817 ER PT J AU Ng, CH Cheung, N Wang, JJ Islam, AFM Kawasaki, R Meuer, SM Cotch, MF Klein, BEK Klein, R Wong, TY AF Ng, Ching Hui Cheung, Ning Wang, Jie Jin Islam, Amirul F. M. Kawasaki, Ryo Meuer, Stacy M. Cotch, Mary Frances Klein, Barbara E. K. Klein, Ronald Wong, Tien Yin TI Prevalence and Risk Factors for Epiretinal Membranes in a Multi-Ethnic United States Population SO OPHTHALMOLOGY LA English DT Article ID RETINAL VASCULAR CALIBER; BLUE MOUNTAINS EYE; JAPANESE POPULATION; ASSOCIATIONS; ATHEROSCLEROSIS; CHINESE AB Purpose: To describe the prevalence of and risk factors for epiretinal membrane (ERM) in a multi-ethnic population and to evaluate possible racial or ethnic differences. Design: Cross-sectional study. Participants: Participants of the Multi-Ethnic Study of Atherosclerosis (MESA), examined at the second visit of the MESA when retinal photography was performed. Methods: Data on 5960 participants aged 45 to 84 years from MESA, including white, black, Hispanic, and Chinese persons from 6 United States communities, were analyzed. Epiretinal membrane was assessed from digital nonstereoscopic fundus photographs and was defined as cellophane macular reflex (CMR) without retinal folds or preretinal macular fibrosis (PMF) with retinal folds. Risk factors were assessed from standardized interviews, clinical examinations, and laboratory investigations. Main Outcome Measures: Epiretinal membrane prevalence by ethnic or racial group and risk factors associated with ERM. Results: The prevalence of any ERM was 28.9%, of which 25.1% were CMR cases and 3.8% were PMF cases. The prevalence of ERM was significantly higher in Chinese persons (39.0%), compared with Hispanic (29.3%), white (27.5%), or black (26.2%; P<0.001) persons. In multivariate models, increasing age (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06-1.34, per year increase in age), diabetes (OR, 1.92; 95% CI, 1.39-2.65), and hypercholesterolemia (OR, 1.33; 95% CI, 1.04-1.69) were significantly associated with CMR. Conclusions: This study showed that ERM was significantly more common in Chinese persons compared with whites, blacks, and Hispanics. Risk factors for ERM were increasing age, presence of diabetes, and hypercholesterolemia. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2011;118:694-699 (C) 2011 by the American Academy of Ophthalmology. C1 [Ng, Ching Hui; Cheung, Ning; Wang, Jie Jin; Islam, Amirul F. M.; Kawasaki, Ryo; Wong, Tien Yin] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. [Islam, Amirul F. M.] Deakin Univ, Sch Hlth & Social Dev, Melbourne, Vic, Australia. [Meuer, Stacy M.; Klein, Barbara E. K.; Klein, Ronald] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI USA. [Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Wong, Tien Yin] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117595, Singapore. RP Wang, JJ (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM jiejin_wang@wmi.usyd.edu.au RI Cheung, Ning Danny/F-2043-2013; Wang, Jie Jin/P-1499-2014; OI Wang, Jie Jin/0000-0001-9491-4898; Cotch, Mary Frances/0000-0002-2046-4350; Klein, Ronald/0000-0002-4428-6237 FU National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [N01-HC-95159, N01-HC-95165, N01-HC-95169]; National Institutes of Health, Bethesda, Maryland [HL69979-03]; National Eye Institute, National Institutes of Health, Bethesda, Maryland [Z01EY000403] FX Supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (grant nos.: N01-HC-95159 through N01-HC-95165 and N01-HC-95169); the National Institutes of Health, Bethesda, Maryland (grant no.: HL69979-03 [RK and TYW); and the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: Z01EY000403 [MFC]). The funding source had no role in the design or conduct of this research. NR 19 TC 40 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2011 VL 118 IS 4 BP 694 EP 699 DI 10.1016/j.ophtha.2010.08.009 PG 6 WC Ophthalmology SC Ophthalmology GA 744DS UT WOS:000289075200013 PM 21035863 ER PT J AU Sen, HN Sangave, AA Goldstein, DA Suhler, EB Cunningham, D Vitale, S Nussenblatt, RB AF Sen, H. Nida Sangave, Amit A. Goldstein, Debra A. Suhler, Eric B. Cunningham, Denise Vitale, Susan Nussenblatt, Robert B. TI A Standardized Grading System for Scleritis SO OPHTHALMOLOGY LA English DT Article ID UVEITIS; INFLAMMATION; AGREEMENT AB Objective: This study evaluated the performance of a standardized grading system for scleritis using standard digital photographs. Design: Cross-sectional interobserver agreement study. Participants: Photo archives from the National Eye Institute. Methods: Three uveitis specialists from 3 different centers graded 79 randomly arranged images of the sclera with various degrees of inflammation. Grading was done using standard screen resolution (1024x768 pixels) on a 0 to 4+ scale in 2 sessions: (1) without using reference photographs and (2) with reference to a set of standard photographs (proposed grading system). The graders were masked to the order of images, and the order of images was randomized. Interobserver agreement in grading the severity of inflammation with and without the use of grading system was evaluated. Main Outcome Measures: Interobserver agreement. Results: The proposed grading system for assessing activity in scleritis demonstrated a good interobserver agreement. Interobserver agreement (pooled kappa) was poor (0.289) without photographic guidance and improved substantially when the "grading system" with standardized photographs was used (kappa = 0.603). Conclusions: This system of standardized images for scleritis grading provides significantly more consistent grading of scleral inflammation in this study and has clear applications in clinical settings and clinical research. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2011;118:768-771 (C) 2011 by the American Academy of Ophthalmology. C1 [Sen, H. Nida; Sangave, Amit A.; Cunningham, Denise; Vitale, Susan; Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA. [Goldstein, Debra A.] Univ Illinois, Chicago, IL USA. [Suhler, Eric B.] Oregon Hlth & Sci Univ, Portland, OR USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Sen, HN (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM senh@nei.nih.gov FU Celgene; Abbott; Genentech; Novartis; Department of Veterans' Affairs; National Eye Institute FX Dr Eric Suhler receives financial support from Celgene, Abbott, Genentech, Novartis, and the Department of Veterans' Affairs, and institutional support from Research to Prevent Blindness.; Supported by the National Eye Institute Intramural research program support (HNS, RBN, AS, SV). NR 9 TC 13 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2011 VL 118 IS 4 BP 768 EP 771 DI 10.1016/j.ophtha.2010.08.027 PG 4 WC Ophthalmology SC Ophthalmology GA 744DS UT WOS:000289075200025 PM 21093921 ER PT J AU Gobina, I Valimaa, R Tynjala, J Villberg, J Villerusa, A Iannotti, RJ Godeau, E Gabhainn, SN Andersen, A Holstein, BE AF Gobina, Inese Valimaa, Raili Tynjala, Jorma Villberg, Jari Villerusa, Anita Iannotti, Ronald J. Godeau, Emmanuelle Gabhainn, Saoirse Nic Andersen, Anette Holstein, Bjorn E. CA HBSC Med Use Writing Grp TI The medicine use and corresponding subjective health complaints among adolescents, a cross-national survey SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE medicine use; adolescence; health complaints ID SCHOOL-AGED CHILDREN; SECTIONAL SURVEY; PAIN; CHILDHOOD; SYMPTOMS; HEADACHE; DENMARK; MODEL; GIRLS; RISK AB Background Medicine use among children and young people is under-researched. Studies that investigated cross-national patterns in adolescents' medicine use practice are rare. This study aims to investigate adolescents' medicine use for corresponding health complaints in Europe and USA. Methods Nationally representative samples of adolescents from 19 countries and regions in Europe and USA completed an anonymous, standardised questionnaire as part of the Health Behaviour in School-aged Children 2005/2006 survey. The prevalence of health complaints and medicine use were determined. The influence of the frequency of medicine use, age, gender and country of residence, on the likelihood of medicine use was assessed using multilevel multivariate logistic regression, with separate analyses for boys and girls. Results Both health complaints and medicine use were common among adolescents. Medicine use was strongly associated with the frequency of health complaints. The prevalence of both medicine use and health complaints was higher among girls than boys. Boys and girls with weekly health complaints were both similarly likely to report elevated rates of medicine use. Conclusions The findings indicated that adolescents who report more frequent recurrent health complaints are also more likely to report more frequent medicine use for their health complaints. Adolescent boys with weekly health complaints have the same risk of medicine use as girls with weekly health complaints. The importance of educating school-aged children to interpret their bodily feelings and complaints and to use medicines appropriately is of high priority. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Gobina, Inese; Villerusa, Anita] Riga Stradins Univ, Dept Epidemiol & Publ Hlth, Riga, Latvia. [Valimaa, Raili; Tynjala, Jorma; Villberg, Jari] Univ Jyvaskyla, Dept Hlth Sci, SF-40351 Jyvaskyla, Finland. [Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Bethesda, MD USA. [Godeau, Emmanuelle] Univ Toulouse 3, Serv Med Rectorat Toulouse, INSERM, U558,UMR, F-31062 Toulouse, France. [Gabhainn, Saoirse Nic] Natl Univ Ireland, Hlth Promot Res Ctr, Sch Hlth Sci, Dublin, Ireland. [Andersen, Anette; Holstein, Bjorn E.] Univ So Denmark, Natl Inst Publ Hlth, Odense, Denmark. RP Gobina, I (reprint author), Riga Stradins Univ, Dept Epidemiol & Publ Hlth, Riga, Latvia. EM inese.gobina@rsu.lv RI Borraccino, Alberto/C-9013-2012 OI Borraccino, Alberto/0000-0001-8235-8775 NR 39 TC 12 Z9 13 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 EI 1099-1557 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2011 VL 20 IS 4 BP 424 EP 431 DI 10.1002/pds.2102 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 741HN UT WOS:000288854900014 PM 21246643 ER PT J AU Wald, I Lubin, G Holoshitz, Y Muller, D Fruchter, E Pine, DS Charney, DS Bar-Haim, Y AF Wald, I. Lubin, G. Holoshitz, Y. Muller, D. Fruchter, E. Pine, D. S. Charney, D. S. Bar-Haim, Y. TI Battlefield-like stress following simulated combat and suppression of attention bias to threat SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anxiety; attention bias; combat; PTSD; stress ID GENERALIZED ANXIETY DISORDER; PREFRONTAL CORTEX ACTIVATION; POSTTRAUMATIC-STRESS; SOCIAL ANXIETY; DEHYDROEPIANDROSTERONE-SULFATE; PLASMA DEHYDROEPIANDROSTERONE; NEUROPSYCHOLOGICAL OUTCOMES; PERITRAUMATIC DISSOCIATION; OBJECTIVE PERFORMANCE; COGNITIVE FUNCTION AB Background. Acute stress disorder involves prominent symptoms of threat avoidance. Preliminary cross-sectional data suggest that such threat-avoidance symptoms may also manifest cognitively, as attentional threat avoidance. Confirming these findings in a longitudinal study might provide insights on risk prediction and anxiety prevention in traumatic exposures. Method. Attention-threat bias and post-traumatic symptoms were assessed in soldiers at two points in time : early in basic training and 23 weeks later, during advanced combat training. Based on random assignment, the timing of the repeat assessment occurred in one of two schedules : for a combat simulation group, the repeat assessment occurred immediately following a battlefield simulation exercise, and for a control group, the assessment occurred shortly before this exercise. Results. Both groups showed no threat-related attention bias at initial assessments. Following acute stress, the combat simulation group exhibited a shift in attention away from threat whereas the control group showed no change in attention bias. Stronger threat avoidance in the combat simulation group correlated with severity of post-traumatic symptoms. Such an association was not found in the control group. Conclusions. Acute stress may lead some individuals to shift their attention away from threats, perhaps to minimize stress exposure. This acute attention response may come at a psychological cost, given that it correlates with post-traumatic stress disorder (PTSD) symptoms. Further research is needed to determine how these associations relate to full-blown PTSD in soldier and civilian populations. C1 [Wald, I.; Bar-Haim, Y.] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. [Lubin, G.; Fruchter, E.] Med Corps, Israeli Def Force, Tel Hashomer, Israel. [Holoshitz, Y.; Muller, D.; Charney, D. S.] Mt Sinai Sch Med, New York, NY 10029 USA. [Pine, D. S.] NIMH, Bethesda, MD USA. RP Bar-Haim, Y (reprint author), Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel. EM yair1@post.tau.ac.il FU Leo and Julia Forchheimer Foundation; Mount Sinai School of Medicine; Israeli Science Foundation [964/08] FX Funding for this project was provided by the Leo and Julia Forchheimer Foundation in collaboration with the Mount Sinai School of Medicine, and partially supported by the Israeli Science Foundation (grant no. 964/08) to Y.B.-H. NR 49 TC 31 Z9 33 U1 5 U2 17 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2011 VL 41 IS 4 BP 699 EP 707 DI 10.1017/S0033291710002308 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 729IF UT WOS:000287941200003 PM 21108868 ER PT J AU Alonso, J Vilagut, G Chatterji, S Heeringa, S Schoenbaum, M Ustun, TB Rojas-Farreras, S Angermeyer, M Bromet, E Bruffaerts, R de Girolamo, G Gureje, O Haro, JM Karam, AN Kovess, V Levinson, D Liu, Z Medina-Mora, ME Ormel, J Posada-Villa, J Uda, H Kessler, RC AF Alonso, J. Vilagut, G. Chatterji, S. Heeringa, S. Schoenbaum, M. Uestuen, T. Bedirhan Rojas-Farreras, S. Angermeyer, M. Bromet, E. Bruffaerts, R. de Girolamo, G. Gureje, O. Haro, J. M. Karam, A. N. Kovess, V. Levinson, D. Liu, Z. Medina-Mora, M. E. Ormel, J. Posada-Villa, J. Uda, H. Kessler, R. C. TI Including information about co-morbidity in estimates of disease burden: results from the World Health Organization World Mental Health Surveys SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Co-morbidity; epidemiology; global burden of disease; mental health; visual analog scale ID QUALITY-OF-LIFE; VISUAL ANALOG SCALE; STATE VALUATIONS; DISORDERS; DEPRESSION; IMPACT; COMORBIDITY; DISABILITY; OUTCOMES; VERSION AB Background. The methodology commonly used to estimate disease burden, featuring ratings of severity of individual conditions, has been criticized for ignoring co-morbidity. A methodology that addresses this problem is proposed and illustrated here with data from the World Health Organization World Mental Health Surveys. Although the analysis is based on self-reports about one's own conditions in a community survey, the logic applies equally well to analysis of hypothetical vignettes describing co-morbid condition profiles. Method. Face-to-face interviews in 13 countries (six developing, nine developed; n = 31 067; response rate = 69.6%) assessed 10 classes of chronic physical and nine of mental conditions. A visual analog scale (VAS) was used to assess overall perceived health. Multiple regression analysis with interactions for co-morbidity was used to estimate associations of conditions with VAS. Simulation was used to estimate condition-specific effects. Results. The best-fitting model included condition main effects and interactions of types by numbers of conditions. Neurological conditions, insomnia and major depression were rated most severe. Adjustment for co-morbidity reduced condition-specific estimates with substantial between-condition variation (0.24-0.70 ratios of condition-specific estimates with and without adjustment for co-morbidity). The societal-level burden rankings were quite different from the individual-level rankings, with the highest societal-level rankings associated with conditions having high prevalence rather than high individual-level severity. Conclusions. Plausible estimates of disorder-specific effects on VAS can be obtained using methods that adjust for co-morbidity. These adjustments substantially influence condition-specific ratings. C1 [Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Alonso, J.; Vilagut, G.; Rojas-Farreras, S.] Hosp del Mar, IMIM, Hlth Serv Res Unit, Barcelona, Spain. [Alonso, J.; Vilagut, G.] CIBERESP, Barcelona, Spain. [Uestuen, T. Bedirhan] WHO, EIP HFS, CH-1211 Geneva, Switzerland. [Heeringa, S.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Schoenbaum, M.] NIMH, Bethesda, MD 20892 USA. [Angermeyer, M.] Ctr Publ Mental Hlth, Gosing Am Wagram, Austria. [Bromet, E.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Bruffaerts, R.] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [de Girolamo, G.] IRCCS Ctr S Giovanni di Dio Fatebenefratelli, Brescia, Italy. [Gureje, O.] Univ Coll Hosp, Ibadan, Nigeria. [Haro, J. M.] CIBERSAM, St Joan de Deu SSM, Barcelona, Spain. [Karam, A. N.] IDRAAC, Beirut, Lebanon. [Karam, A. N.] Balamand Univ, Fac Med, Dept Psychiat & Clin Psychol, St George Hosp Univ Med Ctr, Beirut, Lebanon. [Kovess, V.] Univ Paris Descartes3, EA4069, Paris, France. [Levinson, D.] Minist Hlth, Mental Hlth Serv, Jerusalem, Israel. [Liu, Z.] Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China. [Medina-Mora, M. E.] Natl Inst Psychiat Ramon de la Fuente, Mexico City, DF, Mexico. [Ormel, J.] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychiat Epidemiol, Groningen, Netherlands. [Posada-Villa, J.] Colegio Mayor de Cundinamarca Univ, Bogota, Colombia. [Uda, H.] Osumi Reg Promot Bur, Hlth Social Welf & Environm Dept, Aichi, Kagoshima, Japan. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM Kessler@hcp.med.harvard.edu RI Ormel, Johan/C-6094-2013; Vilagut, Gemma/N-8718-2014; Haro, Josep Maria/D-1423-2011; Alonso, Jordi/A-5514-2010; OI Vilagut, Gemma/0000-0002-3714-226X; Haro, Josep Maria/0000-0002-3984-277X; Alonso, Jordi/0000-0001-8627-9636; Liu, Zhaorui/0000-0002-6536-7503 FU Bristol-Myers Squibb; Eli Lilly Company; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil Pharmaceuticals Inc.; Pfizer Inc.; Sanofi-Aventis; United States National Institute of Mental Health [R01MH070884]; Mental Health Burden Study [HHSN271200700030C]; John D. and Catherine T. MacArthur Foundation; Pfizer Foundation; US Public Health Service [R13-MH066849, R01-MH069864, R01 DA016558]; Fogarty International Center [FIRCA R03-TW006481]; Pan American Health Organization; Eli Lilly & Company Foundation; Ortho-McNeil Pharmaceutical, Inc.; Shire; Ministry of Social Protection; European Commission [QLG5-1999-01042, SANCO 2004123]; Piedmont Region (Italy); Fondo de Investigacion Sanitaria; Instituto de Salud Carlos III, Spain [FIS 00/0028]; Ministerio de Ciencia y Tecnologia, Spain [SAF 2000-158-CE]; Departament de Salut, Generalitat de Catalunya, Spain; Instituto de Salud Carlos III [CIBER CB06/02/0046, RETICS RD06/0011]; Ministry of Health; Japan Ministry of Health, Labor and Welfare [H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013]; Lebanese Ministry of Public Health; WHO (Lebanon); Fogarty International; Act for Lebanon; Janssen Cilag; Eli Lilly; Roche; Novartis; National Institute of Psychiatry Ramon de la Fuente [INPRFMDIES 4280]; National Council on Science and Technology [CONACyT-G30544-H]; WHO (Geneva); WHO (Nigeria); Federal Ministry of Health, Abuja, Nigeria; US National Institute of Mental Health [RO1-MH61905]; National Institute of Mental Health (NIMH) [U01-MH60220]; Robert Wood Johnson Foundation (RWJF) [044708] FX R.C.K. has been a consultant for GlaxoSmithKline Inc., Kaiser Permanente, Pfizer Inc., Sanofi-Aventis, Shire Pharmaceuticals and Wyeth-Ayerst; has served on advisory boards for Eli Lilly & Company and Wyeth-Ayerst; and has had research support for his epidemiological studies from Bristol-Myers Squibb, Eli Lilly & Company, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil Pharmaceuticals Inc., Pfizer Inc. and Sanofi-Aventis.; The analysis for this paper was carried out in conjunction with the WHO WMH Survey Initiative. We thank the WMH staff for assistance with instrumentation, fieldwork and data analysis. These activities were supported by the United States National Institute of Mental Health (R01MH070884), the Mental Health Burden Study (contract number HHSN271200700030C), the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (R13-MH066849, R01-MH069864 and R01 DA016558), the Fogarty International Center (FIRCA R03-TW006481), the Pan American Health Organization, the Eli Lilly & Company Foundation, Ortho-McNeil Pharmaceutical, Inc., GlaxoSmithKline, Bristol-Myers Squibb and Shire. A complete list of WMH publications can be found at http://www.hcp.med.harvard.edu/wmh/.; The Chinese WMH Survey Initiative is supported by the Pfizer Foundation. The Colombian National Study of Mental Health (NSMH) is supported by the Ministry of Social Protection. The European Study of the Epidemiology of Mental Disorders (ESEMeD) project is funded by the European Commission (contracts QLG5-1999-01042; SANCO 2004123), the Piedmont Region (Italy), Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Spain (FIS 00/0028), Ministerio de Ciencia y Tecnologia, Spain (SAF 2000-158-CE), Departament de Salut, Generalitat de Catalunya, Spain, Instituto de Salud Carlos III (CIBER CB06/02/0046, RETICS RD06/0011 REM-TAP), and other local agencies and by an unrestricted educational grant from GlaxoSmithKline. The Israel National Health Survey is funded by the Ministry of Health with support from the Israel National Institute for Health Policy and Health Services Research and the National Insurance Institute of Israel. The WMH Japan (WMHJ) Survey is supported by the Grant for Research on Psychiatric and Neurological Diseases and Mental Health (H13-SHOGAI-023, H14-TOKUBETSU-026, H16-KOKORO-013) from the Japan Ministry of Health, Labor and Welfare. The Lebanese National Mental Health Survey (Lebanese Evaluation of the Burden of Ailments and Needs of the Nation; LEBANON) is supported by the Lebanese Ministry of Public Health, the WHO (Lebanon), Fogarty International, Act for Lebanon, anonymous private donations to the Institute for Development, Research, Advocacy and Applied Care (IDRAAC), Lebanon, and unrestricted grants from Janssen Cilag, Eli Lilly, GlaxoSmithKline, Roche and Novartis. The Mexican National Co-morbidity Survey (MNCS) is supported by The National Institute of Psychiatry Ramon de la Fuente (INPRFMDIES 4280) and by the National Council on Science and Technology (CONACyT-G30544-H), with supplemental support from the Pan-American Health Organization (PAHO). The Nigerian Survey of Mental Health and Wellbeing (NSMHW) is supported by the WHO (Geneva), the WHO (Nigeria) and the Federal Ministry of Health, Abuja, Nigeria. The Ukraine Comorbid Mental Disorders during Periods of Social Disruption (CMDPSD) study is funded by the US National Institute of Mental Health (RO1-MH61905). The US National Co-morbidity Survey Replication (NCS-R) is supported by the National Institute of Mental Health (NIMH; U01-MH60220) with supplemental support from the National Institute of Drug Abuse (NIDA), the Substance Abuse and Mental Health Services Administration (SAMHSA), the Robert Wood Johnson Foundation (RWJF; grant 044708) and the John W. Alden Trust. NR 59 TC 31 Z9 31 U1 4 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2011 VL 41 IS 4 BP 873 EP 886 DI 10.1017/S0033291710001212 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 729IF UT WOS:000287941200020 PM 20553636 ER PT J AU Buist, DSM Anderson, ML Haneuse, SJPA Sickles, EA Smith, RA Carney, PA Taplin, SH Rosenberg, RD Geller, BM Onega, TL Monsees, BS Bassett, LW Yankaskas, BC Elmore, JG Kerlikowske, K Miglioretti, DL AF Buist, Diana S. M. Anderson, Melissa L. Haneuse, Sebastien J. P. A. Sickles, Edward A. Smith, Robert A. Carney, Patricia A. Taplin, Stephen H. Rosenberg, Robert D. Geller, Berta M. Onega, Tracy L. Monsees, Barbara S. Bassett, Lawrence W. Yankaskas, Bonnie C. Elmore, Joann G. Kerlikowske, Karla Miglioretti, Diana L. TI Influence of Annual Interpretive Volume on Screening Mammography Performance in the United States SO RADIOLOGY LA English DT Article ID CANCER SURVEILLANCE CONSORTIUM; ACCURACY; RADIOLOGISTS; QUALITY; PROGRAM AB Purpose: To examine whether U. S. radiologists' interpretive volume affects their screening mammography performance. Materials and Methods: Annual interpretive volume measures (total, screening, diagnostic, and screening focus [ratio of screening to diagnostic mammograms]) were collected for 120 radiologists in the Breast Cancer Surveillance Consortium (BCSC) who interpreted 783 965 screening mammograms from 2002 to 2006. Volume measures in 1 year were examined by using multivariate logistic regression relative to screening sensitivity, false-positive rates, and cancer detection rate the next year. BCSC registries and the Statistical Coordinating Center received institutional review board approval for active or passive consenting processes and a Federal Certificate of Confidentiality and other protections for participating women, physicians, and facilities. All procedures were compliant with the terms of the Health Insurance Portability and Accountability Act. Results: Mean sensitivity was 85.2% (95% confidence interval [CI]: 83.7%, 86.6%) and was significantly lower for radiologists with a greater screening focus (P = .023) but did not significantly differ by total (P = .47), screening (P = .33), or diagnostic (P = .23) volume. The mean false-positive rate was 9.1% (95% CI: 8.1%, 10.1%), with rates significantly higher for radiologists who had the lowest total (P = .008) and screening (P = .015) volumes. Radiologists with low diagnostic volume (P = .004 and P = .008) and a greater screening focus (P = .003 and P = .002) had significantly lower false-positive and cancer detection rates, respectively. Median invasive tumor size and proportion of cancers detected at early stages did not vary by volume. Conclusion: Increasing minimum interpretive volume requirements in the United States while adding a minimal requirement for diagnostic interpretation could reduce the number of false-positive work-ups without hindering cancer detection. These results provide detailed associations between mammography volumes and performance for policymakers to consider along with workforce, practice organization, and access issues and radiologist experience when reevaluating requirements. (C) RSNA, 2011 C1 [Buist, Diana S. M.; Anderson, Melissa L.; Haneuse, Sebastien J. P. A.; Miglioretti, Diana L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA. [Haneuse, Sebastien J. P. A.; Miglioretti, Diana L.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. [Sickles, Edward A.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Smith, Robert A.] Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. [Carney, Patricia A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Taplin, Stephen H.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. [Rosenberg, Robert D.] Univ New Mexico, Hlth Sci Ctr, Dept Radiol, Albuquerque, NM 87131 USA. [Geller, Berta M.] Univ Vermont, Coll Med, Burlington, VT USA. [Onega, Tracy L.] Norris Cotton Canc Ctr, Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. [Monsees, Barbara S.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Bassett, Lawrence W.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA 90095 USA. [Yankaskas, Bonnie C.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. [Elmore, Joann G.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. RP Buist, DSM (reprint author), Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM buist.d@ghc.org FU American Cancer Society; Longaberger Company's Horizon of Hope Campaign [SIRGS-07-271-01, SIRGS-07-272-01, SIRGS-07-274-01, SIRGS-07-275-01, SIRGS-06-281-01, ACS A1-07-362]; Breast Cancer Stamp Fund; Agency for Healthcare Research and Quality; National Cancer Institute [CA107623]; National Cancer Institute Breast Cancer Surveillance Consortium [U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, U01CA70040] FX Supported in part by the American Cancer Society and made possible by a generous donation from the Longaberger Company's Horizon of Hope Campaign (grants SIRGS-07-271-01, SIRGS-07-272-01, SIRGS-07-274-01, SIRGS-07-275-01, SIRGS-06-281-01, and ACS A1-07-362), the Breast Cancer Stamp Fund, the Agency for Healthcare Research and Quality and National Cancer Institute (grant CA107623), and the National Cancer Institute Breast Cancer Surveillance Consortium (grants U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). NR 35 TC 48 Z9 48 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2011 VL 259 IS 1 BP 72 EP 84 DI 10.1148/radiol.10101698 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 741FM UT WOS:000288848800011 PM 21343539 ER PT J AU Singh, S Pinsky, P Fineberg, NS Gierada, DS Garg, K Sun, YH Nath, PH AF Singh, Satinder Pinsky, Paul Fineberg, Naomi S. Gierada, David S. Garg, Kavita Sun, Yanhui Nath, P. Hrudaya TI Evaluation of Reader Variability in the Interpretation of Follow-up CT Scans at Lung Cancer Screening SO RADIOLOGY LA English DT Article ID SMALL PULMONARY NODULES; LOW-DOSE CT; INTRAOBSERVER VARIABILITY; SPIRAL CT; INTEROBSERVER; AGREEMENT; SIZE; RADIOLOGISTS; TRIAL AB Purpose: To measure reader agreement in determining whether lung nodules detected at baseline screening computed tomography (CT) had changed at subsequent screening examinations and to evaluate the variability in recommendations for further follow-up. Materials and Methods: All subjects were enrolled in the National Lung Screening Trial (NLST), and each participant consented to the use of their de-identified images for research purposes. The authors randomly selected 100 cases of nodules measuring at least 4.0 mm at 1-year screening CT that were considered by the original screening CT reader to be present on baseline CT scans; nodules considered by the original reader to have changed were oversampled. Selected images from each case showing the entire nodule at both examinations were preloaded on a picture archiving and communication system workstation. Nine radiologists served as readers, and they evaluated whether the nodule was present at baseline and recorded the bidimensional measurements and nodule characteristics at each examination, presence or absence of change, results of screening CT, and follow-up recommendations (high-level follow-up, low-level follow-up, no follow-up). Results: On the basis of reviews during case selection, five nodules seen at follow-up were judged not to have been present at baseline; for 19 of the remaining 95 cases, at least one reader judged the nodule not to have been present at baseline. For the 76 nodules that were unanimously considered to have been present at baseline, 21%-47% (mean 6 standard deviation, 30% +/- 9) were judged to have grown. The kappa values were similar for growth (kappa = 0.55) and a positive screening result (kappa = 0.51) and were lower for a change in margins and attenuation (kappa = 0.27-0.31). The kappa value in the recommendation of high-versus low-level follow-up was high (kappa = 0.66). Conclusion: Reader agreement on nodule growth and screening result was moderate to substantial. Agreement on follow-up recommendations was lower. (C) RSNA, 2011 C1 [Singh, Satinder; Nath, P. Hrudaya] Univ Alabama Hosp & Clin, Dept Radiol, Birmingham, AL 35249 USA. [Fineberg, Naomi S.; Sun, Yanhui] Univ Alabama Hosp & Clin, Dept Biostat, Birmingham, AL 35249 USA. [Pinsky, Paul] NCI, Bethesda, MD 20892 USA. [Gierada, David S.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Garg, Kavita] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. RP Nath, PH (reprint author), Univ Alabama Hosp & Clin, Dept Radiol, 619 19th St South, Birmingham, AL 35249 USA. EM hnath@uabmc.edu FU National Cancer Institute [N01-CN-25516]; National Lung Screening Trial; COPD-NLST FX This research was supported by the National Cancer Institute (contract N01-CN-25516).; S. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is on the GE Imaging in Healthcare Advisory Board. Other relationships: none to disclose. P. P. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. N.S.F. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. D. S. G. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. K. G. Financial activities related to the present article: institution receives money for support for travel to meetings for the study or other purposes from the National Lung Screening Trial. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. Y.S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. P.H.N. Financial activities related to the present article: receives support for travel to meetings for the study or other purposes from COPD-NLST. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. NR 20 TC 24 Z9 24 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2011 VL 259 IS 1 BP 263 EP 270 DI 10.1148/radiol.10101254 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 741FM UT WOS:000288848800032 PM 21248232 ER PT J AU Forooghian, F Meleth, AD Cukras, C Chew, EY Wong, WT Meyerle, CB AF Forooghian, Farzin Meleth, Annal D. Cukras, Catherine Chew, Emily Y. Wong, Wai T. Meyerle, Catherine B. TI FINASTERIDE FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE finasteride; chronic central serous chorioretinopathy; retina; optical coherence tomography ID INTRAVITREAL BEVACIZUMAB; PIGMENT-EPITHELIUM; TESTOSTERONE; KETOCONAZOLE; ANDROGEN; CORTICOSTEROIDS; IDENTIFICATION; ABNORMALITIES; RETINOPATHY; DETACHMENT AB Purpose: To evaluate the safety and efficacy of finasteride, an inhibitor of dihydrotestosterone synthesis, in the treatment of chronic central serous chorioretinopathy. Methods: Five patients with chronic central serous chorioretinopathy were prospectively enrolled in this pilot study. Patients were administered finasteride (5 mg) daily for 3 months, after which study medication was withheld and patients were observed for 3 months. Main outcome measures included best-corrected visual acuity, central subfield macular thickness, and subretinal fluid volume as assessed by optical coherence tomography. Serum dihydrotestosterone, serum testosterone, and urinary cortisol were also measured. Results: There was no change in mean best-corrected visual acuity. Mean center-subfield macular thickness and subretinal fluid volume reached a nadir at 3 months and rose to levels that were below baseline by 6 months. The changes in both optical coherence tomography parameters paralleled those in serum dihydrotestosterone level. In four patients, center-subfield macular thickness and/or subretinal fluid volume increased after discontinuation of finasteride. In the remaining patient, both optical coherence tomography parameters normalized with finasteride and remained stable when the study medication was discontinued. Conclusion: Finasteride may represent a novel medical treatment for chronic central serous chorioretinopathy. Larger controlled clinical trials are needed to further assess the efficacy of finasteride for the treatment of central serous chorioretinopathy. RETINA 31: 766-771, 2011 C1 [Forooghian, Farzin; Meleth, Annal D.; Cukras, Catherine; Chew, Emily Y.; Wong, Wai T.; Meyerle, Catherine B.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Meyerle, CB (reprint author), NEI, Div Epidemiol & Clin Res, NIH, Bldg 10,Magnuson Room 10S235,10 Ctr Dr, Bethesda, MD 20892 USA. EM meyerlec@nei.nih.gov RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute FX Supported by the National Eye Institute Intramural Research Program. NR 31 TC 19 Z9 19 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2011 VL 31 IS 4 BP 766 EP 771 DI 10.1097/IAE.0b013e3181f04a35 PG 6 WC Ophthalmology SC Ophthalmology GA 740HR UT WOS:000288783200020 PM 21273946 ER PT J AU Trinchieri, G AF Trinchieri, Giorgio TI An Aspirin for your Cancer? SO SCIENTIST LA English DT Article ID INFLAMMATION C1 NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 400 MARKET ST, STE 1250, PHILADELPHIA, PA 19106 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD APR PY 2011 VL 25 IS 4 BP 38 EP 43 PG 6 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 739SL UT WOS:000288738200017 ER PT J AU Fields, RD AF Fields, R. Douglas TI Nonsynaptic and nonvesicular ATP release from neurons and relevance to neuron-glia signaling SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE ATP release; Neuron-glia interactions; Axon volume; Intrinsic optical signals; Activity-dependent development; Synaptic-vesicle release; Neurotransmitter release; Axon swelling; Learning; Volume-activated anion channel; White matter ID ADRENERGIC INHIBITORY NERVES; CENTRAL-NERVOUS-SYSTEM; DORSAL-ROOT GANGLION; MAXI-ANION CHANNEL; PIG VAS-DEFERENS; ADENOSINE-TRIPHOSPHATE; ACTION-POTENTIALS; CALCIUM WAVES; MECHANICAL CHANGES; SCHWANN-CELLS AB Studies on the release of ATP from neurons began with the earliest investigations of quantal neurotransmitter release in the 1950s, but in contrast to ATP release from other cells, studies of ATP release from neurons have been narrowly constrained to one mechanism, vesicular release. This is a consequence of the prominence of synaptic transmission in neuronal communication, but nonvesicular mechanisms for ATP release from neurons are likely to have a broader range of functions than synaptic release. Investigations of activity-dependent communication between axons and myelinating glia have stimulated a search for mechanisms that could release ATP from axons and other nonsynaptic regions in response to action potential firing. This has identified volume-activated anion channels as an important mechanism in activity-dependent ATP release from axons, and renewed interest in micromechanical changes in axons that accompany action potential firing. (C) 2011 Published by Elsevier Ltd. C1 NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, Nervous Syst Dev & Plast Sect, NIH, Bldg 35,Room 2A211,MSC 3713,35 Lincoln Dr, Bethesda, MD 20892 USA. EM fieldsd@mail.nih.gov FU National Institutes of Child Health; Human Development funds for intramural research FX This work was supported by National Institutes of Child Health and Human Development funds for intramural research. NR 111 TC 38 Z9 40 U1 1 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD APR PY 2011 VL 22 IS 2 BP 214 EP 219 DI 10.1016/j.semcdb.2011.02.009 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 744CP UT WOS:000289071500013 PM 21320624 ER PT J AU Cirstea, CM Brooks, WM Craciunas, SC Popescu, EA Choi, IY Lee, P Bani-Ahmed, A Yeh, HW Savage, CR Cohen, LG Nudo, RJ AF Cirstea, Carmen M. Brooks, William M. Craciunas, Sorin C. Popescu, Elena A. Choi, In-Young Lee, Phil Bani-Ahmed, Ali Yeh, Hung-Wen Savage, Cary R. Cohen, Leonardo G. Nudo, Randolph J. TI Primary Motor Cortex in Stroke A Functional MRI-Guided Proton MR Spectroscopic Study SO STROKE LA English DT Article DE (1)H-MRS; motor impairment; plasticity; primary motor cortex; stroke; plasticity ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN BRAIN; RESONANCE-SPECTROSCOPY; WHITE-MATTER; DIASCHISIS; INFARCTION; RECOVERY; PERFORMANCE; MYOINOSITOL; METABOLISM AB Background and Purpose-Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal-glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke. Methods-Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate, myo-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5x5 mm(2)) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated. Results-The stroke survivors showed lower N-acetylaspartate and higher myo-inositol across ipsilesional and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke. Conclusions-Our preliminary data demonstrated significant alterations of neuronal-glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke. (Stroke. 2011;42:1004-1009.) C1 [Cirstea, Carmen M.; Brooks, William M.; Craciunas, Sorin C.; Popescu, Elena A.; Choi, In-Young; Lee, Phil; Bani-Ahmed, Ali; Savage, Cary R.] Univ Kansas, Hoglund Brain Imaging Ctr, Med Ctr, Kansas City, KS 66160 USA. [Nudo, Randolph J.] Univ Kansas, Landon Ctr Aging, Med Ctr, Kansas City, KS 66160 USA. [Cirstea, Carmen M.; Bani-Ahmed, Ali] Univ Kansas, Dept Phys Therapy & Rehabil Sci, Med Ctr, Kansas City, KS 66160 USA. [Brooks, William M.; Choi, In-Young] Univ Kansas, Dept Neurol, Med Ctr, Kansas City, KS 66160 USA. [Nudo, Randolph J.] Univ Kansas, Dept Mol & Integrat Physiol, Med Ctr, Kansas City, KS 66160 USA. [Yeh, Hung-Wen] Univ Kansas, Dept Biostat, Med Ctr, Kansas City, KS 66160 USA. [Savage, Cary R.] Univ Kansas, Dept Psychiat & Behav Sci, Med Ctr, Kansas City, KS 66160 USA. [Cohen, Leonardo G.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. [Cohen, Leonardo G.] NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. RP Cirstea, CM (reprint author), Univ Kansas, Hoglund Brain Imaging Ctr, Med Ctr, 3901 Rainbow Blvd,Mail Stop 1052, Kansas City, KS 66160 USA. EM ccirstea@kumc.edu OI Lee, Phil/0000-0002-2087-8887; brooks, william/0000-0001-6227-7636; Cirstea, Mihaela Carmen/0000-0002-4059-9893 FU Natural Sciences and Engineering Research Council of Canada; American Heart Association [0860041Z, 0655759Z] FX This work was supported by Natural Sciences and Engineering Research Council of Canada (CMC) and American Heart Association (0860041Z C.M.C.; 0655759Z W.M.B.). The Hoglund Brain Imaging Center is supported by a generous gift from Forrest and Sally Hoglund and the United States National Institutes of Health (P30 HD 002528). NR 35 TC 13 Z9 13 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2011 VL 42 IS 4 BP 1004 EP 1009 DI 10.1161/STROKEAHA.110.601047 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 741IK UT WOS:000288857200034 PM 21330627 ER PT J AU Luby, M Ku, KD Latour, LL Merino, JG Hsia, AW Lynch, JK Warach, S AF Luby, Marie Ku, Katherine D. Latour, Lawrence L. Merino, Jose G. Hsia, Amie W. Lynch, John K. Warach, Steven TI Visual Perfusion-Diffusion Mismatch Is Equivalent to Quantitative Mismatch SO STROKE LA English DT Article DE acute ischemic stroke; diffusion-weighted imaging; magnetic resonance imaging; mismatch; perfusion-weighted imaging ID CEREBRAL-ISCHEMIA; STROKE; MRI; DESMOTEPLASE; RELIABILITY; WINDOW; VOLUME AB Background and Purpose-The concept of stroke MRI mismatch based on qualitative evaluation of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) has been applied in clinical practice for several years. The benefit of MRI in providing pathological evidence of ischemia before thrombolytic treatment has been demonstrated. The purpose of this study is to determine the reliability of the qualitative method and compare it with quantitative mismatch measurement in thrombolytic-treated patients. Methods-Patients (n=70) were selected from the Lesion Evolution of Stroke and Ischemic On Neuroimaging (LESION) database if they: (1) were treated with intravenous recombinant tissue plasminogen activator; (2) had a pretreatment MRI with evaluable DWI and PWI; and (3) had acute ischemic lesion volume >10 mL on DWI as determined by core imaging laboratory measurements. Quantitative mismatch was defined as a difference of >50 mL between abnormal mean transit time and DWI volumes. Sample characteristics and postdischarge modified Rankin Scale for the positive mismatch patients were compared between the subgroups identified by qualitative versus quantitative methods. Results-Patient characteristics and thrombolytic outcomes (sex, age, National Institutes of Health Stroke Scale, mismatch volume, and modified Rankin Scale) did not differ for mismatch patients identified by qualitative versus quantitative methods. Qualitative mismatch selection among neurologists had a high sensitivity (0.82), specificity (0.80), accuracy (0.81), and positive predictive value (0.88) compared with quantitative measurements. Conclusions-We observed that qualitative evaluation of mismatch identified the same thrombolytic-treated patients compared with retrospective quantitative mismatch measurements. (Stroke. 2011;42:1010-1014.) C1 [Luby, Marie] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA. [Merino, Jose G.] Suburban Hosp Stroke Ctr, Bethesda, MD USA. [Hsia, Amie W.] Washington Hosp Ctr Stroke Ctr, Bethesda, MD USA. RP Luby, M (reprint author), NINDS, Sect Stroke Diagnost & Therapeut, 10 Ctr Dr,MSC 1063,Bldg 10,Room B1D733, Bethesda, MD 20892 USA. EM lubym@ninds.nih.gov OI Merino, Jose/0000-0002-6676-0008 FU Division of Intramural Research of the National Institutes of Health; National Institute of Neurological Disorders and Stroke FX This research was supported by the Division of Intramural Research of the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. NR 14 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2011 VL 42 IS 4 BP 1010 EP 1014 DI 10.1161/STROKEAHA.110.603290 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 741IK UT WOS:000288857200035 PM 21311057 ER PT J AU Mitmaker, EJ Griff, NJ Grogan, RH Sarkar, R Kebebew, E Duh, QY Clark, OH Shen, WT AF Mitmaker, Elliot J. Griff, Nicholas J. Grogan, Raymon H. Sarkar, Rajabrata Kebebew, Electron Duh, Quan-Yang Clark, Orlo H. Shen, Wen T. TI Modulation of matrix metalloproteinase activity in human thyroid cancer cell lines using demethylating agents and histone deacetylase inhibitors SO SURGERY LA English DT Article ID NA+/I-SYMPORTER; GROWTH-FACTOR; PROTEIN EXPRESSION; TISSUE INHIBITORS; MESSENGER-RNA; CYCLE ARREST; LUNG-CANCER; METASTASIS; CARCINOMA; APOPTOSIS AB Background. The purpose of this study was to investigate the effects. of treating human. thyroid cancer cell lines with demethylating agents and histone deacetylase (HDAC) inhibitors to see if they would downregulate expression and activity of the matrix metalloproteinases (MMP)-2 and MMP-9, resulting in inhibition of growth and invasion. Methods. A total of I papillary cancer cell line (TPC-I) and 3 follicular thyroid cancer cell lines (FTC-133, FIC-236, and FTC-238) were treated with the demethylating agent 5-azacylidine (5-AZC) and the HDAC inhibitors trichostatin A (TSA) and valproic acid (VA). The activity of MMP proteins was determined using gelatin zymography, and commercially available assays were used to quantify growth inhibition and thyroid cancer cell invasion. Results. Treatment with TSA and VA resulted in decreased protein activity of MMP-2 and MMP-9 in all cell lines in. a dose-dependent manner after 48 hours of treatment compared with untreated controls. In. addition, 5-, TSA, and VA caused inhibition of growth in the range of 25-80% for all cell lines at 24,48 and 72 hours VA and TSA significantly decreased cell invasion in the FTC-133 and TPC-I cell lines. Conclusion. The HDAC inhibitors TSA and VA decreased the protein activity of MMP-2 and MMP-9 and, in combination with the demethylating agent 5-AZC inhibited cellular growth in human papillary and follicular thyroid cancer cell lines. These results elucidate our understanding of the pathways affected by the demethylating agents and HDAC inhibitors, and provide further evidence that MMPs are a potentially useful target for molecular therapies in patients with aggressive or refractory thyroid cancers. (Surgery 2011;149:504-11). C1 [Mitmaker, Elliot J.; Griff, Nicholas J.; Grogan, Raymon H.; Duh, Quan-Yang; Clark, Orlo H.; Shen, Wen T.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Sarkar, Rajabrata] Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. [Kebebew, Electron] NCI, Endocrine Surg Sect, Surg Branch, Bethesda, MD 20892 USA. RP Mitmaker, EJ (reprint author), Univ Calif San Francisco, Dept Surg, 1600 Divisadero St,C-347,Hellman Bldg, San Francisco, CA 94143 USA. EM ellmit@yahoo.com FU McGill University Health Centre, Montreal, Quebec, Canada; Friends of Endocrine Surgery FX Supported in part by research grants from the Cedars Cancer Institute from the McGill University Health Centre, Montreal, Quebec, Canada (Henry R. Shibata Fellowship Award to E.J.M.) and the Friends of Endocrine Surgery. NR 40 TC 14 Z9 16 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2011 VL 149 IS 4 BP 504 EP 511 DI 10.1016/j.surg.2010.10.007 PG 8 WC Surgery SC Surgery GA 743KP UT WOS:000289017500005 PM 21193210 ER PT J AU Farhat, T Simons-Morton, B Luk, JW AF Farhat, Tilda Simons-Morton, Bruce Luk, Jeremy W. TI Psychosocial correlates of adolescent marijuana use: Variations by status of marijuana use SO ADDICTIVE BEHAVIORS LA English DT Article DE Marijuana use; Experimentation; Psychosocial correlates; Gender differences ID CANNABIS USE; MENTAL-HEALTH; SUBSTANCE USE; BEHAVIOR; SCHOOL; FAMILY; ADJUSTMENT; KNOWLEDGE; PATHWAYS; CHILDREN AB Introduction: This study examined the associations between psychosocial factors and status of marijuana use: former experimentation, current occasional, and current frequent use. Methods: Data were collected from a nationally-representative sample of U.S. tenth-graders who participated in the 2005/6 Health Behavior in School-aged Children Study (n = 1465). Multinomial regressions, run separately by gender, examined the association of risk and protective factors from the individual (life satisfaction; academic achievement; aggression, bullying) and contextual (mothers and fathers' knowledge of adolescents' activities, school climate) domains with status of marijuana use (former experimentation, current occasional use, current frequent use). Results: Former experimental and current marijuana uses were negatively associated with protective factors such as academic achievement, mothers' and fathers' knowledge of adolescents' activities, and life satisfaction, but not with positive school climate. Former experimental and current marijuana uses were positively associated with aggression and bullying perpetration. Most associations varied by gender and status of marijuana use. In adjusted analyses, aggression emerged as the sole risk factor and fathers' knowledge as the sole protective factor associated with most statuses of marijuana use, across gender. Conclusion: Fathers may be particularly important in preventing adolescent marijuana use, and interventions promoting fathers' knowledge of adolescents' activities are warranted. Published by Elsevier Ltd. C1 [Farhat, Tilda; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. [Luk, Jeremy W.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Farhat, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, 6100 Execut Blvd Room 7B13L, Bethesda, MD 20892 USA. EM farhatti@mail.nih.gov OI Simons-Morton, Bruce/0000-0003-1099-6617 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [N01-HD-5-3401]; Maternal and Child Health Bureau of the Health Resources and Services Administration (HRSA) FX This research was supported in part by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (Contract # N01-HD-5-3401) and the Maternal and Child Health Bureau of the Health Resources and Services Administration (HRSA). NICHD and HRSA had no role in the study design, collection, analysis or interpretation of the data, writing the manuscript, or the decision to submit the paper for publication. NR 20 TC 10 Z9 11 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2011 VL 36 IS 4 BP 404 EP 407 DI 10.1016/j.addbeh.2010.11.017 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 734PC UT WOS:000288346700020 PM 21186082 ER PT J AU Wannasilp, N Solomon, BD Warren-Mora, N Clegg, NJ Delgado, MR Lacbawan, F Hu, P Winder, TL Roessler, E Muenke, M AF Wannasilp, Nilrat Solomon, Benjamin D. Warren-Mora, Nicole Clegg, Nancy J. Delgado, Mauricio R. Lacbawan, Felicitas Hu, Ping Winder, Thomas L. Roessler, Erich Muenke, Maximilian TI Holoprosencephaly in a Family Segregating Novel Variants in ZIC2 and GLI2 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE holoprosencephaly; HPE; GLI2; ZIC2 ID SONIC-HEDGEHOG GENE; LOSS-OF-FUNCTION; HUMAN SIX3 GENE; MUTATIONS CAUSE; PHENOTYPE; SUPPRESSOR; SPECTRUM; TRANSCRIPTION; DEGRADATION; GENOTYPE AB Holoprosencephaly (HPE) is the most common malformation of the human forebrain. Typical manifestations in affected patients include a characteristic pattern of structural brain and craniofacial anomalies. HPE may be caused by mutations in over 10 identified genes; the inheritance is traditionally viewed as autosomal dominant with highly variable expressivity and incomplete penetrance. We present the description of a family simultaneously segregating two novel variants in the HPE-associated genes, ZIC2 and GLI2, as well as the results of extensive population-based studies of the variant region in GLI2. This is the first time that multiple HPE-associated variants in these genes have been reported in one family, and raises important questions about how clinicians and researchers should view the inheritance of conditions such as HPE. (C) 2011 Wiley-Liss, Inc. C1 [Wannasilp, Nilrat; Solomon, Benjamin D.; Warren-Mora, Nicole; Lacbawan, Felicitas; Hu, Ping; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Clegg, Nancy J.; Delgado, Mauricio R.] Texas Scottish Rite Hosp Children, Dallas, TX 75219 USA. [Delgado, Mauricio R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Winder, Thomas L.] Prevent Genet, Marshfield, WI USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU Division of Intramural Research; National Human Genome Research Institute; National Institutes of Health; Department of Health and Human Services, United States of America; Don and Linda Carter Foundation; Crowley-Carter Foundation FX Grant sponsor: Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, United States of America; Grant sponsor: Don and Linda Carter Foundation, Crowley-Carter Foundation NR 33 TC 12 Z9 13 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR PY 2011 VL 155A IS 4 BP 860 EP 864 DI 10.1002/ajmg.a.33903 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 740KP UT WOS:000288792700028 PM 21416594 ER PT J AU de Gonzalez, AB Kim, KP Knudsen, AB Lansdorp-Vogelaar, I Rutter, CM Smith-Bindman, R Yee, J Kuntz, KM van Ballegooijen, M Zauber, AG Berg, CD AF de Gonzalez, Amy Berrington Kim, Kwang Pyo Knudsen, Amy B. Lansdorp-Vogelaar, Iris Rutter, Carolyn M. Smith-Bindman, Rebecca Yee, Judy Kuntz, Karen M. van Ballegooijen, Marjolein Zauber, Ann G. Berg, Christine D. TI Radiation-Related Cancer Risks From CT Colonography Screening: A Risk-Benefit Analysis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colonography; colorectal cancer; CT; CT colonography radiation risk; radiation risk; screening ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL-CANCER; EXTRACOLONIC FINDINGS; IONIZING-RADIATION; TASK-FORCE; POPULATION; COLONOSCOPY; POLYPS; COST AB OBJECTIVE. The purpose of this study was to estimate the ratio of cancers prevented to induced (benefit-risk ratio) for CT colonography (CTC) screening every 5 years from the age of 50 to 80 years. MATERIALS AND METHODS. Radiation-related cancer risk was estimated using risk projection models based on the National Research Council's Biological Effects of Ionizing Radiation (BEIR) VII Committee's report and screening protocols from the American College of Radiology Imaging Network's National CT Colonography Trial. Uncertainty intervals were estimated using Monte Carlo simulation methods. Comparative modeling with three colorectal cancer microsimulation models was used to estimate the potential reduction in colorectal cancer cases and deaths. RESULTS. The estimated mean effective dose per CTC screening study was 8 mSv for women and 7 mSv for men. The estimated number of radiation-related cancers resulting from CTC screening every 5 years from the age of 50 to 80 years was 150 cases/100,000 individuals screened (95% uncertainty interval, 80-280) for men and women. The estimated number of colorectal cancers prevented by CTC every 5 years from age 50 to 80 ranged across the three microsimulation models from 3580 to 5190 cases/100,000 individuals screened, yielding a benefit-risk ratio that varied from 24: 1 (95% uncertainty interval, 13: 1-45: 1) to 35: 1 (19:1-65:1). The benefit-risk ratio for cancer deaths was even higher than the ratio for cancer cases. Inclusion of radiation-related cancer risks from CT examinations performed to follow up extracolonic findings did not materially alter the results. CONCLUSION. Concerns have been raised about recommending CTC as a routine screening tool because of potential harms including the radiation risks. Based on these models, the benefits from CTC screening every 5 years from the age of 50 to 80 years clearly outweigh the radiation risks. C1 [de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Yongin, Gyeonggi Do, South Korea. [Knudsen, Amy B.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Lansdorp-Vogelaar, Iris; van Ballegooijen, Marjolein] Univ Med Ctr Rotterdam, Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Rutter, Carolyn M.] Grp Hlth Ctr Hlth Studies, Seattle, WA USA. [Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Yee, Judy] Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. [Kuntz, Karen M.] Univ Minnesota, Div Hlth Policy & Management, Minneapolis, MN USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP de Gonzalez, AB (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM berringtona@mail.nih.gov RI Berg , Christine/K-1047-2014 FU GE Healthcare; NCI [U01 CA-97427, U01-CA-088204, U01-CA-097426, U01-CA-115953] FX J. Yee received a research grant from GE Healthcare.; This research was funded by the NCI Intramural Research Program and by NCI grants (U01 CA-97427, U01-CA-088204, U01-CA-097426, and U01-CA-115953). NR 33 TC 50 Z9 50 U1 2 U2 7 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2011 VL 196 IS 4 BP 816 EP 823 DI 10.2214/AJR.10.4907 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738OP UT WOS:000288650600038 PM 21427330 ER PT J AU Narayanan, D Madsen, KS Kalinyak, JE Berg, WA AF Narayanan, Deepa Madsen, Kathleen S. Kalinyak, Judith E. Berg, Wendie A. TI Interpretation of Positron Emission Mammography: Feature Analysis and Rates of Malignancy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast imaging; FDG; lexicon; positron emission mammography ID POSITIVE PREDICTIVE-VALUE; PROBABLY BENIGN LESIONS; FOLLOW-UP; BREAST MRI; FDG PET; BI-RADS; SONOGRAPHY; ENHANCEMENT; CARCINOMAS; SIZE AB OBJECTIVE. The purpose of our study was to define and illustrate standard terminology for describing findings on positron emission mammography (PEM) and provide associated rates of malignancy. SUBJECTS AND METHODS. Three hundred eighty-eight women with newly-diagnosed breast cancer anticipating breast-conserving surgery completed a multicenter trial comparing PEM to MRI in assessment of disease extent. Morphologic terminology to describe PEM findings was patterned on BI-RADS for MRI, and investigators were trained in the PEM lexicon. PEM imaging features of known malignancies and additional PEM lesions were recorded and correlated with outcome. The reference standard was biopsy or at least a 6-month follow-up. RESULTS. Of 166 additional lesions on PEM, 54 (33%) proved malignant, with median invasive tumor size 8 mm (range, 2-60 mm). Among 43 round or oval masses, 16 (37%) were malignant, compared with 16 of 21 (76%) of lobulated or irregular masses (p = 0.003). Among 14 findings of focal or regional nonmass uptake, two (14%) were malignant compared with four of 12 (33%) findings of linear-ductal or segmental uptake (p = 0.350). Malignancy rates for BI-RADS-type final assessments were category 2, one of 31 (3.2%); 3, three of 32 (9.4%); 4a, four of 18 (22%); 4b, nine of 33 (27%); 4c, 15 of 24 (63%); and 5, 22 of 28 (79%). On the basis of modeling, irregular or lobulated morphology was the strongest predictor of malignancy, followed by lesion laterality (i.e., ipsilateral to known cancer) then increasing semiquantitative (18)F-FDG uptake. CONCLUSION. Use of standardized terminology to report PEM findings will facilitate effective communication of results and consistent management. A probably benign category 3 assessment carried a substantial rate of malignancy for lesions seen on PEM, and biopsy may be more appropriate than follow-up. C1 [Narayanan, Deepa; Kalinyak, Judith E.] Naviscan Inc, San Diego, CA USA. [Madsen, Kathleen S.] Certus Int Inc, Chesterfield, MO USA. [Berg, Wendie A.] Amer Coll Radiol Imaging Network, Lutherville Timonium, MD USA. RP Narayanan, D (reprint author), NCI, NIH, Bldg 31,Rm 10A19,31 Ctr Dr, Bethesda, MD 20892 USA. EM mndeepa@gmail.com FU Naviscan, Inc.; National Institutes of Health [5 R44 CA 103102-05] FX Supported by Naviscan, Inc., and grant 5 R44 CA 103102-05 from the National Institutes of Health. NR 27 TC 18 Z9 19 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2011 VL 196 IS 4 BP 956 EP 970 DI 10.2214/AJR.10.4748 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738OP UT WOS:000288650600057 PM 21427350 ER PT J AU Narayanan, D Madsen, KS Kalinyak, JE Berg, WA AF Narayanan, Deepa Madsen, Kathleen S. Kalinyak, Judith E. Berg, Wendie A. TI Interpretation of Positron Emission Mammography and MRI by Experienced Breast Imaging Radiologists: Performance and Observer Reproducibility SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast; breast MRI; MRI; nuclear medicine and molecular imaging; technology assessment ID DIFFERENTIAL-DIAGNOSIS; ENHANCING LESIONS; VARIABILITY; ACCURACY; CANCER AB OBJECTIVE. In preparation for a multicenter trial of positron emission mammography (PEM) and MRI in women with newly diagnosed cancer, the two purposes of this study were to validate training of breast imagers in standardized interpretation of PEM and to validate performance of the same specialists interpreting MRI. MATERIALS AND METHODS. A 2-hour didactic module was developed to train Mammography Quality Standards Act-qualified radiologist observers to interpret PEM images, consisting of a sample feature analysis lexicon analogous to BI-RADS and 12 sample cases. Observers were then asked to review separate interpretive skills tasks for PEM (49 breasts, 20 [41%] of which were malignant) and MRI (32 breasts, 11 [34%] of which were malignant), describe findings, and give assessments analogous to BI-RADS (category 1, 2, 3, 4A, 4B, 4C, or 5). Demographic experience variables were collected for 36 observers from 15 sites. Performance against histopathologic truth was determined, and interobserver agreement for classifying features and final assessments was evaluated using kappa statistics. RESULTS. Across 36 observers, mean sensitivity, specificity, and area under the curve (AUC) for PEM were 96% (range, 75-100%), 84% (range, 66-97%), and 0.95 (range, 0.82-1.0), respectively. Mean sensitivity, specificity, and AUC for the MRI task were 82% (range, 45-100%), 67% (range, 38-91%), and 0.80 (range, 0.48-0.96), respectively. Interobserver agreement for PEM findings ranged from moderate to substantial, with kappa values of 0.57 for lesion type and 0.63 for final assessments. CONCLUSION. With minimal training, experienced breast imagers showed high performance in interpreting PEM images. Performance in MRI interpretation by the same observers validated expected clinical practice. C1 [Narayanan, Deepa; Kalinyak, Judith E.] Naviscan, San Diego, CA USA. [Madsen, Kathleen S.] Certus Int, Chesterfield, MO USA. [Berg, Wendie A.] Amer Coll Radiol Imaging Network, Lutherville Timonium, MD USA. RP Narayanan, D (reprint author), NCI, NIH, 31 Ctr Dr,Rm 10A19, Bethesda, MD 20892 USA. EM narayanand@mail.nih.gov FU Naviscan, Inc.; National Institutes of Health [5 R44 CA103102-05]; The Avon Foundation; National Cancer Institute through the American College of Radiology Imaging Network [U01 CA079778, U01 CA89008] FX This work was funded by Naviscan, Inc. and the National Institutes of Health (grant 5 R44 CA103102-05); development of the MRI qualification task was supported by grants from The Avon Foundation and the National Cancer Institute (grants U01 CA079778 and U01 CA89008) through the American College of Radiology Imaging Network. NR 26 TC 17 Z9 17 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2011 VL 196 IS 4 BP 971 EP 981 DI 10.2214/AJR.10.5081 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738OP UT WOS:000288650600058 PM 21427351 ER PT J AU Concheiro, M Shakleya, DM Huestis, MA AF Concheiro, Marta Shakleya, Diaa M. Huestis, Marilyn A. TI Simultaneous analysis of buprenorphine, methadone, cocaine, opiates and nicotine metabolites in sweat by liquid chromatography tandem mass spectrometry SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Buprenorphine; Methadone; Cocaine; Cotinine; Sweat; Drug monitoring ID ILLICIT HEROIN; GAS-CHROMATOGRAPHY; ORAL FLUID; ACETYLCODEINE; ABUSE; PATCH; DISPOSITION; VALIDATION; CODEINE; MARKER AB A liquid chromatography tandem mass spectrometry method for buprenorphine (BUP), norbuprenorphine (NBUP), methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), cocaine, benzoylecgonine, ecgonine methyl ester (EME), morphine, codeine, 6-acetylmorphine, heroin, 6-acetylcodeine, cotinine, and trans-3'-hydroxycotinine quantification in sweat was developed and comprehensively validated. Sweat patches were mixed with 6 mL acetate buffer at pH 4.5, and supernatant extracted with Strata-XC-cartridges. Reverse-phase separation was achieved with a gradient mobile phase of 0.1% formic acid and acetonitrile in 15 min. Quantification was achieved by multiple reaction monitoring of two transitions per compound. The assay was a linear 1-1,000 ng/patch, except EME 5-1,000 ng/patch. Intra-, inter-day and total imprecision were < 10.1%CV, analytical recovery 87.2-107.7%, extraction efficiency 35.3-160.9%, and process efficiency 25.5-91.7%. Ion suppression was detected for EME (-63.3%) and EDDP (-60.4%), and enhancement for NBUP (42.6%). Deuterated internal standards compensated for these effects. No carryover was detected, and all analytes were stable for 24 h at 22 A degrees C, 72 h at 4 A degrees C, and after three freeze/thaw cycles. The method was applied to weekly sweat patches from an opioid-dependent BUP-maintained pregnant woman; 75.0% of sweat patches were positive for BUP, 93.8% for cocaine, 37.5% for opiates, 6.3% for methadone and all for tobacco biomarkers. This method permits a fast and simultaneous quantification of 14 drugs and metabolites in sweat patches, with good selectivity and sensitivity. C1 [Huestis, Marilyn A.] NIDA, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. [Concheiro, Marta] Univ Santiago de Compostela, Fac Med, Dpto Anat Patol & Ciencias Forenses, Serv Toxicol Forense, Santiago De Compostela 15782, A Coruna, Spain. [Concheiro, Marta; Shakleya, Diaa M.; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse (NIDA) [RO1 DA12220]; National Institutes of Health (NIH) FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), and NIDA grant RO1 DA12220. Sweat patches were generously provided by PharmChem Laboratories, Inc, Fort Worth, Texas, USA. NR 25 TC 19 Z9 19 U1 3 U2 23 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 EI 1618-2650 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD APR PY 2011 VL 400 IS 1 BP 69 EP 78 DI 10.1007/s00216-010-4392-2 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 738RC UT WOS:000288658800008 PM 21125263 ER PT J AU Stewart, PA Coble, JB Vermeulen, R Blair, A Lubin, J Attfield, M Silverman, DT AF Stewart, Patricia A. Coble, Joseph B. Vermeulen, Roel Blair, Aaron Lubin, Jay Attfield, Michael Silverman, Debra T. TI Comments on the Diesel Exhaust in Miners Study Reply SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Letter ID NONMETAL MINING FACILITIES; NONDIFFERENTIAL MISCLASSIFICATION; RETROSPECTIVE EXPOSURE; BIAS C1 [Stewart, Patricia A.; Coble, Joseph B.; Vermeulen, Roel; Blair, Aaron; Lubin, Jay; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, IRAS, NL-3508 TD Utrecht, Netherlands. [Attfield, Michael] NIOSH, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Stewart, PA (reprint author), NCI, Div Canc Epidemiol & Genet, Bldg EPS,Room 8006,6120 Execut Blvd, Bethesda, MD 20892 USA. EM silvermd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 14 TC 4 Z9 4 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD APR PY 2011 VL 55 IS 3 BP 343 EP 346 DI 10.1093/annhyg/mer006 PG 4 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 737JZ UT WOS:000288566400014 ER PT J AU Chaturvedi, V Ramani, R Andes, D Diekema, DJ Pfaller, MA Ghannoum, MA Knapp, C Lockhart, SR Ostrosky-Zeichner, L Walsh, TJ Marchillo, K Messer, S Welshenbaugh, AR Bastulli, C Iqbal, N Paetznick, VL Rodriguez, J Sein, T AF Chaturvedi, Vishnu Ramani, Rama Andes, David Diekema, Daniel J. Pfaller, Michael A. Ghannoum, Mahmoud A. Knapp, Cindy Lockhart, Shawn R. Ostrosky-Zeichner, Luis Walsh, Thomas J. Marchillo, Karen Messer, Shawn Welshenbaugh, Amanda R. Bastulli, Cara Iqbal, Noreen Paetznick, Victor L. Rodriguez, Jose Sein, Tin TI Multilaboratory Testing of Two-Drug Combinations of Antifungals against Candida albicans, Candida glabrata, and Candida parapsilosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; ACUTE MYELOID-LEUKEMIA; IN-VITRO ACTIVITIES; AMPHOTERICIN-B; TIME-KILL; SYNERGISTIC ACTIVITIES; FILAMENTOUS FUNGI; CLINICAL-TRIAL; THERAPY; SUSCEPTIBILITY AB There are few multilaboratory studies of antifungal combination testing to suggest a format for use in clinical laboratories. In the present study, eight laboratories tested quality control (QC) strain Candida parapsilosis ATCC 22019 and clinical isolates Candida albicans 20533.043, C. albicans 20464.007, Candida glabrata 20205.075, and C. parapsilosis 20580.070. The clinical isolates had relatively high azole and echinocandin MICs. A modified CLSI M27-A3 protocol was used, with 96-well custom-made plates containing checkerboard pairwise combinations of amphotericin B (AMB), anidulafungin (AND), caspofungin (CSP), micafungin (MCF), posaconazole (PSC), and voriconazole (VRC). The endpoints were scored visually and on a spectrophotometer or enzyme-linked immunosorbent assay (ELISA) reader for 50% growth reduction (50% inhibitory concentration [IC(50)]). Combination IC(50)s were used to calculate summation fractional inhibitory concentration indices (FICIs) (Sigma FIC) based on the Lowe additivity formula. The results revealed that the IC(50)s of all drug combinations were lower or equal to the IC(50) of individual drugs in the combination. A majority of the Sigma FIC values were indifferent (Sigma FIC = 0.51 to 2.0), but no antagonism was observed (Sigma FIC >= 4). Synergistic combinations (Sigma FIC <= 0.5) were found for AMB-PSC against C. glabrata and for AMB-AND and AMB-CSP against C. parapsilosis by both visual and spectrophotometric readings. Additional synergistic interactions were revealed by either of the two endpoints for AMB-AND, AMB-CSP, AMB-MCF, AMB-PSC, AMB-VRC, AND-PSC, CSP-MCF, and CSP-PSC. The percent agreements among participating laboratories ranged from 37.5% (lowest) for AND-CSP and POS-VOR to 87.5% (highest) for AMB-MCF and AND-CSP. Median Sigma FIC values showed a wide dispersion, and interlaboratory agreements were less than 85% in most instances. Additional studies are needed to improve the interlaboratory reproducibility of antifungal combination testing. C1 [Chaturvedi, Vishnu; Ramani, Rama] Wadsworth Ctr, New York State Dept Hlth, Mycol Lab, Albany, NY 12208 USA. [Andes, David; Marchillo, Karen] Univ Wisconsin, Madison, WI USA. [Diekema, Daniel J.; Pfaller, Michael A.] Univ Iowa, Iowa City, IA USA. [Ghannoum, Mahmoud A.; Messer, Shawn; Welshenbaugh, Amanda R.] Case Western Reserve Univ, Ctr Med Mycol, Cleveland, OH 44106 USA. [Knapp, Cindy; Bastulli, Cara] Trek Diagnost Syst, Cleveland, OH USA. [Lockhart, Shawn R.; Iqbal, Noreen] Ctr Dis Control & Prevent, Atlanta, GA USA. [Ostrosky-Zeichner, Luis; Paetznick, Victor L.; Rodriguez, Jose] Univ Texas Houston, Sch Med, Houston, TX USA. [Walsh, Thomas J.; Sein, Tin] NCI, Bethesda, MD 20892 USA. RP Chaturvedi, V (reprint author), Wadsworth Ctr, New York State Dept Hlth, Mycol Lab, 120 New Scotland Ave, Albany, NY 12208 USA. EM vishnu@wadsworth.org RI Rodriguez Herrera, Juan Jose/I-3210-2015; OI Diekema, Daniel/0000-0003-1273-0724 FU Wadsworth Center Clinical Laboratory Reference System; Astellas USA; Merck Co.; Pfizer Inc.; Schering-Plough Research Institute FX We thank Adriana Verschoor for valuable editorial comments. This study was supported in parts with funds from the Wadsworth Center Clinical Laboratory Reference System (V.C.). Additional support came in the form of investigative grants from Astellas USA, Merck & Co., Pfizer Inc., and Schering-Plough Research Institute (V.C.). Trek Diagnostic Systems partially subsidized the cost of 96-well custom plates. NR 50 TC 13 Z9 14 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2011 VL 55 IS 4 BP 1543 EP 1548 DI 10.1128/AAC.01510-09 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 737US UT WOS:000288594600027 PM 21282457 ER PT J AU Ide, K Aoki, M Amano, M Koh, Y Yedidi, RS Das, D Leschenko, S Chapsal, B Ghosh, AK Mitsuya, H AF Ide, Kazuhiko Aoki, Manabu Amano, Masayuki Koh, Yasuhiro Yedidi, Ravikiran S. Das, Debananda Leschenko, Sofiya Chapsal, Bruno Ghosh, Arun K. Mitsuya, Hiroaki TI Novel HIV-1 Protease Inhibitors (PIs) Containing a Bicyclic P2 Functional Moiety, Tetrahydropyrano-Tetrahydrofuran, That Are Potent against Multi-PI-Resistant HIV-1 Variants SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VIRUS TYPE-1 VARIANTS; LIGAND X-RAY; IN-VITRO; BIOLOGICAL EVALUATION; CLEAVAGE SITES; P2-LIGANDS; DARUNAVIR; REPLICATION; SELECTION; DESIGN AB We identified GRL-1388 and -1398, potent nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) containing a bicyclic P2 functional moiety, tetrahydropyrano-tetrahydrofuran (Tp-THF). GRL-1388 was as potent as darunavir (DRV) against various drug-resistant HIV-1 laboratory strains with 50% effective concentration (EC(50)s) of 2.6 to 32.6 nM. GRL-1398 was significantly more potent against such variants than DRV with EC(50)s of 0.1 to 5.7 nM. GRL-1388 and -1398 were also potent against multiple-PI-resistant clinical HIV-1 variants (CLHIV-1MDR) with EC(50)s ranging from 2.7 to 21.3 nM and from 0.3 to 4.8 nM, respectively. A highly DRV-resistant HIV-1 variant selected in vitro remained susceptible to GRL-1398 with the EC(50) of 21.9 nM, while the EC(50) of DRV was 214.1 nM. When HIV-1NL4-3 was selected with GRL-1398, four amino acid substitutions-leucine to phenylalanine at a position 10 (L10F), A28S, L33F, and M46I-emerged, ultimately enabling the virus to replicate in the presence of > 1.0 mu M the compound beyond 57 weeks of selection. When a mixture of 10 different CLHIV-1MDR strains was selected, the emergence of resistant variants was more substantially delayed with GRL-1398 than with GRL-1388 and DRV. Modeling analyses revealed that GRL-1398 had greater overall hydrogen bonding and hydrophobic interactions than GRL-1388 and DRV and that GRL-1388 and -1398 had hydrogen bonding interactions with the main chain of the active-site amino acids (Asp29 and Asp30) of protease. The present findings warrant that GRL-1398 be further developed as a potential drug for treating individuals with HIV-1 infection. C1 [Ide, Kazuhiko; Aoki, Manabu; Amano, Masayuki; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. [Ide, Kazuhiko; Aoki, Manabu; Amano, Masayuki; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan. [Ide, Kazuhiko; Aoki, Manabu; Amano, Masayuki; Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Rheumatol, Kumamoto 8608556, Japan. [Aoki, Manabu] Kumamoto Hlth Sci Univ, Dept Med Technol, Kumamoto 8615598, Japan. [Yedidi, Ravikiran S.; Das, Debananda; Mitsuya, Hiroaki] NIH, Natl Canc Inst, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. [Leschenko, Sofiya; Chapsal, Bruno; Ghosh, Arun K.] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Leschenko, Sofiya; Chapsal, Bruno; Ghosh, Arun K.] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov RI Amano, Masayuki/N-7407-2016; OI Amano, Masayuki/0000-0003-0516-9502; Yedidi, Ravikiran/0000-0003-2755-1307 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institutes of Health [GM53386]; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Ministry of Health, Labor, and Welfare of Japan FX This study was supported in part by the Intramural Research Program of Center for Cancer Research, National Cancer Institute, National Institutes of Health (D. D. and H. M.); a grant from the National Institutes of Health (GM53386 to A. K. G.); a Grant-in-Aid for Scientific Research (Priority Areas to H. M.) from the Ministry of Education, Culture, Sports, Science, and Technology (Monbu-Kagakusho) of Japan (H. M.); and a Grant for Promotion of AIDS Research from the Ministry of Health, Labor, and Welfare (Kosei-Rodosho) of Japan (H. M.). This study utilized the computational resources of the Biowulf cluster at the National Institutes of Health. NR 36 TC 15 Z9 15 U1 1 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 APR PY 2011 VL 55 IS 4 BP 1717 EP 1727 DI 10.1128/AAC.01540-10 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 737US UT WOS:000288594600049 PM 21282450 ER PT J AU Texel, SJ Mattson, MP AF Texel, Sarah J. Mattson, Mark P. TI Impaired Adaptive Cellular Responses to Oxidative Stress and the Pathogenesis of Alzheimer's Disease SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID TRANSGENIC MOUSE MODEL; BODY-MASS INDEX; HIPPOCAMPAL SYNAPTIC PLASTICITY; HEAT-SHOCK PROTEINS; NERVE GROWTH-FACTOR; MANGANESE SUPEROXIDE-DISMUTASE; ENRICHMENT IMPROVES COGNITION; NEUROTROPHIC FACTOR LEVELS; LONG-TERM POTENTIATION; AMYLOID BETA-PEPTIDE AB As is generally true with other age-related diseases, Alzheimer's disease (AD) involves oxidative damage to cellular components in the affected tissue, in this case the brain. The causes and consequences of oxidative stress in neurons in AD are not fully understood, but considerable evidence points to important roles for accumulation of amyloid beta-peptide upstream of oxidative stress and perturbed cellular Ca(2+) homeostasis and energy metabolism downstream of oxidative stress. The identification of mutations in the beta-amyloid precursor protein and presenilin-1 as causes of some cases of early onset inherited AD, and the development of cell culture and animal models based on these mutations has greatly enhanced our understanding of the AD process, and has greatly expanded opportunities for preclinical testing of potential therapeutic interventions. In this regard, and of particular interest to us, is the elucidation of adaptive cellular stress response pathways (ACSRP) that can counteract multiple steps in the AD neurodegenerative cascades, thereby limiting oxidative damage and preserving cognitive function. ACSRP can be activated by factors ranging from exercise and dietary energy restriction, to drugs and phytochemicals. In this article we provide an overview of oxidative stress and AD, with a focus on ACSRP and their potential for preventing and treating AD. Antioxid. Redox Signal. 14, 1519-1534. C1 [Texel, Sarah J.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Texel, Sarah J.; Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging, NIH FX This work was supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 186 TC 22 Z9 23 U1 6 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2011 VL 14 IS 8 BP 1519 EP 1534 DI 10.1089/ars.2010.3569 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 741GB UT WOS:000288851000012 PM 20849373 ER PT J AU Xu, LB Sun, LG Wang, YH Xie, ZQ Zhu, RB Liu, XD Wang, JH Tang, LY AF Xu, Libin Sun, Liguang Wang, Yuhong Xie, Zhouqing Zhu, Renbin Liu, Xiaodong Wang, Jihuai Tang, Lingyu TI PREHISTORIC CULTURE, CLIMATE AND AGRICULTURE AT YUCHISI, ANHUI PROVINCE, CHINA SO ARCHAEOMETRY LA English DT Article DE YUCHISI SITE; NEOLITHIC PERIOD; HUMAN ACTIVITY; FOOD SUPPLY; CLIMATE CHANGE; MULTI-ELEMENT ANALYSIS; POLLEN ID SCOTTISH HISTORICAL SITES; MULTIELEMENT ANALYSIS; ASIAN MONSOON; SOIL; EAST; RECONSTRUCTION; SETTLEMENT; SEDIMENTS; ESTONIA; RECORD AB A palaeoculture sediment profile from the Yuchisi site, Mengcheng County of Anhui Province, China, was sampled to study the concentrations of elements, total carbon content, grain size and pollen percentages, to reveal information on food supply based on statistical analysis of elements between 5050 cal. yr BP and 4000 cal. yr BP. The variations in the reconstructed food supply and pollen percentages are in good agreement with the results of other archaeological methods. The results from pollen and element analyses indicate that the Longshan Culture at the Yuchisi site was not developed from the local Dawenkou Culture, and the cultural transition corresponds with an extremely dry event, which may have caused the change. C1 [Xu, Libin; Sun, Liguang; Xie, Zhouqing; Zhu, Renbin; Liu, Xiaodong] Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. [Xu, Libin] Chinese Res Inst Environm Sci, Beijing 100012, Peoples R China. [Wang, Yuhong] NIH, Bethesda, MD 20892 USA. [Wang, Jihuai] Chinese Acad Social Sci, Archaeol Inst, Beijing 100710, Peoples R China. [Tang, Lingyu] Chinese Acad Sci, Nanjing Inst Geol & Palaeontol, Nanjing 210008, Peoples R China. RP Sun, LG (reprint author), Univ Sci & Technol China, Inst Polar Environm, Hefei 230026, Anhui, Peoples R China. EM slg@ustc.edu.cn FU Knowledge Innovation of CAS [KZCX3-SW-151]; National Basic Research Program [2003CB415000] FX This research was supported by grants from the Projects of the Knowledge Innovation of CAS (No. KZCX3-SW-151) and the National Basic Research Program (No. 2003CB415000). We are very grateful to Professor Zhang Juzhong for providing material for us and to Luo Honghao for help in the experiments. We thank Professors Mayke Wagner and Liu Yi for their advice with regard to the text. Finally, we thank all the reviewers of this paper for their suggestions. NR 42 TC 0 Z9 2 U1 3 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-813X J9 ARCHAEOMETRY JI Archaeometry PD APR PY 2011 VL 53 BP 396 EP 410 DI 10.1111/j.1475-4754.2010.00551.x PN 2 PG 15 WC Archaeology; Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Geosciences, Multidisciplinary SC Archaeology; Chemistry; Geology GA 736MX UT WOS:000288499900009 ER PT J AU Yang, S Prentice, RL AF Yang, Song Prentice, Ross L. TI Estimation of the 2-sample hazard ratio function using a semiparametric model SO BIOSTATISTICS LA English DT Article DE Clinical trial; Empirical process; Gaussian process; Hazard ratio; Simultaneous inference; Survival analysis; Treatment-time interaction ID ESTROGEN PLUS PROGESTIN; REGRESSION-MODELS; CONFIDENCE BANDS; CENSORED-DATA; SURVIVAL CURVES; SHORT-TERM; COX MODEL; LONG-TERM; COEFFICIENTS; LIKELIHOOD AB The hazard ratio provides a natural target for assessing a treatment effect with survival data, with the Cox proportional hazards model providing a widely used special case. In general, the hazard ratio is a function of time and provides a visual display of the temporal pattern of the treatment effect. A variety of nonproportional hazards models have been proposed in the literature. However, available methods for flexibly estimating a possibly time-dependent hazard ratio are limited. Here, we investigate a semiparametric model that allows a wide range of time-varying hazard ratio shapes. Point estimates as well as pointwise confidence intervals and simultaneous confidence bands of the hazard ratio function are established under this model. The average hazard ratio function is also studied to assess the cumulative treatment effect. We illustrate corresponding inference procedures using coronary heart disease data from the Women's Health Initiative estrogen plus progestin clinical trial. C1 [Yang, Song] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Yang, S (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA. EM yangso@nhlbi.nih.gov FU National Institutes of Health [CA 53996] FX National Institutes of Health (CA 53996 to Ross L. Prentice). NR 26 TC 4 Z9 4 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 EI 1468-4357 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2011 VL 12 IS 2 BP 354 EP 368 DI 10.1093/biostatistics/kxq061 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 740ND UT WOS:000288800600013 PM 20860993 ER PT J AU Robitaille, JM Zheng, B Wallace, K Beis, MJ Tatlidil, C Yang, J Sheidow, TG Siebert, L Levin, AV Lam, WC Arthur, BW Lyons, CJ Jaakkola, E Tsilou, E Williams, CA Weaver, RG Shields, CL Guernsey, DL AF Robitaille, Johane M. Zheng, Binyou Wallace, Karin Beis, M. Jill Tatlidil, Cuneyt Yang, Jenny Sheidow, Tom G. Siebert, Lee Levin, Alex V. Lam, Wai-Ching Arthur, Brian W. Lyons, Christopher J. Jaakkola, Elisa Tsilou, Ekaterini Williams, Charles A. Weaver, Richard Grey, Jr. Shields, Carol L. Guernsey, Duane L. TI The role of Frizzled-4 mutations in familial exudative vitreoretinopathy and Coats disease SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FZD4 MUTATIONS; RETINAL ANGIOGENESIS; GENE; PREMATURITY; RETINOPATHY; PHENOTYPE; IMPACT; NORRIN; LRP5 AB Aim The aim of this study is to assess the role of Frizzled-4 (FZD4) in familial exudative vitreoretinopathy (FEVR) and Coats disease. Methods Tissue samples were collected for DNA extraction and automated DNA sequencing of the two coding exons of FZD4 in both directions. Cases carrying a FZD4 mutation and demonstrating extreme disease severity were selected for direct automated sequencing of all coding exons of LRP5, NDP and TSPAN12. Clinical data were obtained for the purpose of identifying genotype-ephenotype correlations. Results 68 probands were diagnosed as having autosomal dominant or sporadic FEVR. Eleven FZD4 mutations (five missense, three deletions, one insertion, two nonsense) were identified. Six of these mutations are novel, and none were found in 346 control chromosomes. In 16 cases of Coats disease, one polymorphism combination was found in two samples: no mutations were detected. No genotype-ephenotype correlation emerged. Three severely affected cases with FZD4 mutations failed to show additional mutations in the three other FEVR genes. Conclusion The authors identified 12 FEVR probands with FZD4 mutations. FZD4 mutation screening can be a useful tool especially in mild or atypical cases of FEVR. Germ-line mutations in FZD4 do not appear to be a common cause of Coats disease. C1 [Robitaille, Johane M.; Zheng, Binyou; Yang, Jenny; Guernsey, Duane L.] Dalhousie Univ, Halifax, NS, Canada. [Wallace, Karin; Beis, M. Jill] IWK Hlth Ctr, Halifax, NS, Canada. [Tatlidil, Cuneyt] Valley Hlth Reg Hosp, Kentville, NS, Canada. [Sheidow, Tom G.; Siebert, Lee] Univ Western Ontario, London, ON, Canada. [Levin, Alex V.; Shields, Carol L.] Thomas Jefferson Univ, Wills Eye Inst, Philadelphia, PA 19107 USA. [Lam, Wai-Ching] Univ Toronto, Toronto, ON, Canada. [Arthur, Brian W.] Queens Univ, Kingston, ON, Canada. [Lyons, Christopher J.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Jaakkola, Elisa] Oulu Univ, Oulu, Finland. [Tsilou, Ekaterini] NEI, Bethesda, MD 20892 USA. [Williams, Charles A.] Univ Florida, Gainesville, FL USA. [Weaver, Richard Grey, Jr.] Wake Forest Univ, Winston Salem, NC 27109 USA. RP Robitaille, JM (reprint author), Ctr Hlth, Eye Care Team, 5850-5980 Univ Ave,POB 9700, Halifax, NS B3K 6R8, Canada. EM jrobitai@dal.ca OI Sheidow, Tom/0000-0001-6370-1857 FU March of Dimes Birth Defects Foundation: United States; IWK Health Centre: Halifax, Nova Scotia, Canada FX March of Dimes Birth Defects Foundation: United States; IWK Health Centre: Halifax, Nova Scotia, Canada. NR 21 TC 18 Z9 21 U1 2 U2 12 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD APR PY 2011 VL 95 IS 4 BP 574 EP 579 DI 10.1136/bjo.2010.190116 PG 6 WC Ophthalmology SC Ophthalmology GA 736NZ UT WOS:000288502700030 PM 21097938 ER PT J AU Sridhar, SS Canil, CM Chi, KN Hotte, SJ Ernst, S Wang, L Chen, EX Juhasz, A Yen, Y Murray, P Zwiebel, JA Moore, MJ AF Sridhar, Srikala S. Canil, Christina M. Chi, Kim N. Hotte, Sebastien J. Ernst, Scott Wang, Lisa Chen, Eric X. Juhasz, Agnes Yen, Yun Murray, Peter Zwiebel, James A. Moore, Malcolm J. TI A phase II study of the antisense oligonucleotide GTI-2040 plus docetaxel and prednisone as first-line treatment in castration-resistant prostate cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Castrate-resistant prostate cancer; Docetaxel; GTI-2040; Phase II ID RIBONUCLEOTIDE REDUCTASE; CLINICAL-TRIALS; SOLID TUMORS; MITOXANTRONE; R2; GEMCITABINE; GUIDELINES; EXPRESSION; VARIETY; ANTIGEN AB GTI-2040 is a novel antisense oligonucleotide to the R2 subunit of ribonucleotide reductase. This phase II trial was conducted to determine the efficacy and tolerability of GTI-2040 when combined with docetaxel and prednisone for the treatment of patients with castration-resistant prostate cancer (CRPC). Chemo-na < ve CRPC patients with adequate performance status and organ function were treated with docetaxel 75 mg/m(2) IV on day 1 plus GTI-2040 5 mg/kg/day by continuous intravenous infusion day 1-14 on a 21 day cycle, with prednisone 5 mg orally twice daily. The primary endpoint was PSA response rate. Pharmacokinetic studies of GTI-2040 and pharmacodynamic studies on peripheral blood mononuclear cells (PBMC) were also performed. Twenty-two patients in total (19 from this study and 3 from a prior phase I/II study at this institution) were treated at the recommended phase II dose. A confirmed PSA response was seen in 9/22 patients (41%). Of 16 patients with measurable disease, there was 1 partial response (PR) and 12 stable disease (SD) lasting 3.6 months (median), as best response. The most common toxicities were anemia, fatigue, lymphopenia, leucopenia and neutropenia. Grade 3+ toxicities included neutropenia, lymphopenia, leucopenia, fatigue, febrile neutropenia and hypophosphatemia. The PSA response rate of GTI-2040 in combination with docetaxel and prednisone just met the minimum phase II criteria for further enrollment. However, after evaluation of all the clinical data, further study of this dose and schedule of GTI-2040 in CRPC was not recommended. C1 [Sridhar, Srikala S.; Wang, Lisa; Chen, Eric X.; Moore, Malcolm J.] Univ Toronto, Princess Margaret Hosp, Phase Consortium 2, Toronto, ON M5G 2M9, Canada. [Canil, Christina M.] Ottawa Reg Canc Ctr, Ottawa, ON, Canada. [Hotte, Sebastien J.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Ernst, Scott] London Reg Canc Ctr, London, ON N6A 4L6, Canada. [Juhasz, Agnes; Yen, Yun] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Murray, Peter] Lorus Therapeut Inc, Toronto, ON, Canada. [Zwiebel, James A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Chi, Kim N.] BC Canc Agcy, Vancouver, BC, Canada. RP Sridhar, SS (reprint author), Univ Toronto, Princess Margaret Hosp, Phase Consortium 2, 610 Univ Ave,Suite 5-222, Toronto, ON M5G 2M9, Canada. EM srikala.sridhar@uhn.on.ca FU NIH; NCI [N01CM17107, N01CM62203] FX Grant support: NIH grant. NCI contracts N01CM17107, N01CM62203. NR 23 TC 11 Z9 11 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD APR PY 2011 VL 67 IS 4 BP 927 EP 933 DI 10.1007/s00280-010-1389-7 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 740MF UT WOS:000288798100023 PM 20602233 ER PT J AU Castiello, L Sabatino, M Jin, P Clayberger, C Marincola, FM Krensky, AM Stroncek, DF AF Castiello, Luciano Sabatino, Marianna Jin, Ping Clayberger, Carol Marincola, Francesco M. Krensky, Alan M. Stroncek, David F. TI Monocyte-derived DC maturation strategies and related pathways: a transcriptional view SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE Dendritic cells; Gene profiling; Maturation; Th polarization ID DENDRITIC-CELL MATURATION; GENE-EXPRESSION PROFILES; CANCER VACCINES; IFN-BETA; IMMUNOLOGICAL CONSTANT; MEDIATED REGULATION; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; AUTOLOGOUS TUMOR; MESSENGER-RNA AB Ex vivo production of highly stimulator mature dendritic cells (DCs) for cellular therapy has been used to treat different pathological conditions with the aim of inducing a specific immune response. In the last decade, several protocols have been developed to mature monocyte-derived DCs: each one has led to the generation of DCs showing different phenotypes and stimulatory abilities, but it is not yet known which one is the best for inducing effective immune responses. We grouped several different maturation protocols according to the downstream pathways they activated and reviewed the shared features at a transcriptomic level to reveal the potential of DCs matured by each protocol to develop Th-polarized immune responses. C1 [Castiello, Luciano; Sabatino, Marianna; Jin, Ping; Stroncek, David F.] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Clayberger, Carol; Krensky, Alan M.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM DStroncek@cc.nih.gov RI Castiello, Luciano/K-8616-2016 OI Castiello, Luciano/0000-0001-7146-3158 FU National Institutes of Health Clinical Center; National Cancer Institute FX This work is supported by the Intramural Programs of the National Institutes of Health Clinical Center and National Cancer Institute. NR 82 TC 28 Z9 31 U1 1 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2011 VL 60 IS 4 BP 457 EP 466 DI 10.1007/s00262-010-0954-6 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 737GI UT WOS:000288556700001 PM 21258790 ER PT J AU Bustos, DM Bailey, MJ Sugden, D Carter, DA Rath, MF Moller, M Coon, SL Weller, JL Klein, DC AF Bustos, Diego M. Bailey, Michael J. Sugden, David Carter, David A. Rath, Martin F. Moller, Morten Coon, Steven L. Weller, Joan L. Klein, David C. TI Global daily dynamics of the pineal transcriptome SO CELL AND TISSUE RESEARCH LA English DT Review DE Pineal gland; Suprachiasmatic nucleus; Circadian rhythm; Gene expression; Transcriptome; Microarray; Systems biology ID PROTEIN-KINASE-C; ARYLALKYLAMINE-N-ACETYLTRANSFERASE; ADRENERGIC-CAMP MECHANISM; RAT PINEALOCYTES; GENE-TRANSCRIPTION; DAILY RHYTHM; GLAND; EXPRESSION; CELLS; ADENOSINE-3',5'-MONOPHOSPHATE AB Transcriptome profiling of the pineal gland has revealed night/day differences in the expression of a major fraction of the genes active in this tissue, with two-thirds of these being nocturnal increases. A set of over 600 transcripts exhibit two-fold to > 100-fold daily differences in abundance. These changes appear to be primarily attributable to adrenergic-cyclic-AMP-dependent mechanisms, which are controlled via a neural pathway that includes the suprachiasmatic nucleus, the master circadian oscillator. In addition to melatonin synthesis, night/day differences in gene expression impact genes associated with several specialized functions, including the immune/inflammation response, photo-transduction, and thyroid hormone/retinoic acid biology. The following nonspecialized cellular features are also affected: adhesion, cell cycle/cell death, cytoskeleton, DNA modification, endothelium, growth, RNA modification, small molecule biology, transcription factors, vesicle biology, signaling involving Ca2+, cyclic nucleotides, phospholipids, mitogen-activated protein kinases, the Wnt signaling pathway, and protein phosphorylation. C1 [Bustos, Diego M.] Inst Tecnol Chascomus, Inst Invest Biotecnol, Chascomus, Argentina. [Bailey, Michael J.] Texas A&M Univ, Dept Poultry Sci, College Stn, TX 77843 USA. [Sugden, David] Kings Coll London, Div Reprod & Endocrinol, Sch Biomed & Hlth Sci, London SE1 1UL, England. [Carter, David A.] Cardiff Univ, Sch Biosci, Cardiff CF10 3AX, S Glam, Wales. [Rath, Martin F.; Moller, Morten] Univ Copenhagen, Dept Neurosci & Pharmacol, Fac Hlth Sci, DK-2200 Copenhagen, Denmark. [Coon, Steven L.; Weller, Joan L.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuroendocrinol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NIH 49-6A82, Bethesda, MD 20892 USA. EM Kleind@mail.nih.gov RI Carter, David/A-4479-2010; OI Carter, David/0000-0002-8419-3975; Rath, Martin/0000-0002-4047-6324 NR 57 TC 8 Z9 8 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X EI 1432-0878 J9 CELL TISSUE RES JI Cell Tissue Res. PD APR PY 2011 VL 344 IS 1 BP 1 EP 11 DI 10.1007/s00441-010-1094-1 PG 11 WC Cell Biology SC Cell Biology GA 739XG UT WOS:000288754300001 PM 21302120 ER PT J AU Barbey, AK Koenigs, M Grafman, J AF Barbey, Aron K. Koenigs, Michael Grafman, Jordan TI Orbitofrontal Contributions to Human Working Memory SO CEREBRAL CORTEX LA English DT Article DE lesion data; orbitofrontal cortex; prefrontal cortex; working memory ID DORSOLATERAL PREFRONTAL CORTEX; DECISION-MAKING; BRAIN-LESIONS; FRONTAL LOBES; TASK; ORGANIZATION; METAANALYSIS; INVOLVEMENT; EXPERIENCE; ATTENTION AB Although cognitive neuroscience has made remarkable progress in understanding the involvement of the prefrontal cortex in human memory, the necessity of the orbitofrontal cortex for key competencies of working memory remains largely unexplored. We therefore studied human brain lesion patients to determine whether the orbitofrontal cortex is necessary for working memory function, administering subtests of the Wechsler memory scale, the Wechsler adult intelligence scale, and the n-back task to 3 participant groups: orbitofrontal lesions (n = 24), prefrontal lesions not involving orbitofrontal cortex (n = 40), and no brain lesions (n = 54). Orbitofrontal damage was reliably associated with deficits on neuropsychological tests involving the coordination of working memory maintenance, manipulation, and monitoring processes (n-back task) but not on pure tests of working memory maintenance (digit/spatial span forward) or manipulation (digit/spatial span backward and letter-number sequencing). Our findings elucidate a central component of the neural architecture of working memory, providing key neuropsychological evidence for the necessity of the orbitofrontal cortex in executive control functions underlying the joint maintenance, manipulation, and monitoring of information in working memory. C1 [Barbey, Aron K.; Grafman, Jordan] NINDS, Cognit Neurosci Sect, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Barbey, Aron K.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Koenigs, Michael] Univ Wisconsin, Dept Psychiat, Wisconsins Psychiat Inst & Clin, Madison, WI 53719 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, US Natl Inst Hlth, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1440, Bethesda, MD 20892 USA. EM GrafmanJ@ninds.nih.gov RI Barbey, Aron/L-7312-2015; OI Barbey, Aron/0000-0002-6092-0912; Grafman, Jordan H./0000-0001-8645-4457; Koenigs, Michael/0000-0002-5799-4881 FU US National Institute of Neurological Disorders and Stroke; US Army Medical Research and Material Command [DAMD17-01-1-0675] FX US National Institute of Neurological Disorders and Stroke Intramural Research Program; Project grant from the US Army Medical Research and Material Command administered by the Henry M. Jackson Foundation (Vietnam Head Injury Study Phase 3: a 30-year post-injury follow-up study, grant DAMD17-01-1-0675). NR 53 TC 40 Z9 40 U1 2 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 APR PY 2011 VL 21 IS 4 BP 789 EP 795 DI 10.1093/cercor/bhq153 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 737JC UT WOS:000288564100006 PM 20724371 ER PT J AU Memoli, MJ AF Memoli, Matthew J. TI Severity of pH1N1 influenza A reply SO CRITICAL CARE MEDICINE LA English DT Letter ID MORTALITY; VIRUS C1 NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Memoli, MJ (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2011 VL 39 IS 4 BP 926 EP 927 DI 10.1097/CCM.0b013e31820f70d4 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 736ZD UT WOS:000288533000076 ER PT J AU Tanigawa, S Wang, HG Yang, YL Sharma, N Tarasova, N Ajima, R Yamaguchi, TP Rodriguez, LG Perantoni, AO AF Tanigawa, Shunsuke Wang, Honghe Yang, Yili Sharma, Nirmala Tarasova, Nadya Ajima, Rieko Yamaguchi, Terry P. Rodriguez, Luis G. Perantoni, Alan O. TI Wnt4 induces nephronic tubules in metanephric mesenchyme by a non-canonical mechanism SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Wnt; beta-Catenin; Mesenchymal-epithelial transition; Kidney; Tubulogenesis; Peptidomimetic ID TRANSCRIPTION FACTOR SNAIL; HOMEOBOX GENE CUX-1; KIDNEY DEVELOPMENT; SIGNALING PATHWAY; BETA-CATENIN; EPITHELIAL TRANSFORMATION; NUCLEAR-LOCALIZATION; MOUSE KIDNEY; CELL GROWTH; NF-ATC AB Wnt4 and beta-catenin are both required for nephrogenesis, but studies using TCF-reporter mice suggest that canonical Wnt signaling is not activated in metanephric mesenchyme (MM) during its conversion to the epithelia of the nephron. To better define the role of Wnt signaling, we treated rat metanephric mesenchymal progenitors directly with recombinant Wnt proteins. These studies revealed that Wnt4 protein, which is required for nephron formation, induces tubule formation and differentiation markers Lim1 and E-cadherin in MM cells, but does not activate a TCF reporter or up regulate expression of canonical Wnt target gene Axin-2 and has little effect on the stabilization of beta-catenin or phosphorylation of disheveled-2. Furthermore, Wnt4 causes membrane localization of ZO-1 and occludin in tight junctions. To directly examine the role of beta-catenin/FCF-dependent transcription, we developed synthetic cell-permeable analogs of beta-catenin's helix C, which is required for transcriptional activation, in efforts to specifically inhibit canonical Wnt signaling. One inhibitor blocked TCF-dependent transcription and induced degradation of beta-catenin but did not affect tubule formation and stimulated the expression of Lim 1 and E-cadherin. Since a canonical mechanism appears not to be operative in tubule formation, we assessed the involvement of the non-canonical Ca(2+)-dependent pathway. Treatment of MM cells with Wnt4 induced an influx of Ca(2+) and caused phosphorylation of CaMKII. Moreover, lonomycin, a Ca(2+)-dependent pathway activator, stimulated tubule formation. These results demonstrate that the canonical Wnt pathway is not responsible for mesenchymal-epithelial transition (MET) in nephron formation and suggest that the non-canonical calcium/Wnt pathway mediates Wnt4-induced tubulogenesis in the kidney. Published by Elsevier Inc. C1 [Tanigawa, Shunsuke; Wang, Honghe; Yang, Yili; Sharma, Nirmala; Ajima, Rieko; Yamaguchi, Terry P.; Perantoni, Alan O.] Natl Canc Inst, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA. [Tarasova, Nadya] NCI, Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21701 USA. [Rodriguez, Luis G.] SAIC Frederick Inc, Adv Technol Program, Opt Microscopy & Anal Lab, Frederick, MD USA. RP Perantoni, AO (reprint author), Natl Canc Inst, Canc & Dev Biol Lab, Ctr Canc Res, Bldg 538,Room 221, Frederick, MD 21702 USA. EM perantoa@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We are grateful to Dr. Joost Oppenheim, Dr. O.M. Zack Howard, and Nathan Kadan (Laboratory of Molecular Immunoregulation, NCI-Frederick) for Calcium influx experiments. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 60 TC 48 Z9 48 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2011 VL 352 IS 1 BP 58 EP 69 DI 10.1016/j.ydbio.2011.01.012 PG 12 WC Developmental Biology SC Developmental Biology GA 736VJ UT WOS:000288522800006 PM 21256838 ER PT J AU Brown, RJ Wijewickrama, RC Harlan, DM Rother, KI AF Brown, Rebecca J. Wijewickrama, Rohan C. Harlan, David M. Rother, Kristina I. TI Uncoupling Intensive Insulin Therapy from Weight Gain and Hypoglycemia in Type 1 Diabetes SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Article ID COMPLICATIONS; MELLITUS AB Background: Intensive insulin therapy has been associated with weight gain and increased hypoglycemia. In this pilot study, we determined the effect of optimized insulin therapy on weight gain and frequency of hypoglycemia in patients with long-standing type 1 diabetes mellitus. Methods: Sixteen patients with long-standing type 1 diabetes participated in an interventional clinical trial. Before any pharmacologic intervention began, diabetes management was optimized by thorough review of carbohydrate counting and insulin dose adjustment. Results: Optimizing insulin therapy and carbohydrate counting for 4-6 months decreased the enrollees' hemoglobin A1C (-0.7 +/- 0.6%, P = 0.0003) without weight gain (-0.6 +/- 2.9 kg, P = 0.44) or increased frequency of hypoglycemia (-0.5 +/- 1.5 events per week, P = 0.22). The improved blood glucose control was achieved in most subjects by lowering their basal or long-acting insulin doses while making compensatory increases in meal-associated insulin doses. Conclusions: "Fine tuning'' of diabetes management with intensive insulin therapy was accomplished without inducing weight gain or worsening hypoglycemia. This was achieved by readjusting the ratio of basal to meal-associated insulin without increasing the total daily insulin dose. C1 [Brown, Rebecca J.; Wijewickrama, Rohan C.; Harlan, David M.; Rother, Kristina I.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Rother, KI (reprint author), NIDDK, NIH, Bldg 10-8C432A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kristinar@mail.nih.gov FU National Institute of Diabetes, Digestive and Kidney Diseases FX This research was supported by the intramural research program of the National Institute of Diabetes, Digestive and Kidney Diseases. NR 10 TC 8 Z9 8 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2011 VL 13 IS 4 BP 457 EP 460 DI 10.1089/dia.2010.0159 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 741FL UT WOS:000288848700007 PM 21355723 ER PT J AU Liu, Z Segawa, H Aydin, C Reyes, M Erben, RG Weinstein, LS Chen, M Marshansky, V Frohlich, LF Bastepe, M AF Liu, Zun Segawa, Hiroko Aydin, Cumhur Reyes, Monica Erben, Reinhold G. Weinstein, Lee S. Chen, Min Marshansky, Vladimir Froehlich, Leopold F. Bastepe, Murat TI Transgenic Overexpression of the Extra-Large Gs alpha Variant XL alpha s Enhances Gs alpha-Mediated Responses in the Mouse Renal Proximal Tubule in Vivo SO ENDOCRINOLOGY LA English DT Article ID PSEUDOHYPOPARATHYROIDISM-TYPE-IB; ALBRIGHT HEREDITARY OSTEODYSTROPHY; G(S)ALPHA KNOCKOUT MICE; G-PROTEIN; PARATHYROID-HORMONE; CONTROL REGION; TARGETED DISRUPTION; GNAS LOCUS; SUBUNIT; GENE AB XL alpha s, a variant of the stimulatory G protein alpha-subunit (Gs alpha), can mediate receptor-activated cAMP generation and, thus, mimic the actions of Gs alpha in transfected cells. However, it remains unknown whether XL alpha s can act in a similar manner in vivo. We have now generated mice with ectopic transgenic expression of rat XL alpha s in the renal proximal tubule (rptXL alpha s mice), where Gs alpha mediates most actions of PTH. Western blots and quantitative RT-PCR showed that, while Gs alpha and type-1 PTH receptor levels were unaltered, protein kinase A activity and 25-hydroxyvitamin D 1-alpha-hydroxylase (Cyp27b1) mRNAlevels were significantly higher in renal proximal tubules of rptXL alpha s mice than wild-type littermates. Immunohistochemical analysis of kidney sections showed that the sodium- phosphate cotransporter type 2a was modestly reduced in brush border membranes of male rptXL alpha s mice compared to gender-matched controls. Serum calcium, phosphorus, and 1,25 dihydroxyvitamin D were within the normal range, but serum PTH was similar to 30% lower in rptXL alpha s mice than in controls (152 +/- 16 vs. 222 +/- 41 pg/ml; P < 0.05). After crossing the rptXL alpha s mice to mice with ablation of maternal Gnas exon 1 (E1m(-/+)), male offspring carrying both the XL alpha s transgene and maternal Gnas exon 1 ablation (rptXL alpha s/E1m(-/+)) were significantly less hypocalcemic than gender-matched E1m(-/+) littermates. Both E1m(-/+) and rptXL alpha s/E1m(-/+) offspring had higher serum PTH than wild-type littermates, but the degree of secondary hyperparathyroidism tended to be lower in rptXL alpha s/E1m(-/+) mice. Hence, transgenic XL alpha s expression in the proximal tubule enhanced Gs alpha-mediated responses, indicating that XL alpha s can mimic Gs alpha in vivo. (Endocrinology 152: 1222-1233, 2011) C1 [Liu, Zun; Segawa, Hiroko; Aydin, Cumhur; Reyes, Monica; Froehlich, Leopold F.; Bastepe, Murat] Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Boston, MA 02114 USA. [Marshansky, Vladimir] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Segawa, Hiroko] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Mol Nutr, Tokushima 7708503, Japan. [Aydin, Cumhur] Gulhane Mil Med Acad, Ctr Dent Sci, Dept Endodont, TR-06018 Ankara, Turkey. [Erben, Reinhold G.] Univ Vet Med, Dept Biomed Sci, A-1210 Vienna, Austria. [Weinstein, Lee S.; Chen, Min] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Froehlich, Leopold F.] Med Univ Graz, Inst Pathol, A-8036 Graz, Austria. RP Bastepe, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM bastepe@helix.mgh.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) [R01DK073911]; NIH [DK038452]; Boston Area Diabetes Endocrinology Research Center (BADERC) [DK057521-08]; Gulhane Military Medical Academy, Ankara, Turkey FX This work was supported in part by a research grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (R01DK073911 to M. B). Part of this study was also supported by a NIH Grant DK038452 and by Boston Area Diabetes Endocrinology Research Center (BADERC) Grant DK057521-08 (to V. M.). This work was also partially supported by the Intramural Research Program of NIDDK, NIH. C. A. received a research fellowship award from Gulhane Military Medical Academy, Turkish General Staff, Ankara, Turkey. NR 47 TC 15 Z9 17 U1 0 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2011 VL 152 IS 4 BP 1222 EP 1233 DI 10.1210/en.2010-1034 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 739EM UT WOS:000288696300005 PM 21303955 ER PT J AU Spiga, F Waite, EJ Liu, Y Kershaw, YM Aguilera, G Lightman, SL AF Spiga, Francesca Waite, Eleanor J. Liu, Ying Kershaw, Yvonne M. Aguilera, Greti Lightman, Stafford L. TI ACTH-Dependent Ultradian Rhythm of Corticosterone Secretion SO ENDOCRINOLOGY LA English DT Article ID RECEPTOR ANTAGONIST ORG-34850; ACUTE REGULATORY PROTEIN; STRESS RESPONSIVENESS; ADRENAL SENSITIVITY; MESSENGER-RNA; HORMONE; RATS; ADRENOCORTICOTROPIN; STEROIDOGENESIS; TRANSCRIPTION AB The activity of the hypothalamic-pituitary-adrenal axis is characterized by an ultradian pulsatile pattern of glucocorticoid secretion. Despite increasing evidence for the importance of pulsatility in regulating glucocorticoid-responsive gene transcription, little is known about the mechanism underlying the pulsatility of glucocorticoid synthesis and release. We tested the hypothesis that pulsatile ACTH release is critical for optimal adrenocortical function. Hypothalamic-pituitary-adrenal activity was suppressed by oral methylprednisolone, and ACTH (4 ng/h) was infused for 24h either as a constant infusion or in 5-min pulses at hourly intervals. Control methylprednisolone-treated rats had very low plasma corticosterone (CORT) levels with undetectable pulses and also had steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage (P450scc) heteronuclear RNA levels reduced to approximately 50% of that seen in untreated animals. Pulsatile but not constant ACTH infusion restored pulsatile CORT secretion, and this was accompanied by parallel rises in StAR and P450scc heteronuclear RNA levels during the rising phase of the CORT pulse, which then fell during the falling phase. The pulsatile pattern of StAR and P450scc was paralleled by pulsatile transcription of the melanocortin 2 receptor accessory protein. Pulsatile ACTH activation of the adrenal cortex not only is critical for the secretion of CORT but also induces episodic transcription of the rate-limiting enzymes necessary for physiological steroidogenic responses. Because constant infusion of identical amounts of ACTH did not activate CORT secretion, pulsatility of ACTH provides a more effective signaling system for the activation of adrenocortical activity. (Endocrinology 152: 1448-1457, 2011) C1 [Spiga, Francesca; Waite, Eleanor J.; Kershaw, Yvonne M.; Lightman, Stafford L.] Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Sch Clin Sci, Bristol BS1 3NY, Avon, England. [Liu, Ying; Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. RP Spiga, F (reprint author), Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Sch Clin Sci, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England. EM F.Spiga@bristol.ac.uk RI Waite, Eleanor/D-5165-2013 FU Biotechnology and Biological Sciences Research Council [BB/H015779/1]; Wellcome Trust [074112/Z/04/Z]; Neuroendocrinology Charitable Trust; National Institutes of Health (NIH)/National Institute of Child Health and Human Development; British Society for Neuroendocrinology FX This work was supported by the Biotechnology and Biological Sciences Research Council (Grant BB/H015779/1), The Wellcome Trust (Program Grant 074112/Z/04/Z), the Neuroendocrinology Charitable Trust, and the Intramural Research program of the National Institutes of Health (NIH)/National Institute of Child Health and Human Development. The collaborative visit of F. S. to NIH was supported by the British Society for Neuroendocrinology. NR 40 TC 40 Z9 40 U1 0 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2011 VL 152 IS 4 BP 1448 EP 1457 DI 10.1210/en.2010-1209 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 739EM UT WOS:000288696300026 PM 21303945 ER PT J AU Etemadi, A Golozar, A Ghassabian, A Zarei, M Taheri, APH Dawsey, SM Malekzadeh, R AF Etemadi, Arash Golozar, Asieh Ghassabian, Akhgar Zarei, Mahsa Taheri, Amir Pejman Hashemi Dawsey, Sanford M. Malekzadeh, Reza TI Cavernous hemangioma of the liver: factors affecting disease progression in general hepatology practice SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE benign tumors; hemangioma; liver; ultrasonography ID BENIGN HEPATIC-TUMORS; SEX-HORMONES; MANAGEMENT; RESECTION; EXPERIENCE; DIAGNOSIS; GROWTH; ADULTS AB Background Although for asymptomatic hepatic hemangiomas conservative management is generally recommended, factors affecting the disease course are still not very well understood. Aim To determine disease characteristics of cavernous hemangioma and factors affecting its progression in patients from a general hepatology clinic in Tehran, Iran. Methods We reviewed medical records of 198 patients with cavernous hemangioma of the liver visiting a large private hepatology clinic in Tehran from 1997 to 2007. Of a total of 198 cases, 129 could be followed up for a period of 3.2 +/- 2.5 years, and 80 of these had 1-5 repeated sonographies. Results Patients were between 27 and 84 years old (mean age: 44.3 +/- 10.9 years), and 131 (66.2%) were female. Thirty-six patients (18.2%) had giant hemangiomas. Abdominal pain was the primary reason for evaluation in 100 (50.5%) patients. Abdominal pain at the beginning of the follow-up was significantly associated with having irritable bowel syndrome [odds ratio (OR)=8.3; 95% confidence interval (CI): 3.1-28.7] or other gastrointestinal diseases (OR=3.9; 95% CI: 2.6-10.2), but not with hemangioma size, number, or location. During follow-up, having a single giant lesion at the time of diagnosis, adjusted for age, sex, and presence of irritable bowel syndrome, was a strong predictor of persistent pain during follow-up (OR=11.1; 95% CI: 3.2-38.6). In repeated sonographies, 35% showed an increased size, which was significantly associated only with having a single lesion (P=0.04). Conclusion Many symptoms in hepatic hemangioma are attributable to accompanying gastrointestinal diseases. Patients with a single giant lesion are more likely to have persistent pain, and single lesions are more likely to grow in size. Eur J Gastroenterol Hepatol 23:354-358 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Taheri, Amir Pejman Hashemi] Univ Tehran Med Sci, Dept Radiol, Shariati Hosp, Sch Med, Tehran, Iran. [Etemadi, Arash; Golozar, Asieh; Ghassabian, Akhgar; Zarei, Mahsa; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. [Etemadi, Arash; Golozar, Asieh; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Ghassabian, Akhgar] Erasmus Med Ctr Sophia Childrens Hosp, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands. RP Taheri, APH (reprint author), Univ Tehran Med Sci, Dept Radiol, Shariati Hosp, Sch Med, N Kargar Ave, Tehran, Iran. EM apejmanht@yahoo.com RI Etemadi, Arash/C-1386-2016; OI Etemadi, Arash/0000-0002-3458-1072; Malekzadeh, Reza/0000-0003-1043-3814; Ghassabian, Akhgar/0000-0001-9551-4706 FU Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran; National Cancer Institute, National Institutes of Health, USA FX This study was supported by a research grant from Digestive Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran. It was also supported in part by intramural funds from the National Cancer Institute, National Institutes of Health, USA. NR 25 TC 5 Z9 14 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD APR PY 2011 VL 23 IS 4 BP 354 EP 358 DI 10.1097/MEG.0b013e3283451e7d PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 739UH UT WOS:000288743200010 PM 21383624 ER PT J AU Barochia, A Solomon, S Cui, XZ Natanson, C Eichacker, PQ AF Barochia, Amisha Solomon, Steven Cui, Xizhong Natanson, Charles Eichacker, Peter Q. TI Eritoran tetrasodium (E5564) treatment for sepsis: review of preclinical and clinical studies SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE E5564; endotoxin; eritoran tetrasodium; inflammation; sepsis; therapy; TLR4; toll-like receptor ID PLACEBO-CONTROLLED TRIAL; RECEPTOR 4 ANTAGONIST; ISCHEMIA-REPERFUSION INJURY; ESCHERICHIA-COLI INFECTION; INNATE IMMUNE-RESPONSE; GRAM-NEGATIVE SEPSIS; TOLL-LIKE RECEPTOR-4; LPS-BINDING-PROTEIN; SEPTIC SHOCK; DOUBLE-BLIND AB Areas covered: This review focuses on the rationale for the use of eritoran tetrasodium in sepsis as well as on its pharmacokinetics, pharmacodynamics, efficacy and safety. Preclinical and clinical studies from a MEDLINE/PubMed literature search in August 2010 with the search terms ''eritoran'' and ''E5564'' are discussed. Expert opinion: Preclinical in vitro and in vivo studies of eritoran tetrasodium indicate it can limit excessive inflammatory mediator release associated with LPS and improve survival in sepsis models. While early clinical results are promising, its efficacy and safety for treating patients with sepsis are currently under investigation. Even if the ongoing Phase III clinical trial enrolling patients with severe sepsis and increased risk of death shows benefit from eritoran, questions remain and confirmatory studies would be necessary to define its clinical usage. C1 [Barochia, Amisha; Solomon, Steven; Cui, Xizhong; Natanson, Charles; Eichacker, Peter Q.] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Barochia, A (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM barochiaav@mail.nih.gov FU National Institutes of Health FX The authors declare intramural funding from the National Institutes of Health and do not have any other potential conflicts of interest to disclose. NR 66 TC 56 Z9 65 U1 0 U2 14 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD APR PY 2011 VL 7 IS 4 BP 479 EP 494 DI 10.1517/17425255.2011.558190 PG 16 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 737ZL UT WOS:000288609000008 PM 21323610 ER PT J AU Kohonen-Corish, MRJ Macrae, F Genuardi, M Aretz, S Bapat, B Bernstein, IT Burn, J Cotton, RGH den Dunnen, JT Frebourg, T Greenblatt, MS Hofstra, R Holinski-Feder, E Lappalainen, I Lindblom, A Maglott, D Moller, P Morreau, H Moslein, G Sijmons, R Spurdle, AB Tavtigian, S Tops, CMJ Weber, TK de Wind, N Woods, MO AF Kohonen-Corish, Maija R. J. Macrae, Finlay Genuardi, Maurizio Aretz, Stefan Bapat, Bharati Bernstein, Inge T. Burn, John Cotton, Richard G. H. den Dunnen, Johan T. Frebourg, Thierry Greenblatt, Marc S. Hofstra, Robert Holinski-Feder, Elke Lappalainen, Ilkka Lindblom, Annika Maglott, Donna Moller, Pal Morreau, Hans Moeslein, Gabriela Sijmons, Rolf Spurdle, Amanda B. Tavtigian, Sean Tops, Carli M. J. Weber, Thomas K. de Wind, Niels Woods, Michael O. CA Contributors InSiGHT-HVP Workshop TI Deciphering the Colon Cancer Genes-Report of the InSiGHT-Human Variome Project Workshop, UNESCO, Paris 2010 SO HUMAN MUTATION LA English DT Editorial Material DE colon; cancer; HNPCC; Pathogenicity; variant; InSiGHT; HVP ID MISMATCH-REPAIR GENES; COLORECTAL-CANCER; SEQUENCE VARIANTS; CLASSIFICATION; MUTATIONS; DATABASE; MLH1 AB The Human Variome Project (HVP) has established a pilot program with the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) to compile all inherited variation affecting colon cancer susceptibility genes. An HVP-InSiGHT Workshop was held on May 10, 2010, prior to the HVP Integration and Implementation Meeting at UNESCO in Paris, to review the progress of this pilot program. A wide range of topics were covered, including issues relating to genotype-phenotype data submission to the InSiGHT Colon Cancer Gene Variant Databases (chromium.liacs.nl/LOVD2/colon_cancer/home.php). The meeting also canvassed the recent exciting developments in models to evaluate the pathogenicity of unclassified variants using in silico data, tumor pathology information, and functional assays, and made further plans for the future progress and sustainability of the pilot program. Hum Mutat 32: 491-494, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Kohonen-Corish, Maija R. J.] Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia. [Kohonen-Corish, Maija R. J.] Univ NSW, St Vincents Clin Sch, Sydney, NSW, Australia. [Macrae, Finlay] Depatment Colorectal Med & Genet, Parkville, Vic, Australia. [Macrae, Finlay] Univ Melbourne, Dept Med, Parkville, Vic 3052, Australia. [Macrae, Finlay] Royal Melbourne Hosp, Parkville, Vic 3050, Australia. [Macrae, Finlay] Int Soc Gastrointestinal Hereditary Tumours InSiG, San Antonio, TX USA. [Genuardi, Maurizio] Univ Florence, Dept Clin Pathophysiol, Sesto Fiorentino, Italy. [Genuardi, Maurizio] Fiorgen Fdn Pharmacogen, Sesto Fiorentino, Italy. [Genuardi, Maurizio] Tuscany Tumor Inst, Florence, Italy. [Aretz, Stefan] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Bapat, Bharati] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Bernstein, Inge T.] Hvidovre Univ Hosp, HNPCC Registret, Copenhagen, Denmark. [Burn, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cotton, Richard G. H.] Genom Disorders Res Ctr, Melbourne, Vic 3053, Australia. [Frebourg, Thierry] Univ Rouen, Fac Med, INSERM, U614, Rouen, France. [Greenblatt, Marc S.] Univ Vermont, Coll Med, Burlington, VT USA. [Hofstra, Robert; Sijmons, Rolf] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Holinski-Feder, Elke] Univ Munich, Univ Hosp, Munich, Germany. [Lappalainen, Ilkka] European Bioinformat Inst, Cambridge, England. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Maglott, Donna] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Moller, Pal] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Med Genet, Sect Inherited Canc, Oslo, Norway. [Morreau, Hans] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Moeslein, Gabriela] HELIOS St Josefs Hosp, Bochum, Germany. [Spurdle, Amanda B.] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia. [Tavtigian, Sean] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA. [Tops, Carli M. J.] Leiden Univ, Med Ctr, Lab Diagnost Genome Anal, Leiden, Netherlands. [Weber, Thomas K.] SUNY Downstate, Dept Surg, New York, NY USA. [de Wind, Niels] Leiden Univ, Med Ctr, Dept Toxicogenet, Leiden, Netherlands. [Woods, Michael O.] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada. RP Kohonen-Corish, MRJ (reprint author), Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Sydney, NSW 2010, Australia. EM m.corish@garvan.org.au RI Sijmons, Rolf/E-5829-2012; Bapat, Bharati/B-5839-2014; Spurdle, Amanda/A-4978-2011 OI Burn, John/0000-0002-9823-2322; Sijmons, Rolf/0000-0001-8446-2779; Hofstra, Robert/0000-0001-7498-3829; Lappalainen, Ilkka/0000-0001-5762-893X; Spurdle, Amanda/0000-0003-1337-7897 NR 14 TC 10 Z9 12 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD APR PY 2011 VL 32 IS 4 BP 491 EP 494 DI 10.1002/humu.21450 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 736BI UT WOS:000288464100023 PM 21387463 ER PT J AU McMurtry, V Saavedra, JE Nieves-Alicea, R Simeone, AM Keefer, LK Tari, AM AF McMurtry, Vanity Saavedra, Joseph E. Nieves-Alicea, Rene Simeone, Ann-Marie Keefer, Larry K. Tari, Ana M. TI JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE JS-K; apoptosis; autophagy; breast cancer; nitric oxide ID S-TRANSFERASE-PI; HEME OXYGENASE-1; SYNTHASE GENE; EXPRESSION; N-(4-HYDROXYPHENYL)RETINAMIDE; METASTASIS; SUPPRESSES; AUTOPHAGY; PROTEINS; PATHWAYS AB Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC(50)s of JS-K against the breast cancer cells ranged from 0.8 to 3 mu M. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-mu M concentration, and HMECs were unaffected by 10 mu M JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective antitumor activity of JS-K warrants its further investigation in breast tumors. C1 [Tari, Ana M.] Univ Florida, Div Hematol & Oncol, Gainesville, FL 32610 USA. [McMurtry, Vanity; Nieves-Alicea, Rene; Simeone, Ann-Marie; Tari, Ana M.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Keefer, Larry K.] NCI, Lab Comparat Carcinogenesis, Frederick, MD 21701 USA. [Saavedra, Joseph E.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. RP Tari, AM (reprint author), Univ Florida, Div Hematol & Oncol, 2033 Mowry Rd,POB 103633, Gainesville, FL 32610 USA. EM ana.tari@medicine.ufl.edu RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Cancer Research and Prevention Foundation; Cancer Center [NCI CA 16672]; NCI [NO1-CO12400]; SAIC-Frederick Inc.; NIH, National Cancer Institute, Center for Cancer Research FX This work was conducted in The University of Texas M.D. Anderson Cancer Center, and was supported by the Cancer Research and Prevention Foundation (A.M.T.), the Cancer Center Core Grant NCI CA 16672, NCI Contract NO1-CO12400 with SAIC-Frederick Inc. (J.E.S.) and the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (L.K.K.). We thank Wendy Schober (The University of Texas M.D. Anderson Cancer Center Department of Blood and Marrow Transplantation Core Lab), and Kenneth Dunner Jr (The University of Texas M.D. Anderson Cancer Center Department of Cancer Biology Core Lab) for their technical assistance. NR 38 TC 23 Z9 24 U1 1 U2 6 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD APR PY 2011 VL 38 IS 4 BP 963 EP 971 DI 10.3892/ijo.2011.925 PG 9 WC Oncology SC Oncology GA 737PQ UT WOS:000288581100008 PM 21271218 ER PT J AU Lengruber, RB Delviks-Frankenberry, KA Nikolenko, GN Baumann, J Santos, AF Pathak, VK Soares, MA AF Lengruber, Renan B. Delviks-Frankenberry, Krista A. Nikolenko, Galina N. Baumann, Jessica Santos, Andre F. Pathak, Vinay K. Soares, Marcelo A. TI Phenotypic characterization of drug resistance-associated mutations in HIV-1 RT connection and RNase H domains and their correlation with thymidine analogue mutations SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE resistance mutations; AZT; NVP; TAMs ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE INHIBITORS; TREATMENT-EXPERIENCED PATIENTS; DUAL RESISTANCE; CONFERS ZIDOVUDINE; NUCLEOSIDE; SUBDOMAIN; N348I; 3'-AZIDO-3'-DEOXYTHYMIDINE; MECHANISM AB Objectives: HIV-1 reverse transcriptase (RT) mutations associated with antiviral drug resistance have been extensively characterized in the enzyme polymerase domain. Recent studies, however, have verified the involvement of the RT C-terminal domains (connection and RNase H) in drug resistance to RT inhibitors. In this work, we have characterized the correlation of recently described C-terminal domain mutations with thymidine analogue mutations (TAMs), as well as their phenotypic impact on susceptibility to zidovudine and nevirapine. Methods: HIV-1 RT sequences from Brazilian patients and from public sequence databases for which the C-terminal RT domains and treatment status were also available were retrieved and analysed for the association of C-terminal mutations and the presence of TAMs and treatment status. Several C-terminal RT mutations previously characterized were introduced by site-directed mutagenesis into an HIV-1 subtype B molecular clone in a wild-type, TAM-1 or TAM-2 pathway context. Mutants were tested for drug susceptibility to the prototypic drugs zidovudine and nevirapine. Results: Subtype B-infected patient database analysis showed that mutations N348I, A360V/T, T377M and D488E were found to be selected independently of TAMs, whereas mutations R358K, G359S, A371V, A400T, K451R and K512R increased in frequency with the number of TAMs in a dose-dependent fashion. Phenotypic analysis of C-terminal mutations showed that N348I, T369V and A371V conferred reduced susceptibility to zidovudine in the context of the TAM-1 and/or TAM-2 pathway, and also conferred dual resistance to nevirapine. Other mutations, such as D488E and Q547K, showed TAM-specific enhancement of resistance to zidovudine. Finally, mutation G359S displayed a zidovudine hypersusceptibility phenotype, both per se and when combined with A371V. Conclusions: This study demonstrates that distinct RT C-terminal mutations can act as primary or secondary drug resistance mutations, and are associated in a complex array of phenotypes with RT polymerase domain mutations. C1 [Lengruber, Renan B.; Santos, Andre F.; Soares, Marcelo A.] Univ Fed Rio de Janeiro, Dept Genet, Rio De Janeiro, Brazil. [Delviks-Frankenberry, Krista A.; Nikolenko, Galina N.; Baumann, Jessica; Pathak, Vinay K.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Soares, Marcelo A.] Inst Nacl Canc, Rio De Janeiro, Brazil. RP Soares, MA (reprint author), Ilha Fundao, CCS, Bloco A,Sala A2-120, BR-21949570 Rio De Janeiro, Brazil. EM masoares@biologia.ufrj.br RI Delviks-Frankenberry, Krista/M-4822-2013; Santos, Andre/I-5734-2016 FU Rio de Janeiro State Foundation (FAPERJ) [E-26/102.858-2008]; Brazilian Science Council (CNPq) [134969/2007-3]; SAIC-Frederick, Inc.; National Institutes of Health, National Cancer Institute, Center for Cancer Research; Intramural AIDS Targeted Antiviral Program, USA FX This work was supported by the Rio de Janeiro State Foundation (FAPERJ) grant no. E-26/102.858-2008, the Brazilian Science Council (CNPq) grant no. 134969/2007-3, SAIC-Frederick, Inc. and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and the Intramural AIDS Targeted Antiviral Program, USA. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 31 TC 15 Z9 15 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2011 VL 66 IS 4 BP 702 EP 708 DI 10.1093/jac/dkr005 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 737EI UT WOS:000288551300003 PM 21393163 ER PT J AU Lenroot, RK Giedd, JN AF Lenroot, Rhoshel K. Giedd, Jay N. TI Developmental considerations of gene by environment interactions SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Review DE Development; child; brain; heritability; epigenetics ID NEUROTROPHIC FACTOR VAL66MET; STRESSFUL LIFE EVENTS; AGE-RELATED-CHANGES; PSYCHIATRIC-DISORDERS; BRAIN STRUCTURE; DEPRESSIVE SYMPTOMS; MONOZYGOTIC TWINS; PRENATAL EXPOSURE; MAJOR DEPRESSION; RHESUS MACAQUES AB Biological development is driven by a complex dance between nurture and nature, determined not only by the specific features of the interacting genetic and environmental influences but also by the timing of their rendezvous. The initiation of large-scale longitudinal studies, ever-expanding knowledge of genetics, and increasing availability of neuroimaging data to provide endophenotypic bridges between molecules and behavior are beginning to provide some insight into interactions of developmental stage, genes, and the environment, although daunting challenges remain. Prominent amongst these challenges are difficulties in identifying and quantifying relevant environmental factors, discerning the relative contributions to multiply determined outcomes, and the likelihood that brain development is a non-linear dynamic process in which small initial differences may yield large later effects. Age-sensitive mechanisms include developmental changes in gene expression, epigenetic modifications, synaptic arborization/pruning, and maturational improvements in our capacity to seek out environments of our choosing. Greater understanding of how genetic and environmental factors interact differently across ages is an important step toward elucidating the mechanisms by which phenotypes are created - and how they may differ in health and disease. This knowledge may also provide clues to guide the type and timing of interventions to maximize outcomes. C1 [Giedd, Jay N.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [Lenroot, Rhoshel K.] Univ New S Wales, Randwick, NSW, Australia. [Lenroot, Rhoshel K.] Neurosci Res Australia, Randwick, NSW, Australia. RP Giedd, JN (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA. EM jg@nih.gov RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS [Z99 MH999999] NR 111 TC 35 Z9 36 U1 2 U2 30 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD APR PY 2011 VL 52 IS 4 BP 429 EP 441 DI 10.1111/j.1469-7610.2011.02381.x PG 13 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 736AH UT WOS:000288461400007 PM 21391998 ER PT J AU Ching, KH Burbelo, PD Gonzalez-Begne, M Roberts, MEP Coca, A Sanz, I Iadarola, MJ AF Ching, K. H. Burbelo, P. D. Gonzalez-Begne, M. Roberts, M. E. P. Coca, A. Sanz, I. Iadarola, M. J. TI Salivary anti-Ro60 and anti-Ro52 Antibody Profiles to Diagnose Sjogren's Syndrome SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE Sjogren's Syndrome; saliva; autoantigen ID PAROTID-SALIVA; AUTOANTIGEN; INFECTION; PROTEOMES; GLANDS; RO/SSA AB Simple and non-invasive saliva-based diagnostics may be useful for the identification, understanding, and monitoring of autoimmune and infectious diseases. Previously, Luciferase Immunoprecipitation Systems (LIPS) were used for sensitive detection of patient serum autoantibodies in Sjogren's Syndrome (SjS), a chronic autoimmune disease affecting the salivary and lacrimal glands. Here we explored the ability of LIPS to diagnose SjS based on IgG autoantibodies in patient saliva. From LIPS testing, anti-Ro60 autoantibodies were detected in the saliva of 70% (19/27) of SjS patients with 96% specificity. Positive anti-Ro60 autoantibodies were also found in 70% of the matched serum samples (96% specificity). LIPS detected Ro52 autoantibodies in the saliva and serum of 67% of SjS patients with 100% specificity. Overall, the autoantibody titers in saliva were approximately 4000-fold lower by volume than serum, but still distinguished seropositive patients from controls. These results suggest that LIPS salivary-based testing for SjS autoantibodies is a practical alternative to serum and compatible with point-of-care testing. C1 [Ching, K. H.; Burbelo, P. D.; Iadarola, M. J.] Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, Bethesda, MD 20892 USA. [Gonzalez-Begne, M.] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA. [Roberts, M. E. P.; Coca, A.; Sanz, I.] Univ Rochester, Med Ctr, Div Allergy Immunol Rheumatol, Dept Med, Rochester, NY 14642 USA. RP Ching, KH (reprint author), Natl Inst Dent & Craniofacial Res, Neurobiol & Pain Therapeut Sect, Lab Sensory Biol, Bldg 49,Room 1C20,49 Convent Dr, Bethesda, MD 20892 USA. EM chingk@nidcr.nih.gov FU Division of Intramural Research, National Institute of Dental and Craniofacial Research; NIH [RO1DE017585-04, KL2 RR024136-04] FX This work was supported by the Division of Intramural Research, National Institute of Dental and Craniofacial Research, and by NIH grants to IS (RO1DE017585-04) and MGB (KL2 RR024136-04). The authors thank Drs. Anolik and Watson for their contributions to the SjS database and Charlene Chung and Tracey Sanford for saliva and serum collections. NR 28 TC 16 Z9 16 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 2011 VL 90 IS 4 BP 445 EP 449 DI 10.1177/0022034510390811 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 740MK UT WOS:000288798600008 PM 21212317 ER PT J AU Budhu, A Wang, XW AF Budhu, Anuradha Wang, Xin Wei TI Power play: Scoring our goals for liver cancer with better GWAS study design SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID HEPATOCELLULAR-CARCINOMA; POLYMORPHISMS AB To identify susceptibility variants for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we conducted a genome-wide association study by genotyping 440,794 SNPs in 355 chronic HBV carriers with HCC and 360 chronic HBV carriers without HCC, all of Chinese ancestry. We identified one intronic SNP (rs17401966) in KIF1B on chromosome 1p36.22 that was highly associated with HBV-related HCC and confirmed this association in five additional independent samples, consisting of 1962 individuals with HCC, 1430 control subjects, and 159 family trios. Across the six studies, the association with rs17401966 was highly statistically significant (joint odds ratio = 0.61, P = 1.7 x 10(-18)). In addition to KIF1B, the association region tagged two other plausible causative genes, UBE4B and PGD. Our findings provide evidence that the 1p36.22 locus confers susceptibility to HBV-related HCC, and suggest that KIF1B-, UBE4B-, or PGD-related pathways might be involved in the pathogenesis of this malignancy. C1 [Budhu, Anuradha; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), 37 Convent Dr,Bldg 37,Rm 3044, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 NR 5 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2011 VL 54 IS 4 BP 823 EP 824 DI 10.1016/j.jhep.2010.10.035 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740YX UT WOS:000288831400027 PM 21167853 ER PT J AU Yu, Q Sharma, A Ghosh, A Sen, JM AF Yu, Qing Sharma, Archna Ghosh, Amalendu Sen, Jyoti Misra TI T Cell Factor-1 Negatively Regulates Expression of IL-17 Family of Cytokines and Protects Mice from Experimental Autoimmune Encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; T(H)17 CELLS; DIFFERENTIAL REGULATION; INTERLEUKIN-7 RECEPTOR; INTERFERON-GAMMA; TGF-BETA; TH17; WNT; INFLAMMATION; GENERATION AB Activated CD4 T cells are associated with protective immunity and autoimmunity. The manner in which the inflammatory potential of T cells and resultant autoimmunity is restrained is poorly understood. In this article, we demonstrate that T cell factor-1 (TCF1) negatively regulates the expression of IL-17 and related cytokines in activated CD4 T cells. We show that TCF1 does not affect cytokine signals and expression of transcription factors that have been shown to regulate Th17 differentiation. Instead, TCF1 regulates IL-17 expression, in part, by binding to the regulatory regions of the Il17 gene. Moreover, TCF1-deficient Th17 CD4 T cells express higher levels of IL-7R alpha, which potentially promotes their survival and expansion in vivo. Accordingly, TCF1-deficient mice are hyperresponsive to experimental autoimmune encephalomyelitis. Thus, TCF1, a constitutively expressed T cell-specific transcription factor, is a critical negative regulator of the inflammatory potential of TCR-activated T cells and autoimmunity. The Journal of Immunology, 2011, 186: 3946-3952. C1 [Yu, Qing; Sharma, Archna; Ghosh, Amalendu; Sen, Jyoti Misra] NIA, Lymphocyte Dev Unit, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Lymphocyte Dev Unit, Lab Mol Biol & Immunol, NIH, 8C210,BRC Bldg,251 Bayview Blvd, Baltimore, MD 21224 USA. EM Jyoti-Sen@nih.gov RI Sharma, Archna/R-9377-2016 OI Sharma, Archna/0000-0003-4745-0220 FU National Institute on Aging at the National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging at the National Institutes of Health and in part by an appointment to the Oak Ridge Institute for Science and Education's Research Associates Program at the National Institutes of Health. NR 45 TC 33 Z9 34 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 APR 1 PY 2011 VL 186 IS 7 BP 3946 EP 3952 DI 10.4049/jimmunol.1003497 PG 7 WC Immunology SC Immunology GA 739WH UT WOS:000288751200019 PM 21339363 ER PT J AU Ansari, NA Kumar, R Gautam, S Nylen, S Singh, OP Sundar, S Sacks, D AF Ansari, Nasim Akhtar Kumar, Rajiv Gautam, Shalini Nylen, Susanne Singh, Om Prakash Sundar, Shyam Sacks, David TI IL-27 and IL-21 Are Associated with T Cell IL-10 Responses in Human Visceral Leishmaniasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INDIAN KALA-AZAR; INTERFERON-GAMMA; DONOVANI INFECTIONS; GENE-EXPRESSION; CUTTING EDGE; T(H)17 CELLS; IN-VIVO; INTERLEUKIN-27; TRANSCRIPTION AB IL-10 is believed to underlie many of the immunologic defects in human visceral leishmaniasis (VL). We have identified CD4(+)CD25(-)Foxp3(-) T cells as the major source of IL-10 in the VL spleen. IL-27, a member of the IL-6/IL-12 cytokine family, has been shown to promote development of IL-10-producing T cells, in part by upregulating their production of autocrine IL-21. We investigated whether IL-27 and IL-21 are associated with human VL. IL-27 was elevated in VL plasma, and at pretreatment, spleen cells showed significantly elevated mRNA levels of both IL-27 subunits, IL-27p28 and EBI-3, as well as IL-21, compared with posttreatment biopsies. CD14(+) spleen cells were the main source of IL-27 mRNA, whereas CD3(+) T cells were the main source of IL-21. IL-27 mRNA could be strongly upregulated in normal donor macrophages with IFN-gamma and IL-1 beta, conditions consistent with those in the VL spleen. Last, a whole-blood assay revealed that most VL patients could produce Ag-specific IFN-gamma and IL-10 and that the IL-10 could be augmented with recombinant human IL-21. Thus, proinflammatory cytokines acting on macrophages in the VL spleen have the potential to upregulate IL-27, which in turn can induce IL-21 to expand IL-10-producing T cells as a mechanism of feedback control. The Journal of Immunology, 2011, 186: 3977-3985. C1 [Ansari, Nasim Akhtar; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Ansari, Nasim Akhtar; Kumar, Rajiv; Gautam, Shalini; Singh, Om Prakash; Sundar, Shyam] Banaras Hindu Univ, Inst Med Sci, Dept Med, Infect Dis Res Lab, Varanasi 221005, Uttar Pradesh, India. [Nylen, Susanne] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA. EM dsacks@nih.gov OI Nylen, Susanne/0000-0002-3875-3353; Kumar, Rajiv/0000-0003-2338-1494 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases; National Institutes of Health, National Institute of Allergy and Infectious Diseases, Tropical Medicine Research Centers [1P50AI074321]; Indian Council of Medical Research (New Delhi, India); Swedish Society for Medicine; Sitaram Memorial Trust (Muzaffarpur, Bahir, India) FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases; National Institutes of Health, National Institute of Allergy and Infectious Diseases, Tropical Medicine Research Centers Grant 1P50AI074321, the Extramural Research Program of the National Institutes of Health, National Institutes of Allergy and Infectious Diseases; the Indian Council of Medical Research (New Delhi, India); and the Swedish Society for Medicine. The care of the patients was supported by the Sitaram Memorial Trust (Muzaffarpur, Bahir, India). NR 48 TC 62 Z9 68 U1 1 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 APR 1 PY 2011 VL 186 IS 7 BP 3977 EP 3985 DI 10.4049/jimmunol.1003588 PG 9 WC Immunology SC Immunology GA 739WH UT WOS:000288751200022 PM 21357266 ER PT J AU Ghoreschi, K Jesson, MI Li, XO Lee, JL Ghosh, S Alsup, JW Warner, JD Tanaka, M Steward-Tharp, SM Gadina, M Thomas, CJ Minnerly, JC Storer, CE LaBranche, TP Radi, ZA Dowty, ME Head, RD Meyer, DM Kishore, N O'Shea, JJ AF Ghoreschi, Kamran Jesson, Michael I. Li, Xiong Lee, Jamie L. Ghosh, Sarbani Alsup, Jason W. Warner, James D. Tanaka, Masao Steward-Tharp, Scott M. Gadina, Massimo Thomas, Craig J. Minnerly, John C. Storer, Chad E. LaBranche, Timothy P. Radi, Zaher A. Dowty, Martin E. Head, Richard D. Meyer, Debra M. Kishore, Nandini O'Shea, John J. TI Modulation of Innate and Adaptive Immune Responses by Tofacitinib (CP-690,550) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-HELPER-CELLS; COLLAGEN-INDUCED ARTHRITIS; GROWTH-FACTOR-BETA; INTERFERON-GAMMA; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; AUTOIMMUNE-DISEASE; JAK2 INHIBITOR; TGF-BETA; IN-VIVO AB Inhibitors of the JAK family of nonreceptor tyrosine kinases have demonstrated clinical efficacy in rheumatoid arthritis and other inflammatory disorders; however, the precise mechanisms by which JAK inhibition improves inflammatory immune responses remain unclear. In this study, we examined the mode of action of tofacitinib (CP-690,550) on JAK/STAT signaling pathways involved in adaptive and innate immune responses. To determine the extent of inhibition of specific JAK/STAT-dependent pathways, we analyzed cytokine stimulation of mouse and human T cells in vitro. We also investigated the consequences of CP-690,550 treatment on Th cell differentiation of naive murine CD4(+) T cells. CP-690,550 inhibited IL-4-dependent Th2 cell differentiation and interestingly also interfered with Th17 cell differentiation. Expression of IL-23 receptor and the Th17 cytokines IL-17A, IL-17F, and IL-22 were blocked when naive Th cells were stimulated with IL-6 and IL-23. In contrast, IL-17A production was enhanced when Th17 cells were differentiated in the presence of TGF-beta. Moreover, CP-690,550 also prevented the activation of STAT1, induction of T-bet, and subsequent generation of Th1 cells. In a model of established arthritis, CP-690,550 rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. Furthermore, efficacy in this disease model correlated with the inhibition of both JAK1 and JAK3 signaling pathways. CP-690,550 also modulated innate responses to LPS in vivo through a mechanism likely involving the inhibition of STAT1 signaling. Thus, CP-690,550 may improve autoimmune diseases and prevent transplant rejection by suppressing the differentiation of pathogenic Th1 and Th17 cells as well as innate immune cell signaling. The Journal of Immunology, 2011, 186: 4234-4243. C1 [Ghoreschi, Kamran; Steward-Tharp, Scott M.; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Jesson, Michael I.; Li, Xiong; Lee, Jamie L.; Ghosh, Sarbani; Alsup, Jason W.; Warner, James D.; Minnerly, John C.; Storer, Chad E.; LaBranche, Timothy P.; Radi, Zaher A.; Dowty, Martin E.; Head, Richard D.; Meyer, Debra M.; Kishore, Nandini] Pfizer Global Res & Dev, St Louis Labs, Chesterfield, MO 63017 USA. [Tanaka, Masao; Gadina, Massimo] NIAMSD, Translat Immunol Sect, Off Sci & Technol, NIH, Bethesda, MD 20892 USA. [Thomas, Craig J.] NHGRI, Natl Inst Hlth Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. RP Ghoreschi, K (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Room 13C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM ghoreschik@mail.nih.gov; osheajo@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; Pfizer, Inc. FX This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Pfizer, Inc. NR 79 TC 183 Z9 191 U1 1 U2 16 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2011 VL 186 IS 7 BP 4234 EP 4243 DI 10.4049/jimmunol.1003668 PG 10 WC Immunology SC Immunology GA 739WH UT WOS:000288751200048 PM 21383241 ER PT J AU Venturi, V Quigley, MF Greenaway, HY Ng, PC Ende, ZS McIntosh, T Asher, TE Almeida, JR Levy, S Price, DA Davenport, MP Douek, DC AF Venturi, Vanessa Quigley, Maire F. Greenaway, Hui Yee Ng, Pauline C. Ende, Zachary S. McIntosh, Tina Asher, Tedi E. Almeida, Jorge R. Levy, Samuel Price, David A. Davenport, Miles P. Douek, Daniel C. TI A Mechanism for TCR Sharing between T Cell Subsets and Individuals Revealed by Pyrosequencing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN CYTOMEGALOVIRUS; RECEPTOR DIVERSITY; SIV INFECTION; VIRAL ESCAPE; IN-VIVO; RESPONSES; REPERTOIRE; MEMORY; SELECTION; ANTIGEN AB The human naive T cell repertoire is the repository of a vast array of TCRs. However, the factors that shape their hierarchical distribution and relationship with the memory repertoire remain poorly understood. In this study, we used polychromatic flow cytometry to isolate highly pure memory and naive CD8(+) T cells, stringently defined with multiple phenotypic markers, and used deep sequencing to characterize corresponding portions of their respective TCR repertoires from four individuals. The extent of interindividual TCR sharing and the overlap between the memory and naive compartments within individuals were determined by TCR clonotype frequencies, such that higher-frequency clonotypes were more commonly shared between compartments and individuals. TCR clonotype frequencies were, in turn, predicted by the efficiency of their production during V(D)J recombination. Thus, convergent recombination shapes the TCR repertoire of the memory and naive T cell pools, as well as their interrelationship within and between individuals. The Journal of Immunology, 2011, 186: 4285-4294. C1 [Quigley, Maire F.; Ende, Zachary S.; Asher, Tedi E.; Almeida, Jorge R.; Price, David A.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Venturi, Vanessa; Greenaway, Hui Yee] Univ New S Wales, Computat Biol Grp, Ctr Vasc Res, Sydney, NSW 2052, Australia. [Ng, Pauline C.] Genome Inst Singapore, Dept Computat & Math Biol, Singapore, Singapore. [Ng, Pauline C.; McIntosh, Tina] J Craig Venter Inst, Rockville, MD 20850 USA. [Levy, Samuel] Scripps Res Inst, La Jolla, CA 92037 USA. [Price, David A.] Cardiff Univ, Sch Med, Dept Infect Immun & Biochem, Cardiff CF14 4XN, S Glam, Wales. [Davenport, Miles P.] Univ New S Wales, Complex Syst Biol Grp, Ctr Vasc Res, Sydney, NSW 2052, Australia. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3509, Bethesda, MD 20892 USA. EM dprice1@mail.nih.gov; m.davenport@unsw.edu.au; ddouek@mail.nih.gov RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Ramos de Almeida, Jorge/0000-0002-5009-8478 FU Intramural Research Program; Office of AIDS Research of the National Institutes of Health; Australian Research Council; Australian National Health and Medical Research Council FX This work was supported by the Intramural Research Program and the Office of AIDS Research of the National Institutes of Health, the Australian Research Council, and the Australian National Health and Medical Research Council. D.A.P. is a Medical Research Council (U.K.) senior clinical fellow, M.F.Q. is a Marie Curie International outgoing fellow, M.P.D. is an Australian National Health and Medical Research Council senior research fellow, and V.V. is an Australian Research Council future fellow. NR 43 TC 81 Z9 82 U1 0 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2011 VL 186 IS 7 BP 4285 EP 4294 DI 10.4049/jimmunol.1003898 PG 10 WC Immunology SC Immunology GA 739WH UT WOS:000288751200054 PM 21383244 ER PT J AU Qian, L Wu, HM Chen, SH Zhang, D Ali, SF Peterson, L Wilson, B Lu, RB Hong, JS Flood, PM AF Qian, Li Wu, Hung-ming Chen, Shih-Heng Zhang, Dan Ali, Syed F. Peterson, Lynda Wilson, Belinda Lu, Ru-Band Hong, Jau-Shyong Flood, Patrick M. TI beta 2-Adrenergic Receptor Activation Prevents Rodent Dopaminergic Neurotoxicity by Inhibiting Microglia via a Novel Signaling Pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; BETA-ADRENERGIC AGONISTS; TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; PARKINSONS-DISEASE; NADPH OXIDASE; MEDIATED NEUROTOXICITY; REACTIVE MICROGLIOSIS; SELECTIVE-INHIBITION; CYTOKINE PRODUCTION AB The role of the beta 2 adrenergic receptor (beta 2AR) in the regulation of chronic neurodegenerative inflammation within the CNS is poorly understood. The purpose of this study was to determine neuroprotective effects of long-acting beta 2AR agonists such as salmeterol in rodent models of Parkinson's disease. Results showed salmeterol exerted potent neuroprotection against both LPS and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium-induced dopaminergic neurotoxicity both in primary neuron-glia cultures (at subnanomolar concentrations) and in mice (1-10 mu g/kg/day doses). Further studies demonstrated that salmeterol-mediated neuroprotection is not a direct effect on neurons; instead, it is mediated through the inhibition of LPS-induced microglial activation. Salmeterol significantly inhibited LPS-induced production of microglial proinflammatory neurotoxic mediators, such as TNF-alpha, superoxide, and NO, as well as the inhibition of TAK1-mediated phosphorylation of MAPK and p65 NF-kappa B. The anti-inflammatory effects of salmeterol required beta 2AR expression in microglia but were not mediated through the conventional G protein-coupled receptor/cAMP pathway. Rather, salmeterol failed to induce microglial cAMP production, could not be reversed by either protein kinase A inhibitors or an exchange protein directly activated by cAMP agonist, and was dependent on beta-arrestin2 expression. Taken together, our results demonstrate that administration of extremely low doses of salmeterol exhibit potent neuroprotective effects by inhibiting microglial cell activation through a beta 2AR/beta-arrestin2-dependent but cAMP/protein kinase A-independent pathway. The Journal of Immunology, 2011, 186: 4443-4454. C1 [Qian, Li; Peterson, Lynda; Flood, Patrick M.] Univ N Carolina, N Carolina Oral Hlth Inst, Chapel Hill, NC 27599 USA. [Qian, Li; Wu, Hung-ming; Chen, Shih-Heng; Zhang, Dan; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Ali, Syed F.] US FDA, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70428, Taiwan. RP Flood, PM (reprint author), Univ N Carolina, N Carolina Oral Hlth Inst, CB 7454, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU National Institutes of Health, National Institute for Dental and Craniofacial Research [DE-13079]; Michael J. Fox Foundation; National Institutes of Health/National Institute on Environmental Health Sciences FX This work was supported by National Institutes of Health Grant DE-13079 from the National Institute for Dental and Craniofacial Research and a grant from the Michael J. Fox Foundation. This work was also supported in part by the Intramural Research Program of the National Institutes of Health/National Institute on Environmental Health Sciences. NR 56 TC 26 Z9 27 U1 2 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2011 VL 186 IS 7 BP 4443 EP 4454 DI 10.4049/jimmunol.1002449 PG 12 WC Immunology SC Immunology GA 739WH UT WOS:000288751200072 PM 21335487 ER PT J AU Scher, AI Xu, YA Korf, ESC Hartley, SW Witter, MP Scheltens, P White, LR Thompson, PM Toga, AW Valentino, DJ Launer, LJ AF Scher, Ann I. Xu, Yuan Korf, Esther S. C. Hartley, Stephen W. Witter, Menno P. Scheltens, Philip White, Lon R. Thompson, Paul M. Toga, Arthur W. Valentino, Daniel J. Launer, Lenore J. TI Hippocampal morphometry in population-based incident Alzheimer's disease and vascular dementia: the HAAS SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID LATE-LIFE; BRAIN; AD AB Background Hippocampal changes may be a useful biomarker for Alzheimer's disease if they are specific to dementia sub-type. We compare hippocampal volume and shape in population-based incident cases of Alzheimer's disease and vascular dementia (VaD). Methods Participants are Japanese-American men from the Honolulu Asia Aging Study. The following analysis is based on a sub-group of men with mild incident Alzheimer's disease (n=24: age=82.5 +/- 64.6) or incident VaD (n=14: age=80.5 +/- 64.5). To estimate hippocampal volume, one reader, blinded to dementia diagnosis, manually outlined the left and right formation of the hippocampus using published criteria. We used 3-D mapping methods developed at the Laboratory of Neuro Imaging (LONI) to compare regional variation in hippocampal width between dementia groups. Results Hippocampal volume was about 5% smaller in the Alzheimer's disease group compared to the VaD group, but the difference was not significant. Hippocampal shape differed between the two case groups for the left (p<0.04) but not right (p<0.21) hippocampus. The specific region of the hippocampus that most consistently differed between the Alzheimer's disease and VaD cases was in the lateral portion of the left hippocampus. Our interpretation of this region is that it intersects the CA1 sub-region to a great extent but also includes the dentate gyrus (and hilar region) and subiculum. Conclusion As indicated by shape analysis, there are some differences in atrophy localisation between the Alzheimer's disease and VaD cases, despite the finding that volume of the hippocampi did not differ. These findings suggest hippocampal atrophy in Alzheimer's disease may be more focal than in VaD. C1 [Scher, Ann I.; Hartley, Stephen W.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Scher, Ann I.; Hartley, Stephen W.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. [Xu, Yuan] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Korf, Esther S. C.; Scheltens, Philip] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Amsterdam, Netherlands. [Korf, Esther S. C.; Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Amsterdam, Netherlands. [Witter, Menno P.] Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. [White, Lon R.] Kuakini Med Ctr, Honolulu, HI USA. [Thompson, Paul M.; Toga, Arthur W.; Valentino, Daniel J.] Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. RP Scher, AI (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM ascher@usuhs.mil FU National Institute on Aging, NIH; NIH; Uniformed Services University Intramural Research Program FX National Institute on Aging, NIH Other Funders: NIH; Uniformed Services University Intramural Research Program. NR 14 TC 20 Z9 20 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD APR PY 2011 VL 82 IS 4 BP 373 EP 376 DI 10.1136/jnnp.2008.165902 PG 4 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 734ZY UT WOS:000288384100007 PM 20826877 ER PT J AU Zanotti-Fregonara, P Hindie, E AF Zanotti-Fregonara, Paolo Hindie, Elif TI Lognormal Distribution of Cellular Uptake of Radiopharmaceuticals: Implications for Biologic Response in Cancer Treatment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID RADIOACTIVITY; DOSIMETRY; THERAPY; LEVEL; CELLS; I-131 C1 [Zanotti-Fregonara, Paolo] Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hindie, Elif] St Louis Hosp, Paris, France. RP Zanotti-Fregonara, P (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, Bldg 10,Room B1D43K6,10 Ctr Dr,MSC 2035, Bethesda, MD 20892 USA. EM zanottifregonp@mail.nih.gov FU Intramural NIH HHS NR 16 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR 1 PY 2011 VL 52 IS 4 BP 501 EP 503 DI 10.2967/jnumed.110.084590 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 740OO UT WOS:000288804500006 PM 21421707 ER PT J AU Jacobson, O Weiss, ID Niu, G Balboni, G Congiu, C Onnis, V Kiesewetter, DO Lattanzi, R Salvadori, S Chen, XY AF Jacobson, Orit Weiss, Ido D. Niu, Gang Balboni, Gianfranco Congiu, Cenzo Onnis, Valentina Kiesewetter, Dale O. Lattanzi, Roberta Salvadori, Severo Chen, Xiaoyuan TI Prokineticin Receptor 1 Antagonist PC-10 as a Biomarker for Imaging Inflammatory Pain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prokineticin receptor; inflammation; positron emission tomography (PET); (18)F ID PROTEIN-COUPLED RECEPTORS; ENDOTHELIAL GROWTH-FACTOR; SUPRACHIASMATIC NUCLEUS; TUMOR ANGIOGENESIS; MICE LACKING; BV8; IDENTIFICATION; HOMOLOG; LOCALIZATION; PEPTIDE AB Prokineticin receptor 1 (PKR1) and its ligand Bv8 were shown to be expressed in inflammation-induced pain and by tumor-supporting fibroblasts. Blocking this receptor might prove useful for reducing pain and for cancer therapy. However, there is no method to quantify the levels of these receptors in vivo. Methods: A nonpeptidic PKR1 antagonist, N-{2-[5-(4-fluorobenzyl)- 1-(4-methoxy-benzyl)-4,6-dioxo-1,4,5,6-tetrahydro-[1,3,5] triazin-2-ylamino]-ethyl}-guanidine, which contains a free guanidine group, was labeled with (18)F by reacting the guanidine function with N-succinimidyl-4-(18)F-fluorobenzoate to give the guanidinyl amide N-(4-(18)F-fluoro-benzoyl)-N9-{2-[5-(4-fluorobenzyl)- 1-(4-methoxy-benzyl)-4,6-dioxo-1,4,5,6-tetrahydro-[1,3,5] triazin-2-ylamino]-ethyl}-guanidine ((18)F-PC-10). Inflammation was induced in C57BL/6 mice by subcutaneous injection of complete Freund adjuvant in the paw. The mice were imaged with (18)F-PC10, (18)F-FDG, and (64)Cu-pyruvaldehyde bis(4-methyl-3-thiosemicarbazone) ((64)Cu-PTSM) at 24 h after complete Freund adjuvant injection using a small-animal PET device. Results: (18)F-PC-10 was synthesized with a radiochemical yield of 16% +/- 3% (decay-corrected). (18)F-PC-10 accumulated specifically in the inflamed paw 4- to 5-fold more than in the control paw. Compared with (18)F-PC-10, (18)F-FDG and (64)Cu-PTSM displayed higher accumulation in the inflamed paw but also had higher accumulation in the control paw, demonstrating a reduced signal-to-background ratio. (18)F-PC-10 also accumulated in PKR1-expressing organs, such as the salivary gland and gastrointestinal tract. Conclusion: (18)F-PC-10 can be used to image PKR1, a biomarker of the inflammation process. However, the high uptake of (18)F-PC-10 in the gastrointestinal tract, due to specific uptake and the metabolic processing of this highly lipophilic molecule, would restrict its utility. C1 [Jacobson, Orit; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. [Weiss, Ido D.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Balboni, Gianfranco; Congiu, Cenzo; Onnis, Valentina] Univ Cagliari, Dept Toxicol, Cagliari, Italy. [Lattanzi, Roberta] Univ Roma La Sapienza, Dept Physiol & Pharmacol Vittorio Erspamer, Rome, Italy. [Salvadori, Severo] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. [Salvadori, Severo] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. RP Chen, XY (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA. EM shawn.chen@nih.gov RI Onnis, Valentina/B-1649-2008; OI Onnis, Valentina/0000-0002-2438-725X; Congiu, Cenzo/0000-0003-2600-4221; LATTANZI, Roberta/0000-0002-6377-9256; SALVADORI, Severo/0000-0002-8224-2358 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); National Science Foundation of China (NSFC) [81028009]; Italian Ministry of University and Scientific Research FX We thank Weihua Li for skillful assistance with data acquisition and Dr. Roberta Lattanzi for the preliminary in vivo assay of cold PC-10. This research was supported in part by the Intramural Research Program (IRP) of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), International Cooperative Program of National Science Foundation of China (NSFC) (81028009), and Italian Ministry of University and Scientific Research (PRIN 2007). NR 38 TC 3 Z9 3 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR 1 PY 2011 VL 52 IS 4 BP 600 EP 607 DI 10.2967/jnumed.110.084772 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 740OO UT WOS:000288804500021 PM 21421710 ER PT J AU Hapdey, S Buvat, I Carson, JM Carrasquillo, JA Whatley, M Bacharach, SL AF Hapdey, Sebastien Buvat, Irene Carson, Joan M. Carrasquillo, Jorge A. Whatley, Millie Bacharach, Stephen L. TI Searching for Alternatives to Full Kinetic Analysis in F-18-FDG PET: An Extension of the Simplified Kinetic Analysis Method SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE oncology; PET; radiotracer tissue kinetics; Patlak; simplified kinetic analysis ID POSITRON-EMISSION-TOMOGRAPHY; STANDARDIZED UPTAKE VALUES; INPUT FUNCTION; BODY-WEIGHT; FDG UPTAKE; CANCER; THERAPY; BRAIN; TIME; FLUORODEOXYGLUCOSE AB The most accurate way to estimate the glucose metabolic rate (or its influx constant) from F-18-FDG PET is to perform a full kinetic analysis (or its simplified Patlak version), requiring dynamic imaging and the knowledge of arterial activity as a function of time. To avoid invasive arterial blood sampling, a simplified kinetic analysis (SKA) has been proposed, based on blood curves measured from a control group. Here, we extend the SKA by allowing for a greater variety of arterial input function (A(t)) curves among patients than in the original SKA and by accounting for unmetabolized F-18-FDG in the tumor. Methods: Ten A(t)s measured in patients were analyzed using a principal-component analysis to derive 2 principal components describing most of the variability of the A(t). The mean distribution volume of F-18-FDG in tumors for these patients was used to estimate the corresponding quantity in other patients. In subsequent patient studies, the A(t) was described as a linear combination of the 2 principal components, for which the 2 scaling factors were obtained from an early and a late venous sample drawn for the patient. The original and extended SKA (ESKA) were assessed using fifty-seven F-18-FDG PET scans with various tumor types and locations and using different injection and acquisition protocols, with the K-i derived from Patlak analysis as a reference. Results: ESKA improved the accuracy or precision of the input function (area under the blood curve) for all protocols examined. The mean errors (+/- SD) in Ki estimates were -12% +/- 33% for SKA and -7% +/- 22% for ESKA for a 20-s injection protocol with a 55-min postinjection PET scan, 20% +/- 42% for SKA and 1% +/- 29% for ESKA (P < 0.05) for a 120-s injection protocol with a 55-min postinjection PET scan, and -37% +/- 19% for SKA and -4% +/- 6% for ESKA (P < 0.05) for a 20-s injection protocol with a 120-min postinjection PET scan. Changes in Ki between the 2 PET scans in the same patients also tended to be estimated more accurately and more precisely with ESKA than with SKA. Conclusion: ESKA, compared with SKA, significantly improved the accuracy and precision of Ki estimates in F-18-FDG PET. ESKA is more robust than SKA with respect to various injection and acquisition protocols. C1 [Hapdey, Sebastien] Univ Rouen, Lab QuantIF LITIS EA 4108, Rouen, France. [Buvat, Irene] Univ Paris 11, Univ Paris 07, Lab Imaging & Modelling Neurobiol & Oncol, CNRS,UMR 8165, Orsay, France. [Carson, Joan M.; Whatley, Millie] NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. [Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Bacharach, Stephen L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hapdey, Sebastien] Ctr Henri Becquerel, Dept Nucl Med, F-76000 Rouen, France. RP Hapdey, S (reprint author), Ctr Henri Becquerel, Dept Nucl Med, 1 Rue Amiens, F-76000 Rouen, France. EM sebastien.hapdey@rouen.fnclcc.fr OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 19 TC 7 Z9 7 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR 1 PY 2011 VL 52 IS 4 BP 634 EP 641 DI 10.2967/jnumed.110.079079 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 740OO UT WOS:000288804500025 PM 21421718 ER PT J AU Zhou, Y Yan, X Kim, Y Jacobson, O Chen, X AF Zhou, Y. Yan, X. Kim, Y. Jacobson, O. Chen, X. TI Dual modality imaging of cancer with copper-labeled lissamine rhodamine SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 [Zhou, Y.; Yan, X.; Kim, Y.] Purdue Univ, W Lafayette, IN 47907 USA. [Jacobson, O.; Chen, X.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR 1 PY 2011 VL 52 IS 4 MA 11 BP 665 EP 665 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 740OO UT WOS:000288804500041 ER PT J AU Sousa, AA Azari, AA Zhang, GF Leapman, RD AF Sousa, Alioscka A. Azari, Afrouz A. Zhang, Guofeng Leapman, Richard D. TI Dual-axis electron electron tomography of biological specimens: Extending the limits of specimen thickness with bright-field STEM imaging SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Electron tomography; Scanning transmission electron microscopy; STEM tomography; Monte Carlo simulations ID RESOLUTION; CELLS; MICROSCOPE; NANOSCALE AB The absence of imaging lenses after the specimen in the scanning transmission electron microscope (STEM) enables electron tomography to be performed in the STEM mode on micrometer-thick plastic-embedded specimens without the deleterious effect of chromatic aberration, which limits spatial resolution and signal-to-noise ratio in conventional TEM. Using Monte Carlo calculations to simulate electron scattering from gold nanoparticles situated at the top and bottom surfaces of a plastic section, we assess the optimal acquisition strategy for axial bright-field STEM electron tomography at a beam-energy of 300 key. Dual tilt-axis STEM tomography with optimized axial bight-field detector geometry is demonstrated by application to micrometer-thick sections of beta cells from mouse pancreatic islet. The quality of the resulting three-dimensional reconstructions is comparable to that obtained from much thinner (0.3-micrometer) sections using conventional TEM tomography. The increased range of specimen thickness accessible to axial STEM tomography without the need for serial sectioning enables the 3-D visualization of more complex and larger subcellular structures. Published by Elsevier Inc. C1 [Sousa, Alioscka A.; Azari, Afrouz A.; Zhang, Guofeng; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA. EM leapmanr@mail.nih.gov FU National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health FX The authors are grateful to Dr. David Mastronarde for helpful discussions and to Dr. Tao Cai for providing us with the isolated islets from mouse pancreata. This work was supported by the Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. NR 27 TC 29 Z9 29 U1 0 U2 14 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 APR PY 2011 VL 174 IS 1 BP 107 EP 114 DI 10.1016/j.jsb.2010.10.017 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 738LA UT WOS:000288640100013 PM 21055473 ER PT J AU Khan, M Kamal, AK AF Khan, Maria Kamal, Ayeesha Kamran TI Atrial Fibrillation, is Warfarin the only option for stroke prevention? SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CLOPIDOGREL PLUS ASPIRIN; EVENTS ACTIVE-W; VASCULAR EVENTS; ORAL ANTICOAGULATION; IRBESARTAN; TRIAL C1 [Khan, Maria] Aga Khan Univ Hosp, Int CerebrovascTranslat Clin Res & Training Progr, Fogarty Int Ctr, Karachi, Pakistan. Aga Khan Univ Hosp, Natl Inst Hlth, USA, Karachi, Pakistan. RP Khan, M (reprint author), Aga Khan Univ Hosp, Int CerebrovascTranslat Clin Res & Training Progr, Fogarty Int Ctr, Karachi, Pakistan. NR 4 TC 0 Z9 0 U1 0 U2 0 PU PAKISTAN MEDICAL ASSOC PI KARACHI PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN SN 0030-9982 J9 J PAK MED ASSOC JI J. Pak. Med. Assoc. PD APR PY 2011 VL 61 IS 4 BP 406 EP 407 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 738DL UT WOS:000288619500027 PM 21465988 ER PT J AU Reynolds, HY AF Reynolds, Herbert Y. TI Bronchoalveolar Lavage and Other Methods to Define the Human Respiratory Tract Milieu in Health and Disease SO LUNG LA English DT Review DE Bronchoalveolar lavage; Connective tissue diseases; Hypersensitivity pneumonitis; Idiopathic pulmonary fibrosis; Interstitial lung disease; Sarcoidosis; Scleroderma ID OBSTRUCTIVE PULMONARY-DISEASE; INTERSTITIAL LUNG-DISEASE; EXHALED BREATH CONDENSATE; ACTIVATED-RECEPTOR-GAMMA; HYPERSENSITIVITY PNEUMONITIS; ALVEOLAR MACROPHAGES; BRONCHIAL LAVAGE; DIAGNOSTIC-TOOL; CYSTIC-FIBROSIS; NITRIC-OXIDE AB During fiber-optic bronchoscopy (FOB), surface sampling of the human respiratory airways and alveolar unit can be done with bronchoalveolar lavage (BAL), plus selective sites can be brushed for cells and transbronchial biopsies made in adjacent tissue. This permits analysis of the respiratory tract's milieu in healthy normals, in those with disease, and in control subjects. These combined procedures have been an established approach for obtaining specimens for research and for clinical assessment for over four decades. However, now new less invasive sampling methods are emerging. This review emphasizes BAL and the cellular and noncellular components recovered in fluid that have contributed to improving knowledge of how the respiratory tree's innate immunity can protect, and how airway structures can become deranged and manifest disease. After a discussion of training for FOB and procedural issues, a spectrum of respiratory diseases studied with BAL is presented, including airway illness (asthma and chronic obstructive pulmonary disease), diffuse interstitial lung diseases [idiopathic pulmonary fibrosis, rheumatoid interstitial lung disease (ILD), granulomatous ILDs], lung infections, lung malignancy, and upper and lower tract airway problems. Some recent studies with exhaled breath condensate analyses are given. C1 NHLBI, Lung Biol & Dis Branch, Div Lung Dis, Bethesda, MD 20892 USA. RP Reynolds, HY (reprint author), NHLBI, Lung Biol & Dis Branch, Div Lung Dis, 6701 Rockledge Dr,Suite 10042,2 Rockledge Ctr,MSC, Bethesda, MD 20892 USA. EM reynoldh@nhlbi.nih.gov NR 109 TC 7 Z9 8 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD APR PY 2011 VL 189 IS 2 BP 87 EP 99 DI 10.1007/s00408-011-9284-5 PG 13 WC Respiratory System SC Respiratory System GA 738UK UT WOS:000288667800001 PM 21350888 ER PT J AU Lefman, J Scott, K Stranick, S AF Lefman, Jonathan Scott, Keana Stranick, Stephan TI Live, Video-Rate Super-Resolution Microscopy Using Structured Illumination and Rapid GPU-Based Parallel Processing SO MICROSCOPY AND MICROANALYSIS LA English DT Article DE structured illumination; fluorescence microscopy; CUDA; GPU; real time; super-resolution ID LIMIT AB Structured illumination fluorescence microscopy is a powerful super-resolution method that is capable of achieving a resolution below 100 nm. Each super-resolution image is computationally constructed from a set of differentially illuminated images. However, real-time application of structured illumination microscopy (SIM) has generally been limited due to the computational overhead needed to generate super-resolution images. Here, we have developed a real-time SIM system that incorporates graphic processing unit (GPU) based in-line parallel processing of raw/differentially illuminated images. By using GPU processing, the system has achieved a 90-fold increase in processing speed compared to performing equivalent operations on a multiprocessor computer-the total throughput of the system is limited by data acquisition speed, but not by image processing. Overall, more than 350 raw images (16-bit depth, 512 x 512 pixels) can be processed per second, resulting in a maximum frame rate of 39 super-resolution images per second. This ultrafast processing capability is used to provide immediate feedback of super-resolution images for real-time display. These developments are increasing the potential for sophisticated super-resolution imaging applications. C1 [Lefman, Jonathan; Scott, Keana; Stranick, Stephan] NIST, Gaithersburg, MD 20899 USA. [Lefman, Jonathan] NCI, Oncogenom Sect, Pediat Oncol Branch, Adv Technol Ctr,NIH, Gaithersburg, MD USA. RP Stranick, S (reprint author), NIST, Gaithersburg, MD 20899 USA. EM stranick@nist.gov RI Scott, Keana/J-5717-2015 FU National Research Council at NIST and NIH FX We thank Dr. Javed Khan [National Cancer Institute/National Institutes of Health (NIH)] for helpful discussions and support. We thank Tyler Dye [National Institute of Standards and Technology (NIST)] for designing the schematic presentation of the SIM system. This research was performed while Jonathan Lefman held a National Research Council Research Associateship Award at NIST and NIH. NR 11 TC 3 Z9 4 U1 2 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1431-9276 EI 1435-8115 J9 MICROSC MICROANAL JI Microsc. microanal. PD APR PY 2011 VL 17 IS 2 BP 191 EP 196 DI 10.1017/S1431927611000158 PG 6 WC Materials Science, Multidisciplinary; Microscopy SC Materials Science; Microscopy GA 738BE UT WOS:000288613500005 PM 21385522 ER PT J AU De, S Wurster, AL Precht, P Wood, WH Becker, KG Pazin, MJ AF De, Supriyo Wurster, Andrea L. Precht, Patricia Wood, William H., III Becker, Kevin G. Pazin, Michael J. TI Dynamic BRG1 Recruitment during T Helper Differentiation and Activation Reveals Distal Regulatory Elements SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHROMATIN REMODELING COMPLEXES; CYTOKINE GENE-EXPRESSION; TRANSCRIPTION FACTOR GATA-3; LOCUS-CONTROL REGION; CELL-DIFFERENTIATION; BAF COMPLEX; THYMOCYTE DEVELOPMENT; HYPERSENSITIVE SITES; HISTONE ACETYLATION; MULTIPLE-SCLEROSIS AB T helper cell differentiation and activation require specific transcriptional programs accompanied by changes in chromatin structure. However, little is known about the chromatin remodeling enzymes responsible. We performed genome-wide analysis to determine the general principles of BRG1 binding, followed by analysis of specific genes to determine whether these general rules were typical of key T cell genes. We found that binding of the remodeling protein BRG1 was programmed by both lineage and activation signals. BRG1 binding positively correlated with gene activity at protein-coding and microRNA (miRNA) genes. BRG1 binding was found at promoters and distal regions, including both novel and previously validated distal regulatory elements. Distal BRG1 binding correlated with expression, and novel distal sites in the Gata3 locus possessed enhancer-like activity, suggesting a general role for BRG1 in long-distance gene regulation. BRG1 recruitment to distal sites in Gata3 was impaired in cells lacking STAT6, a transcription factor that regulates lineage-specific genes. Together, these findings suggest that BRG1 interprets both differentiation and activation signals and plays a causal role in gene regulation, chromatin structure, and cell fate. Our findings suggest that BRG1 binding is a useful marker for identifying active cis-regulatory regions in protein-coding and miRNA genes. C1 [De, Supriyo; Wood, William H., III; Becker, Kevin G.] NIA, Res Resources Branch, NIH, Baltimore, MD 21224 USA. [Wurster, Andrea L.; Precht, Patricia; Pazin, Michael J.] NIA, Lab Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. RP Pazin, MJ (reprint author), NHGRI, NIH, 5635 Fishers Lane, Rockville, MD 20892 USA. EM pazinm@mail.nih.gov OI De, Supriyo/0000-0002-2075-7655; Becker, Kevin/0000-0002-6794-6656; Pazin, Michael/0000-0002-7561-3640 FU NIH, National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 89 TC 29 Z9 31 U1 0 U2 5 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 APR PY 2011 VL 31 IS 7 BP 1512 EP 1527 DI 10.1128/MCB.00920-10 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 735SI UT WOS:000288437100016 PM 21262765 ER PT J AU Kanamaluru, D Xiao, Z Fang, SS Choi, SE Kim, DH Veenstra, TD Kemper, JK AF Kanamaluru, Deepthi Xiao, Zhen Fang, Sungsoon Choi, Sung-E Kim, Dong-Hyun Veenstra, Timothy D. Kemper, Jongsook Kim TI Arginine Methylation by PRMT5 at a Naturally Occurring Mutation Site Is Critical for Liver Metabolic Regulation by Small Heterodimer Partner SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BILE-ACID SYNTHESIS; NEGATIVE FEEDBACK-REGULATION; NUCLEAR RECEPTOR SHP; MOLECULAR-BASIS; PATHWAYS; FXR; BIOSYNTHESIS; COMPLEX; GENE; MECHANISMS AB Small Heterodimer Partner (SHP) inhibits numerous transcription factors that are involved in diverse biological processes, including lipid and glucose metabolism. In response to increased hepatic bile acids, SHP gene expression is induced and the SHP protein is stabilized. We now show that the activity of SHP is also increased by posttranslational methylation at Arg-57 by protein arginine methyltransferase 5 (PRMT5). Adenovirus-mediated hepatic depletion of PRMT5 decreased SHP methylation and reversed the suppression of metabolic genes by SHP. Mutation of Arg-57 decreased SHP interaction with its known cofactors, Brm, mSin3A, and histone deacetylase 1 (HDAC1), but not with G9a, and decreased their recruitment to SHP target genes in mice. Hepatic overexpression of SHP inhibited metabolic target genes, decreased bile acid and hepatic triglyceride levels, and increased glucose tolerance. In contrast, mutation of Arg-57 selectively reversed the inhibition of SHP target genes and metabolic outcomes. The importance of Arg-57 methylation for the repression activity of SHP provides a molecular basis for the observation that a natural mutation of Arg-57 in humans is associated with the metabolic syndrome. Targeting posttranslational modifications of SHP may be an effective therapeutic strategy by controlling selected groups of genes to treat SHP-related human diseases, such as metabolic syndrome, cancer, and infertility. C1 [Fang, Sungsoon; Choi, Sung-E; Kim, Dong-Hyun; Kemper, Jongsook Kim] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA. [Kanamaluru, Deepthi] Univ Illinois, Dept Biochem, Urbana, IL USA. [Xiao, Zhen; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Kemper, JK (reprint author), Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. EM jongsook@uiuc.edu FU NIH [DK062777, DK080032]; American Diabetes Association Basic Science; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This study was supported by NIH DK062777, NIH DK080032, and an American Diabetes Association Basic Science Award to J.K.K. This project has been funded in whole or in part with federal funds from the National Cancer Institute and the National Institutes of Health and under contract N01-CO-12400 to T.D.V. NR 39 TC 15 Z9 18 U1 0 U2 3 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 APR PY 2011 VL 31 IS 7 BP 1540 EP 1550 DI 10.1128/MCB.01212-10 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 735SI UT WOS:000288437100018 PM 21262773 ER PT J AU Kauvar, EF Hu, P Pineda-Alvarez, DE Solomon, BD Dutra, A Pak, E Blessing, B Proud, V Shanske, AL Stevens, CA Rosenfeld, JA Shaffer, LG Roessler, E Muenke, M AF Kauvar, Emily F. Hu, Ping Pineda-Alvarez, Daniel E. Solomon, Benjamin D. Dutra, Amalia Pak, Evgenia Blessing, Brooke Proud, Virginia Shanske, Alan L. Stevens, Cathy A. Rosenfeld, Jill A. Shaffer, Lisa G. Roessler, Erich Muenke, Maximilian TI Minimal evidence for a direct involvement of twisted gastrulation homolog 1 (TWSG1) gene in human holoprosencephaly SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Twisted gastrulation homolog 1; TWSG1; Tsg; Holoprosencephaly; HPE; 18p; BMP ID GENOTYPE-PHENOTYPE CORRELATIONS; VERTEBRATE NERVOUS-SYSTEM; FOREBRAIN DEVELOPMENT; FUNCTIONAL-ANALYSIS; MELTING ANALYSIS; RISK-FACTORS; MUTATIONS; CHORDIN; TGIF; MICE AB Holoprosencephaly (HPE) is the most common disorder of human forebrain and facial development. Presently understood etiologies include both genetic and environmental factors, acting either alone, or more likely, in combination. The majority of patients without overt chromosomal abnormalities or recognizable associated syndromes have unidentified etiologies. A potential candidate gene, Twisted Gastrulation Homolog I (TWSG1), was previously suggested as a contributor to the complex genetics of human HPE based on (1) cytogenetic studies of patients with 18p deletions, (2) animal studies of TWSG1 deficient mice, and (3) the relationship of TWSG1 to bone morphogenetic protein (BMP) signaling, which modulates the primary pathway implicated in HPE, Sonic Hedgehog (SHH) signaling. Here we present the first analysis of a large cohort of patients with HPE for coding sequence variations in TWSG1. We also performed fine mapping of 18p for a subset of patients with partial 18p deletions. Surprisingly, minimal evidence for alterations of TWSG1 was found, suggesting that sequence alterations of TWSG1 are neither a common direct cause nor a frequent modifying factor for human HPE pathologies. Published by Elsevier Inc. C1 [Kauvar, Emily F.; Hu, Ping; Pineda-Alvarez, Daniel E.; Solomon, Benjamin D.; Roessler, Erich; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Kauvar, Emily F.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. [Dutra, Amalia; Pak, Evgenia] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Blessing, Brooke; Proud, Virginia] Childrens Hosp Kings Daughters, Div Med Genet, Norfolk, VA USA. [Shanske, Alan L.] Montefiore Med Ctr, Ctr Craniofacial Disorders, Childrens Hosp, Bronx, NY 10467 USA. [Stevens, Cathy A.] Univ Tennessee, Coll Med, Dept Pediat, Chattanooga, TN USA. [Rosenfeld, Jill A.; Shaffer, Lisa G.] Signature Genom Labs, Spokane, WA USA. RP Muenke, M (reprint author), 35 Convent Dr,MSC 3717,Bldg 35,Rm 18-203, Bethesda, MD 20892 USA. EM mamuenke@mail.nih.gov FU National Institutes of Health (NIH); Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA FX Funding received from the National Institutes of Health (NIH).; This research was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA. NR 66 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2011 VL 102 IS 4 BP 470 EP 480 DI 10.1016/j.ymgme.2010.12.008 PG 11 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 740GT UT WOS:000288780300012 PM 21227728 ER PT J AU Zhang, R Lu, SM Qiu, C Liu, XG Gao, CG Guo, TW Valenzuela, RK Deng, HW Ma, J AF Zhang, R. Lu, S. M. Qiu, C. Liu, X. G. Gao, C. G. Guo, T. W. Valenzuela, R. K. Deng, H. W. Ma, J. TI Population-based and family-based association studies of ZNF804A locus and schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Letter ID GENOME; TESTS C1 [Zhang, R.; Lu, S. M.; Ma, J.] Xi An Jiao Tong Univ, Sch Med, Dept Genet & Mol Biol, Xian 710049, Shaanxi, Peoples R China. [Qiu, C.; Liu, X. G.; Deng, H. W.] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Inst Mol Genet, Xian 710049, Shaanxi, Peoples R China. [Gao, C. G.] Xi An Jiao Tong Univ, Affiliated Hosp 1, Sch Med, Dept Psychiat, Xian 710049, Shaanxi, Peoples R China. [Guo, T. W.] NIDDKD, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. [Valenzuela, R. K.] Univ Arizona, Dept Pediat, Arizona Hlth Sci Ctr, Tucson, AZ 85721 USA. RP Ma, J (reprint author), Xi An Jiao Tong Univ, Sch Med, Dept Genet & Mol Biol, Xian 710049, Shaanxi, Peoples R China. EM shemin.lu@gmail.com; majie.paper@gmail.com RI Liu, Xiao-Gang/H-3596-2013; OI Liu, Xiao-Gang/0000-0002-4161-9833; Lu, Shemin/0000-0001-8250-850X; Deng, Hong-Wen/0000-0002-0387-8818 NR 6 TC 35 Z9 40 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD APR PY 2011 VL 16 IS 4 BP 360 EP 361 DI 10.1038/mp.2010.55 PG 3 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 739TK UT WOS:000288740700004 PM 20458322 ER PT J AU Cannon, DM Klaver, JK Gandhi, SK Solorio, G Peck, SA Erickson, K Savitz, J Akula, N Eckelman, WC Furey, ML Sahakian, BJ McMahon, FJ Drevets, WC AF Cannon, D. M. Klaver, J. K. Gandhi, S. K. Solorio, G. Peck, S. A. Erickson, K. Savitz, J. Akula, N. Eckelman, W. C. Furey, M. L. Sahakian, B. J. McMahon, F. J. Drevets, W. C. TI Genetic variation in cholinergic muscarinic-2 receptor gene modulates M-2 receptor binding in vivo and accounts for reduced binding in bipolar disorder SO MOLECULAR PSYCHIATRY LA English DT Article DE depression; muscarinic M-2 binding; CHRM2; G-protein coupled receptor; [F-18]FP-TZTP; PET ID MAJOR DEPRESSIVE DISORDER; ANTERIOR-PITUITARY ACTH; M2 CHRM2 GENE; SUPER-SENSITIVITY; THETA-SYNCHRONIZATION; COGNITIVE-PROCESSES; ALCOHOL DEPENDENCE; EPISODIC RETRIEVAL; MOOD DISORDERS; MANIC SYMPTOMS AB Genetic variation in the cholinergic muscarinic-2 (M-2) receptor gene (CHRM2) has been associated with the risk for developing depression. We previously reported that M-2-receptor distribution volume (V-T) was reduced in depressed subjects with bipolar disorder (BD) relative to depressed subjects with major depressive disorder (MDD) and healthy controls (HCs). In this study, we investigated the effects of six single-nucleotide polymorphisms (SNPs) for CHRM2 on M-2-receptor binding to test the hypotheses that genetic variation in CHRM2 influences M-2-receptor binding and that a CHRM2 polymorphism underlies the deficits in M-2-receptor V-T observed in BD. The M-2-receptor V-T was measured using positron emission tomography and [F-18]FP-TZTP in unmedicated, depressed subjects with BD (n = 16) or MDD (n = 24) and HCs (n = 25), and the effect of genotype on V-T was assessed. In the controls, one SNP (with identifier rs324650, in which the ancestral allele adenine (A) is replaced with one or two copies of thymine (T), showed a significant allelic effect on V-T in the pregenual and subgenual anterior cingulate cortices in the direction AA < AT < TT. In contrast, in BD subjects with the TT genotype, V-T was significantly lower than in BD subjects with the AT genotype in these regions. The BD subjects homozygous for the T -allele also showed markedly lower V-T (by 27 to 37% across regions) than HCs of the same genotype. Post hoc analyses suggested that T homozygosity was associated with a more severe illness course, as manifested by lower socioeconomic function, poorer spatial recognition memory and a greater likelihood of having attempted suicide. These data represent novel preliminary evidence that reduced M-2-receptor V-T in BD is associated with genetic variation within CHRM2. The differential impact of the M-2-receptor polymorphism at rs324650 in the BD and HC samples suggests interactive effects with an unidentified vulnerability factor for BD. Molecular Psychiatry (2011) 16, 407-418; doi:10.1038/mp.2010.24; published online 30 March 2010 C1 [Cannon, D. M.] Natl Univ Ireland, Dept Psychiat, Clin Neuroimaging Lab, Galway, Ireland. [Cannon, D. M.; Klaver, J. K.; Gandhi, S. K.; Solorio, G.; Peck, S. A.; Erickson, K.; Akula, N.; Furey, M. L.; McMahon, F. J.; Drevets, W. C.] NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20892 USA. [Eckelman, W. C.] Mol Tracer LLC, Bethesda, MD USA. [Sahakian, B. J.] Univ Cambridge, Addenbrookes Hosp, Sch Clin Med, Dept Psychiat, Cambridge CB2 2QQ, England. RP Cannon, DM (reprint author), Natl Univ Ireland, Dept Psychiat, Clin Neuroimaging Lab, 201 Comerford Bldg, Galway, Ireland. EM dara.cannon@nuigalway.ie RI Cannon, Dara/C-1323-2009; Savitz, Jonathan/C-3088-2009; Furey, Maura/H-5273-2013; OI Cannon, Dara/0000-0001-7378-3411; Savitz, Jonathan/0000-0001-8143-182X; McMahon, Francis/0000-0002-9469-305X FU NIH/NIMH; National Alliance for Research on Schizophrenia and Depression FX We acknowledge Peter Herscovitch, MD, and the Clinical Center PET Department for providing the radioligand and for technical assistance; Michele Drevets, RN, and Joan Williams, RN, for evaluation and recruitment of the research subjects; the staff of the NIH Clinical Center, Allison Nugent, Stephen Fromm, Kelly Anastasi and Laurentina Cizza for assistance in data management; and Dave Luckenbaugh, PhD, for advice regarding the statistical analysis of the PET data. This study was supported by the intramural research program of the NIH/NIMH and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award. NR 95 TC 19 Z9 21 U1 6 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 APR PY 2011 VL 16 IS 4 BP 407 EP 418 DI 10.1038/mp.2010.24 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 739TK UT WOS:000288740700008 PM 20351719 ER PT J AU Kim, HW Rapoport, SI Rao, JS AF Kim, H-W Rapoport, S. I. Rao, J. S. TI Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients SO MOLECULAR PSYCHIATRY LA English DT Article DE PLA(2); inflammation; mood stabilizers; COX; PGES; excitotoxicity ID DNA-BINDING ACTIVITY; SPINAL-CORD NEURONS; CYTOSOLIC PHOSPHOLIPASE A(2); ALZHEIMERS-DISEASE BRAIN; CENTRAL-NERVOUS-SYSTEM; RAT FRONTAL-CORTEX; TRANSCRIPTION FACTOR; ADMINISTRATION INCREASES; INTERLEUKIN-1 RECEPTOR; DOCOSAHEXAENOIC ACID AB Mood stabilizers that are approved for treating bipolar disorder (BD), when given chronically to rats, decrease expression of markers of the brain arachidonic metabolic cascade, and reduce excitotoxicity and neuroinflammation-induced upregulation of these markers. These observations, plus evidence for neuroinflammation and excitotoxicity in BD, suggest that arachidonic acid (AA) cascade markers are upregulated in the BD brain. To test this hypothesis, these markers were measured in postmortem frontal cortex from 10 BD patients and 10 age-matched controls. Mean protein and mRNA levels of AA-selective cytosolic phospholipase A(2) (cPLA(2)) IVA, secretory sPLA(2) IIA, cyclooxygenase (COX)-2 and membrane prostaglandin E synthase (mPGES) were significantly elevated in the BD cortex. Levels of COX-1 and cytosolic PGES (cPGES) were significantly reduced relative to controls, whereas Ca(2+)-independent iPLA(2)VIA, 5-, 12-, and 15-lipoxygenase, thromboxane synthase and cytochrome p450 epoxygenase protein and mRNA levels were not significantly different. These results confirm that the brain AA cascade is disturbed in BD, and that certain enzymes associated with AA release from membrane phospholipid and with its downstream metabolism are upregulated. As mood stabilizers downregulate many of these brain enzymes in animal models, their clinical efficacy may depend on suppressing a pathologically upregulated cascade in BD. An upregulated cascade should be considered as a target for drug development and for neuroimaging in BD. Molecular Psychiatry (2011) 16, 419-428; doi:10.1038/mp.2009.137; published online 29 December 2009 C1 [Kim, H-W; Rapoport, S. I.; Rao, J. S.] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S-126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov FU PHS [R24MH068855]; National Institute on Aging, National Institutes of Health, Bethesda, MD, USA FX We thank the Harvard Brain Bank, Boston, MA for providing the postmortem brain samples under PHS Grant number R24MH068855. This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. We also thank the Fellows' Editorial Board at NIH for reviewing the manuscript. NR 86 TC 52 Z9 52 U1 0 U2 5 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 APR PY 2011 VL 16 IS 4 BP 419 EP 428 DI 10.1038/mp.2009.137 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 739TK UT WOS:000288740700009 PM 20038946 ER PT J AU Bossert, JM Stern, AL Theberge, FRM Cifani, C Koya, E Hope, BT Shaham, Y AF Bossert, Jennifer M. Stern, Anna L. Theberge, Florence R. M. Cifani, Carlo Koya, Eisuke Hope, Bruce T. Shaham, Yavin TI Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin SO NATURE NEUROSCIENCE LA English DT Article ID NUCLEUS-ACCUMBENS; SEEKING; RATS; REINSTATEMENT; EXTINCTION; FEAR AB In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relapse. C1 [Bossert, Jennifer M.; Stern, Anna L.; Theberge, Florence R. M.; Cifani, Carlo; Koya, Eisuke; Hope, Bruce T.; Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, US Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, US Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014; OI Hope, Bruce/0000-0001-5804-7061; Cifani, Carlo/0000-0001-6180-828X FU National Institute on Drug Abuse (US National Institutes of Health, Department of Health and Human Services) FX We thank B. Navarre and K. Wihbey for their help in conducting the experiments and thank M. van den Oever for the CamKII and GAD67 immunofluorescence protocol. We also thank M. Heilig for helpful comments on the manuscript. This work was supported by the Intramural Research Program of the National Institute on Drug Abuse (US National Institutes of Health, Department of Health and Human Services). NR 15 TC 99 Z9 107 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2011 VL 14 IS 4 BP 420 EP 422 DI 10.1038/nn.2758 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 741FQ UT WOS:000288849400010 PM 21336273 ER PT J AU Hollander, MC Blumenthal, GM Dennis, PA AF Hollander, M. Christine Blumenthal, Gideon M. Dennis, Phillip A. TI PTEN loss in the continuum of common cancers, rare syndromes and mouse models SO NATURE REVIEWS CANCER LA English DT Review ID TUMOR-SUPPRESSOR GENE; CELL LUNG-CANCER; PROTEIN PHOSPHATASE-ACTIVITY; HEMATOPOIETIC STEM-CELLS; LHERMITTE-DUCLOS-DISEASE; GROWTH-FACTOR RECEPTOR; HIGH-GRADE GLIOMA; PROSTATE-CANCER; IN-VIVO; PROMOTER METHYLATION AB PTEN is among the most frequently inactivated tumour suppressor genes in sporadic cancer. PTEN has dual protein and lipid phosphatase activity, and its tumour suppressor activity is dependent on its lipid phosphatase activity, which negatively regulates the PI3K-AKT-mTOR pathway(1,2). Germline mutations in PTEN have been described in a variety of rare syndromes that are collectively known as the PTEN hamartoma tumour syndromes (PHTS). Cowden syndrome is the best-described syndrome within PHTS, with approximately 80% of patients having germline PTEN mutations(3). Patients with Cowden syndrome have an increased incidence of cancers of the breast, thyroid and endometrium, which correspond to sporadic tumour types that commonly exhibit somatic PTEN inactivation. Pten deletion in mice leads to Cowden syndrome-like phenotypes, and tissue-specific Pten deletion has provided clues to the role of PTEN mutation and loss in specific tumour types. Studying PTEN in the continuum of rare syndromes, common cancers and mouse models provides insight into the role of PTEN in tumorigenesis and will inform targeted drug development. C1 [Hollander, M. Christine; Blumenthal, Gideon M.; Dennis, Phillip A.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, 37 Convent Dr,Room 1118B, Bethesda, MD 20892 USA. EM pdennis@nih.gov NR 211 TC 328 Z9 337 U1 7 U2 64 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2011 VL 11 IS 4 BP 289 EP 301 DI 10.1038/nrc3037 PG 13 WC Oncology SC Oncology GA 739TP UT WOS:000288741300014 PM 21430697 ER PT J AU O'Shea, JJ Lahesmaa, R Vahedi, G Laurence, A Kanno, Y AF O'Shea, John J. Lahesmaa, Riitta Vahedi, Golnaz Laurence, Arian Kanno, Yuka TI Genomic views of STAT function in CD4(+) T helper cell differentiation SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HYPER-IGE SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; TRANSCRIPTION FACTOR-BINDING; MICE LACKING JAK3; ROR-GAMMA-T; WIDE ASSOCIATION; IN-VIVO; GENE-EXPRESSION; DNA-BINDING; TH17 CELLS AB Signal transducer and activator of transcription (STAT) proteins are well known for their essential roles in transmitting cytokine-mediated signals and specifying T helper (T-H) cell differentiation. Recent technological advances have revealed that STAT proteins have broad and complex roles in gene regulation and epigenetic control, including important roles as functional repressors. However, the challenge of how to link signal transduction, nucleosome biology and gene regulation remains. The relevance of tackling this problem is highlighted by genome-wide association studies that link cytokine signalling and STATs to various autoimmune or immune deficiency disorders. Defining exactly how extrinsic signals control the specification and plasticity of T-H cells will provide important insights and perhaps therapeutic opportunities in these diseases. C1 [O'Shea, John J.; Vahedi, Golnaz; Laurence, Arian; Kanno, Yuka] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Lahesmaa, Riitta] Univ Turku, Turku Ctr Biotechnol, FI-20521 Turku, Finland. [Lahesmaa, Riitta] Abo Akad Univ, FI-20521 Turku, Finland. RP O'Shea, JJ (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov RI Laurence, Arian/A-8770-2009; Kanno, Yuka/B-5802-2013; OI Laurence, Arian/0000-0003-0942-8292; Kanno, Yuka/0000-0001-5668-9319 NR 146 TC 111 Z9 112 U1 0 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2011 VL 11 IS 4 BP 239 EP 250 DI 10.1038/nri2958 PG 12 WC Immunology SC Immunology GA 740HE UT WOS:000288781400008 PM 21436836 ER PT J AU Grice, EA Segre, JA AF Grice, Elizabeth A. Segre, Julia A. TI The skin microbiome SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID INNATE IMMUNE-RESPONSE; ATOPIC-DERMATITIS; PROPIONIBACTERIUM-ACNES; STAPHYLOCOCCUS-EPIDERMIDIS; BACTERIAL DIVERSITY; MOLECULAR ANALYSIS; HUMAN-BODY; ANTIMICROBIAL PEPTIDES; PSORIATIC LESIONS; AXILLARY ODOR AB The skin is the human body's largest organ, colonized by a diverse milieu of microorganisms, most of which are harmless or even beneficial to their host. Colonization is driven by the ecology of the skin surface, which is highly variable depending on topographical location, endogenous host factors and exogenous environmental factors. The cutaneous innate and adaptive immune responses can modulate the skin microbiota, but the microbiota also functions in educating the immune system. The development of molecular methods to identify microorganisms has led to an emerging view of the resident skin bacteria as highly diverse and variable. An enhanced understanding of the skin microbiome is necessary to gain insight into microbial involvement in human skin disorders and to enable novel promicrobial and antimicrobial therapeutic approaches for their treatment. C1 [Grice, Elizabeth A.; Segre, Julia A.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Segre, JA (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. EM jsegre@nhgri.nih.gov OI Grice, Elizabeth/0000-0003-3939-2200 FU US National Institute of General Medical Sciences; US National Human Genome Research Institute; US National Institutes of Health [AR057504] FX We thank H. Kong and E. Hobbs for critical reading of the manuscript and J. Fekecs and D. Leja for graphical assistance. E.A.G. is supported by a Pharmacology Research Associate Training Fellowship, US National Institute of General Medical Sciences. This work was supported by the US National Human Genome Research Institute Intramural Research Program and the US National Institutes of Health Common Fund AR057504. NR 106 TC 474 Z9 490 U1 36 U2 275 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 EI 1740-1534 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD APR PY 2011 VL 9 IS 4 BP 244 EP 253 DI 10.1038/nrmicro2537 PG 10 WC Microbiology SC Microbiology GA 735SD UT WOS:000288436600011 PM 21407241 ER PT J AU Skinner, M AF Skinner, Mhairi TI GENE EXPRESSION Transcriptional activators do double-duty SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Editorial Material C1 NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. RP Skinner, M (reprint author), NCI, Nat Pathway Interact Database, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD APR PY 2011 VL 12 IS 4 BP 205 EP 205 DI 10.1038/nrm3087 PG 1 WC Cell Biology SC Cell Biology GA 739EQ UT WOS:000288696700002 PM 21407238 ER PT J AU Koike, T Kan, S Misaki, M Miyauchi, S AF Koike, Takahiko Kan, Shigeyuki Misaki, Masaya Miyauchi, Satoru TI Connectivity pattern changes in default-mode network with deep non-REM and REM sleep SO NEUROSCIENCE RESEARCH LA English DT Article DE EEG; fMRI; Default mode network; Sleep; Consciousness ID MEDIAL PREFRONTAL CORTEX; RESTING HUMAN BRAIN; SLOW-WAVE SLEEP; FUNCTIONAL CONNECTIVITY; SPONTANEOUS FLUCTUATIONS; AUTOBIOGRAPHICAL MEMORY; COGNITIVE NEUROSCIENCE; TEMPORAL CORTEX; VISUAL-CORTEX; GLOBAL SIGNAL AB Recent studies have compared default-mode network (DMN) connectivity in different arousal levels to investigate the relationship between consciousness and DMN. The comparison between the DMN in rapid eye movement (REM) sleep with that in non-REM (NREM) sleep is useful for revealing the relationship between arousal level and DMN, because the arousal level is at its lowest during deep NREM, while during REM sleep it is as high as wakefulness. Functional magnetic resonance imaging (fMRI) and polysomnogram data were acquired from participants in REM, deep NREM, and light NREM sleep, and the DMN was compared using functional connectivity analysis. Our analysis revealed that functional connectivity among the DMN core regions - the posterior cingulate cortex, rostra] anterior cingulate cortex, and inferior parietal lobule - remained consistent across sleep states. In contrast, connectivity involving the DMN subsystems of REM sleep differs from that of NREM sleep, and the change well accounts for the characteristics of REM sleep. Our results suggest that both the DMN core region and subsystems may not relate to the maintenance of arousal. The DMN core network and subsystems may respectively serve to integrate brain regions and perform function specific to each level of arousal. (c) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved. C1 [Koike, Takahiko; Kan, Shigeyuki; Miyauchi, Satoru] Natl Inst Informat & Commun Technol, Kobe Adv ICT Res Ctr, Kobe, Hyogo 6512492, Japan. [Koike, Takahiko; Kan, Shigeyuki; Miyauchi, Satoru] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan. [Misaki, Masaya] NIMH, LBC SFIM, NIH, Bethesda, MD 20892 USA. RP Koike, T (reprint author), Natl Inst Informat & Commun Technol, Kobe Adv Res Ctr, Nishi Ku, 588-2 Iwaoka,Iwaoka cho, Kobe, Hyogo 6512492, Japan. EM takahikoike@po.nict.go.jp; miyauchi@po.nict.go.jp FU CREST of Japan Science and Technology (JST); MEXT [22700287] FX We thank two anonymous reviewers for their useful suggestions. This work was supported by CREST of Japan Science and Technology (JST), and Grant-in-Aid for Young Scientists (B) from the MEXT (No. 22700287). NR 56 TC 43 Z9 43 U1 4 U2 14 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD APR PY 2011 VL 69 IS 4 BP 322 EP 330 DI 10.1016/j.neures.2010.12.018 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 741DR UT WOS:000288843800008 PM 21238510 ER PT J AU Steiner, AZ Herring, AH Kesner, JS Meadows, JW Stanczyk, FZ Hoberman, S Baird, DD AF Steiner, Anne Z. Herring, Amy H. Kesner, James S. Meadows, Juliana W. Stanczyk, Frank Z. Hoberman, Steven Baird, Donna D. TI Antimullerian Hormone as a Predictor of Natural Fecundability in Women Aged 30-42 Years SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; ANTI-MULLERIAN HORMONE; OVARIAN RESERVE TESTS; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; PROVEN FERTILITY; INHIBIN-B; SERUM; POPULATION; PREGNANCY AB OBJECTIVE: To generate estimates of the association between markers of ovarian aging and natural fertility in a community sample at risk for ovarian aging. METHODS: Women aged 30-44 years with no history of infertility who had been trying to conceive for less than 3 months provided early-follicular phase serum and urine (N=100). Subsequently, these women kept a diary to record menstrual bleeding and intercourse and conducted standardized pregnancy testing for up to 6 months. Serum was analyzed for estradiol, follicle-stimulating hormone (FSH), antimullerian hormone, and inhibin B. Urine was analyzed for FSH and estrone 3-glucuronide. Diary data on menstrual cycle day and patterns of intercourse were used to calculate day-specific fecundability ratios. RESULTS: Sixty-three percent of participants conceived within 6 months. After adjusting for age, 18 women (18%) with serum antimullerian hormone levels of 0.7 ng/mL or less had significantly reduced fecundability given intercourse on a fertile day compared with women with higher antimullerian hormone levels (fecundability ratio 0.38; 95% confidence interval [CI] 0.08-0.91). The day-specific fecundability for women with early-follicular phase serum FSH values greater than 10 milli-international units/mL compared with women with lower FSH levels was also reduced, although nonsignificantly (11% of women affected; fecundability ratio 0.44; 95% CI 0.08-1.10). The association with urinary FSH was weaker (27% women affected; fecundability ratio 0.61; 95% CI 0.26-1.26), and the associations for the other markers were weaker still. CONCLUSION: Early-follicular phase antimullerian hormone appears to be associated with natural fertility in the general population. (Obstet Gynecol 2011;117:798-804) DOI: 10.1097/AOG.0b013e3182116bc8 C1 [Steiner, Anne Z.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIOSH, Cincinnati, OH 45226 USA. Univ So Calif, Dept Obstet & Gynecol & Prevent Med, Los Angeles, CA USA. NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Steiner, AZ (reprint author), Univ N Carolina, Dept Obstet & Gynecol, CB 7570,4001 Old Clin Bldg, Chapel Hill, NC 27599 USA. EM asteiner@med.unc.edu RI Baird, Donna/D-5214-2017 OI Baird, Donna/0000-0002-5544-2653 FU National Institutes of Health (NIH) (University of North Carolina Women's Reproductive Health Research Center) [R21 HD060229, 5 K12 HD050113]; NIH, National Institute of Environmental Health Sciences FX Supported by National Institutes of Health (NIH) R21 HD060229 and 5 K12 HD050113 (University of North Carolina Women's Reproductive Health Research Center). Also supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ie, support for coauthor D.B.). NR 32 TC 58 Z9 61 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 798 EP 804 DI 10.1097/AOG.0b013e3182116bc8 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500006 PM 21422850 ER PT J AU Laughon, SK Zhang, J Troendle, J Sun, LP Reddy, UM AF Laughon, S. Katherine Zhang, Jun Troendle, James Sun, Liping Reddy, Uma M. TI Using a Simplified Bishop Score to Predict Vaginal Delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID INDUCTION; LABOR; INDUCIBILITY; HYPERTENSION; SYSTEMS AB OBJECTIVE: The Bishop score is the most commonly used method to assess the readiness of the cervix for induction. However, it was created without modern statistical methods. Our objective was to determine whether a simplified score can predict vaginal delivery equally well. METHODS: Data were analyzed for 5,610 nulliparous women with singleton, uncomplicated pregnancies between 37 0/7 and 41 6/7 weeks of gestation undergoing labor induction. These women had all five components of the Bishop score recorded. Logistic regression was performed and a simplified score created with significant components. Positive and negative predictive values and positive likelihood ratios were calculated. RESULTS: In the regression model, only dilation, station, and effacement were significantly associated with vaginal delivery (P <.01). The simplified Bishop score was then devised using these three components (range 0-9) and compared with the original Bishop score (range 0-13) for prediction of successful induction, resulting in vaginal delivery. Compared with the original Bishop score (greater than 8), the simplified Bishop score (greater than 5) had a similar or better positive predictive value (87.7% compared with 87.0%), negative predictive value (31.3% compared with 29.8%), positive likelihood ratio (2.34 compared with 2.19), and correct classification rate (51.0% compared with 47.3%). Application of the simplified Bishop score in other populations, including indicated induction and spontaneous labor at term and preterm, were associated with similar vaginal delivery rates compared with the original Bishop score. CONCLUSION: The simplified Bishop score comprised of dilation, station, and effacement attains a similarly high predictive ability of successful induction as the original score. (Obstet Gynecol 2011;117:805-11) DOI: 10.1097/AOG.0b013e3182114ad2 C1 [Laughon, S. Katherine; Zhang, Jun; Troendle, James; Sun, Liping; Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Laughon, SK (reprint author), NICHD, Epidemiol Branch, NIH, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM laughonsk@mail.nih.gov OI Grantz, Katherine/0000-0003-0276-8534 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX The data included in this article were obtained from the Consortium on Safe Labor, which was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract No. HHSN267200603425C. Institutions involved in the Consortium include, in alphabetical order: Baystate Medical Center, Springfield, Massachusetts; Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles, California; Christiana Care Health System, Newark, Delaware; Georgetown University Hospital, MedStar Health, Washington, DC; Indiana University Clarian Health, Indianapolis, Indiana; Intermountain Healthcare and the University of Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, New York; MetroHealth Medical Center, Cleveland, Ohio; Summa Health System, Akron City Hospital, Akron, Ohio; The EMMES Corporation, Rockville, Maryland (Data Coordinating Center); University of Illinois at Chicago, Chicago, Illinois; University of Miami, Miami, Florida; and University of Texas Health Science Center at Houston, Houston, Texas. NR 17 TC 30 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 805 EP 811 DI 10.1097/AOG.0b013e3182114ad2 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500007 PM 21383643 ER PT J AU Durnwald, CP Mele, L Spong, CY Ramin, SM Varner, MW Rouse, DJ Sciscione, A Catalano, P Saade, G Sorokin, Y Tolosa, JE Casey, B Anderson, GD AF Durnwald, Celeste P. Mele, Lisa Spong, Catherine Y. Ramin, Susan M. Varner, Michael W. Rouse, Dwight J. Sciscione, Anthony Catalano, Patrick Saade, George Sorokin, Yoram Tolosa, Jorge E. Casey, Brian Anderson, Garland D. CA Eunice Kennedy Shriver Natl Inst C TI Glycemic Characteristics and Neonatal Outcomes of Women Treated for Mild Gestational Diabetes SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PIMA INDIAN WOMEN; BODY-COMPOSITION; BIRTH-WEIGHT; PREGNANCY; MELLITUS; OBESITY; ADIPOSITY; INFANTS; MOTHERS; AGE AB OBJECTIVE: To estimate the association between fasting and 2-hour postprandial blood glucose levels and neonatal outcomes in women treated for mild gestational diabetes. METHODS: In this secondary analysis of a multicenter randomized treatment trial of mild gestational diabetes, the median fasting and 2-hour postprandial glucose levels were analyzed in 2-week intervals and change over time (slope) was calculated for women with gestational diabetes (abnormal oral glucose tolerance test) and a fasting glucose less than 95 mg/dL who received nutritional management with self blood glucose monitoring and insulin as needed. Regression analyses were performed to estimate the relationship between median fasting and postprandial glucose and neonatal fat mass, cord blood C-peptide, birth weight, large-for-gestational-age neonates, macrosomia (greater than 4,000 g), and neonatal hypoglycemia. RESULTS: Among 460 women with gestational diabetes, median fasting (P <.001), postprandial breakfast (P <.001), and postprandial lunch (P <.001) glucose values declined over the treatment period, whereas postprandial dinner values remained stable (P=.83). Higher median fasting glucose during the first 2 weeks of treatment was significantly associated with increased odds ratios for neonatal fat mass (1.35; 95% CI 1.09-1.66; P=.006) and elevated C-peptide (1.29; CI 1.09-1.52; P=.003). Higher median fasting glucose during the last 2 weeks before delivery was associated with higher rates of large-for-gestational-age neonates (1.27; CI 1.05-1.53; P=.01), macrosomia (1.32; CI 1.04-1.65; P=.02), and elevated C-peptide (1.19; CI 1.03-1.38; P=.02). CONCLUSION: In women treated for mild gestational diabetes, higher fasting glucose during initiation of diet therapy was associated with increased neonatal fat mass and elevated C-peptide and during the last 2 weeks before delivery with macrosomia, large-for-gestational age, and elevated C-peptide. (Obstet Gynecol 2011;117:819-27) DOI: 10.1097/AOG.0b013e31820fc6cf C1 [Durnwald, Celeste P.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. Univ Utah, Salt Lake City, UT USA. Univ Alabama, Birmingham, AL USA. Drexel Univ, Philadelphia, PA 19104 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA. Univ Texas Med Branch, Galveston, TX USA. Wayne State Univ, Detroit, MI USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Durnwald, CP (reprint author), Ohio State Univ, Dept Obstet & Gynecol, 395 W 12th Ave,Room 544, Columbus, OH 43210 USA. EM celeste.durnwald@osumc.edu RI Varner, Michael/K-9890-2013 OI Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers [M01-RR00034]; National Center for Research Resources [UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD; HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118, HD36801); General Clinical Research Centers Grant (M01-RR00034); and the National Center for Research Resources (UL1-RR024989, M01-RR00080, UL1-RR025764, C06-RR11234), and does not necessarily represent the official views of the NICHD or the National Institutes of Health. NR 18 TC 9 Z9 10 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 819 EP 827 DI 10.1097/AOG.0b013e31820fc6cf PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500009 PM 21422852 ER PT J AU Balchin, I Whittaker, JC Lamont, RF Steer, PJ AF Balchin, Imelda Whittaker, John C. Lamont, Ronald F. Steer, Philip J. TI Maternal and Fetal Characteristics Associated With Meconium-Stained Amniotic Fluid SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; PERINATAL-MORTALITY; APGAR SCORES; LABOR; BIRTH; GESTATION; PREGNANCIES; MANAGEMENT; DELIVERY; HAZARD AB OBJECTIVE: To estimate the rates of meconium-stained amniotic fluid (AF) and adverse outcome in relation to gestational age and racial group, and to investigate the predictors of meconium-stained AF. METHODS: We studied 499,096 singleton births weighing at least 500 g, at 24 or more weeks of gestation, from 1988 to 2000. The predictors of meconium-stained AF from 37 weeks of gestation onward were determined using multiple logistic regression. RESULTS: The crude meconium-stained AF rates in pre-term, term, and postterm births were 5.1% (95% confidence interval [CI] 4.9-5.4), 16.5% (95% CI 16.4-16.6), and 27.1% (95% CI 26.5-27.6), respectively; the rates in blacks, South Asians, and whites were 22.6% (95% CI 22.2-23.1), 16.8% (95% CI 16.5-17.1), and 15.7% (95% CI 15.6-15.8), respectively. Independent predictors of meconium-stained AF included being black (odds ratio [OR] 8.4, 95% CI 2.4-28.8), vaginal breech delivery (OR 4.7, 95% CI 4.2-5.3), being South Asian (OR 3.3, 95% CI 1.3-8.3), and being in an advancing week of gestation (OR 1.39, 95% CI 1.38-1.40). More blacks (17.9%, 95% CI 17.3-18.4) and South Asians (11.8%, 95% CI 11.5-12.1) with good outcome and no risk factors for fetal hypoxia had meconium-stained AF than did whites (11.2%, 95% CI 11.1-11.4). Using white neonates born at 40 weeks as reference, the absolute risk of adverse outcome at 41 and 42 weeks were 2% and 5% in whites, 3% and 7%, in South Asians, and 7% and 11% in blacks. CONCLUSION: Meconium-stained AF rates are different among races and across gestational age, and overall risk of adverse outcomes in meconium stained AF is low. (Obstet Gynecol 2011;117:828-35) DOI: 10.1097/AOG.0b013e3182117a26 C1 [Balchin, Imelda] Royal London Hosp, Dept Obstet & Gynaecol, Barts & London NHS Trust, London E1 8PR, England. London Sch Hyg & Trop Med, London WC1, England. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. Univ London Imperial Coll Sci Technol & Med, Acad Dept Obstet & Gynaecol, Chelsea & Westminster Hosp, London, England. RP Balchin, I (reprint author), Royal London Hosp, Dept Obstet & Gynaecol, Barts & London NHS Trust, Whitechapel Rd, London E1 8PR, England. EM balchin@doctors.org.uk RI Whittaker, John/B-8609-2012 OI Whittaker, John/0000-0002-3529-2379 FU Ferring Pharmaceuticals; Alliance Medical; Pfizer; Milupa; Obstetric Anaesthetist's Association; University of Copenhagen; North Midlands Urogynaecological Society; Postgraduate Education and Academic Affairs Department at the National Guard Health Affairs in Riyadh, Saudi Arabia; BabyLifeline; Welsh Health Legal Authority; Northwick Park Hospitals National Health Service Trust; United Kingdom FX Dr. Whittaker is employed by GlaxoSmithKline (GSK) and holds stock in GSK. He is also employed by London School of Hygiene and Tropical Medicine. Professor Steer has received funding and honoraria to support speaking at meetings from Ferring Pharmaceuticals, Alliance Medical, Pfizer, Milupa, the Obstetric Anaesthetist's Association, The University of Copenhagen, the North Midlands Urogynaecological Society, Postgraduate Education and Academic Affairs Department at the National Guard Health Affairs in Riyadh, Saudi Arabia, the University of Copenhagen, and BabyLifeline. He has received funding to defray the expenses of attendance at meetings from the International Federation of Gynecology and Obstetrics (speakers honorarium), Bristol Hospitals Healthcare Trust, the Icelandic Medical Association, Capetown University, Rome University, the 3rd Military Hospital Chonqing, AsiaPacific Congress of Fetal/Maternal Medicine, the British Maternal and Fetal Medicine Society, the British Association of Perinatal Medicine, the European Congress of Perinatal Medicine, the Swedish Society of Obstetricians and Gynaecologists, the National Perinatal Society of Jordan, the National Perinatal Society of Turkey, Zurich University, Leuven University, the Royal College of Obstetricians and Gynaecologists, the University of Nottingham, and the International Association for Adult Congenital Heart Disease. He has received travel expenses and honoraria for examining from the Universities of Hong Kong, Lund, and Stockholm. He has been treated to dinner while attending a meeting with representatives of Hewlett Packard Ltd to discuss fetal monitoring. He has received fees for medicolegal opinions from the Welsh Health Legal Authority, Northwick Park Hospitals National Health Service Trust, Her Majesty's Police, and various solicitors. He receives publication royalties from Elsevier and the Authors' Licensing and Collecting Society. He chairs the medical advisory panel of "Group B Strep Support" (unpaid). His research is funded by public bodies in the United Kingdom (including the Health Technology Assessment programme). The other authors did not report any potential conflicts of interest. NR 35 TC 25 Z9 30 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 828 EP 835 DI 10.1097/AOG.0b013e3182117a26 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500010 PM 21383642 ER PT J AU Richter, HE Litman, HJ Lukacz, ES Sirls, LT Rickey, L Norton, P Lemack, GE Kraus, S Moalli, P Fitzgerald, MP Dandreo, KJ Huang, LY Kusek, JW AF Richter, Holly E. Litman, Heather J. Lukacz, Emily S. Sirls, Larry T. Rickey, Leslie Norton, Peggy Lemack, Gary E. Kraus, Stephen Moalli, Pamela Fitzgerald, Mary Pat Dandreo, Kimberly J. Huang, Liyuan Kusek, John W. CA Urinary Incontinence Treatment Net TI Demographic and Clinical Predictors of Treatment Failure One Year After Midurethral Sling Surgery SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Scientific Meeting of the American-Urogynecologic-Society CY SEP 29-OCT 02, 2010 CL Long Beach, CA SP Amer Urogynecol Soc ID STRESS URINARY-INCONTINENCE; FREE VAGINAL TAPE; FOLLOW-UP; WOMEN; TVT; STANDARDIZATION; QUESTIONNAIRE; TERMINOLOGY AB OBJECTIVE: To identify clinical and demographic factors predictive of midurethral sling failure. METHODS: Overall treatment failure was defined by one or more of the following objective outcomes: a positive stress test, positive 24-hour pad test or retreatment for stress urinary incontinence (SUI); subjective outcomes: self reported SUI by the Medical, Epidemiologic and Social Aspect of Aging questionnaire, incontinent episodes by 3-day diary, or retreatment for SUI, or a combination of these. Logistic regression models adjusting for sling type and clinical site were used to predict odds of overall treatment failure after univariable analysis. Models were also fit to compare factors associated with objective failure and subjective failure only. RESULTS: Previous UI surgery (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.47); maximum Q-tip excursion < 30 degrees (OR 1.89, 95% CI 1.16-3.05); Medical, Epidemiologic and Social Aspect of Aging questionnaire urge score per 10 points (OR 1.97, 95% CI 1.21-3.21); and pad weight per 10 g (OR 1.06, 95% CI 1.02-1.10) were predictors of overall failure. Having concomitant surgery (OR 0.44, 95% CI 0.22-0.90) was predictive of subjective failure only rather than objective failure. Age per 10 years (OR 1.48, 95% CI 1.14-1.90); Urogenital Distress Inventory score per 10 points (OR 1.09, 95% CI 1.02-1.17); pad weight per 10 g (OR 1.05, 95% CI 1.01-1.10) were predictive of objective failure compared with subjective failure only. Associations of risk factors and failure were similar independent of sling type (retropubic or transobturator). CONCLUSION: Twelve months after surgery, risk factors for overall and objective treatment failure were similar in women undergoing retropubic and transobturator sling procedures. This information may assist in counseling patients regarding efficacy of sling procedures and in setting expectations for women at increased odds for treatment failure. C1 Univ Alabama, Birmingham, AL USA. New England Res Inst, Watertown, MA 02172 USA. Univ Calif San Diego, San Diego, CA 92103 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Utah, Salt Lake City, UT USA. Univ Texas SW, Dallas, TX USA. Univ Texas San Antonio, San Antonio, TX USA. Magee Womens Hosp, Pittsburgh, PA USA. Loyola Univ, Maywood, IL 60153 USA. NIDDKD, Bethesda, MD 20892 USA. RP Richter, HE (reprint author), 619 20th St S,176 F,Suite 10382, Birmingham, AL 35249 USA. EM hrichter@uab.edu OI Wadie, Bassem/0000-0002-6977-6849 FU NIDDK NIH HHS [U01 DK060397, 2K24-DK068389, K24 DK068389, U01 DK058225, U01 DK058229, U01 DK058231, U01 DK058234, U01 DK060379, U01 DK060380, U01 DK060380-08, U01 DK060393, U01 DK060395, U01 DK060401, U01 DK58229, U01 DK58231, U01 DK58234, U01 DK60379, U01 DK60380, U01 DK60393, U01 DK60395, U01 DK60397, U01 DK60401, U01DK58225] NR 26 TC 29 Z9 29 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 913 EP 921 DI 10.1097/AOG.0b013e31820f3892 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500023 PM 21422865 ER PT J AU Signore, C Spong, CY Krotoski, D Shinowara, NL Blackwell, SC AF Signore, Caroline Spong, Catherine Y. Krotoski, Danuta Shinowara, Nancy L. Blackwell, Sean C. TI Pregnancy in Women With Physical Disabilities SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SPINAL-CORD-INJURY; HEALTH-CARE ACCESS; LOWER BIRTH-WEIGHT; RHEUMATOID-ARTHRITIS; CEREBRAL-PALSY; AUTONOMIC HYPERREFLEXIA; MULTIPLE-SCLEROSIS; DISEASE-ACTIVITY; REPRODUCTIVE HEALTH; MYOTONIC-DYSTROPHY AB The Eunice Kennedy Shriver National Institute of Child Health and Human Development sponsored a 2-day workshop to assess the body of evidence on pregnancy in women with physical disabilities, identify gaps in knowledge, and formulate recommendations for further research. A multidisciplinary group of experts discussed available data on pregnancy outcomes among women with varying physically disabling conditions, medical and psychosocial risks for mothers and children, and barriers to prenatal care and parenting for women with physical disabilities. Existing evidence is limited by a preponderance of retrospective single-site studies of small sample sizes. For most women, pregnancy outcomes are favorable. However, increased rates of certain adverse outcomes, such as low birth weight (related to preterm birth or growth restriction) and cesarean delivery, have been reported in women with spinal cord injuries, rheumatoid arthritis, multiple sclerosis, or other conditions. Common morbidities across conditions may include urinary tract infections, decreased mobility and independence, skin ulceration, respiratory compromise, interpersonal abuse, stress, and mood disorders. Socioeconomic, physical, and attitudinal barriers to antenatal care and independent parenting can be problematic. Current evidence, although limited, indicates that most women with physical disabilities will have good pregnancy outcomes; however, some data suggest that rates of a range of complications may be more common among women with physical disabilities, depending on the nature and severity of the underlying condition. Many questions remain unanswered. Establishment of a systematic and comprehensive registry of pregnancy course and outcomes among women with physical disabilities is of high priority for addressing persistent gaps in knowledge. (Obstet Gynecol 2011;117:935-47) DOI: 10.1097/AOG.0b013e3182118d59 C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Off Director, NIH,US Dept Hlth & Human Serv, Bethesda, MD USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Ctr Med Rehabil Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. Univ Texas Hlth Sci Ctr, Larry C Gilstrap MD Ctr Perinatal & Womens Hlth R, Div Maternal Fetal Med, Dept Obstet Gynecol & Reprod Sci, Houston, TX USA. RP Signore, C (reprint author), NICHD, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM signorec@mail.nih.gov NR 65 TC 32 Z9 34 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 935 EP 947 DI 10.1097/AOG.0b013e3182118d59 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500026 PM 21422868 ER PT J AU Spong, CY Iams, J Goldenberg, R Hauck, FR Willinger, M AF Spong, Catherine Y. Iams, Jay Goldenberg, Robert Hauck, Fern R. Willinger, Marian TI Disparities in Perinatal Medicine Preterm Birth, Stillbirth, and Infant Mortality SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID RACIAL DISPARITY; BACTERIAL VAGINOSIS; AFRICAN-AMERICAN; UNITED-STATES; ETHNIC-GROUPS; RISK-FACTORS; WEIGHT; WOMEN; PREGNANCY; DISCRIMINATION AB Infant mortality, stillbirths, and preterm births are major public health priorities with significant disparities based on race and ethnicity. Interestingly, when evaluating the rates over the past 30 to 50 years, the disparity persists in all three and is remarkably consistent. In the United States, the infant mortality rate is 6.7 deaths per 1,000 live births, the stillbirth rate is 6.2 per 1,000 deliveries, and the preterm birth rate is 12.8% of live births. The rates among non-Hispanic African Americans are dramatically higher, nearly double the infant mortality at 13.4 infant deaths per 1,000 live births, nearly double the stillbirth rate at 11.1 stillbirths per 1,000 deliveries, and one third higher with preterm births at 18.4% of live births. Despite numerous conferences, workshops, articles, and investigators focusing on this line of work, the disparities persist and, in some cases, are growing. In this article, we summarize a Eunice Kennedy Shriver National Institute of Child Health and Human Development workshop that focused on these disparities to identify the associated factors to determine their relative contributions, identify gaps in knowledge, and develop specific strategies to address the disparities in the short-term and long-term. ( Obstet Gynecol 2011;117:948-55) DOI: 10.1097/AOG.0b013e318211726f C1 [Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Obstet, Columbus, OH 43210 USA. Ohio State Univ, Dept Gynecol, Columbus, OH 43210 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Virginia, Charlottesville, VA USA. RP Spong, CY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov NR 30 TC 42 Z9 43 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2011 VL 117 IS 4 BP 948 EP 955 DI 10.1097/AOG.0b013e318211726f PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 738NW UT WOS:000288647500027 PM 21422869 ER PT J AU Kopach, O Kao, SC Petralia, RS Belan, P Tao, YX Voitenko, N AF Kopach, Olga Kao, Sheng-Chin Petralia, Ronald S. Belan, Pavel Tao, Yuan-Xiang Voitenko, Nana TI Inflammation alters trafficking of extrasynaptic AMPA receptors in tonically firing lamina II neurons of the rat spinal dorsal horn SO PAIN LA English DT Article DE Extrasynaptic AMPA receptors; GluR1 and GluR2 subunits; Peripheral inflammation; Receptor trafficking; Substantia gelatinosa neurons ID SUBSTANTIA-GELATINOSA NEURONS; LONG-TERM DEPRESSION; GLUTAMATE-RECEPTOR; SYNAPTIC PLASTICITY; CA2+-PERMEABLE AMPA; SUBUNIT COMPOSITION; CA2+ TRANSIENTS; PLASMA-MEMBRANE; PAIN BEHAVIOR; CORD AB Peripheral inflammation alters AMPA receptor (AMPAR) subunit trafficking and increases AMPAR Ca2+ permeability at synapses of spinal dorsal horn neurons. However, it is unclear whether AMPAR trafficking at extrasynaptic sites of these neurons also changes under persistent inflammatory pain conditions. Using patch-clamp recording combined with Ca2+ imaging and cobalt staining, we found that, under normal conditions, an extrasynaptic pool of AMPARs in rat substantia gelatinosa (SG) neurons of spinal dorsal horn predominantly consists of GluR2-containing Ca2+-impermeable receptors. Maintenance of complete Freund's adjuvant (CFA)-induced inflammation was associated with a marked enhancement of AMPA-induced currents and [Ca2+](i) transients in SG neurons, while, as we previously showed, the amplitude of synaptically evoked AMPAR-mediated currents was not changed 24 h after CFA. These findings indicate that extrasynaptic AMPARs are upregulated and their Ca2+ permeability increases dramatically. This increase occurred in SG neurons characterized by intrinsic tonic firing properties, but not in those exhibited strong adaptation. This increase was also accompanied by an inward rectification of AMPA-induced currents and enhancement of sensitivity to a highly selective Ca2+-permeable AMPAR blocker, IEM-1460. Electron microcopy and biochemical assays additionally showed an increase in the amount of GluR1 at extrasynaptic membranes in dorsal horn neurons 24 h post-CFA. Taken together, our findings indicate that CFA-induced inflammation increases functional expression and proportion of extrasynaptic GluR1-containing Ca2+-permeable AMPARs in tonically firing excitatory dorsal horn neurons, suggesting that the altered extrasynaptic AMPAR trafficking might participate in the maintenance of persistent inflammatory pain. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Kao, Sheng-Chin; Tao, Yuan-Xiang] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Kopach, Olga; Belan, Pavel; Voitenko, Nana] Bogomoletz Inst Physiol, Dept Gen Physiol Nervous Syst, UA-01024 Kiev, Ukraine. [Kao, Sheng-Chin] Chung Gung Mem Hosp, Lin Kou Med Ctr, Dept Anesthesiol, Taoyaun Cty 333, Taiwan. [Petralia, Ronald S.] Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Tao, YX (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, 720 Rutland Ave,370 Ross, Baltimore, MD 21205 USA. EM ytao1@jhmi.edu; nana@biph.kiev.ua OI Voitenko, Nana/0000-0002-2450-3134; Kopach, Olga/0000-0002-3921-3674 FU NASU Biotechnology; INTAS [8061]; NIH [NS058886]; Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund; Johns Hopkins University; NIDCD FX This work was supported by NASU Biotechnology and INTAS 8061 Grants (N.V.), NIH Grant NS058886, Mr. David Koch and the Patrick C. Walsh Prostate Cancer Research Fund, and the Johns Hopkins University Blaustein Pain Research Fund (Y.X.T.), and the Intramural Research Program of NIDCD (R.S.P.). We thank Mrs. Ya-Xian Wang for help with the immunogold experiments. The authors thank Claire F. Levine, MS, for her editorial assistance. The authors declare no conflict of interests. NR 57 TC 24 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD APR PY 2011 VL 152 IS 4 BP 912 EP 923 DI 10.1016/j.pain.2011.01.016 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 740JF UT WOS:000288788200030 PM 21282008 ER PT J AU Meng, CY Smith, BL Bodhidatta, L Richard, SA Vansith, K Ban, T Srijan, A Serichantalergs, O Mason, CJ AF Meng, Chhour Y. Smith, Bryan L. Bodhidatta, Ladaporn Richard, Stephanie A. Vansith, Ket Ban Thy Srijan, Apichai Serichantalergs, Oralak Mason, Carl J. TI Etiology of Diarrhea in Young Children and Patterns of Antibiotic Resistance in Cambodia SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE diarrhea; antibiotic; rotavirus; children; Cambodia ID ENTEROAGGREGATIVE ESCHERICHIA-COLI; CAMPYLOBACTER-JEJUNI; THAI CHILDREN; DISEASE; PATHOGENS; SUSCEPTIBILITY; INDONESIA; VIETNAM; CELLS; PROBE AB Background: Little is known about diarrhea etiology and antibiotic resistance in developing countries where diarrhea is a major public health problem. Methods: To describe diarrhea etiology and antibiotic resistance patterns in Cambodia, 600 children aged 3 months to 5 years with acute diarrhea (cases) and 578 children without diarrhea (controls) were enrolled from a hospital in Phnom Penh. Stool samples were collected, and pathogens and antibiotic resistance patterns were described. Results: The most frequently isolated pathogens in these cases were enteroaggregative Escherichia coli (20%) and rotavirus (26%). Enterotoxigenic E. coli, enteroaggregative E. coli, Shigella, Aeromonas, rotavirus, and adenovirus were statistically significantly associated with diarrhea. Among cases, vomiting was associated with viral infections, whereas bloody stool was associated with Shigella. Enterotoxigenic E. coli isolates were highly resistant to ampicillin, sulfonamides, and tetracycline. Approximately 50% of Campylobacter coli and 30% of Campylobacter jejuni isolates were resistant to nalidixic acid and ciprofloxacin. Over 33% of Salmonella isolates were resistant to ampicillin and tetracycline, and almost 100% of Shigella isolates were resistant to trimethoprim/sulfamethoxazole. Conclusions: These data on the etiology of diarrhea and antibiotic resistance patterns in Cambodia will have significant effect on local public health policies and on local resource prioritization practices. C1 [Bodhidatta, Ladaporn; Srijan, Apichai; Serichantalergs, Oralak; Mason, Carl J.] Armed Forces Res Inst Med Sci, Dept Enter Dis, Bangkok 10400, Thailand. [Smith, Bryan L.] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD USA. [Meng, Chhour Y.; Vansith, Ket; Ban Thy] Natl Pediat Hosp, Phnom Penh, Cambodia. [Richard, Stephanie A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Richard, Stephanie A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. RP Bodhidatta, L (reprint author), Armed Forces Res Inst Med Sci, Dept Enter Dis, 315-6 Rajvithi Rd, Bangkok 10400, Thailand. EM ladapornb@afrims.org RI Valle, Ruben/A-7512-2013; OI MASON, CARL/0000-0002-3676-2811 FU Global Emerging Infections Surveillance and Response System, a Division of the Armed Forces Health Surveillance Center, Washington, DC FX Supported by Global Emerging Infections Surveillance and Response System, a Division of the Armed Forces Health Surveillance Center, Washington, DC. NR 32 TC 34 Z9 37 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2011 VL 30 IS 4 BP 331 EP 335 DI 10.1097/INF.0b013e3181fb6f82 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 735SU UT WOS:000288438700014 PM 21412204 ER PT J AU Osei-Hwedieh, DO Amar, M Sviridov, D Remaley, AT AF Osei-Hwedieh, David O. Amar, Marcelo Sviridov, Dmitri Remaley, Alan T. TI Apolipoprotein mimetic peptides: Mechanisms of action as anti-atherogenic agents SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Apolipoproteins; Peptides; Atherosclerosis; Cholesterol efflux; High density lipoproteins ID HIGH-DENSITY-LIPOPROTEIN; REVERSE CHOLESTEROL TRANSPORT; AMPHIPATHIC HELICAL PEPTIDES; E-NULL MICE; RANDOMIZED CONTROLLED-TRIAL; A-I; CELLULAR CHOLESTEROL; APOA-I; CORONARY ATHEROSCLEROSIS; INFLAMMATORY RESPONSE AB Apolipoprotein mimetic peptides are short synthetic peptides that share structural, as well as biological features of native apolipoproteins. The early positive clinical trials of intravenous preparations of apoA-I, the main protein component of high density lipoproteins (HDL), have stimulated great interest in the use of apolipoprotein mimetic peptides as possible therapeutic agents. Currently, there are a wide variety of apolipoprotein mimetic peptides at various stages of drug development. These peptides typically have been designed either promote cholesterol efflux or act as anti-oxidants, but they usually exert other biological effects, such as anti-inflammatory and anti-thrombotic effects. Uncertainty about which of these biological properties is the most important for explaining their anti-atherogenic effect is a major unresolved question in the field. Structure function studies relating the in vitro properties of these peptides to their ability to reduce atherosclerosis in animal models may uncover the best rationale for the design of these peptides and may lead to a better understanding of the mechanisms behind the atheroprotective effect of HDL Published by Elsevier Inc. C1 [Osei-Hwedieh, David O.; Amar, Marcelo; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bethesda, MD 20892 USA. [Sviridov, Dmitri] Baker Heart & Diabet Inst, Melbourne, Vic, Australia. RP Remaley, AT (reprint author), NHLBI, Lipoprot Metab Sect, Cardiopulm Branch, NIH, Bldg 10,Room 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@cc.nih.gov FU National Heart, Lung and Blood Institute of the NIH FX Research by David O. Osei-Hwedieh, Marcelo Amar, and Alan T. Remaley are supported by intramural funds from the National Heart, Lung and Blood Institute of the NIH. NR 104 TC 32 Z9 32 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD APR PY 2011 VL 130 IS 1 BP 83 EP 91 DI 10.1016/j.pharmthera.2010.12.003 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738II UT WOS:000288633100008 PM 21172387 ER PT J AU Spelman, K Aldag, R Hamman, A Kwasnik, EM Mahendra, MA Obasi, TM Morse, J Williams, EJ AF Spelman, K. Aldag, R. Hamman, A. Kwasnik, E. M. Mahendra, M. A. Obasi, T. M. Morse, J. Williams, E. J. TI Traditional Herbal Remedies that Influence Cell Adhesion Molecule Activity SO PHYTOTHERAPY RESEARCH LA English DT Review DE cell adhesion molecules; phytotherapy; ICAM; VCAM; integrins; selectins ID VEIN ENDOTHELIAL-CELLS; NF-KAPPA-B; ANTIINFLAMMATORY COMPOUNDS; PROMOTES ADHESION; MEDICINAL-PLANTS; NITRIC-OXIDE; T-CELLS; EXTRACT; EXPRESSION; ACTIVATION AB Many traditional medicines have demonstrated immune activity, however, research has largely neglected their effects on cell adhesion molecules (CAMs). This review reports on extracts from 37 medicinal plant species, similar to or replicating traditional preparations, that up- or downregulate either gene or protein activity of CAMs. The majority of the investigations were in vitro, primarily of the immunoglobulin superfamily of CAMs, specifically intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and secondarily on the integrin (CD11b or MAC-1) and selectin (E-selectin and P-selectin) families of CAMs. The following plant species have demonstrated modulation of multiple CAMs: Artemisia asiatica, Boswellia serrata, Canscora decussata, Cinnamomum povectum, Dehaasia incrassate, Ganoderma lucidum, Ginkgo biloba, Hypericum perforatum, Juglans regia, Lycopus lucidus, Panax notoginseng, Rheum undulatum, Salvia miltiorrhiza. Many other species have documented activity on one CAM. Currently there are limited in vivo/ex vivo investigations, including a clinical trial on Mahonia aquifolium. Although further evidence is needed, the data suggest that the reviewed botanical medicines may have the potential to provide therapeutic potential in disease processes involving CAMs. Additionally, the reported success of many of these plant extracts by traditional cultures and modern phytotherapists may involve the modulation of CAMs. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Spelman, K.; Aldag, R.; Hamman, A.; Kwasnik, E. M.; Mahendra, M. A.; Obasi, T. M.; Morse, J.; Williams, E. J.] Tai Sophia Inst, Dept Herbal Med, Laurel, MD USA. RP Spelman, K (reprint author), NIA, Clin Invest Lab, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM phytochemks@gmail.com NR 61 TC 13 Z9 15 U1 0 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD APR PY 2011 VL 25 IS 4 BP 473 EP 483 DI 10.1002/ptr.3350 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 741IL UT WOS:000288857300001 PM 21105177 ER PT J AU Flynn, KE Jeffery, DD Keefe, FJ Porter, LS Shelby, RA Fawzy, MR Gosselin, TK Reeve, BB Weinfurt, KP AF Flynn, Kathryn E. Jeffery, Diana D. Keefe, Francis J. Porter, Laura S. Shelby, Rebecca A. Fawzy, Maria R. Gosselin, Tracy K. Reeve, Bryce B. Weinfurt, Kevin P. TI Sexual functioning along the cancer continuum: focus group results from the Patient-Reported Outcomes Measurement Information System (PROMIS (R)) SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; focus groups; oncology; qualitative research; quality of life; sexual function; intimacy ID QUALITY-OF-LIFE; PROSTATE-CANCER; BREAST-CANCER; IMPACT; MEN; ONCOLOGY AB Objective: Cancer and treatments for cancer affect specific aspects of sexual functioning and intimacy; however, limited qualitative work has been done in diverse cancer populations. As part of an effort to improve measurement of self-reported sexual functioning, we explored the scope and importance of sexual functioning and intimacy to patients across cancer sites and along the continuum of care. Methods: We conducted 16 diagnosis- and sex-specific focus groups with patients recruited from the Duke University tumor registry and oncology/hematology clinics (N=109). A trained note taker produced field notes summarizing the discussions. An independent auditor verified field notes against written transcripts. The content of the discussions was analyzed for major themes by two independent coders. Results: Across all cancers, the most commonly discussed cancer-or treatment-related effects on sexual functioning and intimacy were fatigue, treatment-related hair loss, weight gain and organ loss or scarring. Additional barriers were unique to particular diagnoses, such as shortness of breath in lung cancer, gastrointestinal problems in colorectal cancers and incontinence in prostate cancer. Sexual functioning and intimacy were considered important to quality of life. While most effects of cancer were considered negative, many participants identified improvements to intimacy after cancer. Conclusion: Overall evaluations of satisfaction with sex life did not always correspond to specific aspects of functioning ( e. g. erectile dysfunction), presenting a challenge to researchers aiming to measure sexual functioning as an outcome. Health-care providers should not assume that level of sexual impairment determines sexual satisfaction and should explore cancer patients' sexual concerns directly. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Flynn, Kathryn E.; Fawzy, Maria R.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC 27715 USA. [Flynn, Kathryn E.; Keefe, Francis J.; Porter, Laura S.; Weinfurt, Kevin P.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27715 USA. [Jeffery, Diana D.] TRICARE Management Act, Dept Def, Ctr Hlth Care Management Studies, Hlth Program Anal & Evaluat, Falls Church, VA USA. [Shelby, Rebecca A.; Weinfurt, Kevin P.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27715 USA. [Gosselin, Tracy K.] Duke Univ Hlth Syst, Oncol Serv, Durham, NC USA. [Reeve, Bryce B.] NCI, Bethesda, MD 20892 USA. RP Flynn, KE (reprint author), Duke Univ, Sch Med, Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC 27715 USA. EM kathryn.flynn@duke.edu RI Flynn, Kathryn/M-5346-2013; OI Flynn, Kathryn/0000-0002-4427-3583; Jeffery, Diana D./0000-0002-2368-6952 FU National Cancer Institute, National Institutes of Health [U01AR052186] FX Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views of the Department of Defense. This work was supported by a National Cancer Institute supplement to grant U01AR052186 from the National Institutes of Health. The authors thank Elizabeth A. Hahn of Northwestern University for participation in the PROMIS Sexual Function Domain Committee. NR 22 TC 37 Z9 37 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD APR PY 2011 VL 20 IS 4 BP 378 EP 386 DI 10.1002/pon.1738 PG 9 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 741JQ UT WOS:000288860400005 PM 20878833 ER PT J AU Cirulli, F Reif, A Herterich, S Lesch, KP Berry, A Francia, N Aloe, L Barr, CS Suomi, SJ Alleva, E AF Cirulli, Francesca Reif, Andreas Herterich, Sabine Lesch, K. Peter Berry, Alessandra Francia, Nadia Aloe, Luigi Barr, Christina S. Suomi, Stephen J. Alleva, Enrico TI A novel BDNF polymorphism affects plasma protein levels in interaction with early adversity in rhesus macaques SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Brain-derived neurotrophic factor (BDNF); Polymorphism; Stress; Depression; Non-human primates ID SEROTONIN TRANSPORTER GENE; NERVE GROWTH-FACTOR; EARLY-LIFE STRESS; NEUROTROPHIC FACTOR EXPRESSION; ACTIVITY-DEPENDENT SECRETION; VAL66MET POLYMORPHISM; MAJOR DEPRESSION; ENVIRONMENT INTERACTIONS; SOCIAL ENRICHMENT; REARING CONDITION AB Early stressful events can increase vulnerability for psychopathology, although knowledge on the effectors is still limited. In this report we describe the characterization of a single nucleotide polymorphism (SNP) in rhesus macaques, which results in a Val to Met transition in the pro-BDNF domain, similar to a well described variant in the human gene. Further, we tested the hypothesis that peripheral levels of BDNF, which is involved in the response to stress and in the pathophysiology of anxiety and depression, might be differentially affected in a non-human primate model of early adverse rearing in a genotype-dependent manner. Males and females rhesus macaques reared either with their mothers (MR), in peer-only groups (PR), or in a "surrogate/peer-reared" (SPR) condition with limited peer interactions, were used as experimental subjects. BDNF levels were determined at baseline on postnatal days (PND) 14, 30 and 60 by means of specific ELISA procedure. Data indicate that BDNF levels were increased as a result of peer-rearing and that this increase was moderated by the presence of the SNP. Overall these data indicate that a SNP, which results in a Val to Met transition in the pro-BDNF domain, is present in rhesus macaques and is able to affect BDNF peripheral levels, thus making this primate model a fundamental tool to study gene by environment interactions involving the BDNF gene. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Cirulli, Francesca; Berry, Alessandra; Francia, Nadia; Alleva, Enrico] Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, I-00161 Rome, Italy. [Reif, Andreas; Lesch, K. Peter] Univ Wurzburg, UMP, Dept Psychiat & Psychotherapy, Wurzburg, Germany. [Herterich, Sabine] Univ Wurzburg, Cent Lab, Dept Clin Biochem & Pathobiochem, Wurzburg, Germany. [Aloe, Luigi] CNR EBRI, Inst Neurobiol & Mol Med, I-00143 Rome, Italy. [Barr, Christina S.] NIAAA, Sect Comparat Behav Genom, Rockville, MD 20852 USA. [Suomi, Stephen J.] NICHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Cirulli, F (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Sect Behav Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM francesca.cirulli@iss.it RI Cirulli, Francesca/B-1581-2013; Alleva, Enrico/B-1630-2013; Lesch, Klaus-Peter/J-4906-2013; OI Lesch, Klaus-Peter/0000-0001-8348-153X; Berry, Alessandra/0000-0001-6562-9043; cirulli, francesca/0000-0001-9440-1873 FU ISS-NIH [530F/51]; Italian Ministry of Health; Deutsche Forschungsgemeinschaft (DFG) [SFB-TRR-58 Z02]; AR [KFO 125, DE357/4-1, RE1632/5]; BMBF; Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; NIH FX Funding for this study was provided by the ISS-NIH Collaborative Project to FC and EA (530F/51), by the Italian Ministry of Health (Ricerca Finalizzata ex art. 12-2006) and by the Deutsche Forschungsgemeinschaft (DFG; SFB-TRR-58 Z02 to AR; Grant KFO 125 to AR; DE357/4-1 to AR; RE1632/5 to AR) and the BMBF (Panic-Net, to AR; details see webpage http: // www.paniknetz.de/netzwerk.html). This research was also supported by funds from the Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; the NIH and the Italian Ministry of Health had no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 62 TC 9 Z9 9 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2011 VL 36 IS 3 SI SI BP 372 EP 379 DI 10.1016/j.psyneuen.2010.10.019 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 741CD UT WOS:000288839800006 PM 21145664 ER PT J AU Fernandes, F Chen, K Ehrlich, LS Jin, J Chen, MH Medina, GN Symons, M Montelaro, R Donaldson, J Tjandra, N Carter, CA AF Fernandes, Fiona Chen, Kang Ehrlich, Lorna S. Jin, Jing Chen, Min H. Medina, Gisselle N. Symons, Marc Montelaro, Ronald Donaldson, Julie Tjandra, Nico Carter, Carol A. TI Phosphoinositides Direct Equine Infectious Anemia Virus Gag Trafficking and Release SO TRAFFIC LA English DT Article DE bimolecular fluorescence complementation; EIAV; HIV-1; PI(3)P; PI(3,5)P(2); PI(4,5)P(2); multivesicular bodies; VLP ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLATHRIN-MEDIATED ENDOCYTOSIS; HIV-1 GAG; PLASMA-MEMBRANE; MATRIX PROTEIN; TYPE-1 GAG; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PARTICLE RELEASE; SYNAPTOJANIN 2; BINDING AB Phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2)], the predominant phosphoinositide (PI) on the plasma membrane, binds the matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P(2) is critical for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in internal compartments; hence, the significance of its interaction with PI(4,5)P(2) is unclear. We therefore investigated the binding in vitro of other PIs to EIAV MA and whether intracellular association with compartments bearing these PIs was important for assembly and release of virus-like particles (VLPs) formed by Gag. In vitro, EIAV MA bound phosphatidylinositol 3-phosphate [PI(3)P] with higher affinity than PI(4,5)P(2) as revealed by nuclear magnetic resonance (NMR) spectra upon lipid titration. Gag was detected on the plasma membrane and in compartments enriched in phosphatidylinositol 3,5-biphosphate [PI(3,5)P(2)]. Treatment of cells with YM201636, a kinase inhibitor that blocks production of PI(3,5)P(2) from PI(3)P, caused Gag to colocalize with aberrant compartments and inhibited VLP release. In contrast to HIV-1, release of EIAV VLPs was not significantly diminished by coexpression with 5-phosphatase IV, an enzyme that specifically depletes PI(4,5)P(2) from the plasma membrane. However, coexpression with synaptojanin 2, a phosphatase with broader specificity, diminished VLP production. PI-binding pocket mutations caused striking budding defects, as revealed by electron microscopy. One of the mutations also modified Gag-Gag interaction, as suggested by altered bimolecular fluorescence complementation. We conclude that PI-mediated targeting to peripheral and internal membranes is a critical factor in EIAV assembly and release. C1 [Fernandes, Fiona; Ehrlich, Lorna S.; Chen, Min H.; Medina, Gisselle N.; Carter, Carol A.] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. [Chen, Kang; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Jin, Jing] Yale Univ, Sch Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA. [Symons, Marc] Feinstein Inst, Manhasset, NY 11030 USA. [Montelaro, Ronald] Univ Pittsburgh, Dept Microbiol & Mol Genet, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. [Donaldson, Julie] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Carter, CA (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, Life Sci Bldg,Room 248, Stony Brook, NY 11794 USA. EM ccarter@ms.cc.sunysb.edu FU NIH [AI068463]; NIH, National Heart, Lung, and Blood Institute FX We thank W. Mothes for helpful discussion and critical reading of the manuscript and we also thank G. Piszczek for sedimentation analysis of matrix. This study was supported by NIH R56 and R01 awards AI068463 (to C. C.), and the Intramural Research Program of the NIH, National Heart, Lung, and Blood Institute (to J. D. and N. T.). We thank the NHLBI-NIH electron microscopy facility and the Stony Brook University Central Microscopy Imaging electron microscopy Core facility for their services. NR 38 TC 23 Z9 25 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD APR PY 2011 VL 12 IS 4 BP 438 EP 451 DI 10.1111/j.1600-0854.2010.01153.x PG 14 WC Cell Biology SC Cell Biology GA 737CT UT WOS:000288546900007 PM 21176037 ER PT J AU Yu, T Calvo, L Anta, B Lopez-Benito, S Southon, E Chao, MV Tessarollo, L Arevalo, JC AF Yu, Tao Calvo, Laura Anta, Begona Lopez-Benito, Saray Southon, Eileen Chao, Moses V. Tessarollo, Lino Arevalo, Juan C. TI Regulation of Trafficking of Activated TrkA Is Critical for NGF-Mediated Functions SO TRAFFIC LA English DT Article DE Nedd4-2; neurons; NGF; trafficking; TrkA ID NERVE GROWTH-FACTOR; UBIQUITIN-PROTEIN LIGASES; FACTOR RECEPTOR TRKA; NEUROTROPHIN RECEPTORS; RETROGRADE TRANSPORT; SYMPATHETIC NEURONS; DIFFERENTIAL REGULATION; DROSOPHILA NEDD4; DOWN-REGULATION; LATE ENDOSOMES AB Upon activation by nerve growth factor (NGF), TrkA is internalized, trafficked and sorted through different endosomal compartments. Proper TrkA trafficking and sorting are crucial events as alteration of these processes hinders NGF-mediated functions. However, it is not fully known which proteins are involved in the trafficking and sorting of TrkA. Here we report that Nedd4-2 regulates the trafficking of TrkA and NGF functions in sensory neurons. Depletion of Nedd4-2 disrupts the correct sorting of activated TrkA at the early and late endosome stages, resulting in an accumulation of TrkA in these compartments and, as a result of the reduced trafficking to the degradative pathway, TrkA is either reverted to the cell surface through the recycling pathway or retrogradely transported to the cell body. In addition, Nedd4-2 depletion enhances TrkA signaling and the survival of NGF-dependent dorsal root ganglion neurons, but not those of brain-derived neurotrophic factor-dependent neurons. Furthermore, neurons from a knock-in mouse expressing a TrkA mutant that does not bind Nedd4-2 protein exhibit increased NGF-mediated signaling and cell survival. Our data indicate that TrkA trafficking and sorting are regulated by Nedd4-2 protein. C1 [Yu, Tao; Calvo, Laura; Anta, Begona; Lopez-Benito, Saray; Arevalo, Juan C.] Univ Salamanca, Dept Cell Biol & Pathol, Inst Neurociencias Castilla & Leon INCyL, Salamanca 37007, Spain. [Southon, Eileen; Tessarollo, Lino] NCI, Neurol Dev Grp, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. [Chao, Moses V.] NYU, Sch Med, Dept Cell Biol, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Physiol & Neurosci, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Psychiat, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. [Chao, Moses V.] NYU, Sch Med, Dept Neurol Sci, Mol Neurobiol Program,Skirball Inst Biomol Med, New York, NY 10016 USA. RP Arevalo, JC (reprint author), Univ Salamanca, Dept Cell Biol & Pathol, Inst Neurociencias Castilla & Leon INCyL, Salamanca 37007, Spain. EM arevalojc@usal.es RI 2011, Secribsal/D-9425-2012; ArAvalo, Juan Carlos/J-8154-2014; OI ArAvalo, Juan Carlos/0000-0003-1994-3095; Chao, Moses/0000-0002-6969-3744 FU Ministerio de Ciencia e Innovacion [BFU2008-00162]; European Community; Conserjeria de Educacion [SA074A08]; Conserjeria de Sanidad de Junta Castilla y Leon; University of Salamanca; NIH, Center for Cancer Research, National Cancer Institute FX We thank D. Trono for the lentiviral plasmids; Dionisio Martin-Zanca and Raquel Rodriguez for critical review of the manuscript and helpful discussions and Pilar Perez for helpful discussions; Enrique Lopez-Poveda for his help writing the MATLAB custom program to quantify immunofluorescence images. We also thank a reviewer for his/her perseverance helping us to interpret the results. This work was supported by Ministerio de Ciencia e Innovacion Grant (BFU2008-00162), by a Marie Curie International Reintegration Grant within the 7th European Community Framework Programme, by Conserjeria de Educacion (SA074A08) and Conserjeria de Sanidad de Junta Castilla y Leon to J. C. A. J. C. A. is a 'Ramon y Cajal' Investigator from the University of Salamanca and NARSAD 2009 Young Investigator Awardee. This research was supported by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute (for E. S. and L. T.). NR 53 TC 25 Z9 25 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1398-9219 J9 TRAFFIC JI Traffic PD APR PY 2011 VL 12 IS 4 BP 521 EP 534 DI 10.1111/j.1600-0854.2010.01156.x PG 14 WC Cell Biology SC Cell Biology GA 737CT UT WOS:000288546900013 PM 21199218 ER PT J AU Damani, MR Zhao, LA Fontainhas, AM Amaral, J Fariss, RN Wong, WT AF Damani, Mausam R. Zhao, Lian Fontainhas, Aurora M. Amaral, Juan Fariss, Robert N. Wong, Wai T. TI Age-related alterations in the dynamic behavior of microglia SO AGING CELL LA English DT Article DE microglia; aging; retina; age-related macular degeneration; imaging; laser ID NORMAL ADULT-MOUSE; AGING HUMAN BRAIN; OPTIC-NERVE HEAD; IN-VIVO; RETINAL MICROGLIA; INTRACEREBRAL HEMORRHAGE; MACULAR DEGENERATION; ACTIVATED MICROGLIA; RESTING MICROGLIA; DENDRITIC CELLS AB P>Microglia, the primary resident immune cells of the central nervous system (CNS), exhibit dynamic behavior involving rapid process motility and cellular migration that is thought to underlie key functions of immune surveillance and tissue repair. Although age-related changes in microglial activation have been implicated in the pathogenesis of neurodegenerative diseases of aging, how dynamic behavior in microglia is influenced by aging is not fully understood. In this study, we employed live imaging of retinal microglia in situ to compare microglial morphology and behavioral dynamics in young and aged animals. We found that aged microglia in the resting state have significantly smaller and less branched dendritic arbors, and also slower process motilities, which probably compromise their ability to survey and interact with their environment continuously. We also found that dynamic microglial responses to injury were age-dependent. While young microglia responded to extracellular ATP, an injury-associated signal, by increasing their motility and becoming more ramified, aged microglia exhibited a contrary response, becoming less dynamic and ramified. In response to laser-induced focal tissue injury, aged microglia demonstrated slower acute responses with lower rates of process motility and cellular migration compared with young microglia. Interestingly, the longer term response of disaggregation from the injury site was retarded in aged microglia, indicating that senescent microglial responses, while slower to initiate, are more sustained. Together, these altered features of microglial behavior at rest and following injury reveal an age-dependent dysregulation of immune response in the CNS that may illuminate microglial contributions to age-related neuroinflammatory degeneration. C1 [Damani, Mausam R.; Zhao, Lian; Fontainhas, Aurora M.; Wong, Wai T.] NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bethesda, MD 20892 USA. [Amaral, Juan] NEI, Mech Dis Sect, NIH, Bethesda, MD 20892 USA. RP Wong, WT (reprint author), NEI, Unit Neuron Glia Interact Retinal Dis, NIH, Bldg 6,Room 215, Bethesda, MD 20892 USA. EM wongw@nei.nih.gov RI duan, hf/F-9166-2011; Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU National Eye Institute; American Health Assistance Foundation (AHAF) FX This study was supported by the National Eye Institute Intramural Research Program and a grant from the American Health Assistance Foundation (AHAF). Acknowledgement is made to the donors of Macular Degeneration Research (MDR), a program of the American Health Assistance Foundation, for support of this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 90 Z9 90 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD APR PY 2011 VL 10 IS 2 BP 263 EP 276 DI 10.1111/j.1474-9726.2010.00660.x PG 14 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 734YH UT WOS:000288378900009 PM 21108733 ER PT J AU Rausch, D Dieffenbach, C Cheever, L Fenton, KA AF Rausch, Dianne Dieffenbach, Carl Cheever, Laura Fenton, Kevin A. TI Towards a More Coordinated Federal Response to Improving HIV Prevention and Sexual Health among Men Who Have Sex with Men SO AIDS AND BEHAVIOR LA English DT Article ID UNITED-STATES; ANTIRETROVIRAL THERAPY; INFECTIONS; HIV/AIDS C1 [Fenton, Kevin A.] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30333 USA. [Rausch, Dianne] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA. [Dieffenbach, Carl] NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. [Cheever, Laura] Hlth Resources & Serv Adm, HIV AIDS Bur, Rockville, MD USA. RP Fenton, KA (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, 1600 Clifton Rd, Atlanta, GA 30333 USA. EM kif2@cdc.gov NR 19 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD APR PY 2011 VL 15 SU 1 BP S107 EP S111 DI 10.1007/s10461-011-9908-z PG 5 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 814EG UT WOS:000294428800015 PM 21365306 ER PT J AU Agrawal, A Freedman, ND Bierut, LJ AF Agrawal, Arpana Freedman, Neal D. Bierut, Laura J. TI Genome-wide association studies of alcohol intake-a promising cocktail? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID GENETIC INFLUENCES; 1ST DRINK; DEPENDENCE; CONSUMPTION; ENVIRONMENT; DEHYDROGENASE; GENOTYPE; AGE C1 [Agrawal, Arpana; Bierut, Laura J.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Freedman, Neal D.] NCI, Div Canc & Epidemiol Genet, Bethesda, MD 20892 USA. RP Agrawal, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,CB 8134, St Louis, MO 63110 USA. EM arpana@wustl.edu RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 FU Intramural NIH HHS; NIAAA NIH HHS [U10 AA008401]; NIDA NIH HHS [K02 DA021237, DA23668, DA25886] NR 29 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2011 VL 93 IS 4 BP 681 EP 683 DI 10.3945/ajcn.111.012641 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 736YS UT WOS:000288531600002 PM 21367945 ER PT J AU Lipsky, LM Just, DR Nansel, TR Haynie, DL AF Lipsky, Leah M. Just, David R. Nansel, Tonja R. Haynie, Denise L. TI Fundamental misunderstanding of the relation between energy density (kcal/g) and energy cost ($/kcal) SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID FOODS; DIET C1 [Lipsky, Leah M.; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Just, David R.] Cornell Univ, Charles H Dyson Sch Appl Econ & Management, Ithaca, NY USA. RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Suite 7B13, Bethesda, MD 20892 USA. EM lipskylm@mail.nih.gov RI Just, David/K-7302-2012; OI Just, David/0000-0002-7471-5178; Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079; Lipsky, Leah/0000-0003-2645-4388 FU Intramural NIH HHS NR 10 TC 4 Z9 4 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2011 VL 93 IS 4 BP 867 EP 868 DI 10.3945/ajcn.110.011072 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 736YS UT WOS:000288531600032 PM 21325439 ER PT J AU Mahon, PB Pirooznia, M Goes, FS Seifuddin, F Steele, J Lee, PH Huang, J Hamshere, ML DePaulo, JR Kelsoe, JR Rietschel, M Nothen, M Cichon, S Gurling, H Purcell, S Smoller, JW Craddock, N Schulze, TG McMahon, FJ Potash, JB Zandi, PP AF Mahon, Pamela Belmonte Pirooznia, Mehdi Goes, Fernando S. Seifuddin, Fayaz Steele, Jo Lee, Phil Hyoun Huang, Jie Hamshere, Marian L. DePaulo, J. Raymond, Jr. Kelsoe, John R. Rietschel, Marcella Noethen, Markus Cichon, Sven Gurling, Hugh Purcell, Shaun Smoller, Jordan W. Craddock, Nick Schulze, Thomas G. McMahon, Francis J. Potash, James B. Zandi, Peter P. CA Bipolar Genome Study BiGS Consort TI Genome-Wide Association Analysis of Age at Onset and Psychotic Symptoms in Bipolar Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article ID I AFFECTIVE-DISORDER; FAMILIAL AGGREGATION; DIAGNOSTIC INTERVIEW; EUROPEAN ANCESTRY; LINKAGE ANALYSES; METAANALYSIS; PEDIGREES; SCHIZOPHRENIA; LOCUS; GENE AB Genome-wide association studies (GWAS) have identified several susceptibility loci for bipolar disorder (BP), most notably ANK3. However, most of the inherited risk for BP remains unexplained. One reason for the limited success may be the genetic heterogeneity of BP. Clinical sub-phenotypes of BP may identify more etiologically homogeneous subsets of patients, which can be studied with increased power to detect genetic variation. Here, we report on a mega-analysis of two widely studied sub-phenotypes of BP, age at onset and psychotic symptoms, which are familial and clinically significant. We combined data from three GWAS: NIMH Bipolar Disorder Genetic Association Information Network (GAIN-BP), NIMH Bipolar Disorder Genome Study (BiGS), and a German sample. The combined sample consisted of 2,836 BP cases with information on sub-phenotypes and 2,744 controls. Imputation was performed, resulting in 2.3 million SNPs available for analysis. No SNP reached genome-wide significance for either sub-phenotype. In addition, no SNP reached genome-wide significance in a meta-analysis with an independent replication sample. We had 80% power to detect associations with a common SNP at an OR of 1.6 for psychotic symptoms and a mean difference of 1.8 years in age at onset. Age at onset and psychotic symptoms in BP may be influenced by many genes of smaller effect sizes or other variants not measured well by SNP arrays, such as rare alleles. (C) 2011 Wiley-Liss, Inc. C1 [Zandi, Peter P.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. [Mahon, Pamela Belmonte; Pirooznia, Mehdi; Goes, Fernando S.; Seifuddin, Fayaz; DePaulo, J. Raymond, Jr.; Potash, James B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Steele, Jo; Schulze, Thomas G.; McMahon, Francis J.] NIMH, US Dept HHS, NIH, Intramural Res Program, Bethesda, MD 20892 USA. [Lee, Phil Hyoun; Huang, Jie; Purcell, Shaun; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Hamshere, Marian L.; Craddock, Nick] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, S Glam, Wales. [Kelsoe, John R.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Rietschel, Marcella] Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Rietschel, Marcella] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. [Noethen, Markus] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Noethen, Markus; Cichon, Sven] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Gurling, Hugh] UCL, Dept Mental Hlth Sci, London, England. RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI Liu, Chunyu/G-7561-2012; Schulze, Thomas/H-2157-2013; Gurling, Hugh/A-5029-2010; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; OI Liu, Chunyu/0000-0002-5986-4415; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Pirooznia, Mehdi/0000-0002-4210-6458; McMahon, Francis/0000-0002-9469-305X; Nothen, Markus/0000-0002-8770-2464 FU [R01 MH079799] FX The authors express their profound appreciation to the families who participated in this project, and to the many clinicians who facilitated the referral of participants to the study. Data and biomaterials for the NIMH samples were collected as part of 10 projects that participated in the NIMH Bipolar Disorder Genetics Initiative. From 1991 to 1998, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, U01 MH46282-John Nurnberger, M. D., Ph. D., Marvin Miller, M. D. and Elizabeth Bowman, M. D.; Washington University, St Louis, MO, U01 MH46280-Theodore Reich, M. D., Allison Goate, Ph. D. and John Rice, Ph. D.; Johns Hopkins University, Baltimore, MD U01 MH46274-J Raymond DePaulo Jr, M. D. Sylvia Simpson, M. D., MPH and Colin Stine, Ph. D.; NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, M. D.-Elliot Gershon, M. D., Diane Kazuba, BA and Elizabeth Maxwell, M. S. W. From 1999 to 2003, the Principal Investigators and Co-Investigatorswere: Indiana University, Indianapolis, IN, R01 MH59545-John Nurn-berger, M. D., Ph. D., Marvin J. Miller, M. D., Elizabeth S. Bowman, M. D., N. Leela Rau, M. D., P. Ryan Moe, M. D., Nalini Samavedy, M. D., Rif El-Mallakh, M. D. (at University of Louisville), Husseini Manji, M. D. (at Wayne State University), Debra A. Glitz, M. D. (at Wayne State University), Eric T. Meyer, MS, Carrie Smiley, RN, Tatiana Foroud, Ph. D., Leah Flury, MS, Danielle M. Dick, Ph. D. and Howard Edenberg, Ph. D.; Washington University, St Louis, MO, R01 MH059534, John Rice, Ph. D., Theodore Reich, M. D., Allison Goate, Ph. D. and Laura Bierut, M. D.; Johns Hopkins University, Baltimore, MD, R01 MH59533-Melvin McInnis, M. D., J. Raymond DePaulo Jr, M. D., Dean F. MacKinnon, M. D., Francis M. Mondimore, M. D., James B. Potash, M. D., Peter P. Zandi, Ph. D., Dimitrios Avramopoulos and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553-Wade Berrettini, M. D., Ph. D.; University of California at Irvine, CA, R01 MH60068-William Byerley, M. D. and Mark Vawter, M. D.; University of Iowa, IA, R01 MH059548-William Coryell, M. D. and Raymond Crowe, M. D.; University of Chicago, Chicago, IL, R01 MH59535-Elliot Gershon, M. D., Judith Badner, Ph. D., Francis McMahon, M. D., Chunyu Liu, Ph. D., Alan Sanders, M. D., Maria Caserta, Steven Dinwiddie, M. D., Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567-John Kelsoe, M. D., Rebecca McKinney, B. A.; Rush University, IL, R01 MH059556-William Scheftner, M. D., Howard M. Kravitz, DO, MPH, Diana Marta, B. A., Annette Vaughn-Brown, MSN, RN and Laurie Bederow, MA; NIMH Intramural Research Program, Bethesda, M. D., 1Z01MH002810-01, Francis J. McMahon, M. D., Layla Kassem, PsyD, Sevilla Detera-Wadleigh, Ph. D., Lisa Austin, Ph. D., Dennis L. Murphy, M. D. From 2003 to 2007, the Principal Investigators and Co-Investigators were: Indiana University, Indianapolis, IN, R01 MH59545, John Nurnberger, M. D., Ph. D., Marvin J. Miller, M. D., Elizabeth S. Bowman, M. D., N. Leela Rau, M. D., P. Ryan Moe, M. D., Nalini Samavedy, M. D., Rif El-Mallakh, M. D. (at University of Louisville), Husseini Manji, M. D. (at Johnson and Johnson), Debra A. Glitz, M. D. (at Wayne State University), Eric T. Meyer, Ph. D., M. S. (at Oxford University, UK), Carrie Smiley, R. N., Tatiana Foroud, Ph. D., Leah Flury, M. S., Danielle M. Dick, Ph. D (at Virginia Commonwealth University), Howard Edenberg, Ph. D.; Washington University, St. Louis, MO, R01 MH059534, John Rice, Ph. D, Theodore Reich, M. D., Allison Goate, Ph. D.; , Laura Bierut M. D. K02 DA21237; Johns Hopkins University, Baltimore, MD, R01 MH59533, Melvin McInnis, M. D., J. Raymond DePaulo, Jr., M. D., Dean F. MacKinnon, M. D., Francis M. Mondimore, M. D., James B. Potash, M. D., Peter P. Zandi, Ph. D, Dimitrios Avramopoulos, and Jennifer Payne; University of Pennsylvania, PA, R01 MH59553, Wade Berrettini, M. D., Ph. D.; University of California at San Francisco, CA, R01 MH60068, William Byerley, M. D., and Sophia Vinogradov, M. D.; University of Iowa, IA, R01MH059548, WilliamCoryell, M. D., and Raymond Crowe, M. D.; University of Chicago, IL, R01 MH59535, Elliot Gershon, M. D., Judith Badner, Ph. D., Francis McMahon, M. D., Chunyu Liu, Ph. D., Alan Sanders, M. D., Maria Caserta, Steven Dinwiddie, M. D., Tu Nguyen, Donna Harakal; University of California at San Diego, CA, R01 MH59567, John Kelsoe, M. D., Rebecca McKinney, B. A.; Rush University, IL, R01 MH059556, William Scheftner, M. D., Howard M. Kravitz, D. O., M. P. H., Diana Marta, B. S., Annette Vaughn-Brown, M. S. N., R. N., and Laurie Bederow, M. A.; NIMH Intramural Research Program, Bethesda, M. D., 1Z01MH002810-01, Francis J. McMahon, M. D., Layla Kassem, Psy. D., Sevilla Detera-Wadleigh, Ph. D, Lisa Austin, Ph. D, Dennis L. Murphy, M. D.; Howard University, William B. Lawson, M. D., Ph. D., Evarista Nwulia, M. D., and Maria Hipolito, M. D. Control subjects from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH-GI), data and biomaterials are being collected by the `` Molecular Genetics of Schizophrenia II'' (MGS-2) collaboration. The investigators and coinvestigators are: ENH/ Northwestern University, Evanston, IL, MH059571, Pablo V. Gejman, M. D. (Collaboration Coordinator; PI), Alan R. Sanders, M. D.; Emory University School of Medicine, Atlanta, GA, MH59587, Farooq Amin, M. D. (PI); Louisiana State University Health Sciences Center; New Orleans, Louisiana, MH067257, Nancy Buccola APRN, BC, MSN (PI); University of California-Irvine, Irvine, CA, MH60870, William Byerley, M. D. (PI); Washington University, St. Louis, MO, U01, MH060879, C. Robert Cloninger, M. D. (PI); University of Iowa, Iowa, IA, MH59566, Raymond Crowe, M. D. (PI), Donald Black, M. D.; University of Colorado, Denver, CO, MH059565, Robert Freedman, M. D. (PI); University of Pennsylvania, Philadelphia, PA, MH061675, Douglas Levinson M. D. (PI); University of Queensland, Queensland, Australia, MH059588, Bryan Mowry, M. D. (PI); Mt. Sinai School of Medicine, New York, NY, MH59586, Jeremy Silverman, Ph. D. (PI). Genome-wideSNPgenotyping of theNIMH samples was performed through the Genetic Association Information Network under the direction of the Bipolar Genetics Studies Collaboration. The Principal Investigators and Co-Investigators were: University of California San Diego, La Jolla, CA, John R. Kelsoe, M. D. (PI), Tiffany A. Greenwood, Ph. D., Paul D. Shilling, Ph. D., Caroline Nievergelt, Ph. D.; Scripps Research Institute, La Jolla, CA: Nicholas Schork, Ph. D. (PI), Erin N. Smith, Ph. D., Cinnamon Bloss, Ph. D.; Indiana University, Bloomington, IN, John Nurnberger, M. D. (PI), Howard J. Edenberg, Ph. D., Tatiana Foroud, Ph. D.; University of Chicago, Chicago, IL, Elliot Gershon, M. D. (PI), Chunyu Liu, Ph. D., Judith A. Badner, Ph. D.; Rush University Medical Center, Chicago, IL, William A. Scheftner, M. D.; Howard University, Washington, DC, William B. Lawson, M. D. (PI), Evaristus A. Nwulia, M. D., Maria Hipolito, M. D.; University of Iowa, Iowa City, IA, William Coryell, M. D. (PI); Washington University, St.; Louis, MO, John Rice, Ph D. (PI); University of California San Francisco, San Francisco, CA, William Byerley, M. D. (PI); National Institute of Mental Health, Bethesda, M. D., Francis McMahon, M. D. (PI), Thomas G. Schulze, M. D.; University of Pennsylvania, Philadelphia, PA, Wade Berrettini, M. D., Ph. D. (PI); JohnsHopkins University, Baltimore, MD, James B. Potash, M. D. (PI), Peter P. Zandi, Ph. D., Pamela Belmonte Mahon, Ph. D.; University of Michigan, Ann Arbor, MI, Melvin G. McInnis, M. D. (PI), Sebastian Zollner, Ph. D.; Translation Genomic Research Institute, Phoenix, AZ, David Craig, Ph. D. (PI), Szabolics Szelinger. Data and biomaterials for the subjects in the Wellcome Trust Case-Control Consortium were collected by: University of Aberdeen, Foresterhill, Aberdeen, UK, Gerome Breen, David St Clair; Birmingham University, Birmingham, UK, Sian Caesar, Katherine Gordon-Smith, Lisa Jones; Cardiff University, Cardiff, UK, Christine Fraser, Elaine K. Green, Detelina Grozeva, Marian L. Hamshere, Peter A. Holmans, Ian R. Jones, George Kirov, Valentina Moskvina, Ivan Nikolov, Michael C. O'Donovan, Michael J. Owen, Nick Craddock; The Institute of Psychiatry, King's College, London, UK, David A. Collier, Amanda Elkin, Anne Farmer, Richard Williamson, Peter McGuffin; Royal Victoria Infirmary, Newcastle upon Tyne, UK, Allan H. Young, I. Nicol Ferrier; Supported in part by R01 MH079799 (Smoller). NR 42 TC 23 Z9 23 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR PY 2011 VL 156B IS 3 BP 370 EP 378 DI 10.1002/ajmg.b.31172 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 734KI UT WOS:000288332600015 ER PT J AU Chew, EY AF Chew, Emily Y. TI The Value of Randomized Clinical Trials in Ophthalmology SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID WOMENS HEALTH C1 NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 17 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2011 VL 151 IS 4 BP 575 EP 578 DI 10.1016/j.ajo.2010.12.006 PG 4 WC Ophthalmology SC Ophthalmology GA 742VZ UT WOS:000288974700004 PM 21420522 ER PT J AU Fee, E AF Fee, Elizabeth TI Abel Wolman (1892-1989): Sanitary Engineer of the World SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,MSC-3819, Bethesda, MD 20894 USA. NR 5 TC 0 Z9 0 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 APR PY 2011 VL 101 IS 4 BP 645 EP 645 DI 10.2105/AJPH.2009.190876 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 740UN UT WOS:000288820000018 PM 21330595 ER PT J AU Olsson, AC Gustavsson, P Kromhout, H Peters, S Vermeulen, R Bruske, I Pesch, B Siemiatycki, J Pintos, J Bruning, T Cassidy, A Wichmann, HE Consonni, D Landi, MT Caporaso, N Plato, N Merletti, F Mirabelli, D Richiardi, L Jockel, KH Ahrens, W Pohlabeln, H Lissowska, J Szeszenia-Dabrowska, N Zaridze, D Stucker, I Benhamou, S Bencko, V Foretova, L Janout, V Rudnai, P Fabianova, E Dumitru, RS Gross, IM Kendzia, B Forastiere, F Bueno-de-Mesquita, B Brennan, P Boffetta, P Straif, K AF Olsson, Ann C. Gustavsson, Per Kromhout, Hans Peters, Susan Vermeulen, Roel Brueske, Irene Pesch, Beate Siemiatycki, Jack Pintos, Javier Bruening, Thomas Cassidy, Adrian Wichmann, Heinz-Erich Consonni, Dario Landi, Maria Teresa Caporaso, Neil Plato, Nils Merletti, Franco Mirabelli, Dario Richiardi, Lorenzo Joeckel, Karl-Heinz Ahrens, Wolfgang Pohlabeln, Hermann Lissowska, Jolanta Szeszenia-Dabrowska, Neonila Zaridze, David Stuecker, Isabelle Benhamou, Simone Bencko, Vladimir Foretova, Lenka Janout, Vladimir Rudnai, Peter Fabianova, Eleonora Dumitru, Rodica Stanescu Gross, Isabelle M. Kendzia, Benjamin Forastiere, Francesco Bueno-de-Mesquita, Bas Brennan, Paul Boffetta, Paolo Straif, Kurt TI Exposure to Diesel Motor Exhaust and Lung Cancer Risk in a Pooled Analysis from Case-Control Studies in Europe and Canada SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE epidemiologic studies; lung neoplasm; occupational exposure; vehicle emissions ID OCCUPATIONAL-EXPOSURE; ENGINE EXHAUST; WORKERS; POPULATION; PARTICLES AB Rationale: Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationships. Objectives: Investigate lung cancer risk associated with occupational exposure to diesel motor exhaust, while controlling for potential confounders. Methods: The SYNERGY project pooled information on lifetime work histories and tobacco smoking from 13,304 cases and 16,282 controls from 11 case-control studies conducted in Europe and Canada. A general population job exposure matrix based on ISCO-68 occupational codes, assigning no, low, or high exposure to diesel motor exhaust, was applied to determine level of exposure. Measurements and Main Results: Odds ratios of lung cancer and 95% confidence intervals were estimated by unconditional logistic regression, adjusted for age, sex, study, ever-employment in an occupation with established lung cancer risk, cigarette pack-years, and time-since-quitting smoking. Cumulative diesel exposure was associated with an increased lung cancer risk highest quartile versus unexposed (odds ratio 1.31; 95% confidence interval, 1.19-1.43), and a significant exposure-response relationship (P value <0.01). Corresponding effect estimates were similar in workers never employed in occupations with established lung cancer risk, and in women and never-smokers, although not statistically significant. Conclusions: Our results show a consistent association between occupational exposure to diesel motor exhaust and increased risk of lung cancer. This association is unlikely explained by bias or confounding, which we addressed by adjusted models and subgroup analyses. C1 [Olsson, Ann C.; Brennan, Paul; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon 08, France. [Olsson, Ann C.; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Kromhout, Hans; Peters, Susan; Vermeulen, Roel] Inst Risk Assessment Sci, Utrecht, Netherlands. [Brueske, Irene; Wichmann, Heinz-Erich] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol, Neuherberg, Germany. [Pesch, Beate; Bruening, Thomas; Gross, Isabelle M.; Kendzia, Benjamin] Ruhr Univ Bochum, Inst Prevent & Occupat Med, German Social Accid Insurance Inst, Bochum, Germany. [Siemiatycki, Jack; Pintos, Javier] Univ Montreal, Univ Montreal Hosp Ctr, Res Ctr, Montreal, PQ, Canada. [Cassidy, Adrian] Univ Liverpool, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L69 3BX, Merseyside, England. [Wichmann, Heinz-Erich] Univ Munich, Inst Med Informat Biometrie Epidemiol, Munich, Germany. [Consonni, Dario] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Epidemiol Unit, Milan, Italy. [Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA. [Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] Univ Turin, Turin, Italy. [Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] CPO Piemonte, Canc Epidemiol Unit, Turin, Italy. [Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany. [Ahrens, Wolfgang; Pohlabeln, Hermann] Bremen Inst Prevent Res & Social Med, Bremen, Germany. [Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland. [Lissowska, Jolanta] Inst Oncol, Warsaw, Poland. [Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland. [Zaridze, David] Russian Canc Res Ctr, Moscow, Russia. [Stuecker, Isabelle] INSERM, U754, IFR69, Villejuif, France. [Benhamou, Simone] INSERM, U946, Paris, France. [Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic. [Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic. [Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic. [Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary. [Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia. [Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania. [Forastiere, Francesco] ASL RomaE, Dept Epidemiol, Rome, Italy. [Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm Protect, NL-3720 BA Bilthoven, Netherlands. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. RP Straif, K (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon 08, France. EM straif@iarc.fr RI Szeszenia-Dabrowska, Neonila/F-7190-2010; Peters, Susan/A-5845-2013; Zaridze, David/K-5605-2013; Bruske, Irene/N-3125-2013; Janout, Vladimir/M-5133-2014; Vermeulen, Roel/F-8037-2011; Bruning, Thomas/G-8120-2015; Benhamou, Simone/K-6554-2015; Forastiere, Francesco/J-9067-2016; OI Ahrens, Wolfgang/0000-0003-3777-570X; richiardi, lorenzo/0000-0003-0316-9402; Peters, Susan/0000-0001-5662-1971; Vermeulen, Roel/0000-0003-4082-8163; Bruning, Thomas/0000-0001-9560-5464; Forastiere, Francesco/0000-0002-9162-5684; Lissowska, Jolanta/0000-0003-2695-5799 FU German Social Accident Insurance (DGUV); Swedish council; Industrial Mineral Association; NIH; NCI; EUROBITUME; Deutscher Asphaltverband; Concawe; Zentralverband des deutschen Dachdeckerhandwerks and Aksys; Industrieverband Bitumen; Dach- und Dichtungsbahnen; NHLBI; EAPA FX The SYNERGY project is funded by the German Social Accident Insurance (DGUV).; A.C.O. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.G. received more than $100,001 from the Swedish council as a research grant. H.K. received $40,000 annually from the Industrial Mineral Association in collaborative grants for research on crystalline silica. S.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.V. received more than $100,001 from the NIH, NCI in sponsored grants. I.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. B.P. received $10,001-$50,000 from EUROBITUME, $10,001-$50,000 from Deutscher Asphaltverband, $10,001-$50,000 from Concawe, $5,001-$10,000 from Zentralverband des deutschen Dachdeckerhandwerks and Aksys, and $10,001-$50,000 from Industrieverband Bitumen,- Dach- und Dichtungsbahnen in industry-sponsored grants for the Human Bitumen Study. J.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.B. received $10,001-$50,000 from EUROBITUME, $10,001-$50,000 from Deutscher Asphaltverband, $10,001-S50,000 from Concawe, $5,001-$10,000 from Zentralverband des deutschen Dachdeckerhandwerks and Aksys, and $10,001-$50,000 from Industrieverband Bitumen,- Dach- und Dichtungsbahnen in industry-sponsored grants for the Human Bitumen Study. A.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H-E.W. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. M.T.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.C. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. K-H.J. received $50,001-$100,000 for serving as a member of the C-TOR study data oversight committee and $10,001-$50,000 from the Weinberg Group for serving as a board member, ending within this year (2004-2010). W.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. H.P. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. N.S-D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. D.Z. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. I.S.; does not have a financial relationshi with a commercial entity that has an interest in the subject of this manuscript. S.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. V.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. L.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. V.J. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.R. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. E.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.S.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. I.M.G does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. B.K. received $10,001-$50,000 from EUROBITUME, $10,001-$50,000 from Deutscher Asphaltverband, $10,001-$50,000 from Concawe, $5,001-$10,000 from Zentralverband des deutschen Dachdeckerhandwerks and Aksys, and $10,001-$50,000 from Industrieverband Bitumen,- Dach- und Dichtungsbahnen in industry-sponsored grants for the Human Bitumen Study. F.F. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. B.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.B. received, as the PI of the study, more than $100,001 from EAPA, Concawe, Eurobitume, NAPA, and two American roofing associations as a grant to International Agency for Research on Cancer for a study of lung cancer nested in a cohort of European asphalt workers; more than $100,001 from the NIH in research grants on lung cancer; and more than $100,001 from the NHLBI in research grants on COPD. K.S. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. NR 34 TC 76 Z9 76 U1 2 U2 27 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2011 VL 183 IS 7 BP 941 EP 948 DI 10.1164/rccm.201006-0940OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 747KN UT WOS:000289318800021 PM 21037020 ER PT J AU Avila, NA Dwyer, AJ Moss, J AF Avila, Nilo A. Dwyer, Andrew J. Moss, Joel TI Imaging Features of Lymphangioleiomyomatosis: Diagnostic Pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE lung disease; lymphangioleiomyoma; lymphangioleiomyomatosis; pleurodesis; renal angiomyolipoma ID PATHOLOGICAL CORRELATION; RENAL ANGIOMYOLIPOMA; DIURNAL-VARIATION; CT DIAGNOSIS; PLEURODESIS; MANAGEMENT; PULMONARY AB OBJECTIVE. The objective of this article is to illustrate CT findings that may be misinterpreted and lead to unnecessary biopsy or surgical procedures in patients with lymphangioleiomyomatosis. CONCLUSION. Sequelae of pleurodesis, acutely hemorrhagic renal angiomyolipomas, and lymphatic involvement with lymphangioleiomyomatosis including enlarged lymph nodes and lymphangioleiomyomas are common benign conditions seen in patients with lymphangioleiomyomatosis that may be misdiagnosed on CT for malignancy and may prompt unnecessary biopsy and surgery. Ruptured abdominal pelvic lymphangioleiomyomas may be mistaken for appendicitis and other acute abdominal pelvic events. C1 [Avila, Nilo A.] Vet Affairs Med Ctr, Serv Radiol, Washington, DC 20422 USA. [Avila, Nilo A.; Dwyer, Andrew J.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Avila, NA (reprint author), Vet Affairs Med Ctr, Serv Radiol, 50 Irving St NW,Rm BH-223, Washington, DC 20422 USA. FU National Institutes of Health/NHLBI FX The research was supported by the Intramural Research Program of the National Institutes of Health/NHLBI. The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the National Institutes of Health. NR 16 TC 3 Z9 4 U1 0 U2 4 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2011 VL 196 IS 4 BP 982 EP 986 DI 10.2214/AJR.10.4185 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 738OP UT WOS:000288650600059 PM 21427352 ER PT J AU Brunengraber, LN Turner, M Lee, CCR Stratton, P AF Brunengraber, Lisa N. Turner, Maria Lee, Chyi-Chia Richard Stratton, Pamela TI Bilateral Areolar Lesions in a Patient With Acute Cutaneous Graft-vs-Host Disease SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 [Brunengraber, Lisa N.; Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA. [Turner, Maria] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bldg 10 CRC,Room 1-3140,10 Ctr Dr MSC 1109, Bethesda, MD 20892 USA. EM ps79c@nih.gov RI Lee, Chyi-Chia/I-1938-2013 OI Lee, Chyi-Chia/0000-0002-5306-7781 FU Intramural NIH HHS [Z99 HD999999] NR 8 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2011 VL 147 IS 4 BP 509 EP 511 PG 4 WC Dermatology SC Dermatology GA 752FY UT WOS:000289677800026 PM 21482910 ER PT J AU Baek, JH Reiter, CEN Manalo, DJ Buehler, PW Hider, RC Alayash, AI AF Baek, Jin Hyen Reiter, Chad E. N. Manalo, Dominador J. Buehler, Paul W. Hider, Robert C. Alayash, Abdu I. TI Induction of hypoxia inducible factor (HIF-1 alpha) in rat kidneys by iron chelation with the hydroxypyridinone, CP94 SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Article DE Iron chelator; Hypoxia inducible factor; Erythropoietin ID PROLYL HYDROXYLATION; THALASSEMIA MAJOR; FACTOR 1-ALPHA; O-2 TENSION; HIF; INHIBITION; VHL; THERAPEUTICS; ANGIOGENESIS; PURIFICATION AB Hypoxia inducible factor (HIF-1 alpha) is a master regulator of tissue adaptive responses to hypoxia whose stability is controlled by an iron containing prolyl hydroxylase domain (PHD) protein. A catalytic redox cycle in the PHD's iron center that results in the formation of a ferryl (Fe+4) intermediate has been reported to be responsible for the hydroxylation and subsequent degradation of HIF-1 alpha under normoxia. We show that induction of HIF-1 alpha in rat kidneys can be achieved by iron reduction by the hydroxypyridin-4 one (CP94), an iron chelator administered intraperitoneally in rats. The extent of HIP protein stabilization as well as the expression of HIF target genes, including erythropoietin (EPO), in kidney tissues was comparable to those induced by known inhibitors of the PHD enzyme, such as desferrioxamine (DFO) and cobalt chloride (CoCl2). In human kidney cells and in vitro PHD activity assay, we were able to show that the HIF-1 alpha protein can be stabilized by addition of CP94. This appears to inactivate PHD; and thus prevents the hydroxylation of HIF-1 alpha. In conclusion, we have identified the inhibition of iron-binding pocket of PHD as an underlying mechanism of HIF induction in vivo and in vitro by a bidentate hydroxypyridinone. Published by Elsevier B.V. C1 [Baek, Jin Hyen; Reiter, Chad E. N.; Manalo, Dominador J.; Buehler, Paul W.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Hider, Robert C.] Coll London, Div Pharmaceut Sci, London SE1 9NH, England. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, NIH Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU Defense Advanced Research Projects Agency (DARPA); CBER FX This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) and CBER Critical Path Research Program. NR 43 TC 9 Z9 10 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD APR-JUN PY 2011 VL 1809 IS 4-6 BP 262 EP 268 DI 10.1016/j.bbagrm.2011.04.010 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 780ZK UT WOS:000291900200006 PM 21558026 ER PT J AU Kim, S Jiao, GS Moayeri, M Crown, D Cregar-Hernandez, L McKasson, L Margosiak, SA Leppla, SH Johnson, AT AF Kim, Seongjin Jiao, Guan-Sheng Moayeri, Mahtab Crown, Devorah Cregar-Hernandez, Lynne McKasson, Linda Margosiak, Stephen A. Leppla, Stephen H. Johnson, Alan T. TI Antidotes to anthrax lethal factor intoxication. Part 2: Structural modifications leading to improved in vivo efficacy SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Anthrax; Lethal factor; Inhibitor; Small molecule ID TOXIN AB New anthrax lethal factor inhibitors (LFIs) were designed based upon previously identified potent inhibitors 1a and 2. Combining the new core structures with modifications to the C2-side chain yielded analogs with improved efficacy in the rat lethal toxin model. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Kim, Seongjin; Jiao, Guan-Sheng; Cregar-Hernandez, Lynne; McKasson, Linda; Margosiak, Stephen A.; Johnson, Alan T.] PanThera Biopharma LLC, Aiea, HI 96701 USA. [Moayeri, Mahtab; Crown, Devorah; Leppla, Stephen H.] NIAID, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Johnson, AT (reprint author), PanThera Biopharma LLC, Aiea, HI 96701 USA. EM ajohnson@pantherabio.com FU National Institutes of Health [R44 AI052587, U01 AI078067]; NIH, National Institute of Allergy and Infectious Diseases FX We thank the National Institutes of Health for their support of this work with grants R44 AI052587 and U01 AI078067. Animal studies were supported by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the NIH. NR 15 TC 12 Z9 13 U1 0 U2 1 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 APR 1 PY 2011 VL 21 IS 7 BP 2030 EP 2033 DI 10.1016/j.bmcl.2011.02.010 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 733EM UT WOS:000288245100027 PM 21334206 ER PT J AU Grkovic, T Whitson, EL Rabe, DC Gardella, RS Bottaro, DP Linehan, WM McMahon, JB Gustafson, KR McKee, TC AF Grkovic, Tanja Whitson, Emily L. Rabe, Daniel C. Gardella, Roberta S. Bottaro, Donald P. Linehan, W. Marston McMahon, James B. Gustafson, Kirk R. McKee, Tawnya C. TI Identification and evaluation of soft coral diterpenes as inhibitors of HIF-2 alpha induced gene expression SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE HIF; Renal carcinoma; Soft coral; Alcyonaceae; Sarcophyton sp.; Lobophytum sarcophytoides; Asterospicularia laurae; Bioassay-guided fractionation; Marine natural products; Cembrane ID CEMBRANOID DITERPENES; MARINE-INVERTEBRATES; CANCER AB Kidney cancer was the cause of almost 13,000 deaths in the United States in 2009. Loss of function of the VHL tumor suppressor gene (von Hippel-Lindau disease) dramatically increases the risk of developing clear cell kidney cancer. The VHL protein is best understood for its regulation of hypoxia inducible factor (HIF). HIF responds to changes in oxygen levels in the cell and is responsible for mediating the transcriptional response to hypoxia. Of the three known HIF alpha gene products, HIF-2 alpha appears to play a fundamental role in renal carcinoma. A high throughput screen was developed to identify small molecule inhibitors of HIF-2 gene expression. The screen was performed and yielded 153 confirmed active natural product extracts. Three of the active extracts were from marine soft corals of the order Alcyonacea: Sarcophyton sp., Lobophytum sarcophytoides and Asterospicularia laurae. Bioassay-guided fractionation led to the isolation of two new cembrane diterpenes, (4Z,8S*, 9R*, 12E, 14E)-9-hydroxy-1-(prop-1-en-2-yl)-8,12-dimethyl-oxabicyclo[9.3.2]-hexadeca-4,12,14-trien-18-one (1), and (1E, 3E, 7R*, 8R*, 11E)-1-(2-methoxypropan-2-yl)-4,8,12-trimethyloxabicyclo[12.1.0]-pentadeca-1,3,11-triene (7), as well as eight known compounds, 2-6 and 8-10. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Grkovic, Tanja; Whitson, Emily L.; Gardella, Roberta S.; McMahon, James B.; Gustafson, Kirk R.; McKee, Tawnya C.] NCI, Mol Targets Lab, Frederick, MD 21702 USA. [Rabe, Daniel C.; Bottaro, Donald P.; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Gardella, Roberta S.] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA. RP McKee, TC (reprint author), NCI, Mol Targets Lab, Frederick, MD 21702 USA. EM mckeeta@mail.nih.gov RI Grkovic, Tanja/B-8874-2012; Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center for Cancer Research FX The authors thank D. Newman (NPB) and P. Colin (Coral Reef Research Foundation) for contract collection and T. McCloud (NPSG) for extraction of the animal material, and M. Dyba and S. Terasov (Biophysics Resource, SBL, NCI-Frederick) for help with HRESIMS data acquisition. P. Alderslade and L. van Ofwegen provided taxonomic identifications. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of NIH, National Cancer Institute, Center for Cancer Research. NR 18 TC 12 Z9 14 U1 1 U2 8 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 APR 1 PY 2011 VL 21 IS 7 BP 2113 EP 2115 DI 10.1016/j.bmcl.2011.01.127 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 733EM UT WOS:000288245100044 PM 21353547 ER PT J AU George, SM Irwin, ML Smith, AW Neuhouser, ML Reedy, J McTiernan, A Alfano, CM Bernstein, L Ulrich, CM Baumgartner, KB Moore, SC Albanes, D Mayne, ST Gail, MH Ballard-Barbash, R AF George, Stephanie M. Irwin, Melinda L. Smith, Ashley W. Neuhouser, Marian L. Reedy, Jill McTiernan, Anne Alfano, Catherine M. Bernstein, Leslie Ulrich, Cornelia M. Baumgartner, Kathy B. Moore, Steven C. Albanes, Demetrius Mayne, Susan T. Gail, Mitchell H. Ballard-Barbash, Rachel TI Postdiagnosis diet quality, the combination of diet quality and recreational physical activity, and prognosis after early-stage breast cancer SO CANCER CAUSES & CONTROL LA English DT Article DE Diet; Exercise; Breast neoplasm; Prognosis ID HEALTHY EATING INDEX-2005; OF-LIFE; COLORECTAL-CANCER; SURVIVORS; PATTERNS; DIAGNOSIS; MORTALITY; RISK; QUESTIONNAIRE; RECURRENCE AB To investigate, among women with breast cancer, how postdiagnosis diet quality and the combination of diet quality and recreational physical activity are associated with prognosis. This multiethnic, prospective observational cohort included 670 women diagnosed with local or regional breast cancer. Thirty months after diagnosis, women completed self-report assessments on diet and physical activity and were followed for 6 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for death from any cause and breast cancer death. Women consuming better-quality diets, as defined by higher Healthy Eating Index-2005 scores, had a 60% reduced risk of death from any cause (HR(Q4:Q1): 0.40, 95% CI: 0.17, 0.94) and an 88% reduced risk of death from breast cancer (HR(Q4:Q1): 0.12, 95% CI: 0.02, 0.99). Compared with inactive survivors consuming poor-quality diets, survivors engaging in any recreational physical activity and consuming better-quality diets had an 89% reduced risk of death from any cause (HR: 0.11, 95% CI: 0.04, 0.36) and a 91% reduced risk of death from breast cancer (HR: 0.09, 95% CI: 0.01, 0.89). Associations observed were independent of obesity status. Women diagnosed with localized or regional breast cancer may improve prognosis by adopting better-quality dietary patterns and regular recreational physical activity. Lifestyle interventions emphasizing postdiagnosis behavior changes are advisable in breast cancer survivors. C1 [George, Stephanie M.; Moore, Steven C.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [George, Stephanie M.; Irwin, Melinda L.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, Div Chron Dis Epidemiol, New Haven, CT USA. [Smith, Ashley W.; Reedy, Jill; Ballard-Barbash, Rachel] NCI, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Neuhouser, Marian L.; McTiernan, Anne; Ulrich, Cornelia M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. [Bernstein, Leslie] City Hope Med Ctr & Beckman Res Ctr, Dept Populat Sci, Duarte, CA USA. [Baumgartner, Kathy B.] Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. [Ulrich, Cornelia M.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumor Dis, Heidelberg, Germany. [Bernstein, Leslie] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA 91010 USA. [Bernstein, Leslie] Beckman Res Ctr, Duarte, CA USA. RP George, SM (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320,MSC 7232, Rockville, MD 20852 USA. EM materess@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016 OI Moore, Steven/0000-0002-8169-1661 FU National Cancer Institute [N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, T32 CA105666] FX We would like to thank Dr. Charles L. Wiggins, HEAL Study managers, Eric Meier of the Fred Hutchinson Cancer Research Center Nutrition Assessment Shared Resource, Todd Gibson of Information Management Systems, and the HEAL Study participants. This study is supported by National Cancer Institute Grants: N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010, and T32 CA105666. NR 36 TC 43 Z9 44 U1 1 U2 19 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2011 VL 22 IS 4 BP 589 EP 598 DI 10.1007/s10552-011-9732-9 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736QL UT WOS:000288509100007 PM 21340493 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 female sex hormone concentrations during adolescence: results from the Dietary Intervention Study in Children SO CANCER CAUSES & CONTROL LA English DT Article DE Birth weight; Sex steroid hormones; Breast cancer risk factors; Adolescence; Puberty ID BREAST-CANCER RISK; MAMMARY TUMORIGENESIS; PRECOCIOUS PUBARCHE; PREMENOPAUSAL WOMEN; OPPOSING INFLUENCES; SERUM HORMONES; EARLY PUBERTY; FETAL-GROWTH; SOY INTAKE; BODY-SIZE AB Birth characteristics and adult hormone concentrations influence breast cancer risk, but little is known about the influence of birth characteristics on hormone concentrations, particularly during adolescence. We evaluated the association of birth characteristics (birth weight, birth length, and gestational age) with serum sex hormone concentrations during late childhood and adolescence in 278 female participants of the Dietary Intervention Study in Children. Repeated measures analysis of variance models were used to assess the relationships of birth characteristics and serum estrogens and androgens at five different time points over a mean period of 7 years. In analyses that did not take into account time from blood draw until menarche, birth weight was inversely associated with pre-menarche concentrations of estradiol, estrone sulfate, androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS). In the post-menarche analyses, birth weight was not significantly associated with concentration of any of the hormones under investigation. Birth length and gestational age were not associated with hormone concentrations before or after menarche. Birth weight is inversely associated with sex hormone concentrations before menarche in the model unadjusted for time from blood draw until menarche. The in utero environment has long-term influences on the hormonal milieu, which could potentially contribute to breast cancer risk. C1 [Ruder, Elizabeth H.] NCI, Canc Prevent Fellowship Program, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet,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, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet,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. NR 38 TC 6 Z9 6 U1 2 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2011 VL 22 IS 4 BP 611 EP 621 DI 10.1007/s10552-011-9734-7 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 736QL UT WOS:000288509100009 PM 21327460 ER PT J AU Leyk, S Phillips, TP Smith, JM Nuckols, JR AF Leyk, Stefan Phillips, Thomas P. Smith, Jeremy M. Nuckols, John R. TI Spatio-temporal Trends of Diarrheal Mortality of Children in Association with Hydrographic Regions of Brazil SO CARTOGRAPHY AND GEOGRAPHIC INFORMATION SCIENCE LA English DT Article; Proceedings Paper CT AutoCarto 2010 Conference/Internatiional-Society-for-Photogrammetry-and-Remote-Sensing (ISPRS)/Conference on American-Society-for-Photogrammetry-and-Remote-Sensing (ASPRS) CY NOV 14-16, 2010 CL Orlando, FL SP Int Soc Photogrammetry & Remote Sensing, Amer Soc Photogrammetry & Remote Sensing DE spatial modeling; health geographies; watershed science; hydrology; waterborne disease ID TEMPORAL TRENDS; ANISOTROPIC DIFFUSION; ENTERIC DISEASES; PUBLIC-HEALTH; UNITED-STATES; RISK-FACTORS; PATTERNS; VIETNAM AB In this paper, we analyze trends in average annual peak timing values (MPT) of pediatric mortality attributed to diarrhea] disease in Brazil for the period 1979-1989 using a novel approach for environmental health risk studies, that is using natural boundaries instead of politically derived boundaries to define the unit of analysis (UOA). We evaluate the approach at varying spatial scales: (1) Country-wide based on observed Municipal level mortality data aggregated to Census Micro Regions (CMR); (2) Country-wide based on a grid of 20 Km2 raster cells generated by geostatistical modeling of MPT values; (3) Within eight officially designated Hydrographic Regions of Brazil based on results from the geostatistical models, and (4) Along longitudinal "vectors" of 1 km raster cells defining the stream network (hydrologic regime) within each Hydrographic Region. At the country level, we found evidence of a trend west to east of increasing MPT over an annual cycle (May to April) using the CMR-level estimates. However, when we examined the model results at finer scales i.e., Hydrographic Regions, we discovered greater geographic heterogeneity in MPT across units. At the spatial scale of the stream network within the Hydrographic Regions, we observed consistent trends of increasing MPT from the source areas (upper watersheds) to downstream locations in some Hydrographic Regions, especially those composed of a single river basin. Here, trends were no longer predominantly east to west as at the country level, but oriented in the direction of flow of the major river draining the basin. Our study results indicate substantial spatial variation in peak timing of pediatric mortality attributed to diarrheal disease in Brazil over our study period. This could have important ramifications in studies concerning known or suspected risk factors with significant temporal variation over an annual cycle. We found the geographic orientation of trend in mortality peak timing to be highly dependent on the geographic extent and derivation of the UOA. We demonstrate that a UOA based on natural boundaries, e.g., stream segments or watershed boundaries can result in more consistent and robust prediction of trends in mortality peak timing attributed to diarrhea. C1 [Leyk, Stefan; Phillips, Thomas P.] Univ Colorado, Dept Aerosp Engn, Boulder, CO 80309 USA. [Nuckols, John R.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Leyk, S (reprint author), Univ Colorado, Dept Aerosp Engn, Boulder, CO 80309 USA. EM stefan.leyk@colorado.edu; thomas.phillips@colorado.edu; jmsmith@cotorado.edu; john.nuckols@colostate.edu NR 23 TC 0 Z9 0 U1 1 U2 4 PU CARTOGRAPHY & GEOGRAPHIC INFOR SOC PI GAITHERSBURG PA 6 MONTGOMERY VILLAGE AVE, STE 403, GAITHERSBURG, MD 20879 USA SN 1523-0406 J9 CARTOGR GEOGR INF SC JI Cartogr. Geogr. Inf. Sci. PD APR PY 2011 VL 38 IS 2 BP 223 EP 232 DI 10.1559/15230406382223 PG 10 WC Geography SC Geography GA 781HI UT WOS:000291921100018 ER PT J AU Brown, JM Nemeth, K Kushnir-Sukhov, NM Metcalfe, DD Mezey, E AF Brown, J. M. Nemeth, K. Kushnir-Sukhov, N. M. Metcalfe, D. D. Mezey, E. TI Bone marrow stromal cells inhibit mast cell function via a COX2-dependent mechanism SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergy; COX2; EP4 receptor; mesenchymal stem cell; stromal cell ID MESENCHYMAL STEM-CELLS; PROSTAGLANDIN E-2; DENDRITIC CELLS; LYMPHOCYTE-PROLIFERATION; CD34(+) CELLS; T-CELLS; DEGRANULATION; DISEASE; RELEASE; DIFFERENTIATION AB P>Background Mast cells (MCs) have a central role in the induction of allergic inflammation, such as seen in asthma, and contribute to the severity of certain autoimmune diseases, such as rheumatoid arthritis. The MC thus represents an important inflammatory cell, and one which has resisted therapeutic attempts to alter its role in disease. Objective Because bone marrow-derived stromal cells (BMSC, also known as mesenchymal stem cells or MSCs) have been reported to alter allergic inflammation in vivo, we chose to study the interaction between mouse BMSC and mouse bone marrow-derived MCs. Methods MC degranulation, cytokine production and chemotaxis were evaluated in vitro following co-culture with BMSCs either in cell contact or a transwell. In addition, MC degranulation was assessed in vivo following administration of BMSCs in a model of passive cutaneous anaphylaxis and a peritoneal degranulation assay. Mechanisms of MC suppression by BMSCs were determined through use of inhibitors or antibodies to COX1, COX2, nitric oxide, indoleamine 2, 3-dioxygenase, EP1-4 receptors, TGF-beta and IL-10. Lastly, we utilized either BMSCs or MCs deficient in COX1, COX2 or EP1-4 receptors to confirm the mechanisms of inhibition of MC function by BMSCs. Results We discovered that BMSCs will effectively suppress specific MC functions in vitro as well as in vivo. When MCs are cocultured with BMSCs to allow cell-to-cell contact, BMSCs suppressed MC degranulation, pro-inflammatory cytokine production, chemokinesis and chemotaxis. Similarly, MC degranulation within mouse skin or the peritoneal cavity was suppressed following in vivo administration of BMSCs. Further, we found that these inhibitory effects were dependent on up-regulation of COX2 in BMSCs; and were facilitated through the activation of EP4 receptors on MCs. Conclusion and Clinical Relevance These observations support the concept that BMSCs have the ability to suppress MC activation and therefore could be the basis for a novel cell based therapeutic approach in the treatment of MC driven inflammatory diseases. C1 [Brown, J. M.; Kushnir-Sukhov, N. M.; Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Nemeth, K.; Mezey, E.] NIDCR, CSDB, NIH, Bethesda, MD USA. RP Brown, JM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C207, Bethesda, MD 20892 USA. EM brownja@ecu.edu FU Division of Intramural Research programs of NIDCR; NIAID FX This research was supported by the Division of Intramural Research programs of NIDCR and NIAID. NR 39 TC 36 Z9 38 U1 2 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 2011 VL 41 IS 4 BP 526 EP 534 DI 10.1111/j.1365-2222.2010.03685.x PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 735BA UT WOS:000288387200011 PM 21255158 ER PT J AU Wei, BR Martin, PL Hoover, SB Spehalski, E Kumar, M Hoenerhoff, MJ Rozenberg, J Vinson, C Simpson, RM AF Wei, Bih-Rong Martin, Philip L. Hoover, Shelley B. Spehalski, Elizabeth Kumar, Mia Hoenerhoff, Mark J. Rozenberg, Julian Vinson, Charles Simpson, R. Mark TI Capacity for Resolution of Ras-MAPK-Initiated Early Pathogenic Myocardial Hypertrophy Modeled in Mice SO COMPARATIVE MEDICINE LA English DT Article ID DEPENDENT KINASE INHIBITORS; CYCLE REGULATORY MOLECULES; ACTIVATED PROTEIN-KINASE; MYOCYTE CELL-CYCLE; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; VENTRICULAR HYPERTROPHY; CARDIOVASCULAR-DISEASE; SIGNALING PATHWAYS; HEART AB Activation of Ras signaling in cardiomyocytes has been linked to pathogenic myocardial hypertrophy progression and subsequent heart failure. Whether cardiomyopathy can regress once initiated needs to be established more fully. A 'tet-off' system was used to regulate expression of H-Ras-G12V in myocardium to examine whether Ras-induced pathogenic myocardial hypertrophy could resolve after removal of Ras signaling in vivo. Ras activation at weaning for 2 wk caused hypertrophy, whereas activation for 4 to 8 wk led to cardiomyopathy and heart failure. Discontinuing H-Ras-G12V transgene expression after cardiomyopathy onset led to improved survival and cardiomyopathy lesion scores, with reduced heart:body weight ratios, demonstrating the reversibility of early pathogenic hypertrophy. Activation of Ras and downstream ERK 1/2 was associated with elevated expression of proliferating cell nuclear antigen and cyclins B1 and D1, indicating cell-cycle activation and reentry. Coordinate elevation of broad-spectrum cyclin-dependent kinase inhibitors (p21, p27, and p57) and Tyr15 phosphorylation of cdc2 signified the activation of cell-cycle checkpoints; absence of cell-cycle completion and cardiomyocyte replication were documented by using immunohistochemistry for mitosis and cytokinesis markers. After resolution of cardiomyopathy, cell-cycle activators and inhibitors examined returned to basal levels, a change that we interpreted as exit from the cell cycle. Cardiac cell-cycle regulation plays a role in recovery from pathogenic hypertrophy. The model we present provides a means to further explore the underlying mechanisms governing cell-cycle capacity in cardiomyocytes, as well as progression and regression of pathogenic cardiomyocyte hypertrophy. C1 [Wei, Bih-Rong; Martin, Philip L.; Hoover, Shelley B.; Spehalski, Elizabeth; Kumar, Mia; Hoenerhoff, Mark J.; Simpson, R. Mark] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. [Rozenberg, Julian; Vinson, Charles] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Simpson, RM (reprint author), NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. EM ms43b@nih.gov FU Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; [N01-CO-12400] FX The study was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland. We acknowledge the scholarly support provided by Jennifer Edwards and Joshua Webster. All authors declare there are no actual or potential conflicts of interest, including any financial, personal, or other relationships with people or organizations that could inappropriately influence this work.; Bih-Rong Wei and Philip L Martin are employees of the Science Applications International Corporation-Frederick, Frederick, Maryland, on contract to the National Cancer Institute Intramural Research Program (Award N01-CO-12400). NR 42 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2011 VL 61 IS 2 BP 109 EP 118 PG 10 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 915QP UT WOS:000302042800002 PM 21535921 ER PT J AU Nowland, MH Hugunin, KMS Rogers, KL AF Nowland, Megan H. Hugunin, Kelly M. S. Rogers, Karen L. TI Effects of Short-Term Fasting in Male Sprague-Dawley Rats SO COMPARATIVE MEDICINE LA English DT Article ID CHRONIC MILD STRESS; CORTICOSTERONE LEVELS; PLASMA-CORTICOSTERONE; FOOD-DEPRIVATION; SERUM CORTICOSTERONE; CALORIC RESTRICTION; SELF-STIMULATION; IMMUNOGLOBULIN-A; HOUSING DENSITY; MICE AB Fasting is a common procedure for animals in experiments. Although fasting may be necessary for scientific reasons, it should be minimized. In the current study, jugular-catheterized male Sprague Dawley rats in metabolism cages were fasted for 0 to 24 h before measurement of various physiologic markers (serum chemistry, CBC analysis, serum corticosterone). When controlled for cohort, rats fasted for 6 and 16 h had significantly lower serum glucose than did nonfasted rats. Other values did not differ from controls. Only rats fasted for 24 h had elevated serum corticosterone levels. Therefore, fasting for as long as 16 h has fewer effects on rats that does fasting for 24 h. Fasting for 24 h or more therefore should receive appropriate consideration by both scientists and the IACUC in the experimental design and the animal-use protocol. C1 [Nowland, Megan H.] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. [Hugunin, Kelly M. S.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Rogers, Karen L.] Lab Anim Vet Consultant, Schwenksville, PA USA. RP Nowland, MH (reprint author), Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. EM meganmur@umich.edu NR 39 TC 15 Z9 15 U1 2 U2 7 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2011 VL 61 IS 2 BP 138 EP 144 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 915QP UT WOS:000302042800005 PM 21535924 ER PT J AU Gozalo, AS Ragland, DR StClaire, MC Elkins, WR Michaud, CR AF Gozalo, Alfonso S. Ragland, Dan R. StClaire, Marisa C. Elkins, William R. Michaud, Carmen R. TI Intracardiac Thrombosis and Aortic Dissecting Aneurysms in Mustached Tamarins (Saguinus mystax) with Cardiomyopathy SO COMPARATIVE MEDICINE LA English DT Article ID MYOCARDIAL FIBROSIS; CEBUS-APELLA; MONKEY; DISEASE; AOTUS; HYPERTENSION; HYPERTROPHY; CAPTIVITY; GORILLA AB Spontaneous intracardiac thrombosis is rarely reported in animals, particularly nonhuman primates. The finding of 2 cases of intracardiac thrombi in mustached tamarins (Saguinus mystax) that died as a consequence of congestive heart failure prompted us to do a retrospective study to determine the frequency of this condition. Clinical records, necropsy reports, and tissues from 60 mustached tamarins that died or were euthanized between 1996 and 2009 were reviewed. Of the 60 monkeys whose cases were reviewed, 10 (16.6%) had intracardiac thrombi, and 4 (6.6%) had dissecting aortic aneurysms. Of the 10 animals with intracardiac thrombosis, 3 had left ventricular involvement alone; 4 monkeys had thrombi only in the right ventricle, and the remaining 3 animals exhibited thrombi in both ventricles. Myocardial fibrosis and chronic renal disease were common findings in affected animals. The causes of the intracardiac thrombosis in the tamarins in the present study are not known, but the clinical signs and gross and microscopic lesions suggest that congestive heart failure secondary to cardiomyopathy is the primary contributor. In addition, the cause of the aortic dissecting aneurysms in the tamarins in this study is not known. Further studies are required to determine whether factors including aortic curvature, genetic background, or hypertension alone or in combination play a role. To our knowledge, the current retrospective study is the first report of intracardiac thrombosis and aortic aneurysms in mustached tamarins. C1 [Gozalo, Alfonso S.; Elkins, William R.; Michaud, Carmen R.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Ragland, Dan R.; StClaire, Marisa C.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Gozalo, Alfonso S.] SoBran, Bethesda, MD USA. [Ragland, Dan R.] Charles River Labs, Germantown, MD USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID); NIAID; Comparative Medicine Branch; Office of Research Support FX This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), Comparative Medicine Branch, the Office of Research Support, and a NIAID contract to SoBran and Bioqual. We thank Dr Robert Purcell and Dr Sue Emerson for letting us use tamarin tissue samples from their previous studies and Lawrence Faucette and JoAnne Malinowski for technical assistance. NR 34 TC 1 Z9 1 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD APR PY 2011 VL 61 IS 2 BP 176 EP 181 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 915QP UT WOS:000302042800011 PM 21535930 ER PT J AU Boja, ES AF Boja, Emily S. TI Quantitative Proteomics Using Isobaric Chemical Tagging and HCD SO CURRENT PROTEOMICS LA English DT Review DE iTRAQ; TMT; high energy collisional-activated dissociation; LTQ-Orbitrap ID TRAP MASS-SPECTROMETER; COMPLEX PROTEIN MIXTURES; BIOMARKER DISCOVERY; LTQ ORBITRAP; QUANTIFICATION; ITRAQ; DISSOCIATION; TAGS; PEPTIDE; PHOSPHOPEPTIDES AB Multiplexed stable isotope reagents such as iTRAQ and Tandem Mass Tag (TMT) designed for MS/MS-based quantitation of peptides rely on accurate and robust detection of low mass fragments for peptide precursor ions. In the past, such analyses depended upon mass spectrometers capable of producing the so-called "triple-quadrupole-like" fragmentation including triple quadrupole mass spectrometers (TQMS) and quadrupole time-of-flight (Q-TOF) instruments. The "one-third rule" on an ion trap (IT) instrument precluded the use of these reagents on this widely available instrument platform until the invention of Pulsed Q Dissociation (PQD), which in itself manifests problems in generating sufficient reporter ion intensities for accurate quantitation. The introduction of high energy collisional-activated dissociation (HCD) on LTQ-Orbitrap XL and LTQ-Orbitrap Velos platforms has opened up great opportunities for accurate quantitative analysis of proteins and their post-translational modifications (PTMs) using chemical tagging by generating "triple-quadrupole-like" fragmentation mainly in the low mass range in MS/MS mode. C1 [Boja, Emily S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Boja, ES (reprint author), NCI, Off Canc Clin Prote Res, Ctr Strateg Sci Initiat, NIH, Room 10A52,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA. EM bojae@mail.nih.gov NR 41 TC 1 Z9 1 U1 4 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-1646 J9 CURR PROTEOMICS JI Curr. Proteomics PD APR PY 2011 VL 8 IS 1 BP 31 EP 38 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 909PH UT WOS:000301576200004 ER PT J AU Goldbach-Mansky, R AF Goldbach-Mansky, Raphaela TI Current Status of Understanding the Pathogenesis and Management of Patients With NOMID/CINCA SO CURRENT RHEUMATOLOGY REPORTS LA English DT Review DE IL-1; Autoinflammatory diseases; NOMID; CINCA; NLRP3; CIAS1; CAPS; IL-1Ra; Anakinra; Neonatal disorder; Genetic disease AB Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, and arthritis (CINCA) syndrome is the most severe clinical phenotype in the spectrum of cryopyrin-(NLRP3/NALP3) associated periodic syndromes (CAPS). The study of patients with NOMID/CINCA has been instrumental in characterizing the extent of organ-specific inflammatory manifestations and damage that can occur with chronic interleukin (IL)-1 beta overproduction. Mutations in CIAS1/NLRP3 lead to constitutive activation of the "NLRP3 inflammasome," an intracellular platform that processes and secretes increased amounts of IL-1 beta. The pivotal role of IL-1 beta in NOMID/CINCA has been demonstrated in several clinical studies using IL-1-blocking agents that lead to rapid resolution of the inflammatory disease manifestations. NOMID/CINCA is a monogenic autoinflammatory syndrome; and the discovery of the role of IL-1 in NOMID has led to the exploration in the role of IL-1 in other disorders including gout and Type II diabetes. The inflammation in NOMID/CINCA is continuous with intermittent flares, and organ manifestations encompus the central nervous system, eye, inner ear, and bones. This review discusses updates on the pathogenesis of NOMID/CAPS, emerging long term-outcome data regarding IL-1-blocking agents that have influenced our considerations for optimal treatment, and a monitoring approach tailored to the patient's disease severity and organ manifestations. C1 NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA. RP Goldbach-Mansky, R (reprint author), NIAMSD, Translat Autoinflammatory Dis Sect, NIH, Bldg 10,Room 6D-47B,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov FU Novartis; Regeneron Pharmaceuticals FX Dr. Goldbach-Mansky has received grant support from Novartis and Regeneron Pharmaceuticals. NR 44 TC 43 Z9 45 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1523-3774 J9 CURR RHEUMATOL REP JI Curr. Rheumatol. Rep. PD APR PY 2011 VL 13 IS 2 BP 123 EP 131 DI 10.1007/s11926-011-0165-y PG 9 WC Rheumatology SC Rheumatology GA V29TO UT WOS:000208770900006 PM 21538043 ER PT J AU Gea-Banacloche, J AF Gea-Banacloche, Juan TI Granulocyte transfusions: where is the controversy? SO CYTOTHERAPY LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; INFECTIONS; NEUTROPENIA; EXPERIENCE C1 NCI, Infect Dis Sect, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Gea-Banacloche, J (reprint author), NCI, Infect Dis Sect, Expt Transplantat & Immunol Branch, 10 Ctr Dr,Room 3E 3-3330, Bethesda, MD 20892 USA. EM banacloj@mail.nih.gov NR 11 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD APR PY 2011 VL 13 IS 4 BP 389 EP 390 DI 10.3109/14653249.2011.555096 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 734JP UT WOS:000288330700001 PM 21271943 ER PT J AU Nelson, EL Emery, MS Babcock, SM Novak, MFSX Suomi, SJ Novak, MA AF Nelson, Eliza L. Emery, Michelle S. Babcock, Samantha M. Novak, Matthew F. S. X. Suomi, Stephen J. Novak, Melinda A. TI Head Orientation and Handedness Trajectory in Rhesus Monkey Infants (Macaca mulatta) SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE handedness; laterality; head orientation; neonatal; primate ID CHIMPANZEES PAN-TROGLODYTES; HAND PREFERENCES; NEMESTRINA; LATERALIZATION; ASYMMETRIES AB In human and chimpanzee infants, neonatal rightward supine head orientation bias predicts later right hand use preference. In an evolutionarily older primate species such as the rhesus monkey, a left hand preference has been reported, but there are no data on head orientation biases. Supine head orientation bias was measured experimentally in 16 rhesus monkey neonates and compared with prone head orientation bias as well as with various measures of hand use preference. A group-level leftward supine head bias was found that corresponded to greater activity in the left hand while supine; however, supine head orientation did not predict later hand preference as measured by reaching or manipulation on a coordinated bimanual task. These data suggest that a trajectory for handedness in rhesus monkeys may be different from that of humans and chimpanzees. (C) 2010 Wiley Periodicals, Inc. Dev Psychobiol 53: 246-255, 2011. C1 [Nelson, Eliza L.; Emery, Michelle S.; Babcock, Samantha M.; Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Novak, Matthew F. S. X.; Suomi, Stephen J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, US Dept HHS, Comparat Ethol Lab, Poolesville, MD USA. RP Nelson, EL (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall, Amherst, MA 01003 USA. EM eliza_nelson@unc.edu OI Nelson, Eliza/0000-0003-0058-8409 FU Division of Intramural Research (NICHD) FX Contract grant sponsor: Division of Intramural Research (NICHD) NR 29 TC 5 Z9 5 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD APR PY 2011 VL 53 IS 3 BP 246 EP 255 DI 10.1002/dev.20517 PG 10 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 734KH UT WOS:000288332500003 PM 21400487 ER PT J AU Abeliovich, H Ecker, N Journo, D AF Abeliovich, Hagai Ecker, Nitai Journo, Dikla TI Induction of Autophagic Flux by Amino Acid Deprivation Is Distinct from Nitrogen Starvation-Induced Macroautophagy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Abeliovich, Hagai] NINDS, NIH, Bethesda, MD 20892 USA. [Abeliovich, Hagai; Ecker, Nitai; Journo, Dikla] Hebrew Univ Jerusalem, IL-76100 Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402653 ER PT J AU Ammosova, T Yedavalli, VRK Jerebtsova, M Van Eynde, A Beullens, M Bollen, M Jeang, KT Nekhai, S AF Ammosova, Tatiana Yedavalli, Venkat R. K. Jerebtsova, Marina Van Eynde, Aleyde Beullens, Monique Bollen, Mathieu Jeang, Kuan-Teh Nekhai, Sergei TI Expression of PP1 inhibitor inhibits CDK9 and HIV-1 transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Ammosova, Tatiana; Nekhai, Sergei] Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Yedavalli, Venkat R. K.; Jeang, Kuan-Teh] NIAID, NIH, Bethesda, MD 20892 USA. [Jerebtsova, Marina] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Van Eynde, Aleyde; Beullens, Monique; Bollen, Mathieu] Catholic Univ Louvain, B-3000 Louvain, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404804 ER PT J AU Amzel, LM Chufan, E Rudzka, K Eipper, B Mains, R AF Amzel, L. Mario Chufan, Eduardo Rudzka, Katarzyna Eipper, Betty Mains, Richard TI Structural and mechanistic studies of peptidylglycine alpha-amidating monooxygenase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Amzel, L. Mario; Rudzka, Katarzyna] Johns Hopkins Univ, Dept Biophys & Biophys Chem, Baltimore, MD USA. [Chufan, Eduardo] NCI, Transport Biochem Sect, Bethesda, MD 20892 USA. [Eipper, Betty; Mains, Richard] Univ Connecticut, Ctr Hlth, Dept Neurosci, Farmington, CT USA. RI Rudzka, Katarzyna/D-3867-2013 NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401747 ER PT J AU Andrews, K Roseland, J Holden, J Zhao, CW Middleton, A Feinberg, M Dwyer, J Bailey, R Saldanha, L AF Andrews, Karen Roseland, Janet Holden, Joanne Zhao, Cuiwei Middleton, Angela Feinberg, Matthew Dwyer, Johanna Bailey, Regan Saldanha, Leila TI Analytical vitamin D levels in multivitamin/mineral (MVM) products from the Dietary Supplment Ingredient Database (DSID) studies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Andrews, Karen; Roseland, Janet; Holden, Joanne; Zhao, Cuiwei; Middleton, Angela; Feinberg, Matthew] ARS, NDL, BHNRC, USDA, Beltsville, MD USA. [Dwyer, Johanna; Bailey, Regan; Saldanha, Leila] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401977 ER PT J AU Arana, ME Kerns, RT Bushel, PR Kunkel, TA AF Arana, Mercedes E. Kerns, Robnet T. Bushel, Pierre R. Kunkel, Thomas A. TI Transcriptional response to loss of RNase H2 activity in Saccharomyces cerevisiae SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Arana, Mercedes E.; Kunkel, Thomas A.] NIEHS, Labs Mol Gent & Struct Biol, Res Triangle Pk, NC 27709 USA. [Kerns, Robnet T.; Bushel, Pierre R.] NIEHS, Microarray & Genome Bioinformat Grp, Res Triangle Pk, NC 27709 USA. [Kerns, Robnet T.] NIEHS, SRA Int, Res Triangle Pk, NC 27709 USA. [Bushel, Pierre R.] NIEHS, Bioinfomat Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402560 ER PT J AU Artis, ML Meneses, C Elnaiem, DE AF Artis, Monica L. Meneses, Claudio Elnaiem, Dia-Eldin TI Comparison of the Life Cycle and the Survival Strategies of two Sand Fly Vectors of Leishmanaisis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Artis, Monica L.; Elnaiem, Dia-Eldin] Univ Maryland Eastern Shore, Princess Anne, MD USA. [Meneses, Claudio] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403420 ER PT J AU Bachran, CH Morley, T Abdelazim, S Liu, SH Leppla, S AF Bachran, Christopher Holger Morley, Thomas Abdelazim, Suzanne Liu, Shihui Leppla, Stephen TI Ubiquitin-modulated intracellular processing as a determinant of the potency of tumor-targeted anthrax toxins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Bachran, Christopher Holger; Morley, Thomas; Abdelazim, Suzanne; Liu, Shihui; Leppla, Stephen] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404830 ER PT J AU Bailey, RL Carmel, R Green, R Pfeiffer, CM Yetley, EA AF Bailey, Regan L. Carmel, Ralph Green, Ralph Pfeiffer, Christine M. Yetley, Elizabeth A. TI Defining low B12 status in the US SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Bailey, Regan L.; Yetley, Elizabeth A.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Carmel, Ralph] New York Methodist Hosp, Brooklyn, NY USA. [Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Green, Ralph] Univ Calif Davis, Dept Med Pathol & Lab Med, Sacramento, CA 95817 USA. [Pfeiffer, Christine M.] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402207 ER PT J AU Bailey, RL Gahche, JJ Dodd, KW Dwyer, JT AF Bailey, Regan L. Gahche, Jaime J. Dodd, Kevin W. Dwyer, Johanna T. TI Changes in the Dietary Supplement Collection System in NHANES 2007-2008: Implications for Researchers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Bailey, Regan L.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Gahche, Jaime J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Dodd, Kevin W.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401974 ER PT J AU Balaban, RS Taylor, J Phillips, D AF Balaban, Robert Stephen Taylor, Joni Phillips, Darci TI Oxidative phosphorylation enzyme molar activities scale with metabolic dynamic range: Inter-organ and allometric relationships SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Balaban, Robert Stephen; Taylor, Joni; Phillips, Darci] NHBLI, Cardiac Energet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406107 ER PT J AU Balagopalan, L Ashwell, B Bernot, K Akpan, I Quasba, N Barr, V Samelson, LE AF Balagopalan, Lakshmi Ashwell, Benjamin Bernot, Kelsie Akpan, Itoro Quasba, Naeha Barr, Valarie Samelson, Lawrence E. TI Enhanced T cell signaling in cells bearing LAT molecules resistant to ubiquitylation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Balagopalan, Lakshmi; Ashwell, Benjamin; Bernot, Kelsie; Akpan, Itoro; Quasba, Naeha; Barr, Valarie; Samelson, Lawrence E.] NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402890 ER PT J AU Balasubramanian, R Tosh, DK Lloyd, JR Gao, ZG Jacobson, KA AF Balasubramanian, Ramachandran Tosh, Dilip K. Lloyd, John R. Gao, Zhan-Guo Jacobson, Kenneth A. TI Characterization of fluorescent GPCR-ligand dendrimer (GLiDe) conjugates in binding to the A(3) adenosine receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Balasubramanian, Ramachandran; Tosh, Dilip K.; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. [Lloyd, John R.] NIH, Mass Spectrometry Facil, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403564 ER PT J AU Basu, NK Basu, M Mitra, PS Owens, IS AF Basu, Nikhil Kumar Basu, Mousumi Mitra, Partha S. Owens, Ida S. TI Phosphorylation by Tyrosine Kinases Dictates Endogenous Substrate-Selection for UDP-glucuronosyltransferase(UGT)-2B7 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Basu, Nikhil Kumar; Basu, Mousumi; Mitra, Partha S.; Owens, Ida S.] NICHD, SGDDM, PDEGEN, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404806 ER PT J AU Basu, SK Malik, R Huggins, C Lee, S Sebastian, T Sakchaisri, K Quinones, O Alvord, G Johnson, PF AF Basu, Sandip Kumar Malik, Radek Huggins, Christopher Lee, Sook Sebastian, Thomas Sakchaisri, Krisada Quinones, Octavio Alvord, Gregory Johnson, Peter F. TI Functional Regulation of the Transcription Factor C/EBP beta by Its 3'UTR SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Basu, Sandip Kumar; Malik, Radek; Huggins, Christopher; Lee, Sook; Sebastian, Thomas; Sakchaisri, Krisada; Johnson, Peter F.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA. [Quinones, Octavio; Alvord, Gregory] NCI, Data Management Serv, Frederick, MD 21701 USA. [Malik, Radek] Acad Sci Czech Republic, Inst Mol Genet, Videnska, Czech Republic. [Sebastian, Thomas] QIAGEN Res & Dev, Germantown, MD USA. RI Malik, Radek/G-3578-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404422 ER PT J AU Batkai, S Mukhopadhyay, P Horvath, B Rajesh, M Hasko, G Wink, DA Mechoulam, R AF Batkai, Sandor Mukhopadhyay, Partha Horvath, Bela Rajesh, Mohanraj Hasko, George Wink, David A. Mechoulam, Raphael TI Cannabidiol protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and cell death SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Batkai, Sandor; Mukhopadhyay, Partha; Horvath, Bela; Rajesh, Mohanraj] NIAAA, NIH, Bethesda, MD 20892 USA. [Wink, David A.] NCI, Bethesda, MD USA. [Hasko, George] UMDNJ, Newark, NJ USA. [Mechoulam, Raphael] Hebrew Univ Jerusalem, Jerusalem, Israel. RI Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403697 ER PT J AU Batkai, S Zoerner, AA Pischke, S Wedemeyer, H Jordan, J Tsikas, D AF Batkai, Sandor Zoerner, Alexander A. Pischke, Sven Wedemeyer, Heiner Jordan, Jens Tsikas, Dimitrios TI SIMULTANEUS DETECTION OF OXIDIZED AND NITRATED OLEIC ACID METABOLITES IN PATIENTS WITH CHRONIC LIVER DISEASE SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Batkai, Sandor] NIAAA, Inst Clin Pharmacol, D-3000 Bethesda, MD USA. [Batkai, Sandor; Zoerner, Alexander A.; Jordan, Jens; Tsikas, Dimitrios] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany. [Pischke, Sven; Wedemeyer, Heiner] Hannover Med Sch, Hannover, Germany. RI Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402289 ER PT J AU Begum, N Hockman, S Manganiello, VC AF Begum, Najma Hockman, Steven Manganiello, Vincent C. TI PDE3A Deletion Suppresses Mouse VSMC Proliferation via Inhibition of MAPK Signaling and Cell Cycle Arrest SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Begum, Najma; Hockman, Steven; Manganiello, Vincent C.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402321 ER PT J AU Bellani, MA Muniandy, P Paramasivam, M Smogorzewska, A Wang, WD de Winter, J Seidman, MM AF Bellani, Marina Andrea Muniandy, Parames Paramasivam, Manikandian Smogorzewska, Agata Wang, Weidong de Winter, Johan Seidman, Michael M. TI Dissecting cellular inter-strand crosslink repair pathways through the recruitment kinetics of Fanconi Anemia (FA) proteins to localized ICLs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Bellani, Marina Andrea; Paramasivam, Manikandian; Seidman, Michael M.] LMG, Baltimore, MD USA. [Wang, Weidong] NIA, LG, NIH, Baltimore, MD 21224 USA. [Muniandy, Parames] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smogorzewska, Agata] Rockefeller Univ, New York, NY 10021 USA. [de Winter, Johan] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402580 ER PT J AU Benicky, J Sanchez-Lemus, E Honda, M Wang, J Orecna, M Saavedra, JM AF Benicky, Julius Sanchez-Lemus, Enrique Honda, Masaru Wang, Juan Orecna, Martina Saavedra, Juan M. TI Angiotensin II AT1 receptor blockade ameliorates the response of brain to the systemic immune challenge SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Benicky, Julius; Sanchez-Lemus, Enrique; Honda, Masaru; Wang, Juan; Orecna, Martina; Saavedra, Juan M.] NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403927 ER PT J AU Bergman, J Olajire, S Goldberg, SR Makriyannis, A Justinova, Z Goldberg, SR AF Bergman, Jack Olajire, Shakiru Goldberg, Steven R. Makriyannis, Alex Justinova, Zuzana Goldberg, Steven R. TI Discriminative-stimulus and reinforcing effects of FAAH inhibitors in CB-1 trained subjects SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Bergman, Jack] Harvard Univ, Sch Med, Preclin Pharmacol Program, McLean Hosp, Belmont, MA 02178 USA. [Olajire, Shakiru; Makriyannis, Alex] Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. [Goldberg, Steven R.; Justinova, Zuzana; Goldberg, Steven R.] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405359 ER PT J AU Beydoun, HA Shroff, M Mohan, R Beydoun, MA AF Beydoun, Hind A. Shroff, Monal Mohan, Ravinder Beydoun, May A. TI Associations of serum vitamin A and carotenoid levels with markers of prostate cancer progression among US men SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Shroff, Monal] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Beydoun, May A.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402199 ER PT J AU Beydoun, MA Shroff, MR Chen, XL Beydoun, HA Wang, YF Zonderman, AB AF Beydoun, May A. Shroff, Monal R. Chen, Xiaoli Beydoun, Hind A. Wang, Youfa Zonderman, Alan B. TI Serum antioxidant status and its association with metabolic syndrome among US adults: Findings from recent national data SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Beydoun, May A.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Shroff, Monal R.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Chen, Xiaoli; Wang, Youfa] Johns Hopkins Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406868 ER PT J AU Beydoun, MA Beydoun, HA Boueiz, A Shroff, MR Zonderman, AB AF Beydoun, May A. Beydoun, Hind A. Boueiz, Adel Shroff, Monal R. Zonderman, Alan B. TI Antioxidant status and its association with elevated depressive symptoms among US adults: National Health and Nutrition Examination Surveys 2005-06 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Beydoun, May A.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Boueiz, Adel] Johns Hopkins Sch Med, Baltimore, MD USA. [Shroff, Monal R.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406869 ER PT J AU Beydoun, MA Ding, EL Beydoun, HA Tanaka, T Ferrucci, L Zonderman, AB AF Beydoun, May A. Ding, Eric L. Beydoun, Hind A. Tanaka, Toshiko Ferrucci, Luigi Zonderman, Alan B. TI Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change among US adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Beydoun, May A.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Ding, Eric L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ding, Eric L.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Ding, Eric L.] HMS, Boston, MA USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406771 ER PT J AU Beydoun, MA Beydoun, HA Shroff, MR Kitner-Triolo, MH Zonderman, AB AF Beydoun, May A. Beydoun, Hind A. Shroff, Monal R. Kitner-Triolo, Melissa H. Zonderman, Alan B. TI Serum leptin, thyroxine and thyroid stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Beydoun, May A.; Kitner-Triolo, Melissa H.; Zonderman, Alan B.] NIA, Lab Behav Neurosci, Baltimore, MD 21224 USA. [Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA. [Shroff, Monal R.] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404875 ER PT J AU Boateng, KA Bellani, MA Pratto, F Camerini-Otero, RD AF Boateng, Kingsley A. Bellani, Marina A. Pratto, Florencia Camerini-Otero, Rafael Daniel TI A new role for SPO11 during mouse spermatogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Boateng, Kingsley A.; Pratto, Florencia; Camerini-Otero, Rafael Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. [Bellani, Marina A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406316 ER PT J AU Borgmann, A Abdala, APL Zhang, RL Rybak, IA Paton, JFR Smith, JC AF Borgmann, Anke Abdala, Ana P. L. Zhang, Ruli Rybak, Ilya A. Paton, Julian F. R. Smith, Jeffrey C. TI Spiking behavior and membrane potential trajectories of pre-BotC and hypoglossal neurons recorded from the rat in situ SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Borgmann, Anke; Zhang, Ruli; Smith, Jeffrey C.] NINDS, NIH, Bethesda, MD 20892 USA. [Abdala, Ana P. L.; Paton, Julian F. R.] Univ Bristol, Dept Physiol & Pharmacol, Bristol, Avon, England. [Rybak, Ilya A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400968 ER PT J AU Boudreau, HE Korzeniowska, A Leto, T AF Boudreau, Howard E. Korzeniowska, Agnieszka Leto, Thomas TI TGF-beta Signaling Regulates NADPH Oxidase 4 (Nox4) - Dependent Oxidative Stress and Migration of Human Breast Epithelial Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Boudreau, Howard E.; Korzeniowska, Agnieszka; Leto, Thomas] NIAID, Host Def Lab, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401661 ER PT J AU Breslow, R Chen, C Graubard, BI Mukamal, KJ AF Breslow, Rosalind Chen, Chiung Graubard, Barry I. Mukamal, Kenneth J. TI Prospective study of alcohol consumption quantity, frequency, and cancer-specific mortality in the US population SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Breslow, Rosalind] NIAAA, NIH, Bethesda, MD 02215 USA. [Chen, Chiung] CSR Inc, Arlington, VA USA. [Graubard, Barry I.] NCI, NIH, Rockville, MD USA. [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401805 ER PT J AU Brick, K Gregoretti, I Smagulova, F Khil, P Camerini-Otero, RD Petukhova, G AF Brick, Kevin Gregoretti, Ivan Smagulova, Fatima Khil, Pavel Camerini-Otero, Rafael Daniel Petukhova, Galina TI Genome-wide Analysis Reveals Novel Molecular Features of Mouse Recombination SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Brick, Kevin; Gregoretti, Ivan; Khil, Pavel; Camerini-Otero, Rafael Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD USA. [Smagulova, Fatima; Petukhova, Galina] Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406317 ER PT J AU Brunelli, L Kuehn, MR Lezin, G AF Brunelli, Luca Kuehn, Michael R. Lezin, George TI Hofmeister series salts enhance purification of plasmid DNA by non-ionic detergents SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Brunelli, Luca; Lezin, George] Univ Utah, Salt Lake City, UT USA. [Kuehn, Michael R.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402773 ER PT J AU Brunelli, L Kuehn, MR Lezin, G AF Brunelli, Luca Kuehn, Michael R. Lezin, George TI A one-solution, one-tube plasmid DNA miniprep SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Brunelli, Luca; Lezin, George] Univ Utah, Salt Lake City, UT USA. [Kuehn, Michael R.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402768 ER PT J AU Byun, JS Fufa, TD Wakano, C Haggerty, C Gardner, K AF Byun, Jung S. Fufa, Temesgen D. Wakano, Clay Haggerty, Cynthia Gardner, Kevin TI Hierarchical requirement for ELL in multiple steps during RNA polymerase II transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Byun, Jung S.; Fufa, Temesgen D.; Wakano, Clay; Haggerty, Cynthia; Gardner, Kevin] NCI, LRBGE, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404434 ER PT J AU Callahan, KE Hickman, AB Jones, CE Ghirlando, R Furano, AV AF Callahan, Kathryn E. Hickman, Alison B. Jones, Charles E. Ghirlando, Rodolfo Furano, Anthony V. TI Unexpected Properties of the Human LINE-1 Retrotransposon ORF1p SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Callahan, Kathryn E.; Hickman, Alison B.; Jones, Charles E.; Ghirlando, Rodolfo; Furano, Anthony V.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406326 ER PT J AU Camberg, JL Hoskins, JR Wickner, S AF Camberg, Jodi L. Hoskins, Joel R. Wickner, Sue TI ClpXP modulates cell division in E. coli by a mechanism that involves ATP-dependent degradation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Camberg, Jodi L.; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402655 ER PT J AU Cameron, H AF Cameron, Heather TI Maturation and function of new neurons in the adult hippocampus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cameron, Heather] NIMH, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401731 ER PT J AU Cao, Z Maul, R Gearhart, P AF Cao, Zheng Maul, Robert Gearhart, Patricia TI Transcription-dependent AID targeting to immunoglobulin variable regions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cao, Zheng; Maul, Robert; Gearhart, Patricia] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402599 ER PT J AU Carlson, BA Patterson, AD Yoo, MH Conrad, M Gonzalez, FJ Hatfield, DL AF Carlson, Bradley A. Patterson, Andrew D. Yoo, Min-Hyuk Conrad, Marcus Gonzalez, Frank J. Hatfield, Dolph L. TI The thioredoxin reductase system is a critical factor in mediating acetaminophen-induced liver damage SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Hatfield, Dolph L.] MBSS LCP, Bethesda, MD USA. [Patterson, Andrew D.; Gonzalez, Frank J.] NCI NIH, LM CCR, Bethesda, MD USA. [Conrad, Marcus] Helmholtz Zentrum Munchen, Inst Clin Mol Biol & Tumor Genet, Munich, Germany. RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400015 ER PT J AU Chan, CCW Moser, JM Dyer, KD Rosenberg, HF AF Chan, Calvin Chuen-Wing Moser, Jennifer M. Dyer, Kimberly D. Rosenberg, Helene F. TI Antimicrobial RNases: genetic diversity and novel structure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chan, Calvin Chuen-Wing; Dyer, Kimberly D.; Rosenberg, Helene F.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. [Moser, Jennifer M.] Dept Vet Affairs, Genome Med Program, Washington Dc, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402304 ER PT J AU Chan, PYS von Leupoldt, A Bradley, MM Lang, PJ Davenport, PW AF Chan, Pei-Ying Sarah von Leupoldt, Andreas Bradley, Margret M. Lang, Peter J. Davenport, Paul W. TI The effect of anxiety on respiratory sensory gating measured by the respiratory related evoked potential (RREP) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chan, Pei-Ying Sarah] Chang Gung Univ, Tao Yuan, Taiwan. [Bradley, Margret M.; Lang, Peter J.] Univ Florida, NIMH, Gainesville, FL USA. [von Leupoldt, Andreas] Univ Hamburg, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401486 ER PT J AU Chattopadhyay, MK Fernandez, C Sharma, D McPhie, P Tabor, H AF Chattopadhyay, Manas Kumar Fernandez, Cristina Sharma, Deepak McPhie, Peter Tabor, Herbert TI Antizyme, an unusual regulatory protein: studies on the yeast antizyme-ornithine decarboxylase complex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chattopadhyay, Manas Kumar; Fernandez, Cristina; Sharma, Deepak; McPhie, Peter; Tabor, Herbert] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404794 ER PT J AU Chen, CY Chi, YH Starost, MF Stewart, CL Jeang, KT AF Chen, Chia-Yen Chi, Ya-Hui Starost, Matthew F. Stewart, Colin L. Jeang, Kuan-Teh TI Removal of Sun1 rescues loss-of-lamin A (Lmna(-/-)) associated dystrophic lethality SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chen, Chia-Yen; Jeang, Kuan-Teh] NIAID, NIH, Bethesda, MD 20892 USA. [Starost, Matthew F.] NIH, DVR, Bethesda, MD 20892 USA. [Chi, Ya-Hui] Natl Hlth Res Inst, Inst Cellular & Syst Med, Zhunan, Taiwan. [Stewart, Colin L.] Inst Med Biol, Singapore, Singapore. RI Chi, Ya-Hui/B-1080-2010 NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404629 ER PT J AU Cheng, J Chen, C Gonzalez, FJ AF Cheng, Jie Chen, Chi Gonzalez, Frank J. TI Identification of 2-Piperidone as a Biomarker of CYP2E1 Activity through Metabolomic Phenotyping SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cheng, Jie; Gonzalez, Frank J.] NIH, Bethesda, MD 20892 USA. [Chen, Chi] Univ Minnesota, Dept Food Sci & Nutr, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405484 ER PT J AU Cheon, Y Kim, HW Igarashi, M Modi, HR Chang, L Ma, KZ Greenstein, D Wohltmann, M Turk, J Rapoport, SI Taha, AM AF Cheon, Yewon Kim, Hyung-Wook Igarashi, Miki Modi, Hiren R. Chang, Lisa Ma, Kaizong Greenstein, Deanna Wohltmann, Mary Turk, John Rapoport, Stanley I. Taha, Ameer M. TI Reduced docosahexaenoic acid metabolism and concentration in brain phospholipids of calcium-independent phospholipase A2 VIA (iPLA2 beta) - knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cheon, Yewon; Kim, Hyung-Wook; Igarashi, Miki; Modi, Hiren R.; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.; Taha, Ameer M.] NIA, BPMS, Bethesda, MD 20892 USA. [Greenstein, Deanna] NIMH, NIH, Bethesda, MD 20892 USA. [Wohltmann, Mary; Turk, John] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403094 ER PT J AU Chess, DJ Balaban, RS AF Chess, David J. Balaban, Robert S. TI Simultaneous Monitoring of Oxidative Phosphorylation Chromophores: Regulation of State 3 Crossover in Complex III SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chess, David J.; Balaban, Robert S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404660 ER PT J AU Chiu, CT Chuang, DM AF Chiu, Chi-Tso Chuang, De-Maw TI Combinatory treatment with mood stabilizers lithium and valproate produces multiple beneficial effects in transgenic mouse models of Huntington's disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chiu, Chi-Tso; Chuang, De-Maw] NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400109 ER PT J AU Chong, L Sankavaram, K Freake, HC AF Chong, Leelyn Sankavaram, Kavitha Freake, Hedley C. TI LIV-1 regulates zinc uptake and E-cadherin (CDH1) expression in MDA-MB-231 breast cancer cells but does not influence SNAI1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chong, Leelyn; Freake, Hedley C.] Univ Connecticut, Storrs, CT USA. [Sankavaram, Kavitha] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406912 ER PT J AU Chou, CL Agrawal, P Knepper, MA AF Chou, C. L. Agrawal, P. Knepper, M. A. TI Slc14a2 urea transporters UT-A1 and UT-A3 coexist in a high molecular weight complex in rat inner medullary collecting duct (IMCD) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chou, C. L.; Agrawal, P.; Knepper, M. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405883 ER PT J AU Chung, YW Chen, Y Gucek, M Murphy, E Manganiello, V AF Chung, Youn Wook Chen, Yong Gucek, Marjan Murphy, Elizabeth Manganiello, Vincent TI Targeted disruption of Pde3b, but not Pde3a, protects murine heart from ischemia/reperfusion injury: Proteomic approaches to possible mechanisms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chung, Youn Wook; Manganiello, Vincent] NHLBI, CPB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406726 ER PT J AU Cline, SD Marnett, LJ Copeland, WC AF Cline, Susan D. Marnett, Lawrence J. Copeland, William C. TI Disruption of mitochondrial DNA polymerase gamma replication by the aldehyde adduct of DNA, M1dG SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cline, Susan D.] Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. [Marnett, Lawrence J.] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37212 USA. [Copeland, William C.] NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406304 ER PT J AU Collins, FS AF Collins, Francis S. TI NIH and the Biomedical Research Community: Opportunities and Concerns SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Collins, Francis S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401777 ER PT J AU Conroy, JL Hazelwood, LA Free, RB Roof, RA Furman, CA Titus, SA Southall, N Ferrer, M Sibley, DR AF Conroy, Jennie L. Hazelwood, Lisa A. Free, R. Benjamin Roof, Rebecca A. Furman, Cheryse A. Titus, Steven A. Southall, Noel Ferrer, Marc Sibley, David R. TI High-Throughput Screening for Novel Modulators of the D-1 Dopamine Receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Conroy, Jennie L.; Hazelwood, Lisa A.; Free, R. Benjamin; Roof, Rebecca A.; Furman, Cheryse A.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. [Titus, Steven A.; Southall, Noel; Ferrer, Marc] NIH, NIH Chem Genom Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405393 ER PT J AU Cozzi, NV Daley, PF Evans, DL Partilla, JS Rothman, RB Ruoho, AE Baumann, MH AF Cozzi, Nicholas V. Daley, Paul F. Evans, Darin L. Partilla, John S. Rothman, Richard B. Ruoho, Arnold E. Baumann, Michael H. TI Trifluoromethyl ring-substituted methcathinone analogs: activity at monoamine uptake transporters SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Cozzi, Nicholas V.; Ruoho, Arnold E.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Daley, Paul F.] Calif Pacific Med Ctr, Res Inst, Addict Pharmacol Res Lab, San Francisco, CA USA. [Partilla, John S.; Rothman, Richard B.; Baumann, Michael H.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Baltimore, MD USA. [Evans, Darin L.] PhysioGenix, Wauwatosa, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401111 ER PT J AU Csiszar, A Bagi, Z Feher, A Recchia, FA Sonntag, WE Ungvari, Z Pearson, K de Cabo, R AF Csiszar, Anna Bagi, Zsolt Feher, Attila Recchia, Fabio A. Sonntag, W. E. Ungvari, Zoltan Pearson, Kevin de Cabo, Rafael TI Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Csiszar, Anna; Sonntag, W. E.; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA. [Bagi, Zsolt; Feher, Attila; Recchia, Fabio A.] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. [Pearson, Kevin; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401250 ER PT J AU Csiszar, A Bailey-Downs, L Guatam, T Zhang, CH Sonntag, WE Ungvari, Z Pearson, K de Cabo, R AF Csiszar, Anna Bailey-Downs, Lora Guatam, Tripti Zhang, Cuihua Sonntag, W. E. Ungvari, Zoltan Pearson, Kevin de Cabo, Rafael TI Adaptive induction of NF-E2-Related Factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Csiszar, Anna; Bailey-Downs, Lora; Guatam, Tripti; Sonntag, W. E.; Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA. [Zhang, Cuihua] Univ Missouri, Dept Physiol, Columbia, MO 65212 USA. [Pearson, Kevin; de Cabo, Rafael] NIA, Lab Expt Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401249 ER PT J AU Currington, R Justinova, Z Ladenheim, B Goldberg, SR Krasnova, IN Cadet, JL AF Currington, Rashalai Justinova, Zuzana Ladenheim, Bruce Goldberg, Steven R. Krasnova, Irina N. Cadet, Jean Lud TI Methamphetamine Self-Administration is Associated with Changes in the Expression of Glutamate AMPA Receptors in the Rat Striatum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Currington, Rashalai] Univ Maryland Eastern Shore, Princess Anne, MD USA. [Justinova, Zuzana; Goldberg, Steven R.] Natl Inst Drug Abuse, Behav Neurosci Res Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406088 ER PT J AU Daniel, CR Cross, AJ Park, Y Hollenbeck, AR Schatzkin, A Sinha, R AF Daniel, Carrie Rose Cross, Amanda J. Park, Yikyung Hollenbeck, Albert R. Schatzkin, Arthur Sinha, Rashmi TI Intake of poultry and fish and risk of cancer in the NIH-AARP Diet and Health Study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Daniel, Carrie Rose; Cross, Amanda J.; Park, Yikyung; Schatzkin, Arthur; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Hollenbeck, Albert R.] AARP, Washington, DC USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402120 ER PT J AU Das, S Bagorda, A Rericha, E Parent, C AF Das, Satarupa Bagorda, Anna Rericha, Erin Parent, Carole TI cAMP signal relay and streaming during Dictyostelium development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Das, Satarupa; Bagorda, Anna; Parent, Carole] NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. [Rericha, Erin] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406556 ER PT J AU David, A Hickman, H Strader, MB Monaco, MC Bennink, JR Yewdell, JW AF David, Alexandre Hickman, Heather Strader, Michael Brad Monaco, Maria Chiara Bennink, Jack R. Yewdell, Jonathan W. TI RiboPuromycylation Method (RPM): A New Technique for Visualizing Active Cellular Translation Sites and Exploring Translation Compartmentalization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [David, Alexandre; Hickman, Heather; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, NIH, Bethesda, MD 20892 USA. [Strader, Michael Brad] NIMH, NIH, Bethesda, MD 20892 USA. [Monaco, Maria Chiara] NINDS, NIH, Bethesda, MD 20892 USA. RI David, Alexandre/B-2447-2013 OI David, Alexandre/0000-0003-3365-1339 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402675 ER PT J AU Davidoff, K Soule, E Daniels, S Davis, D Yarchoan, R AF Davidoff, Katharine Soule, Erin Daniels, Sarah Davis, David Yarchoan, Robert TI Evaluating the potency of HIV-1 protease inhibitors in blocking the initial step of HIV gagpol processing SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Davidoff, Katharine; Soule, Erin; Daniels, Sarah; Davis, David; Yarchoan, Robert] NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402668 ER PT J AU Deckman, KH Dempster, K Khalsa, A David, V O'Brien, SJ Narfstrom, K Menotti-Raymond, M AF Deckman, Koren Holland Dempster, Katrina Khalsa, Amrit David, Victor O'Brien, Stephen J. Narfstroem, Kristina Menotti-Raymond, Marilyn TI Analysis of CRX Protein Profile in the Rdy Cat Model Suggests Molecular Mechanism of Pathology SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Deckman, Koren Holland; Dempster, Katrina; Khalsa, Amrit] Gettysburg Coll, Gettysburg, PA 17325 USA. [David, Victor; O'Brien, Stephen J.; Menotti-Raymond, Marilyn] NCI, Lab Genom Div, Frederick, MD 21701 USA. [Narfstroem, Kristina] Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406521 ER PT J AU DellaValle, DM Haas, JD AF DellaValle, Diane M. Haas, Jere D. TI Iron supplementation improves lactate response and energetic (work) efficiency after training in non-anemic female rowers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [DellaValle, Diane M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [DellaValle, Diane M.; Haas, Jere D.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401940 ER PT J AU Dickherber, A Myers, K Sawyer, S Vaught, J Compton, C AF Dickherber, Anthony Myers, Kimberly Sawyer, Sherilyn Vaught, Jim Compton, Carolyn TI caHUB: The First US Public Biobank SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Dickherber, Anthony; Myers, Kimberly; Sawyer, Sherilyn; Vaught, Jim; Compton, Carolyn] NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405299 ER PT J AU Ding, YF Ding, M Graham, S Akopova, I Muallem, S Birnbaumer, L Ma, R AF Ding, Yanfeng Ding, Min Graham, Sarabeth Akopova, Irina Muallem, Shmuel Birnbaumer, Lutz Ma, Rong TI Reactive Oxygen Species (ROS) mediate agonist-induced TRPC6 activation in vascular smooth muscle cells (VSMCS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Akopova, Irina] Univ N Texas Hlth Sci Ctr, Ctr Commercializat Fluorescence Technol, Ft Worth, TX USA. [Muallem, Shmuel] NIH, Bethesda, MD 20892 USA. [Birnbaumer, Lutz] NIH, Transmembrane Signaling Grp, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403733 ER PT J AU Dmitrieva, NI Cui, KR Zhao, KJ Burg, MB AF Dmitrieva, Natalia I. Cui, Kairong Zhao, Keji Burg, Maurice B. TI DNA double-strand breaks induced by high NaCl occur predominantly in gene deserts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Dmitrieva, Natalia I.; Cui, Kairong; Zhao, Keji; Burg, Maurice B.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406318 ER PT J AU Dmitrieva, NI Burg, MB AF Dmitrieva, Natalia I. Burg, Maurice B. TI Increased insensible water loss contributes to the aging related disturbance of water balance SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Dmitrieva, Natalia I.; Burg, Maurice B.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401078 ER PT J AU Dong, LH Wang, SB Tropea, M Ferreyra, GA Danner, R AF Dong, Lihua Wang, Shuibang Tropea, Margaret Ferreyra, Gabriela A. Danner, Robert TI Like Glucocorticoids (GCs), Mineralocorticoids (MCs) Inhibit Activation-induced Apoptosis and Cytokine Production in Human Peripheral Blood T Lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Dong, Lihua; Wang, Shuibang; Tropea, Margaret; Ferreyra, Gabriela A.; Danner, Robert] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406760 ER PT J AU Dougherty, EJ Guo, CH Ong, KM Chow, CC Simons, SS AF Dougherty, Edward John Guo, Chunhua Ong, Karen M. Chow, Carson C. Simons, S. Stoney, Jr. TI Temporal ordering of SMRT and TIF2 function in steroid-regulated gene transcription SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Dougherty, Edward John; Guo, Chunhua; Simons, S. Stoney, Jr.] NIDDK, CEB, NIH, Bethesda, MD USA. [Ong, Karen M.; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RI Guo, Chunhua/N-2586-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404450 ER PT J AU Douglass, J Gunaratne, R Pisitkun, T Hoffert, J Knepper, M AF Douglass, Jacqueline Gunaratne, Ruwan Pisitkun, Trairak Hoffert, Jason Knepper, Mark TI Determining consensus substrate motifs for protein kinases using mass spectrometry: Protein Kinase A SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Douglass, Jacqueline; Gunaratne, Ruwan; Pisitkun, Trairak; Hoffert, Jason; Knepper, Mark] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404603 ER PT J AU Doyle, SM Hoskins, JR Wickner, S AF Doyle, Shannon M. Hoskins, Joel R. Wickner, Sue TI Influence of the DnaK chaperone system on ClpB-substrate interactions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Doyle, Shannon M.; Hoskins, Joel R.; Wickner, Sue] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406396 ER PT J AU Eiden, LE Stroth, N Holighaus, Y Samal, B Ait-Ali, D AF Eiden, Lee E. Stroth, Nikolas Holighaus, Yvonne Samal, Babru Ait-Ali, Djida TI Microarray-based analysis of the 'stress transcriptome': application to gene discovery and therapeutics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Eiden, Lee E.; Stroth, Nikolas; Holighaus, Yvonne; Samal, Babru; Ait-Ali, Djida] NIMH, Mol Neurosci Sect, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401199 ER PT J AU Engel, JS Thomas, PR Bailey, RL Thurn, AL AF Engel, Jody S. Thomas, Paul R. Bailey, Regan L. Thurn, Anne L. TI MyDS: A Mobile Application to Track Dietary Supplement Use SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Engel, Jody S.; Thomas, Paul R.; Bailey, Regan L.; Thurn, Anne L.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402177 ER PT J AU Erinosho, TO Berrigan, D Thompson, FE Moser, RP Nebeling, LC Yaroch, AL AF Erinosho, Temitope O. Berrigan, David Thompson, Frances E. Moser, Richard P. Nebeling, Linda C. Yaroch, Amy L. TI Dietary intake of preschool-aged children in relation to caregivers' race/ethnicity, demographic characteristics, and acculturation: The 2007 California Health Interview Survey SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Erinosho, Temitope O.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Erinosho, Temitope O.] Univ N Carolina, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA. [Berrigan, David; Thompson, Frances E.; Moser, Richard P.; Nebeling, Linda C.] US Natl Canc Inst, Rockville, MD USA. [Yaroch, Amy L.] Ctr Human Nutr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404932 ER PT J AU Fanning, AS Van Itallie, C Anderson, JM AF Fanning, Alan S. Van Itallie, Christina Anderson, James Melvin TI Zonula Occludins (ZO)-1 and-2 Regulate Apical Morphogenesis and Zonula Adherens (ZA) Assembly in Polarized MDCK cells. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Fanning, Alan S.] Univ N Carolina, Chapel Hill, NC USA. [Van Itallie, Christina; Anderson, James Melvin] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401949 ER PT J AU Fei, G Igarashi, M Taha, A Rapoport, SI AF Fei Gao Igarashi, Miki Taha, Ameer Rapoport, Stanley I. TI Decreased liver synthesis-secretion of esterified docosahexaenoic acid (DHA) from circulating unesterified alpha-linolenic acid in aging rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Fei Gao; Taha, Ameer; Rapoport, Stanley I.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402210 ER PT J AU Finckbeiner, SM Ko, PJ Bishop, K Sood, R Gross, K Dolnick, B Sufrin, J Liu, P AF Finckbeiner, Steven Michael Ko, Pin-Joe Bishop, Kevin Sood, Raman Gross, Kenneth Dolnick, Bruce Sufrin, Janice Liu, Paul TI Zebrafish as a vertebrate model of ENOSF1 function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Finckbeiner, Steven Michael; Ko, Pin-Joe; Bishop, Kevin; Sood, Raman; Liu, Paul] NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. [Gross, Kenneth; Dolnick, Bruce; Sufrin, Janice] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402472 ER PT J AU Free, RB Roof, RA Conroy, JL Furman, CA Titus, SA Southall, N Ferrer, M Han, Y Javitch, JA Sibley, DR AF Free, R. Benjamin Roof, Rebecca A. Conroy, Jennie L. Furman, Cheryse A. Titus, Steven A. Southall, Noel Ferrer, Marc Han, Yang Javitch, Jonathan A. Sibley, David R. TI High-Throughput Screening for Allosteric Modulators of the D-2 Dopamine Receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Free, R. Benjamin; Roof, Rebecca A.; Conroy, Jennie L.; Furman, Cheryse A.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. [Titus, Steven A.; Southall, Noel; Ferrer, Marc] NIH, NIH Chem Genom Ctr, Rockville, MD USA. [Han, Yang; Javitch, Jonathan A.] Columbia Univ, Ctr Mol Recognit, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405391 ER PT J AU Furman, CA Free, RB Roof, RA Conroy, JL Titus, SA Southall, N Sibley, DR AF Furman, Cheryse A. Free, R. Benjamin Roof, Rebecca A. Conroy, Jennie L. Titus, Steven A. Southall, Noel Sibley, David R. TI High-Throughput Screening for Novel Modulators of the D-3 Dopamine Receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Furman, Cheryse A.; Free, R. Benjamin; Roof, Rebecca A.; Conroy, Jennie L.; Sibley, David R.] NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. [Titus, Steven A.; Southall, Noel] NIH, NIH Chem Genom Ctr, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405392 ER PT J AU Gegonne, A Zhang, JH Wu, G Zhu, JJ Hanson, J Cultraro, C Guinter, T Yang, ZH Hathcock, K Singer, A Rodriguez-Canales, J Tessarollo, L Mackem, S Meerzaman, D Buetow, K Singer, DS AF Gegonne, Anne Zhang, Jinghui Wu, Gang Zhu, Jianjian Hanson, Jeffrey Cultraro, Constance Guinter, Terry Yang, Zhihui Hathcock, Karen Singer, Alfred Rodriguez-Canales, Jaime Tessarollo, Lino Mackem, Susan Meerzaman, Daoud Buetow, Ken Singer, Dinah S. TI TAF7 is essential for early embryonic mouse development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Gegonne, Anne] NCI, EIB, NIH, Bethesda, MD 20892 USA. [Zhang, Jinghui] NCI, Lab Populat Genet 2, NIH, Bethesda, MD 20892 USA. [Wu, Gang; Cultraro, Constance; Yang, Zhihui; Buetow, Ken] NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. [Hanson, Jeffrey; Rodriguez-Canales, Jaime] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Guinter, Terry; Singer, Alfred; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. [Zhu, Jianjian; Mackem, Susan] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21701 USA. [Tessarollo, Lino] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402601 ER PT J AU Geng, H Hsieh, P AF Geng, Hui Hsieh, Peggy TI In vitro studies of MutSalpha protein in mismatch excision repair and DNA damage signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Geng, Hui; Hsieh, Peggy] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402571 ER PT J AU Giles, KE Lefevre, G Felsenfeld, G AF Giles, Keith E. Lefevre, Gaelle Felsenfeld, Gary TI An analysis of the epigenetic basis of Argonaute 2 function at DNA repetitive sequences in human cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Giles, Keith E.; Lefevre, Gaelle; Felsenfeld, Gary] NIDDK, LMB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406334 ER PT J AU Glancy, B Balaban, RS AF Glancy, Brian Balaban, Robert S. TI Mitochondrial Contribution to Energetic Homeostasis in Skeletal Muscle: Role of Calcium and Fiber Type SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Glancy, Brian; Balaban, Robert S.] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400736 ER PT J AU Gottesman, MM Hall, MD Handley, M Goldsborough, A Fung, A Gillet, JP AF Gottesman, Michael M. Hall, Matthew D. Handley, Misty Goldsborough, Andrew Fung, Andy Gillet, Jean-Pierre TI What have we learned about multidrug resistance in cancer? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Gottesman, Michael M.; Hall, Matthew D.; Handley, Misty; Goldsborough, Andrew; Fung, Andy; Gillet, Jean-Pierre] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402050 ER PT J AU Gottesman, S De Lay, N AF Gottesman, Susan De Lay, Nicholas TI Hfq-dependent sRNAs: Mechanism of action and Physiological Roles SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Gottesman, Susan; De Lay, Nicholas] NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404460 ER PT J AU Guirguis, E Hockman, S Manganiello, V AF Guirguis, Emilia Hockman, Steven Manganiello, Vincent TI Potential Role of PDE3B in Acquisition of Brown Fat Characteristic by White Adipose Tissue in Mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Guirguis, Emilia; Hockman, Steven; Manganiello, Vincent] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406484 ER PT J AU Guo, CH Dougherty, EJ Ong, KM Chow, CC Simons, SS AF Guo, Chunhua Dougherty, Edward J. Ong, Karen M. Chow, Carson C. Simons, S. Stoney, Jr. TI A mathematically-based method for ordering cofactor function in glucocorticoid receptor transactivation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Guo, Chunhua; Dougherty, Edward J.; Simons, S. Stoney, Jr.] NIDDK, CEB, NIH, Bethesda, MD USA. [Ong, Karen M.; Chow, Carson C.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. RI Guo, Chunhua/N-2586-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404453 ER PT J AU Guzman-Hernandez, ML Potter, G Kim, YJ Kiss, JZ Balla, T AF Guzman-Hernandez, Maria Luisa Potter, Gael Kim, Yeun J. Kiss, Jozsef Z. Balla, Tamas TI The intracellular trafficking and distribution of VEGF165 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Guzman-Hernandez, Maria Luisa; Kim, Yeun J.; Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA. [Potter, Gael; Kiss, Jozsef Z.] Univ Geneva, Dept Neurosci, Geneva, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404725 ER PT J AU Haines, DC Stern, S Hall, J Patri, A McNeil, S AF Haines, Diana C. Stern, Stephen Hall, Jennifer Patri, Anil McNeil, Scott TI Distribution of Intravenously Administered Gold Nanoparticles at the Light Microscope Level SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Haines, Diana C.] NCI, Pathol Histotechnol Lab, SAIC Frederick, Frederick, MD 21701 USA. [Stern, Stephen; Hall, Jennifer; Patri, Anil; McNeil, Scott] NCI, Nanotechnol Characterizat Lab, SAIC Frederick, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400072 ER PT J AU Hall, K AF Hall, Kevin TI The Calculus of Calories: Quantitative Physiology of Energy Metabolism and Body Weight Regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hall, Kevin] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404512 ER PT J AU Hegde, R AF Hegde, Ramanujan TI A ribosome-associating chaperone that facilitates membrane protein targeting SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hegde, Ramanujan] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405383 ER PT J AU Hiranita, T Tanda, G Soto, PL Kohut, SJ Kopajtic, TA Katz, JL AF Hiranita, Takato Tanda, Gianluigi Soto, Paul L. Kohut, Stephen J. Kopajtic, Theresa A. Katz, Jonathan L. TI Cocaine Self Administration Induces the Reinforcing Effects of the Selective sigma 1-Receptor Agonists SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hiranita, Takato; Tanda, Gianluigi; Soto, Paul L.; Kohut, Stephen J.; Kopajtic, Theresa A.; Katz, Jonathan L.] NIDA, NIH, US Dept HHS, Baltimore, MD USA. [Hiranita, Takato] NIH, Baltimore, MD USA. RI Tanda, Gianluigi/B-3318-2009; Hiranita, Takato/G-6567-2011 OI Tanda, Gianluigi/0000-0001-9526-9878; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403501 ER PT J AU Hoenerhoff, MJ Pandiri, A Lahousse, S Hong, HH Ton, TV Masinde, T Auerbach, S Bushel, P Shockley, K Peddada, S Sills, R AF Hoenerhoff, Mark James Pandiri, Arun Lahousse, Stephanie Hong, Hue-Hua (Lily) Ton, Thai-Vu (Kiki) Masinde, Tiwanda Auerbach, Scott Bushel, Pierre Shockley, Keith Peddada, Shyamal Sills, Robert TI Global gene expression profiling of spontaneous HCC in the B6C3F1 mouse identifies similarly dysregulated gene networks in mouse and humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hoenerhoff, Mark James; Pandiri, Arun; Lahousse, Stephanie; Hong, Hue-Hua (Lily); Ton, Thai-Vu (Kiki); Masinde, Tiwanda; Sills, Robert] NIEHS, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Auerbach, Scott] NIEHS, Biomol Screening Branch, NIH, Res Triangle Pk, NC 27709 USA. [Bushel, Pierre; Shockley, Keith; Peddada, Shyamal] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402414 ER PT J AU Hoffert, J Pisitkun, T Saeed, F Song, J Knepper, M AF Hoffert, Jason Pisitkun, T. Saeed, F. Song, J. Knepper, M. TI Large-scale iTRAQ-based quantification of phosphorylation changes during vasopressin signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hoffert, Jason; Pisitkun, T.; Saeed, F.; Song, J.; Knepper, M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400530 ER PT J AU Horvath, B Mukhopadhyay, P Rajesh, M Matsumoto, S Saito, K Batkai, S Gao, YR Cravatt, BF Hasko, G Pacher, P AF Horvath, Bela Mukhopadhyay, Partha Rajesh, Mohanraj Matsumoto, Shingo Saito, Keita Batkai, Sandor Gao, Yue R. Cravatt, Benjamin F. Hasko, Gyoergy Pacher, Pal TI Fatty acid amide hydrolase is a key regulator of the endocannabinoid-induced myocardial tissue injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Horvath, Bela; Mukhopadhyay, Partha; Rajesh, Mohanraj; Batkai, Sandor; Gao, Yue R.; Pacher, Pal] NIAAA, NIH, Bethesda, MD 20892 USA. [Matsumoto, Shingo; Saito, Keita] NCI, NIH, Bethesda, MD 92037 USA. [Cravatt, Benjamin F.] Scripps Res Inst, La Jolla, CA USA. [Hasko, Gyoergy] UMDNJ, Newark, NJ USA. RI Batkai, Sandor/H-7983-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400030 ER PT J AU Hu, JX Zhou, YR Thor, D Wang, Y McMillin, SM Costanzi, S Wess, J AF Hu, Jianxin Zhou, Yaru Thor, Doreen Wang, Yan McMillin, Sara M. Costanzi, Stefano Wess, Jurgen TI Identification of an intracellular surface involved in M3 muscarinic receptor dimerization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Hu, Jianxin; Zhou, Yaru; Thor, Doreen; Wang, Yan; McMillin, Sara M.; Wess, Jurgen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Costanzi, Stefano] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403568 ER PT J AU Huang, BX Kim, HY AF Huang, Bill X. Kim, Hee-Yong TI Identification of Akt-interacting proteins using on-beads cross-linking, co-immunoprecipitation and mass spectrometry SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Huang, Bill X.; Kim, Hee-Yong] NIAAA, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402774 ER PT J AU Iwamoto, T Ono, M Nakamura, T Yamada, A Yamada, Y Fukumoto, S AF Iwamoto, Tsutomu Ono, Mariko Nakamura, Takashi Yamada, Aya Yamada, Yoshihiko Fukumoto, Satoshi TI Expression and Functional Roles of Pannexin 3 in Odontoblast Proliferation and Differentiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Iwamoto, Tsutomu; Ono, Mariko; Nakamura, Takashi; Yamada, Aya; Fukumoto, Satoshi] Tohoku Univ, Grad Sch Dent, Div Pediat Dent, Sendai, Miyagi 980, Japan. [Yamada, Yoshihiko] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402859 ER PT J AU Izumi, Y Dmitrieva, N Ferraris, J Burg, M AF Izumi, Yuichiro Dmitrieva, Natalia Ferraris, Joan Burg, Maurice TI NFAT5 chromatin immunoprecipitation assay using NFAT5 knockdown cells as control SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Izumi, Yuichiro; Dmitrieva, Natalia; Ferraris, Joan; Burg, Maurice] NHLBI, LKEM, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404012 ER PT J AU Jain, S Guettier, JM Wess, J AF Jain, Shalini Guettier, Jean-Marc Wess, Juergen TI Beneficial metabolic effects of conditional activation of Gq signaling in pancreatic beta-cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Jain, Shalini; Guettier, Jean-Marc; Wess, Juergen] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402738 ER PT J AU Jang, H Arce, FT Ramachandran, S Capone, R Lal, R Nussinov, R AF Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Capone, Ricardo Lal, Ratnesh Nussinov, Ruth TI Modeling Transmembrane beta-Amyloid (A beta) Barrels of Alzheimer's Ion Channels SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Jang, Hyunbum; Nussinov, Ruth] NCI, Ctr Canc Res Nanobiol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Arce, Fernando Teran; Ramachandran, Srinivasan; Capone, Ricardo; Lal, Ratnesh] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404504 ER PT J AU Jayanthi, S McCoy, MT Ladenheim, B Martin, T Beauvais, G Krasnova, IN Hodges, AB AF Jayanthi, Subramaniam McCoy, Michael T. Ladenheim, Bruce Martin, Tracey Beauvais, Genevieve Krasnova, Irina N. Hodges, Amber B. TI Differential histone modifications induced by chronic methamphetamine exposure in the rat striatum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Jayanthi, Subramaniam; McCoy, Michael T.; Ladenheim, Bruce; Martin, Tracey; Beauvais, Genevieve; Krasnova, Irina N.; Hodges, Amber B.] NIDA, Mol Neuropsychiat Branch, Baltimore, MD USA. [Hodges, Amber B.] Morgan State Univ, Dept Psychol, Baltimore, MD 21239 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406351 ER PT J AU Johnston, D Doyle, SM Hoskins, JR Wickner, S AF Johnston, Danielle Doyle, Shannon M. Hoskins, Joel R. Wickner, Sue TI Substrate recognition by Clp/Hsp100 proteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Johnston, Danielle; Doyle, Shannon M.; Hoskins, Joel R.; Wickner, Sue] NIH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406397 ER PT J AU Jovic, M Szentpetery, Z Kean, M Gingras, AC Brill, J Balla, T AF Jovic, Marko Szentpetery, Zsofia Kean, Michelle Gingras, Anne-Claude Brill, Julie Balla, Tamas TI Distinct roles of two lipid kinases in lysosomal transport of the Gaucher disease enzyme glucocerebrosidase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Jovic, Marko; Szentpetery, Zsofia; Balla, Tamas] NICHHD, Bethesda, MD 20892 USA. [Kean, Michelle; Gingras, Anne-Claude] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Brill, Julie] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406567 ER PT J AU Justinova, Z Redhi, GH Goldberg, SR AF Justinova, Zuzana Redhi, Godfrey H. Goldberg, Steven R. TI The endocannabinoid 2-arachidonoylglycerol (2-AG) is intravenously self-administered by nonhuman primates SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Justinova, Zuzana; Redhi, Godfrey H.; Goldberg, Steven R.] NIDA, IRP, NIH, DHHS, Baltimore, MD USA. [Justinova, Zuzana] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405360 ER PT J AU Katakura, M Kim, HY AF Katakura, Masanori Kim, Hee-Yong TI Docosapentaenoic Acid Also Induces Neurogenesis in Cultured Neural Stem Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Katakura, Masanori; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402806 ER PT J AU Kaur, S Pendrak, ML Garfield, SH Roberts, DD AF Kaur, Sukhbir Pendrak, Michael L. Garfield, Susan H. Roberts, David D. TI Thrombospndin 1 accelerates VEGFR2 trafficking and directs towards lysosomes for degradation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kaur, Sukhbir; Pendrak, Michael L.; Roberts, David D.] NIH, Pathol Lab, Bethesda, MD 20892 USA. [Garfield, Susan H.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401204 ER PT J AU Kellom, M Basselin, M Chen, M Rapoport, SI Rao, JS AF Kellom, Matthew Basselin, Mireille Chen, Mei Rapoport, Stanley I. Rao, Jagadeesh S. TI Increased Neuroinflammatory and Arachidonic Acid Cascade Markers with Synaptic Marker Loss in Lipopolysaccharide Infused Rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kellom, Matthew; Basselin, Mireille; Chen, Mei; Rapoport, Stanley I.; Rao, Jagadeesh S.] NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403926 ER PT J AU Khan, F Park, SJ Chung, J Manganiello, V AF Khan, Faiyaz Park, Sung-Jun Chung, Jay Manganiello, Vincent TI Some effects of resveratrol and SRT1720 on PKA-signaling and AMP-kinase in adipocytes may be related to inhibition of Cyclic Nucleotide Phosphodiesterases (PDEs) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Khan, Faiyaz; Manganiello, Vincent] NHLBI, CPB, NIH, Bethesda, MD 20892 USA. [Park, Sung-Jun; Chung, Jay] NHLBI, GDBC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406438 ER PT J AU Kim, HY Huang, B Akbar, M Kevala, K AF Kim, Hee-Yong Huang, Bill Akbar, Mohammed Kevala, Karl TI Phosphatidylserine is a critical modulator for Akt activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kim, Hee-Yong; Huang, Bill; Akbar, Mohammed; Kevala, Karl] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402682 ER PT J AU Kim, YJ Balla, T AF Kim, Yeun Ju Balla, Tamas TI Studying the distribution of phosphatidylinositol and its roles in maintaining organelle structure and signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kim, Yeun Ju; Balla, Tamas] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402799 ER PT J AU Kimura, AK Kim, HY AF Kimura, Atsuko Kakio Kim, Hee-Yong TI Purification, reconstitution and characterization of Phosphatidylserine Synthase 2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kimura, Atsuko Kakio; Kim, Hee-Yong] NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404480 ER PT J AU Kirkpatrick, SI Krebs-Smith, SM Dodd, KW Reedy, J AF Kirkpatrick, Sharon I. Krebs-Smith, Susan M. Dodd, Kevin W. Reedy, Jill TI Income and race/ethnicity: drivers of adherence to dietary guidance among the US population SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kirkpatrick, Sharon I.; Krebs-Smith, Susan M.; Reedy, Jill] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Dodd, Kevin W.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404941 ER PT J AU Kirkpatrick, SI Tarasuk, V Dodd, KW Garriguet, D AF Kirkpatrick, Sharon I. Tarasuk, Valerie Dodd, Kevin W. Garriguet, Didier TI Nutritional vulnerability among adults and children in food-insecure households: a Canada-US comparison SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kirkpatrick, Sharon I.; Dodd, Kevin W.] NCI, Bethesda, MD 20892 USA. [Tarasuk, Valerie] Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada. [Garriguet, Didier] STAT Canada, Hlth Anal Div, Ottawa, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401873 ER PT J AU Klase, ZA Jeang, KT AF Klase, Zachary Alan Jeang, Kuan-Teh TI HIV-1 Env can pseudotype HTLV-I and provide envelope-mediated protection against super-infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Klase, Zachary Alan; Jeang, Kuan-Teh] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406742 ER PT J AU Kochukov, MY Noel, RC Abramowitz, J Birnbaumer, L Marrelli, SP AF Kochukov, Mikhail Y. Noel, Rebecca C. Abramowitz, Joel Birnbaumer, Lutz Marrelli, Sean P. TI Endothelial TRPC1 and TRPC3 channels contribute to ATP-mediated relaxation in mouse cerebral arteries SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kochukov, Mikhail Y.; Noel, Rebecca C.; Marrelli, Sean P.] Baylor Coll Med, Houston, TX 77030 USA. [Abramowitz, Joel; Birnbaumer, Lutz] Inst Environm Hlth Sci, Lab Neurobiol, Div Intramural Res, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400281 ER PT J AU Koek, W France, CP Cheng, KJ Rice, KC AF Koek, Wouter France, Charles P. Cheng, Kejun Rice, Kenner C. TI Effects of positive GABA-B receptor modulators in pigeons trained to discriminate baclofen or gamma-hydroxybutyrate (GHB) from saline SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Koek, Wouter; France, Charles P.] UTHSCSA, San Antonio, TX 20892 USA. [Cheng, Kejun; Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD USA. [Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405348 ER PT J AU Kohr, MJ Sun, JH Aponte, A Wang, GH Gucek, M Murphy, E Steenbergen, C AF Kohr, Mark Jeffrey Sun, Junhui Aponte, Angel Wang, Guanghui Gucek, Marjan Murphy, Elizabeth Steenbergen, Charles TI Identification of potential S-nitrosylation sites in the myocardium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kohr, Mark Jeffrey; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. [Kohr, Mark Jeffrey; Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA. [Aponte, Angel; Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401265 ER PT J AU Kortum, RL Sommers, CL Alexander, CP Pinski, JM Nath, NN Grinberg, A Love, PE Samelson, LE AF Kortum, Robert L. Sommers, Connie L. Alexander, Clayton P. Pinski, John M. Nath, Nandan N. Grinberg, Alexander Love, Paul E. Samelson, Lawrence E. TI Conditional deletion reveals a role for Sos1 in pre-TCR signaling and thymocyte development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kortum, Robert L.; Sommers, Connie L.; Alexander, Clayton P.; Pinski, John M.; Nath, Nandan N.; Samelson, Lawrence E.] NCI, LCMB, CCR, Bethesda, MD 20892 USA. [Grinberg, Alexander; Love, Paul E.] NICHD, SCDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402897 ER PT J AU Korzeniowski, MK Manjarres, IM Varnai, P Balla, T AF Korzeniowski, Marek Krzysztof Martin Manjarres, Isabel Varnai, Peter Balla, Tamas TI Activation of STIM1-Orai1 involves an intramolecular switching mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Korzeniowski, Marek Krzysztof; Balla, Tamas] NICHD, NIH, Bethesda, MD USA. [Martin Manjarres, Isabel] Univ Valladolid, IBGM, Valladolid, Spain. [Varnai, Peter] Semmelweis Univ, Dept Physiol, H-1085 Budapest, Hungary. RI Korzeniowski, Marek/G-7214-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406709 ER PT J AU Krasnova, IN Chiflikyan, M Justinova, Z Ladenheim, B McCoy, MT Wood, WH Becker, KG Goldberg, SR Cadet, JL AF Krasnova, Irina N. Chiflikyan, Margarit Justinova, Zuzana Ladenheim, Bruce McCoy, Michael T. Wood, William H. Becker, Kevin G. Goldberg, Steven R. Cadet, Jean Lud TI Methamphetamine self-administration alters gene expression in the rat striatum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Krasnova, Irina N.; Chiflikyan, Margarit; Justinova, Zuzana; Ladenheim, Bruce; McCoy, Michael T.; Goldberg, Steven R.; Cadet, Jean Lud] NIDA, NIH, DHHS, Baltimore, MD USA. [Wood, William H.; Becker, Kevin G.] NIA, NIH, DHHS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400100 ER PT J AU Krivega, I Dean, A AF Krivega, Ivan Dean, Ann TI Homodimerization of LDB1 is necessary for activation of the mouse beta-globin gene in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Krivega, Ivan; Dean, Ann] NIDDK, LCDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406339 ER PT J AU Kumari, D Biacsi, RE Usdin, K AF Kumari, Daman Biacsi, Rea Erika Usdin, Karen TI Repeat expansion in intron 1 of the Frataxin gene reduces transcription initiation in Friedreich ataxia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kumari, Daman; Biacsi, Rea Erika; Usdin, Karen] NIDDK, LMCB, NIH, Bethesda, MD USA. [Biacsi, Rea Erika] Cent Hungarian Reg Inst Natl Publ Hlth, Lab Publ Hlth Biol, Budapest, Hungary. [Biacsi, Rea Erika] Med Officers Serv, Budapest, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406345 ER PT J AU Kunduri, SS Nayeem, MA Ponnoth, DS Tilley, SS Schnermann, J Mustafa, SJ AF Kunduri, Swati S. Nayeem, Mohammed A. Ponnoth, Dovenia S. Tilley, Stephen S. Schnermann, Jurgen Mustafa, S. Jamal TI omega-hydroxylase modulates adenosine A(1) receptor-induced vascular tone SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Kunduri, Swati S.; Nayeem, Mohammed A.; Ponnoth, Dovenia S.; Mustafa, S. Jamal] W Virginia Univ, Morgantown, WV 26506 USA. [Tilley, Stephen S.] Univ N Carolina, Chapel Hill, NC USA. [Schnermann, Jurgen] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401536 ER PT J AU Lakatta, EG AF Lakatta, Edward G. TI Arterial Aging: A Journey Into Subclinical Arterial Disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403594 ER PT J AU Lee, J Song, SH Dean, A AF Lee, JongJoo Song, Sang-Hyun Dean, Ann TI Complex regulation of a carbonic anhydrase gene cluster SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lee, JongJoo; Song, Sang-Hyun; Dean, Ann] NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406340 ER PT J AU Lee, TL Xiao, A Chan, WY Rennert, OM AF Lee, Tin-Lap Xiao, Amy Chan, Wai-Yee Rennert, Owen M. TI Identification of novel long non-coding RNA candidates in male germ cell development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lee, Tin-Lap; Xiao, Amy; Chan, Wai-Yee; Rennert, Owen M.] NICHD, Lab Clin & Dev Genom, Natt Inst Hlth, Bethesda, MD USA. [Lee, Tin-Lap; Chan, Wai-Yee] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China. RI Lee, Tin-Lap/A-7853-2009 OI Lee, Tin-Lap/0000-0002-6654-0988 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406513 ER PT J AU Levine, B Orvedahl, A Sumpter, R Xiao, GH Ng, A Zou, ZJ Tang, Y Zhang, YE Luby-Phelps, K Xavier, R Xie, Y AF Levine, Beth Orvedahl, Anthony Sumpter, Rhea Xiao, Guanghua Ng, Aylwin Zou, Zhongju Tang, Yi Zhang, Ying E. Luby-Phelps, Kate Xavier, Ramnik Xie, Yang TI Image-Based Genome Wide siRNA Screen Identifies Host Factors Involved in Selective Autophagy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Levine, Beth; Orvedahl, Anthony; Sumpter, Rhea; Xiao, Guanghua; Zou, Zhongju; Luby-Phelps, Kate; Xie, Yang] UT SW Med Ctr, Dallas, TX USA. [Levine, Beth] Univ Texas Dallas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX USA. [Ng, Aylwin] Harvard Univ, Sch Med, Boston, MA USA. [Tang, Yi; Zhang, Ying E.; Xavier, Ramnik] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402363 ER PT J AU Li, CC Kuo, JC Kiyama, R Moss, J Vaughan, M AF Li, Chun-Chun Kuo, Jean-Cheng Kiyama, Ryoiti Moss, Joel Vaughan, Martha TI Effects of BIG1 and KANK1 on cell polarity and directed migration during wound healing SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Li, Chun-Chun; Moss, Joel; Vaughan, Martha] NIH, Cardiovasc Pulm Branch, Bethesda, MD 20892 USA. [Kuo, Jean-Cheng] NIH, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Kiyama, Ryoiti] Inst Adv Ind Sci & Technol, Biomed Res Inst, Signaling Mol Res Grp, Tsukuba, Ibaraki, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406548 ER PT J AU Lin, YH Strandjord, S Loewke, JD Hyun, DY Leazer, J Hibbeln, JR AF Lin, Yu Hong Strandjord, Sarah Loewke, James D. Hyun, Duk Y. Leazer, Jay Hibbeln, Joseph R. TI Direct, rapid, and efficient transesterification of total lipids in human serum by microwave irradiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lin, Yu Hong; Strandjord, Sarah; Loewke, James D.; Hyun, Duk Y.; Hibbeln, Joseph R.] NIH, Bethesda, MD 20892 USA. [Leazer, Jay] CEM Corp, Matthews, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402778 ER PT J AU Lindgren, JA Miller, P DuBrock, C Manni, A Hartman, TJ Mitchell, DC AF Lindgren, Jessica A. Miller, Paige DuBrock, Cynthia Manni, Andrea Hartman, Terryl J. Mitchell, Diane C. TI The role of diet and physical activity in breast cancer prevention SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lindgren, Jessica A.; Hartman, Terryl J.; Mitchell, Diane C.] Penn State Univ, University Pk, PA 16802 USA. [Miller, Paige] NCI, Bethesda, MD 20892 USA. [DuBrock, Cynthia; Manni, Andrea] Penn State Hershey Canc Inst, Hershey, PA USA. [Manni, Andrea] Penn State Coll Med, Div Endocrinol Diabet & Metab, Hershey, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404896 ER PT J AU Lipsky, L Nansel, T Haynie, D AF Lipsky, Leah Nansel, Tonja Haynie, Denise TI Development and validation of an interpretable measure of dietary intake of whole plant foods SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lipsky, Leah; Nansel, Tonja; Haynie, Denise] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405185 ER PT J AU Lipsky, L Olson, C Strawderman, M AF Lipsky, Leah Olson, Christine Strawderman, Myla TI Relations of early pregnancy BMI, gestational weight gain and 1-year weight retention to maternal body weight outcomes between 1 and 2 years postpartum SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lipsky, Leah] NIH, Bethesda, MD 20892 USA. [Olson, Christine; Strawderman, Myla] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404919 ER PT J AU Liu, JK May, WD Fox, CS Penman, A Dubbert, PM Wilson, JG Taylor, HA AF Liu, Jiankang May, Warren D. Fox, Caroline S. Penman, Alan Dubbert, Patricia M. Wilson, James G. Taylor, Herman A. TI Accuracy of Anthropometric Parameters as Indicators of Abdominal Adipose Tissue: Comparisons of the Areas under Receiver Operating Characteristic Curves Using a Nonparametric Approach SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Liu, Jiankang; May, Warren D.; Penman, Alan; Wilson, James G.; Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Fox, Caroline S.] NHLBI Framingham Heart Study, Framingham, MA USA. [Dubbert, Patricia M.] S Cent Vet Affairs Mental Illness Res Educ & Clin, MIRECC MI 16, Improving Clin Care, N Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403313 ER PT J AU Liu, J Nussinov, R AF Liu, Jin Nussinov, Ruth TI Molecular dynamics simulations reveal distinct conformational changes of three cullins in cullin-RING E3 ubiquitin ligases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Liu, Jin; Nussinov, Ruth] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404526 ER PT J AU Liu, M Cao, XG Villasmil, R Tuo, JS Shen, DF Chan, CC AF Liu, Melissa Cao, Xiaoguang Villasmil, Rafael Tuo, Jingsheng Shen, Defen Chan, Chi-Chao TI Macrophage polarization in C57BL/6 and Ccl2-/-/Cx3cr1-/- mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Liu, Melissa; Cao, Xiaoguang; Villasmil, Rafael; Tuo, Jingsheng; Shen, Defen; Chan, Chi-Chao] NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403407 ER PT J AU Locatelli-Hoops, S Gawrisch, K Yeliseev, A AF Locatelli-Hoops, Silvia Gawrisch, Klaus Yeliseev, Alexei TI Expression, Characterization and purification of Recombinant Cannabinoid Receptor CB2 as a Fusion with Halo- and C-terminal Rhodopsin Tags SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Locatelli-Hoops, Silvia; Gawrisch, Klaus; Yeliseev, Alexei] NIAAA, NMR Sect, LMBB, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404766 ER PT J AU Loewen, C Young, B Shin, J Orij, R Chao, J Li, SC Guan, XL Khong, A Jan, E Wenk, M Prinz, W Smits, G AF Loewen, Christopher Young, Barry Shin, John Orij, Rick Chao, Jesse Li, Shu Chen Guan, Xue Li Khong, Anthony Jan, Eric Wenk, Markus Prinz, William Smits, Gertien TI Lipid Signaling Regulated by pH: Phosphatidic Acid as a pH Biosensor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Loewen, Christopher; Young, Barry; Shin, John; Chao, Jesse; Li, Shu Chen; Khong, Anthony; Jan, Eric] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Orij, Rick; Smits, Gertien] Univ Amsterdam, Amsterdam, Netherlands. [Guan, Xue Li; Wenk, Markus] Natl Univ Singapore, Singapore 117548, Singapore. [Prinz, William] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. RI Smits, Gertien/I-4327-2014 OI Smits, Gertien/0000-0002-8439-7791 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402093 ER PT J AU Logan, TT Yu, PP Geller, HM Mungunsukh, O Day, RM Symes, AJ AF Logan, Trevor T. Yu, Panpan Geller, Herbert M. Mungunsukh, Ognoon Day, Regina M. Symes, Aviva J. TI The potential of HGF and 2xInlB to activate the Met receptor and attenuate chondroitin sulfate proteoglycan expression in astrocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Logan, Trevor T.; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Neurosci Program, Bethesda, MD 20814 USA. [Mungunsukh, Ognoon; Day, Regina M.; Symes, Aviva J.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. [Yu, Panpan; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402885 ER PT J AU Lokanga, AR Kumari, D Usdin, K AF Lokanga, Adihe Rachel Kumari, Daman Usdin, Karen TI The effect of Msh2 mutations on CGG.CCG-repeat expansion in Fragile X Premutation mouse model SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lokanga, Adihe Rachel; Kumari, Daman; Usdin, Karen] NIDDK, LMCB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404411 ER PT J AU Lu, ZP Bourdi, M Aponte, A Lombard, DB Gucek, M Pohl, LR Sack, MN AF Lu, Zhongping Bourdi, Mohammed Aponte, Angel Lombard, David B. Gucek, Marjan Pohl, Lance R. Sack, Michael N. TI SIRT3-dependent protein deacetylation modulates susceptibility to acetaminophen-induced liver injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lu, Zhongping; Sack, Michael N.] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA. [Bourdi, Mohammed; Pohl, Lance R.] NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. [Aponte, Angel; Gucek, Marjan] NHLBI, NHLBI Prote Core Facil, Bethesda, MD 20892 USA. [Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402701 ER PT J AU Lyon, AM Tesmer, VM Dhamsania, V Gutierrez, J Chowdhury, S Suddala, K Northup, JK Tesmer, JJG AF Lyon, Angeline M. Tesmer, Valerie M. Dhamsania, Vishan Gutierrez, Joanne Chowdhury, Shoaib Suddala, Krishna Northup, John K. Tesmer, John J. G. TI Regulation and Activation of Phospholipase C beta SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Lyon, Angeline M.; Tesmer, Valerie M.; Dhamsania, Vishan; Suddala, Krishna; Tesmer, John J. G.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Tesmer, John J. G.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Gutierrez, Joanne; Chowdhury, Shoaib; Northup, John K.] NIH, Cell Biol Lab, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400133 ER PT J AU Matsuda, M Chitnis, A AF Matsuda, Miho Chitnis, Ajay TI Distinct roles for FGF3 and FGF10 in the transition from proneuromast initiation to proneuromast maturation and deposition in the zebrafish lateral line primordium SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Matsuda, Miho; Chitnis, Ajay] NICHD, LMG, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402460 ER EF